U.S. patent application number 15/435332 was filed with the patent office on 2017-06-08 for pesticidal compositions and processes related thereto.
This patent application is currently assigned to Dow AgroSciences LLC. The applicant listed for this patent is Dow AgroSciences LLC. Invention is credited to Joshodeep Boruwa, James E. Hunter, Pravin S. Iyer, William C. Lo, Akshay Patny, Gerald B. Watson.
Application Number | 20170158675 15/435332 |
Document ID | / |
Family ID | 50931591 |
Filed Date | 2017-06-08 |
United States Patent
Application |
20170158675 |
Kind Code |
A1 |
Lo; William C. ; et
al. |
June 8, 2017 |
PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
Abstract
This document discloses molecules having the following formula
("Formula One"): ##STR00001## and processes associated
therewith.
Inventors: |
Lo; William C.; (Fishers,
IN) ; Hunter; James E.; (Indianapolis, IN) ;
Watson; Gerald B.; (Zionsville, IN) ; Patny;
Akshay; (Waltham, MA) ; Iyer; Pravin S.;
(Secunderabad, IN) ; Boruwa; Joshodeep; (Noida,
IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Dow AgroSciences LLC |
Indianapolis |
IN |
US |
|
|
Assignee: |
Dow AgroSciences LLC
Indianapolis
IN
|
Family ID: |
50931591 |
Appl. No.: |
15/435332 |
Filed: |
February 17, 2017 |
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9622477 |
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15435332 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 47/28 20130101;
A61P 33/10 20180101; C07D 209/08 20130101; C07C 317/44 20130101;
C07D 307/14 20130101; A01N 47/18 20130101; A01N 37/18 20130101;
C07C 211/29 20130101; A01N 33/04 20130101; C07C 327/48 20130101;
C07D 213/56 20130101; C07D 239/26 20130101; C07D 295/192 20130101;
A01N 43/38 20130101; A01N 53/00 20130101; A01N 43/60 20130101; C07C
327/46 20130101; C07D 207/16 20130101; A01N 43/36 20130101; C07C
259/06 20130101; C07C 235/80 20130101; A01N 47/38 20130101; A01N
37/36 20130101; C07D 249/14 20130101; A01N 43/40 20130101; A01N
47/32 20130101; C07C 255/57 20130101; C07C 323/60 20130101; C07D
295/096 20130101; C07C 63/74 20130101; C07C 255/58 20130101; C07C
271/14 20130101; C07D 207/27 20130101; C07D 211/58 20130101; C07D
237/32 20130101; C07D 401/10 20130101; A01N 37/34 20130101; C07D
307/52 20130101; C07D 209/48 20130101; C07D 271/10 20130101; C07D
209/50 20130101; C07C 243/38 20130101; C07C 233/56 20130101; C07D
277/30 20130101; C07D 331/04 20130101; A01N 41/10 20130101; A01N
37/10 20130101; A01N 43/16 20130101; A01N 43/54 20130101; C07C
243/36 20130101; C07C 323/59 20130101; C07C 2601/02 20170501; C07D
213/74 20130101; C07C 335/12 20130101; A01N 43/50 20130101; C07C
2602/08 20170501; C07D 213/64 20130101; C07D 241/12 20130101; C07D
307/16 20130101; C07C 237/22 20130101; C07C 233/66 20130101; C07C
323/62 20130101; C07C 327/42 20130101; C07D 277/64 20130101; C07D
213/61 20130101; C07D 233/64 20130101; A61P 33/14 20180101; A01N
43/653 20130101; A01N 43/08 20130101; C07C 211/27 20130101; C07C
233/83 20130101; C07D 249/10 20130101; A01N 37/28 20130101; C07C
233/14 20130101; C07C 233/59 20130101; C07D 277/32 20130101; C07C
323/63 20130101; C07D 309/14 20130101; A01N 43/82 20130101; C07C
233/13 20130101; C07C 275/24 20130101; C07D 295/073 20130101; C07D
405/04 20130101; A01N 43/84 20130101; A01N 43/80 20130101; A01N
25/08 20130101; C07C 259/08 20130101; A01N 43/20 20130101; A01N
43/58 20130101; C07C 63/70 20130101; C07C 233/65 20130101; C07C
243/34 20130101; C07C 2602/10 20170501; C07D 213/75 20130101; C07D
249/08 20130101; C07D 295/155 20130101; A01N 37/46 20130101; C07C
237/06 20130101; A01N 37/32 20130101; C07C 317/32 20130101; C07C
335/14 20130101; A01N 47/36 20130101; A01N 43/78 20130101; C07C
211/42 20130101; C07C 233/76 20130101; C07D 213/40 20130101 |
International
Class: |
C07D 405/04 20060101
C07D405/04; C07C 63/74 20060101 C07C063/74; A01N 37/10 20060101
A01N037/10; C07C 255/57 20060101 C07C255/57; A01N 37/34 20060101
A01N037/34; C07C 233/65 20060101 C07C233/65; A01N 37/18 20060101
A01N037/18; C07C 233/66 20060101 C07C233/66; C07D 295/192 20060101
C07D295/192; A01N 43/84 20060101 A01N043/84; C07D 213/61 20060101
C07D213/61; A01N 43/40 20060101 A01N043/40; C07D 207/27 20060101
C07D207/27; A01N 43/36 20060101 A01N043/36; C07D 331/04 20060101
C07D331/04; A01N 43/20 20060101 A01N043/20; C07D 213/40 20060101
C07D213/40; C07D 277/32 20060101 C07D277/32; A01N 43/80 20060101
A01N043/80; C07C 243/38 20060101 C07C243/38; C07D 239/26 20060101
C07D239/26; A01N 43/54 20060101 A01N043/54; C07D 307/14 20060101
C07D307/14; A01N 43/08 20060101 A01N043/08; C07D 307/52 20060101
C07D307/52; C07D 277/64 20060101 C07D277/64; C07D 241/12 20060101
C07D241/12; A01N 43/60 20060101 A01N043/60; C07C 243/36 20060101
C07C243/36; C07D 233/64 20060101 C07D233/64; A01N 43/50 20060101
A01N043/50; C07D 309/14 20060101 C07D309/14; A01N 43/16 20060101
A01N043/16; C07D 213/75 20060101 C07D213/75; C07D 271/10 20060101
C07D271/10; A01N 43/82 20060101 A01N043/82; C07C 327/48 20060101
C07C327/48; C07D 213/74 20060101 C07D213/74; C07D 213/64 20060101
C07D213/64; C07D 211/58 20060101 C07D211/58; C07C 259/06 20060101
C07C259/06; C07C 243/34 20060101 C07C243/34; C07C 335/14 20060101
C07C335/14; A01N 47/32 20060101 A01N047/32; C07C 233/14 20060101
C07C233/14; C07C 233/59 20060101 C07C233/59; C07D 213/56 20060101
C07D213/56; C07C 211/42 20060101 C07C211/42; C07D 209/08 20060101
C07D209/08; C07D 237/32 20060101 C07D237/32; C07D 209/48 20060101
C07D209/48; C07C 211/29 20060101 C07C211/29; C07C 323/59 20060101
C07C323/59; A01N 37/36 20060101 A01N037/36; C07C 275/24 20060101
C07C275/24; C07C 271/14 20060101 C07C271/14; C07C 235/80 20060101
C07C235/80; C07C 237/06 20060101 C07C237/06; C07D 295/073 20060101
C07D295/073; C07D 295/096 20060101 C07D295/096; C07D 249/08
20060101 C07D249/08; C07D 249/14 20060101 C07D249/14; C07D 249/10
20060101 C07D249/10; C07D 295/155 20060101 C07D295/155; C07C 327/42
20060101 C07C327/42; C07C 317/32 20060101 C07C317/32 |
Claims
1. A composition comprising a molecule according to Formula One:
##STR00917## wherein: (a) R1 is selected from (1) H, F, Cl, Br, I,
CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, (4) substituted
(C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and (5) substituted halo(C.sub.1-C.sub.8)alkoxy,
wherein said substituted halo(C.sub.1-C.sub.8)alkoxy has one or
more substituents selected from CN and NO.sub.2; (b) R2 is selected
from (1) H, F, Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, (4) substituted
(C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and (5) substituted halo(C.sub.1-C.sub.8)alkoxy,
wherein said substituted halo(C.sub.1-C.sub.8)alkoxy has one or
more substituents selected from CN and NO.sub.2; (c) R3 is selected
from (1) H, F, Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, (4) substituted
(C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and (5) substituted halo(C.sub.1-C.sub.8)alkoxy,
wherein said substituted halo(C.sub.1-C.sub.8)alkoxy has one or
more substituents selected from CN and NO.sub.2; (d) R4 is selected
from (1) H, F, Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, (4) substituted
(C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and (5) substituted halo(C.sub.1-C.sub.8)alkoxy,
wherein said substituted halo(C.sub.1-C.sub.8)alkoxy has one or
more substituents selected from CN and NO.sub.2; (e) R5 is selected
from (1) H, F, Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, (4) substituted
(C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and (5) substituted halo(C.sub.1-C.sub.8)alkoxy,
wherein said substituted halo(C.sub.1-C.sub.8)alkoxy has one or
more substituents selected from CN and NO.sub.2; (f) R6 is a
(C.sub.1-C.sub.8)haloalkyl; (g) R7 is selected from H, F, Cl, Br,
I, OH, (C.sub.1-C.sub.8)alkoxy, and halo(C.sub.1-C.sub.8)alkoxy;
(h) R8 is selected from H, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, OR14, and N(R14)(R15); (i) R9 is
selected from H, F, Cl, Br, I, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, OR14, and N(R14)(R15); (j) R10 is
selected from (1) H, F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), NR14R15, C(.dbd.O)H,
C(.dbd.O)N(R14)(R15), CN(R14)(R15)(.dbd.NOH),
(C.dbd.O)O(C.sub.1-C.sub.8)alkyl, (C.dbd.O)OH, heterocyclyl,
(C.sub.2-C.sub.5)alkenyl, halo(C.sub.2-C.sub.5)alkenyl,
(C.sub.2-C.sub.5)alkynyl, (2) substituted (C.sub.1-C.sub.8)alkyl,
wherein said substituted (C.sub.1-C.sub.8)alkyl has one or more
substituents selected from OH, (C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(O)(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(C.sub.1-C.sub.8)alkyl, NR14R15, and (3) substituted
halo(C.sub.1-C.sub.8)alkyl, wherein said substituted
halo(C.sub.1-C.sub.8)alkyl, has one or more substituents selected
from (C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(O)(C.sub.1-C.sub.8)alkyl, S(O).sub.2(C.sub.1-C.sub.8)alkyl, and
N(R14)(R15); (k) R11 is selected from
C(.dbd.X5)N(R14)((C.sub.1-C.sub.8)alkylC(.dbd.X5)N(R14)(R15))
wherein each X5 is independently selected from O, or S; (l) R12 is
selected from (v), H, F, Cl, Br, I, CN, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, and cyclo(C.sub.3-C.sub.6)alkyl; (m)
R13 is selected from (v), H, F, Cl, Br, I, CN,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, and halo(C.sub.1-C.sub.8)alkoxy; (n) each
R14 is independently selected from H, (C.sub.1-C.sub.8)alkyl,
(C.sub.2-C.sub.5)alkenyl, substituted (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, substituted
halo(C.sub.1-C.sub.8)alkyl), (C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl), N(R16)(R17),
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)N(R16)(R17),
C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)(halo(C.sub.1-C.sub.8)alkyl),
C(.dbd.O)(C.sub.3-C.sub.6)cycloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, C(.dbd.O)H
wherein each said substituted (C.sub.1-C.sub.8)alkyl has one or
more substituents selected from CN, and NO.sub.2, wherein each said
substituted halo(C.sub.1-C.sub.8)alkyl), has one or more
substituents selected from CN, and NO.sub.2, wherein each said
substituted-aryl has one or more substituents selected from F, Cl,
Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
and oxo, and wherein each said substituted-heterocyclyl has one or
more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
(C.sub.3-C.sub.6)cycloalkyl S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
heterocyclyl, C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, and oxo, (wherein said alkyl,
alkoxy, and heterocyclyl, may be further substituted with one or
more of F, Cl, Br, I, CN, and NO.sub.2); (o) each R15 is
independently selected from H, (C.sub.1-C.sub.8)alkyl,
(C.sub.2-C.sub.5)alkenyl, substituted (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, substituted
halo(C.sub.1-C.sub.8)alkyl), (C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
0-(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl), N(R16)(R17),
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)N(R16)(R17),
C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)(halo(C.sub.1-C.sub.8)alkyl),
C(.dbd.O)(C.sub.3-C.sub.6)cycloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, C(.dbd.O)H
wherein each said substituted (C.sub.1-C.sub.8)alkyl has one or
more substituents selected from CN, and NO.sub.2, wherein each said
substituted halo(C.sub.1-C.sub.8)alkyl), has one or more
substituents selected from CN, and NO.sub.2, wherein each said
substituted-aryl has one or more substituents selected from F, Cl,
Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
and oxo, and wherein each said substituted-heterocyclyl has one or
more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
(C.sub.3-C.sub.6)cycloalkyl S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
heterocyclyl, C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, and oxo, (wherein said alkyl,
alkoxy, and heterocyclyl, may be further substituted with one or
more of F, Cl, Br, I, CN, and NO.sub.2); (p) each R16 is
independently selected from H, (C.sub.1-C.sub.8)alkyl,
substituted-(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
substituted-halo(C.sub.1-C.sub.8)alkyl,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl wherein each said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN, and NO.sub.2, wherein each said substituted
halo(C.sub.1-C.sub.8)alkyl), has one or more substituents selected
from CN, and NO.sub.2, wherein each said substituted-aryl has one
or more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo, and
wherein each said substituted-heterocyclyl has one or more
substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo; (q)
each R17 is independently selected from H, (C.sub.1-C.sub.8)alkyl,
substituted-(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
substituted-halo(C.sub.1-C.sub.8)alkyl,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl wherein each said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN, and NO.sub.2, wherein each said substituted
halo(C.sub.1-C.sub.8)alkyl), has one or more substituents selected
from CN, and NO.sub.2, wherein each said substituted-aryl has one
or more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo, and
wherein each said substituted-heterocyclyl has one or more
substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo; (r) X1
is selected from N and CR12; (s) X2 is selected from N, CR9, and
CR13; (t) X3 is selected from N and CR9; and (v) R12 and R13
together form a linkage containing 3 to 4 atoms selected from C, N,
O, and S, wherein said linkage connects back to the ring to form a
5 to 6 member saturated or unsaturated cyclic ring, wherein said
linkage has at least one substituent X4 wherein X4 is selected from
R14, N(R14)(R15), N(R14)(C(.dbd.O)R14), N(R14)(C(.dbd.S)R14),
N(R14)(C(
.dbd.O)N(R14)(R14)), N(R14)(C(.dbd.S)N(R14)(R14)),
N(R14)(C(.dbd.O)N(R14)((C.sub.2-C.sub.8)alkenyl)),
N(R14)(C(.dbd.S)N(R14)((C.sub.2-C.sub.8)alkenyl)), wherein each R14
is independently selected.
2. A composition according to claim 1 further comprising: (a) one
or more compounds having acaricidal, algicidal, avicidal,
bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal,
nematicidal, rodenticidal, or virucidal properties; or (b) one or
more compounds that are antifeedants, bird repellents,
chemosterilants, herbicide safeners, insect attractants, insect
repellents, mammal repellents, mating disrupters, plant activators,
plant growth regulators, or synergists; or (c) both (a) and
(b).
3. A composition according to claim 1 wherein further comprising
one or more compounds selected from: (3-ethoxypropyl)mercury
bromide, 1,2-dichloropropane, 1,3-dichloropropene,
1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol,
2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium,
2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T,
2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,
2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl,
2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl,
2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,
2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,
2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,
2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,
2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,
2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,
2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP,
2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl,
2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium,
2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl,
2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl,
2,4-D-tetradecylammonium, 2,4-D-triethylammonium,
2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,
2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB,
3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium,
4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline
sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid,
ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor,
acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl,
acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen,
acrep, acrinathrin, acrolein, acrylonitrile, acypetacs,
acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole,
aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin,
allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl
alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan,
ametoctradin, ametridione, ametryn, amibuzin, amicarbazone,
amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb,
aminocyclopyrachlor, aminocyclopyrachlor-methyl,
aminocyclopyrachlor-potassium, aminopyralid,
aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium,
amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate,
amitraz, amitrole, ammonium sulfamate, ammonium
.alpha.-naphthaleneacetate, amobam, ampropylfos, anabasine,
ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu,
apholate, aramite, arsenous oxide, asomate, aspirin, asulam,
asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,
aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,
azadirachtin, azafenidin, azamethiphos, azimsulfuron,
azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram,
azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh,
barban, barium hexafluorosilicate, barium polysulfide, barthrin,
BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin,
benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium,
bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb,
benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox,
bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron,
bentazone, bentazone-sodium, benthiavalicarb,
benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,
benzadox-ammonium, benzalkonium chloride, benzamacril,
benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,
benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,
benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl
benzoate, benzyladenine, berberine, berberine chloride,
beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone,
bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos,
bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin,
bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir,
bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron,
bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux
mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl,
brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil,
bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin,
bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide,
bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl,
bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate,
bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,
brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb,
buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan,
butacarb, butachlor, butafenacil, butamifos, butathiofos,
butenachlor, butethrin, buthidazole, buthiobate, buthiuron,
butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,
butroxydim, buturon, butylamine, butylate, cacodylic acid,
cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium
cyanamide, calcium polysulfide, calvinphos, cambendichlor,
camphechlor, camphor, captafol, captan, carbamorph, carbanolate,
carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate,
carbendazim sulfite, carbetamide, carbofuran, carbon disulfide,
carbon tetrachloride, carbophenothion, carbosulfan, carboxazole,
carboxide, carboxin, carfentrazone, carfentrazone-ethyl,
carpropamid, cartap, cartap hydrochloride, carvacrol, carvone,
CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat,
chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben,
chloramben-ammonium, chloramben-diolamine, chloramben-methyl,
chloramben-methylammonium, chloramben-sodium, chloramine
phosphorus, chloramphenicol, chloraniformethan, chloranil,
chloranocryl, chlorantraniliprole, chlorazifop,
chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron,
chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone,
chlordimeform, chlordimeform hydrochloride, chlorempenthrin,
chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium,
chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol,
chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos,
chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl,
chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron,
chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride,
chlornidine, chlornitrofen, chlorobenzilate,
chlorodinitronaphthalenes, chloroform, chloromebuform,
chloromethiuron, chloroneb, chlorophacinone,
chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate,
chlorothalonil, chlorotoluron, chloroxuron, chloroxynil,
chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos,
chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl,
chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl,
chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate,
choline chloride, chromafenozide, cinerin I, cinerin II, cinerins,
cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide,
cismethrin, clethodim, climbazole, cliodinate, clodinafop,
clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,
clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,
clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,
clopyralid-olamine, clopyralid-potassium,
clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,
cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,
clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,
codlelure, colophonate, copper acetate, copper acetoarsenite,
copper arsenate, copper carbonate, basic, copper hydroxide, copper
naphthenate, copper oleate, copper oxychloride, copper silicate,
copper sulfate, copper zinc chromate, coumachlor, coumafuryl,
coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF,
CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos,
crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam,
cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine,
cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid,
cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate,
cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron,
cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid,
cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin,
cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil,
cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat
chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole,
cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine,
cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium,
dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium,
DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin,
decarbofuran, dehydroacetic acid, delachlor, deltamethrin,
demephion, demephion-O, demephion-S, demeton, demeton-methyl,
demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl,
demeton-S-methylsulphon, desmedipham, desmetryn,
d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate,
diamidafos, diatomaceous earth, diazinon, dibutyl phthalate,
dibutyl succinate, dicamba, dicamba-diglycolamine,
dicamba-dimethylammonium, dicamba-diolamine,
dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine,
dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon,
dichlobenil, dichlofenthion, dichlofluanid, dichlone,
dichloralurea, dichlorbenzuron, dichlorflurenol,
dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen,
dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl,
dichlorprop-dimethylammonium, dichlorprop-ethylammonium,
dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,
dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,
dichlorprop-potassium, dichlorprop-sodium, dichlorvos,
dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl,
diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol,
dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon,
dieldrin, dienochlor, diethamquat, diethamquat dichloride,
diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl
pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,
difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat,
difenzoquat metilsulfate, difethialone, diflovidazin,
diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,
diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif,
dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone,
dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid,
dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph,
dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos,
dimetilan, dimexano, dimidazon, dimoxystrobin, dinex,
dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M,
dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton,
dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb
acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,
dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb
acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb,
dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl
sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione,
diquat, diquat dibromide, disparlure, disul, disulfiram,
disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos,
dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC,
DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph
acetate, dodemorph benzoate, dodicin, dodicin hydrochloride,
dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin,
drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos,
eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC,
empenthrin, endosulfan, endothal, endothal-diammonium,
endothal-dipotassium, endothal-disodium, endothion, endrin,
enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,
eprinomectin, epronaz, EPTC, erbon, ergocalciferol,
erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb,
etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor,
ethalfluralin, ethametsulfuron, ethametsulfuron-methyl,
ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate,
ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl,
ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,
ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl
formate, ethyl .alpha.-naphthaleneacetate, ethyl-DDD, ethylene,
ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin,
ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate,
ethylmercury bromide, ethylmercury chloride, ethylmercury
phosphate, etinofen, etnipromid, etobenzanid, etofenprox,
etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone,
famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil,
fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,
fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,
fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid,
fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop,
fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl,
fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl,
fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil,
fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl,
fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin,
fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,
fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,
fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,
fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,
fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,
fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil,
flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl,
flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron,
flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim,
fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P,
fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide,
flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron,
fluchloralin, flucofuron, flucycloxuron, flucythrinate,
fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,
flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,
flufiprole, flumethrin, flumetover, flumetralin, flumetsulam,
flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin,
flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram,
fluorbenside, fluoridamid, fluoroacetamide, fluorodifen,
fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine,
fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin,
flupoxam, flupropacil, flupropadine, flupropanate,
flupropanate-sodium, flupyradifurone, flupyrsulfuron,
flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium,
fluquinconazole, flurazole, flurenol, flurenol-butyl,
flurenol-methyl, fluridone, flurochloridone, fluroxypyr,
fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid,
flurtamone, flusilazole, flusulfamide, fluthiacet,
fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate,
fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium,
fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,
formetanate hydrochloride, formothion, formparanate, formparanate
hydrochloride, fosamine, fosamine-ammonium, fosetyl,
fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,
frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,
fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,
furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,
furfural, furilazole, furmecyclox, furophanate, furyloxyfen,
gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid,
gibberellins, gliftor, glufosinate, glufosinate-ammonium,
glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium,
glyodin, glyoxime, glyphosate, glyphosate-diammonium,
glyphosate-dimethylammonium, glyphosate-isopropylammonium,
glyphosate-monoammonium, glyphosate-potassium,
glyphosate-sesquisodium, glyphosate-trimesium, glyphosine,
gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates,
halacrinate, halfenprox, halofenozide, halosafen, halosulfuron,
halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl,
haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,
haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,
heptachlor, heptenophos, heptopargil, heterophos,
hexachloroacetone, hexachlorobenzene, hexachlorobutadiene,
hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure,
hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf,
huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen,
hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb,
IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil
sulfate, imazamethabenz, imazamethabenz-methyl, imazamox,
imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr,
imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium,
imazaquin-methyl, imazaquin-sodium, imazethapyr,
imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,
imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,
iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,
indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,
iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,
iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,
ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole,
ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam,
ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan,
isocarbamid, isocarbophos, isocil, isodrin, isofenphos,
isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate,
isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam,
isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben,
isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole,
isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure,
japothrins, jasmolin I, jasmolin II, jasmonic acid,
jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,
jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II,
juvenile hormone III, kadethrin, karbutilate, karetazan,
karetazan-potassium, kasugamycin, kasugamycin hydrochloride,
kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin,
kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin,
latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane,
lineatin, linuron, lirimfos, litlure, looplure, lufenuron,
lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic
hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb,
mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl,
MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine,
MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,
MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium,
MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl,
MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop,
mecoprop-2-ethylhexyl, mecoprop-dimethylammonium,
mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl,
mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,
mecoprop-P-dimethylammonium, mecoprop-P-isobutyl,
mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium,
mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate,
medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide,
mefluidide-diolamine, mefluidide-potassium, megatomoic acid,
menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan,
mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil,
meptyldinocap, mercuric chloride, mercuric oxide, mercurous
chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl,
mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl,
metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,
metamitron, metam-potassium, metam-sodium, metazachlor,
metazosulfuron, metazoxolon, metconazole, metepa, metflurazon,
methabenzthiazuron, methacrifos, methalpropalin, methamidophos,
methasulfocarb, methazole, methfuroxam, methidathion,
methiobencarb, methiocarb, methiopyrisulfuron, methiotepa,
methiozolin, methiuron, methocrotophos, methometon, methomyl,
methoprene, methoprotryne, methoquin-butyl, methothrin,
methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate,
methyl bromide, methyl eugenol, methyl iodide, methyl
isothiocyanate, methylacetophos, methylchloroform, methyldymron,
methylene chloride, methylmercury benzoate, methylmercury
dicyandiamide, methylmercury pentachlorophenoxide,
methylneodecanamide, metiram, metobenzuron, metobromuron,
metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam,
metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax,
metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan,
milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF,
moguchun, molinate, molosultap, monalide, monisouron,
monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,
monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat
dichloride, moroxydine, moroxydine hydrochloride, morphothion,
morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin,
N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,
naphthalene, naphthaleneacetamide, naphthalic anhydride,
naphthoxyacetic acids, naproanilide, napropamide, naptalam,
naptalam-sodium, natamycin, neburon, niclosamide,
niclosamide-olamine, nicosulfuron, nicotine, nifluridide,
nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,
nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene,
nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron,
novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether,
octhilinone, ofurace, omethoate, orbencarb, orfralure,
ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin,
oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon,
oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine,
oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper,
oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin,
oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,
oxymatrine, oxytetracycline, oxytetracycline hydrochloride,
paclobutrazol, paichongding, para-dichlorobenzene, parafluron,
paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,
parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,
penconazole, pencycuron, pendimethalin, penflufen, penfluron,
penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad,
pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid,
phenamacril, phenazine oxide, phenisopham, phenkapton,
phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin,
phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate,
phenylmercury chloride, phenylmercury derivative of pyrocatechol,
phenylmercury nitrate, phenylmercury salicylate, phorate,
phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,
phosglycin, phosmet, phosnichlor, phosphamidon, phosphine,
phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide,
picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,
picloram-olamine, picloram-potassium, picloram-triethylammonium,
picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,
pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,
piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,
piprotal, pirimetaphos, pirimicarb, pirimioxyphos,
pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate,
polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium
arsenite, potassium azide, potassium cyanate, potassium
gibberellate, potassium naphthenate, potassium polysulfide,
potassium thiocyanate, potassium .alpha.-naphthaleneacetate,
pp'-DDT, prallethrin, precocene I, precocene II, precocene III,
pretilachlor, primidophos, primisulfuron, primisulfuron-methyl,
probenazole, prochloraz, prochloraz-manganese, proclonol,
procyazine, procymidone, prodiamine, profenofos, profluazol,
profluralin, profluthrin, profoxydim, proglinazine,
proglinazine-ethyl, prohexadione, prohexadione-calcium,
prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit,
propachlor, propamidine, propamidine dihydrochloride, propamocarb,
propamocarb hydrochloride, propanil, propaphos, propaquizafop,
propargite, proparthrin, propazine, propetamphos, propham,
propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,
propoxycarbazone-sodium, propyl isome, propyrisulfuron,
propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb,
prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride,
prothioconazole, prothiofos, prothoate, protrifenbute, proxan,
proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,
pyraclofos, pyraclonil, pyraclostrobin, pyraflufen,
pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin,
pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos,
pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen,
pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins,
pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,
pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol,
pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox,
pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen,
pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate,
pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen,
pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon,
pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,
quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,
quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,
quinonamid, quinothion, quinoxyfen, quintiofos, quintozene,
quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,
quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole,
rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III,
ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao,
saisentong, salicylanilide, sanguinarine, santonin, schradan,
scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,
semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim,
shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica
gel, silthiofam, simazine, simeconazole, simeton, simetryn,
sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium
chlorate, sodium fluoride, sodium fluoroacetate, sodium
hexafluorosilicate, sodium naphthenate, sodium
orthophenylphenoxide, sodium pentachlorophenoxide, sodium
polysulfide, sodium thiocyanate, sodium .alpha.-naphthaleneacetate,
sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,
spirotetramat, spiroxamine, streptomycin, streptomycin
sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium,
sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid,
sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep,
sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl
fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate,
tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl,
TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,
tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,
tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,
tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,
terallethrin, terbacil, terbucarb, terbuchlor, terbufos,
terbumeton, terbuthylazine, terbutryn, tetcyclacis,
tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon,
tetrafluron, tetramethrin, tetramethylfluthrin, tetramine,
tetranactin, tetrasul, thallium sulfate, thenylchlor,
theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor,
thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos,
thicyofen, thidiazimin, thidiazuron, thiencarbazone,
thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl,
thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim,
thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate,
thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,
thiohempa, thiomersal, thiometon, thionazin, thiophanate,
thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,
thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,
thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,
tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,
tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,
tralocythrin, tralomethrin, tralopyril, transfluthrin,
transpermethrin, tretamine, triacontanol, triadimefon, triadimenol,
triafamone, tri-allate, triamiphos, triapenthenol, triarathene,
triarimol, triasulfuron, triazamate, triazbutil, triaziflam,
triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos,
tributyltin oxide, tricamba, trichlamide, trichlorfon,
trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl,
triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole,
tridemorph, tridiphane, trietazine, trifenmorph, trifenofos,
trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium,
triflumizole, triflumuron, trifluralin, triflusulfuron,
triflusulfuron-methyl, trifop, trifop-methyl, trifopsime,
triforine, trihydroxytriazine, trimedlure, trimethacarb,
trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,
triptolide, tritac, triticonazole, tritosulfuron, trunc-call,
uniconazole, uniconazole-P, urbacide, uredepa, valerate,
validamycin, valifenalate, valone, vamidothion, vangard,
vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium,
warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC,
xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin,
zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide,
zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong,
.alpha.-chlorohydrin, .alpha.-ecdysone, .alpha.-multistriatin, and
.alpha.-naphthaleneacetic acid.
4. A composition according to claim 1 further comprising an
agriculturally acceptable carrier.
5. A process comprising applying a composition according to claim
1, to an area to control a pest, in an amount sufficient to control
such pest.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of, and claims the
benefit of, U.S. patent application Ser. No. 14/880,790, which was
filed on Oct. 12, 2015, which is a continuation of, and claims the
benefit of, U.S. patent application Ser. No. 14/133,094, which was
filed on Dec. 18, 2013, which claims the benefit of, and priority
from, U.S. provisional patent application Ser. No. 61/739,025,
which was filed on Dec. 19, 2012, the entire disclosures of these
applications are expressly incorporated herein by reference.
FIELD OF THE DISCLOSURE
[0002] The invention disclosed in this document is related to the
field of processes to produce molecules that are useful as
pesticides (e.g., acaricides, insecticides, molluscicides, and
nematicides), such molecules, and processes of using such molecules
to control pests.
BACKGROUND OF THE DISCLOSURE
[0003] Pests cause millions of human deaths around the world each
year. Furthermore, there are more than ten thousand species of
pests that cause losses in agriculture. The world-wide agricultural
losses amount to billions of U.S. dollars each year.
[0004] Termites cause damage to all kinds of private and public
structures. The world-wide termite damage losses amount to billions
of U.S. dollars each year.
[0005] Stored food pests eat and adulterate stored food. The
world-wide stored food losses amount to billions of U.S. dollars
each year, but more importantly, deprive people of needed food.
[0006] There is an acute need for new pesticides. Certain pests are
developing resistance to pesticides in current use. Hundreds of
pest species are resistant to one or more pesticides. The
development of resistance to some of the older pesticides, such as
DDT, the carbamates, and the organophosphates, is well known. But
resistance has even developed to some of the newer pesticides, for
example, imidacloprid.
[0007] Therefore, for many reasons, including the above reasons, a
need exists for new pesticides.
DEFINITIONS
[0008] The examples given in the definitions are generally
non-exhaustive and must not be construed as limiting the invention
disclosed in this document. It is understood that a substituent
should comply with chemical bonding rules and steric compatibility
constraints in relation to the particular molecule to which it is
attached.
[0009] "Alkenyl" means an acyclic, unsaturated (at least one
carbon-carbon double bond), branched or unbranched, substituent
consisting of carbon and hydrogen, for example, vinyl, allyl,
butenyl, pentenyl, and hexenyl.
[0010] "Alkenyloxy" means an alkenyl further consisting of a
carbon-oxygen single bond, for example, allyloxy, butenyloxy,
pentenyloxy, hexenyloxy.
[0011] "Alkoxy" means an alkyl further consisting of a
carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy,
isopropoxy, butoxy, isobutoxy, and tert-butoxy.
[0012] "Alkyl" means an acyclic, saturated, branched or unbranched,
substituent consisting of carbon and hydrogen, for example, methyl,
ethyl, (C.sub.3)alkyl which represents n-propyl and isopropyl),
(C.sub.4)alkyl which represents n-butyl, sec-butyl, isobutyl, and
tert-butyl.
[0013] "Alkynyl" means an acyclic, unsaturated (at least one
carbon-carbon triple bond), branched or unbranched, substituent
consisting of carbon and hydrogen, for example, ethynyl, propargyl,
butynyl, and pentynyl.
[0014] "Alkynyloxy" means an alkynyl further consisting of a
carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy,
heptynyloxy, and octynyloxy.
[0015] "Aryl" means a cyclic, aromatic substituent consisting of
hydrogen and carbon, for example, phenyl, naphthyl, and
biphenyl.
[0016] "(C.sub.x-C.sub.y)" where the subscripts "x" and "y" are
integers such as 1, 2, or 3, means the range of carbon atoms for a
substituent--for example, (C.sub.1-C.sub.4)alkyl means methyl,
ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and
tert-butyl, each individually.
[0017] "Cycloalkenyl" means a monocyclic or polycyclic, unsaturated
(at least one carbon-carbon double bond) substituent consisting of
carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl,
cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl,
tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
[0018] "Cycloalkenyloxy" means a cycloalkenyl further consisting of
a carbon-oxygen single bond, for example, cyclobutenyloxy,
cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.
[0019] "Cycloalkyl" means a monocyclic or polycyclic, saturated
substituent consisting of carbon and hydrogen, for example,
cyclopropyl, cyclobutyl, cyclopentyl, norbornyl,
bicyclo[2.2.2]octyl, and decahydronaphthyl.
[0020] "Cycloalkoxy" means a cycloalkyl further consisting of a
carbon-oxygen single bond, for example, cyclopropyloxy,
cyclobutyloxy, cyclopentyloxy, norbornyloxy, and
bicyclo[2.2.2]octyloxy.
[0021] "Halo" means fluoro, chloro, bromo, and iodo.
[0022] "Haloalkoxy" means an alkoxy further consisting of, from one
to the maximum possible number of identical or different, halos,
for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy,
chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and
pentafluoroethoxy.
[0023] "Haloalkyl" means an alkyl further consisting of, from one
to the maximum possible number of, identical or different, halos,
for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl,
chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.
[0024] "Heterocyclyl" means a cyclic substituent that may be fully
saturated, partially unsaturated, or fully unsaturated, where the
cyclic structure contains at least one carbon and at least one
heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen.
In the case of sulfur, that atom can be in other oxidation states
such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls
include, but are not limited to, benzofuranyl, benzoisothiazolyl,
benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl,
cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl,
isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl,
oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl,
pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,
quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl,
thienyl, triazinyl, and triazolyl. Examples of fully saturated
heterocyclyls include, but are not limited to, piperazinyl,
piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl,
tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl.
Examples of partially unsaturated heterocyclyls include, but are
not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl,
4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and
2,3-dihydro-[1,3,4]-oxadiazolyl.
[0025] Additional examples include the following
##STR00002##
DETAILED DESCRIPTION OF THE DISCLOSURE
[0026] This document discloses molecules having the following
formula ("Formula One"):
##STR00003##
wherein:
[0027] (a) R1 is selected from [0028] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), [0029] (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, [0030] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, [0031] (4)
substituted (C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and [0032] (5) substituted
halo(C.sub.1-C.sub.8)alkoxy, wherein said substituted
halo(C.sub.1-C.sub.8)alkoxy has one or more substituents selected
from CN and NO.sub.2;
[0033] (b) R2 is selected from [0034] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), [0035] (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, [0036] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, [0037] (4)
substituted (C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and [0038] (5) substituted
halo(C.sub.1-C.sub.8)alkoxy, wherein said substituted
halo(C.sub.1-C.sub.8)alkoxy has one or more substituents selected
from CN and NO.sub.2;
[0039] (c) R3 is selected from [0040] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), [0041] (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, [0042] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, [0043] (4)
substituted (C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and [0044] (5) substituted
halo(C.sub.1-C.sub.8)alkoxy, wherein said substituted
halo(C.sub.1-C.sub.8)alkoxy has one or more substituents selected
from CN and NO.sub.2;
[0045] (d) R4 is selected from [0046] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), [0047] (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, [0048] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, [0049] (4)
substituted (C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and [0050] (5) substituted
halo(C.sub.1-C.sub.8)alkoxy, wherein said substituted
halo(C.sub.1-C.sub.8)alkoxy has one or more substituents selected
from CN and NO.sub.2;
[0051] (e) R5 is selected from [0052] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
S(O)(C.sub.1-C.sub.8)alkyl, S(O)(halo(C.sub.1-C.sub.8)alkyl),
S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), N(R14)(R15), [0053] (2)
substituted (C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN and NO.sub.2, [0054] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from CN and NO.sub.2, [0055] (4)
substituted (C.sub.1-C.sub.8)alkoxy, wherein said substituted
(C.sub.1-C.sub.8)alkoxy has one or more substituents selected from
CN and NO.sub.2, and [0056] (5) substituted
halo(C.sub.1-C.sub.8)alkoxy, wherein said substituted
halo(C.sub.1-C.sub.8)alkoxy has one or more substituents selected
from CN and NO.sub.2;
[0057] (f) R6 is a (C.sub.1-C.sub.8)haloalkyl;
[0058] (g) R7 is selected from H, F, Cl, Br, I, OH,
(C.sub.1-C.sub.8)alkoxy, and halo(C.sub.1-C.sub.8)alkoxy;
[0059] (h) R8 is selected from H, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, OR14, and N(R14)(R15);
[0060] (i) R9 is selected from H, F, Cl, Br, I,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy, OR14, and
N(R14)(R15);
[0061] (j) R10 is selected from [0062] (1) H, F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), S(O)(C.sub.1-C.sub.8)alkyl,
S(O)(halo(C.sub.1-C.sub.8)alkyl), S(O).sub.2(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(halo(C.sub.1-C.sub.8)alkyl), NR14R15, C(.dbd.O)H,
C(.dbd.O)N(R14)(R15), CN(R14)(R15)(.dbd.NOH),
(C.dbd.O)O(C.sub.1-C.sub.8)alkyl, (C.dbd.O)OH, heterocyclyl,
(C.sub.2-C.sub.8)alkenyl, halo(C.sub.2-C.sub.8)alkenyl,
(C.sub.2-C.sub.8)alkynyl, [0063] (2) substituted
(C.sub.1-C.sub.8)alkyl, wherein said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
OH, (C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(O)(C.sub.1-C.sub.8)alkyl, S(O).sub.2(C.sub.1-C.sub.8)alkyl,
NR14R15, and [0064] (3) substituted halo(C.sub.1-C.sub.8)alkyl,
wherein said substituted halo(C.sub.1-C.sub.8)alkyl, has one or
more substituents selected from (C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(O)(C.sub.1-C.sub.8)alkyl,
S(O).sub.2(C.sub.1-C.sub.8)alkyl, and N(R14)(R15);
[0065] (k) R11 is selected from
C(.dbd.X5)N(R14)((C.sub.1-C.sub.8)alkylC(.dbd.X5)N(R14)(R15))
wherein each X5 is independently selected from O, or S;
[0066] (l) R12 is selected from (v), H, F, Cl, Br, I, CN,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy, and
cyclo(C.sub.3-C.sub.6)alkyl;
[0067] (m) R13 is selected from (v), H, F, Cl, Br, I, CN,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, and halo(C.sub.1-C.sub.8)alkoxy;
[0068] (n) each R14 is independently selected from H,
(C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, substituted
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl, substituted
halo(C.sub.1-C.sub.8)alkyl), (C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl), N(R16)(R17),
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)N(R16)(R17),
C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)(halo(C.sub.1-C.sub.8)alkyl),
C(.dbd.O)(C.sub.3-C.sub.6)cycloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, C(.dbd.O)H
[0069] wherein each said substituted (C.sub.1-C.sub.8)alkyl has one
or more substituents selected from CN, and NO.sub.2, [0070] wherein
each said substituted halo(C.sub.1-C.sub.8)alkyl), has one or more
substituents selected from CN, and NO.sub.2, [0071] wherein each
said substituted-aryl has one or more substituents selected from F,
Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
and oxo, and [0072] wherein each said substituted-heterocyclyl has
one or more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
(C.sub.3-C.sub.6)cycloalkyl S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
heterocyclyl, C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, and oxo, (wherein said alkyl,
alkoxy, and heterocyclyl, may be further substituted with one or
more of F, Cl, Br, I, CN, and NO.sub.2);
[0073] (o) each R15 is independently selected from H,
(C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, substituted
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl, substituted
halo(C.sub.1-C.sub.8)alkyl), (C.sub.1-C.sub.8)alkoxy,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl), N(R16)(R17),
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)N(R16)(R17),
C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)(halo(C.sub.1-C.sub.8)alkyl),
C(.dbd.O)(C.sub.3-C.sub.6)cycloalkyl,
(C.sub.1-C.sub.8)alkyl-C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, C(.dbd.O)H
[0074] wherein each said substituted (C.sub.1-C.sub.8)alkyl has one
or more substituents selected from CN, and NO.sub.2, [0075] wherein
each said substituted halo(C.sub.1-C.sub.8)alkyl), has one or more
substituents selected from CN, and NO.sub.2, [0076] wherein each
said substituted-aryl has one or more substituents selected from F,
Cl, Br, I, CN, NO.sub.2, (C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)alkoxy,
halo(C.sub.1-C.sub.8)alkoxy, S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
and oxo, and [0077] wherein each said substituted-heterocyclyl has
one or more substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
(C.sub.3-C.sub.6)cycloalkyl S(C.sub.1-C.sub.8)alkyl,
S(halo(C.sub.1-C.sub.8)alkyl), N((C.sub.1-C.sub.8)alkyl).sub.2
(wherein each (C.sub.1-C.sub.8)alkyl is independently selected),
heterocyclyl, C(.dbd.O)(C.sub.1-C.sub.8)alkyl,
C(.dbd.O)O(C.sub.1-C.sub.8)alkyl, and oxo, (wherein said alkyl,
alkoxy, and heterocyclyl, may be further substituted with one or
more of F, Cl, Br, I, CN, and NO.sub.2);
[0078] (p) each R16 is independently selected from H,
(C.sub.1-C.sub.8)alkyl, substituted-(C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, substituted-halo(C.sub.1-C.sub.8)alkyl,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl [0079] wherein each said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN, and NO.sub.2, [0080] wherein each said substituted
halo(C.sub.1-C.sub.8)alkyl), has one or more substituents selected
from CN, and NO.sub.2, [0081] wherein each said substituted-aryl
has one or more substituents selected from F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo, and
[0082] wherein each said substituted-heterocyclyl has one or more
substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo; [0083]
(q) each R17 is independently selected from H,
(C.sub.1-C.sub.8)alkyl, substituted-(C.sub.1-C.sub.8)alkyl,
halo(C.sub.1-C.sub.8)alkyl, substituted-halo(C.sub.1-C.sub.8)alkyl,
cyclo(C.sub.3-C.sub.6)alkyl, aryl, substituted-aryl,
(C.sub.1-C.sub.8)alkyl-aryl,
(C.sub.1-C.sub.8)alkyl-(substituted-aryl),
O--(C.sub.1-C.sub.8)alkyl-aryl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-aryl), heterocyclyl,
substituted-heterocyclyl, (C.sub.1-C.sub.8)alkyl-heterocyclyl,
(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl-heterocyclyl,
O--(C.sub.1-C.sub.8)alkyl-(substituted-heterocyclyl),
O--(C.sub.1-C.sub.8)alkyl [0084] wherein each said substituted
(C.sub.1-C.sub.8)alkyl has one or more substituents selected from
CN, and NO.sub.2, [0085] wherein each said substituted
halo(C.sub.1-C.sub.8)alkyl), has one or more substituents selected
from CN, and NO.sub.2, [0086] wherein each said substituted-aryl
has one or more substituents selected from F, Cl, Br, I, CN,
NO.sub.2, (C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo, and
[0087] wherein each said substituted-heterocyclyl has one or more
substituents selected from F, Cl, Br, I, CN, NO.sub.2,
(C.sub.1-C.sub.8)alkyl, halo(C.sub.1-C.sub.8)alkyl,
(C.sub.1-C.sub.8)alkoxy, halo(C.sub.1-C.sub.8)alkoxy,
S(C.sub.1-C.sub.8)alkyl, S(halo(C.sub.1-C.sub.8)alkyl),
N((C.sub.1-C.sub.8)alkyl).sub.2 (wherein each
(C.sub.1-C.sub.8)alkyl is independently selected), and oxo; [0088]
(r) X1 is selected from N and CR12; [0089] (s) X2 is selected from
N, CR9, and CR13; [0090] (t) X3 is selected from N and CR9; and
[0091] (v) R12 and R13 together form a linkage containing 3 to 4
atoms selected from C, N, O, and S, wherein said linkage connects
back to the ring to form a 5 to 6 member saturated or unsaturated
cyclic ring, wherein said linkage has at least one substituent X4
wherein X4 is selected from R14, N(R14)(R15), N(R14)(C(.dbd.O)R14),
N(R14)(C(.dbd.S)R14), N(R14)(C(.dbd.O)N(R14)(R14)),
N(R14)(C(.dbd.S)N(R14)(R14)),
N(R14)(C(.dbd.O)N(R14)((C.sub.2-C.sub.8)alkenyl)),
N(R14)(C(.dbd.S)N(R14)((C.sub.2-C.sub.8)alkenyl)), wherein each R14
is independently selected.
[0092] In another embodiment of this invention R1 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, NO.sub.2, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0093] In another embodiment of this invention R2 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, NO.sub.2, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0094] In another embodiment of this invention R3 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, NO.sub.2, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0095] In another embodiment of this invention R4 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, NO.sub.2, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0096] In another embodiment of this invention R5 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, NO.sub.2, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0097] In another embodiment of this invention R2 and R4 are
selected from F, Cl, Br, I, CN, and NO.sub.2 and R1, R3, and R5 are
H.
[0098] In another embodiment of this invention R2, R3, and R4 are
selected from F, Cl, Br, I, CN, and NO.sub.2 and R1, and R5 are
H.
[0099] In another embodiment of this invention R2, R3, and R4 are
independently selected from F and Cl and R1 and R5 are H.
[0100] In another embodiment of this invention R1 is selected from
Cl and H.
[0101] In another embodiment of this invention R2 is selected from
CF.sub.3, CH.sub.3, Cl, F, and H.
[0102] In another embodiment of this invention R3 is selected from
OCH.sub.3, CH.sub.3, F, Cl, or H.
[0103] In another embodiment of this invention R4 is selected from
CF.sub.3, CH.sub.3, Cl, F, and H.
[0104] In another embodiment of this invention R5 is selected from
F, Cl, and H.
[0105] In another embodiment of this invention R6 may be selected
from any combination of one or more of the following--halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl, and
halo(C.sub.8)alkyl.
[0106] In another embodiment of this invention R6 is
trifluoromethyl.
[0107] In another embodiment of this invention R7 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
and I.
[0108] In another embodiment of this invention R7 is selected from
H, OCH.sub.3, and OH.
[0109] In another embodiment of this invention R8 may be selected
from any combination of one or more of the following--H, methyl,
ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl, and
halo(C.sub.8)alkyl.
[0110] In another embodiment of this invention R8 is selected from
CH.sub.3 and H.
[0111] In another embodiment of this invention R9 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0112] In another embodiment of this invention R10 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, CN, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl,
(C.sub.5)alkyl, (C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl,
halomethyl, haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methoxy, ethoxy, (C.sub.3)alkoxy,
(C.sub.4)alkoxy, (C.sub.5)alkoxy, (C.sub.6)alkoxy, (C.sub.7)alkoxy,
(C.sub.8)alkoxy, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, halo(C.sub.8)alkoxy, cyclopropyl, cyclobutyl,
cyclopentyl, and cyclohexyl.
[0113] In another embodiment of this invention R10 may be selected
from any combination of one or more of the following--H, Cl, Br,
CH.sub.3, and CF.sub.3.
[0114] In another embodiment of this invention R10 is selected from
Br, C(.dbd.NOH)NH.sub.2, C(.dbd.O)H, C(.dbd.O)NH.sub.2,
C(.dbd.O)OCH.sub.2CH.sub.3, C(.dbd.O)OH, CF.sub.3,
CH.sub.2CH.sub.3, CH.sub.2OH, CH3, Cl, CN, F, H, NH.sub.2,
NHC(.dbd.O)H, NHCH.sub.3, NO.sub.2, OCH.sub.3, OCHF.sub.2, and
pyridyl.
[0115] In another embodiment of this invention R11 may be selected
from any combination of one or more of the
following--C(.dbd.O)N(H)(C((CH.sub.3).sub.2)C(.dbd.O)N(H)(CH.sub.2CF.sub.-
3)), C(.dbd.O)N(H)(CH(CH.sub.3)C(.dbd.O)N(H)(CH.sub.2CF.sub.3)),
C(.dbd.O)N(H)(CH(CH.sub.2CH.sub.3)C(.dbd.O)N(H)(CH.sub.2CF.sub.3)),
C(.dbd.O)N(H)(CH(CH.sub.3)C(.dbd.S)N(H)(CH.sub.2CF.sub.3)),
C(.dbd.O)N(H)(C((CH.sub.3).sub.2)C(.dbd.S)N(H)(CH.sub.2CF.sub.3)),
and
C(.dbd.S)N(H)(C((CH.sub.3).sub.2)C(.dbd.S)N(H)(CH.sub.2CF.sub.3)).
[0116] In another embodiment of this invention R11 is C(.dbd.(O or
S))N(H)(((C.sub.1-C.sub.8)alkyl)C(.dbd.(O or
S))N(H)(halo(C.sub.1-C.sub.8)alkyl)), which may be used in
combination with any embodiment of R1 through R10 and X1 through
X3.
[0117] In another embodiment of this invention R12 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0118] In another embodiment of this invention R12 is selected from
CH3, and H.
[0119] In another embodiment of this invention R13 may be selected
from any combination of one or more of the following--H, F, Cl, Br,
I, methyl, ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, halomethoxy, haloethoxy, halo(C.sub.3)alkoxy,
halo(C.sub.4)alkoxy, halo(C.sub.5)alkoxy, halo(C.sub.6)alkoxy,
halo(C.sub.7)alkoxy, and halo(C.sub.8)alkoxy.
[0120] In another embodiment of this invention R13 is selected from
CH.sub.3, Cl and H.
[0121] In another embodiment of this invention R12-R13 are a
hydrocarbyl linkage containing CH.dbd.CHCH.dbd.CH.
[0122] In another embodiment of this invention R14 may be selected
from any combination of one or more of the following--H, methyl,
ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methyl-aryl, ethyl-aryl, (C.sub.3)alkyl-aryl,
(C.sub.4)alkyl-aryl, (C.sub.5)alkyl-aryl, (C.sub.6)alkyl-aryl,
(C.sub.7)alkyl-aryl, (C.sub.8)alkyl-aryl,
methyl-(substituted-aryl), ethyl-(substituted-aryl),
(C.sub.3)alkyl-(substituted-aryl),
(C.sub.4)alkyl-(substituted-aryl),
(C.sub.5)alkyl-(substituted-aryl),
(C.sub.6)alkyl-(substituted-aryl),
(C.sub.7)alkyl-(substituted-aryl),
(C.sub.8)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,
O--(C.sub.3)alkyl-aryl, O--(C.sub.4)alkyl-aryl,
O--(C.sub.5)alkyl-aryl, O--(C.sub.6)alkyl-aryl,
O--(C.sub.7)alkyl-aryl, O--(C.sub.8)alkyl-aryl,
O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl),
O--(C.sub.3)alkyl-(substituted-aryl),
O--(C.sub.4)alkyl-(substituted-aryl),
O--(C.sub.5)alkyl-(substituted-aryl),
O--(C.sub.6)alkyl-(substituted-aryl),
O--(C.sub.7)alkyl-(substituted-aryl),
O--(C.sub.8)alkyl-(substituted-aryl), methyl-heterocyclyl,
ethyl-heterocyclyl, (C.sub.3)alkyl-heterocyclyl,
(C.sub.4)alkyl-heterocyclyl, (C.sub.5)alkyl-heterocyclyl,
(C.sub.6)alkyl-heterocyclyl, (C.sub.7)alkyl-heterocyclyl,
(C.sub.8)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl),
ethyl-(substituted-heterocyclyl),
(C.sub.3)alkyl-(substituted-heterocyclyl),
(C.sub.4)alkyl-(substituted-heterocyclyl),
(C.sub.5)alkyl-(substituted-heterocyclyl),
(C.sub.6)alkyl-(substituted-heterocyclyl),
(C.sub.7)alkyl-(substituted-heterocyclyl),
(C.sub.8)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,
O-ethyl-heterocyclyl, O--(C.sub.3)alkyl-heterocyclyl,
O--(C.sub.4)alkyl-heterocyclyl, O--(C.sub.5)alkyl-heterocyclyl,
O--(C.sub.6)alkyl-heterocyclyl, O--(C.sub.7)alkyl-heterocyclyl,
O--(C.sub.8)alkyl-heterocyclyl,
O-methyl-(substituted-heterocyclyl),
O-ethyl-(substituted-heterocyclyl),
O--(C.sub.3)alkyl-(substituted-heterocyclyl),
O--(C.sub.4)alkyl-(substituted-heterocyclyl),
O--(C.sub.5)alkyl-(substituted-heterocyclyl),
O--(C.sub.6)alkyl-(substituted-heterocyclyl),
O--(C.sub.7)alkyl-(substituted-heterocyclyl),
O--(C.sub.8)alkyl-(substituted-heterocyclyl),
methyl-C(.dbd.O)N(R16)(R17), ethyl-C(.dbd.O)N(R16)(R17),
(C.sub.3)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.4)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.5)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.6)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.7)alkyl-C(.dbd.O)N(R16)(R17), and
(C.sub.8)alkyl-C(.dbd.O)N(R16)(R17).
[0123] In another embodiment of this invention R14 may be selected
from any combination of one or more of the following--H, CH.sub.3,
CH.sub.2CF.sub.3, CH.sub.2-halopyridyl, oxo-pyrrolidinyl,
halophenyl, thietanyl, CH.sub.2-phenyl, CH.sub.2-pyridyl,
thietanyl-dioxide, CH.sub.2-halothiazolyl,
C((CH.sub.3).sub.2)-pyridyl, N(H)(halophenyl),
CH.sub.2-pyrimidinyl, CH.sub.2-tetrahydrofuranyl, CH.sub.2-furanyl,
O--CH.sub.2-halopyridyl, and
CH.sub.2C(.dbd.O)N(H)(CH.sub.2CF.sub.3).
[0124] In another embodiment of this invention R15 may be selected
from any combination of one or more of the following--H, methyl,
ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methyl-aryl, ethyl-aryl, (C.sub.3)alkyl-aryl,
(C.sub.4)alkyl-aryl, (C.sub.5)alkyl-aryl, (C.sub.6)alkyl-aryl,
(C.sub.7)alkyl-aryl, (C.sub.8)alkyl-aryl,
methyl-(substituted-aryl), ethyl-(substituted-aryl),
(C.sub.3)alkyl-(substituted-aryl),
(C.sub.4)alkyl-(substituted-aryl),
(C.sub.5)alkyl-(substituted-aryl),
(C.sub.6)alkyl-(substituted-aryl),
(C.sub.7)alkyl-(substituted-aryl),
(C.sub.8)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,
O--(C.sub.3)alkyl-aryl, O--(C.sub.4)alkyl-aryl,
O--(C.sub.5)alkyl-aryl, O--(C.sub.6)alkyl-aryl,
O--(C.sub.7)alkyl-aryl, O--(C.sub.8)alkyl-aryl,
O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl),
O--(C.sub.3)alkyl-(substituted-aryl),
O--(C.sub.4)alkyl-(substituted-aryl),
O--(C.sub.5)alkyl-(substituted-aryl),
O--(C.sub.6)alkyl-(substituted-aryl),
O--(C.sub.7)alkyl-(substituted-aryl),
O--(C.sub.8)alkyl-(substituted-aryl), methyl-heterocyclyl,
ethyl-heterocyclyl, (C.sub.3)alkyl-heterocyclyl,
(C.sub.4)alkyl-heterocyclyl, (C.sub.5)alkyl-heterocyclyl,
(C.sub.6)alkyl-heterocyclyl, (C.sub.7)alkyl-heterocyclyl,
(C.sub.8)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl),
ethyl-(substituted-heterocyclyl),
(C.sub.3)alkyl-(substituted-heterocyclyl),
(C.sub.4)alkyl-(substituted-heterocyclyl),
(C.sub.5)alkyl-(substituted-heterocyclyl),
(C.sub.6)alkyl-(substituted-heterocyclyl),
(C.sub.7)alkyl-(substituted-heterocyclyl),
(C.sub.8)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,
O-ethyl-heterocyclyl, O--(C.sub.3)alkyl-heterocyclyl,
O--(C.sub.4)alkyl-heterocyclyl, O--(C.sub.5)alkyl-heterocyclyl,
O--(C.sub.6)alkyl-heterocyclyl, O--(C.sub.7)alkyl-heterocyclyl,
O--(C.sub.8)alkyl-heterocyclyl,
O-methyl-(substituted-heterocyclyl),
O-ethyl-(substituted-heterocyclyl),
O--(C.sub.3)alkyl-(substituted-heterocyclyl),
O--(C.sub.4)alkyl-(substituted-heterocyclyl),
O--(C.sub.5)alkyl-(substituted-heterocyclyl),
O--(C.sub.6)alkyl-(substituted-heterocyclyl),
O--(C.sub.7)alkyl-(substituted-heterocyclyl),
O--(C.sub.8)alkyl-(substituted-heterocyclyl),
methyl-C(.dbd.O)N(R16)(R17), ethyl-C(.dbd.O)N(R16)(R17),
(C.sub.3)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.4)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.5)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.6)alkyl-C(.dbd.O)N(R16)(R17),
(C.sub.7)alkyl-C(.dbd.O)N(R16)(R17), and
(C.sub.8)alkyl-C(.dbd.O)N(R16)(R17).
[0125] In another embodiment of this invention R15 may be selected
from any combination of one or more of the following--H, CH.sub.3,
CH.sub.2CF.sub.3, CH.sub.2-halopyridyl, oxo-pyrrolidinyl,
halophenyl, thietanyl, CH.sub.2-phenyl, CH.sub.2-pyridyl,
thietanyl-dioxide, CH.sub.2-halothiazolyl,
C((CH.sub.3).sub.2)-pyridyl, N(H)(halophenyl),
CH.sub.2-pyrimidinyl, CH.sub.2-tetrahydrofuranyl, CH.sub.2-furanyl,
O--CH.sub.2-halopyridyl, and
CH.sub.2C(.dbd.O)N(H)(CH.sub.2CF.sub.3).
[0126] In another embodiment of this invention R16 may be selected
from any combination of one or more of the following--H, methyl,
ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methyl-aryl, ethyl-aryl, (C.sub.3)alkyl-aryl,
(C.sub.4)alkyl-aryl, (C.sub.5)alkyl-aryl, (C.sub.6)alkyl-aryl,
(C.sub.7)alkyl-aryl, (C.sub.8)alkyl-aryl,
methyl-(substituted-aryl), ethyl-(substituted-aryl),
(C.sub.3)alkyl-(substituted-aryl),
(C.sub.4)alkyl-(substituted-aryl),
(C.sub.5)alkyl-(substituted-aryl),
(C.sub.6)alkyl-(substituted-aryl),
(C.sub.7)alkyl-(substituted-aryl),
(C.sub.8)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,
O--(C.sub.3)alkyl-aryl, O--(C.sub.4)alkyl-aryl,
O--(C.sub.5)alkyl-aryl, O--(C.sub.6)alkyl-aryl,
O--(C.sub.7)alkyl-aryl, O--(C.sub.8)alkyl-aryl,
O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl),
O--(C.sub.3)alkyl-(substituted-aryl),
O--(C.sub.4)alkyl-(substituted-aryl),
O--(C.sub.5)alkyl-(substituted-aryl),
O--(C.sub.6)alkyl-(substituted-aryl),
O--(C.sub.7)alkyl-(substituted-aryl),
O--(C.sub.8)alkyl-(substituted-aryl), methyl-heterocyclyl,
ethyl-heterocyclyl, (C.sub.3)alkyl-heterocyclyl,
(C.sub.4)alkyl-heterocyclyl, (C.sub.5)alkyl-heterocyclyl,
(C.sub.6)alkyl-heterocyclyl, (C.sub.7)alkyl-heterocyclyl,
(C.sub.8)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl),
ethyl-(substituted-heterocyclyl),
(C.sub.3)alkyl-(substituted-heterocyclyl),
(C.sub.4)alkyl-(substituted-heterocyclyl),
(C.sub.5)alkyl-(substituted-heterocyclyl),
(C.sub.6)alkyl-(substituted-heterocyclyl),
(C.sub.7)alkyl-(substituted-heterocyclyl),
(C.sub.8)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,
O-ethyl-heterocyclyl, O--(C.sub.3)alkyl-heterocyclyl,
O--(C.sub.4)alkyl-heterocyclyl, O--(C.sub.5)alkyl-heterocyclyl,
O--(C.sub.6)alkyl-heterocyclyl, O--(C.sub.7)alkyl-heterocyclyl,
O--(C.sub.8)alkyl-heterocyclyl,
O-methyl-(substituted-heterocyclyl),
O-ethyl-(substituted-heterocyclyl),
O--(C.sub.3)alkyl-(substituted-heterocyclyl),
O--(C.sub.4)alkyl-(substituted-heterocyclyl),
O--(C.sub.5)alkyl-(substituted-heterocyclyl),
O--(C.sub.6)alkyl-(substituted-heterocyclyl),
O--(C.sub.7)alkyl-(substituted-heterocyclyl), and
O--(C.sub.8)alkyl-(substituted-heterocyclyl).
[0127] In another embodiment of this invention R16 may be selected
from any combination of one or more of the following--H,
CH.sub.2CF.sub.3, cyclopropyl, thietanyl, thietanyl dioxide, and
halophenyl.
[0128] In another embodiment of this invention R17 may be selected
from any combination of one or more of the following--H, methyl,
ethyl, (C.sub.3)alkyl, (C.sub.4)alkyl, (C.sub.5)alkyl,
(C.sub.6)alkyl, (C.sub.7)alkyl, (C.sub.8)alkyl, halomethyl,
haloethyl, halo(C.sub.3)alkyl, halo(C.sub.4)alkyl,
halo(C.sub.5)alkyl, halo(C.sub.6)alkyl, halo(C.sub.7)alkyl,
halo(C.sub.8)alkyl, methyl-aryl, ethyl-aryl, (C.sub.3)alkyl-aryl,
(C.sub.4)alkyl-aryl, (C.sub.5)alkyl-aryl, (C.sub.6)alkyl-aryl,
(C.sub.7)alkyl-aryl, (C.sub.8)alkyl-aryl,
methyl-(substituted-aryl), ethyl-(substituted-aryl),
(C.sub.3)alkyl-(substituted-aryl),
(C.sub.4)alkyl-(substituted-aryl),
(C.sub.5)alkyl-(substituted-aryl),
(C.sub.6)alkyl-(substituted-aryl),
(C.sub.7)alkyl-(substituted-aryl),
(C.sub.8)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl,
O--(C.sub.3)alkyl-aryl, O--(C.sub.4)alkyl-aryl,
O--(C.sub.5)alkyl-aryl, O--(C.sub.6)alkyl-aryl,
O--(C.sub.7)alkyl-aryl, O--(C.sub.8)alkyl-aryl,
O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl),
O--(C.sub.3)alkyl-(substituted-aryl),
O--(C.sub.4)alkyl-(substituted-aryl),
O--(C.sub.5)alkyl-(substituted-aryl),
O--(C.sub.6)alkyl-(substituted-aryl),
O--(C.sub.7)alkyl-(substituted-aryl),
O--(C.sub.8)alkyl-(substituted-aryl), methyl-heterocyclyl,
ethyl-heterocyclyl, (C.sub.3)alkyl-heterocyclyl,
(C.sub.4)alkyl-heterocyclyl, (C.sub.5)alkyl-heterocyclyl,
(C.sub.6)alkyl-heterocyclyl, (C.sub.7)alkyl-heterocyclyl,
(C.sub.8)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl),
ethyl-(substituted-heterocyclyl),
(C.sub.3)alkyl-(substituted-heterocyclyl),
(C.sub.4)alkyl-(substituted-heterocyclyl),
(C.sub.5)alkyl-(substituted-heterocyclyl),
(C.sub.6)alkyl-(substituted-heterocyclyl),
(C.sub.7)alkyl-(substituted-heterocyclyl),
(C.sub.8)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl,
O-ethyl-heterocyclyl, O--(C.sub.3)alkyl-heterocyclyl,
O--(C.sub.4)alkyl-heterocyclyl, O--(C.sub.5)alkyl-heterocyclyl,
O--(C.sub.6)alkyl-heterocyclyl, O--(C.sub.7)alkyl-heterocyclyl,
O--(C.sub.8)alkyl-heterocyclyl,
O-methyl-(substituted-heterocyclyl),
O-ethyl-(substituted-heterocyclyl),
O--(C.sub.3)alkyl-(substituted-heterocyclyl),
O--(C.sub.4)alkyl-(substituted-heterocyclyl),
O--(C.sub.5)alkyl-(substituted-heterocyclyl),
O--(C.sub.6)alkyl-(substituted-heterocyclyl),
O--(C.sub.7)alkyl-(substituted-heterocyclyl), and
O--(C.sub.7)alkyl-(substituted-heterocyclyl).
[0129] In another embodiment of this invention R17 may be selected
from any combination of one or more of the following--H,
CH.sub.2CF.sub.3, cyclopropyl, thietanyl, thietanyl dioxide, and
halophenyl.
[0130] In another embodiment of this invention X1 is CR12, X2 is
CR13, and X3 is CR9.
[0131] In another embodiment of this invention a heterocyclyl has
preferably about 6 to 10 atoms in the ring structure, more
preferably, 6 to 8 atoms.
[0132] The molecules of Formula One will generally have a molecular
mass of about 100 Daltons to about 1200 Daltons. However, it is
generally preferred if the molecular mass is from about 120 Daltons
to about 900 Daltons, and it is even more generally preferred if
the molecular mass is from about 140 Daltons to about 600
Daltons.
[0133] The benzyl alcohol of Formula IV, wherein R1, R2, R3, R4,
R5, R6, and R7 are as previously disclosed, can be synthesized in
two ways. One way, disclosed in step a of Scheme I, is by treatment
of the ketone of Formula II, wherein R1, R2, R3, R4, R5, and R6 are
as previously disclosed, with a reducing agent, such as sodium
borohydride (NaBH.sub.4), under basic conditions, such as aqueous
sodium hydroxide (NaOH), in a polar protic solvent, such as methyl
alcohol (MeOH) at 0.degree. C. Alternatively, an aldehyde of
Formula III, wherein R1, R2, R3, R4, R5, and R7 are as previously
disclosed, is allowed to react with trifluorotrimethylsilane in the
presence of a catalytic amount of tetrabutylammonium fluoride
(TBAF) in a polar aprotic solvent, such as tetrahydrofuran (THF),
as in step b of Scheme I. The compound of Formula IV can be
transformed into the compound of Formula V, wherein Y is selected
from Br, Cl or I, and R1, R2, R3, R4, R5, R6, and R7 are as
previously disclosed, by reaction with a halogenating reagent, such
as N-bromosuccinimide (NBS) and triethyl phosphite in a
non-reactive solvent, such as dichloromethane (CH.sub.2Cl.sub.2) at
reflux temperature to provide Y.dbd.Br, or such as thionyl chloride
and pyridine in a hydrocarbon solvent, such as toluene at reflux
temperature to provide Y.dbd.Cl, as in step c of Scheme I.
##STR00004##
[0134] Formation of the styrene coupling partners can be
accomplished as in Schemes II, III IV and V.
[0135] In Scheme II, a vinylbenzoic acid of Formula VI, wherein R11
is (C.dbd.O)OH and R8, R9, R10, R12, R13, X1, X2, and X3 are as
previously disclosed, can be converted in two steps to the
vinylbenzamide of Formula VIIa, wherein R11 is
(C.dbd.O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, and X
are as previously disclosed. As in step d of Scheme II, the benzoic
acid of Formula VI is treated with oxalyl chloride in the presence
of a catalytic amount of N,N-dimethylformamide (DMF) in a
non-reactive solvent such as CH.sub.2Cl.sub.2 to form the acid
chloride, which is subsequently allowed to react with an amine
(HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, in
the presence of a base, such as triethylamine (TEA), in a polar
aprotic solvent, such as THF, to provide the vinyl benzamide of
Formula VIIa, wherein R11 is (C.dbd.O)N(R14)(R15), and R8, R9, R10,
R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, as
in step e of Scheme II.
##STR00005##
[0136] In Schemes III and IV, a halobenzoic acid of Formula VIII,
wherein R18 is Br or I, R11 is (C.dbd.O)OH and R9, R10, R12, R13,
X1, X2, and X3 are as previously disclosed can be converted to a
vinylbenzoic acid ester of Formula VIIb1 or Formula VIIb2, wherein
R18 is Br or I, R11 is (C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R8,
R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. In
step f of Scheme III, the halobenzoic acid of Formula VIII, wherein
R18 is Br, is treated with a base, such as n-butyllithium (n-BuLi),
and DMF in a polar, aprotic solvent, such as THF, at a temperature
of about -78.degree. C. The resulting formyl benzoic acid is
allowed to react with an acid, such as sulfuric acid
(H.sub.2SO.sub.4), in the presence of an alcohol, such as ethyl
alcohol (EtOH), as in step g, to provide the formyl benzoic acid
ethyl ester of Formula IX, wherein R11 is
(C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R9, R10, R12, R13, X1, X2,
and X3 are as previously disclosed. The vinyl benzoic acid ester of
Formula VIIb1 is accessed via reaction of the compounds of Formula
IX, with a base, such as potassium carbonate (K.sub.2CO.sub.3), and
methyl triphenyl phosphonium bromide in a polar aprotic solvent,
such as 1,4-dioxane, at ambient temperature, as in step h of Scheme
III.
##STR00006##
[0137] In step i of Scheme IV, the halobenzoic acid of Formula
VIII, wherein R18 is Br, R11 is (C.dbd.O)OH, and R8, R9, R10, R12,
R13, X1, X2, and X3 are as previously disclosed, is treated with
di-tert-butyl dicarbonate in the presence of a base, such as TEA
and a catalytic amount of 4-(dimethylamino)pyridine (DMAP) in a
polar aprotic solvent, such as THF, at ambient temperature. The
resulting benzoic acid tert-butyl ester is allowed to react with
vinyl boronic anhydride pyridine complex in the presence of a
palladium catalyst, such a tetrakis(triphenylphospine)palladium(0)
(Pd(PPh.sub.3).sub.4), and a base, such as K.sub.2CO.sub.3, in a
non-reactive solvent such as toluene at reflux temperature, as in
step j, to provide the vinyl benzoic acid ester of Formula VIIb2,
wherein R11 is (C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R8, R9, R10,
R12, R13, X1, X2, and X3 are as previously disclosed.
##STR00007##
[0138] In step k of Scheme V, the vinyl benzoic acid ester of
Formula VIIb2, wherein R10 is Br, R11 is (C.dbd.O)O(C.sub.1-C.sub.6
alkyl), and R8, R9, R12, R13, X1, X2, and X3 are as previously
defined, can be further transformed into the corresponding vinyl
benzoic acid ester of Formula VIIb3, wherein R10 is CN, R11 is
(C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R8, R9, R12, R13, X1, X2,
and X3 are as previously disclosed, by reaction with copper(I)
cyanide (CuCN) in a polar aprotic solvent, such as DMF, at
140.degree. C.
##STR00008##
[0139] Coupling of the compounds of Formula V with the compounds of
Formula VIIa, VIIb1, VIIb2 and VIIb3 can be accomplished as in
Schemes VI, VII, and VIII. In step l of Scheme VI, a compound of
Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as
previously disclosed, and the vinylbenzamide of Formula VIIa,
wherein R11 is (C.dbd.O)N(R14)(R15), and R8, R9, R10, R12, R13,
R14, R15, X1, X2, and X3 are as previously disclosed, are allowed
to react in the presence of copper(I) chloride (CuCl) and
2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a
temperature of about 180.degree. C. to provide the molecules of
Formula One, wherein R11 is (C.dbd.O)N(R14)(R15), and R1, R2, R3,
R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are
as previously disclosed.
##STR00009##
[0140] In step l of Scheme VII, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the vinylbenzoic acid ester of Formula VIIb1, wherein R11 is
(C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R8, R9, R10, R12, R13, X1,
X2, and X3 are as previously disclosed, are allowed to react in the
presence of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the compounds of Formula Xa, wherein R11 is
(C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R1, R2, R3, R4, R5, R6, R7,
R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.
The compounds of Formula Xa are then converted to the molecules of
Formula One, wherein R11 is (C.dbd.O)N(R14)(R15), and R1, R2, R3,
R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are
as previously disclosed, by either a two-step process as disclosed
in steps m and n or in one step as disclosed in step o. In step m
of Scheme VII, the ester of Formula Xa is saponified to the
corresponding acid under acidic conditions, such as about 11 Normal
(N) hydrochloric acid (HCl), in a polar aprotic solvent, such as
1,4-dioxane, at about 100.degree. C. The acid can subsequently be
coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as
previously disclosed using peptide coupling reagents, such as
1-hydroxybenzotriazole (HOBt),
N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride
(EDC.HCl), benzotriazol-1-yl-oxytripyrrolidinophosphonium
hexafluorophosphate (PyBOP), 2-chloro-1,3-dimethylimidazolidinium
hexafluorophosphate (CIP), 1-hydroxy-7-azabenzotriazole (HOAt), or
O-benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluoro-phosphate
(HBTU) in the presence of a base, such as N,N-diisopropylethylamine
(DIPEA) or DMAP to give the molecules of Formula One, wherein R11
is (C.dbd.O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, R14, R15, X1, X2, and X3 are as previously
disclosed. Alternatively, the ester of Formula Xa is allowed to
react with an amine (HN(R14)(R15)) in the presence of a solution of
trimethylaluminum in toluene in a non-reactive solvent, such as
CH.sub.2Cl.sub.2, at ambient temperature, as in step o of Scheme
VII, to access the molecules of Formula One, wherein R11 is
(C.dbd.O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.
##STR00010##
[0141] In step l of Scheme VIII, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the vinylbenzoic acid ester of Formula VIIb2 or VIIb3, wherein R11
is (C.dbd.O)O(C.sub.1-C.sub.6 alkyl), and R8, R9, R10, R12, R13,
X1, X2, and X3 are as previously disclosed, are allowed to react in
the presence of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the compounds of Formula Xb, wherein R11 is (C.dbd.O)OH,
and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15,
X1, X2, and X3 are as previously disclosed. The compounds of
Formula Xb are then converted to the molecules of Formula One,
wherein R11 is (C.dbd.O)N(R14)(R15), and R1, R2, R3, R4, R5, R6,
R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as
previously disclosed, in one step as disclosed in step n. In step n
of Scheme VIII, the acid of Formula Xb can be coupled to an amine
(HN(R14)(R15)), wherein R14 and R15 are as previously disclosed,
using peptide coupling reagents, such as HOBt, EDC.HCl, PyBOP, CIP,
HOAt, or HBTU in the presence of a base, such as DIPEA or DMAP to
give the molecules of Formula One, wherein R11 is
(C.dbd.O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10,
R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.
##STR00011##
[0142] In step t of Scheme XIII, the vinyl benzyl chloride of
Formula XIa, wherein R11 is --CH.sub.2C.sub.1 and R8, R9, R10, R12,
R13, X1, X2, and X3 are as previously defined, can be transformed
into the corresponding phthalimide-protected benzyl amine of
Formula XIIa, wherein R11 is CH.sub.2N(Phthalimide), and R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with potassium phthalimide in a polar aprotic solvent,
such as DMF, at 70.degree. C.
##STR00012##
[0143] In step u of Scheme XIV, the 4-methylbenzonitrile of Formula
XIIIa, wherein R11 is CH.sub.3 and R9, R10, R12, R13, X1, X2, and
X3 are as previously defined, can be transformed into the
corresponding benzyl bromide of Formula XIVa, wherein R11 is
CH.sub.2Br and R8, R9, R10, R12, R13, X1, X2, and X3 are as
previously disclosed, by reaction with NBS and
azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as
carbon tetrachloride (CCl.sub.4) at 77.degree. C. The nitrile group
(CN) of Formula XIVa can be reduced to the corresponding aldehyde
of Formula XVa, wherein R11 is CH.sub.2Br and R9, R10, R12, R13,
X1, X2, and X3 are as previously defined via reaction with
diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as
toluene, at 0.degree. C., followed by quenching with 1.0 M HCl as
in step v of Scheme XIV. The compound of Formula XVa can be further
transformed to the corresponding phthalimide-protected benzyl amine
of Formula XVIa, wherein R11 is CH.sub.2N(Phthalimide) and R9, R10,
R12, R13, X1, X2, and X3 are as previously disclosed, by reaction
with potassium phthalimide in a polar aprotic solvent, such as DMF,
at 60.degree. C. as in step t of Scheme XIV. In step w of Scheme
XIV, the aldehyde of Formula XVIa can be converted to the olefin of
Formula XIIb, wherein R11 is CH.sub.2N(Phthalimide) and R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with methyl triphenyl phosphonium bromide in a polar
aprotic solvent, such as 1,4-dioxane, in the presence of a base,
such as K.sub.2CO.sub.3, at ambient temperature.
##STR00013##
[0144] The aldehyde of Formula XVa, wherein R11 is CH.sub.2Br and
R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be
reacted with a nucleophile, such as 2-aminopyridine, in a polar
aprotic solvent, such as N,N-dimethylacetamide (DMA), in the
presence of a base, such as K.sub.2CO.sub.3, at ambient temperature
to provide the compound of Formula XVII, wherein R11 is
CH.sub.2NH(2-pyridine) and R9, R10, R12, R13, X1, X2, and X3 are as
previously disclosed, as in step x of Scheme XV. In step w of
Scheme XV, the compound of Formula XVII can be converted to the
olefin of Formula XVIII, wherein R11 is CH.sub.2NH(2-pyridine) and
R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed.
##STR00014##
[0145] In a two-step, one-pot reaction as in steps y and z of
Scheme XVI, the compound of Formula XIX can be reacted with the
compounds of Formula XX, wherein R10 and R11 are Cl, X1 is N, and
R9, R13, X2, and X3 are as previously disclosed, in the presence of
a base, such as sodium hydride (NaH), and a polar aprotic solvent,
such as DMF, at ambient temperature to provide the compounds of
Formula XXI, wherein R10 is Cl, R11 is
(CH)NH.sub.2CO.sub.2CH.sub.2CH.sub.3, X1 is N, and R9, R13, X2, and
X3 are as previously defined.
[0146] Hydrolysis and decarboxylation of the compounds of Formula
XXI can be accomplished by reaction under acidic conditions, such
as with 3 N HCl, at reflux temperature, to afford the compounds of
Formula XXII, wherein R10 is Cl, R11 is CH.sub.2NH.sub.2.HCl, X1 is
N, and R9, R13, X2, and X3 are as previously disclosed, as in step
aa in Scheme XVI. The compounds of Formula XXII can be further
transformed to the corresponding phthalimide-protected benzyl
amines of Formula XXIIIa, wherein R10 is Cl, R11 is
CH.sub.2N(Phthalimide), X1 is N, and R9, R13, X1, X2, and X3 are as
previously disclosed, by reaction with phthalic anhydride in the
presence of a base, such as TEA, and an aprotic solvent, such as
toluene, at reflux temperature as in step ab of Scheme XVI. The
bromide of Formula XXIIIa can be converted to the olefin of Formula
XIIc, wherein R10 is Cl, R11 is CH.sub.2N(Phthalimide), X1 is N,
and R8, R9, R13, X2 and X3 are as previously disclosed, by reaction
with vinyl boronic anhydride pyridine complex in the presence of a
palladium catalyst, such as Pd(PPh.sub.3).sub.4, and a base, such
as K.sub.2CO.sub.3, in a non-reactive solvent such as toluene at
reflux temperature, as in step ac of Scheme XVI.
##STR00015##
[0147] In step u of Scheme XVII, the 4-methylnaphthonitrile of
Formula XIIIb, wherein X3 is CR9, R10 and X3 together form a
linkage having 4 carbon atoms and with the ring carbon atoms form a
6-membered aromatic ring, R11 is CH.sub.3, and R12, R13, X1 and X2
are as previously defined, can be transformed into the
corresponding naphthyl bromide of Formula XIVb, wherein X3 is CR9,
R10 and X3 together form a linkage having 4 carbon atoms and with
the ring carbon atoms form a 6-membered aromatic ring, R11 is
CH.sub.2Br, and R12, R13, X1 and X2 are as previously disclosed, by
reaction with NBS and AIBN in a non-reactive solvent, such as
CCl.sub.4 at 77.degree. C. The nitrile group (CN) of Formula XIVb
can be reduced to the corresponding aldehyde of Formula XVb,
wherein X3 is CR9, R10 and X3 together form a linkage having 4
carbon atoms and with the ring carbon atoms form a 6-membered
aromatic ring (or if desired a non-aromatic ring), R11 is
CH.sub.2Br, and R12, R13, X1 and X2 are as previously defined via
reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic
solvent, such as toluene, at 0.degree. C., followed by quenching
with 1.0 M HCl as in step v of Scheme XVII. The compound of Formula
XVb can be further transformed to the corresponding
phthalimide-protected benzyl amine of Formula XVIb, wherein X3 is
CR9, R10 and X3 together form a linkage having 4 carbon atoms and
with the ring carbon atoms form a 6-membered aromatic ring, R11 is
CH.sub.2N(Phthalimide), and R12, R13, X1 and X2 are as previously
disclosed, by reaction with potassium phthalimide in a polar
aprotic solvent, such as DMF, at 60.degree. C. as in step t of
Scheme XVII. In step w of Scheme XVII, the aldehyde of Formula XVIb
can be converted to the olefin of Formula XIId, wherein X3 is CR9,
R10 and X3 together form a linkage having 4 carbon atoms and with
the ring carbon atoms form a 6-membered aromatic ring, R11 is
CH.sub.2N(Phthalimide), and R8, R12, R13, X1 and X2 are as
previously disclosed, by reaction with methyl triphenyl phosphonium
bromide in a polar aprotic solvent, such as 1,4-dioxane, in the
presence of a base, such as K.sub.2CO.sub.3, at ambient
temperature.
##STR00016##
[0148] The compound of Formula XXIV, wherein R11 is NHNH.sub.2.HCl
and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed,
can be transformed into the corresponding phthalimide-protected
hydrazine of Formula XXV, wherein R11 is NHN(Phthalimide) and R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with phthalic anhydride in glacial acetic acid (AcOH) at
reflux temperature as in step ad of Scheme XVIII. The bromide of
Formula XXV can be converted to the olefin of Formula XIIe, wherein
R11 is NHN(Phthalimide) and R8, R9, R10, R13, X1, X2 and X3 are as
previously disclosed, by reaction with vinyl boronic anhydride
pyridine complex in the presence of a palladium catalyst, such as
Pd(PPh.sub.3).sub.4, and a base, such as K.sub.2CO.sub.3, in a
polar aprotic solvent such as 1,2-dimethoxyethane at 150.degree. C.
under microwave conditions, as in step ae of Scheme XVIII.
##STR00017##
[0149] In step af of Scheme XIX, the compound of Formula XXVI,
wherein R11 is B(OH).sub.2, and R8, R9, R10, R12, R13, X1, X2, and
X3 are as previously disclosed, are allowed to react with
2-hydroxyisoindoline-1,3-dione in the presence of CuCl and pyridine
in a solvent, such as 1,2-dichlorobenzene, at ambient temperature
to provide the compound of Formula XIIf, wherein R11 is
ON(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as
previously disclosed.
##STR00018##
[0150] In step l of Scheme XX, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XIIa, wherein R11 is
CH.sub.2N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3
are as previously disclosed, are allowed to react in the presence
of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compounds of Formula XXVIIa, wherein R11
is CH.sub.2N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed. The
phthalimide protecting group in the compounds of Formula XXVIIa is
removed as in step ag of Scheme XX by reaction with hydrazine
hydrate in a polar protic solvent such as EtOH at 90.degree. C. to
provide the compounds of Formula XXVIIIa, wherein R11 is
CH.sub.2NH.sub.2 and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,
R13, X1, X2, and X3 are as previously disclosed. The compounds of
Formula XXVIIIa can be transformed into the compounds of Formula
One, wherein R11 is CH.sub.2N(C.dbd.O)(R14) and R1, R2, R3, R4, R5,
R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed, by acylation with an anhydride, such as acetic
anhydride, and a base, such as TEA, in a non-reactive solvent such
as CH.sub.2Cl.sub.2 at 0.degree. C. as in step ah.sub.1 of Scheme
XX.
##STR00019##
[0151] In step l of Scheme XXI, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XIIb, wherein R11 is
CH.sub.2N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3
are as previously disclosed, are allowed to react in the presence
of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compounds of Formula XXVIIb, wherein R11
is CH.sub.2N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed. The
phthalimide protecting group in the compounds of Formula XXVIIb is
removed as in step ag of Scheme XXI by reaction with hydrazine
hydrate in a polar protic solvent such as EtOH at 90.degree. C. to
provide the compounds of Formula XXVIIIb, wherein R11 is
CH.sub.2NH.sub.2 and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,
R13, X1, X2, and X3 are as previously disclosed. The compounds of
Formula XXVIIIb can be transformed into the compounds of Formula
One, wherein R11 is CH.sub.2N(C.dbd.O)(R14) and R1, R2, R3, R4, R5,
R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed, by reaction with an acid in the presence of
HOBt.H.sub.2O, EDC.HCl and a base, such as DIPEA, in a polar
aprotic solvent, such as DMF, as in step ah.sub.2a of Scheme
XXI.
[0152] In another embodiment, the compounds of Formula XXVIIIb can
be transformed into the compounds of Formula One, wherein R11 is
CH.sub.2N(C.dbd.S)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with a thioacid in the presence of HOBt.H.sub.2O, EDC.HCl
and a base, such as DIPEA, in a polar aprotic solvent, such as DMF,
as in step ah.sub.2 of Scheme XXI.
[0153] In another embodiment, the compounds of Formula XXVIIIb can
be transformed into the compounds of Formula One, wherein R11 is
CH.sub.2N(C.dbd.O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8,
R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, in
two steps. The first step (step ah.sub.3a of Scheme XXI) involves
reaction with an aldehyde in a polar protic solvent such as MeOH,
followed by reaction with NaBH.sub.4. The second step (step
ah.sub.3b of Scheme XXI) involves acylation with an acid chloride,
such as cyclopropylcarbonyl chloride, and a base, such as TEA, in a
non-reactive solvent such as CH.sub.2Cl.sub.2 at ambient
temperature of Scheme XXI.
[0154] In another embodiment, the compounds of Formula XXVIIIb can
be transformed into the compounds of Formula One, wherein R11 is
CH.sub.2N(C.dbd.O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8,
R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with an isocyanate (step ai.sub.1 of Scheme XXI) or a
carbamoyl chloride (step ai.sub.2 of Scheme XXI) in the presence of
a base such as TEA and in a non-reactive solvent such as
CH.sub.2Cl.sub.2 at 0.degree. C.
[0155] In another embodiment, the compounds of Formula XXVIIIb can
be transformed into the compounds of Formula One, wherein R11 is
CH.sub.2N(C.dbd.S)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8,
R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with an isothiocyanate in the presence of a base such as
TEA and in a non-reactive solvent such as CH.sub.2Cl.sub.2 at
0.degree. C., as in steps aj of Scheme XXI.
[0156] In another embodiment, the compounds of Formula XXVIIIb can
be transformed into the compounds of Formula One, wherein R11 is
CH.sub.2N(C.dbd.O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed, by
reaction with a dicarbonate, such as di-tert-butyl dicarbonate in
the presence of a base such as TEA and in a non-reactive solvent
such as CH.sub.2Cl.sub.2 at ambient temperature, as in steps ak of
Scheme XXI.
[0157] In yet another embodiment, the compounds of Formula XXVIIIb
can be transformed into the compounds of Formula One, wherein R11
is CH.sub.2N(C.dbd.O)(C.dbd.O)O(R14) and R1, R2, R3, R4, R5, R6,
R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed, by reaction with a chlorooxalic acid ester, such as
2-chloro-2-oxoacetate in the presence of a base such as TEA and in
a non-reactive solvent such as CH.sub.2Cl.sub.2 at 0.degree. C., as
in steps al of Scheme XXI.
##STR00020##
[0158] In step l of Scheme XXII, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XIIc, wherein R10 is C.sub.1, R11 is
CH.sub.2N(Phthalimide), X1 is N, and R8, R9, R12, R13, X2, and X3
are as previously disclosed, are allowed to react in the presence
of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compounds of Formula XXVIIc, wherein R10
is Cl, R11 is CH.sub.2N(Phthalimide), X1 is N, and R1, R2, R3, R4,
R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously
disclosed. The phthalimide protecting group in the compounds of
Formula XXVIIc is removed as in step ag of Scheme XXII by reaction
with hydrazine hydrate in a polar protic solvent such as EtOH at
90.degree. C. to provide the compounds of Formula XXVIIIc, wherein
R10 is C.sub.1, R11 is CH.sub.2NH.sub.2, X1 is N, and R1, R2, R3,
R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously
disclosed. The compounds of Formula XXVIIIc can be transformed into
the compounds of Formula One, wherein R10 is Cl, R11 is
CH.sub.2N(C.dbd.O)(R14), X1 is N, and R1, R2, R3, R4, R5, R6, R7,
R8, R9, R12, R13, X2, and X3 are as previously disclosed, by
reaction with an acid in the presence of HOBt.H.sub.2O, EDC.HCl and
a base, such as DIPEA, in a polar aprotic solvent, such as
CH.sub.2Cl.sub.2, as in step ah.sub.2b of Scheme XXII.
##STR00021##
[0159] In step l of Scheme XXIII, the compound of Formula V,
wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously
disclosed, and the compounds of Formula XIId, wherein X3 is CR9,
R10 and X3 together form a linkage having 4 carbon atoms and with
the ring carbon atoms form a 6-membered aromatic ring (or if
desired a non-aromatic ring), R11 is CH.sub.2N(Phthalimide) and R8,
R9, R12, R13, X1 and X2 are as previously disclosed, are allowed to
react in the presence of CuCl and 2,2-bipyridyl in a solvent, such
as 1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compounds of Formula XXVIId, wherein X3
is CR9, R10 and X3 together form a linkage having 4 carbon atoms
and with the ring carbon atoms form a 6-membered aromatic ring, R11
is CH.sub.2N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R12, R13, X1 and X2 are as previously disclosed. The phthalimide
protecting group in the compounds of Formula XXVIId is removed as
in step ag of Scheme XXIII by reaction with hydrazine hydrate in a
polar protic solvent such as EtOH at 90.degree. C. to provide the
compounds of Formula XXVIIId, wherein X3 is CR9, R10 and X3
together form a linkage having 4 carbon atoms and with the ring
carbon atoms form a 6-membered aromatic ring, R11 is
CH.sub.2NH.sub.2 and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13,
X1 and X2 are as previously disclosed. The compounds of Formula
XXVIIId can be transformed into the compounds of Formula One,
wherein X3 is CR9, R10 and X3 together form a linkage having 4
carbon atoms and with the ring carbon atoms form a 6-membered
aromatic ring, R11 is CH.sub.2N(C.dbd.O)(R14) and R1, R2, R3, R4,
R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously
disclosed, by reaction with an acid in the presence of
HOBt.H.sub.2O, EDC.HCl and a base, such as DIPEA, in a polar
aprotic solvent, such as CH.sub.2Cl.sub.2, as in step ah.sub.2b of
Scheme XXIII.
[0160] In another embodiment, the compounds of Formula XXVIIId can
be transformed into the compounds of Formula One, wherein X3 is
CR9, R10 and X3 together form a linkage having 4 carbon atoms and
with the ring carbon atoms form a 6-membered aromatic ring, R11 is
CH.sub.2N(C.dbd.O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8,
R9, R10, R12, R13, X1 and X2 are as previously disclosed, by
reaction with an isocyanate in the presence of a base such as TEA
and in a non-reactive solvent such as CH.sub.2Cl.sub.2 at 0.degree.
C. as in step ai.sub.1 of Scheme XXIII.
##STR00022##
[0161] In step l of Scheme XXIV, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XIIe, wherein R11 is NHN(Phthalimide) and
R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, are
allowed to react in the presence of CuCl and 2,2-bipyridyl in a
solvent, such as 1,2-dichlorobenzene, at a temperature of about
180.degree. C. to provide the corresponding compounds of Formula
XXVIIe, wherein R11 is NHN(Phthalimide) and R1, R2, R3, R4, R5, R6,
R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed.
The phthalimide protecting group in the compounds of Formula XXVIIe
is removed as in step ag of Scheme XXIV by reaction with hydrazine
hydrate in a polar protic solvent such as EtOH at 90.degree. C. to
provide the compounds of Formula XXVIIIe, wherein R11 is NHNH.sub.2
and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3
are as previously disclosed. The compounds of Formula XXVIIIe can
be transformed into the compounds of Formula One, wherein R11 is
NHN(C.dbd.O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13,
X1, X2, and X3 are as previously disclosed, by reaction with an
acid in the presence of HOBt.H.sub.2O, EDC.HCl and a base, such as
DIPEA, in a polar aprotic solvent, such as CH.sub.2Cl.sub.2, as in
step ah.sub.2b of Scheme XXIV.
##STR00023##
[0162] In step l of Scheme XXV, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XIIf, wherein R11 is ON(Phthalimide) and
R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed,
are allowed to react in the presence of CuCl and 2,2-bipyridyl in a
solvent, such as 1,2-dichlorobenzene, at a temperature of about
180.degree. C. to provide the corresponding compounds of Formula
XXVIIf, wherein R11 is ON(Phthalimide) and R1, R2, R3, R4, R5, R6,
R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed. The phthalimide protecting group in the compounds of
Formula XXVIIf is removed as in step ag of Scheme XXV by reaction
with hydrazine hydrate in a polar protic solvent such as EtOH at
90.degree. C. to provide the compounds of Formula XXVIIIf, wherein
R11 is ONH.sub.2 and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12,
R13, X1, X2, and X3 are as previously disclosed. The compounds of
Formula XXVIIIf can be transformed into the compounds of Formula
One, wherein R11 is ON(C.dbd.O)(R14) and R1, R2, R3, R4, R5, R6,
R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously
disclosed, by reaction with an acid in the presence of
HOBt.H.sub.2O, EDC.HCl and a base, such as DIPEA, in a polar
aprotic solvent, such as CH.sub.2Cl.sub.2, as in step ah.sub.2b of
Scheme XXV.
##STR00024##
[0163] In step l of Scheme XXVI, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XVIII, wherein R11 is
CH.sub.2NH(2-pyridine) and R8, R9, R10, R12, R13, X1, X2, and X3
are as previously disclosed, are allowed to react in the presence
of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compounds of Formula One, wherein R11 is
CH.sub.2NH(2-pyridine), and R1, R2, R3, R4, R5, R6, R7, R8, R9,
R10, R12, R13, X1, X2, and X3 are as previously disclosed.
[0164] The compounds of Formula One can be further elaborated by
standard methods. For example, when R11 contains a thioether, the
thioether can be oxidized to the sulfone by treatment with oxone in
the presence of an acetone:water mixture at ambient temperature.
When R11 contains an oxalate ester, the compound of Formula One can
be transformed into the corresponding oxalamide by reaction with an
amine hydrochloride and a solution of trimethylaluminum in toluene
in a non-reactive solvent such as CH.sub.2Cl.sub.2.
##STR00025##
[0165] In Scheme XXVII, a fluorobenzaldehyde of Formula XXIX,
wherein R10, X1, X2, and X3 are as previously disclosed can be
converted to a (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX,
wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl
group, and R10, X1, X2, and X3 are as previously disclosed by
reaction with a substituted or unsubstituted 1,2,4-triazole in the
presence of a base, such as K.sub.2CO.sub.3, in a solvent such as
DMF as in step aj. In step ak, the (1,2,4-triazol-1-yl)benzaldehyde
of Formula XXX is converted to a (1,2,4-triazol-1-yl)vinyl benzene
of Formula XXXIa wherein R11 is a substituted or unsubstituted
1,2,4-triazol-1-yl group, and R8, R10, X1, X2, and X3 are as
previously disclosed by reaction with triphenyl phosphonium bromide
in the presence of a base, such as K.sub.2CO.sub.3, in an aprotic
solvent, such as 1,4-dioxane.
##STR00026##
[0166] In Scheme XXVIII, a bromofluorobenzene of Formula XXXII,
wherein R10, X1, X2, and X3 are as previously disclosed can be
converted to a (1,2,4-triazol-1-yl)vinylbenzene of Formula XXXIb,
wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl
group, and R8, R10, X1, X2, and X3 are as previously disclosed in
two steps. In step al, the bromofluorobenzene is reacted with a
substituted or unsubstituted 1,2,4-triazole in the presence of a
base, such as K.sub.2CO.sub.3, in a solvent such as DMF to generate
the (1,2,4-triazol-1-yl)bromobenzene. In step cl, the
(1,2,4-triazol-1-yl)bromobenzene is reacted with vinyl boronic
anhydride pyridine complex in the presence of a catalyst, such as
Pd(PPh.sub.3).sub.4, and a base, such as K.sub.2CO.sub.3 in a
solvent such as toluene.
##STR00027##
[0167] Coupling of the compounds of Formula V with compounds of
Formula XXXIa and XXXIb can be accomplished as in Schemes XXIX. In
step l, a compound of Formula V, wherein Y is Br, R1, R2, R3, R4,
R5, R6, and R7 are as previously disclosed, and a vinylbenzene of
Formula XXXIa or XXXIb, wherein R11 is a substituted or
unsubstituted 1,2,4-triazol-1-yl group, and R8, R9, R10, X1, X2,
and X3 are as previously disclosed, are allowed to react in the
presence of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the molecules of Formula One, wherein R11 is a substituted
or unsubstituted 1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5,
R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed.
##STR00028##
[0168] In Scheme XXX, compounds of Formula XXXIII wherein R11 is a
3-nitro-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7,
R8, R10, X1, X2, and X3 are as previously disclosed can be
converted to compounds of Formula One, wherein R11 is a
3-amido-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7,
R8, R10, X1, X2, and X3 are as previously disclosed by a two-step
process. In step am, the 3-nitro-1,2,4-triazol-1-yl group is
reduced to a 3-amino-1,2,4-triazol-1-yl group in the presence of
zinc dust and ammonium chloride (NH.sub.4Cl) in a protic solvent,
such as MeOH. In step an, the 3-amino-1,2,4-triazol-1-yl group is
acylated with an acid chloride, such as cyclopropylcarbonyl
chloride or acetyl chloride, in the presence of a base, such as
TEA, in a solvent such as CH.sub.2Cl.sub.2.
##STR00029##
[0169] In step ao of Scheme XXXI, a bromophenyl methyl ketone of
Formula XXXIV wherein R10, X1, X2, and X3 are as previously
disclosed is converted to an phenyl methyl ketone of the Formula
XXXV wherein R11 is a 1,2,4-triazol-1-yl group, and R10, X1, X2,
and X3 are as previously disclosed by treatment with 1,2,4-triazole
in the presence of a base, such as cesium carbonate
(Cs.sub.2CO.sub.3), and a catalyst, such as copper iodide (CuI), in
a solvent, such as DMF. In step ap, the 1,2,4-triazolylacetophenone
of Formula XXXV is converted to the trimethylsilyl enol ether of
Formula XXXVI by treatment with trimethylsilyl
trifluoromethanesulfonate in the presence of a base, such as TEA,
in an aprotic solvent, such as CH.sub.2Cl.sub.2. In step aq, the
silyl enol ether is reacted with a compound of Formula V, wherein Y
is Br, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed
in the presence of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene at a temperature of about 180.degree. C. to
generate a ketone of the Formula XXXVII, wherein R11 is a
1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R10, X1,
X2, and X3 are as previously disclosed. In step ar, the ketone of
the Formula XXXVII is treated with methylmagnesium bromide in an
aprotic solvent, such as THF to generate the tertiary alcohol. The
tertiary alcohol then undergoes an elimination reaction when
treated with a catalytic amount of p-toluenesulfonic acid in a
solvent, such as toluene, when heated to a temperature to allow
azeotropic removal of water to produce compounds of Formula One
wherein R11 is a 1,2,4-triazol-1-yl group, R8 is methyl, and R1,
R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previously
disclosed, as in step as.
##STR00030##
[0170] In Scheme XXXII, a compound of Formula XXXVIII, wherein R10
and R11 together form a linkage, having 3-4 carbon atoms and an oxo
substituent and with the ring carbon atoms form a 5- or 6-membered
cyclic ring, and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are
as previously disclosed is converted to a molecule of Formula One,
wherein R10 and R11 together form a linkage, having 3-4 carbon
atoms and an alkylamine substituent with the ring carbon atoms form
a 5- or 6-membered cyclic ring and R1, R2, R3, R4, R5, R6, R7, R8,
X1, X2, and X3 are as previously disclosed, by treatment with an
alkylamine, such as 3,3,3-trifluoropropylamine, in the presence of
a reducing agent, such as sodium cyanoborohydride (NaBH.sub.3CN),
in a solvent, such as 1,2-dichloroethane (DCE).
##STR00031##
[0171] In Scheme XXXIII, a compound of Formula XXXIX, wherein X1,
X2, and X3 are as previously disclosed is converted to a molecule
of Formula XL, wherein X1, X2, and X3 are as previously disclosed,
by treatment with a reducing agent, such as NaBH.sub.3CN, in a
solvent, such as AcOH, as in step au. In step av, the nitrogen atom
is protected with a tert-butyloxycarbonyl (BOC) group by reaction
with di-tert-butyl dicarbonate in the presence of a catalyst, such
as DMAP, in a solvent, such as acetonitrile (MeCN). The bromide of
Formula XL can be converted to the olefin of Formula XLI, wherein
R8, X1, X2 and X3 are as previously disclosed, by reaction with
potassium vinyl trifluoroborate in the presence of a palladium
catalyst, such as PdCl.sub.2(dppf), and a base, such as
K.sub.2CO.sub.3, in a polar aprotic solvent such as
dimethylsulfoxide (DMSO) at 100.degree. C., as in step aw.
##STR00032##
[0172] In Scheme XXXIV, a compound of Formula XXXIX, wherein X1,
X2, and X3 are as previously disclosed is converted to a molecule
of Formula XLII, wherein X1, X2, and X3 are as previously disclosed
in two steps. In step ax, the olefin is formed by treatment of the
bromide with potassium vinyl trifluoroborate in the presence of a
palladium catalyst, such as PdCl.sub.2, and a ligand, such as
triphenylphosphine, and a base, such as Cs.sub.2CO.sub.3, in a
solvent mixture such as THF/water. In step ay, the nitrogen atom is
protected with a BOC group by reaction with di-tert-butyl
dicarbonate in the presence of a catalyst, such as DMAP, in a
solvent, such as MeCN.
##STR00033##
[0173] In step l of Scheme XXXV, the compound of Formula V, wherein
Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and
the compounds of Formula XLI or XLII, wherein R8, X1, X2 and X3 are
as previously disclosed, are allowed to react in the presence of
CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene,
at a temperature of about 150.degree. C. to provide the
corresponding compounds of Formula XLIIIa or XLIIIb, wherein R1,
R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously
disclosed.
##STR00034##
[0174] In Scheme XXXVI, a compound of Formula XLIIIa, wherein R1,
R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously
disclosed is converted to a molecule of Formula XLIV, wherein R1,
R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously
disclosed by treatment with trifluoroacetic acid (TFA), in a
solvent such as CH.sub.2Cl.sub.2, as in step az. Compounds of the
Formula XLIV can then be transformed into compounds of the Formula
XLV wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as
previously disclosed, in two steps. In step ba, the indoline is
treated with sodium nitrite (NaNO.sub.2), in an acid, such as
concentrated HCl, at a temperature around 5.degree. C., to form the
nitrosoindole. In step bb, the nitrosoindole is reacted with
NH.sub.4Cl in the presence of zinc powder in a protic solvent, such
as MeOH. In step be, compounds of the Formula XLV are transformed
into compounds of the Formula XLVI, wherein X4 is
N(R14)(C(.dbd.O)R14) and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2,
and X3 are as previously disclosed, by treatment with and acid,
such as 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as
DIPEA, in a polar aprotic solvent, such as CH.sub.2Cl.sub.2.
##STR00035##
[0175] In Scheme XXXVII, a compound of Formula XLIIIb, wherein R1,
R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously
disclosed is converted to an indole of Formula XLVII, wherein R1,
R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously
disclosed by treatment with TFA, in a solvent such as
CH.sub.2Cl.sub.2, as in step bd. Compounds of the Formula XLVII can
be transformed into compounds of the Formula XLVIII wherein R1, R2,
R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed,
by reaction with
4-nitrophenyl-2-((tert-butoxycarbonyl)amino)acetate in the presence
of potassium fluoride (KF) and a crown ether, such as
18-crown-6-ether, in a solvent, such as MeCN, as in step be.
Compounds of the Formula XLVIII can be transformed into compounds
of the Formula XLIX, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1,
X2, and X3 are as previously disclosed in two steps. In step bf,
the Boc group is removed by treatment with TFA, in a solvent such
as CH.sub.2Cl.sub.2. In step bg, the amine is treated with
3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in
a polar aprotic solvent, such as CH.sub.2Cl.sub.2.
##STR00036##
[0176] In Scheme XXXVIII, a compound of Formula L, wherein X1, X2,
and X3 are as previously disclosed is converted to a compound of
the Formula LI, wherein X1, X2, and X3 are as previously disclosed
by treatment with copper (II) sulfate pentahydrate and Zn powder in
a base, such as NaOH as in step bh. Compounds of the Formula LI can
be transformed into compounds of the Formula LII wherein X1, X2,
and X3 are as previously disclosed, by reaction with hydrazine, in
a solvent such as water, at a temperature around 95.degree. C., as
in step bi. In step bj, the olefin of the Formula LIII wherein X1,
X2, and X3 are as previously disclosed is formed by treatment of
the bromide with potassium vinyl trifluoroborate in the presence of
a palladium catalyst, such as PdCl.sub.2(dppf), and a base, such as
K.sub.2CO.sub.3, in a solvent mixture such as DMSO. Compounds of
the Formula LIV, wherein X1, X2, and X3 are as previously
disclosed, can be formed from compounds of the Formula LIII by
reaction with ethyl bromoacetate, in the presence of a base, such
as Cs.sub.2CO.sub.3, in a solvent, such as DMF.
##STR00037##
[0177] In step l of Scheme XXXIX, the compound of Formula V,
wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously
disclosed, and the compound of Formula LIV, wherein R8, X1, X2 and
X3 are as previously disclosed, are allowed to react in the
presence of CuCl and 2,2-bipyridyl in a solvent, such as
1,2-dichlorobenzene, at a temperature of about 180.degree. C. to
provide the corresponding compound of Formula LV, wherein R1, R2,
R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed.
The compound of Formula LV can be further transformed into a
compound of the Formula LVI, wherein R1, R2, R3, R4, R5, R6, R7,
R8, X1, X2, and X3 are as previously disclosed, in two steps. In
step bl, the ester is hydrolyzed to the acid in the presence of HCl
and AcOH, at a temperature of about 100.degree. C. In step bm, the
acid is treated with an amine, such as 2,2,2-trifluoroethylamine,
PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such
as CH.sub.2Cl.sub.2.
##STR00038##
[0178] In step bn of Scheme XL, carboxylic acids of the Formula
LVII, wherein R11 is C(.dbd.O)OH and R8, R10, X1, X2, and X3 are as
previously disclosed and compounds of the Formula V, wherein Y is
Br and R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed
are allowed to react in the presence of CuCl and 2,2-bipyridyl in a
solvent, such as N-methyl pyrrolidine, at a temperature of about
150.degree. C. to afford compounds of Formula LVIII, wherein R11 is
(C.dbd.O)OH and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2,
and X3 are as previously disclosed. Compounds of the Formula LVIII
can be further transformed to the corresponding benzamides of
Formula LIX, wherein R11 is (C.dbd.O)N(R14)(R15), and R1, R2, R3,
R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previously
disclosed, by treatment with an amine, such as
2-amino-N-(2,2,2-trifluoroethyl)acetamide, PyBOP, and a base, such
as DIPEA, in a polar aprotic solvent, such as CH.sub.2Cl.sub.2, as
in step bo.
##STR00039##
EXAMPLES
[0179] The examples are for illustration purposes and are not to be
construed as limiting the invention disclosed in this document to
only the embodiments disclosed in these examples.
[0180] Starting materials, reagents, and solvents that were
obtained from commercial sources were used without further
purification. Anhydrous solvents were purchased as Sure/Seal.TM.
from Aldrich and were used as received. Melting points were
obtained on a Thomas Hoover Unimelt capillary melting point
apparatus or an OptiMelt Automated Melting Point System from
Stanford Research Systems and are uncorrected. Molecules are given
their known names, named according to naming programs within ISIS
Draw, ChemDraw, or ACD Name Pro. If such programs are unable to
name a molecule, the molecule is named using conventional naming
rules. .sup.1H NMR spectral data are in ppm (.delta.) and were
recorded at 300, 400, or 600 MHz, and .sup.13C NMR spectral data
are in ppm (.delta.) and were recorded at 75, 100, or 150 MHz,
unless otherwise stated.
Example 1: Preparation of
1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)
##STR00040##
[0181] Step 1 Method A.
1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)
[0182] To a stirred solution of
1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (procured from Rieke
Metals, UK; 5.0 grams (g), 20.5 millimoles (mmol)) in MeOH (100
milliliters (mL)) at 0.degree. C. were added NaBH.sub.4 (3.33 g,
92.5 mL) and 1 N aqueous NaOH solution (10 mL). The reaction
mixture was warmed to 25.degree. C. and stirred for 2 hours (h).
After the reaction was deemed complete by thin layer chromatography
(TLC), saturated aqueous NH.sub.4Cl solution was added to the
reaction mixture, and the mixture was concentrated under reduced
pressure. The residue was diluted with diethyl ether (Et.sub.2O)
and washed with water (3.times.50 mL). The organic layer was dried
over sodium sulfate (Na.sub.2SO.sub.4) and concentrated under
reduced pressure to afford the title compound as a liquid (4.0 g,
79%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.41 (m, 3H), 5.00
(m, 2H), 2.74 (s, 1H); ESIMS m/z 242.97 ([M-H].sup.-).
Step 1 Method B. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol
(AI2)
[0183] To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57
mmol) in THF (250 mL) were added trifluoromethyltrimethylsilane
(9.79 g, 69.2 mmol) and a catalytic amount of TBAF. The reaction
mixture was stirred at 25.degree. C. for 8 h. After the reaction
was deemed complete by TLC, the reaction mixture was diluted with 3
N HCl and then was stirred for 16 h. The reaction mixture was
diluted with water and was extracted with ethyl acetate (EtOAc; 3
x). The combined organic extracts were washed with brine, dried
over Na.sub.2SO.sub.4, and concentrated under reduced pressure to
afford the title compound as a liquid (8.41 g, 60%).
[0184] The following compounds were made in accordance with the
procedures disclosed in Step 1 Method A of Example 1 above.
2,6-Difluoro-4-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile
##STR00041##
[0186] The product was isolated as a brown solid: mp 83-87.degree.
C.; .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.26 (d, J=9.0 Hz,
2H), 5.12 (d, J=6.0 Hz, 1H), 3.06 (s, 1H); ESIMS m/z 237.1
([M+H].sup.+).
1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanol
##STR00042##
[0188] The product was isolated as a pale yellow liquid: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 7.06 (d, J=8.4 Hz, 2H), 4.97-4.94
(m, 1H), 4.03 (s, 3H), 2.64 (s, 1H); EIMS m/z 242.1 ([M].sup.+); IR
(thinfilm) 3459, 1135 cm.sup.-1.
1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-ol
##STR00043##
[0190] The product was isolated as a colorless liquid: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.65-7.62 (m, 2H), 7.41 (d, J=8.4
Hz, 1H), 6.49 (d, J=5.1 Hz, 1H), 4.87-4.78 (m, 1H), 1.53 (t, J=18.9
Hz, 3H); EIMS m/z 240.0 ([M].sup.+); IR (thinfilm) 3434, 1131, 801,
512 cm.sup.-1.
[0191] The following compounds were made in accordance with the
procedures disclosed in Step 1 Method B of Example 1 above.
2,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethanol (AI3)
##STR00044##
[0193] The product was isolated as a pale yellow liquid (500 mg,
65%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.45 (s, 2H), 5.00
(m, 1H), 2.80 (s, 1H); ESIMS m/z 278 ([M+H].sup.+); IR (thin film)
3420, 1133, 718 cm.sup.-1.
1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (AI4)
##STR00045##
[0195] The product was isolated as a pale yellow liquid (500 mg,
65%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.41 (s, 2H), 5.00
(m, 1H), 2.80 (s, 1H); ESIMS m/z 262 ([M+H].sup.+); IR (thin film)
3420, 1133, 718 cm.sup.-1.
1-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (AI5)
##STR00046##
[0197] The product was isolated as a pale yellow liquid (500 mg,
65%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.60 (s, 1H), 7.51
(m, 1H), 7.35 (m, 1H), 5.01 (m, 1H), 2.60 (s, 1H); EIMS m/z 244
([M].sup.+).
1-(3,5-Dibromophenyl)-2,2,2-trifluoroethanol
##STR00047##
[0199] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.67 (s, 1H), 7.58 (s,
2H), 5.08-5.02 (m, 1H), 4.42 (bs, 1H); EIMS m/z 333.7 ([M].sup.+);
IR (thin film) 3417, 2966, 1128, 531 cm.sup.-1.
2,2,2-Trifluoro-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethanol
##STR00048##
[0201] The title molecule was isolated as a clear, colorless oil:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.56 (s, 1H), 7.45-7.37
(m, 2H), 5.11 (q, J=6.4 Hz, 1H), 3.22 (bs, 1H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 162.42 (d, J=249.5 Hz), 137.46 (d, J=7.8
Hz), 132.89 (qd, J=33.5, 7.9 Hz), 123.67 (q, J=283.8 Hz), 122.92
(q, J=270.68 Hz), 120.10 (t, J=4.1 Hz), 118.13 (d, J=23.0 Hz),
113.94 (dq, J=24.2, 3.9 Hz), 71.57 (q, J=32.4 Hz); EIMS m/z 262
([M].sup.+).
1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol
##STR00049##
[0203] The product was isolated as a white solid (4.98 g, 77%): mp
42-46.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.83-7.50 (m, 3H), 5.10 (p, J=6.2 Hz, 1H), 2.88 (d, J=4.3 Hz, 1H);
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 137.12, 135.84, 131.4,
133.03 (q, J=33.3 Hz), 127.15 (q, J=3.8 Hz), 124.50 (q, J=308.0
Hz), 123.45 (q, J=301.8 Hz), 123.04, 72.06 (q, J=32.5 Hz); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -62.93, -78.43; EIMS m/z 278
([M].sup.+).
2,2,2-Trifluoro-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanol
##STR00050##
[0205] The product was isolated as a brown liquid: .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.76 (d, J=6.8 Hz, 1H), 7.69-7.67 (m, 1H),
7.28-7.23 (m, 1H), 5.05-5.02 (m, 1H); ESIMS m/z 261.1
([M-H].sup.-); IR (thin film) 3418, 1131 cm.sup.-1.
2,2,2-Trifluoro-1-(3,4,5-trifluorophenyl)ethanol
##STR00051##
[0207] The product was isolated as a colorless liquid: .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.19-7.10 (m, 2H), 5.03-4.96 (m, 1H),
2.85 (bs, 1H); EIMS m/z 230.1 ([M].sup.+).
2,2,2-Trifluoro-1-(2,3,4-trifluorophenyl)ethanol
##STR00052##
[0209] The product was isolated as a clear colorless liquid (4.61 g
66%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.23 (qd, J=7.4,
6.1, 4.2 Hz, 1H), 6.93 (tdd, J=9.2, 6.9, 2.2 Hz, 1H), 5.25 (q,
J=6.3 Hz, 1H), 3.02-2.74 (m, 1H); .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 151.79 (ddd, J=254.5, 9.8, 3.4 Hz), 149.52
(ddd, J=253.5, 11.0, 3.5 Hz), 139.67 (dt, J=252.5, 15.3 Hz), 123.68
(q, J=282.2 Hz), 122.48 (dt, J=8.2, 4.1 Hz), 118.95 (dd, J=10.6,
3.6 Hz), 112.73 (dd, J=17.7, 3.9 Hz), 66.58-64.42 (m); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -78.95 (d, J=6.2 Hz), -132.02 (dd,
J=20.0, 8.2 Hz), -137.89 (m), 159.84 (t, J=20.3 Hz); EIMS m/z 230
([M].sup.+).
2,2,2-Trifluoro-1-(2,4,5-trichlorophenyl)ethanol
##STR00053##
[0211] The product was isolated as a white solid (3.37 g, 73%): mp
70-73.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.63
(d, J=2.5 Hz, 1H), 7.54 (d, J=2.5 Hz, 1H), 5.72-5.57 (m, 1H), 2.85
(d, J=4.8 Hz, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-77.84.
1-(4-Chloro-3-nitrophenyl)-2,2,2-trifluoroethanol
##STR00054##
[0213] The product was isolated as a yellow oil (6.52 g, 73%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.04 (d, J=2.0 Hz, 1H),
7.75-7.51 (m, 2H), 5.16 (m, 1H), 3.41 (d, J=4.3 Hz, 1H); .sup.13C
NMR (101 MHz, CDCl3) .delta. 147.65, 134.44, 132.23, 132.17,
128.11, 124.66, 123.60 (q, J=283.8), 70.99 (q, J=32.6 Hz); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -78.47; EIMS m/z 230
([M].sup.+).
2,2,2-Trifluoro-1-(4-fluoro-3,5-dimethylphenyl)ethanol
##STR00055##
[0215] The product was isolated as a white solid (6.49 g, 84%): mp
45-49.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.10
(d, J=6.8 Hz, 2H), 4.89 (m, 1H), 2.63 (d, J=4.3 Hz, 1H), 2.27 (d,
J=2.2 Hz, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 160.45
(d, J=246.0 Hz), 128.73, 127.97, 124.92 (d, J=18.6 Hz), 124.19 (q,
J=279.1 Hz), 72.36 (q, J=32.0 Hz), 14.61 (d, J=4.1 Hz); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -78.48, -120.14; EIMS m/z 222
([M].sup.+).
2,2,2-Trifluoro-1-(4-fluoro-3-methylphenyl)ethanol
##STR00056##
[0217] The product was isolated as a white solid (2.12 g, 33%): mp
40-46.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.28
(d, J=7.4 Hz, 1H), 7.25-7.14 (m, 1H), 7.01 (t, J=8.9 Hz, 1H),
5.05-4.63 (m, 1H), 3.03 (d, J=4.2 Hz, 1H); .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 161.91 (d, J=247.0 Hz), 130.62 (d, J=5.6 Hz),
129.41 (d, J=3.5 Hz), 126.55 (d, J=8.5 Hz), 115.19 (d, J=22.9 Hz),
72.23 (q, J=32.1 Hz), 14.44 (d, J=3.6 Hz); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -78.57, -116.15; EIMS m/z 208 ([M].sup.+).
1-(3-Chloro-4-methylphenyl)-2,2,2-trifluoroethanol
##STR00057##
[0219] The product was isolated as a clear colorless oil (4.99 g,
75%): .sup.1H NMR (400 MHz, CDCl3) .delta. 7.31 (s, 1H), 7.10 (m,
2H), 4.79 (q, J=6.1 Hz, 1H), 2.89 (bs, 1H), 2.25 (s, 3H); .sup.13C
NMR (101 MHz, CDCl3) .delta. 137.64, 134.67, 132.99, 131.09,
128.01, 125.58, 124.02 (q, J=284.8 Hz), 72.08 (q, J=32.3 Hz);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -78.39; EIMS m/z 224.5
([M].sup.+).
1-(3,4-Dibromophenyl)-2,2,2-trifluoroethanol
##STR00058##
[0221] The product was isolated as a clear colorless oil (5.92 g,
88%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.76 (d, J=2.0 Hz,
1H), 7.66 (d, J=8.3 Hz, 1H), 7.29 (dd, J=8.3, 2.0 Hz, 1H), 4.99
(qd, J=6.4, 4.2 Hz, 1H), 2.75 (d, J=4.3 Hz, 1H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 134.52, 133.81, 132.60, 127.45, 126.19,
125.16, 123.71 (q, J=283.8 Hz), 71.57 (q, J=32.5 Hz); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -78.44; EIMS m/z 334 ([M].sup.+).
2,2,2-Trifluoro-1-(3-(trifluoromethoxy)phenyl)ethanol
##STR00059##
[0223] The product was isolated as a clear colorless oil (20.9 g,
79%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.55-7.36 (m, 3H),
7.33-7.14 (m, 1H), 5.06 (m, 1H), 2.80 (br m, 1H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 149.36 (q, J=2.0 Hz), 136.04, 129.99,
125.78, 123.91 (q, J=282.8 Hz), 121.90, 120.31 (q, J=258.6
Hz),120.12, 72.04 (q, J=32.3 Hz); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -57.92, -78.49; EIMS m/z 260 ([M].sup.+).
2-Fluoro-5-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile
##STR00060##
[0225] The product was isolated as a clear colorless oil (5.47 g,
58%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.80 (dd, J=5.9,
2.2 Hz, 1H), 7.76 (ddd, J=7.8, 5.0, 2.3 Hz, 1H), 7.30 (d, J=8.6 Hz,
1H), .delta. 5.09 (qd, J=6.3, 4.2 Hz, 1H), 3.12 (bm, 1H); .sup.13C
NMR (101 MHz, CDCl.sub.3) .delta. 163.49 (d, J=261.7 Hz), 134.23
(d, J=8.6 Hz), 132.67, 131.17, 123.66 (q, J=282.4 Hz), 116.79 (d,
J=20.1 Hz), 113.39, 100.96 (d, J=194.9), 71.07 (q, J=32.5 Hz);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -78.70, -105.22; EIMS
m/z 219 ([M].sup.+).
1-(3-Bromo-5-chlorophenyl)-2,2,2-trifluoroethanol
##STR00061##
[0227] The product was isolated as a yellow liquid: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.78 (s, 1H), 7.67 (s, 1H), 7.57
(s, 1H), 7.15 (d, J=5.7 Hz, 1H); EIMS m/z 288 ([M].sup.+); IR (thin
film) 3435, 1175, 750 cm.sup.-1.
1-(3-Bromo-5-fluorophenyl)-2,2,2-trifluoroethanol
##STR00062##
[0229] The product was isolated as a pale yellow liquid: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.43 (s, 1H), 7.29-7.26 (m, 1H),
7.18 (d, J=8.8 Hz, 1H), 5.03-4.98 (m, 1H), 3.60 (bs, 1H); EIMS m/z
272.0 ([M].sup.+); IR (thin film) 3400, 1176, 520 cm.sup.-1.
1-(3,5-Dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-ol
##STR00063##
[0231] Using pentafluoroethyltrimethylsilane, the product was
isolated as a white solid (6.22 g, 88%): mp 71-73.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.42 (t, J=1.9 Hz, 1H),
7.37 (d, J=1.8 Hz, 2H), 5.11 (dt, J=16.2, 5.7 Hz, 1H), 2.62 (d,
J=4.9 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 136.90,
135.31, 129.84, 126.38, 70.94 (dd, J=28.2, 23.1 Hz); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -81.06, -120.94 (d, J=277.5 Hz),
-129.18 (d, J=277.5 Hz); EIMS m/z 295 ([M].sup.+).
2,2,3,3,3-Pentafluoro-1-(3,4,5-trichlorophenyl)propan-1-ol
##STR00064##
[0233] Using pentafluoroethyltrimethylsilane, the product was
isolated as an off white semi solid: .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 7.78 (s, 2H), 7.29 (d, J=5.4 Hz,), 5.50-5.40
(m, 1H); EIMS m/z 328.0 ([M].sup.+); IR (thin film) 3459, 1188, 797
cm.sup.-1.
2,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanol
##STR00065##
[0235] The product was isolated as a light yellow (13.8 g, 89%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.77 (s, 1H), 7.70-7.67
(m, 2H), 7.55 (t, J=7.8 Hz, 1H), 5.12 (q, J=6.6 Hz, 1H), 2.76 (s,
1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -62.8, -78.5; EIMS
m/z 244 ([M].sup.+).
1-(3,4-Dichloro-5-methylphenyl)-2,2,2-trifluoroethanol
##STR00066##
[0237] The product was isolated as an off pale yellow solid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.44 (s, 1H), 7.26 (s,
1H), 4.98-4.95 (m, 1H), 2.61 (d, J=4.4 Hz, 1H), 2.44 (s, 3H); EIMS
m/z 258.1 ([M].sup.+); IR (thin film) 3421, 2926, 1129, 748
cm.sup.-1.
1-(3-Chloro-5-ethylphenyl)-2,2,2-trifluoroethanol
##STR00067##
[0239] The product was isolated as an off brown liquid (0.43 g,
85%): .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.34 (s, 1H),
7.31-7.30 (m, 2H), 6.99 (d, J=5.7 Hz, 1H), 5.23-5.16 (m, 1H), 2.67
(m, 2H), 1.19 (t, J=7.8 Hz, 3H); EIMS m/z 238.0 ([M].sup.+); IR
(thin film) 3361, 1172, 749 cm.sup.-1.
1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol
##STR00068##
[0241] The product was isolated as a colorless liquid: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.75 (s, 2H), 7.24 (d, J=6.0 Hz,
1H), 5.34-5.29 (m, 1H); EIMS m/z 321.88 ([M].sup.+); IR (thin film)
3420, 1706, 1267, 804, 679 cm.sup.-1.
1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol
##STR00069##
[0243] The product was isolated as a pale yellow gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.89 (s, 2H), 7.20 (d, J=6.0 Hz,
1H) 5.34-5.30 (m, 1H); EIMS m/z 366.0 ([M].sup.+).
Step 2. 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene
(AI1)
[0244] To a stirred solution of
1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol (4.0 g, 16.3 mmol) in
CH.sub.2Cl.sub.2 (50 mL), were added NBS (2.9 g, 16.3 mmol) and
triphenyl phosphite (5.06 g, 16.3 mmol), and the resultant reaction
mixture was heated at reflux for 18 h. After the reaction was
deemed complete by TLC, the reaction mixture was cooled to
25.degree. C. and was concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; eluting with 100% pentane) afforded the title compound as a
liquid (2.0 g, 40%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.41
(s, 3H), 5.00 (m, 1H); EIMS m/z 306 ([M].sup.+).
[0245] The following compounds were made in accordance with the
procedures disclosed in Step 2 of Example 1.
5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (AI6)
##STR00070##
[0247] The product was isolated as a colorless oil (300 mg, 60%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.59 (s, 2H), 5.00 (m,
1H); EIMS m/z 340.00 ([M].sup.+).
5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene
(AI7)
##STR00071##
[0249] The product was isolated as a colorless oil (320 mg, 60%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.45 (s, 2H), 5.00 (m,
2H); EIMS m/z 324.00 ([M].sup.+).
4-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichlorobenzene (AI8)
##STR00072##
[0251] The product was isolated as a colorless oil (300 mg, 60%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.63 (s, 1H), 7.51 (m,
1H), 7.35 (m, 1H), 5.01 (m, 1H); EIMS m/z 306.00 ([M].sup.+).
1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)benzene
##STR00073##
[0253] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.71 (s, 1H), 7.59 (s,
2H), 5.04-4.97 (m, 1H); EIMS m/z 394.6 ([M].sup.+); IR (thin film)
1114, 535 cm.sup.-1.
1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluoro-5-(trifluoromethyl)benzene
##STR00074##
[0255] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.90 (d, J=8.4 Hz, 1H),
7.79-7.77 (m, 2H), 6.40-6.34 (m, 1H); EIMS m/z 324.00 ([M].sup.+);
IR (thin film) 1175, 525 cm.sup.-1.
1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene
##STR00075##
[0257] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, CDCl3) .delta. 7.71 (s, 1H), 7.67 (s, 1H),
7.64 (s, 1H), 5.15-5.09 (m, 1H); EIMS m/z 340.00 ([M].sup.+); IR
(thin film) 1178, 750, 540 cm.sup.-1.
4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-(trifluoromethyl)benzene
##STR00076##
[0259] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.75-7.72 (m, 2H),
7.28-7.24 (m, 1H), 5.19-5.16 (m, 1H); EIMS m/z 326.0 ([M].sup.+);
IR (thin film) 1114, 571 cm.sup.-1.
5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trifluorobenzene
##STR00077##
[0261] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 7.23-7.12 (m, 2H), 5.05-4.98 (m,
1H); EIMS m/z 292.0 ([M].sup.+); IR (thin film) 1116, 505
cm.sup.-1.
1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,4-trifluorobenzene
##STR00078##
[0263] The title molecule was isolated as a colorless oil: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 7.44 (qd, J=m, 1H), 7.11-7.03 (m,
1H), 5.53-5.45 (m, 1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-2,4,5-trichlorobenzene
##STR00079##
[0265] The title molecule was isolated as an off white solid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 8.06 (d, J=2.1 Hz, 1H),
7.71 (s, 1H), 6.45-6.37 (m, 1H); EIMS m/z 340.0 ([M].sup.+); IR
(thin film) 1186, 764, 576 cm.sup.-1.
4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-nitrobenzene
##STR00080##
[0267] The title molecule was isolated as an off white solid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 8.30 (s, 1H), 7.92 (d,
J=9.0 Hz, 1H), 6.43-6.35 (m, 1H); EIMS m/z 317.0 ([M].sup.+); IR
(thin film) 2927, 1540, 1353, 1177, 766, 530 cm.sup.-1.
5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluoro-1,3-dimethylbenzene
##STR00081##
[0269] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.32 (d, J=7.2 Hz, 2H),
6.15-6.07 (m, 1H), 3.23 (s, 6H); ESIMS m/z 284.1 ([M+H].sup.+); IR
(thin film) 2962, 1112, 500 cm.sup.-1.
4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-methylbenzene
##STR00082##
[0271] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.34-7.28 (m, 2H),
7.04-6.98 (m, 1H), 5.10-5.03 (m, 1H), 2.29 (s, 3H); EIMS m/z 270.1
([M].sup.+); IR (thin film) 2989, 1163 cm.sup.-1.
1-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-3,5-dichlorobenzene
##STR00083##
[0273] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.79 (t, J=2.0 Hz, 1H),
7.63 (S, 2H), 6.37-6.29 (m, 1H); EIMS m/z 356 ([M].sup.+); IR (thin
film) 1673, 1130, 715, 518 cm.sup.-1.
4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-methylbenzene
##STR00084##
[0275] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.55-7.50 (m, 2H), 7.44
(d, J=8.4 Hz, 1H), 6.24-6.16 (m, 1H); IR (thin film) 2983, 1112,
749, 564 cm.sup.-1.
1,2-Dibromo-4-(1-bromo-2,2,2-trifluoroethyl)benzene
##STR00085##
[0277] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.75 (s, 1H), 7.67 (d,
J=8.4 Hz, 1H), 7.33-7.30 (m, 1H), 5.07-5.00 (m, 1H); EIMS m/z 393.8
([M].sup.+); IR (thin film) 2981, 1644, 1165 cm.sup.-1.
1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethoxy)benzene
##STR00086##
[0279] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.65-7.60 (m, 2H),
7.56-7.50 (m, 2H), 6.35-6.27 (m, 1H); EIMS m/z 322 ([M].sup.+); IR
(thin film) 3413, 1161, 564 cm.sup.-1.
5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzonitrile
##STR00087##
[0281] The title molecule was isolated as a pale yellow liquid:
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 8.15-8.12 (m, 1H),
8.00-7.98 (m, 1H), 7.69-7.63 (m, 1H), 6.31-6.26 (m, 1H); EIMS m/z
280.9 ([M].sup.+).
1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-chlorobenzene
##STR00088##
[0283] The title molecule was isolated as a pale yellow liquid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.90 (s, 1H), 7.74 (s,
1H), 7.65 (s, 1H), 6.26-6.20 (m, 1H); EIMS m/z 349.9 ([M].sup.+);
IR (thin film) 1114, 764 cm.sup.-1.
1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-fluorobenzene
##STR00089##
[0285] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.43 (s, 1H), 7.32-7.29
(m, 1H), 7.22 (d, J=8.8 Hz, 1H), 1.06 (q, 1H); EIMS m/z 334.0
([M].sup.+); IR (thin film) 3087, 1168, 533 cm.sup.-1.
5-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-1,2,3-trichlorobenzene
##STR00090##
[0287] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.85 (s, 2H), 6.38-6.29
(m, 1H); EIMS m/z 389.9 ([M].sup.+); IR (thin film) 1208, 798, 560
cm.sup.-1.
4-(1-Bromo-2,2,2-trifluoroethyl)-2,6-difluorobenzonitrile
##STR00091##
[0289] The title molecule was isolated as a purple solid: mp
59-63.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.25
(s, 2H), 5.11-5.07 (m, 1H); ESIMS m/z 299.0 ([M+H].sup.+).
1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethyl)benzene
##STR00092##
[0291] The title molecule was isolated as a colorless liquid: mp
59-63.degree. C.; .sup.1H NMR (300 MHz, CDCl3) .delta. 7.75-7.67
(m, 3H), 7.57-7.52 (m, 1H), 5.20-5.13 (m, 1H); ESIMS m/z 306.0
([M].sup.+); IR (thinfilm) 3436, 2925, 1265, 749 cm.sup.-1.
5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-difluoro-2-methoxybenzene
##STR00093##
[0293] The title molecule was isolated as a pale yellow liquid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.08 (d, J=8.4 Hz, 2H),
5.03-4.98 (m, 1H), 4.04 (s, 3H); ESIMS m/z 304.1 ([M+H].sup.+); IR
(thinfilm) 1114, 613 cm.sup.-1.
5-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichloro-3-methylbenzene
##STR00094##
[0295] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.46 (s, 1H), 7.27 (s,
1H), 5.04-4.99 (m, 1H), 2.44 (s, 3H); EIMS m/z 320.0 ([M].sup.+);
IR (thinfilm) 2925, 1112, 752, 580 cm.sup.-1.
4-(1-Bromo-2,2-difluoropropyl)-1,2-dichlorobenzene
##STR00095##
[0297] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.76-7.70 (m, 2H), 7.54
(dd, J=8.4 1.8 Hz, 1H), 5.81-5.73 (m, 1H), 1.67 (d, J=18.9 Hz, 3H);
EIMS m/z 304.0 ([M].sup.+); IR (thinfilm) 1118, 800, 499
cm.sup.-1.
1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-ethylbenzene
##STR00096##
[0299] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.43 (d, J=5.6 Hz, 2H),
7.39 (s, 1H), 6.20-6.16 (m, 1H), 2.68-2.62 (m, 2H), 1.19 (t, J=7.6
Hz, 3H); EIMS m/z 300.0 ([M].sup.+); IR (thinfilm) 2970, 1167, 716,
539 cm.sup.-1.
2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene
##STR00097##
[0301] The title molecule was isolated as a colorless liquid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.79 (s, 2H), 6.27-6.21
(m, 1H); EIMS m/z 383.9 ([M].sup.+); IR (thinfilm) 2924, 1114, 749,
534 cm.sup.-1.
1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene
##STR00098##
[0303] The title molecule was isolated as a pale yellow liquid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.97 (s, 2H), 6.27-6.19
(m, 1H); EIMS m/z 428.0 ([M].sup.+).
Example 2: Preparation of N-Methyl-4-vinylbenzamide (AI9)
##STR00099##
[0304] Step 1. 4-Vinylbenzoyl chloride (AI10)
[0305] To a stirred solution of 4-vinylbenzoic acid (1 g, 6.75
mmol) in CH.sub.2Cl.sub.2 (20 mL) at 0.degree. C. were added a
catalytic amount of DMF and oxalyl chloride (1.27 g, 10.12 mmol)
dropwise over a period of 15 minutes (min). The reaction mixture
was stirred at 25.degree. C. for 6 h. After the reaction was deemed
complete by TLC, the reaction mixture was concentrated under
reduced pressure to give the crude acid chloride.
Step 2. N-Methyl-4-vinylbenzamide (AI9)
[0306] To 1 M N-methylamine in THF (13.5 mL, 13.5 mmol) at
0.degree. C. were added TEA (1.34 mL, 10.12 mmol) and the acid
chloride from Step 1 above in THF (10 mL), and the reaction mixture
was stirred at 25.degree. C. for 3 h. After the reaction was deemed
complete by TLC, the reaction mixture was quenched with water and
then was extracted with EtOAc (3.times.). The combined EtOAc layer
was washed with brine and dried over Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the title compound as
an off-white solid (650 mg, 60%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m,
1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz,
1H); ESIMS m/z 161.95 ([M+H].sup.+).
[0307] The following compounds were made in accordance with the
procedures disclosed in accordance with Example 2.
N,N-Dimethyl-4-vinylbenzamide (AI11)
##STR00100##
[0309] The product was isolated as an off-white solid (650 mg,
60%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.42 (m, 4H), 6.71
(m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.31 (d, J=10.8 Hz, 1H), 3.05 (s,
3H), 3.00 (s, 3H); ESIMS m/z 176.01 ([M+H].sup.+).
N-(2,2,3-Trifluoromethyl)-4-vinylbenzamide (AI12)
##STR00101##
[0311] The product was isolated as an off-white solid (900 mg,
60%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.76 (d, J=8.0 Hz,
2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82
(d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.19 (m, 2H); ESIMS
m/z 230.06 ([M+H].sup.+).
Morpholino(4-vinylphenyl)methanone (AI13)
##STR00102##
[0313] The product was isolated as a white solid (850 mg, 60%):
ESIMS m/z 218.12 ([M+H].sup.+).
Example 3: Preparation of Ethyl 2-methyl-4-vinylbenzoate (AI14)
##STR00103##
[0314] Step 1. 4-Formyl-2-methylbenzoic acid (AI15)
[0315] To a stirred solution of 4-bromo-2-methylbenzoic acid (10 g,
46.4 mmol) in dry THF (360 mL) at -78.degree. C. was added n-BuLi
(1.6 M solution in hexanes; 58.17 mL, 93.0 mmol) and DMF (8 mL).
The reaction mixture was stirred at -78.degree. C. for 1 h then was
warmed to 25.degree. C. and stirred for 1 h. The reaction mixture
was quenched with 1 N HCl solution and extracted with EtOAc. The
combined EtOAc extracts were washed with brine and dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure. The
residue was washed with n-hexane to afford the title compound as a
solid (3.0 g, 40%): mp 196-198.degree. C.; .sup.1H NMR (400 MHz,
DMSO-d.sub.6) .delta. 13.32 (br s, 1H), 10.05 (s, 1H), 7.98 (m,
1H), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z 163.00
([M-H].sup.-).
Step 2. Ethyl 4-formyl-2-methylbenzoate (AI16)
[0316] To a stirred solution of 4-formyl-2-methylbenzoic acid (3 g,
18.2 mmol) in EtOH (30 mL) was added H.sub.2SO.sub.4 and the
reaction mixture was heated at 80.degree. C. for 18 h. The reaction
mixture was cooled to 25.degree. C. and concentrated under reduced
pressure. The residue was diluted with EtOAc and washed with water.
The combined EtOAc extracts were washed with brine, dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
the title compound as a solid (2.8 g, 80%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 10.05 (s, 1H), 8.04 (m, 1H), 7.75 (m, 2H), 4.43
(m, 2H), 2.65 (s, 3H), 1.42 (m, 3H).
Step 3. Ethyl 2-methyl-4-vinylbenzoate (AI14)
[0317] To a stirred solution of ethyl 4-formyl-2-methylbenzoate
(2.8 g, 4 mmol) in 1,4-dioxane (20 mL) were added K.sub.2CO.sub.3
(3.01 g, 21.87 mmol) and methyltriphenyl phosphonium bromide (7.8
g, 21.87 mmol) at 25.degree. C. Then the reaction mixture was
heated at 100.degree. C. for 18 h. After the reaction was deemed
complete by TLC, the reaction mixture was cooled to 25.degree. C.
and filtered, and the filtrate was concentrated under reduced
pressure. The crude compound was purified by flash chromatography
(SiO.sub.2, 100-200 mesh; eluting with 25-30% EtOAc in n-Hexane) to
afford the title compound as a solid (2.0 g, 72%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd,
J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz,
1H), 4.39 (m, 2H), 2.60 (s, 3H), 1.40 (m, 3H); ESIMS m/z 191.10
([M-H].sup.-); IR (thin film) 2980, 1716, 1257 cm.sup.-1.
Example 4: Preparation of tert-Butyl 2-chloro-4-vinylbenzoate
(AI17)
##STR00104##
[0318] Step 1. tert-Butyl 4-bromo-2-chlorobenzoate (AI18)
[0319] To a stirred solution of 4-bromo-2-chlorobenzoic acid (5 g,
21.37 mmol) in THF (30 mL) was added di-tert-butyl dicarbonate
(25.5 g, 25.58 mmol), TEA (3.2 g, 31.98 mmol) and DMAP (0.78 g,
6.398 mmol), and the reaction mixture was stirred at 25.degree. C.
for 18 h. The reaction mixture was diluted with EtOAc and washed
with water. The combined organic layer was washed with brine, dried
over Na.sub.2SO.sub.4 and concentrated under reduced pressure. The
residue was purified by flash chromatography (SiO.sub.2, 100-200
mesh; eluting with 2-3% EtOAc in n-hexane) to afford the title
compound as a liquid (3.2 g, 51%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.62 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 1.59 (s,
9H); ESIMS m/z 290.10 ([M+H].sup.+); IR (thin film) 1728
cm.sup.-1.
[0320] The following compounds were made in accordance with the
procedures disclosed in Step 1 of Example 4.
tert-Butyl 2-bromo-4-iodobenzoate (AI19)
##STR00105##
[0322] The product was isolated as a colorless oil (1.2 g, 50%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.01 (s, 1H), 7.68 (d,
J=8.4 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 1.59 (s, 9H); ESIMS m/z
382.10 ([M+H].sup.+); IR (thin film) 1727 cm.sup.-1.
tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate (AI20)
##STR00106##
[0324] The product was isolated as a colorless oil (1 g, 52%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.85 (s, 1H), 7.73 (d,
J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 1.57 (s, 9H); ESIMS m/z
324.10 ([M+H].sup.+); IR (thin film) 1725 cm.sup.-1.
Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (AI17)
[0325] To a stirred solution of tert-butyl 4-bromo-2-chlorobenzoate
(1.6 g, 5.50 mmol) in toluene (20 mL) was added Pd(PPh.sub.3).sub.4
(0.31 mg, 0.27 mmol), K.sub.2CO.sub.3 (2.27 g, 16.5 mmol) and
vinylboronic anhydride pyridine complex (2.0 g, 8.3 mmol) and the
reaction mixture was heated to reflux for 16 h. The reaction
mixture was filtered, and the filtrate was washed with water and
brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure. Purification by flash column chromatography (SiO.sub.2,
100-200 mesh; eluting with 5-6% EtOAc in n-hexane) afforded the
title compound as a liquid (0.6 g, 46%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.72 (d, J=8.1 Hz, 1H), 7.44 (m, 1H), 7.31 (d,
J=8.0 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.85 (d, J=17.6 Hz,
1H), 5.40 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 238.95
([M+H].sup.+); IR (thin film) 2931, 1725, 1134 cm.sup.-1.
[0326] The following compounds were made in accordance with the
procedures disclosed in Step 2 of Example 4.
tert-Butyl 2-bromo-4-vinylbenzoate (AI21)
##STR00107##
[0328] The product was isolated as a colorless oil (1 g, 52%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.68 (m, 2H), 7.36 (d,
J=8.0 Hz, 1H), 6.68 (dd, J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz,
1H), 5.39 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 282.10
([M+H].sup.+); IR (thin film) 2978, 1724, 1130 cm.sup.-1.
tert-Butyl 2-(trifluoromethyl)-4-vinylbenzoate (AI22)
##STR00108##
[0330] The product was isolated as a colorless oil (1.2 g, 50%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.71 (d, J=6.4 Hz, 2H),
7.59 (d, J=7.6 Hz, 1H), 6.77 (dd, J=17.6, 10.8 Hz, 1H), 5.89 (d,
J=17.6 Hz, 1H), 5.44 (d, J=10.8 Hz, 1H), 1.58 (s, 9H); ESIMS m/z
272.20 ([M+H].sup.+); IR (thin film) 2982, 1727, 1159
cm.sup.-1.
Example 5: Preparation of tert-Butyl 2-cyano-4-vinylbenzoate
(AI23)
##STR00109##
[0332] To a stirred solution of tert-butyl 2-bromo-4-vinylbenzoate
(0.5 g, 1.77 mmol) in DMF (20 mL) was added CuCN (0.23 g, 2.65
mmol), and the reaction mixture was heated at 140.degree. C. for 3
h. The reaction mixture was cooled to 25.degree. C., diluted with
water, and extracted with EtOAc. The combined organic layer was
washed with brine, dried over Na.sub.2SO.sub.4, and concentrated
under reduced pressure. The residue was purified by flash
chromatography (SiO.sub.2, 100-200 mesh; eluting with 15% EtOAc in
n-hexane) to afford the title compound as a white solid (0.3 g,
72%): mp 51-53.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.03 (s, 1H), 7.77 (s, 1H), 7.64 (d, J=8.4 Hz, 1H), 6.75
(dd, J=17.6, 10.8 Hz, 1H), 5.93 (d, J=17.6 Hz, 1H), 5.51 (d, J=10.8
Hz, 1H), 1.65 (s, 9H); ESIMS m/z 229.84 ([M+H].sup.+); IR (thin
film) 2370, 1709, 1142 cm.sup.-1.
Example 6: Preparation of Ethyl 2-bromo-4-iodobenzoate (AI46)
##STR00110##
[0334] To a stirred solution of 4-iodo-2-bromobenzoic acid (5 g,
15.29 mmol) in EtOH (100 mL) was added H.sub.2SO.sub.4 (5 mL), and
the reaction mixture was heated at 80.degree. C. for 18 h. The
reaction mixture was cooled to 25.degree. C. and concentrated under
reduced pressure. The residue was diluted with EtOAc (2.times.100
mL) and washed with water (100 mL). The combined EtOAc extracts
were washed with brine, dried over Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the compound as a
pale yellow solid (5 g, 92%): .sup.1H NMR (400 MHz, DMSO-d.sub.6)
.delta. 8.04 (d, J=1.2 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.51 (d,
J=8.4 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H).
[0335] The following compounds were made in accordance with the
procedures disclosed in Example 6.
Ethyl 4-bromo-2-chlorobenzoate (AI47)
##STR00111##
[0337] The title compound was isolated as an off-white solid (2.0
g, 80%): .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 8.25 (d, J=1.2
Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 4.65 (q,
J=7.2 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H).
Ethyl 4-bromo-2-methylbenzoate (AI48)
##STR00112##
[0339] The title compound was isolated as a pale yellow liquid (3.0
g, 83%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.4
Hz, 1H), 7.41 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 4.42 (q, J=7.2 Hz,
2H), 2.60 (s, 3H), 1.40 (t, J=7.2 Hz, 3H)ESIMS m/z 229.11
([M+H].sup.+); IR (thin film) 1725 cm.sup.-1.
Ethyl 4-bromo-2-fluorolbenzoate (AI49)
##STR00113##
[0341] The title compound was isolated as a colorless liquid (9.0
g, 79%): .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.84 (t, J=8.4
Hz, 1H), 7.76 (d, J=2.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 4.34 (q,
J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H); ESIMS m/z 246.99
([M+H].sup.+), IR (thin film) 1734 cm.sup.-1.
Example 7: Preparation of Ethyl 4-bromo-2-ethylbenzoate (AI50)
##STR00114##
[0343] To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0
g, 9.17 mmol) in THF (16 mL), was added 1.0 M ethyl magnesium
bromide in THF (32 mL, 32.0 mmol) dropwise at 0.degree. C. and the
resultant reaction mixture was stirred at ambient temperature for
18 h. The reaction mixture was quenched with 2 N HCl and extracted
with EtOAc. The combined EtOAc layer was dried over anhydrous
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
crude 4-bromo-2-ethylbenzoic acid as a colorless liquid that was
used in the next step without purification (0.4 g): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.64 (d, J=8.4 Hz, 1H), 7.47 (m, 1H),
7.43 (m, 1H), 2.95 (q, J=4.0 Hz, 2H), 1.32 (t, J=4.0 Hz, 3H); ESIMS
m/z 228.97 ([M+H].sup.+).
[0344] The title compound was synthesized from
4-bromo-2-ethylbenzoic acid in accordance to the procedure in
Example 6, isolated as a colorless liquid (0.15 g, 68%): .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 7.90 (d, J=8.4 Hz, 1H), 7.47
(m, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.06 (q, J=7.6 Hz, 2H), 1.42 (t,
J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 226.96
([M-H].sup.-); IR (thin film) 3443, 1686, 568 cm.sup.-1.
Example 8: Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51)
##STR00115##
[0346] To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g,
14.3 mmol) in THF/water (100 mL, 9:1) was added potassium
vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs.sub.2CO.sub.3 (18.27
g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the
reaction mixture was degassed with argon for 20 min, then charged
with PdCl.sub.2 (0.05 g, 0.28 mmol). The reaction mixture was
heated to reflux for 16 h. The reaction mixture was cooled to
ambient temperature and filtered through a Celite.RTM. bed and
washed with EtOAc. The filtrate was again extracted with EtOAc and
the combined organic layers washed with water and brine, dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
crude compound. The crude compound was purified by column
chromatography (SiO.sub.2, 100-200 mesh; eluting with 2%
EtOAc/petroleum ether) to afford the title compound as a light
brown gummy material (2 g, 56%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d,
J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz,
1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t,
J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H].sup.+); IR (thin film) 1729
cm.sup.-1.
[0347] The following compounds were made in accordance with the
procedures disclosed in Example 8.
Ethyl 2-methyl-4-vinylbenzoate (AI52)
##STR00116##
[0349] The title compound was isolated as a colorless liquid (0.8
g, 80%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.89 (d, J=8.4
Hz, 1H), 7.27 (m, 2H), 6.79 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d,
J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H),
2.60 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 191.10
([M+H].sup.+); IR (thin film) 1717, 1257 cm.sup.-1.
Ethyl 2-fluoro-4-vinylbenzoate (AI53)
##STR00117##
[0351] The title compound was isolated as a pale yellow liquid (2.0
g, 50%): .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.87 (t, J=8.0
Hz, 1H), 7.51 (d, J=16.0 Hz, 1H), 7.48 (d, J=16.0 Hz, 1H), 6.82
(dd, J=17.6, 10.8 Hz, 1H), 6.09 (d, J=17.6 Hz, 1H), 5.50 (d, J=10.8
Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H); ESIMS m/z
195.19 ([M+H].sup.+); IR (thin film) 1728 cm.sup.-1.
Example 9: Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54)
##STR00118##
[0353] To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2
g, 7.63 mmol) in DMSO (20 mL) was added potassium
vinyltrifluoroborate (3.06 g, 22.9 mmol) and K.sub.2CO.sub.3 (3.16
g, 22.9 mmol). The reaction mixture was degassed with argon for 30
min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium
dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture
was heated to 80.degree. C. for 1 h. The reaction mixture was
diluted with water (100 mL), extracted with EtOAc (2.times.50 mL),
washed with brine, dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure to obtain the compound as brown gummy
material (1.1 g, 69%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70
(dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8
Hz, 1H), 4.41 (q, J=7.2 Hz,2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z
211.22 ([M+H].sup.+); IR (thin film) 1729, 886 cm.sup.-1.
[0354] The following compounds were made in accordance with the
procedures disclosed in Example 9.
Ethyl 2-ethyl-4-vinylbenzoate (AI55)
##STR00119##
[0356] The title compound was isolated as a color less liquid (1.0
g, 66%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.85 (m, 1H),
7.29 (m, 2H), 6.76 (d, J=10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H),
5.36 (d, J=10.5 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 3.10 (q, J=7.2 Hz,
2H), 1.40 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H); ESIMS m/z
205.26 ([M+H].sup.+); IR (thin film) 1720, 1607, 1263
cm.sup.-1.
Methyl 2-methoxy-4-vinylbenzoate (AI56)
##STR00120##
[0358] The title compound was isolated as a pale yellow liquid (1.2
g, 75%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.0
Hz, 1H), 7.04 (d, J=1.2 Hz, 1H), 6.97 (s, 1H), 6.74 (dd, J=11.2,
11.2 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.39 (d, J=17.6 Hz, 1H) 3.93
(s, 3H), 3.91 (s, 3H); ESIMS m/z 193.18 ([M+H].sup.+); IR (thin
film) 1732 cm.sup.-1.
Ethyl 2-(methylthio)-4-vinylbenzoate
##STR00121##
[0360] The title compound was isolated as a brown liquid: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 7.98 (d, J=8.4 Hz, 1H), 7.23-7.18
(m, 2H), 6.78 (dd, J=17.7, 10.8, Hz, 1H), 5.89 (d, J=17.4 Hz, 1H),
5.42 (d, J=10.8 Hz, 1H), 4.39-4.36 (m, 2H), 2.48 (s, 3H), 1.39 (t,
J=6.9 Hz, 3H); ESIMS m/z 221.9 ([M+H].sup.+); IR (thin film) 1708
cm.sup.-1.
Example 10: Preparation of (E)-Ethyl
4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate
(AI24)
##STR00122##
[0362] To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (2.0
g, 10.5 mmol) in 1,2-dichlorobenzene (25 mL) were added
1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (6.44 g, 21.0
mmol), CuCl (208 mg, 21 mmol) and 2,2bipyridyl (0.65 g, 4.1 mmol).
The reaction mixture was degassed with argon for 30 min and then
stirred at 180.degree. C. for 24 h. After the reaction was deemed
complete by TLC, the reaction mixture was cooled to 25.degree. C.
and filtered, and the filtrate was concentrated under reduced
pressure. Purification by flash chromatography (SiO.sub.2, 100-200
mesh; eluting with 25-30% EtOAc in petroleum ether) afforded the
title compound as a solid (1.7 g, 40%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.91 (d, J=8.0 Hz, 1H), 7.37 (m, 1H), 7.27-7.24
(m, 4H), 6.59 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz, 1H),
4.38 (q, J=7.2 Hz, 2H), 4.08 (m, 1H), 2.62 (s, 3H), 1.42 (t, J=7.2
Hz, 3H); ESIMS m/z 415.06 ([M-H].sup.-); IR (thin film) 1717, 1255,
1114 cm.sup.-1.
[0363] Compounds AI25, AI57-AI68 and AC1-AC5 (Table 1) were made in
accordance with the procedures disclosed in Example 10.
(E)-Ethyl
4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifl-
uoromethyl)-benzoic acid (AI25)
##STR00123##
[0365] The product was isolated as a pale brown gummy liquid (500
mg, 40%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.0
Hz, 1H), 7.71 (m, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.42 (s, 2H), 6.70
(d, J=16.0 Hz, 1H), 6.57 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.2
Hz, 2H), 4.19 (m, 1H), 1.40 (t, J=7.6 Hz, 3H); ESIMS m/z 502.99
([M-H]); IR (thin film) 1730, 1201, 1120, 749 cm.sup.-1.
(E)-Ethyl
4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluoroben-
zoate (AI57)
##STR00124##
[0367] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.38 (s, 1H), 7.26
(s, 3H), 7.21 (d, J=8.4 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d,
J=16.0 Hz, 1H), 6.47 (dd, J=,16.0, 8.0 Hz, 1H), 4.41 (q, J=6.8 Hz,
2H), 4.18 (m, 1H), 1.41 (t, J=6.8 Hz, 3H); ESIMS m/z 419.33
([M-H].sup.-); IR (thin film) 1723, 1115, 802 cm.sup.-1.
(E)-Ethyl
4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-bromobenz-
oate (AI58)
##STR00125##
[0369] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.0 Hz,
1H), 7.67 (s, 1H), 7.38 (m, 2H), 7.26 (m, 2H), 6.56 (d, J=16.0 Hz,
1H), 6.45 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.39
(m, 1H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 481.22 ([M-H].sup.-); IR
(thin film) 1727, 1114, 801, 685 cm.sup.-1.
(E)-Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)
but-1-enyl)benzoate (AI59)
##STR00126##
[0371] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.0 Hz,
1H), 7.67 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.36 (d, J=1.6 Hz, 1H),
6.56 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q,
J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z
514.74 ([M-H].sup.-); IR (thin film) 1726, 1115, 808, 620
cm.sup.-1.
(E)-Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)
but-1-enyl)benzoate (AI60)
##STR00127##
[0373] The title compound was isolated as a light brown gummy
material: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.90 (d, J=8.8
Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d,
J=16.0 Hz, 1H), 6.42 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz,
2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H).
(E)-Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)
but-1-enyl)benzoate (AI61)
##STR00128##
[0375] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.87 (d, J=8.0 Hz,
1H), 7.46 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.31 (d, J=1.6 Hz, 1H),
6.57 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.42 (q,
J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z
470.73 ([M-H].sup.-); IR (thin film) 1726, 1115, 809, 3072
cm.sup.-1.
(E)-Ethyl
4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifl-
uoromethyl)benzoate (AI62)
##STR00129##
[0377] The title compound was isolated as a pale brown liquid (1.0
g, 46.3%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.0
Hz, 1H), 7.71 (s, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.41 (s, 2H) 6.65
(d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.6
Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=7.6 Hz, 3H); ESIMS m/z 502.99
([M-H].sup.-); IR (thin film) 1730, 1202, 1120, 750 cm.sup.-1.
(E)-Ethyl
2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-
-enyl)benzoate (AI63)
##STR00130##
[0379] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.85 (d, J=6.0 Hz,
1H), 7.46 (d, J=1.8 Hz, 2H), 7.34 (m, 1H), 7.24 (m, 1H), 6.57 (d,
J=16.2 Hz, 1H), 6.45 (dd, J=16.2, 7.2 Hz, 1H), 4.43 (q, J=7.2 Hz,
2H), 4.13 (m, 1H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 455.0
([M+H].sup.+); IR (thin film) 1728, 1115, 817 cm.sup.-1.
(E)-Ethyl
2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-
-enyl)benzoate (AI64)
##STR00131##
[0381] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.93 (t, J=7.6 Hz,
1H), 7.34 (d, J=5.6 Hz, 2H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d,
J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 7.6 Hz,
1H), 4.42 (q, J=7.6 Hz, 2H), 4.13 (m, 1H), 1.41 (t, J=7.6 Hz, 3H);
ESIMS m/z 436.81 ([M-H].sup.-); IR (thin film) 1725 cm.sup.-1.
(E)-Ethyl
2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1--
enyl)benzoate (AI65)
##STR00132##
[0383] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.94 (d, J=8.0 Hz,
1H), 7.67 (s, 1H), 7.36 (m, 3H), 6.56 (d, J=15.6 Hz, 1H), 6.44 (dd,
J=15.6, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t,
J=6.8 Hz, 3H); ESIMS m/z 498.74 ([M-H].sup.-); IR (thin film) 1726,
1114, 820, 623 cm.sup.-1.
(E)-Ethyl
2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-
-enyl)benzoate (AI66)
##STR00133##
[0385] The title compound was isolated as a brown semi-solid:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.90 (d, J=8.8 Hz, 1H),
7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz,
1H), 6.42 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.19
(m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 432.90
([M-H].sup.-); IR (thin film) 1715 cm.sup.-1.
(E)-Methyl
2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-
-1-enyl)benzoate (AI67)
##STR00134##
[0387] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.80 (d, J=8.4 Hz,
1H), 7.35 (d, J=6.0 Hz, 2H), 7.03 (d, J=1.2 Hz, 1H), 6.92 (s, 1H),
6.59 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.13 (m,
1H), 3.93 (s, 3H), 3.88 (s, 3H); ESIMS m/z 437.29 ([M+H].sup.+); IR
(thin film) 1724 cm.sup.-1.
(E)-Ethyl
2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1--
enyl)benzoate (AI68)
##STR00135##
[0389] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.85 (d, J=8.0 Hz,
1H), 7.35 (d, J=9.6 Hz, 2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d,
J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz,
2H), 4.14 (m, 1H), 3.01 (q, J=7.6 Hz 2H), 1.41 (t, J=7.2 Hz, 3H),
1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 447.05 ([M-H].sup.-); IR (thin
film) 1715, 1115, 817 cm.sup.-1.
(E)-Ethyl
4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-
-2-(methylthio)benzoate
##STR00136##
[0391] Isolated as a brown liquid: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.99 (d, J=8.1 Hz, 2H), 7.35-7.32 (m, 2H),
7.21-7.16 (m, 2H), 6.63 (d, J=15.8 Hz, 1H), 6.45 (dd, J=15.9, 7.8
Hz, 1H), 4.41-4.31 (m, 2H), 4.30-4.10 (m, 1H), 2.47 (s, 3H), 1.40
(t, J=7.5 Hz, 3H); ESIMS m/z 466.88 ([M+H].sup.+); IR (thin film)
1705, 1114 cm.sup.-1.
(E)-Ethyl
2-bromo-4-(3-(3,5-difluoro-4-methoxyphenyl)-4,4,4-trifluorobut-1-
-en-1-yl)benzoate
##STR00137##
[0393] The product was isolated as a pale yellow liquid: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.78 (d, J=8.0 Hz, 1H), 7.66 (d,
J=1.6 Hz, 1H), 7.35-7.33 (m, 1H), 6.96-6.90 (m, 2H), 6.54 (d,
J=15.6 Hz, 1H), 6.43 (dd, J=15.6, 8.0 Hz, 1H), 4.39 (q, J=6.8 Hz,
2H), 4.09-4.05 (m, 1H), 4.02 (s, 3H), 1.40 (t, J=7.2 Hz, 3H); EIMS
m/z 478.2 ([M].sup.+); IR (thin film) 1727, 1113 cm.sup.-1.
Example 11: Preparation of
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic
acid (AI32)
##STR00138##
[0395] To a stirred solution of (E)-ethyl
4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate
(1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added 11 N HCl (30
mL), and the reaction mixture was heated at 100.degree. C. for 48
h. The reaction mixture was cooled to 25.degree. C. and
concentrated under reduced pressure. The residue was diluted with
water and extracted with chloroform (CHCl.sub.3). The combined
organic layer was dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure, and the crude compound was washed with
n-hexane to afford the title compound as a white solid (0.7 g,
50%): mp 142-143.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6)
.delta. 12.62 (br s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.66 (s, 3H),
7.52-7.44 (m, 2H), 6.89 (dd, J=16.0, 8.0 Hz, 1H), 6.78-6.74 (d,
J=16.0 Hz, 1H), 4.84 (m, 1H), 2.50 (s, 3H); ESIMS m/z 387.05
([M-H].sup.-); IR (thin film) 3448, 1701, 1109, 777 cm.sup.-1.
[0396] The following compounds were made in accordance with the
procedures disclosed in Example 11.
(E)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoi-
c acid (AI26)
##STR00139##
[0398] The product was isolated as a pale brown gummy liquid (1 g,
46%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.97 (d, J=8.0 Hz,
1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz,
1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.50 (s, 3H);
ESIMS m/z 422.67 ([M-H].sup.-).
(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoi-
c acid (AI27)
##STR00140##
[0400] The product was isolated as an off-white semi-solid (1 g,
45%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.99 (d, J=8.4 Hz,
1H), 7.50 (m, 1H), 7.40 (s, 1H), 7.36 (m, 2H), 6.59 (d, J=15.6 Hz,
1H), 6.48 (dd, J=15.6, 7.6 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 442.72
([M-H].sup.-); IR (thin film) 3472, 1704, 1113, 808 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic
acid (AI28)
##STR00141##
[0402] The product was isolated as a brown solid (1 g, 45%): mp
70-71.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.99
(d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m, 3H), 6.58 (d, J=16.0 Hz,
1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 484.75
([M-H].sup.-); IR (thin film) 3468, 1700 cm.sup.-1.
(E)-2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic
acid (AI29)
##STR00142##
[0404] The product was isolated as an off-white solid (500 mg,
45%): mp 100-101.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.90 (s, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.72 (d, J=8.0 Hz,
1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58
(dd, J=16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 431.93
([M-H].sup.-).
E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic
acid (AI30)
##STR00143##
[0406] The product was isolated as a pale brown liquid (500 mg,
46%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.03 (m, 1H), 7.49
(m, 2H), 7.29 (m, 1H), 7.22 (m, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58
(dd, J=16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.64 (s, 3H); ESIMS m/z
386.84 ([M-H].sup.-); IR (thin film) 3428, 1690, 1113, 780
cm.sup.-1.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-
benzoic acid (AI31)
##STR00144##
[0408] The product was isolated as a white solid (500 mg, 50%): mp
91-93.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.02
(d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.61 (d,
J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.65
(s, 3H); ESIMS m/z 406.87 ([M-H].sup.-).
(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluorome-
thyl)benzoic acid (AI33)
##STR00145##
[0410] The product was isolated as a white solid (500 mg, 45%): mp
142-143.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.97
(d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68
(d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H);
ESIMS m/z 474.87 ([M-H].sup.-).
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic
acid (AI69)
##STR00146##
[0412] The title compound was isolated as a brown solid (0.8 g,
28%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 13.42 (br, 1H),
7.98 (d, J=1.5 Hz, 1H), 7.94 (m, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.65
(m, 1H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.80 (d, J=15.9 Hz, 1H),
4.91 (m, 1H); ESIMS m/z 484.75 ([M-H].sup.-); IR (thin film) 3469,
1700 cm.sup.-1.
(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluo
robut-1-enyl)benzoic acid (AI70)
##STR00147##
[0414] The title compound was isolated as a yellow liquid (0.3 g,
crude): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.79 (d, J=8.1
Hz, 1H), 7.67 (s, 1H), 7.34 (m, 3H), 6.56 (d, J=15.9 Hz, 1H), 6.45
(dd, J=15.9, 7.6 Hz, 1H), 4.43 (m, 1H); ESIMS m/z 471.0
([M-H].sup.-).
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-ethylb-
enzoic acid (AI71)
##STR00148##
[0416] The title compound was isolated as a brown gummy material
(0.2 g, crude): .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 12.5
(br, 1H), 7.85 (d, J=6.3 Hz, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.52 (m,
2H), 6.96 (dd, J=8.7, 8.7 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.80
(m, 1H), 4.06 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H); ESIMS m/z
419.06 ([M-H].sup.-).
(E)-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-
benzoic acid (AI72)
##STR00149##
[0418] The title compound was isolated as a yellow liquid (0.7 g,
95%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.85 (d, J=6.0 Hz,
1H), 7.46 (d, J=1.8 Hz, 1H), 7.41 (s, 3H), 6.57 (d, J=16.0 Hz, 1H),
6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 455.0
([M+H].sup.+); IR (thin film) 1728, 1115, 817 cm.sup.-1.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-
benzoic acid (AI73)
##STR00150##
[0420] The title compound was isolated as a light brown gummy
material (0.7 g, 38%): mp 91-93.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H),
7.30 (m, 3H), 6.10 (d, J=16.0 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz,
1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87
([M-H].sup.-).
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoic
acid (AI74)
##STR00151##
[0422] The title compound was isolated as a light brown liquid (0.3
g, crude): ESIMS m/z 393.15 ([M-H].sup.-).
(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic
acid (AI75)
##STR00152##
[0424] The title compound was isolated as a light brown liquid
(0.35 g, crude): ESIMS m/z 451.91 ([M-H].sup.-).
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(me-
thylthio)benzoic acid
##STR00153##
[0426] .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.88-7.85 (m, 3H),
7.46 (d, J=6.8 Hz, 1H), 7.37 (s, 1H), 6.99 (dd, J=15.6, 8.8 Hz,
1H), 6.85 (d, J=16.0 Hz, 1H), 4.85-4.81 (m, 2H), 2.45 (s, 3H);
ESIMS m/z 436.89 [(M-H)-]; IR (thinfilm) 3469, 1686, 1259, 714
cm.sup.-1.
(E)-2-Bromo-4-(3-(3,5-difluoro-4-methoxyphenyl)-4,4,4-trifluorobut-1-en-1--
yl)benzoic acid
##STR00154##
[0428] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.48 (bs, 1H), 8.03 (s, 1H),
7.81 (d, J=7.8 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 7.48 (d, J=9.3 Hz,
2H), 7.05 (dd, J=15.6, 9.0 Hz, 1H), 6.83 (d, J=15.9 Hz, 1H),
4.86-4.74 (m, 1H), 4.00 (s, 3H); EIMS m/z 451.18 ([M].sup.+); IR
(thin film) 3431, 1132 cm.sup.-1.
[0429] Prophetically, compounds AI34, AI36-AI41, AI44-AI45 (Table
1) could be made in accordance with the procedures disclosed in
Example 10, or Examples 10 and 11.
Example 12: Preparation of
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,-
2-trifluoroethyl)benzamide (AC6)
##STR00155##
[0431] To a stirred solution of
(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic
acid in DMF was added 2,2,2-trifluoroethylamine, HOBt.H.sub.2O,
EDC.HCl and DIPEA, and the reaction mixture was stirred at
25.degree. C. for 18 h. The reaction mixture was diluted with water
and extracted with EtOAc. The combined organic layer was washed
with brine, dried over Na.sub.2SO.sub.4 and concentrated under
reduced pressure. Purification by flash column chromatography
(SiO.sub.2, 100-200 mesh; eluting with hexane:EtOAc afforded a
white semi-solid (110 mg, 50%): .sup.1H NMR (400 MHz, CDCl3) 7.40
(m, 2H), 7.26 (m, 3H), 6.56 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0,
8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMS m/z
468.40 ([M-H].sup.-); IR (thin film) 1657, 1113, 804 cm.sup.-1.
[0432] Compounds AC7-AC38, AC40-AC58, AC110-AC112, AC117, and AC118
(Table 1) were made in accordance with the procedures disclosed in
Example 12.
Example 13: Preparation of
4-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-((pyr-
imidin-5-yl)methyl)benzamide (AC39)
##STR00156##
[0434] To a stirred solution of (pyrimidin-5-yl)methanamine (0.15
g, 1.43 mmol) in CH.sub.2Cl.sub.2 (10 mL) was added drop wise
trimethylaluminum (2 M solution in toluene; 0.71 mL, 1.43 mmol),
and the reaction mixture was stirred at 25.degree. C. for 30 min. A
solution of ethyl
4-((E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate
(0.3 g, 0.71 mmol) in CH.sub.2Cl.sub.2 was added drop wise to the
reaction mixture at 25.degree. C. The reaction mixture was stirred
at reflux for 18 h, cooled to 25.degree. C., quenched with 0.5 N
HCl solution (50 mL) and extracted with EtOAc (2.times.50 mL). The
combined organic extracts were washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure. The
crude compound was purified by flash chromatography (SiO.sub.2,
100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the
title compound (0.18 g, 55%): mp 141-144.degree. C.; .sup.1H (400
MHz, CDCl.sub.3) .delta. 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H),
7.23 (m, 2H), 7.21 (m, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.40 (dd,
J=16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46
(s, 3H); ESIMS m/z 477.83 ([M-H].sup.-).
Example 14: Preparation of
(E)-2-Chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trif-
luoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC64)
##STR00157##
[0436] To a stirred solution of glycine amide (0.15 g, 0.58 mmol)
in CH.sub.2Cl.sub.2 (5 mL) was added trimethylaluminum (2 M
solution in toluene; 1.45 mL, 2.91 mmol) dropwise, and the reaction
mixture was stirred at 28.degree. C. for 30 min. A solution of
(E)-ethyl
2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate
(0.3 g, 0.58 mmol) in CH.sub.2Cl.sub.2 (5 mL) was added drop wise
to the reaction mixture at 28.degree. C. The reaction mixture was
stirred at reflux for 18 h, cooled to 25.degree. C., quenched with
1N HCl solution (50 mL) and extracted with CH.sub.2Cl.sub.2
(2.times.50 mL). The combined organic extracts were washed with
brine, dried over Na.sub.2SO.sub.4, and concentrated under reduced
pressure. The crude compound was purified by flash chromatography
(SiO.sub.2, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to
afford the title compound as yellow solid (0.15 g, 50%): mp
83-85.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.72
(d, J=8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J=6.8 Hz,
1H), 7.05 (t, J=5.2 Hz, 1H), 6.70 (t, J=5.2 Hz, 1H), 6.57 (d,
J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.23 (d, J=5.6 Hz,
2H), 4.15 (m, 1H), 4.01 (m, 2H); ESIMS m/z 580.72
([M-H].sup.-).
[0437] Compounds AC59-AC75 (Table 1) were made in accordance with
the procedures disclosed in Example 14.
Example 15: Preparation of
(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1--
yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide
(AC79)
##STR00158##
[0439] To a stirred solution of
(E)-2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-
benzoic acid (300 mg, 0.638 mmol) in CH.sub.2Cl.sub.2 (5.0 mL) was
added 2-amino-N-(2,2,2-trifluoroethyl)acetamide (172. mg, 0.638
mmol) followed by PyBOP (364.5 mg, 0.701 mmol) and DIPEA (0.32 mL,
1.914 mmol), and the resultant reaction mixture was stirred at
ambient temperature for 18 h. The reaction mixture was diluted with
water and extracted with CH.sub.2Cl.sub.2. The combined
CH.sub.2Cl.sub.2 layer was washed with brine, dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; eluting with 40% EtOAc/petroleum ether) afforded the title
compound as an off-white solid (121 mg, 31%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.69 (t, J=6.0 Hz, 1H), 8.58 (t, J=6.0 Hz, 1H),
7.92 (s, 1H), 7.87 (d, J=6.4 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.45
(d, J=8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.83 (t,
J=8.0 Hz, 1H), 3.98 (m, 4H); ESIMS m/z 610.97 ([M+H].sup.+); IR
(thin film) 3303, 1658, 1166, 817 cm.sup.-1.
[0440] Compounds AC76-AC80, AC96-AC102, and AC113 (Table 1) were
made in accordance with the procedures disclosed in Example 15.
Example 16: Preparation of
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(1,1-dioxid-
othietan-3-yl)-2-fluorobenzamide (AC83)
##STR00159##
[0442] To a stirred solution of
(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluoro-N-(thie-
tan-3-yl)benzamide (100 mg, 0.2159 mmol) in acetone/water (1:1, 5.0
mL) was added oxone (266 mg, 0.4319 mmol) and the resultant
reaction mixture was stirred at ambient temperature for 4 h. The
reaction mixture was diluted with water and extracted with EtOAc.
The combined EtOAc layer was dried over anhydrous Na.sub.2SO.sub.4
and concentrated under reduced pressure. Purification by flash
column chromatography (SiO.sub.2, 100-200 mesh; eluting with 30%
EtOAc/pet ether) afforded the title compound as an off white solid
(70.0 mg, 66%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.07 (t,
J=8.4 Hz, 1H), 7.39 (t, J=1.6 Hz, 1H), 7.31 (d, J=1.2 Hz, 1H), 7.26
(m, 2H), 7.23 (m, 2H), 7.19 (d, J=1.6 Hz, 1H), 6.60 (d, J=16.8 Hz,
1H), 6.49 (dd, J=16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H),
4.14 (m, 2H; ESIMS m/z 493.83 ([M-H].sup.-); IR (thin film) 1527,
1113, 801, 1167, 1321 cm.sup.-1.
[0443] Compounds AC81-AC87 (Table 1) were made in accordance with
the procedures disclosed in Example 16.
Example 17: Preparation of
(E)-N-((5-Cyclopropyl-1,3,4-oxadiazol-2-yl)methyl)-4-(3-(3,5-dichlorophen-
yl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzamide (AC89)
##STR00160##
[0445] A solution of
(E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5-dichl-
orophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (200 mg,
0.379 mmol) in phosphoryl chloride (POCl.sub.3, 2.0 mL) was stirred
at ambient temperature for 10 min, then the resultant reaction
mixture was heated to 50.degree. C. for 1 h. The reaction mixture
was quenched with ice water at 0.degree. C. and extracted with
EtOAc. The combined EtOAc layer was washed with saturated sodium
bicarbonate (NaHCO.sub.3) solution and brine solution, dried over
anhydrous Na.sub.2SO.sub.4, and concentrated under reduced
pressure. Purification by flash column chromatography (SiO.sub.2,
100-200 mesh; eluting with 50% EtOAc/pet ether) afforded the title
compound as a light brown gummy material (70.0 mg, 36%): .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.43 (m, 2H), 7.27 (m, 2H), 7.23
(m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.41 (dd, J=16.0, 7.6 Hz, 1H),
4.79 (d, J=5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H),
1.16 (m, 4H); ESIMS m/z 509.89 ([M+H].sup.+); IR (thin film) 1666,
1166, 1112, 800 cm.sup.-1.
Example 18: Preparation of
(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-tr-
ifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzothioamide
(AC90)
##STR00161##
[0447] To a stirred solution of
(E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifl-
uoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg,
0.638 mmol) in 5 mL of THF at ambient temperature was added
2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide
(Lawesson's reagent) (336 mg, 0.830 mmol) in one portion. The
resulting reaction mixture was stirred for 18 h. TLC showed the
reaction was not complete, therefore additional Lawesson's reagent
(168 mg, 0.415 mmol) was added and reaction stirred for 48 h. After
the reaction was deemed complete by TLC, the reaction mixture was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 230-400 mesh; eluting with 20% EtOAc in
hexanes) afforded the title compound as a yellow glassy oil (188
mg, 44.7%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.34 (m, 1H),
8.27 (m, 1H), 7.60 (d, J=1.6 Hz, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.40
(s, 2H), 7.36 (dd, J=8.2, 1.7 Hz, 1H), 6.53 (d, J=16.0 Hz, 1H),
6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.89 (d, J=8.4, 5.5 Hz, 2H), 4.48
(qd, J=9.0, 6.0 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 656.9 ([M-H]).
Example 19: Preparation of
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
phenylthioamido)-N-(2,2,2-trifluoroethyl)acetamide (AC91)
##STR00162##
[0449] To a stirred solution of
(E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifl-
uoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg,
0.638 mmol) in 5 mL of THF at ambient temperature was added
Lawesson's reagent (64.5 mg, 0.160 mmol) in one portion. The
resulting reaction mixture was stirred for 18 h, after which time,
the reaction mixture was concentrated under reduced pressure.
Purification by flash chromatography (SiO.sub.2, 230-400 mesh;
eluting with 20% EtOAc in hexanes) afforded the title compounds as
a yellow oil (18.5 mg, 4.51%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.18 (t, J=5.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 7.47 (d,
J=8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J=8.1, 1.6 Hz, 1H), 6.52 (m,
2H), 6.37 (dd, J=15.9, 7.9 Hz, 1H), 4.54 (d, J=4.9 Hz, 2H), 4.12
(m, 1H), 3.99 (qd, J=8.9, 6.5 Hz, 2H); ESIMS m/z 640.9
([M-H].sup.-).
[0450] The following compound was made in accordance with the
procedures disclosed in Example 19.
(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-tri-
fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC92)
##STR00163##
[0452] The product was isolated as a colorless oil (17.9 mg,
4.36%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 9.16 (d, J=6.1
Hz, 1H), 7.65 (d, J=1.6 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.41 (m,
3H), 7.21 (t, J=5.6 Hz, 1H), 6.55 (d, J=15.9 Hz, 1H), 6.41 (dd,
J=15.9, 7.8 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.45 (qd, J=9.0, 6.0
Hz, 2H), 4.12 (q, J=7.2 Hz, 1H); ESIMS m/z 640.9 ([M-H].sup.-).
Example 106: Preparation of Ethyl
(Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ben-
zoate (AI76)
##STR00164##
[0454] The title compound was made in accordance with the procedure
disclosed in Example 88 and was isolated as a yellow viscous oil
(416 mg, 23%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.80 (d,
J=8.0 Hz, 1H), 7.40 (d, J=1.7 Hz, 1H), 7.35 (s, 2H), 7.12 (dd,
J=8.0, 1.7 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.23-5.91 (m, 1H),
4.42 (q, J=7.1 Hz, 2H), 4.33-4.10 (m, 1H), 1.42 (t, J=7.2 Hz, 3H);
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -69.34 (d, J=8.3 Hz);
EIMS m/z 514.10 ([M].sup.-); IR (thin film) 2983, 1727, 1247, 1204,
1116 cm.sup.-1.
Example 107: Preparation of
(Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ben-
zoic acid (AI77)
##STR00165##
[0456] To a stirred solution of (Z)-ethyl
2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoat-
e (360 mg, 0.70 mmol) in CH.sub.3CN (1.0 mL) was added
iodotrimethylsilane (0.28 mL, 2.8 mmol). The reaction mixture was
heated to reflux for 20 h, allowed to cool to ambient temperature
and partitioned between CH.sub.2Cl.sub.2 and aqueous 10% sodium
thiosulfate (Na.sub.2S.sub.2O.sub.3). The organic phase was washed
once with aqueous 10% Na.sub.2S.sub.2O.sub.3 and dried over
magnesium sulfate (MgSO.sub.4) and concentrated in vacuo. Passing
the material through a silica plug with 10% EtOAc in hexanes,
followed by 20% MeOH in CH.sub.2Cl.sub.2) as the eluting solvents
afforded the title compound as a yellow foam (143 mg, 42%): mp
54-64.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 11.36
(s, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 2H), 7.14
(d, J=7.9 Hz, 1H), 6.85 (d, J=11.4 Hz, 1H), 6.15 (t, J=10.9 Hz,
1H), 4.36-4.09 (m, 1H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-69.30.
Example 108: Preparation of
(Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifl-
uoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC95)
##STR00166##
[0458] To a stirred solution of
(Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ben-
zoic acid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added
carbonyldiimidazole (82 mg, 0.51 mmol). The mixture was heated in a
50.degree. C. oil bath for 1.5 h, treated with
2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (109 mg,
0.057 mmol) and the resulting mixture heated to reflux for 8 h.
After cooling to ambient temperature, the mixture was taken up in
Et.sub.2O and washed twice with aqueous 5% sodium bisulfate
(NaHSO.sub.4) (2.times.) and once with saturated NaCl (1.times.).
After dying over MgSO.sub.4, concentration in vacuo and
purification by medium pressure chromatography on silica with
EtOAc/Hexanes as the eluents, the title compound was obtained as a
white foam (160 mg, 41%) mp 48-61.degree. C.: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.58 (d, J=7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14
(dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.76 (t, J=5.9
Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J=5.5 Hz,
1H), 3.98 (qd, J=9.0, 6.5 Hz, 2H); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -69.31, -72.3; EIMS m/z 626.9
([M+1].sup.+).
Example 109a: Preparation of
(E)-2-Bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-en-1-yl)benzamide (AC114)
##STR00167##
[0460] (E)-tert-Butyl
4-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzami-
do)piperidine-1-carboxylate (0.75 g, 1.11 mmol) was added to
dioxane HCl (10 mL) at 0.degree. C. and was stirred for 18 h. The
reaction mixture was concentrated under reduced pressure and
triturated with diethylether to afford the compound as a light
brown solid (0.6 g, 88%).
Example 109b: Preparation of
(E)-N-(1-Acetylpiperidin-4-yl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichl-
orophenyl)but-1-en-1-yl)benzamide (AC103)
##STR00168##
[0462] To a stirred solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in CH.sub.2Cl.sub.2 (10.0
mL) was added TEA (0.046 mL, 0.35 mmol) and stirred for 10 min.
Then acetyl chloride (0.014, 0.18 mmol) was added and stirred for
16 h at ambient temperature. The reaction mixture was diluted with
CH.sub.2Cl.sub.2 and washed with saturated NaHCO.sub.3 solution and
brine solution. The combined CH.sub.2Cl.sub.2 layer was dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
crude compound. The crude compound was washed with 5%
Et.sub.2O/n-pentane to afford the title compound as a white solid
(0.054 g, 50%).
Example 110: Preparation of
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N--
(1-(3,3,3-trifluoropropanoyl)piperidin-4-yl)benzamide (AC104)
##STR00169##
[0464] To a stirred solution of 3,3,3-trifluoropropanoic acid (0.02
g, 0.16 mmol) in CH.sub.2Cl.sub.2 (10.0 mL),
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4-trifluoro-3-(3,4,5-trichlorophenyl)-
but-1-enyl)benzamide (0.1 g, 0.16 mmol), PYBOP (0.09 g, 0.17 mmol),
and DIPEA (0.06 g, 0.48 mmol) were added at ambient temperature.
The reaction mixture was stirred at ambient temperature for 5 h.
The reaction mixture was diluted with CH.sub.2Cl.sub.2. The
combined CH.sub.2Cl.sub.2 layer was washed with 3N HCl and
saturated NaHCO.sub.3 solution, the separated CH.sub.2Cl.sub.2
layer was dried over anhydrous Na.sub.2SO.sub.4 and concentrated
under reduced pressure to afford crude compound. The crude compound
was purified by column chromatography (SiO.sub.2, 100-200 mesh;
eluting with 2% MeOH in CH.sub.2Cl.sub.2) to afford the title
compound as an off white gummy material (0.035 g, 29.%).
Example 111: Preparation of
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N--
(1-(2,2,2-trifluoroethyl)piperidin-4-yl)benzamide (AC105)
##STR00170##
[0466] To a stirred solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in THF (5.0 mL) was added
TEA (0.06 mL, 0.64 mmol) and stirred for 10 min. Then
2,2,2-trifluoroethyl trifluoromethanesulfonate (0.03, 0.16 mmol)
was added and stirred for 16 h at ambient temperature. The reaction
mixture was diluted with EtOAc and washed with saturated
NaHCO.sub.3 solution and brine solution. The combined EtOAc layer
was dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure to afford the title compound as a brown solid (0.05 g,
44%).
Example 112: Preparation of
(E)-2-Bromo-N-(1-methylpiperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichl-
orophenyl)but-1-en-1-yl)benzamide (AC106)
##STR00171##
[0468] A solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.1 g, 0.16 mmol), formaldehyde (30% in
water) (0.1 mL, 0.16 mmol) and AcOH (0.01 mL) in MeOH (5.0 mL) was
stirred at ambient temperature for 30 min. After that NaBH.sub.3CN
(0.01 g, 0.16 mmol) was added at 0.degree. C. and the reaction was
stirred for 8 h at ambient temperature. The solvent was removed
under reduced pressure to obtain residue which was diluted with
EtOAc and washed with saturated aqueous NaHCO.sub.3 solution and
brine solution. The combined EtOAc layer was dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to obtain
a residue, which was triturated with Et.sub.2O/pentane to afford
the title compound as a pale yellow gummy material (0.06 g,
59%).
Example 113: Preparation of
((E)-2-Bromo-N-(1-(cyanomethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,-
5-trichlorophenyl)but-1-en-1-yl)benzamide (AC107)
##STR00172##
[0470] To a stirred solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was
added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10
min. Then 2-bromoacetonitrile (0.07, 0.65 mmol) was added and the
reaction was stirred for 8 h at ambient temperature. The reaction
mixture was diluted with EtOAc and washed with saturated brine
solution. The combined EtOAc layer was dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure to afford the title
compound as an off-white solid (0.125 g, 46.8%).
Example 114: Preparation of
(E)-2-Bromo-N-(1-(oxetan-3-yl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-
-trichlorophenyl)but-1-en-1-yl)benzamide (AC108)
##STR00173##
[0472] A solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.2 g, 0.35 mmol), oxetan-3-one (0.027 g,
0.38 mmol) and AcOH (0.01 mL) in MeOH (5.0 mL) was stirred at
ambient temperature for 30 min. After that NaBH.sub.3CN (0.022 g,
0.35 mmol) was added at 0.degree. C. slowly lot wise over the
period of 10 min and the reaction was stirred for 8 h at ambient
temperature. The solvent was removed under reduced pressure to
obtain a residue which was diluted with EtOAc and washed with
saturated NaHCO.sub.3 solution and brine solution. The combined
EtOAc layer was dried over Na.sub.2SO.sub.4 and concentrated under
reduced pressure to obtain a residue, which was triturated with
Et.sub.2O/pentane to afford the title compound as an off-white
solid (0.05 g, 23%).
Example 115: Preparation of
(E)-2-Bromo-N-(1-(2-hydroxyethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,-
4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC109)
##STR00174##
[0474] To a stirred solution of
(E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichloropheny-
l)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was
added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10
min. Then 2-chloroethanol (0.05, 0.65 mmol) was added and the
reaction was stirred for 8 h at ambient temperature. The reaction
mixture was diluted with EtOAc and washed with saturated brine
solution. The combined EtOAc layer was dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure to afford the title
compound as an off-white solid (0.09 g, 34%).
Example 116: Preparation of
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
benzamido)acetic acid (AI78)
##STR00175##
[0476] To a stirred solution of (E)-tert-butyl
2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzami-
do)acetate (440 mg, 0.734 mmol) in CH.sub.2Cl.sub.2 (36.0 ml), was
added TFA (4.0 mL) and the reaction mixture was stirred at ambient
temperature for 1 h. The reaction mixture was concentrated under
reduced pressure to obtain residue which was washed with n-pentane
to afford the title compound as an off-white solid (310 mg, 78%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 13.0 (s, 1H), 8.75 (t,
J=5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, J=7.5 Hz, 1H), 7.40 (d, J=8.1
Hz, 1H), 6.96 (dd, J=15.3, 9.3 Hz, 1H), 6.78 (d, J=15.3 Hz, 1H),
4.83 (m, 1H), 3.90 (d, J=5.7 Hz, 2H); ESIMS m/z 543.61
([M+H].sup.+); IR (thin film) 3429, 1635, 1114, 772 cm.sup.-1.
Example 117: Preparation of
(E)-N-((6-Chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trif-
luorobut-1-en-1-yl)-2-methylbenzothioamide (AC115)
##STR00176##
[0478] To the stirred solution of
(E)-N-((6-chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trif-
luorobut-1-enyl)-2-methylbenzamide (0.06 g, 0.117 mmol) in toluene
(3 mL) was added Lawesson's reagent (0.14 g, 0.351 mmol) and the
reaction was irradiated at 100.degree. C. for 1 h, then cooled to
ambient temperature and concentrated under reduced pressure to
provide crude compound. The crude product was purified by
preparative HPLC to afford the product as yellow color solid (0.03
g, 49%).
Example 118: Preparation of
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-
-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide
(AC116)
##STR00177##
[0479] Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79)
[0480] To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic
acid (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium
vinyltrifluoroborate (1.47 g, 11.02 mmol) and K.sub.2CO.sub.3 (1.52
g, 11.02 mmol). The reaction mixture was degassed with argon for 30
min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium
dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture
was heated to 80.degree. C. for 1 h. The reaction mixture was
diluted with water (100 mL), extracted with EtOAc (2.times.50 mL),
washed with brine, and dried over Na.sub.2SO.sub.4. Concentration
under reduced pressure furnished the crude compound which was
purified by flash column chromatography to afford the product as
pale yellow gummy material (0.4 g, 47%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H),
7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz,
1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H].sup.+).
Step 2.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)--
2-(trifluoromethoxy)benzoic acid (AI80)
[0481] To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic
acid (0.356 g, 1.53 mmol) in 1N methyl pyrrolidine (5.0 mL) was
added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene
(1.0 g, 3.07 mmol), CuCl (0.03 g, 0.307 mmol) and 2,2 bipyridyl
(0.095 g, 0.614 mmol). The reaction mixture was stirred at
150.degree. C. for 1 h. After the reaction was complete by TLC, the
reaction mixture was diluted with water (100 mL) and extracted with
EtOAc (2.times.50 mL). The combined organic layers were washed with
brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure to obtain the crude compound which was purified by flash
column chromatography to afford the product as pale yellow gummy
material (0.3 g, 21%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35 (s, 3H), 6.63
(d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15 (m, 1H);
ESIMS m/z 474.81 ([M-H]).
Step 3.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)--
N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)-2-(trifluoromethoxy)benzamide
(AC116)
[0482] A mixture of
(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trif-
luoromethoxy)benzoic acid (0.25 g, 0.52 mmol),
2-amino-N-(2,2,2-trifluoroethyl)acetamide (0.158 g, 0.62 mmol),
PyBOP (0.40 g, 0.78 mmol) and DIPEA (0.134 g, 1.04 mmol) in
CH.sub.2Cl.sub.2 (10.0 mL) were stirred at ambient temperature for
16 h. The reaction mixture was diluted with water and extracted
with CH.sub.2Cl.sub.2. The combined CH.sub.2Cl.sub.2 layer was
washed with brine, dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure. Purification by flash column chromatography
(SiO.sub.2, 100-200 mesh; eluting with 20% EtOAc/pet ether)
afforded the title compound as a pale yellow gummy material (0.15
g, 47%). The following molecules were made in accordance with the
procedures disclosed in Example 118, Step 2:
(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoic
acid
##STR00178##
[0484] The title molecule was isolated as a brown solid: .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 12.90 (bs, 1H), 7.85 (s, 1H),
7.78-7.75 (m, 3H), 7.47-7.41 (m, 2H), 6.89 (dd, J=15.6, 9.2 Hz,
1H), 6.72 (d, J=15.6 Hz, 1H), 4.80-4.75 (m, 1H), 2.33 (s, 3H);
ESIMS m/z 474.90 ([M-H].sup.-); IR (thin film) 3437, 1689, 1165,
579 cm.sup.-1.
(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromet-
hyl)benzoic acid
##STR00179##
[0486] The title molecule was isolated as a brown solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.5 (bs, 1H), 8.03 (s, 1H),
7.95-7.85 (m, 4H), 7.81 (d, J=7.8 Hz, 1H), 7.14 (dd, J=15.6, 9.6
Hz, 1H), 6.90 (d, J=15.9 Hz, 1H), 4.86-4.79 (m, 1H); ESIMS m/z
528.82 ([M-H].sup.+); IR (thin film) 3437, 1707, 1153, 555
cm.sup.-1.
(E)-2-Bromo-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic
acid
##STR00180##
[0488] The title molecule was isolated as a brown liquid: .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 13.90 (bs, 1H), 7.98 (s, 1H),
7.88 (s, 1H), 7.84 (s, 2H), 7.74 (d, J=7.6 Hz, 1H), 7.64 (d, J=8.8
Hz, 1H), 7.04 (dd, J=15.6, 8.8 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H),
4.80-4.78 (m, 1H); ESIMS m/z 538.74 ([M-H].sup.-); IR (thin film)
3424, 1695, 1168, 578 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-fluoro-5-(trifluoromethyl)phenyl)but-1-
-en-1-yl)benzoic acid
##STR00181##
[0490] The title molecule was isolated as a brown liquid: .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 13.3 (bs, 1H), 7.93 (s, 1H),
7.82-7.77 (m, 2H), 7.72-7.66 (m, 2H), 7.59 (d, J=8.0 Hz, 1H), 7.03
(dd, J=15.6, 9.2 Hz, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.94-4.90 (m,
1H); ESIMS m/z 469.02 ([M-H].sup.-); IR (thin film) 3444, 1704,
1172, 513 cm.sup.-1.
(E)-4-(3-(3,5-Bis(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-en-1-yl)-2--
bromobenzoic acid
##STR00182##
[0492] The title molecule was isolated as a brown solid: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.98 (d, J=7.6 Hz, 1H), 7.92 (s,
1H), 7.83 (s, 2H), 7.73 (d, J=1.6 Hz, 1H), 7.42-7.40 (m, 1H), 6.62
(d, J=16.4 Hz, 1H), 6.55 (dd, J=16.0, 8.0 Hz, 1H), 4.40-4.30 (m,
1H); ESIMS m/z 518.94 ([M-H].sup.-); IR (thin film) 3447, 1705,
1171, 526 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)-
benzoic acid
##STR00183##
[0494] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.50 (bs, 1H), 7.97-7.87 (m,
3H), 7.78-7.61 (m, 4H), 7.08 (dd, J=15.9, 9.3 Hz, 1H), 6.81 (d,
J=15.9 Hz, 1H), 4.97-4.84 (m, 1H); ESIMS m/z 518.94 ([M-H].sup.-);
IR (thin film) 3447, 1705, 1171, 526 cm.sup.-1.
(E)-2-Bromo-4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-
-en-1-yl)benzoic acid
##STR00184##
[0496] The title molecule was isolated as a pale yellow gum:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 13.9 (s, 1H), 8.03 (s,
1H), 7.96-7.91 (m, 3H), 7.72 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H),
7.11 (dd, J=15.9, 9.6 Hz, 1H), 6.79 (d, J=15.9 Hz, 1H), 4.98-4.91
(m, 1H); ESIMS m/z 484.94 ([M-H].sup.-); IR (thin film) 3444, 1705,
1171, 764 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-
-en-1-yl)benzoic acid
##STR00185##
[0498] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 8.00 (d, J=8.1 Hz, 1H), 7.71 (s,
1H), 7.61-7.59 (m, 2H), 7.41 (d, J=8.1 Hz, 1H), 7.30-7.24 (m, 1H),
6.59 (dd, J=16.2, 6.0 Hz, 1H), 6.48 (d, J=16.5 Hz, 1H), 4.26-4.21
(m, 1H); ESIMS m/z 469.0 ([M-H].sup.-); IR (thin film) 3444, 1699,
1327 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)benz-
oic acid
##STR00186##
[0500] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.60 (bs, 1H), 7.97 (s, 2H), 7.72
(d, J=7.2 Hz, 1H), 7.41-7.31 (m, 2H), 7.04 (dd, J=15.6, 9.0 Hz,
1H), 6.71 (d, J=15.9 Hz, 1H), 4.15-4.11 (m, 1H); ESIMS m/z 438.8
([M+H].sup.+).
(E)-4-(4,4,4-Trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)-2-(trifluor-
omethyl)benzoic acid
##STR00187##
[0502] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 8.00 (s, 1H), 7.93 (d, J=8.4 Hz,
1H), 7.81 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H), 7.47-7.44 (m, 1H),
7.02-7.01 (m, 1H), 5.10-4.90 (m, 1H).
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)benz-
oic acid
##STR00188##
[0504] The title molecule was isolated as a brown gum and the crude
acid was taken on directly to the next step: .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 13.65 (bs, 1H), 7.95 (s, 1H), 7.75 (d, J=7.8
Hz, 1H), 7.62-7.59 (m, 2H), 7.50 (dd, J=15.6, 9.0 Hz, 1H), 6.95 (d,
J=15.9 Hz, 1H), 4.86-4.74 (m, 1H); ESIMS m/z 436.92 ([M-H].sup.-);
IR (thin film) 3445, 1641, 1116 cm.sup.-1.
(E)-4-(4,4,4-Trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluor-
omethyl)benzoic acid
##STR00189##
[0506] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.6 (s, 1H), 8.04 (s, 1H), 7.96
(d, J=8.4 Hz, 3H), 7.83 (d, J=8.1 Hz, 1H), 7.17-7.03 (m, 2H),
5.16-5.05 (m, 1H); ESIMS m/z 476.9 ([M-H].sup.-); IR (thin film)
3436, 1651, 1116, 661 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)benz-
oic acid
##STR00190##
[0508] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. (300 MHz, DMSO-d.sub.6) .delta.
13.4 (s, 1H), 7.99 (d, J=10.2 Hz, 3H), 7.76 (d, J=8.1 Hz, 1H), 7.65
(d, J=7.8 Hz, 1H), 7.09-6.91 (m, 2H), 5.11-5.05 (m, 1H); ESIMS m/z
486.8 ([M-H].sup.-); IR (thin film) 3436, 1651, 1115, 737
cm.sup.-1.
(E)-4-(3-(4-Chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluo-
romethyl)benzoic acid
##STR00191##
[0510] The title molecule was isolated as a brown gum and the crude
acid was taken on directly to the next step: .sup.1H NMR (300 MHz,
DMSO-d.sub.6) 13.80 (bs, 1H), 8.33 (s, 1H), 7.94-7.81 (m, 5H),
7.75-7.72 (m, 1H), 7.06 (dd, J=15.9, 8.7 Hz, 1H), 6.90 (d, J=15.9
Hz, 1H), 5.02-4.81 (m, 1H).
(E)-2-Bromo-4-(3-(4-chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)ben-
zoic acid
##STR00192##
[0512] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) 13.50 (bs, 1H), 8.31 (s, 1H), 8.00-7.77 (m,
3H), 7.75-7.72 (m, 1H), 7.63-7.55 (m, 1H), 7.03 (dd, J=15.9, 9.0
Hz, 1H), 6.81 (d, J=15.9 Hz, 1H), 5.04-4.91 (m, 1H); ESIMS m/z
462.16 ([M-H]); IR (thin film) 3428, 1697, 1113, 749 cm.sup.-1.
(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-yl)-2-(tr-
ifluoromethyl)benzoic acid
##STR00193##
[0514] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.96 (s, 1H), 7.92 (d, J=8.4 Hz,
1H), 7.80-7.75 (m, 1H), 7.27 (d, J=6.9 Hz, 2H), 6.96 (dd, J=15.6,
8.7 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H), 4.68-4.56 (m, 1H), 2.23 (s,
6H); ESIMS m/z 419.03 ([M-H].sup.-); IR (thin film) 3445, 2928,
1713, 1146 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-y-
l)benzoic acid
##STR00194##
[0516] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 7.91 (s, 1H), 7.74 (d, J=7.8 Hz,
1H), 7.61-7.58 (m, 1H), 7.26 (d, J=6.6 Hz, 2H), 6.93 (dd, J=15.9,
8.7 Hz, 1H), 6.87 (d, J=15.9 Hz, 1H), 4.59-4.53 (m, 1H), 2.23 (s,
6H); ESIMS m/z 428.97 ([M-H].sup.-); IR (thin film) 3473, 1701,
1111, 581 cm.sup.-1.
(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)-2-(triflu-
oromethyl)benzoic acid
##STR00195##
[0518] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.58 (bs, 1H), 7.98 (s, 1H),
7.92-7.90 (m, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.48-7.45 (m, 1H),
7.42-7.37 (m, 1H), 7.22-7.16 (m, 1H), 7.04 (dd, J=15.9, 8.7 Hz,
1H), 6.88 (d, J=15.9 Hz, 1H), 4.70-4.60 (m, 1H), 4.04-3.99 (m, 1H),
2.26 (s, 3H); ESIMS m/z 405.05 ([M-H].sup.-); IR (thin film) 3437,
1710, 1145 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)be-
nzoic acid
##STR00196##
[0520] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.39 (bs, 1H), 7.91 (s, 1H),
7.72 (d, J=8.1 Hz, 1H), 7.61-7.58 (m 1H), 7.47-7.44 (m, 1H),
7.38-7.36 (m, 1H), 7.18 (t, J=9.6 Hz, 1H), 6.95 (dd, J=15.6, 8.7
Hz, 1H), 6.76 (d, J=15.9 Hz, 1H), 4.67-4.61 (m, 1H), 2.25 (s, 3H);
ESIMS m/z 415.0 ([M-H].sup.-); IR (thin film) 3435, 2989, 1700,
1260 cm.sup.-1.
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)-2-(trif-
luoromethyl)benzoic acid
##STR00197##
[0522] The title molecule was isolated as a brown semi solid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.70 (bs, 1H), 8.01
(s, 1H), 7.91 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (J=1.6 Hz, 2H),
7.66 (t, J=3.2 Hz, 1H), 7.15 (dd, J=15.6, 9.6 Hz, 1H), 6.91 (d,
J=15.6 Hz, 1H), 4.86-4.78 (m, 1H); ESIMS m/z 491.0 ([M-H].sup.-);
IR (thin film) 3446, 1712, 1141, 749 cm.sup.-1.
(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)-
benzoic acid
##STR00198##
[0524] The title molecule was isolated as a brown gum: .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 7.85 (s, 1H), 7.70 (s, 2H),
7.65-7.64 (m, 1H), 7.56-7.52 (m, 2H), 6.94 (d, J=9.2 Hz, 1H), 6.76
(d, J=16 Hz, 1H), 4.82-4.80 (m, 1H); ESIMS m/z 500.8 ([M-H].sup.-);
IR (thin film) 3422, 1683, 1184, 750, 575 cm.sup.-1.
(E)-4-(3-(3,4-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromet-
hyl)benzoic acid
##STR00199##
[0526] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.5 (bs, 1H), 8.01-7.99 (m, 2H),
7.94-7.91 (m, 1H), 7.85-7.78 (m, 2H), 7.53-7.50 (m, 1H), 7.09 (dd,
J=15.6, 8.7 Hz, 1H), 6.89 (d, J=15.9 Hz, 1H), 4.85-4.78 (m, 1H);
ESIMS m/z 528.8 ([M-H].sup.-); IR (thin film) 3437, 1722, 1168
cm.sup.-1.
(E)-2-Bromo-4-(3-(3,4-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic
acid
##STR00200##
[0528] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.38 (bs, 1H), 7.98-7.96 (m, 2H),
7.84 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.63-7.61 (m, 1H),
7.51-7.49 (m, 1H), 7.01 (dd, J=15.9, 9.0 Hz, 1H), 6.78 (d, J=15.6
Hz, 1H), 4.82-4.76 (m, 1H); ESIMS m/z 538.8 ([(M-H].sup.-); IR
(thin film) 3446, 1699, 1166, 581 cm.sup.-1.
(E)-4-(4,4,4-Trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl)-2-(tri-
fluoromethyl)benzoic acid
##STR00201##
[0530] The title molecule was isolated as a brown semi solid:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 8.01 (s, 1H), 7.94 (d,
J=8.7 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.63-7.55 (m, 3H), 7.41 (d,
J=7.5 Hz, 1H), 7.11 (dd, J=15.6, 9.0 Hz, 1H), 6.92 (d, J=15.9 Hz,
1H), 4.89-4.82 (m, 1H); ESIMS m/z 456.98 ([M-H].sup.-); IR (thin
film) 3413, 1668, 1161 cm.sup.-1.
(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl-
)benzoic acid
##STR00202##
[0532] The title molecule was isolated as a brown solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 7.73 (s, 1H), 7.59 (m, 3H),
7.44 (s, 1H), 7.40 (d, J=7.6 Hz, 2H), 6.88 (dd, J=15.6, 9.0 Hz,
1H), 6.73 (d, J=15.9 Hz, 1H), 4.85-4.82 (m, 1H); ESIMS m/z 466.93
([M-H].sup.-); IR (thin film) 3437, 1703, 1111 cm.sup.-1.
(E)-4-(3-(3-Cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluo-
romethyl)benzoic acid
##STR00203##
[0534] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.60 (bs, 1H), 8.21-8.19 (m,
1H), 8.01-7.91 (m, 3H), 7.81 (d, J=8.4 Hz, 1H), 7.12 (dd, J=15.9,
8.1 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.92-4.86 (m, 1H); ESIMS m/z
416.27 ([M-H]); IR (thin film) 3429, 2238, 1713, 1116
cm.sup.-1.
(E)-2-Bromo-4-(3-(3-cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)ben-
zoic acid
##STR00204##
[0536] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.56 (bs, 1H), 8.21-8.18 (m, 1H),
8.00-7.95 (m, 2H), 7.73-7.59 (m, 3H), 7.03 (dd, J=15.9, 9.3 Hz,
1H), 6.79 (d, J=15.3 Hz, 1H), 4.87-4.84 (m, 1H); ESIMS m/z 426.0
([M-H].sup.-).
(E)-2-Bromo-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic
acid
##STR00205##
[0538] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.4 (s, 1H), 7.96 (d, J=1.2 Hz,
1H), 7.88 (d, J=1.8 Hz, 1H), 7.74-7.68 (m, 2H), 7.63 (dd, J=8.1,
1.2 Hz, 1H), 7.57 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (dd, J=15.9, 9.3
Hz, 1H), 6.78 (dd, J=5.9 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z
451.0 ([M-H].sup.-); IR (thin film) 3445, 1704, 1113, 740
cm.sup.-1.
(E)-4-(3-(3-Bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluo-
romethyl)benzoic acid
##STR00206##
[0540] The title molecule was isolated as a brown solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.50 (bs, 1H), 7.91 (s, 1H),
7.86-7.64 (m, 5H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.87 (d, J=15.9
Hz, 1H), 4.85-4.78 (m, 1H); ESIMS m/z 485.17 ([M-H].sup.-); IR
(thin film) 3438, 1708, 1114, 774, 516 cm.sup.-1.
(E)-2-Bromo-4-(3-(3-bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)ben-
zoic acid
##STR00207##
[0542] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.38 (bs, 1H), 7.98 (s, 1H),
7.80-7.72 (m, 4H), 7.64-7.61 (m, 1H), 7.06 (dd, J=15.9, 9.3 Hz,
1H), 6.79 (d, J=15.6 Hz, 1H), 4.88-4.80 (m, 1H); ESIMS m/z 495.05
([M-H].sup.-); IR (thin film) 3436, 1699, 1116, 750, 531
cm.sup.-1.
(E)-4-(3-(3-Bromo-5-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluo-
romethyl)benzoic acid
##STR00208##
[0544] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.6 (bs, 1H), 8.02 (s, 1H),
7.91-7.89 (m, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.69 (s, 1H), 7.63-7.59
(m, 1H), 7.55 (d, J=9.3 Hz, 1H), 7.11 (dd, J=15.9, 9.0 Hz, 1H),
6.91 (d, J=15.9 Hz, 1H), 4.87-4.80 (m, 1H); ESIMS m/z 469.07
([M-H].sup.-); IR (thin film) 3428, 1712, 1171, 523 cm.sup.-1.
(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic
acid
##STR00209##
[0546] The title molecule was isolated as a yellow solid: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 8.18-8.03 (m, 2H), 7.49 (d, J=8.3
Hz, 2H), 7.42 (s, 2H), 6.66 (d, J=15.9 Hz, 1H), 6.47 (dd, J=15.9,
8.0 Hz, 1H), 4.13 (p, J=8.6 Hz, 1H); .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -68.65; ESIMS m/z 409.1 ([M-H].sup.-).
(E)-2-Bromo-4-(3-(3-chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)be-
nzoic acid
##STR00210##
[0548] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.30 (bs, 1H), 7.93 (d, J=1.2
Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.62 (dd, J=1.5, 8.1 Hz, 1H), 7.53
(s, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 6.96 (dd,
J=15.6, 8.7 Hz, 1H), 6.77 (d, J=15.6 Hz, 1H), 4.73-4.61 (m, 1H),
2.35 (s, 3H); ESIMS m/z 431.77 ([M-H].sup.-1); IR (thin film) 3435,
1701, 1111, 750 cm.sup.-1.
(E)-4-(3-(3-Chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(triflu-
oromethyl)benzoic acid
##STR00211##
[0550] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.50 (bs, 1H), 7.98 (s, 1H), 7.92
(d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.53 (s, 1H), 7.48 (d,
J=8.1 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.04 (dd, J=15.6, 8.4 Hz,
1H), 6.88 (d, J=15.6 Hz, 1H), 4.72-4.66 (m, 1H), 2.35 (s, 3H);
ESIMS m/z 421.82 ([M-H].sup.-); IR (thin film) 3460, 2926, 1712,
1170, 750 cm.sup.-1.
(E)-4-(4,4,5,5,5-Pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(t-
rifluoromethyl)benzoic acid
##STR00212##
[0552] The title molecule was isolated as a dark brown gum: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.6 (bs, 1H), 8.03 (s, 1H),
7.95-7.86 (m, 3H), 7.81 (d, J=8.1 Hz, 1H), 7.16 (dd, J=15.3, 9.3
Hz, 1H), 6.92 (d, J=15.6 Hz, 1H), 4.95-4.88 (m, 1H); .sup.19F NMR
(300 MHz, DMSO-d.sub.6) .delta. -80.35, -58.02; ESIMS m/z 526.8
([M+H].sup.+).
(E)-2-Bromo-4-(4,4,5,5,5-pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1--
yl)benzoic acid
##STR00213##
[0554] The title molecule was isolated as a dark brown gum: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.6 (bs, 1H), 7.94 (s, 2H),
7.78 (d, J=7.8 Hz, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.60 (d, J=7.5 Hz
1H), 7.07 (dd, J=15.0, 8.7 Hz, 1H), 6.79 (d, J=15.6 Hz, 1H),
4.93-4.78 (m, 1H); ESIMS m/z 538.9 ([M+H].sup.+); IR (thinfilm)
3420, 1602, 1123, 746 cm.sup.-1.
(E)-2-Bromo-4-(3-(4-cyano-3,5-difluorophenyl)-4,4,4-trifluorobut-1-en-1-yl-
)benzoic acid
##STR00214##
[0556] The title molecule was isolated as a brown gum: ESIMS m/z
443.91 ([M-H].sup.-); IR (thin film) 3447, 2244, 1703, 1114
cm.sup.-1.
(E)-2-Chloro-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic
acid
##STR00215##
[0558] The title molecule was isolated as a brown liquid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 13.39 (bs, 1H), 7.95-7.70 (m,
5H), 7.61 (d, J=8.1 Hz, 1H), 7.07 (dd, J=15.6, 9.3 Hz, 1H), 6.80
(d, J=15.6 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z 496.77
([M-H].sup.-); IR (thin film) 3439, 2920, 1707, 1165 cm.sup.-1.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(tr-
ifluoromethyl)benzoic acid
##STR00216##
[0560] The title molecule was isolated as an off white solid: mp
140-143.degree. C.; .sup.1H NMR (400 MHz, DMSO) .delta.13.60 (bs,
1H), 8.02 (s, 1H), 7.94-7.90 (m, 1H), 7.88-7.86 (m, 2H), 7.81-7.79
(m, 1H), 7.12 (dd, J=15.6, 8.8 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H),
4.86-4.81 (m, 2H); ESIMS m/z 458.88 ([M-H].sup.-).
(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic
acid
##STR00217##
[0562] The title molecule was isolated as a light orange
crystalline solid (875 mg, 88%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 12.35 (s, 1H), 8.08 (d, J=8.4 Hz, 2H), 7.55-7.41 (m, 4H),
7.24 (dd, J=8.3, 2.1 Hz, 1H), 6.64 (d, J=15.8 Hz, 1H), 6.51 (dd,
J=15.9, 7.7 Hz, 1H), 4.15 (p, J=8.7 Hz, 1H); .sup.19F NMR 376 MHz,
CDCl.sub.3) .delta. -68.75; ESIMS m/z 375 ([M+H].sup.+).
(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluorome-
thyl)benzoic acid
##STR00218##
[0564] The title molecule was isolated was isolated as a brown gum:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.6 (s, 1H), 8.02 (s,
1H), 7.93-7.89 (m, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.73 (d, J=8.4, Hz,
1H), 7.58 (dd, J=8.4, 2.0 Hz, 1H), 7.09 (dd, J=15.6, 8.8, Hz, 1H),
6.89 (d, J=15.6, Hz, 1H), 4.86-4.81 (m, 1H); ESIMS m/z 441.0
([M-H].sup.-); IR (thinfilm) 3447, 1710, 1169, 749 cm.sup.-1.
(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluorome-
thyl)benzoic acid
##STR00219##
[0566] The title molecule was isolated was isolated as a brown gum:
.sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 13.6 (bs, 1H), 7.98 (s,
1H), 7.91 (d, J=7.8 Hz 1H), 7.75-7.66 (m, 1H), 7.10 (dd, J=15.6,
9.0 Hz, 1H), 6.89 (d, J=15.9 Hz 1H), 4.86-4.80 (m, 1H); ESIMS m/z
441.1 ([M-H].sup.-); IR (thinfilm) 3460, 2928, 1721, 1170, 764
cm.sup.-1.
(E)-4-(3-(3,4-Dichloro-5-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(tr-
ifluoromethyl)benzoic acid
##STR00220##
[0568] The title molecule was isolated as a pale yellow semi solid:
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.58 (bs, 1H), 8.00
(s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (s,
1H), 7.55 (s, 1H), 7.07 (dd, J=16.4, 9.6 Hz, 1H), 6.89 (d, J=15.6
Hz, 1H), 4.78-4.73 (m, 1H), 2.42 (s, 3H); ESIMS m/z 455.0
([M-H].sup.-); IR (thin film) 1713, 1170, 750 cm.sup.-1.
(E)-2-Bromo-4-(3-(3,4-dichlorophenyl)-4,4-difluoropent-1-en-1-yl)benzoic
acid
##STR00221##
[0570] The title molecule was isolated as a brown gum: .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 13.3 (s, 1H), 7.92 (s, 1H),
7.77-7.71 (m, 2H), 7.68-7.63 (m, 1H), 7.61-7.60 (m, 1H), 7.60-7.58
(m, 1H), 6.98 (dd, J=15.6, 9.2 Hz, 1H), 6.65 (d, J=15.6 Hz, 1H),
4.83-4.80 (m, 1H), 1.59-1.54 (m, 3H); ESIMS m/z 448.8
([M-H].sup.-).
(E)-2-Bromo-4-(3-(3-chloro-5-ethylphenyl)-4,4,4-trifluorobut-1-en-1-yl)ben-
zoic acid
##STR00222##
[0572] The title molecule was isolated as a brown liquid: .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 13.4 (bs, 1H), 7.97 (s, 2H),
7.91 (s, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.66-7.61 (m, 1H), 7.03 (dd,
J=16.0, 8.4 Hz, 1H), 6.8 (d, J=15.6 Hz, 1H), 4.89-4.84 (m, 1H),
2.66-2.65 (m, 2H), 1.25 (t, J=9.2 Hz, 3H); ESIMS m/z 446.8
([M+H].sup.+).
(E)-2,6-Dimethyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)be-
nzoic acid
##STR00223##
[0574] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.1 (s, 1H), 7.87 (s, 2H), 7.27
(s, 2H), 6.81 (dd, J=15.6, 8.7 Hz, 1H), 6.69 (d, J=15.3 Hz, 1H),
4.85-4.79 (m, 1H), 2.27 (s, 6H); ESIMS m/z 437.01 ([M-H].sup.-); IR
(thin film) 3285, 1621, 1162, 954 cm.sup.-1.
(E)-2-Bromo-4-(3-(3,5-dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl-
)benzoic acid
##STR00224##
[0576] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.40 (bs, 1H), 8.07 (d, J=7.5 Hz,
1H), 7.94-7.89 (m, 2H), 7.66-7.60 (m, 2H), 7.10 (dd, J=8.7, 16.0
Hz, 1H), 6.96 (d, J=15.6 Hz, 1H), 4.82-4.80 (m, 1H); ESIMS m/z
574.7 ([M+H].sup.+).
(E)-4-(3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(tri-
fluoromethyl)benzoic acid
##STR00225##
[0578] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.36 (bs, 1H) 8.05 (s, 2H), 7.95
(d, J=8.1 Hz, 1H), 7.87-7.67 (m, 2H), 7.14 (dd, J=9.0, 15.6 Hz,
1H), 6.96 (d, J=15.6 Hz, 1H), 4.88-4.82 (m, 1H); ESIMS m/z 564.58
([M+H].sup.+).
(E)-2-Bromo-4-(3-(4-bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl-
)benzoic acid
##STR00226##
[0580] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.40 (bs, 1H), 7.98 (s, 1H), 7.87
(s, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.65-7.62 (m, 1H), 7.06 (dd,
J=15.9, 9.3 Hz, 1H), 6.80 (d, J=15.9 Hz, 1H), 4.87-4.80 (m, 1H);
ESIMS m/z 518.9 ([M-H].sup.-).
(E)-4-(3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(tri-
fluoromethyl)benzoic acid
##STR00227##
[0582] The title molecule was isolated as a brown gum: .sup.1H NMR
(300 MHz, DMSO-d.sub.6) .delta. 13.6 (bs, 1H) 8.03 (s, 1H), 7.95
(d, J=8.4 Hz, 1H), 7.88 (s, 2H), 7.81 (d, J=8.1 Hz, 1H), 7.13 (dd,
J=16.2, 7.5 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.89-4.83 (m, 1H);
ESIMS m/z 532.0 ([M+H].sup.+).
(E)-2-Bromo-4-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-4,4,4-trifluorobut--
1-en-1-yl)benzoic acid
##STR00228##
[0584] The title molecule was isolated as a brown gum: .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 13.36 (bs, 1H) 7.95 (s, 1H), 7.73
(d, J=7.6 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.46 (s, 1H) 7.35-7.31
(m, 2H), 7.04 (dd, J=16.0, 8.8 Hz, 1H), 6.78 (d, J=16.4 Hz, 1H),
4.71-4.68 (m, 1H); ESIMS m/z 500.8 ([M-H].sup.-).
Example 20: Preparation of 5-vinyl-2,3-dihydro-1H-inden-1-one
(BI1)
##STR00229##
[0586] To a stirred solution of 5-bromo-2,3-dihydro-1H-inden-1-one
(5 g, 23.7 mmol) in toluene were added vinylboronic anhydride
pyridine complex (8.55 g, 35.54 mmol), Pd(PPh.sub.3).sub.4 (0.1 g,
0.094 mmol), K.sub.2CO.sub.3 (22.88 g, 165.83 mmol). The resultant
reaction mixture was heated at reflux for 16 h. The reaction
mixture was cooled to 25.degree. C. and filtered, and the filtrate
was concentrated under reduced pressure. The residue was diluted
with EtOAc and washed with water and brine. The combined organic
extracts were dried over anhydrous Na.sub.2SO.sub.4 and
concentrated under reduced pressure. The obtained residue was
purified by flash column chromatography (SiO.sub.2, 5% EtOAc in
petroleum ether) afforded the title compound as a solid (1.8 g,
48%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.74 (d, J=7.2 Hz,
1H), 7.49 (br s, 1H), 7.44 (d, J=7.2 Hz, 1H), 6.82 (m, 1H), 5.90
(d, J=7.4 Hz, 1H), 5.42 (d, J=6.4 Hz, 1H), 3.20 (m, 2H), 2.70 (m,
2H); ESIMS m/z 159.06 ([M+H].sup.-).
[0587] The following compound was made in accordance with the
procedures disclosed in Example 20.
6-Vinyl-3,4-dihydronaphthalen-1(2H)-one (BI2)
##STR00230##
[0589] The product was isolated as an off-white solid (5 g, 48%):
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 7.85 (d, J=8.4 Hz, 1H),
7.48 (m, 2H), 6.82 (m, 1H), 6.02 (d, J=7.4 Hz, 1H), 5.44 (d, J=6.4
Hz, 1H), 2.95 (m, 2H), 2.60 (m, 2H), 2.00 (m, 2H); ESIMS m/z 173.14
([M-H].sup.-); IR (thin film) 1681 cm.sup.-1.
Example 21: Preparation of
(E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1-
H-inden-1-one (BI3)
##STR00231##
[0591] 5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (4
g, 11.7 mmol), 5-vinyl-2,3-dihydro-1H-inden-1-one (0.92 g, 5.8
mmol), CuCl (0.115 g, 1.171 mmol) and 2,2-bipyridyl (0.053 g, 0.34
mmol) in 1,2-dichlorobenzene (25 mL) were heated at 180.degree. C.
for 16 h. The reaction mixture was cooled to 25.degree. C. and
concentrated under reduced pressure. The residue was purified by
flash column chromatography (SiO.sub.2, 5% EtOAc in petroleum
ether) to afford the title compound as a liquid (1.28 g, 25%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.76 (d, J=7.4 Hz, 1H),
7.52 (m, 3H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H),
3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 419.14 ([M+H].sup.-); IR
(thin film) 1708.94, 1113.60, 807.77 cm.sup.-1.
[0592] The following compound was made in accordance with the
procedures disclosed in Example 21.
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-d-
ihydro-1H-inden-1-one (BI4)
##STR00232##
[0594] The product was isolated as a brown semi-solid (1.2 g, 16%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.76 (d, J=7.4 Hz, 1H),
7.54 (m, 3H), 7.30 (s, 1H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H),
4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 400.84
([M-H].sup.-); IR (thin film) 815, 1113, 1709 cm.sup.-1.
(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronap-
hthalen-1(2H)-one (BI5)
##STR00233##
[0596] The product was isolated as a pale yellow semi solid (1.2 g,
30%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.20 (d, J=8.0 Hz,
1H), 7.42 (s, 2H), 7.35 (m, 1H), 7.24 (m, 2H), 6.62 (d, J=16 Hz,
1H), 6.46 (m, 1H), 4.18 (m, 1H), 2.95 (m, 2H), 2.65 (m, 2H), 2.19
(m, 2H); ESIMS m/z 432.94 ([M-H].sup.-); IR (thin film) 1680, 1113,
808 cm.sup.-1.
Example 22: Preparation of
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fl-
uoro-2,3-dihydro-1H-inden-1-one (BI6)
##STR00234##
[0598] To a stirred solution of
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dih-
ydro-1H-inden-1-one (0.5 g, 1.24 mmol) in MeCN (20 mL), was added
Selectfluor.RTM. (0.52 g, 1.48 mmol) and the reaction was heated to
reflux temperature for 16 h. The reaction mixture was cooled to
room temperature, concentrated under reduced pressure and diluted
with CH.sub.2Cl.sub.2. The solution was washed with water and
brine, dried over anhydrous Na.sub.2SO.sub.4 and concentrated under
reduced pressure to give the crude product which was purified by
flash column chromatography (SiO.sub.2, 100-200 mesh; 15% EtOAc in
petroleum ether) to afford the title compound as a pale yellow semi
solid (0.1 g, 24%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.80
(m, 1H), 7.48 (m, 2H), 7.32 (m, 2H), 6.65 (d, J=16.0 Hz, 1H), 6.54
(dd, J=16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H),
3.32 (m, 1H); ESIMS m/z 419.06 ([M-H].sup.-); IR (thin film) 1728,
1114, 817 cm.sup.-1.
Example 23: Preparation of
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(3-
,3,3-trifluoropropyl)-2,3-dihydro-1H-inden-1-amine (BC10)
##STR00235##
[0600] To a stirred solution of
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dih-
ydro-1H-inden-1-one (0.15 g, 0.35 mmol) in DCE (10 mL), was added
trifluoropropyl amine (0.048 g, 0.42 mmol) and NaBH.sub.3CN (0.055
g, 0.875 mmol) in cooling and the reaction mixture was stirred at
room temperature for 16 h. The reaction mixture was diluted with
DCE, was washed with water and brine and dried over anhydrous
Na.sub.2SO.sub.4. Concentration under reduced pressure gave the
crude compound, which was purified by flash column chromatography
(SiO.sub.2, 100-200 mesh; 10-15% EtOAc in petroleum ether) to
afford the title compound as a colorless gummy material (0.042 g,
24%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.38-7.20 (m, 5H),
6.62 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.83 (br,
1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50
(m, 2H), 1.82 (m, 1H), 1.42 (m, 1H); ESIMS m/z 497.98
([M-H].sup.-); IR (thin film) 3027, 1654, 815 cm.sup.-1.
Example 24: Preparation of
6-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydrona-
phthalen-1(2H)-one oxime (BI5a)
##STR00236##
[0602] To a stirred solution of
((E)-6-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydron-
aphthalen-1(2H)-one (0.4 g, 0.92 mmol) in EtOH (50 mL) were added
hydroxylamine hydrochloride (0.128 g, 1.85 mmol) and sodium acetate
(NaOAc, 0.23 g, 2.77 mmol), and the reaction mixture was heated at
reflux for 3 h. The reaction mixture was concentrated under reduced
pressure, and the residue was diluted with water and extracted with
EtOAc. The combined organic extracts were washed with brine, dried
over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced
pressure to give the crude compound, which was purified by flash
column chromatography (SiO.sub.2, 100-200 mesh; 10-15% EtOAc in
petroleum ether). The title compound was isolated as a solid (0.3
g, 73%): mp 155-158.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.89 (d, J=8.4 Hz, 1H), 7.41 (s, 2H), 7.24 (m, 1H), 7.17
(m, 1H), 6.57 (d, J=16 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.13
(m, 1H), 2.82 (m, 4H), 2.04 (m, 2H); ESIMS m/z 445.95 ([M-H]I).
Example 25: Preparation of
(E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1-
H-inden-1-amine (BI5b)
##STR00237##
[0604] To a stirred solution of
(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1-
H-inden-1-one (1 g, 2.39 mmol) in MeOH (10 mL) were added ammonium
acetate (NH.sub.4OAc, 1.84 g, 23.9 mmol) and NaBH.sub.3CN (0.44 g,
7.17 mmol) and the reaction mixture was heated at reflux for 16 h.
The reaction mixture was concentrated under reduced pressure, and
the residue was diluted with water and extracted with EtOAc. The
combined organic extracts were washed with water and saturated
aqueous NaHCO.sub.3 solution, dried over anhydrous
Na.sub.2SO.sub.4, and concentrated under reduced pressure to afford
the title compound as a liquid (500 mg, crude): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 7.85 (s, 2H), 7.40 (s, 1H), 7.30 (s,
2H), 6.71 (s, 2H), 4.78 (m, 1H), 4.2 (m, 1H), 2.80 (m, 1H), 2.73
(m, 1H), 1.60 (m, 2H); ESIMS m/z 419.02 ([M+H].sup.+); IR (thin
film) 2924, 1552, 1112, 807 cm.sup.-1.
[0605] The following compound was made in accordance with the
procedures disclosed in Example 25.
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-d-
ihydro-1H-inden-1-amine (BI7)
##STR00238##
[0607] The product was isolated as a light brown gummy material,
taken as such to the next step (0.15 g, crude compound): ESIMS m/z
401.97 ([M-H].sup.-).
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-flu-
oro-2,3-dihydro-1H-inden-1-amine (BI8)
##STR00239##
[0609] The product was isolated as a light brown gummy material,
taken as such to the next step (0.15 g, crude compound): ESIMS m/z
420.15 ([M-H].sup.-).
(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-1,2,3,4-tetrah-
ydronaphthalen-1-amine (BI9)
##STR00240##
[0611] The product was isolated as a pale yellow liquid (500 mg
crude).
Example 26: Preparation of
(E)-1-Methyl-3-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-enyl)--
2,3-dihydro-1H-inden-1-yl)thiourea (BC1)
##STR00241##
[0613] To a stirred solution of
(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1-
H-inden-1-amine (0.1 g, 0.23 mmol) in Et.sub.2O (5 mL) was added
methylisothiocyanate (0.026 g, 0.35 mmol), and the mixture was
stirred for 2 h at 25.degree. C. The reaction mixture was
concentrated under reduced pressure, and the residue was purified
by flash column chromatography (SiO.sub.2, 20% EtOAc in petroleum
ether). The title compound was isolated as a liquid (65 mg, 50%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.39 (s, 2H), 7.25-7.18
(m, 3H), 6.58 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.4 Hz, 1H),
5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05-2.80 (m, 6H), 2.70 (m, 1H),
1.81 (m, 1H); ESIMS m/z 492.17 ([M+H].sup.+); IR (thin film) 3211,
1569, 1113, 806 cm.sup.-1.
[0614] Compounds BC2-BC3 in Table 1 were made in accordance with
the procedures disclosed in Example 26.
Example 27: Preparation of
(E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1--
enyl)-2,3-dihydro-1H-inden-1-yl)propanamide (BC4)
##STR00242##
[0616] To a stirred solution of
(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1-
H-inden-1-amine (0.1 g, 0.23 mmol) in CH.sub.2Cl.sub.2 (10 mL) were
added trifluoropropionic acid (0.044 g, 0.34 mmol), EDC.HCl (0.038
g, 0.35 mmol), HOBt.H.sub.2O (0.07 g, 0.46 mmol) and DIPEA (0.074
g, 0.57 mmol), and the reaction mixture was stirred for 16 h at
25.degree. C. The reaction mixture was diluted with
CH.sub.2Cl.sub.2 and washed with water. The combined organic layer
was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, and
concentrated under reduced pressure. The crude material was
purified by flash column chromatography (SiO.sub.2, 15% EtOAc in
petroleum ether) to afford the title compound as a liquid (65 mg,
65%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.39 (s, 2H),
7.25-7.20 (m, 3H), 6.34 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.0
Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H),
2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); ESIMS m/z 529.02
([M+H].sup.+); IR (thin film) 3283, 1652, 1241, 811 cm.sup.-1.
[0617] Compounds BC5-BC9, BC11 in Table 1 were made in accordance
with the procedures disclosed in Example 27.
Example 28: Preparation of tert-Butyl 5-vinylindoline-1-carboxylate
(BI10)
##STR00243##
[0618] Step 1. 5-Bromo-indoline (BI11)
[0619] To 5-Bromo-1H-indole (2.5 g, 12.82 mmol) in AcOH (10.0 mL),
NaBH.sub.3CN (2.38 g, 38.46 mmol) was added portion wise at
10.degree. C. over the period of 20 min. After that the reaction
mixture was stirred at ambient temperature for 3 h. The reaction
mixture was diluted with water and extracted with Et.sub.2O. The
organic layer was washed with saturated NaHCO.sub.3, water and
brine solution. The combined ether layer was dried over anhydrous
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
title compound as a pale yellow semi-solid (1.8 g, 71%).
Step 2. tert-Butyl-5-bromoindoline-1-carboxylate (BI12)
[0620] To a stirred solution of 5-bromo-indoline (3.0 g, 15 mmol)
in MeCN (100 ml), was added DMAP (0.185 g, 1.522 mmol) and
di-tert-butyl dicarbonate (3.98 g, 18.3 mmol) and the reaction was
stirred at ambient temperature for 16 h. The reaction mixture was
concentrated on reduced pressure to obtain a residue which was
diluted with Et.sub.2O and washed with water and brine solution
(2.times.). The combined ether layer was dried over anhydrous
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
the crude product as an off-white solid, which was used in the next
step without further purification (3.0 g).
Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10)
[0621] A stirred solution of
tert-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol),
potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and
K.sub.2CO.sub.3 (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed
with argon for 20 min at ambient temperature. PdCl.sub.2(dppf)
(0.49 g, 0.67 mmol) was added at ambient temperature, then the
reaction mixture was heated to 100.degree. C. for 3 h. The reaction
mixture was cooled to ambient temperature and filtered through a
Celite.RTM. bed under vacuum and washed with Et.sub.2O. The
reaction mixture was extracted with Et.sub.2O. The combined
Et.sub.2O layer was dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure to afford crude product. The crude compound
was purified by column chromatography (SiO.sub.2, 100-200 mesh;
eluting with 2% EtOAc/petroleum ether) to afford the title compound
as an off-white solid (1.2 g, 73%): mp 85.5-88.6.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.23 (m, 3H), 6.69 (dd,
J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz,
1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs,
9H).
Example 29: Preparation of (E)-tert-Butyl
5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indoline--
1-carboxylate (BI13)
##STR00244##
[0623] To a stirred solution of
tert-butyl-5-vinylindoline-1-carboxylate (1.28 g, 5.23 mmol) in
1,2-dichlorobenzene (10.0 mL), was added
5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.4
g, 10 mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g,
2.092 mmol) and the resultant reaction mixture was degassed with
argon for 30 min and heated to 150.degree. C. for 1 h. The reaction
mixture was cooled to ambient temperature and filtered and the
filtrate was concentrated under reduced pressure. The crude
compound was purified by column chromatography (SiO.sub.2, 100-200
mesh; 2% EtOAc/petroleum ether) to afford the title compound as a
pale yellow gummy solid (0.3 g, 61%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.34 (d, J=6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d,
J=8.4 Hz, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.21 (dd, J=16.0, 7.6 Hz,
1H), 4.07 (m, 3H), 3.10 (t, J=8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z
433.79 ([M-H].sup.-); IR (thin film) 1168, 858 cm.sup.-1.
Example 30: Preparation of
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indol-
in-1-amine (BI14)
##STR00245##
[0624] Step 1.
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline
(BI15)
[0625] To a stirred solution of
(E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-
yl)indoline-1-carboxylate (0.2 g, 0.4 mmol) in CH.sub.2Cl.sub.2
(10.0 mL) was added TFA (0.6 mL) and the reaction was stirred at
ambient temperature for 2 h. The reaction mixture was diluted with
CH.sub.2Cl.sub.2, washed with saturated aq NaHCO.sub.3, water and
brine solution. The separated CH.sub.2Cl.sub.2 layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford the crude product as a light brown gummy material which
was used in the next step without further purification (0.12 g):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.33 (d, J=6.4 Hz, 2H),
7.21 (s, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.57 (d, J=8.4 Hz, 1H), 6.49
(d, J=15.6 Hz, 1H), 6.21 (dd, J=15.6, 8.4 Hz, 1H), 4.07 (m, 1H),
3.61 (t, J=8.4 Hz, 2H), 3.05 (t, J=8.4 Hz, 2H); ESIMS m/z 389.89
([M+H].sup.+); IR (thin film) 3385, 1112, 816 cm.sup.-1.
Step 2.
5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-ni-
trosoindoline (BI16)
[0626] To
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl-
)indoline (0.2 g, 0.5 mmol) in concentrated HCl (5.0 ml) at
5.degree. C., was added slowly NaNO.sub.2 in water and the reaction
was allowed to stir at ambient temperature for 2 h. The reaction
mixture was diluted with CH.sub.2Cl.sub.2, and the CH.sub.2Cl.sub.2
layer washed with water and brine solution. The separated
CH.sub.2Cl.sub.2 layer was dried over anhydrous Na.sub.2SO.sub.4
and concentrated under reduced pressure to afford the crude product
as a pale yellow solid that was used in the next step without
further purification (0.2 g): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.33 (d, J=8.4 Hz, 1H), 7.39 (m, 4H), 6.61 (d, J=16.0 Hz,
1H), 6.35 (dd, J=16.0, 8.4 Hz, 1H), 4.07 (m, 3H), 3.23 (t, J=8.4
Hz, 2H); ESIMS m/z 418.82 ([M+H].sup.+); IR (thin film) 1488, 1112,
860 cm.sup.-1.
Step 3.
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-y-
l)indolin-1-amine (BI14)
[0627] To
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl-
)-1-nitrosoindoline (0.1 g, 0.2 mmol) in MeOH(10.0 mL) was added
zinc powder (77.5 mg) and NH.sub.4Cl (36.9 mg, 0.69 mmol) in water
(2.0 mL). The reaction mixture was stirred at ambient temperature
for 3 h. The reaction mixture was diluted with CH.sub.2Cl.sub.2 and
the CH.sub.2Cl.sub.2 layer was washed with water and brine
solution. The separated CH.sub.2Cl.sub.2 layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford the crude compound, which was purified by column
chromatography (SiO.sub.2, 100-200 mesh; eluting with 2%
EtOAc/petroleum ether) to afford the title compound as a light
brown gummy material (0.08 g): ESIMS m/z 404.86 ([M+H].sup.+).
Example 31: Preparation of
(E)-N-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)in-
dolin-1-yl)-3,3,3-trifluoropropanamide (BC12)
##STR00246##
[0629] To a stirred solution of
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-
-1-amine (0.1 g, 0.247 mmol) in CH.sub.2Cl.sub.2 (10.0 ml) was
added 3,3,3-trifluoropropanoic acid (0.038 g, 0.297 mmol), PyBOP
(0.192 g, 0.370 mmol) and DIPEA (0.047 g, 0.370 mmol) and the
reaction was stirred at ambient temperature for 18 h. The reaction
mixture was diluted with CH.sub.2Cl.sub.2, and the separated
CH.sub.2Cl.sub.2 layer dried over anhydrous Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the crude compound.
The crude compound was purified by column chromatography
(SiO.sub.2, 100-200 mesh; 20-25% EtOAc/petroleum ether) to afford
the title compound as a light brown gummy material (0.12 g, 33%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.32, (d, J=6.0 Hz, 2H)
7.28 (m, 1H), 7.20 (d, J=8.0, 1H), 7.14 (d, J=8.8, 1H), 6.70 (d,
J=8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m,
1H), 3.46 (m, 2H), 3.19 (m, 2H); ESIMS m/z 514.86 ([M+H].sup.+); IR
(thin film) 3428, 1112, 857 cm.sup.-1.
Example 32: Preparation of
tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)
##STR00247##
[0630] Step 1. 5-Vinyl-1H-indole (BI18)
[0631] A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol),
potassium vinyltrifluoroborate (2.57 g, 19.2 mmol),
Cs.sub.2CO.sub.3 (12.53 g, 38.46 mmol) and triphenylphosphine (201
mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon
for 20 min, then charged with PdCl.sub.2 (45.3 mg, 0.256 mmol). The
reaction mixture was heated to reflux for 16 h, then cooled to
ambient temperature, filtered through Celite.RTM. bed and washed
with EtOAc. The filtrate was again extracted with EtOAc, and the
combined organic layer washed with water and brine, dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
the crude compound. The crude compound was purified by column
chromatography (SiO.sub.2, 100-200 mesh; 2% EtOAc/petroleum ether)
to afford the title compound as a light brown gummy material (1.5
g, 83%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.20 (br, 1H),
7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8
Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz,
1H); ESIMS m/z 142.05 ([M-H].sup.-).
Step 2. tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)
[0632] To a stirred solution of 5-vinyl-1H-indole (0.7 g, 4.89
mmol) in MeCN (20 ml) was added DMAP (59.65 mg, 0.489 mmol) and
di-tert-butyl dicarbonate (1.38 g, 6.36 mmol), and the reaction was
stirred at ambient temperature for 3 h. The reaction mixture was
concentrated under reduced pressure to obtain a residue which was
diluted with CH.sub.2Cl.sub.2 and washed with water and brine
solution. The combined CH.sub.2Cl.sub.2 layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford the crude compound. The crude compound was purified by
column chromatography (SiO.sub.2, 100-200 mesh; 2% EtOAc/petroleum
ether) to afford the title compound as an off-white semi-solid (0.7
g, 59%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.15 (d, J=8.0
Hz, 1H), 7.60 (s, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.21 (m, 1H), 6.90
(dd, J=16.0, 10.8 Hz, 1H), 6.59 (s, 1H), 5.75 (d, J=10.5 Hz, 1H),
5.21 (d, J=10.5 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 242.10
([M-H].sup.-); IR (thin film) 1630 cm.sup.-1.
Example 33: Preparation of (E)-tert-Butyl
5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-
e-1-carboxylate (BI19)
##STR00248##
[0634] To a stirred solution of tert-butyl
5-vinyl-1H-indole-1-carboxylate (0.65 g, 2.67 mmol), in
1,2-dichlorobenzene (10.0 mL) was added
5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (1.74
g, 5.37 mmol), CuCl (53 mg, 0.537 mmol) and 2,2-bipyridyl (167 mg,
1.07 mmol). The resultant reaction mixture was degassed with argon
for 30 min and heated to 150.degree. C. for 2 h. The reaction
mixture was cooled to ambient temperature and filtered, and the
filtrate concentrated under reduced pressure. The crude compound
was purified by column chromatography (SiO.sub.2, 100-200 mesh; 2%
EtOAc/petroleum ether) to afford the title compound as a light
brown gummy material (0.25 g, 10%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m,
3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd,
J=16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 1.65 (s, 9H); ESIMS m/z 485.91
([M-H].sup.-); IR (thin film) 1165, 854 cm.sup.-1.
Example 34: Preparation of
(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-i-
ndole (BI20)
##STR00249##
[0636] To a stirred solution of (E)-tert-butyl
5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole-1-
-carboxylate (0.2 g, 0.40 mmol) in CH.sub.2Cl.sub.2 (10.0 mL) was
added TFA (70 mg, 0.61 mmol) and the reaction was stirred at
ambient temperature for 2 h. The reaction mixture was diluted with
CH.sub.2Cl.sub.2 and washed with saturated NaHCO.sub.3 solution,
water and brine solution. The separated CH.sub.2Cl.sub.2 layer was
dried over anhydrous Na.sub.2SO.sub.4 and concentrated under
reduced pressure to afford the title compound as a light brown
solid (0.2 g, 97%): mp 132.9-138.8.degree. C.; .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 11.19 (br, 1H), 8.20 (d, J=8.0 Hz, 1H),
7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d,
J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (m, 1H); ESIMS
m/z 387.98 ([M+H].sup.+).
Example 35: Preparation of 4-Nitrophenyl
2-((tert-butoxycarbonyl)amino)acetate (BI21)
##STR00250##
[0638] To a stirred solution of 4-nitrophenol (1.0 g, 7.19 mmol) in
CH.sub.2Cl.sub.2 (20.0 mL) was added N-Boc glycine (1.38 g, 7.91
mmol) and EDC HCl (2.05 g, 10.785 mmol) and the reaction was
stirred at ambient temperature for 24 h. The reaction mixture was
diluted with CH.sub.2Cl.sub.2 and washed with water and saturated
brine solution. The separated CH.sub.2Cl.sub.2 layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford the title compound as a light brown gummy material that
was used in the next step without further purification (1.1 g):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.29 (d, J=9.2 Hz, 2H),
7.33 (d, J=8.8 Hz, 2H), 5.07 (br, 1H), 4.20 (s, 2H), 1.47 (s, 9H);
ESIMS m/z 296.27 ([M+H].sup.+).
Example 36: Preparation of (E)-tert-Butyl
(2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-i-
ndol-1-yl)-2-oxoethyl)carbamate (BI22)
##STR00251##
[0640] To a stirred solution of
(E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indo-
le (0.1 g, 0.258 mmol) in MeCN (5.0 mL) was added 4-nitrophenyl
2-(tert-butoxycarbonylamino) acetate (0.114 g, 0.387 mmol), KF
(0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol) and
DIPEA (0.0332 g, 0.258 mmol) and the reaction was stirred at
ambient temperature for 16 h. The reaction mixture was concentrated
to obtain a residue which was diluted with CH.sub.2Cl.sub.2 and
washed with water and brine solution. The separated
CH.sub.2Cl.sub.2 layer was dried over anhydrous Na.sub.2SO.sub.4
and concentrated under reduced pressure to afford the crude title
compound as a light brown gummy material which was used in the next
step without further purification (0.1 g): ESIMS m/z 545.23
([M+H].sup.+).
Example 37: Preparation of
(E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl-
)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)
##STR00252##
[0641] Step 1.
(E)-2-Amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-
yl)-1H-indol-1-yl)ethanone (BI23)
[0642] To a stirred solution of (E)-tert-butyl
2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-
-1-yl)-2-oxoethylcarbamate (0.05 g, 0.09 mmol) in CH.sub.2Cl.sub.2
(5.0 mL) was added TFA (0.01 mL) and the reaction was stirred at
ambient temperature for 16 h. The reaction mixture was diluted with
CH.sub.2Cl.sub.2 and washed with saturated NaHCO.sub.3 solution,
water and brine solution. The separated CH.sub.2Cl.sub.2 layer was
dried over anhydrous Na.sub.2SO.sub.4 and concentrated under
reduced pressure to afford the crude title compound which was used
in the next step without further purification (50 mg).
Step 2.
(E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1--
en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide
(BC13)
[0643] To a stirred solution of
(E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-
yl)-1H-indol-1-yl) ethanone (0.04 g, 0.09 mmol) in CH.sub.2Cl.sub.2
(5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136
mmol), PyBOP (70 mg, 0.135 mmol) and DIPEA (29 mg, 0.225 mmol) and
the reaction was stirred at ambient temperature for 16 h. The
reaction mixture was diluted with CH.sub.2Cl.sub.2, and the
CH.sub.2Cl.sub.2 layer was washed with water and saturated brine
solution. The separated CH.sub.2Cl.sub.2 layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford the crude compound, which was purified by column
chromatography (SiO.sub.2, 100-200 mesh; 10% EtOAc/petroleum ether)
to afford the title compound as an off-white solid (30 mg, 60%): mp
121-126.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.33
(br, 1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J=3.6 Hz, 3H), 6.39
(m, 1H), 4.71 (t, J=7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28
(m, 1H); ESIMS m/z 553.06 ([M-H].sup.-).
Example 38: Preparation of Ethyl
2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetate (BI24)
##STR00253##
[0644] Step 1. 5-Bromo-3-hydroxyisoindoline-1-one (BI25)
[0645] A mixture of Zn powder (1.73 g, 26.154 mmol), copper (II)
sulfate pentahydrate (0.02 g, 0.08 mmol) and 2M aq NaOH (27 mL)
were cooled to 0.degree. C. 5-Bromoisoindoline-1,3-dione (5 g, 22
mmol) was added at the same temperature over the period of 30 min.
The reaction mixture was stirred at 0.degree. C. for 30 min and 3 h
at ambient temperature. The reaction mixture was filtered and the
filtrate was neutralized with concentrated HCl. The reaction
mixture was diluted with ethanol and extracted with EtOAc. The
combined EtOAc layer was dried over Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the crude title
compound as a brown solid, which was used in the next step without
further purification (1.3 g): mp 258-261.degree. C.; .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 9.03 (br, 1H), 7.81 (m, 2H), 7.69
(m, 1H), 6.44 (m, 1H), 5.88 (d, J=9.3 Hz, 1H); ESIMS m/z 225.83
([M-H].sup.-); IR (thin film) 1684, 3246, 606 cm.sup.-1.
Step 2. 6-Bromophthalazine-1(2H)-one (BI26)
[0646] To a stirred solution of 5-bromo-3-hydroxyisoindoline-1-one
(1.0 g, 4.40 mmol) in water, was added hydrazine hydrate (0.45 g,
8.80 mmol) and heated to 95.degree. C. for 5 h. The reaction
mixture was cooled to ambient temperature, filtered and washed with
Et.sub.2O and pentane (1:1) to afford the title compound as a white
solid that was used in the next step without further purification
(0.5 g): ESIMS m/z 225.15 ([M+H].sup.+).
Step 3. 6-Vinylphthalazine-1(2H)-one (BI27)
[0647] A solution of 6-bromophthalazine-1(2H)-one (0.25 g, 1.11
mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and
K.sub.2CO.sub.3 (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed
with argon for 20 min at ambient temperature. PdCl.sub.2(dppf)
(0.04 g, 0.055 mmol) was added at ambient temperature, and the
reaction mixture was heated to 80.degree. C. for 2 h. The reaction
mixture was cooled to ambient temperature and filtered through
Celite.RTM. bed under vacuum and washed with EtOAc. The reaction
mixture was extracted with EtOAc and the combined EtOAc layer dried
over Na.sub.2SO.sub.4 and concentrated under reduced pressure to
afford the crude product. The crude compound was purified by column
chromatography (SiO.sub.2, 100-200 mesh; 50% EtOAc/petroleum ether)
to afford the title compound as a brown solid (0.12 g, 63%):
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.61 (br, 1H), 8.33
(m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H),
5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H].sup.+); IR (thin
film) 1748, 1655, 3241 cm.sup.-1.
Step 4. Ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate
(BI24)
[0648] To a stirred solution of 6-vinylphthalazine-1(2H)-one (0.5
g, 2.90 mmol) in DMF (5.0 mL) was added Cs.sub.2CO.sub.3 (0.94 g,
2.90 mmol) and the reaction was stirred for 10 min. Ethyl
bromoacetate (0.48 g, 2.90 mmol) was added to the reaction mixture
at ambient temperature and the reaction was stirred for 8 h at
ambient temperature. The reaction mixture was diluted and extracted
with EtOAc, and the EtOAc layer was washed with water and brine
solution (2.times.). The separated EtOAc layer was dried over
anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure
to afford crude product. The crude compound was purified by column
chromatography (SiO.sub.2, 100-200 mesh; 25% EtOAc/petroleum ether)
to afford the title compound as a brown solid (0.34 g, 45%):
.sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 8.45 (m, 1H), 8.24 (m,
1H), 8.04 (m, 2H), 7.01 (m, 1H), 6.17 (d, J=2.1 Hz, 1H), 5.56 (d,
J=10.8 Hz, 1H), 4.92 (s, 2H), 4.19 (m, 2H), 1.23 (m, 3H). ESIMS m/z
259.10 ([M+H].sup.+); IR (thin film) 1750, 1660 cm.sup.-1.
Example 39: Preparation of (E)-Ethyl
2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxo-
phthalazin-2(1H)-yl)acetate (BI28)
##STR00254##
[0650] To a stirred solution of
ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (0.07 g, 0.27
mmol) in 1,2-dichlorobenzene (1.0 mL) was added
5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2fluorobenzene (0.17
g, 0.54 mmol), CuCl (0.005 g, 0.05 mmol) and 2,2-bipyridyl (0.016
g, 0.10 mmol) and the resultant reaction mixture was degassed with
argon for 30 min and heated to 180.degree. C. for 12 h. The
reaction mixture was cooled to ambient temperature and filtered and
the filtrated was concentrated under reduced pressure. The crude
compound was purified by column chromatography (SiO.sub.2, 100-200
mesh; 10-15% EtOAc/petroleum ether) to afford the title compound as
a brown solid (40 mg, 29%): .sup.1H NMR (400 MHz, DMSO-d.sub.6)
.delta. 8.40 (d, J=8.4 Hz, 1H), 7.84 (d, J=1.5 Hz, 1H), 7.65 (s,
1H), 7.37 (d, J=6.3 Hz, 2H), 6.76 (d, J=16.0 Hz, 1H), 6.59 (dd,
J=16.0, 8.0 Hz, 1H), 4.96 (s, 2H), 4.29 (m, 3H), 1.31 (t, J=7.2 Hz,
3H); ESIMS m/z 503.0 ([M+H].sup.+); IR (thin film) 1660, 1114, 817
cm.sup.-1.
Example 40: Preparation of
(E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-
-oxophthalazin-2(1H)-yl)acetic acid (BI29)
##STR00255##
[0652] A solution of
(E)-ethyl-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl-
)-1-oxophthalazin-2(1H)-yl) acetate (0.04 g, 0.07 mmol) in HCl (0.5
mL) and AcOH (0.5 mL) was heated to 100.degree. C. for 3 h. The
solvent was removed under reduced pressure and the residue diluted
with water. The aqueous layer was extracted with EtOAc and the
separated EtOAc layer dried over anhydrous Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the crude compound.
The crude compound was triturated with Et.sub.2O-pentane mixture to
afford the title compound as a brown solid (0.03 g): .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 13.0 (br s, 1H), 8.43 (m, 1H), 8.23
(d, J=8.1 Hz, 1H), 8.14 (m, 2H), 7.91 (m, 2H), 7.16 (dd, J=16.0,
8.0 Hz, 1H), 6.99 (d, J=16.0 Hz, 1H), 4.96 (m, 3H); ESIMS m/z 473.0
([M-H].sup.-); IR (thin film) 1629, 1168, 817 cm.sup.-1.
Example 41: Preparation of
(E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-
-oxophthalazin-2(1H)-yl)-N-(2,2,2-trifluoroethyl)acetamide
(BC14)
##STR00256##
[0654] To a stirred solution of
(E)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-ox-
ophthalazin-2(1H)-yl)acetic acid (0.15 g, 0.31 mmol) in
CH.sub.2Cl.sub.2 (20.0 ml) was added 2,2,2,-trifluoroethanamine
(0.03 g, 0.31 mmol), PyBOP (0.17 g, 0.34 mmol) and DIPEA (0.15 ml,
0.93 mmol) at ambient temperature, and the reaction was stirred for
18 h. The reaction mixture was diluted with CH.sub.2Cl.sub.2 and
washed with 3N HCl (2.times.20 mL), NaHCO.sub.3 (2.times.20 mL) and
brine solution (2.times.). The separated CH.sub.2Cl.sub.2 layer was
dried over anhydrous Na.sub.2SO.sub.4 and concentrated under
reduced pressure to afford the crude compound. The crude compound
was purified by column chromatography (SiO.sub.2, 100-200 mesh;
20-25% EtOAc/petroleum ether) to afford the title compound as a
brown solid (0.11 g): mp 172-175.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.83 (t, J=6.6 Hz, 1H), 8.42 (t, J=14.7 Hz,
1H), 8.22 (d, J=8.1 Hz, 1H), 8.13 (t, J=6.3 Hz, 1H), 7.98-7.86 (m,
2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H),
4.00-3.88 (m, 2H); ESIMS m/z 554.0 ([M-H].sup.-).
Example 42: Preparation of 2-(4-Vinylbenzyl)isoindoline-1,3-dione
(CI1)
##STR00257##
[0656] To a stirred solution of 1-(chloromethyl)-4-vinylbenzene (10
g, 66 mmol) in DMF (100 mL) was added potassium phthalimide (13.3
g, 72.1 mmol), and the resultant reaction mixture was heated at
70.degree. C. for 16 h. The reaction mixture was diluted with water
and extracted with CHCl.sub.3. The combined CHCl.sub.3 layer was
washed with brine, dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure. Recrystallization from MeOH afforded the
title compound as an off-white solid (8 g, 46%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H),
6.65 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.21 (d,
J=10.8 Hz, 1H), 4.82 (s, 2H); GCMS m/z 263.2 ([M].sup.+); IR (thin
film) 3420, 1133, 718 cm.sup.-1.
Example 43: Preparation of
(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoi-
ndoline-1,3-dione (CI2)
##STR00258##
[0658] Using the procedure of Example 10 with
2-(4-vinylbenzyl)isoindoline-1,3-dione and
1-(1-bromoethyl)-3,5-dichlorobenzene as the starting materials, the
title compound was isolated as an off-white solid (0.3 g, 40-50%):
mp 142-145.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.86 (m, 2H), 7.74 (m, 2H), 7.42 (m, 2H), 7.36 (m, 3H), 7.27 (m,
2H), 6.58 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.82
(s, 2H), 4.05 (m, 1H); ESIMS m/z 488.17 ([M-H].sup.-).
[0659] The following compound was made in accordance with the
procedures disclosed in Example 43.
(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)is-
oindoline-1,3-dione (CI3)
##STR00259##
[0661] The title compound was isolated as an off white solid (0.3
g, 56%): mp 145-146.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.86 (m, 2H), 7.74 (m, 2H), 7.42-7.31 (m, 6H), 6.58 (d,
J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05
(m, 1H); ESIMS m/z 522.2 ([M-H].sup.-); IR (thin film) 1716, 1110,
712 cm.sup.-1.
[0662] Prophetically, compounds CI4-CI5 (Table 1) could be made in
accordance with the procedures disclosed in Example 43.
Example 44: Preparation of
(E)-(4-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanami-
ne (CI6)
##STR00260##
[0664] To a stirred solution of
(E)-2-(4-(3-(3,5-dichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dio-
ne (1.2 g, 2.45 mmol) in EtOH was added hydrazine hydrate (0.61 g,
12 mmol), and the resultant reaction mixture was heated at
90.degree. C. for 1 h. The reaction mixture was filtered, and the
filtrate was concentrated. The residue was dissolved in
CH.sub.2Cl.sub.2, washed with brine, dried over Na.sub.2SO.sub.4,
and concentrated under reduced pressure to afford the crude title
compound as a gummy liquid (0.9 g) which was used without further
purification.
[0665] The following compounds were made in accordance with the
procedures disclosed in Example 44.
(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)meth-
anamine (CI7)
##STR00261##
[0667] The title compound was isolated and used without further
purification.
[0668] Prophetically, compounds CI8-CI9 (Table 1) could be made in
accordance with the procedures disclosed in Example 44.
Example 45: Preparation of 4-(Bromomethyl)-3-chlorobenzonitrile
(CI10)
##STR00262##
[0670] To a stirred solution of 3-chloro-4-methylbenzonitrile (5 g,
25.4 mmol) in CCl.sub.4 (50 mL) under an argon atmosphere was added
NBS (5.16 g, 29 mmol), and the mixture was degassed for 30 min. To
this was added AIBN (0.3 g, 1.8 mmol), and the resultant reaction
mixture was heated at reflux for 4 h. The reaction mixture was
cooled to ambient temperature, washed with water, and extracted
with CH.sub.2Cl.sub.2. The combined CH.sub.2Cl.sub.2 layer was
washed with brine, dried over Na.sub.2SO.sub.4, and concentrated
under reduced pressure. The crude compound was purified by flash
column chromatography (SiO.sub.2, 100-200 mesh; 5% EtOAc in
n-Hexane) to afford the title compound as a white solid (4.8 g,
68%): mp 87-88.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.71 (s, 1H), 7.59 (s, 2H), 4.60 (s, 2H); ESIMS m/z 229.77
([M+H].sup.+); IR (thin film) 2235, 752, 621 cm.sup.-1.
[0671] The following compounds were made in accordance with the
procedures disclosed in Example 45.
4-(Bromomethyl)-3-(trifluoromethyl)benzonitrile (CI11)
##STR00263##
[0673] The title compound was isolated as an off-white gummy
material (5 g, 66%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.96
(s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 4.62 (s,
2H); ESIMS m/z 262.11 ([M-H].sup.-); IR (thin film) 2236, 1132, 617
cm.sup.-1.
3-Bromo-4-(bromomethyl)benzonitrile (CI12)
##STR00264##
[0675] The title compound was isolated as an off-white solid (5 g,
67%): mp 82-83.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.90 (s, 1H), 7.61 (m, 2H), 4.62 (s, 2H); EIMS m/z 272.90;
IR (thin film) 2229, 618 cm.sup.-1.
4-(Bromomethyl)-3-fluorobenzonitrile (CI13)
##STR00265##
[0677] The title compound was isolated as an off-white solid (2 g,
60%): mp 79-81.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.54 (t, J=8.0 Hz, 1H), 7.48 (dd, J=8.0 Hz, 8.0, 1H), 7.38
(dd, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 215.
Example 46: Preparation of 4-(Bromomethyl)-3-chlorobenzaldehyde
(CI14)
##STR00266##
[0679] To a stirred solution of
4-(bromomethyl)-3-chlorobenzonitrile (4.8 g, 17 mmol) in toluene
(50 mL) at 0.degree. C. was added dropwise DIBAl-H (1.0 M solution
in toluene; 23.9 mL), and the reaction mixture was stirred at
0.degree. C. for 1 h. 10 M HCl in water (5 mL) was added until the
reaction mixture turned to a white slurry and then additional 1 N
HCl (20 mL) was added. The organic layer was collected and the
aqueous layer was extracted with CHCl.sub.3. The combined organic
layer was dried over Na.sub.2SO.sub.4 and concentrated under
reduced pressure. The crude compound was purified by flash column
chromatography (SiO.sub.2, 100-200 mesh; 5% EtOAc in n-Hexane) to
afford the title compound as a white solid (3.8 g, 80%): mp
64-66.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 10.00
(s, 1H), 7.92 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.0 Hz,
1H), 4.60 (s, 2H); ESIMS m/z 232.78 ([M+H].sup.+).
[0680] The following compounds were made in accordance with the
procedures disclosed in Example 46.
4-(Bromomethyl)-3-(trifluoromethyl)benzaldehyde (CI15)
##STR00267##
[0682] The title compound was isolated as a pale yellow low-melting
solid (5 g, 60%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 10.09
(s, 1H), 8.19 (s, 1H), 8.09 (m, 1H), 7.81 (m, 1H), 4.61 (s, 2H);
ESIMS m/z 265.04 ([M-H].sup.-); IR (thin film) 1709, 1126, 649
cm.sup.-1.
3-Bromo-4-(bromomethyl)benzaldehyde (CI16)
##STR00268##
[0684] The title compound was isolated as a pale yellow solid (5 g,
62%): mp 94-95.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 9.96 (s, 1H), 8.05 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.62
(d, J=8.0 Hz, 1H), 4.60 (s, 2H); EIMS m/z 275.90 ([M].sup.+).
4-(Bromomethyl)-3-fluorobenzaldehyde (CI17)
##STR00269##
[0686] The title compound was isolated as an off-white solid (5 g,
61%): mp 43-45.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 9.1 (s, 1H), 7.54 (t, J=8 Hz, 1H), 7.48 (d, J=8 Hz, 1H),
7.38 (d, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 216 ([M].sup.+).
Example 47: Preparation of
3-Chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde
(CI18)
##STR00270##
[0688] To a stirred solution of
4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14 mmol) in DMF (40
mL) was added potassium pthalimide (3.54 g, 19.14 mmol), and the
mixture was heated at 60.degree. C. for 6 h. The reaction mixture
was cooled to ambient temperature and diluted with water (100 mL).
The solid obtained was separated by filtration and dried under
vacuum to afford the title compound as a white solid (2.8 g, 60%):
mp 123-126.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m,
1H), 5.05 (s, 2H); ESIMS m/z 298.03 ([M-H].sup.-).
[0689] The following compounds were made in accordance with the
procedures disclosed in Example 47.
4-((1,3-Dioxoisoindolin-2-yl)-3-(trifluoromethyl)benzaldehyde
(CI19)
##STR00271##
[0691] The title compound was isolated as an off white solid (1 g,
62%): mp 142-143.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.05 (s, 1H), 8.15 (s, 1H), 7.91 (m, 2H), 7.80 (m, 3H),
7.27 (m, 1H), 5.19 (s, 2H); ESIMS m/z 332.03 ([M-H].sup.-).
3-Bromo-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI20)
##STR00272##
[0693] The title compound was isolated as an off-white solid (0.5
g, 64%): mp 159-161.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H),
7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 314.00 ([M-CHO].sup.-).
4-((1,3-Dioxoisoindolin-2-yl)-3-fluorobenzaldehyde (CI21)
##STR00273##
[0695] The title compound was isolated as a white solid (2 g, 60%):
mp 154-156.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
9.95 (s, 1H), 7.9 (m, 2H), 7.75 (m, 2H), 7.6 (m, 2H), 7.5 (t, J=7.6
Hz, 1H), 5.05 (s, 2H); EIMS m/z 283.1 ([M].sup.+).
Example 48: Preparation of
2-(2-Chloro-4-vinylbenzyl)isoindoline-1,3-dione (CI22)
##STR00274##
[0697] To a stirred solution of
3-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (2.8 g,
8.2 mmol) in 1,4-dioxane (30 mL) were added K.sub.2CO.sub.3 (1.68
g, 12.24 mmol) and methyl triphenyl phosphonium bromide (4.37 g,
12.24 mmol) at ambient temperature. Then the resultant reaction
mixture was heated at 100.degree. C. for 18 h. After the reaction
was deemed complete by TLC, the reaction mixture was cooled to
ambient temperature and filtered, and the obtained filtrate was
concentrated under reduced pressure. The residue was purified by
flash chromatography (SiO.sub.2, 100-200 mesh; 20% EtOAc in
n-Hexane) to afford the title compound as a white solid (1.94 g,
70%): mp 141-143.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.85 (m, 2H), 7.70 (m, 2H), 7.41 (m, 1H), 7.21 (m, 2H),
6.71 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.23 (d,
J=10.8 Hz, 1H), 4.92 (s, 2H); ESIMS m/z 298.10 ([M-H].sup.-).
[0698] The following compounds were made in accordance with the
procedures disclosed in Example 48.
2-(2-(Trifluoromethyl)-4-vinylbenzyl)isoindoline-1,3-dione
(CI23)
##STR00275##
[0700] The title compound was isolated as a light brown solid (0.5
g, 60%): mp 134-135.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.92 (m, 2H), 7.80 (m, 2H), 7.71 (s, 1H), 7.46 (d, J=8.0
Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.65 (m, 1H), 5.80 (d, J=17.8 Hz,
1H), 5.19 (d, J=10.8 Hz, 1H), 5.09 (s, 2H); ESIMS m/z 332.10
([M+H].sup.+).
2-(2-Bromo-4-vinylbenzyl)isoindoline-1,3-dione (CI24)
##STR00276##
[0702] The title compound was isolated as an off white solid (0.5
g, 62%): mp 126-128.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.92 (m, 2H), 7.79 (m, 2H), 7.62 (s, 1H), 7.21 (m, 1H),
7.16 (d, J=8.0 Hz, 1H), 6.62 (m, 1H), 5.72 (d, J=17.8 Hz, 1H), 5.15
(d, J=10.8 Hz, 1H), 4.95 (s, 2H); EIMS m/z 341.10 ([M].sup.+).
2-(2-Fluoro-4-vinylbenzyl)isoindoline-1,3-dione (CI25)
##STR00277##
[0704] The title compound was isolated as a white solid (0.5 g,
61%): mp 140-142.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.85 (m, 2H), 7.72 (m, 2H), 7.25 (m, 1H), 7.11 (m, 2H),
6.63 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.28 (d, J=10.8 Hz, 1H),
4.92 (s, 2H); EIMS m/z 282.08.
Example 49: Preparation of
(E)-2-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)be-
nzyl)isoindoline-1,3-dione (CI26)
##STR00278##
[0706] To a stirred solution of
2-(2-chloro-4-vinylbenzyl)isoindoline-1,3-dione (2.0 g, 6.51 mmol)
in 1,2-dichlorobenzene (25 mL) were added
1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (3.48 g, 11.36
mmol), CuCl (112 mg, 1.13 mmol) and 2,2-bipyridyl (0.35 g). The
resultant reaction mixture was degassed with argon for 30 min and
then was stirred at 180.degree. C. for 24 h. After the reaction was
deemed complete by TLC, the reaction mixture was cooled to ambient
temperature and filtered, and the filtrate was concentrated under
reduced pressure. The residue was purified by flash chromatography
(SiO.sub.2, 100-200 mesh; 25-30% EtOAc in n-hexane) to afford the
title compound as solid (1.3 g, 50%): mp 141-143.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.92 (m, 2H), 7.79 (m,
2H), 7.42 (m, 2H), 7.24 (m, 2H), 7.20 (m, 2H), 6.54 (d, J=16.0 Hz,
1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.10 (m, 1H);
ESIMS m/z 524.07 ([M+H].sup.+).
[0707] The following compounds were made in accordance with the
procedures disclosed in Example 49.
(E)-2-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
benzyl)isoindoline-1,3-dione (CI27)
##STR00279##
[0709] The title compound was isolated as a pale white solid (0.2
g, 55%): mp 128-129.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 3H), 7.22 (m, 2H),
6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s,
2H), 4.05 (m, 1H); ESIMS m/z 557.99 ([M+H].sup.+).
(E)-2-(2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-
-1-yl)benzyl)isoindoline-1,3-dione (CI28)
##STR00280##
[0711] The title compound was isolated as an off white solid (0.2
g, 54%): mp 177-180.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.90 (m, 2H), 7.77 (m, 2H), 7.42 (s, 1H), 7.32 (d, J=8.0
Hz, 2H), 7.21 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0,
8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 540.08
([M-H].sup.-); IR (thin film) 1716 cm.sup.-1.
(E)-2-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)ben-
zyl)isoindoline-1,3-dione (CI29)
##STR00281##
[0713] The title compound was isolated as an off-white solid (0.2
g, 59%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.89 (m, 2H),
7.76 (m, 2H), 7.47 (m, 3H), 7.21 (m, 3H), 6.50 (d, J=16.0 Hz, 1H),
6.32 (dd, J=16.0, 7.6 Hz, 1H), 4.97 (s, 2H), 4.11 (m, 1H); ESIMS
m/z 522.27 ([M-H]); IR (thin film) 3064, 1717, 1111, 715
cm.sup.-1.
(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluor-
omethyl)-benzyl)isoindoline-1,3-dione (CI30)
##STR00282##
[0715] The title compound was isolated as an off-white solid (0.2
g, 54%): mp 141-142.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 1H), 7.38 (m,
1H), 7.24 (m, 2H), 7.19 (m, 1H), 6.60 (d, J=16.0 Hz, 1H), 6.39 (dd,
J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.11 (m, 1H); ESIMS m/z 556.00
([M-H].sup.-).
(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifl-
uoromethyl)-benzyl)isoindoline-1,3-dione (CI31)
##STR00283##
[0717] The title compound was isolated as an off-white solid (0.2
g, 56%): mp 130-132.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 3H),
7.19 (m, 1H), 6.61 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz,
1H), 5.10 (s, 2H), 4.12 (m, 1H); ESIMS m/z 589.57
([M-2H].sup.-).
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)b-
enzyl)-isoindoline-1,3-dione (CI32)
##STR00284##
[0719] The title compound was isolated as a pale yellow solid (0.2
g, 55%): mp 160-162.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.92 (m, 2H), 7.80 (m, 2H), 7.62 (s, 1H), 7.39 (s, 2H),
7.24 (m, 1H), 7.16 (m, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd,
J=16.0, 8.0 Hz, 1H), 4.98 (s, 2H), 4.12 (m, 1H); ESIMS m/z 599.78
([M-H].sup.-).
(E)-2-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
benzyl)-isoindoline-1,3-dione (CI33)
##STR00285##
[0721] The title compound was isolated as an off-white solid (0.2
g, 55%): mp 72-74.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.88 (m, 2H), 7.74 (m, 2H), 7.38 (s, 2H), 7.34 (m, 1H),
7.18 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz,
1H), 4.91 (s, 2H), 4.08 (m, 1H); ESIMS m/z 539.89 ([M-H].sup.-); IR
(thin film) 1773 cm.sup.-1.
[0722] Prophetically, compounds CI34-CI41 (Table 1) could be made
in accordance with the procedures disclosed in Example 49.
Example 50: Preparation of
(E)-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phen-
yl)methanamine (CI42)
##STR00286##
[0724] To a stirred solution of
(E)-2-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)be-
nzyl)isoindoline-1,3-dione (0.4 g, 0.76 mmol) in EtOH was added
hydrazine hydrate (0.38 g, 7.6 mmol), and the resultant reaction
mixture was heated at 80.degree. C. for 2 h. The reaction mixture
was filtered, and the filtrate was concentrated. The residue was
dissolved in CH.sub.2Cl.sub.2, washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure to afford
the title compound as a gummy liquid (0.3 g), which was carried on
to the next step without further purification.
[0725] The following compounds were made in accordance with the
procedures disclosed in Example 50.
(E)-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ph-
enyl)-methanamine (CI43)
##STR00287##
[0727] The product obtained in this reaction was carried on to the
next step without further purification.
(E)-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)pheny-
l)-methanamine (CI44)
##STR00288##
[0729] The product obtained in this reaction was carried on to the
next step without further purification: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.48 (d, J=8.4 Hz, 2H), 7.39 (m, 2H), 7.23 (m,
2H), 6.52 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz, 1H), 4.12
(m, 1H), 3.90 (s, 2H); ESIMS m/z 391.90 ([M-H].sup.-); IR (thin
film) 3370, 3280, 1111, 817 cm.sup.-1.
(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluo-
romethyl)-phenyl)methanamine (CI45)
##STR00289##
[0731] The title compound was isolated as a gummy material. The
product obtained in this reaction was carried on to the next step
without further purification.
(E)-(2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl-
)-methanamine (CI46)
##STR00290##
[0733] The title compound was isolated as a gummy material: The
product obtained in this reaction was carried on to the next step
without further purification.
(E)-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phe-
nyl)-methanamine (CI47)
##STR00291##
[0735] The title compound was isolated as a gummy material. The
product obtained in this reaction was carried on to the next step
without further purification.
(E)-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ph-
enyl)-methanamine (CI48)
##STR00292##
[0737] The title compound was isolated as a gummy material: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.40 (s, 2H), 7.33 (t, J=7.6 Hz,
1H), 7.13 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.33 (dd, J=16.0, 7.6
Hz, 1H), 4.08 (m, 1H), 3.90 (s, 2H); ESIMS m/z 413.84
([M+H].sup.+); IR (thin film) 3368, 3274, 1114, 808 cm.sup.-1.
[0738] Prophetically, compounds CI49-CI57 (Table 1) could be made
in accordance with the procedures disclosed in Example 50.
Example 51: Preparation of
3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (CI58)
##STR00293##
[0740] To a stirred solution of
4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in
N,N-dimethylacetamide (DMA; 20 mL) was added K.sub.2CO.sub.3 (2.36
g, 17.16 mmol) and 2-aminopyridine (0.84 g, 8.58 mmol), and the
reaction mixture was stirred at ambient temperature for 4 h. The
reaction mixture was diluted with water and extracted with EtOAc.
The combined organic layer was washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure. The
residue was purified by flash column chromatography (SiO.sub.2,
100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound
as off-white solid (1.05 g, 50%): mp 122-123.degree. C.; .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 9.94 (s, 1H), 8.11 (s, 1H), 7.88
(s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H), 7.4 (m,
1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s,
1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H].sup.+).
Example 52: Preparation of
N-(2-Chloro-4-vinylbenzyl)pyridin-2-amine (CI59)
##STR00294##
[0742] To a stirred solution of
3-chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (1 g, 4. mmol)
in 1,4-dioxane (20 mL) were added K.sub.2CO.sub.3 (0.84 g, 6.09
mmol) and methyl triphenyl phosphonium bromide (2.17 g, 6.09 mmol)
at ambient temperature. Then the resultant reaction mixture was
heated at 100.degree. C. for 18 h. After the reaction was deemed
complete by TLC, the reaction mixture was cooled to ambient
temperature and filtered, and the obtained filtrate was
concentrated under reduced pressure. The residue was purified by
flash chromatography (SiO.sub.2, 100-200 mesh; 10% EtOAc in
n-Hexane) to afford the title compound as a white solid (0.5 g,
50%): mp 119-121.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.12 (s, 1H), 7.42-7.40 (m, 3H), 7.26 (s, 1H), 6.66 (m,
2H), 6.36 (d, J=6.3 Hz, 1H), 5.75 (d, J=13.2 Hz, 1H), 4.92 (br s,
1H), 4.60 (s, 2H); ESIMS m/z 245.05 ([M+H].sup.+).
Example 53: Preparation of Ethyl
2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (CI60)
##STR00295##
[0744] Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol)
was added to sodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50
mL) at 0.degree. C., and the mixture was stirred for 30 min. To
this was added 5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol),
and the reaction mixture was stirred for 3 h at ambient
temperature. The reaction mixture was quenched with 2 N HCl
solution and then stirred for 4 h at ambient temperature. The
mixture was extracted with EtOAc. The combined EtOAc layer was
washed with brine, dried over anhydrous Na.sub.2SO.sub.4, and
concentrated under reduced pressure. Purification by flash column
chromatography (20-30% EtOAc in hexane) afforded the title compound
as a liquid (1.3 g, 20%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.52 (s, 1H), 7.89 (s, 1H), 5.09 (s1H), 4.23 (m, 2H), 2.27 (br s,
2H), 1.26 (m, 3H); ESIMS m/z 293.05 ([M+H].sup.+); IR (thin film)
3381, 3306, 1742, 759, 523 cm.sup.-1.
Example 54: Preparation of
(5-Bromo-3-chloropyridin-2-yl)methanamine hydrochloride (CI61)
##STR00296##
[0746] A stirred solution of ethyl
2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (0.5 g, 1.7 mmol)
in 3 N HCl (25 mL) was heated at reflux for 4 h. The reaction
mixture was washed with Et.sub.2O and water. The combined ether
layer was concentrated under reduced pressure to afford the title
compound as an off-white solid (400 mg, 65%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.78 (s, 1H), 8.70 (br s, 2H), 8.45 (s, 1H),
4.56 (m, 2H); ESIMS m/z 221.15 ([M+H].sup.+).
Example 55: Preparation of
2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione
(CI62)
##STR00297##
[0748] To a stirred solution of
(5-bromo-3-chloropyridin-2-yl)methanamine hydrochloride (0.3 g, 1.4
mmol) in toluene (40 mL) was added TEA (0.41 g, 4.08 mmol) and
phthalic anhydride (0.24 g, 1.63 mmol), and the reaction mixture
was heated at reflux for 2 h. The reaction mixture was concentrated
under reduced pressure, and the residue was diluted with water and
extracted with EtOAc. The combined EtOAc layer was washed with
brine, dried over anhydrous Na.sub.2SO.sub.4, and concentrated
under reduced pressure. The residue was purified by column
chromatography (20-30% EtOAc in hexane) to afford the title
compound as a white solid (0.25 g, 65%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m, 2H), 7.74
(m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M-H].sup.-); IR (thin film)
3307, 1665, 1114, 813 cm.sup.-1.
Example 56: Preparation of
2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione
(CI63)
##STR00298##
[0750] To a stirred solution of
2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (0.23
g, 0.65 mmol) in toluene (10 mL) were added Pd(PPh.sub.3).sub.4
(3.7 mg, 0.003 mmol), K.sub.2CO.sub.3 (0.269 g, 1.95 mmol) and
vinyl boronic anhydride pyridine complex (0.78 g, 3.28 mmol), and
the reaction mixture was heated at reflux for 16 h. The reaction
mixture was filtered, and the filtrate was washed with water and
brine, dried over anhydrous Na.sub.2SO.sub.4, and concentrated
under reduced pressure. Purification by flash column chromatography
(20-30% EtOAc in hexane) afforded the title compound as an
off-white solid (0.2 g, 65%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.72 (m, 1H),
6.63 (m, 1H), 5.79 (d, J=16.0 Hz, 1H), 5.39 (d, J=16.0 Hz, 1H),
5.12 (s, 2H); ESIMS m/z 299.20 ([M+H].sup.+).
Example 57: Preparation of
(E)-2-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichloro-phenyl)but-1-en-1--
yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (CI64)
##STR00299##
[0752] To a stirred solution of
2-((3-chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (0.35
g, 1.17 mmol) in 1,2-dichlorobenzene (10 mL) were added
5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.8 g, 2.3
mmol), CuCl (23 mg, 0.12 mmol), 2,2-bipyridyl (0.073 g, 0.234
mmol), and the reaction mixture was heated at 180.degree. C. for 16
h. The reaction mixture was concentrated under reduced pressure and
purified by column chromatography (20-30% EtOAc in hexane) to
afford the title compound as a liquid (0.4 g, 50%): mp
79-82.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.27
(s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.36 (s, 2H), 6.51 (d, J=15.6
Hz, 1H), 6.32 (dd, J=15.6, 8.0 Hz, 1H), 5.30 (s, 2H), 4.13 (m, 1H);
ESIMS m/z 559 ([M+H].sup.+).
Example 58: Preparation of
(E)-(3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)p-
yridin-2-yl)methanamine (CI65)
##STR00300##
[0754] To a stirred solution of
(E)-2-((3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-y-
l)pyridin-2-yl)methyl)isoindoline-1,3-dione (200 mg, 0.358 mmol) in
EtOH (5 mL) was added hydrazine hydrate (89.6 mg, 1.79 mmol), and
the reaction mixture was heated at reflux for 2 h. The reaction
mixture was concentrated under reduced pressure, and the residue
was dissolved in CH.sub.2Cl.sub.2. The organic layer was washed
with water and brine, dried over anhydrous Na.sub.2SO.sub.4, and
concentrated under reduced pressure to afford the title compound as
a solid (100 mg). The product obtained in this reaction was carried
on to the next step without further purification.
Example 59: Preparation of 4-(Bromomethyl)-1-naphthonitrile
(CI66)
##STR00301##
[0756] To a stirred solution of 4-methyl-1-naphthonitrile (5 g, 30
mmol) in CCl.sub.4 (50 mL) under argon atmosphere was added NBS
(6.06 g, 34.09 mmol), and the reaction mixture was degassed for 30
min. AIBN (0.3 g, 2.1 mmol) was added, and the resultant reaction
mixture was heated at reflux for 4 h. The reaction mixture was
cooled to ambient temperature, diluted with water and extracted
with CH.sub.2Cl.sub.2 (3.times.100 mL). The combined
CH.sub.2Cl.sub.2 layer was washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure. The
residue was purified by flash column chromatography (SiO.sub.2,
100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as
a white solid (3.8 g, 52%): mp 131-133.degree. C.; .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.33 (m, 1H), 8.24 (m, 1H), 7.88 (d, J=8.0
Hz, 1H), 7.78 (m, 2H), 7.62 (d, J=8.0 Hz, 1H), 4.95 (s, 2H); ESIMS
m/z 245.92 ([M+H].sup.+); IR (thin film) 2217 cm.sup.-1.
Example 60: Preparation of 4-(Bromomethyl)-1-naphthaldehyde
(CI67)
##STR00302##
[0758] To a stirred solution of 4-(bromomethyl)-1-naphthonitrile (8
g, 33 mmol) in toluene (100 mL) at 0.degree. C. was added dropwise
DIBAL-H (1.0 M solution in toluene; 43 mL), and the reaction
mixture was stirred at 0.degree. C. for 1 h. 3 N HCl in water (50
mL) was added to the mixture until it became a white slurry and
then additional 1 N HCl (20 mL) was added. The organic layer was
collected and the aqueous layer was extracted with EtOAc
(3.times.100 mL). The combined organic layer was dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; 5% EtOAc in petroleum ether) afforded the title compound as a
white solid (7 g, 88%): mp 115-116.degree. C.; .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 10.41 (s, 1H), 9.35 (m, 1H), 8.22 (m, 1H),
7.90 (d, J=8.0 Hz, 1H), 7.75 (m, 3H), 4.95 (s, 2H); ESIMS m/z
248.88 ([M+H].sup.+).
Example 61: Preparation of
4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (CI68)
##STR00303##
[0760] To a stirred solution of 4-(bromomethyl)-1-naphthaldehyde (7
g, 28. mmol) in DMF (100 mL) was added potassium phthalimide (7.3
g, 39.5 mmol), and the mixture was heated at 85.degree. C. for 2 h.
The reaction mixture was cooled to ambient temperature and diluted
with water (100 mL). The obtained solid was separated by filtration
and dried under vacuum to afford the title compound as a white
solid (8.8 g, 98%): mp 190-192.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 10.39 (s, 1H), 9.25 (m, 1H), 8.41 (m, 1H), 8.10
(d, J=8.0 Hz, 1H), 7.95 (m, 4H), 7.80 (m, 4H), 7.61 (m, 4H), 5.39
(s, 2H); ESIMS m/z 316.09 ([M+H].sup.+); IR (thin film) 1708
cm.sup.-1.
Example 62: Preparation of 2-((4-Vinylnaphthalen-1-yl)methyl)
isoindoline-1,3-dione (CI69)
##STR00304##
[0762] To a stirred solution of
4-((1,3-dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (9 g, 28.5
mmol) in 1,4-dioxane (100 mL) were added K.sub.2CO.sub.3 (6 g, 42.8
mmol) and methyl triphenyl phosphonium bromide (15.3 g, 35.7 mmol)
at ambient temperature. The reaction mixture was heated at
100.degree. C. for 14 h and then was cooled to ambient temperature.
The reaction mixture was filtered, and the obtained filtrate was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 100-200 mesh; 20% EtOAc in petroleum
ether) afforded the title compound as a white solid (6 g, 67%): mp
146-147.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.35
(m, 2H), 7.95 (m, 4H), 7.65 (m, 4H), 7.39 (m, 1H), 5.81 (m, 1H),
5.45 (m, 1H), 5.21 (s, 2H); ESIMS m/z 314.13 ([M+H].sup.+).
Example 63: Preparation of
(E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphtha-
len-1-yl)methyl)isoindoline-1,3-dione (CI70)
##STR00305##
[0764] To a stirred solution of
2-((4-vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (1.5 g,
4.79 mmol) in 1,2-dichlorobenzene (15 mL) were added
1-(1-bromo-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzene (3.2 g, 9.5
mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95
mmol), and the resultant reaction mixture was degassed with argon
for 30 min and then stirred at 180.degree. C. for 14 h. After the
reaction was deemed complete by TLC, the reaction mixture was
cooled to ambient temperature and filtered, and the filtrate was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 100-200 mesh; 25-30% EtOAc in petroleum
ether) afforded the title compound as an off-white solid (1.5 g,
56%): mp 158-160.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.40 (m, 1H), 7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H),
7.58 (m, 2H), 7.46 (s, 2H), 7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s,
2H), 4.21 (m, 1H); ESIMS m/z 572.08 ([M-H].sup.-).
Example 64: Preparation of
(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-
-1-yl)methanamine (CI71)
##STR00306##
[0766] To a stirred solution of
(E)-2-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphtha-
len-1-yl)methyl)isoindoline-1,3-dione (0.4 g, 0.7 mmol) in EtOH was
added hydrazine hydrate (0.18 g, 3.5 mmol), and the resultant
reaction mixture was heated at 80.degree. C. for 2 h. The reaction
mixture was filtered, and the filtrate was concentrated. The
residue was dissolved in CH.sub.2Cl.sub.2, and the solution was
washed with brine, dried over Na.sub.2SO.sub.4, and concentrated
under reduced pressure. The title compound was isolated as a gummy
liquid (150 mg, 50%). The product obtained in this reaction was
carried on to the next step without further purification.
Example 65: Preparation of
2-((4-Bromophenyl)amino)isoindoline-1,3-dione (CI72)
##STR00307##
[0768] To a stirred solution of (4-bromophenyl)hydrazine
hydrochloride (0.5 g, 2.2 mmol) in AcOH (8 mL) was added phthalic
anhydride (0.398 g, 2.690 mmol), and the reaction mixture was
stirred at 130.degree. C. for 1 h under a nitrogen atmosphere. The
reaction mixture was quenched with satd aqueous NaHCO.sub.3
solution and filtered to give a solid. Purification by column
chromatography (SiO.sub.2, 0-10% EtOAc in petroleum ether) afforded
the title compound as a solid (60 mg, 84%): mp 205-206.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.71 (s, 1H), 7.99 (m,
4H), 7.32 (d, J=8.8 Hz, 2H), 6.79 (d, J=8.8 Hz, 2H); ESIMS m/z
314.95 ([M-H].sup.-).
Example 66: Preparation of
2-((4-Vinylphenyl)amino)isoindoline-1,3-dione (CI73)
##STR00308##
[0770] To a solution of 2-(4-bromophenylamino)isoindoline-1,3-dione
(2 g, 6. mmol) in 1,2-dimethoxyethane (20 mL) and water (4 mL) were
added vinyl boronic anhydride pyridine complex (4.57 g, 18.98 mmol)
and K.sub.2CO.sub.3 (1.3 g, 9.5 mmol) followed by
Pd(PPh.sub.3).sub.4 (0.219 g, 0.189 mmol). The resultant reaction
mixture was heated at 150.degree. C. in a microwave for 30 min and
then was concentrated under reduced pressure. Purification by
column chromatography (SiO.sub.2, 15% EtOAc in petroleum ether)
afforded the title compound as a solid (200 mg, 13%): mp
174-176.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.65
(s, 1H), 7.94 (m, 4H), 7.29 (d, J=8.4 Hz, 2H), 6.72 (d, J=8.4 Hz,
2H), 6.61 (m, 1H), 5.61 (d, J=17.6 Hz, 1H), 5.05 (d, J=11.2 Hz,
1H); ESIMS m/z 263.18 ([M-H].sup.-).
Example 67: Preparation of
(E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-
amino)isoindoline-1,3-dione (CI74)
##STR00309##
[0772] To a stirred solution of
2-(4-vinylphenylamino)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in
1,2-dichlorobenzene (5 mL) were added CuCl (0.022 g, 0.273 mmol),
2,2-bipyridyl (0.07 g, 0.46 mmol) and
5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.77 g,
2.27 mmol). The reaction mixture was degassed with argon for 30 min
and was heated at 180.degree. C. for 2 h. The reaction mixture was
then concentrated under reduced pressure, and the residue was
purified by column chromatography (SiO.sub.2, 0-30% EtOAc in
petroleum ether) to afford the title compound as a solid (450 mg,
75%): mp 187-189.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.75 (s, 1H), 7.96 (m, 4H), 7.82 (s, 2H), 7.37 (d, J=8.8
Hz, 1H), 6.73 (d, J=8.4 Hz, 2H), 6.61 (m, 2H), 6.58 (m, 1H), 4.59
(m, 1H); ESIMS m/z 523.05 ([M-H].sup.-).
Example 68: Preparation of
(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hyd-
razine (CI75)
##STR00310##
[0774] To a stirred solution of
(E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenylamino-
)isoindoline-1,3-dione (0.16 g, 0.31 mmol) in EtOH (5 mL), was
added hydrazine hydrate (0.076 g, 1.52 mmol), and the reaction
mixture was heated at 85.degree. C. for 1 h. The reaction mixture
was cooled to ambient temperature and filtered, and the filtrate
was concentrated under reduced pressure to afford the title
compound as a solid (0.08 g, 66%) which was carried on to the next
step without further purification.
Example 69: Preparation of 2-(4-Vinylphenoxy)isoindoline-1,3-dione
(CI76)
##STR00311##
[0776] To a stirred solution of 4-vinylphenylboronic acid (2 g, 13
mmol), 2-hydroxyisoindoline-1,3-dione (3.63 g, 24.53 mmol), and
CuCl (1.214 g 12.26 mmol) in 1,2-dichloroethane (50 mL) was added
pyridine (1.065 g, 13.48 mmol), and the resultant reaction mixture
was stirred at ambient temperature for 48 h. The reaction mixture
was diluted with water and extracted with CHCl.sub.3. The combined
CHCl.sub.3 layer was washed with brine, dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure. Purification by flash
column chromatography (SiO.sub.2; 20% EtOAc in petroleum ether)
afforded the title compound as a white solid (2 g, 63%): mp
129-131.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.93
(d, J=2.0 Hz, 2H), 7.82 (d, J=3.2 Hz, 2H), 7.38 (d, J=2.0 Hz, 2H),
7.14 (d, J=2.0 Hz, 2H), 6.70 (m, 1H), 5.83 (d, J=16.0 Hz, 1H), 5.22
(d, J=10.8 Hz, 1H); ESIMS m/z 266.12 ([M+H].sup.+).
Example 70: Preparation of
(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)-
isoindoline-1,3-dione (CI77)
##STR00312##
[0778] To a stirred solution of
2-(4-vinylphenoxy)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in
1,2-dichlorobenzene (10 mL) was added
1-(1-bromoethyl)-3,4,5-trichlorobenzene (769 mg, 2.26 mmol), CuCl
(22 mg, 0.22 mmol) and 2,2-bipyridyl (35 mg, 0.44 mmol), and the
resultant reaction mixture was degassed with argon for 30 min and
heated to 180.degree. C. for 24 h. The reaction mixture was cooled
to ambient temperature and filtered, and the filtrate was
concentrated under reduced pressure. The crude material was
purified by column chromatography (SiO.sub.2, 100-200 mesh; 20%
EtOAc in petroleum ether) to afford the title compound as a solid
(0.29 g, 50%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.90 (m,
1H), 7.62 (m, 2H), 7.50 (m, 1H), 7.40 (s, 2H), 7.12 (s, 1H), 6.90
(m, 2H), 6.60 (m, 2H), 6.20 (m, 1H), 4.08 (m, 1H); ESIMS m/z 524.09
([M-H].sup.-).
Example 71: Preparation of
(E)-O-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)h-
ydroxylamine (CI78)
##STR00313##
[0780] To a stirred solution of
(E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenoxy)iso-
indoline-1,3-dione (0.2 g, 0.4 mmol) in EtOH was added hydrazine
hydrate (0.1 g, 1.9 mmol), and the resultant reaction mixture was
heated at 90.degree. C. for 1 h. The reaction mixture was filtered,
and the filtrate was concentrated. The residue was dissolved in
CH.sub.2Cl.sub.2. washed with brine, dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure to afford the crude title
compound as a gummy liquid (0.08 g, 53%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.40 (s, 2H), 6.98 (s, 1H), 6.82 (s, 2H), 6.48
(m, 1H), 6.20 (m, 1H), 5.02 (s, 1H), 4.08 (m, 1H); ESIMS m/z 394.94
([M-H].sup.-).
Example 72: Preparation of
(E)-N-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzyl)acetami-
de (CC1)
##STR00314##
[0782] To a stirred solution of
(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phen-
yl)methanamine (0.3 g, 0.8 mmol) in CH.sub.2Cl.sub.2 (10 mL) was
added acetic anhydride (0.12 mL, 1.14 mmol), and TEA (0.217 mL,
1.52 mmol), and the resultant reaction mixture was stirred at
ambient temperature for 6 h. The reaction mixture was diluted with
water and extracted with CH.sub.2Cl.sub.2. The combined
CH.sub.2Cl.sub.2 layer was washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; 30-50% EtOAc in hexane) afforded the title compound as an
off-white solid (0.2 g, 60%) mp 107-109.degree. C.; .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d,
J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.75 (br s, 1H),
4.46 (d, J=6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H); ESIMS m/z 402.00
([M+H].sup.+).
[0783] Compounds CC2-CC6 in Table 1 were made in accordance with
the procedures disclosed in Example 72. In addition, compound DC56
in Table 1 was made from compound DC55 in accordance with the
procedures disclosed in Example 72.
Example 73: Preparation of
(E)-N-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)be-
nzyl)acetamide (CC7)
##STR00315##
[0785] To a stirred solution of
(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phen-
yl)methanamine (0.3 g, 0.8 mmol) in DMF (5 mL) was added
2,2,2-trifluoropropanoic acid (97 mg, 0.76 mmol), HOBt.H.sub.2O
(174 mg, 1.14 mmol) and EDC.HCl (217 mg, 1.14 mmol) and DIPEA (196
mg, 1.52 mmol), and the resultant reaction mixture was stirred at
ambient temperature for 18 h. The reaction mixture was diluted with
water and extracted with EtOAc. The combined EtOAc layer was washed
with brine, dried over Na.sub.2SO.sub.4, and concentrated under
reduced pressure. Purification by flash column chromatography
(SiO.sub.2, 100-200 mesh; EtOAc in hexane (30-50% afforded the
title compound as an off-white solid (0.2 g, 60%): mp
127-128.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.42
(m, 4H), 7.24 (m, 2H), 6.53 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0,
8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J=6.0 Hz, 2H), 4.05 (m, 1H),
2.02 (s, 3H); ESIMS m/z 436.03 ([M+H].sup.+).
[0786] Compounds CC8-CC28 in Table 1 were made in accordance with
the procedures disclosed in Example 73.
Example 74: Preparation of
(E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl-
)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide
(CC29)
##STR00316##
[0787] Step 1:
(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-
-enyl)-2-(trifluoromethyl)benzyl)methanamine
[0788]
(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(-
trifluoromethyl)phenyl)methanamine (0.46 g, 1 mmol) was dissolved
in MeOH (3 mL). To this was added pyridine-2-carbaldehyde (0.107 g,
1 mmol). The reaction mixture was stirred for 1 h. After 1 h,
NaBH.sub.4 (0.076 g, 2 mmol) was added and left at ambient
temperature for 3 h. The reaction mixture was concentrated to give
an oily residue. Purification by flash column chromatography
(SiO.sub.2, 100-200 mesh; 30-50% EtOAc in hexane) afforded the
title compound as a pale yellow liquid (0.22 g, 40%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.58 (d, J=4.8 Hz, 1H), 7.74 (m, 1H),
7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H),
6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 4.10 (m,
1H), 4.02 (s, 2H), 3.96 (s, 2H); ESIMS m/z 552.95 ([M+H].sup.+); IR
(thin film) 3338, 1114, 808 cm.sup.-1.
Step 2:
(E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlor-
ophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide
[0789]
(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl-
)but-1-en-1-yl)-2-(trifluoromethyl)benzyl)methanamine (0.27 g, 0.05
mmol) was taken up in CH.sub.2Cl.sub.2 (3 mL). To this was added
TEA (0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10
min. After 10 min, the reaction mixture was cooled to 0.degree. C.,
and cyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added.
The reaction mixture was stirred at ambient temperature for 1 h and
then was washed with water and satd aq NaHCO.sub.3 solution. The
organic layer was dried over anhydrous Na.sub.2SO.sub.4 and
evaporated to obtain pale yellow gummy material (0.15 g, 50%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.58 (d, J=4.6 Hz, 1H),
7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H),
7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz,
1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J=10 Hz, 2H), 4.10 (m, 1H),
1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86
([M-H].sup.-); IR (thin film) 1645, 1115, 808 cm.sup.-1.
Example 75: Preparation of
(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl-
)benzyl)-3-(methylsulfonyl)propanamide (CC30)
##STR00317##
[0791]
(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-e-
n-1-yl)benzyl)-3-(methylthio)propanamide (0.15 g, 0.28 mmol) was
treated with oxone (0.175 g, 0.569 mmol) in 1:1 acetone:water (20
mL) for 4 h at ambient temperature. The acetone was evaporated to
obtain a white solid (0.095 g, 60%): mp 101-104.degree. C.; .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.41 (m, 4H), 7.24 (m, 1H), 6.53
(d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.12 (br s, 1H),
4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m,
2H); ESIMS m/z 559.75 ([M-H].sup.-).
Example 76: Preparation of
(E)-1-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)be-
nzyl)-3-ethylurea (CC31)
##STR00318##
[0793] To a stirred solution of
(E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phen-
yl)methanamine (0.2 g, 0.5 mmol) in CH.sub.2Cl.sub.2 (5 mL) at
0.degree. C. were added TEA (0.141 mL, 1 mmol) and ethylisocyanate
(0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h
at 0.degree. C. The reaction mixture was diluted with
CH.sub.2Cl.sub.2. The organic layer was washed with water and
brine, dried over Na.sub.2SO.sub.4, and concentrated under reduced
pressure. Purification by column chromatography (SiO.sub.2, 100-200
mesh; 30-50% EtOAc in hexane) afforded the title compound as a
solid (0.141 g, 60%): mp 177-178.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53
(d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 4.70 (br s, 1H),
4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); ESIMS m/z
463 ([M-H].sup.-).
[0794] Compounds CC32-CC35 in Table 1 were made in accordance with
the procedures disclosed in Example 76.
Example 77: Preparation of
(E)-3-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl-
)benzyl)-1,1-dimethylurea (CC36)
##STR00319##
[0796] To a stirred solution of
(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)p-
henyl)methanamine (0.2 g, 0.5 mmol) in CH.sub.2Cl.sub.2 (5 mL) at
0.degree. C. were added TEA (0.141 mL, 1 mmol) and
N,N-dimethylcarbamoyl chloride (0.08 g, 0.075 mmol), and the
reaction mixture was stirred for 1 h at 0.degree. C. The reaction
mixture was diluted with CH.sub.2Cl.sub.2. The organic layer was
washed with water and brine, dried over Na.sub.2SO.sub.4, and
concentrated under reduced pressure. Purification by column
chromatography (SiO.sub.2, 100-200 mesh; 30-50% EtOAc in hexane)
afforded the title compound as a solid (0.15 g, 60%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d,
J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H),
4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H);
ESIMS m/z 497 ([M-H].sup.-); IR (thin film) 3350, 1705, 1114, 808
cm.sup.-1.
Example 78: Preparation of
(E)-1-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl-
)benzyl)-3-ethylthiourea (CC37)
##STR00320##
[0798] To a stirred solution of
(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)p-
henyl)methanamine (0.2 g, 0.5 mmol) in CH.sub.2Cl.sub.2 (5 mL) at
0.degree. C. were added TEA (0.141 mL, 1 mmol) and ethyl
isothicyanate (0.053 g, 0.75 mmol), and the reaction mixture was
stirred for 1 h at 0.degree. C. The reaction mixture was diluted
with CH.sub.2Cl.sub.2. The organic layer was washed with water and
brine, dried over Na.sub.2SO.sub.4, and concentrated under reduced
pressure. Purification by column chromatography (SiO.sub.2, 100-200
mesh; 30-50% EtOAc in hexane) afforded the title compound as a
solid (0.14 g, 60%): mp 88-91.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.49 (d, J=8 Hz, 1H), 7.41 (d, J=7.2 Hz, 2H),
7.26 (m, 2H), 6.50 (d, J=16 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H),
6.0 (br s, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H),
1.23 (m, 3H); ESIMS m/z 515.01 ([M+H].sup.+).
[0799] Compound CC38 in Table 1 was made in accordance with the
procedures disclosed in Example 78.
Example 79: Preparation of (E)-tert-Butyl
(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)--
3-ethylurea (CC39)
##STR00321##
[0801] To a stirred solution of
(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)p-
henyl)methanamine (0.2 g, 0.5 mmol in CH.sub.2Cl.sub.2 (5 mL) at
0.degree. C. were added TEA (0.141 mL, 1 mmol) and di-tert-butyl
dicarbonate (0.163 mL, 0.75 mmol), and the reaction mixture was
stirred for 4 h at ambient temperature. The reaction mixture was
diluted with CH.sub.2Cl.sub.2. The organic layer was washed with
water and brine, dried over Na.sub.2SO.sub.4, and concentrated
under reduced pressure. Purification by column chromatography
(SiO.sub.2, 100-200 mesh; 10-20% EtOAc in hexane) afforded the
title compound as a white solid (0.147 g, 60%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d,
J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H),
4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H); ESIMS m/z
526.09 ([M-H].sup.-); IR (thin film) 3350, 1705, 1114, 808
cm.sup.-1.
[0802] Compound CC40 in Table 1 was made in accordance with the
procedures disclosed in Example 79.
Example 80: Preparation of (E)-Methyl
2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)be-
nzyl)amino)-2-oxoacetate (CC41)
##STR00322##
[0804] To a stirred solution of
(E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)p-
henyl)methanamine (0.2 g, 0.5 mmol) in CH.sub.2Cl.sub.2 (5 mL) at
0.degree. C. were added TEA (0.141 mL, 1 mmol) and methyl
2-chloro-2-oxoacetate (0.09 g, 0.75 mmol), and the reaction mixture
was stirred for 1 h at 0.degree. C. The reaction mixture was
diluted with CH.sub.2Cl.sub.2. The organic layer was washed with
water and brine, dried over Na.sub.2SO.sub.4, and concentrated
under reduced pressure. Purification by column chromatography
(SiO.sub.2, 100-200 mesh; 20% EtOAc in hexane) afforded the title
compound as a solid (0.12 g, 50%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.48 (m, 1H). 7.43 (m, 3H), 7.38 (m, 1H), 7.23
(s, 1H), 6.55 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H),
4.60 (d, J=4.4 Hz, 2H), 4.18 (m, 1H), 3.85 (s, 3H); ESIMS m/z
512.22 ([M-H].sup.-); IR (thin film) 1740, 1701, 1114, 808
cm.sup.-1.
Example 81: Preparation of
(E)-N.sup.1-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-e-
n-1-yl)benzyl)-N.sup.2-(2,2,2-trifluoroethyl)oxalamide (CC42)
##STR00323##
[0806] To a stirred solution of 2,2,2-trifluoroethylamine
hydrochloride (0.1 g, 0.77 mmol) in CH.sub.2Cl.sub.2 (10 mL) was
added dropwise trimethylaluminum (2 M solution in toluene; 0.39 mL,
0.77 mmol), and the reaction mixture was stirred at 25.degree. C.
for 30 min. A solution of (E)-methyl
2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)be-
nzyl)-2-oxoacetate (0.2 g, 0.38 mmol) in CH.sub.2Cl.sub.2 (5 mL)
was added dropwise to the reaction mixture at 25.degree. C. The
reaction mixture was stirred at reflux for 18 h, cooled to
25.degree. C., quenched with 0.5 N HCl solution (50 mL) and
extracted with EtOAc (2.times.50 mL). The combined organic extracts
were washed with brine, dried over Na.sub.2SO.sub.4, and
concentrated under reduced pressure. The crude compound was
purified by flash chromatography (SiO.sub.2, 100-200 mesh; 20%-40%
EtOAc in n-hexane) to afford the title compound (0.13 g, 60%): mp
161-163.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (s, 1H), 7.28 (s,
1H), 6.93 (m, 1H), 6.75 (m, 1H), 4.80 (m, 1H), 4.40 (s, 2H), 3.90
(s, 2H); ESIMS m/z 578.96 ([M-H].sup.-).
Example 82: Preparation of
(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl-
)benzyl)pyridin-2-amine (CC43)
##STR00324##
[0808] To a stirred solution of
N-(2-chloro-4-vinylbenzyl)pyridin-2-amine (0.3 g, 1.22 mmol) in
1,2-dichlorobenzene (5 mL) were added
5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.83 g,
2.44 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (76 mg, 0.48
mmol). The resultant reaction mixture was degassed with argon for
30 min and then stirred at 180.degree. C. for 24 h. After the
reaction was deemed complete by TLC, the reaction mixture was
cooled to ambient temperature and filtered, and the filtrate was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 100-200 mesh; 15% EtOAc in n-hexane)
afforded the title compound as an off-white solid (0.2 g, 35%): mp
140-142.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.11
(d, J=4.0 Hz, 1H), 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35
(m, 2H), 4.94 (br s, 1H), 4.61 (d, J=6.4 Hz, 2H), 4.11 (m, 1H);
ESIMS m/z 505.39 ([M+H].sup.+).
Example 83: Preparation of
(E)-N-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-en-1--
yl)pyridin-2-yl)methyl)-3,3,3-trifluoropropanamide (CC44)
##STR00325##
[0810] To a stirred solution of
(E)-(3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)p-
yridin-2-yl)methanamine (0.1 g, 0.2 mmol) in CH.sub.2Cl.sub.2 (5
mL) were added 3,3,3-trifluoropropanoic acid (45 mg, 0.350 mmol),
EDC.HCl (67 mg, 0.350 mmol), HOBt.H.sub.2O (71 mg, 0.467 mmol) and
DIPEA (60.2 mg, 0.467 mmol), and the reaction mixture was stirred
at ambient temperature for 18 h. The reaction mixture was diluted
with CH.sub.2Cl.sub.2 and washed with water. The combined
CH.sub.2Cl.sub.2 layer was washed with brine, dried over anhydrous
Na.sub.2SO.sub.4, and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; 15% EtOAc in petroleum ether) afforded the title compound as
a pale yellow liquid (30 mg, 35%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.41 (s, 1H), 7.77 (s, 1H), 7.47 (br s, 1H),
7.40 (s, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz,
1H), 4.68 (d, J=4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J=10.8 Hz, 2H);
ESIMS m/z 536.88 ([M-H].sup.-); IR (thin film) 3320, 1674, 1114,
808.
[0811] Compound CC45 in Table 1 was made in accordance with the
procedures disclosed in Example 83.
Example 84: Preparation of
(E)-3,3,3-Trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-
-en-1-yl)naphthalen-1-yl)methyl)propanamide (CC46)
##STR00326##
[0813] To a stirred solution of
(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-
-1-yl)methanamine (0.1 g, 0.22 mmol) in CH.sub.2Cl.sub.2 (8 mL)
were added 3,3,3-trifluoropropanoic acid (0.032 g, 0.24 mmol),
HOBt.H.sub.2O (52 mg, 0.33 mmol), EDC.HCl (0.065 g, 0.33 mmol) and
DIPEA (0.044 g, 0.45 mmol), and the resultant reaction mixture was
stirred at ambient temperature for 18 h. The reaction mixture was
diluted with water and extracted with EtOAc (3.times.30 mL). The
combined EtOAc layer was washed with brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2, 100-200
mesh; 15% EtOAc in n-hexane) afforded the title compound as a gummy
material (60 mg, 50%): mp 151-153.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44
(d, J=8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H),
4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H); ESIMS m/z 554.04
([M-H].sup.-).
[0814] Compounds CC47-CC48 in Table 1 were made in accordance with
the procedures disclosed in Example 84.
Example 85: Preparation of
(E)-1-Ethyl-3-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl-
)naphthalen-1-yl)methyl)urea (CC49)
##STR00327##
[0816] To a stirred solution of
(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-
-1-yl)methanamine (0.1 g, 0.22 mmol) in CH.sub.2Cl.sub.2 at
0.degree. C. were added TEA (0.064 mL, 0.44 mmol) and
ethylisocyanate (0.023 mL, 0.33 mmol), and the reaction mixture was
stirred for 1 h at 0.degree. C. The reaction mixture was diluted
with CH.sub.2Cl.sub.2. The organic layer was washed with water and
brine, dried over Na.sub.2SO.sub.4, and concentrated under reduced
pressure. Purification by column chromatography (SiO.sub.2, 100-200
mesh; 30% EtOAc in hexane) afforded the title compound as a solid
(0.07 g, 60%): mp 84-87.degree. C.; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.06 (m, 1H), 7.98 (m, 1H), 7.61 (m, 3H), 7.48
(s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92
(s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J=4.6
Hz, 3H); ESIMS m/z 515.33 ([M+H].sup.+).
Example 86: Preparation of
(E)-N'-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-
cyclopropanecarbohydrazide (CC50)
##STR00328##
[0818] To a stirred solution of
(E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hyd-
razine (0.1 g, 0. 3 mmol) in CH.sub.2Cl.sub.2 (10 mL) was added
DIPEA (65 mg, 0.51 mmol), HOBt.H.sub.2O (59 mg, 0.38 mmol), EDC.HCl
(73 mg, 0.38 mmol) and cyclopropanecarbonyl chloride (0.024 g, 0.28
mmol), and the reaction mixture was stirred at ambient temperature
for 1 h. The reaction mixture was diluted with satd aq NaHCO.sub.3
solution and extracted with CH.sub.2Cl.sub.2. The combined
CH.sub.2Cl.sub.2 layer was washed with brine, dried over anhydrous
Na.sub.2SO.sub.4, and concentrated under reduced pressure.
Purification by flash column chromatography (SiO.sub.2; 5-25% EtOAc
in petroleum ether) afforded the title compound as a solid (65 mg,
55%): mp 138-140.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J=8.4
Hz, 2H), 6.65 (d, J=15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48
(dd, J=15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H);
ESIMS m/z 461.32 ([M-H].sup.-).
[0819] Compound CC51 in Table 1 was made in accordance with the
procedures disclosed in Example 86.
Example 87: Preparation of
(E)-N-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)-
cyclopropanecarboxamide (CC52)
##STR00329##
[0821] To a stirred solution of
(E)-O-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)h-
ydroxylamine (0.15 g, 0.38 mmol) in CH.sub.2Cl.sub.2 (5 mL) was
added EDC.HCl (0.109 g, 0.569 mmol), HOBt.H.sub.2O (0.087 g, 0.569
mmol), DIPEA (0.097 g, 0.758 mmol) and cyclopropanecarboxylic acid
(0.049 g, 0.569 mmol). The resultant reaction mixture was stirred
at ambient temperature for 18 h. The reaction mixture was diluted
with water and extracted with CHCl.sub.3 (35 mL) The combined
CHCl.sub.3 layer was washed with brine, dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure. Purification by flash
column chromatography (SiO.sub.2; 20% EtOAc in hexane) afforded the
title compound as a brown liquid (0.06 g, 34%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.40 (s, 2H), 7.18 (s, 1H), 7.08 (s, 1H),
6.85 (m, 1H), 6.45 (m, 1H), 6.65 (m, 1H), 6.20 (m, 1H), 5.55 (s,
1H), 4.08 (m, 1H), 1.90 (m, 1H), 1.30-1.10 (m, 4H); ESIMS m/z
464.87 ([M-H].sup.-).
[0822] Compound CC53 in Table 1 was made in accordance with the
procedures disclosed in Example 87.
Example 88: Preparation of
(Z)-3,3,3-Trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1--
en-1-yl)benzyl)propanamide (CC54)
##STR00330##
[0824] A silicon borate vial was charged with
(E)-3,3,3-trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1--
en-1-yl)benzyl)propanamide (133 mg, 0.269 mmol) and dimethyl
sulfoxide (DMSO; 10 mL). The mixture was placed within 0.6 to 1
meter (m) of a bank of eight 115 watt Sylvania
FR48T12/350BL/VHO/180 Fluorescent Tube Black Lights and four 115
watt Sylvania (daylight) F48T12/D/VHO Straight T12 Fluorescent Tube
Lights for 72 h. The mixture was concentrated in vacuo and purified
by reverse phase chromatography to give the title compound as a
colorless oil (11 mg, 8%): .sup.1H NMR (300 MHz, CDCl.sub.3)
.delta. 7.28 (s, 2H), 7.25 (m, 2H), 7.10 (d, J=8.0 Hz, 2H), 6.89
(d, J=11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J=5.8
Hz, 2H), 4.34 (m, 1H), 3.12 (q, J=7.5 Hz, 2H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 162.44, 137.20, 135.38, 135.23, 134.82,
134.68, 131.71, 129.00, 128.80, 128.69, 128.10, 127.96, 122.63,
76.70, 47.33 (q, J=28 Hz), 43.59, 42.12 (q, J=30 Hz); ESIMS m/z 504
([M+H].sup.+).
[0825] Compounds DC46, AC93. AC94 in Table 1 were made in
accordance with the procedures disclosed in Example 88.
Example 89: Preparation of
1-(1-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (DI2)
##STR00331##
[0827] The title compound was synthesized in two steps via
1-(3-chlorophenyl)-2,2,2-trifluoroethanol (DI1, prepared as in Step
1, Method B in Example 1); isolated as a colorless viscous oil (1.5
g, 75%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.50 (s, 1H),
7.42-7.35 (m, 3H), 5.02 (m, 1H), 2.65 (br s, 1H)) and Step 2 in
Example 1 and isolated (0.14 g, 22%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.50 (br s, 1H), 7.42-7.35 (m, 3H), 5.07 (m,
1H).
[0828] The following compounds were made in accordance with the
procedures disclosed in Example 89.
(1-Bromo-2,2,2-trifluoroethyl)benzene (DI4)
##STR00332##
[0830] 2,2,2-Trifluoro-1-phenylethanol (DI3) was isolated (10 g,
80%): .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 7.48 (m, 2H), 7.40
(m, 3H), 5.02 (m, 1H), 2.65 (d, J=7.1 Hz, 1H). The title compound
(DI4) was isolated as a liquid (8.0 g, 60%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q, J=7.5 Hz,
1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (DI20)
##STR00333##
[0832] 1-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (DI19) was
isolated an off white solid: .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.05 (s, 2H), 7.02 (s, 1H), 4.95 (m, 1H), 2.32 (s, 6H);
ESIMS m/z 204 ([M].sup.-). The title compound (DI20) was isolated
(3.0 g, 51%).
1-(1-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (DI22)
##STR00334##
[0834] 1-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (DI21) was
isolated as an off white powder (5.3 g, 61%): mp 49-51.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.62-7.66 (d, 1H),
7.42-7.44 (d, 1H), 7.32-7.36 (d, 1H), 5.6 (m, 1H), 2.7 (s, 1H);
ESIMS m/z 244 ([M].sup.+). The title compound (DI22) was isolated
(3.2 g, 50%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.62-7.72
(m, 1H), 7.4-7.42 (m, 1H), 7.3-7.38 (m, 1H), 5.7-5.8 (m, 1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (DI24)
##STR00335##
[0836] 1-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (DI23) was
isolated as a pale yellow oil (5.2 g, 60%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.62-7.64 (d, 1H), 7.52-7.54 (m, 1H), 7.29-7.33
(t, 1H), 5.6-5.76 (m, 1H), 2.7 (s, 1H); ESIMS m/z 243.9
([M].sup.+). The title compound (DI24) was isolated as an oil (8.7
g, 60%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.62-7.71 (m,
1H), 7.44-7.52 (m, 1H), 7.27-7.3 (s, 1H), 5.81-5.91 (m, 1H).
2-(1-Bromo-2,2,2-trifluoroethyl)-1,4-dichlorobenzene (DI26)
##STR00336##
[0838] 1-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (DI25) was
isolated as a yellow oil (4.1 g, 60%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.68-7.7 (s, 1H), 7.3-7.37 (m, 2H), 5.51-5.6
(m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M].sup.+)). The title
compound (DI26) was isolated (3.0 g, 60%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.7-7.78 (m, 1H), 7.3-7.4 (m, 2H), 5.7-5.8 (m,
1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene
(DI28)
##STR00337##
[0840] 1-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol
(DI27) was isolated (3.8 g, 60%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.98 (m, 3H), 5.25 (m, 1H), 3.2 (br, 1H); ESIMS m/z 312.2
([M].sup.+). The title compound (DI28) was prepared and carried on
crude.
1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (DI30)
##STR00338##
[0842] 2,2,2-Trifluoro-1-(2,3,5-trichlorophenyl)ethanol (DI29) was
isolated as a white solid (4.0 g, 60%): mp 113-115.degree. C.;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.62 (d, 1H), 7.50 (d,
1H), 5.60-5.70 (m, 1H), 2.75 (s, 1H); ESIMS m/z 278.0 ([M.sup.+]).
The title compound (DI30) was isolated (2.9 g, 60%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.70 (d, 1H), 7.50 (d, 1H), 5.72-5.82
(m, 1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene
(DI32)
##STR00339##
[0844]
1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol
(DI131) was isolated as a pale yellow oil (2.0 g, 50%): .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.51 (m, 3H), 5.08 (m, 1H), 2.81 (s,
1H); ESIMS m/z 278.1 ([M].sup.+). The title compound (DI132) was
isolated oil (2.0 g, 40%): ESIMS m/z 342 ([M].sup.+).
5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-methoxybenzene
(DI34)
##STR00340##
[0846] 1-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol
(DI33) was isolated as an off white solid (0.8 g, 60%); mp
92-95.degree. C.: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.41
(s, 2H), 5.00 (m, 1H), 3.89 (s, 3H), 2.64 (m, 1H); ESIMS m/z 274
([M].sup.+). The title compound (DI134) was isolated as a colorless
liquid (0.6 g, 57%).
Example 90: Preparation of
1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (DI36)
##STR00341##
[0848] The title compound was synthesized in two steps via
1-(3,5-difluorophenyl)-2,2,2-trifluoroethanol (DI35, prepared as in
Step 1, Method A in Example 1; isolated as a colorless oil (0.2 g,
75%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.05 (m, 2H), 6.88
(m, 1H), 5.06 (m, 1H), 2.66 (s, 1H); ESIMS m/z 212 ([M].sup.+) and
Step 2 in Example 1 and isolated (3.2 g, 50%); .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.05 (m, 2H), 6.86 (m, 1H), 5.03 (q, J=7.4
Hz, 1H).
[0849] The following compounds were made in accordance with the
procedures disclosed in Example 90.
1-(1-Bromo-2,2,2-trifluoroethyl)-4-chlorobenzene (DI38)
##STR00342##
[0851] 1-(4-Chlorophenyl)-2,2,2-trifluoroethanol (DI37) was
isolated as a colorless oil (5.0 g, 99%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.44-7.38 (m, 4H), 5.05 (m, 1H), 2.55 (s, 1H);
ESIMS m/z 210 ([M].sup.+). The title compound (DI38) was isolated
(3.0 g, 46%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.45 (d,
J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz, 2H), 5.10 (q, J=7.2 Hz, 1H).
1-(1-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (DI40)
##STR00343##
[0853] 2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (DI39) was
isolated as a pale yellow liquid: .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.41 (d, J=8.8 Hz, 2H), 6.95 (m, J=8.8 Hz, 2H), 5.00 (m,
1H), 3.82 (s, 3H), 2.44 (s, 1H); ESIMS m/z 206.1 ([M].sup.+). The
title compound (DI40) was isolated (3.8 g, 62%).
1-(1-Bromo-2,2,2-trifluoroethyl)-4-fluorobenzene (DI42)
##STR00344##
[0855] 2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol (DI41) was
isolated as a colorless oil (5 g, 99%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.48-7.45 (m, 2H), 7.13-7.07 (m, 2H), 5.06 (m,
1H), 2.53 (s, 1H); ESIMS m/z 194 ([M].sup.+). The title compound
(DI42) was prepared and carried on as crude intermediate.
1-(1-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (DI44)
##STR00345##
[0857] 2,2,2-Trifluoro-1-(p-tolyl)ethanol (DI43) was isolated as
colorless oil (5.0 g, 99%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.37 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 5.02 (m,
1H), 2.46 (m, 1H), 2.37 (s, 3H); ESIMS m/z 190 ([M].sup.+). The
title compound (DI44) was isolated (3.0 g, 45%).
1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (DI46)
##STR00346##
[0859] 2,2,2-Trifluoro-1-(3-fluorophenyl)ethanol (D145) was
isolated as a colorless viscous oil (2.8 g, 93%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.41 (m, 1H), 7.25 (m, 2H), 7.14 (m, 1H),
5.06 (m, 1H), 2.60 (s, 1H); ESIMS m/z 194 ([M].sup.+). The title
compound (DI46) was isolated (2.0 g, 61%).
1-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (DI48)
##STR00347##
[0861] 2,2,2-Trifluoro-1-(2-fluorophenyl)ethanol (DI47) was
isolated as a colorless oil (2.5 g, 99%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.40 (m, 1H), 7.43 (m, 1H), 7.24 (m, 1H), 7.13
(m, 1H), 5.42 (m, 1H), 2.65 (s, 1H); ESIMS m/z 194 ([M].sup.+). The
title compound (DI48) was isolated (2.0 g, 61%): .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.61 (m, 1H), 7.40 (m, 1H), 7.23 (m, 1H),
7.10 (m, 1H), 5.40 (m, 1H); GCMS m/z 255 ([M-H].sup.-).
Example 91: Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde
(DI5)
##STR00348##
[0863] To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6
mmol) in DMF (150 mL) were added K.sub.2CO.sub.3 (13.3 g, 96.7
mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant
reaction mixture was stirred at 120.degree. C. for 6 h. After
completion of reaction (by TLC), the reaction mixture was diluted
with water and extracted with EtOAc (3.times.100 mL). The combined
EtOAc layer was washed with water and brine, dried over
Na.sub.2SO.sub.4, and concentrated under reduced pressure to afford
the title compound as a solid (9.0 g, 65%): mp 145-149.degree. C.:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 10.08 (s, 1H), 8.70 (s,
1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H);
ESIMS m/z 173.9 ([M+H].sup.+).
[0864] The following compound was made in accordance with the
procedures disclosed in Example 91.
5-Formyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI49)
##STR00349##
[0866] The title compound was isolated (2.8 g, 60%); .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 10.10 (s, 1H), 8.98 (s, 1H), 8.35 (s,
1H), 8.30 (d, 1H), 8.22 (s, 1H), 8.07 (d, 1H); IR (thin film) 3433,
3120, 1702, 1599, 1510 cm.sup.-1.
2-Chloro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI50)
##STR00350##
[0868] The title compound was isolated as an off white solid (3.0
g, 40%): mp 149-151.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.05 (s, 1H), 8.74 (s, 1H), 8.17 (s, 1H), 8.10 (s, 1H),
7.90 (m, 2H); ESIMS m/z 208.10 ([M+H].sup.+).
5-Methyl-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI51)
##STR00351##
[0870] The title compound was isolated as a white solid (0.5 g,
74%): mp 109-111.degree. C.; .sup.1H NMR (400 MHz, D.sub.6-DMSO)
.delta. 10.06 (s, 1H), 9.00 (s, 1H), 8.30 (s, 1H), 7.99 (s, 1H),
7.92 (d, J=9.2 Hz, 1H), 7.69 (d, J=9.2 Hz, 1H), 2.30 (s, 3H); ESIMS
m/z 188.13 ([M+H].sup.+).
Example 92: Preparation of
5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52)
##STR00352##
[0872] To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5
g, 3.3 mmol) in DMF (25 mL) were added K.sub.2CO.sub.3 (0.68 g,
4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the
resultant reaction mixture was stirred at ambient temperature for
14 h. After completion of reaction (TLC), the reaction mixture was
diluted with water and extracted with EtOAc. The combined EtOAc
layer was washed with water and brine then dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to
afforded the title compound as a pale yellow solid (0.36 g, 45%):
mp 170-172.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta.
10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H),
8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H].sup.-); IR (thin
film) 2238, 1705, 1551, 1314 cm.sup.-1.
Example 93: Preparation of
4-(3-Methyl-1H-1,2,4-triazol-1-yl)benzaldehyde (DI53)
##STR00353##
[0874] To a stirring solution of 4-fluorobenzaldehyde (5.0 g, 40.32
mmol) in DMF (50 mL), were added K.sub.2CO.sub.3 (3.34 g, 40.32
mmol) and 3-methyl-1,2,4-trizole (3.34 g, 40.32 mmol) and the
resultant reaction mixture was stirred at ambient temperature for 4
h. After completion of the reaction (TLC), the reaction mixture was
diluted with water and extracted with EtOAc (3.times.). The
combined EtOAc layer was washed with water and brine then dried
over Na.sub.2SO.sub.4 and concentrated under reduced pressure to
afforded the title compound as a white solid (4.1 g, 60%): mp
125-128.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 10.05
(s, 1H), 8.76 (s, 1H), 8.02 (d, 2H), 7.85 (d, 2H), 2.50 (s, 3H);
ESIMS m/z 188.04 ([M+H].sup.+).
[0875] The following compound was made in accordance with the
procedures disclosed in Example 93.
4-(1H-1,2,4-triazol-1-yl)-3-(trifluoromethyl)benzaldehyde
(DI54)
##STR00354##
[0877] The title compound was isolated as white solid (1.05 g,
60%): mp 81-83.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.15 (s, 1H), 8.43 (s, 1H), 8.37 (s, 1H), 8.25 (d, J=7.2
Hz, 1H), 8.18 (s, 1H), 7.79 (d, J=7.2 Hz, 1H); ESIMS m/z 241.0
([M].sup.+).
4-(3-Nitro-1H-1,2,4-triazol-1-yl)benzaldehyde (DI55)
##STR00355##
[0879] The title compound was isolated as pale yellow solid (0.10
g, 23%): mp 159-161.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.10 (s, 1H), 8.89 (s, 1H), 8.15 (m, 2H), 8.00 (m, 2H);
ESIMS m/z 217.11 ([M-H].sup.-).
3-Bromo-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI56)
##STR00356##
[0881] The title compound was isolated as white solid (3.2 g, 51%):
mp 126-128.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
10.04 (s, 1H), 8.69 (s, 1H), 8.27 (M, 1H, 8.18 (s, 1H) 7.99 (d,
J=9.2 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H); ESIMS m/z 250.9
([M].sup.+).
5-Formyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)benzonitrile (DI57)
##STR00357##
[0883] The title compound was isolated as white solid (0.13 g,
30%): mp 147-149.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.07 (s, 1H), 8.89 (s, 1H), 8.32 (d, J=1.8 Hz, 1H), 8.24
(dd, J=8.6, 1.3 Hz, 1H), 8.06 (d, J=8.6 Hz, 1H), 2.54 (s, 3H);
ESIMS m/z 213.09 ([M+H].sup.+); IR (thin film) 2239, 1697
cm.sup.-1.
3-Nitro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI58)
##STR00358##
[0885] The title compound was isolated as pale yellow solid (3.0 g,
60%): mp 116-118.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 10.15 (s, 1H), 8.48 (s, 1H), 8.46 (s, 1H), 8.26 (d, J=6.9
Hz, 1H), 8.16 (s, 1H), 7.83 (d, J=6.9 Hz, 1H); ESIMS m/z 219.00
([M+H].sup.+).
Example 94: Preparation of 1-(4-Vinylphenyl)-1H-1,2,4-triazole
(DI59)
##STR00359##
[0887] To a stirred solution of 4-[1,2,4]triazol-1-yl-benzaldehyde
(9.0 g, 52 mmol) in 1,4-dioxane (100 mL), were added
K.sub.2CO.sub.3 (10.76 g, 78 mmol) and methyl triphenyl phosphonium
bromide (22.2 g, 62.4 mmol) at room temperature. The resultant
reaction mixture was heated to 70.degree. C. for 18 h. After
completion of the reaction (TLC), the reaction mixture was cooled
to room temperature and filtered and the obtained filtrate was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 100-200 mesh; 25-30% EtOAc in petroleum
ether) to afforded the title compound as a white solid (5.6 g,
63%): ESIMS m/z 172.09 ([M+H].sup.+).
[0888] The following compound was made in accordance with the
procedures disclosed in Example 94.
1-(2-Methyl-4-vinylphenyl)-1H-1,2,4-triazole (DI60)
##STR00360##
[0890] The title compound was isolated as an off white solid (1.5
g, 76%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.25 (s, 1H),
8.11 (s, 1H), 7.35 (m, 2H), 7.27 (d, J=8.7 Hz, 1H), 6.74 (m, 1H),
5.82 (d, J=17.3 Hz, 1H), 5.36 (d, J=10.0 Hz, 1H), 2.25 (s, 3H);
ESIMS m/z 186.14 ([M+H].sup.+).
2-(1H-1,2,4-Triazol-1-yl)-5-vinylbenzonitrile (DI61)
##STR00361##
[0892] The title compound was isolated as an off-white solid (1.40
g, 71%): mp 126-129.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.76 (s, 1H), 8.18 (s, 1H), 7.82-7.84 (m, 1H), 7.72-7.80
(m, 2H), 6.70-6.80 (dd, J=17.6, 10.8 Hz, 1H), 5.90-5.95 (d, J=17.6
Hz, 1H), 5.50-5.70 (d, J=10.8 Hz, 1H); ESIMS m/z 197.03
([M+H].sup.+).
Example 95: Preparation of
2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI62)
##STR00362##
[0894] To a stirred solution of
5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (0.36 g,
1.49 mmol) in 1,4-dioxane (25 mL), were added K.sub.2CO.sub.3 (0.3
g, 2.2 mmol) and methyl triphenyl phosphonium bromide (0.63 g, 1.79
mmol). The resultant reaction mixture was heated to 100.degree. C.
for 18 h. After completion of the reaction (TLC), the reaction
mixture was cooled to room temperature and filtered and the
obtained filtrate was concentrated under reduced pressure.
Purification by flash chromatography (SiO.sub.2, 100-200 mesh;
25-30% EtOAc in petroleum ether) to afford the title compound as a
solid (0.25 g, 70%): mp 103-105.degree. C.; .sup.1H NMR (400 MHz,
DMSO-d.sub.6) .delta. 9.50 (s, 1H), 8.34 (m, 1H), 7.98 (d, J=7.8
Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 6.87 (m, 1H), 6.20 (d, J=15.7 Hz,
1H), 5.56 (d, J=11.8 Hz, 1H); ESIMS m/z 240.27 ([M-H].sup.-); IR
(thin film) 2240, 1514, 1312 cm.sup.-1.
[0895] The following compound was made in accordance with the
procedures disclosed in Example 95.
1-(3-Chloro-4-vinylphenyl)-1H-1,2,4-triazole (DI63)
##STR00363##
[0897] The title compound was isolated as an off-white solid (2.3
g, 80%): mp 134-137.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.56 (s, 1H), 8.11 (s, 1H), 7.76 (s, 1H), 7.70 (d, J=9.0
Hz, 1H), 7.57 (d, J=9.0 Hz, 1H), 7.10 (m, 1H), 5.80 (d, J=17.2 Hz,
1H), 5.47 (d, J=12.4 Hz, 1H); ESIMS m/z 206.04 ([M+H].sup.+.
3-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI64)
##STR00364##
[0899] The title compound was isolated as a white solid (0.6 g,
60%): mp 109-111.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.42 (s, 1H), 7.40-7.60 (m, 4H), 6.70-7.00 (dd, J=17.6,
10.8 Hz, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.30 (d, J=17.6 Hz, 1H),
2.50 (s, 3H); ESIMS m/z 186.20 ([M+H].sup.+).
1-(2-(Trifluoromethyl)-4-vinylphenyl)-1H-1,2,4-triazole (DI65)
##STR00365##
[0901] The title compound was isolated as a colorless oil (0.6 g,
60%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.32 (s, 1H), 8.14
(s, 1H), 7.84 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.50 (d, J=7.6 Hz,
1H), 6.70-6.90 (dd, J=17.6, 10.8 Hz, 1H), 5.90-6.00 (d, J=17.6 Hz,
1H), 5.50-5.80 (d, J=10.8 Hz 1H); ESIMS m/z 240.16
([M+H].sup.+).
3-Nitro-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI66)
##STR00366##
[0903] The title compound was isolated as a pale yellow solid (61
mg, 20%): mp 137-139.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.60 (s, 1H), 7.68 (d, J=7.7 Hz, 2H), 7.60 (d, J=8.3 Hz,
2H), 6.77 (dd, J=17.7, 10.8, 1H), 5.87 (d, J=17.7 Hz, 1H), 5.42 (d,
J=10.8 Hz, 1H); ESIMS m/z 217.28 ([M+H].sup.+).
1-(2-Bromo-4-vinylphenyl)-1H-1,2,4-triazole (DI67)
##STR00367##
[0905] The title compound was isolated as a white solid (1.2 g,
40%): mp 75-77.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.48 (s, 1H), 8.12 (s, 1H), 7.75 (s, 1H) 7.42 (s, 2H), 6.70
(m, 1H), 5.83 (d, J=18 Hz, 1H), 5.42 (d, J=12 Hz, 1H); ESIMS m/z
249.1 ([M].sup.+).
2-(3-Methyl-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI68)
##STR00368##
[0907] The title compound was isolated as an off-white solid (0.6
g, 60%): mp 96-97.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.66 (s, 1H), 7.80 (s, 1H), 7.74 (m, 2H), 6.73 (dd, J=17.6
Hz, 10.8 Hz, 1H), 5.88 (d, J=17.6 Hz, 1H), 5.49 (d, J=10.8 Hz, 1H),
2.52 (s, 3H); ESIMS m/z 211.10 ([M+H].sup.+); IR (thin film) 2229
cm.sup.-1.
1-(2-Nitro-4-vinylphenyl)-1H-1,2,4-triazole (DI69)
##STR00369##
[0909] The title compound was isolated as a yellow solid (1.78 g,
60%): mp 102-104.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.40 (s, 1H), 8.12 (s, 1H), 8.02 (s, 1H), 7.72-7.76 (d,
J=8.0 Hz, 1H), 7.52-7.56 (d, J=17.6 Hz, 1H), 6.70-6.82 (dd, J=17.6,
10.8 Hz, 1H), 5.85-6.00 (d, J=17.6 Hz, 1H), 5.50-5.60 (d, J=10.8,
Hz 1H); ESIMS m/z 217.0 ([M+H].sup.+).
Example 96: Preparation of
3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)
##STR00370##
[0910] Step 1. 5-Bromo-2-fluoro-3-methylbenzaldehyde
[0911] To a stirred solution of di-isopropyl amine (4.01 g, 39.88
mmol) in THF (20 mL) was added n-BuLi (1.6 M in hexane) (19.9 mL,
31.91 mmol) at -78.degree. C. slowly dropwise over the period of 10
min, the reaction mixture was stirred at -78.degree. C. for 30 min.
A solution of 4-bromo-1-fluoro-2-methylbenzene (5.0 g, 26.6 mmol)
in THF (30.0 mL) was added at -78.degree. C., and the reaction
mixture was stirred for 1 h at the same temperature. DMF (5.0 mL)
was added and stirred at -78.degree. C. for another 30 min. The
reaction was monitored by TLC; then the reaction mixture was
quenched with 1N HCl solution (aq) at 0.degree. C. The aqueous
layer was extracted with Et.sub.2O, washed with water and saturated
brine solution. The combined organic layer was dried over anhydrous
Na.sub.2SO.sub.4 and concentrated under reduced pressure to obtain
the crude compound purified by flash column chromatography
(SiO.sub.2, 100-200 mesh; eluting with 5% EtOAc/pet ether) to
afford the title compound as a white solid (3.6 g, 64%); mp
48-50.degree. C.: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.33
(s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd,
J=17.6, 10.8 Hz, 1H), 5.92 (dd, J=17.6, 10.8 Hz, 1H), 5.52 (d,
J=17.6 Hz, 1H), 2.21 (s, 3H); ESIMS m/z 211.35 ([M-H].sup.-).
Step 2. ((E)-5-Bromo-2-fluoro-3-methylbenzaldehyde oxime
[0912] To a stirred solution of
5-bromo-2-fluoro-3-methylbenzaldehyde (3.5 g, 16.2 mmol) in ethanol
(50.0 mL) were added NaOAc (2.0 g, 24.3 mmol) and hydroxylamine
hydrochloride (1.69 g, 24.3 mmol) at ambient temperature. The
reaction mixture was stirred at ambient temperature for 3 h. The
reaction mixture was concentrated on rotavapour to obtain crude
compound, which was washed with water filtered and dried under
vacuum to afford the title compound as a white solid: mp
126-127.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.32
(s, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J=2.4 Hz,
1H), 2.25 (s, 3H); ESIMS m/z 232.10 ([M+H].sup.+).
Step 3. 5-Bromo-2-fluoro-3-methylbenzonitrile
[0913] A stirred solution of
(E)-5-bromo-2-fluoro-3-methylbenzaldehyde oxime (0.5 g, 2.2 mmol)
in acetic anhydride (5.0 mL) was heated to reflux for 18 h. The
reaction mixture was diluted with water and extracted with EtOAc.
The combined EtOAc layer was washed with brine and dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
the crude compound as a light brown gummy material (0.4 g, crude):
ESIMS m/z 213.82 ([M+H].sup.+).
Step 4. 5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile
(DI71)
[0914] To a stirred solution of
5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF
(10.0 mL) was added K.sub.2CO.sub.3 (1.95 g, 14.14 mmol) followed
by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) at ambient temperature.
The reaction mixture was heated to 140.degree. C. for 18 h. The
reaction mixture was cooled to ambient temperature, diluted with
water and extracted with EtOAc (2.times.100 mL). The combined EtOAc
layer was washed with brine and dried over Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the crude compound
purified by flash column chromatography (SiO.sub.2, 100-200 mesh;
eluting with 30% EtOAc/pet ether) to afford the title compound as a
pink solid (0.6 g, 49%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.39 (s, 1H), 8.23 (s, 1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H),
ESIMS m/z 262.57 ([M+H].sup.+); IR (thin film) 2231, 554
cm.sup.-1.
Step 5. 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile
(DI70)
[0915] A mixture of
5-bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.6 g, 2.3
mmol), K.sub.2CO.sub.3 (0.95 g, 6.87 mmol), vinyl boronic anhydride
(0.82 g, 3.43 mmol) and triphenylphosphine (0.13 g, 0.114 mmol) in
toluene (20.0 mL) were stirred and degassed with argon for 30 min.
The reaction mixture was heated to reflux for 18 h. The reaction
mixture was cooled to ambient temperature, diluted with water and
extracted with EtOAc (2.times.100 mL). The combined EtOAc layer was
washed with brine, dried over Na.sub.2SO.sub.4 and concentrated
under reduced pressure to afford the crude compound that was
purified by flash column chromatography (SiO.sub.2, 100-200 mesh;
eluting with 30% EtOAc/pet ether) to afford the title compound as a
pink solid (0.25 g, 52%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd,
J=17.6, 10.8 Hz, 1H), 5.92 (d, J=17.6, 1H), 5.52 (d, J=10.8 Hz,
1H), 2.21 (s, 3H), ESIMS m/z 211.35 ([M+H].sup.+); IR (thin film)
2236, 1511 cm.sup.-1.
[0916] The following compound was made in accordance with the
procedures disclosed in Steps 4 and 5 of Example 96.
1-(2-Fluoro-4-vinylphenyl)-1H-1,2,4-triazole (DI72)
##STR00371##
[0918] 1-(4-Bromo-2-fluorophenyl)-1H-1,2,4-triazole (DI73) was
isolated as a pale yellow solid (3.0 g, 75%): mp 113-116.degree.
C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.69 (s, 1H), 8.13
(m, 2H), 7.50 (m, 1H), 7.21 (m, 1H); ESIMS m/z 241.93 ([M].sup.+).
The title compound (DI72) was isolated as a yellow solid (1.0 g,
71%): mp 67-70.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.67 (s, 1H), 8.13 (s, 1H), 7.94 (m, 1H), 7.41 (m, 1H),
7.24 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.81 (d, J=17.6 Hz,
1H), 5.37 (d, J=10.8 Hz, 1H); ESIMS m/z 190.00 ([M+H].sup.+).
Example 119: Preparation of
1-(1-(4-Vinylphenyl)-1H-1,2,4-triazol-5-yl)ethanone (DI78)
##STR00372##
[0920] To a stirred solution of
1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 25 mL of
THF, was added n-BuLi (0.37 g, 5.8 mmol) at -78.degree. C. and
stirred for 30 min. To this N-methoxy-N-methyl acetamide in THF
(0.66 g, 6.4 mmol) was added and the resultant reaction mixture was
stirred at ambient temperature for 16 h. The reaction mixture was
quenched with a saturated aqueous NH.sub.4Cl solution and extracted
with EtOAc (3.times.50 mL). The combined EtOAc layer was washed
with brine and dried over sodium sulphate and concentrated under
reduced pressure. The crude compound was purified by flash
chromatography (SiO.sub.2, 100-200 mesh, 40% EtOAc in Pet ether) to
afford the title compound as an off white solid (280 mg, 23%): mp
97-98.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.10
(s, 1H), 7.50 (d, 2H), 7.38 (d, 2H), 6.68 (dd, 1H), 5.85 (d, 1H),
5.38 (d, 1H), 2.75 (s, 3H); ESIMS m/z 214.14 ([M+H].sup.+).
Example 120: Preparation of
Cyclopropyl(1-(4-vinylphenyl)-1H-1,2,4-triazol-5-yl)methanone
(DI79)
##STR00373##
[0922] To a stirred solution of
1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 25 mL of
THF, was added n-BuLi (0.37 g, 5.8 mmol) at -78.degree. C. and
stirred for 30 min. To this N-methoxy N-methylcyclopropoxide in THF
(0.82 g, 6.4 mmol) was added and the resultant reaction mixture was
stirred at ambient temperature for 16 h. The reaction mixture was
quenched with a saturated aqueous NH.sub.4Cl solution and extracted
with EtOAc (3.times.25 mL). The combined EtOAc layer was washed
with brine and dried over sodium sulphate and concentrated under
reduced pressure. The crude compound was purified by flash
chromatography (SiO.sub.2, 100-200 mesh, 40% EtOAc in Pet ether) to
afford the title compound as an off white solid (420 mg, 30%): mp
90-91.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.12
(s, 1H), 7.50 (d, J=7.8 Hz, 2H), 7.38 (d, J=7.8 Hz, 2H), 6.75 (dd,
J=16.3, 10.7 Hz, 1H), 5.81 (d, J=16.3 Hz, 1H), 5.35 (d, J=10.7 Hz,
1H), 3.22 (m, 1H), 1.27 (m, 2H), 1.18 (m, 2H); ESIMS m/z 240.18
([M+H].sup.+); IR (thin film) 2922, 1630 cm.sup.-1.
Example 121: Preparation of
5-(Methylthio)-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI80)
##STR00374##
[0924] To a stirred solution of
1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 50 mL of
THF, was added n-BuLi (0.41 g, 6.4 mmol) at -78.degree. C. and
stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43
mmol) was added and the resultant reaction mixture was stirred at
ambient temperature for 16 h. The reaction mixture was quenched
with a saturated aqueous NH.sub.4Cl solution and extracted with
EtOAc (3.times.25 mL). The combined EtOAc layer was washed with
brine and dried over sodium sulphate and concentrated under reduced
pressure. The crude compound was purified by flash chromatography
(SiO.sub.2, 100-200 mesh, 40% EtOAc in Pet ether) to afford the
title compound as an off white solid (0.6 g, 48%): mp 68-70.degree.
C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.96 (s, 1H), 7.05
(m, 4H), 6.75 (dd, J=16.4, 10.7 Hz, 1H), 5.81 (d, J=16.4 Hz, 1H),
5.35 (d, J=10.7 Hz, 1H), 2.73 (s, 3H); ESIMS m/z 218.09
([M+H].sup.+).
Example 122: Preparation of
5-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI81)
##STR00375##
[0926] To a stirred solution of
1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (0.5 g, 2.9 mmol) in 10 mL of
THF, was added n-BuLi (0.22 g, 3.5 mmol) at -78.degree. C. and
stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5 mmol)
was added and the resultant reaction mixture was stirred at ambient
temperature for 16 h. The reaction mixture was quenched with a
saturated aqueous NH.sub.4Cl solution and extracted with EtOAc
(3.times.25 mL). The combined EtOAc layer was washed with brine and
dried over sodium sulphate and concentrated under reduced pressure
The crude compound was purified by flash chromatography (SiO.sub.2,
100-200 mesh, 40% EtOAc in Pet ether) afford the title compound as
a pale brown liquid (250 mg, 46%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.93 (s, 1H), 7.55 (d, J=9 Hz, 2H), 7.42 (d,
J=9 Hz, 2H), 6.76 (dd, J=18, 11 Hz, 1H), 5.83 (d, J=18 Hz, 1H),
5.38 (d, J=11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13
([M+H].sup.+); IR (thin film) 1517, 1386, 1182, 847 cm.sup.-1.
Example 97: Preparation of
(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-1H--
1,2,4-triazole (DC1)
##STR00376##
[0928] To a stirred solution of
1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichloro-benzene (2.0 g, 6.51
mmol) in 1,2-dichlorobenzene (25 mL), were added
1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (2.22 g, 13.0 mmol), CuCl (64
mg, 0.65 mmol) and 2,2-bipyridyl (0.2 g, 1.3 mmol). The resultant
reaction mixture was degassed with argon for 30 min, then stirred
at 180.degree. C. for 24 h. After completion of reaction (TLC), the
reaction mixture was cooled to ambient temperature and filtered and
the filtrate concentrated under reduced pressure. Purification by
flash chromatography (SiO.sub.2, 100-200 mesh; 25-30% EtOAc in
petroleum ether) afforded the title compound as an off-white solid
(0.8 g, 32%): mp 93-97.degree. C.; .sup.1H NMR (300 MHz,
CDCl.sub.3) .delta. 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, J=8.4 Hz,
2H), 7.54 (d, J=8.4 Hz, 2H), 7.38 (t, J=1.8 Hz, 1H), 7.29 (s, 2H),
6.62 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.2 Hz, 1H), 4.15 (m,
1H); ESIMS m/z 398.05 ([M+H].sup.+).
[0929] Compounds DC2-DC37, DC44, DC45, DC47-49, DC50, DC51, DC54,
DC58, DC60, DC62, and DC63-DC67 in Table 1 were made in accordance
with the procedures disclosed in Example 97.
Example 98: Preparation of
(E)-2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlo-
rophenyl)but-1-en-1-yl)benzonitrile (DC40)
##STR00377##
[0931] To a stirred solution of
2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (0.9 g, 3.7
mmol) in 1,2-dichlorobenzene (10 mL), were added
5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.5 g, 7.5
mmol), CuCl (73 mg, 0.74 mmol) and 2,2-bipyridyl (0.23 g, 1.49
mmol) and the resultant reaction mixture was degassed with argon
for 30 min and then stirred at 180.degree. C. for 14 h. After
completion of the reaction (TLC), the reaction mixture was cooled
to ambient temperature and filtered and the filtrate was
concentrated under reduced pressure. Purification by flash
chromatography (SiO.sub.2, 100-200 mesh, 25-30% EtOAc in Pet ether)
afforded the title compound as an off white solid (0.9 g, 50%): mp
70-73.degree. C.; .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 8.86
(s, 1H), 7.88 (m, 3H), 7.44 (s, 2H), 6.67 (d, J=16.0 Hz, 1H), 6.56
(dd, J=16.0, 7.6 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 436.11
([M-2H].sup.-).
Example 99: Preparation of
(E)-2-(3-Amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlo-
rophenyl)but-1-en-1-yl)benzonitrile (DC41)
##STR00378##
[0933] To a stirred solution of
(E)-2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlo-
rophenyl)but-1-enyl)benzonitrile (0.6 g, 1.2 mmol) in MeOH (10 mL),
were added Zn dust (0.39 g, 5.98 mmol) and saturated aqueous
NH.sub.4Cl solution (5 mL) and the resultant reaction mixture was
stirred at ambient temperature for 2 h. After completion of the
reaction (TLC), the reaction mass was concentrated under reduced
pressure. The reaction mass was diluted with CH.sub.2Cl.sub.2,
filtered through a Celite.RTM. bed, and the obtained filtrate
concentrated under reduced pressure to afford the title compound as
a solid (0.5 g, 89%): mp 72-75.degree. C.; .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d, J=8.4
Hz, 1H), 7.91 (s, 2H), 7.77 (d, J=8.4 Hz, 1H), 6.42 (dd, J=15.6,
9.2 Hz, 1H), 6.83 (d, J=15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H);
ESIMS m/z 469.95 ([M-H].sup.-).
[0934] Compound DC38 in Table 1 was made in accordance with the
procedures disclosed in Example 99. Also, compound DC55 in Table 1
was made from compound DC54 in accordance with the procedures
disclosed in Example 99, with the exception of using ammonium
formate in place of NH.sub.4Cl.
Example 100: Preparation of
(E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1--
yl)phenyl)-1H-1,2,4-triazol-3-yl)-N-(cyclopropanecarbonyl)cyclopropanecarb-
oxamide (DC42)
##STR00379##
[0936] To a stirred solution of
(E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlo-
rophenyl)but-1-enyl)benzonitrile (0.1 g, 0.21 mmol) in
CH.sub.2Cl.sub.2 at ambient temperature, was added
cyclopropylcarbonyl chloride (0.045 g, 0.42 mmol) and the reaction
mixture was stirred for 2 h at ambient temperature. The reaction
mixture was diluted with CH.sub.2Cl.sub.2 and washed with water and
brine and dried over Na.sub.2SO.sub.4. Concentration under reduced
pressure and purification by preparative HPLC afforded the title
compound as a solid (0.09 g, 79%): mp 104-107.degree. C.; .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 8.78 (s, 2H), 7.83 (s, 1H), 7.80
(m, 2H), 7.42 (s, 2H), 6.65 (d, J=16.4 Hz, 1H), 6.51 (dd, J=7.6,
8.0 Hz, 1H), 4.17 (m, 1H), 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m,
4H); ESIMS m/z 609.98 ([M+H].sup.+); IR (thin film) 2234, 1714,
1114, 807 cm.sup.-1.
Example 101: Preparation of
(E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1--
yl)phenyl)-1H-1,2,4-triazol-3-yl)cyclopropanecarboxamide (DC43)
##STR00380##
[0938] To a stirred solution of
(E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlo-
rophenyl)but-1-enyl)benzonitrile (0.15 g, 0.31 mmol) in
CH.sub.2Cl.sub.2 at 0.degree. C., were added TEA (0.1 g, 1 mmol)
and cyclopropylcarbonyl chloride (0.04 g, 0.38 mmol) and the
reaction mixture was stirred for 1 h at 0.degree. C. The reaction
mixture was diluted with CH.sub.2Cl.sub.2 and washed with water and
brine and dried over Na.sub.2SO.sub.4. Concentration under reduced
pressure and purification by column chromatography (SiO.sub.2,
100-200 mesh) afforded the title compound as a solid (66 mg, 34%):
mp 109-112.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta.
10.94 (br s, 1H), 8.36 (s, 1H), 8.08 (m, J=8.4 Hz, 1H), 7.91 (s,
2H), 7.84 (d, J=8.4 Hz, 1H), 7.13 (dd, J=15.6, 9.2 Hz, 1H), 6.87
(d, J=15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H);
ESIMS m/z 540.04 ([M+H].sup.+); IR (thin film) 3233, 2233, 1699,
1114, 807 cm.sup.-1.
[0939] Compound DC39 in Table 1 was made in accordance with the
procedures disclosed in Example 101.
Example 102: Preparation of
1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (DI74)
##STR00381##
[0941] To a stirred solution of 4-bromoacetophenone (10 g, 50 mmol)
in DMF (100 mL), were added 1,2,4-triazole (5 g, 75 mmol),
Cs.sub.2CO.sub.3 (32.6 g, 100.5 mmol) and CuI (1.4 g, 10.1 mmol)
and the resultant reaction mixture was refluxed for 48 h. After
completion of the reaction (by TLC), the reaction mixture was
cooled to ambient temperature and diluted with water (200 mL) and
extracted with EtOAc. The combined organic layer was washed with
brine and dried over Na.sub.2SO.sub.4 and concentrated under
reduced pressure. Purification by washing with Et.sub.2O afforded
the title compound as a solid (5 g, 96%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.71 (s, 1H), 8.16, (s, 1H), 8.13 (d, J=8.6 Hz,
2H), 7.83 (d, J=8.6 Hz, 2H), 2.66 (s, 3H); ESIMS m/z 186.02
([M-H].sup.-).
Example 103: Preparation of
1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluor-
obutan-1-one (DI75)
##STR00382##
[0942] Step 1.
1-(4-(1-(Trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole
(DI76)
[0943] To a stirred solution of
1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (4.5 g, 24.0 mmol) in
CH.sub.2Cl.sub.2 at 0.degree. C., were added TEA (3.7 g, 36.1 mmol)
and trimethylsilyl trifluoromethanesulfonate (8 g, 36 mmol) and the
resultant reaction mixture was stirred for 1 h. The reaction
mixture was quenched with a mixture of sat aqueous NaHCO.sub.3
solution and ether. The ether layer and was separated, washed with
brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure to afford the title compound (5.5 g) which was taken
directly to next step.
Step 2.
1-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-t-
rifluorobutan-1-one (DI75)
[0944] To a stirred solution of
1-(4-(1-(trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (6 g, 23
mmol) and 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichlorobenzene
(7.1 g, 34.7 mmol) in 1,2-dichlorobenzene (30 mL) was degassed with
argon. To this CuCl (0.23 g, 2.31 mmol) and 2,2-bipyridyl (0.73 g,
4.63 mmol) was added to the above reaction mixture and the
resultant reaction mixture was heated to 180.degree. C. for 18 h.
After completion of the reaction (by TLC), the reaction mixture was
absorbed onto silica gel and purified by column chromatography
(SiO2; 10% EtOAc in petroleum ether) to afford title compound as a
solid (3 g, 31%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.67
(s, 1H), 8.15 (s, 1H), 8.10 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz,
2H), 7.33 (m, 1H), 7.30 (m, 2H), 4.20 (m, 1H), 3.63 (m, 2H); ESIMS
m/z 412. 14 ([M-H].sup.-).
Example 104: Preparation of
2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluor-
opentan-2-ol (DI77)
##STR00383##
[0946] To a solution of
1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluor-
obutan-1-one (300 mg, 0.726 mmol) in THF cooled to 0.degree. C. was
added methylmagnesium bromide (450 mg, 5 mmol) drop wise. The
reaction was stirred for 3 h at 0.degree. C., then the reaction
mixture was quenched with sat aqueous NH.sub.4Cl solution and
extracted with EtOAc. The combined EtOAc layer was washed with
water and brine, dried over Na.sub.2SO.sub.4 and concentrated under
reduced pressure. Purification by column chromatography (SiO.sub.2,
100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title
compound as a solid (100 mg, 32%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. two diastereoisomers 8.58 (s, 1H, minor), 8.48
(s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H, major), 7.70 (d,
J=9.0 Hz, 2H, minor), 7.53 (d, J=9.0 Hz, 2H, minor), 7.40 (d, J=9.0
Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, J=9.0 Hz, 2H, major),
7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H, major), 350
(m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H, minor);
ESIMS m/z 430.05 ([M+H].sup.+).
Example 105: Preparation of
(E)-1-(4-(4-(3,5-Dichlorophenyl)-5,5,5-trifluoropent-2-en-2-yl)phenyl)-1H-
-1,2,4-triazole (DC68)
##STR00384##
[0948] To a solution of
2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluor-
opentan-2-ol (100 mg, 0.233 mmol) in toluene was added a catalytic
amount of p-toluenesulfonic acid and the water was removed by
azeotropic distillation over the course of 12 h. The reaction
mixture was cooled to room temperature and dissolved in EtOAc. The
solution was washed with sat aqueous NaHCO.sub.3 solution and
brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure. Purification by column chromatography (SiO.sub.2, 100-200
mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound
as a solid (30 mg, 31%).
Example 123: Preparation of
(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-t-
riazol-1-yl)benzaldehyde (DC52)
##STR00385##
[0950] To a stirred solution of
(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-t-
riazol-1-yl)benzonitrile (0.3 g, 0.71 mmol) in toluene (10 mL) at
-78.degree. C. was added dropwise diisobutylaluminum hydride
(DIBAL-H, 1.0 M solution in toluene; 0.85 mL), and the reaction
mixture was stirred at -78.degree. C. for 20 min. The reaction
mixture was quenched with the addition of 1 N HCl solution, then
the aqueous layer was extracted with EtOAc (2.times.). The combined
organic layers were washed with brine, dried over Na.sub.2SO.sub.4
and concentrated under reduced pressure. The crude compound was
purified by flash column chromatography (SiO.sub.2; 50% EtOAc/Pet
ether) to afford the title compound as a yellow oil.
[0951] Compound DC53 in Table 1 was made in accordance with the
procedures disclosed in Example 123.
Example 124: Preparation of
(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-methyl-2-(1-
H-1,2,4-triazol-1-yl)aniline (DC57)
##STR00386##
[0953] To a stirred solution of
(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-t-
riazol-1-yl)aniline (0.3 g, 0.7 mmol) in CH.sub.2Cl.sub.2 (10 mL)
was added TEA (0.155 mL, 1.09 mmol) and methyl iodide (0.124 g,
0.873 mmol). The reaction was stirred at ambient temperature for 18
h. The CH.sub.2Cl.sub.2 layer was washed with water and brine,
dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure. The crude compound was purified by flash column
chromatography (SiO.sub.2; 50% EtOAc/Pet ether) to afford the title
compound as a yellow semi-solid (0.07 g, 70%).
Example 125: Preparation of
(E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-t-
riazol-1-yl)benzoic acid (DC61)
##STR00387##
[0955] A solution of (E)-ethyl
5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triaz-
ol-1-yl)benzoate (0.2 g, 0.4 mmol) in 6 N HCl (10 mL) was stirred
at 100.degree. C. for 18 h. The reaction was cooled to ambient
temperature, resulting in a white solid precipitate. The
precipitate was filtered to afford the title compound as a white
solid (0.12 g, 60%).
Example 126: Preparation of
(Z)-5-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N'-hydrox-
y-2-(1H-1,2,4-triazol-1-yl)benzimidamide (DC59)
##STR00388##
[0957] A solution of
(E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-t-
riazol-1-yl)benzonitrile (0.3 g, 0.71 mmol), NaOAc (0.087 g, 1.065
mmol) and hydroxylammonium chloride (0.072 g, 1.065 mmol) in 9:1
ethanol/water mixture (10 mL) was stirred at 70.degree. C. for 8 h.
The reaction was cooled to ambient temperature, and the ethanol was
evaporated. The residue was dissolved in water and extracted with
EtOAc (2.times.). The combined organic layers were washed with
brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced
pressure to afford the title compound as an off white solid.
Example 127: Preparation of
(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)p-
henyl)-1H-1,2,4-triazole (DC70)
##STR00389##
[0958] Step 1.
(E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-
-one
[0959] To a solution of 1-(3,5-dichlorophenyl)ethanone (0.5 g, 2.6
mmol) in ethanol (20 mL) was added
4-(1H-1,2,4-triazol-1-yl)benzaldehyde (0.46 g, 2.65 mmol) and the
reaction was cooled to 0.degree. C. NaOH (0.22 g, 5.29 mmol) in
water (10 mL) was then added and the reaction was allowed to stir
for 2 h at 0.degree. C. The reaction was extracted with EtOAc and
the combined organic layers were dried over Na.sub.2SO.sub.4 and
concentrated under reduced pressure to afford the title compound
(0.149 g, 17%); ESIMS m/z 430.05 ([M+H].sup.+) 344.08
Step 2.
(E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1-
,1-trifluorobut-3-en-2-ol (DC69)
[0960] To a solution of
(E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-
-one (1 g, 3 mmol) in THF (150 mL) was added
trifluoromethyltrimethylsilane (0.517 g, 3.644 mmol) and
tetra-n-butylammonium fluoride (TBAF) (1.0 M, 1 mL) at 0.degree. C.
The reaction was slowly warmed to ambient temperature and allowed
to stir for 2 h. The reaction was then cooled to 0.degree. C. and 5
M HCl solution was added and the reaction was stirred for an
additional 4 h at ambient temperature. The reaction was extracted
with CH.sub.2Cl.sub.2 and the combined organic layers were dried
over Na.sub.2SO.sub.4 and concentrated under reduced pressure. The
crude compound was purified by flash column chromatography
(SiO.sub.2; 25% EtOAc/hexanes) to afford the title compound as an
off-white solid (0.3 g, 25%).
Step 3.
(E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-
-1-yl)phenyl)-1H-1,2,4-triazole (DC70)
[0961] To a solution of
(E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trif-
luorobut-3-en-2-ol (0.15 g, 0.36 mmol) in THF (5 mL) was added NaH
(60%, 10 mg, 0.44 mmol) at 0.degree. C. The reaction was allowed to
stir at 0.degree. C. for 30 min, then methyl iodide (61 mg, 0.44
mmol) was added slowly and the reaction was warmed to ambient
temperature and allowed to stir for 4 h. The reaction was quenched
with aqueous NH.sub.4Cl solution and extracted with
CH.sub.2Cl.sub.2. The combined organic layers were dried over
Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford
the title compound as an off-white solid (55 mg, 35%).
Example 128: Preparation of tert-Butyl
(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)carbamate
##STR00390##
[0963] To a stirred solution of
2-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid (4.58 g, 22.6
mmol) in methylene chloride (50 mL) was added EDC HCl (4.75 g, 24.8
mmol) followed by 2,2,2-trifluoroethylamine (2.67 g, 27.0 mmol) and
DMAP (3.03 g, 24.8 mmol). The reaction mixture was stirred at
ambient temperature for 18 h, then washed with aqueous 5%
NaHSO.sub.4 (2.times.), aqueous 10% HCl (1.times.) and aqueous
saturated NaHCO.sub.3 (2.times.). The organic phase was dried
(MgSO.sub.4) and concentrated in vacuo to afford the title compound
as a white solid (2.97 g, 46%).
[0964] The following molecules were made in accordance with the
procedures disclosed in Example 128:
(S)-tert-Butyl
(1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate
##STR00391##
[0966] The title molecule was isolated as a white solid: mp
108-111.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 6.90
(s, 1H), 5.04 (m, 1H), 4.07 (m, 1H), 3.92 (m, 3H), 1.87 (m, 1H),
1.66 (m, 1H), 1.44 (s, 9H), 0.96 (t, J=7.4 Hz, 3H); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -72.54; .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 173.05, 156.04, 124.03 (q, J=278.5 Hz), 80.30,
55.56, 40.43 (q, J=34.7 Hz), 28.19, 25.63, 9.80;
[.alpha.].sub.D=-33.3 (c, 10.1 mg/mL in CH.sub.2Cl.sub.2).
tert-Butyl
(1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate
##STR00392##
[0968] The title molecule was isolated as a white solid: mp
113-116.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.36
(d, J=8.4 Hz, 1H), 5.43-5.25 (m, 1H), 4.16 (m, 1H), 3.98 (m, 1H),
3.82 (m, 1H), 1.84 (dt, J=14.0, 7.0 Hz, 1H), 1.66 (dt, J=14.2, 7.3
Hz, 1H), 1.44 (s, 9H), 0.95 (t, J=7.3 Hz, 3H); .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -72.51; .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 172.94, 156.02, 124.47 (q, J=380.8 Hz), 80.33, 55.54, 40.46
(q, J=34.8 Hz), 28.19, 25.61, 9.79.
tert-Butyl
(2-oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethyl)carbamate
##STR00393##
[0970] The title molecule was isolated as a white solid: mp
84-88.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 6.89
(s, 1H), 5.44 (t, J=5.8 Hz, 1H), 4.77-4.48 (m, 1H), 3.83 (d, J=5.9
Hz, 2H), 1.45 (s, 9H), 1.33 (d, J=7.0 Hz, 3H); .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -77.63; .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 169.84, 156.33, 125.19 (q, J=280.9 Hz), 80.29, 46.20 (q,
J=31.7 Hz), 44.15, 28.11, 13.88; EIMS m/z 270 ([M].sup.+).
(R)-tert-Butyl
(1-((2-fluoroethyl)amino)-1-oxopropan-2-yl)carbamate
##STR00394##
[0972] The title molecule was isolated as a white solid: mp
91-94.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.98
(bs, 1H), 6.87 (t, J=7.2 Hz, 1H), 4.47 (t, J=4.8 Hz, 1H), 4.32 (t,
J=5.1 Hz, 1H), 3.97-3.92 (m, 1H), 3.41-3.37 (m, 1H), 3.33-3.28 (m,
1H), 1.37 (s, 9H), 1.16 (d, J=7.3 Hz, 3H); ESIMS m/z 235.0
([M+H].sup.+).
tert-Butyl
(3-oxo-3-((2,2,2-trifluoroethyl)amino)propyl)carbamate
##STR00395##
[0974] The title molecule was isolated as a white solid: mp
123-125.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
6.42-6.22 (m, 1H), 5.07 (s, 1H), 3.92 (qd, J=9.1, 6.4 Hz, 2H), 3.43
(q, J=6.2 Hz, 2H), 2.50 (t, J=6.0 Hz, 2H), 1.43 (s, 9H); .sup.19F
NMR (376 MHz, CDCl.sub.3) .delta. -72.50; .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 171.76, 156.30, 124.02 (q, J=278.5 Hz), 79.67,
40.53 (q, J=34.8 Hz), 36.41, 36.27, 28.31.
(R)-tert-Butyl (1-(ethylamino)-1-oxopropan-2-yl)carbamate
##STR00396##
[0976] The title molecule was isolated as a white solid: mp
88-93.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 6.35
(s, 1H), 5.25-5.04 (m, 1H), 4.21-3.99 (m, 1H), 3.29 (dd, J=7.5, 5.9
Hz, 2H), 1.45 (s, 8H), 1.35 (d, J=7.0 Hz, 3H), 1.13 (t, J=7.3 Hz,
3H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 172.79, 155.51,
79.59, 49.97, 34.16, 28.25, 18.77, 14.60.
(R)-tert-Butyl
(1-oxo-1-((3,3,3-trifluoropropyl)amino)propan-2-yl)carbamate
##STR00397##
[0978] The title molecule was isolated as an off white solid: mp
101-105.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta.
7.96 (bs, 1H), 6.90 (d, J=6.9 Hz, 1H), 3.91-3.86 (m, 1H), 3.34-3.19
(m, 2H), 2.50-2.32 (m, 2H), 1.37 (s, 9H), 1.15 (d, J=7.2 Hz,
3H).
(R)-tert-Butyl
(1-oxo-1-((2,2,2-trifluoroethyl)amino)pentan-2-yl)carbamate
##STR00398##
[0980] The title molecule was isolated as a white solid: mp
107-122.degree. C.; .sup.1H NMR (400 MHz, CDCl3)) .delta. 6.90 (s,
1H), 5.00 (d, J=8.0 Hz, 1H), 4.12 (d, J=7.3 Hz, 1H), 3.99-3.76 (m,
2H), 1.87-1.73 (m, 1H), 1.65-1.52 (m, 1H), 1.44 (s, 9H), 1.38 (m,
2H), 0.94 (t, J=7.3 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. rotomer -72.55, -73.27; .sup.13C NMR (101 MHz, CD.sub.3OD)
.delta. rotomers 176.08, 157.86, minor 126.13 (q, J=279.8 Hz),
major 125.83 (q, J=278.8 Hz), 80.65, 55.90, minor 42.27 (q, J=35.4
Hz), major 41.24 (q, J=35.4 Hz), 35.50, 28.73, 20.04, 14.03.
(R)-Benzyl
(3-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carba-
mate
##STR00399##
[0982] The title molecule was isolated as a white solid: mp
157-161.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.46-7.31 (m, 5H), 6.57 (d, J=8.3 Hz, 1H), 5.34 (d, J=8.9 Hz, 1H),
5.11 (s, 2H), 4.02 (dq, J=16.1, 8.8, 7.7 Hz, 2H), 3.78 (td, J=9.0,
4.7 Hz, 1H), 2.15 (q, J=6.7 Hz, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.94
(d, J=6.8 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-72.44.
Example 129: Preparation of N-(2,2,2-Trifluoroethyl)
1-amino-2-methylpropanecarboxamide hydrochloride
##STR00400##
[0984] To tert-butyl
(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)carbamate
(2.61 g, 9.18 mmol) in methylene chloride (20 mL) was added 4 M HCl
in dioxane (20 mL). The solution was stirred for 6 h at ambient
temperature. The reaction mixture was concentrated in vacuo to
afford the title compound as a white solid (2.18 g).
[0985] The following molecules were made in accordance with the
procedures disclosed in Example 129:
(R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-aminium
chloride
##STR00401##
[0987] The title molecule was isolated as a white solid: mp
210-213.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
9.22 (t, J=6.3 Hz, 1H), 8.37-8.27 (m, 3H), 4.07-3.95 (m, 2H),
3.95-3.84 (m, 1H), 1.38 (d, J=7.0 Hz, 3H); .sup.19F NMR (376 MHz,
DMSO-d.sub.6) .delta. -70.75; [.alpha.].sub.D=-6.6 (c, 5.0 mg/mL in
MeOH).
1-Oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-aminium chloride
##STR00402##
[0989] The title molecule was isolated as a white solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 9.12 (t, J=5.7 Hz, 1H), 8.19
(s, 3H), 4.14-3.93 (m, 2H), 3.78 (t, J=6.0 Hz, 1H), 1.81-1.71 (m,
2H), 0.88 (t, J=7.2 Hz, 3H); ESIMS m/z 184.90 ([(M-TFA)+H].sup.+);
IR (thinfilm) 3269, 1681, 1158 cm.sup.-1.
2-Oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethanaminium
chloride
##STR00403##
[0991] The title molecule was isolated as a white solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 8.96 (d, J=8.7 Hz, 1H), 8.09
(bs, 3H), 4.71-4.59 (m, 1H), 3.64-3.62 (m, 2H), 1.27 (d, J=6.9 Hz,
3H); EIMS m/z 170.1 ([M].sup.+).
(R)-1-((2-Fluoroethyl)amino)-1-oxopropan-2-aminium chloride
##STR00404##
[0993] The title molecule was isolated as a white solid: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 8.76 (t, J=5.1 Hz, 1H), 8.21
(bs, 3H), 4.54 (t, J=5.1 Hz, 1H), 4.38 (t, J=4.8 Hz, 1H), 3.85-3.79
(m, 1H), 3.50-3.45 (m, 1H), 3.41-3.36 (m, 1H), 1.36 (d, J=7.2 Hz,
3H); ESIMS m/z 135.1 ([M+H].sup.+); IR (thinfilm) 3331, 2983, 1660,
1161, 597 cm.sup.-1.
3-Oxo-3-((2,2,2-trifluoroethyl)amino)propan-1-aminium chloride
##STR00405##
[0995] The title molecule was isolated as a white solid: mp
193-197.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
8.94 (t, J=6.4 Hz, 1H), 8.16 (s, 3H), 3.99-3.79 (m, 2H), 2.98 (t,
J=7.3 Hz, 2H), 2.64 (t, J=7.3 Hz, 2H); .sup.19F NMR (376 MHz,
DMSO-d.sub.6) .delta. -70.74.
(R)-1-(Ethylamino)-1-oxopropan-2-aminium chloride
##STR00406##
[0997] The title molecule was isolated as a white solid: mp
223-236.degree. C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta.
8.65 (t, J=5.4 Hz, 1H), 8.32 (s, 3H), 3.89-3.66 (m, 1H), 3.12 (p,
J=7.0 Hz, 2H), 1.35 (d, J=6.9 Hz, 3H), 1.05 (t, J=7.2 Hz, 3H);
.sup.13C NMR (101 MHz, DMSO-d.sub.6) .delta. 168.98, 48.08, 33.54,
17.16, 14.43.
(R)-1-Oxo-1-((3,3,3-trifluoropropyl)amino)propan-2-aminium
chloride
##STR00407##
[0999] The title molecule was isolated as an off white solid: mp
128-131.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta.
8.62 (bs, 1H), 8.10 (bs, 3H), 3.82-3.79 (m, 1H), 3.50-3.38 (m, 2H),
2.50-2.37 (m, 2H), 1.34 (d, J=6.9 Hz, 3H).
(R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)pentan-2-aminium
chloride
##STR00408##
[1001] The title molecule was isolated as a white solid: mp
204-210.degree. C.; .sup.1H NMR (400 MHz, CD.sub.3OD) .delta.
4.17-4.00 (m, 1H), 3.98-3.69 (m, 2H), 1.83 (dt, J=15.0, 7.5 Hz,
2H), 1.50-1.35 (m, 2H), 0.99 (t, J=7.3 Hz, 3H); .sup.19F NMR (376
MHz, CD.sub.3OD) .delta. -73.90; .sup.13C NMR (101 MHz, CD.sub.3OD)
.delta. 170.97, 125.72 (q, J=277.9 Hz), 54.37, 41.30 (q, J=34.7
Hz), 34.65, 19.00, 13.94.
Example 130: Preparation of (R)-tert-Butyl
1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate
##STR00409##
[1003] To a stirred solution of (R)-tert-butyl
1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate (100 mg,
0.37 mmol) in CH.sub.2Cl.sub.2 (10 mL) was added P.sub.2S.sub.5 (24
mg, 0.11 mmol) and hexamethyldisiloxane (HMDO) (0.13 mL, 0.59 mmol)
at room temperature and the mixture was refluxed for 3 h. The
reaction mixture was cooled to room temperature and another portion
of P.sub.2S.sub.5 (24 mg, 0.11 mmol) was added and the resulting
mixture was refluxed for 18 h. The volatiles were evaporated,
pentane (25 mL) was added to the residue and stirred for 10-15 min.
The pentane layer was decanted, concentrated in vacuo and the
residue was passed through a short silica pad eluting with pentane
followed by CH.sub.2Cl.sub.2 to give the title compound as
colorless liquid (30 mg, 30%): .sup.1H NMR (400 MHz, DMSO-d.sub.6)
.delta. 10.27 (t, J=5.4 Hz, 1H), 7.00 (d, J=6.8 Hz, 1H), 4.57-4.35
(m, 3H), 1.32 (s, 9H), 1.25 (d, J=7.6 Hz, 3H); ESIMS m/z 286.2
([M+H].sup.+); IR (thin film) 3233, 1683, 1257 cm.sup.-1.
Example 131: Preparation of
(R)-1-Thioxo-1-((2,2,2-trifluoroethyl)amino)propan-2-aminium
2,2,2-trifluoroacetate
##STR00410##
[1005] To a stirred solution of (R)-tert-butyl
1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate (200 mg,
0.69 mmol) in CH.sub.2Cl.sub.2 (5 mL) was added TFA (0.5 mL)
dropwise and the reaction mixture was stirred for 18 h. The
volatiles were evaporated and the residue was triturated with
pentane to give the title compound as colorless gum, which was
taken to next step without further purification (200 mg): .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 10.99 (bs, 1H), 8.23 (bs, 2H),
4.62-4.55 (m, 2H), 4.23-4.19 (m, 1H), 1.43 (d, J=8.4 Hz, 3H); ESIMS
m/z 186.2 ([M+H].sup.+); IR (thin film) 3445, 2967, 1168
cm.sup.-1.
[1006] The following molecule was made in accordance with the
procedures disclosed in Example 131:
(S)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-aminium
2,2,2-trifluoroacetate
##STR00411##
[1008] The title molecule was isolated as a colorless gum: .sup.1H
NMR (300 MHz, DMSO-d.sub.6) .delta. 9.12 (t, J=5.7 Hz, 1H), 8.19
(bs, 2H), 4.14-3.93 (m, 2H), 3.80 (t, J=6.0 Hz, 1H), 1.81-1.71 (m,
2H), 0.88 (t, J=7.2 Hz, 3H); ESIMS m/z 185.00 ([M+H].sup.+); IR
(thin film) 3459, 1674, 1169 cm.sup.-1.
Example 132: Preparation of
2-Bromo-N--((S)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)--
4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
(F10 and F11)
##STR00412##
[1010] The title molecule was prepared as described in Example 15.
The diastereomeric pairs were separated by chiral HPLC using
Chiralpak.RTM. IA (4.6.times.250 mm) 5 .mu.m column using 0.1% TFA
in hexane and isopropanol as the mobile phase (isocratic 70:30)
with a flow rate 1.0 mL/min at ambient temperature. Diastereomer
F10 was collected at a retention time of 4.55 min and possessed an
optical rotation of [.alpha.].sub.D.sup.30=+35.6 (c, 0.5% in
CH.sub.2Cl.sub.2). Diastereomer F11 was collected at 8.71 min and
possessed an optical rotation of [.alpha.].sub.D.sup.30=-82.0 (c,
0.5% in CH.sub.2Cl.sub.2). Characterization data for these
molecules are listed in Table 2.
Example 133: Preparation of
2-Bromo-N--((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)--
4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
(F12 and F13)
##STR00413##
[1012] The title molecule was prepared as described in Example 15.
The diastereomeric pairs were separated by chiral HPLC using
Chiralpak.RTM. IA (4.6.times.250 mm) 5 m column using 0.1% TFA in
hexane and isopropanol as the mobile phase (isocratic 70:30) with a
flow rate 1.0 mL/min at ambient temperature. Diastereomer F12 was
collected at a retention time of 5.62 min and possessed an optical
rotation of [.alpha.].sub.D.sup.30=+59.4 (c, 1% in
CH.sub.2Cl.sub.2). Diastereomer F13 was collected at 8.85 min and
possessed an optical rotation of [.alpha.].sub.D.sup.30=-44.0 (c,
1% in CH.sub.2Cl.sub.2). Characterization data for these molecules
are listed in Table 2.
[1013] The following molecules was prepared in accordance with the
procedures disclosed in Example 133:
N--((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-4,4,4-tri-
fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamid-
e (F20A and F20B)
##STR00414##
[1015] Diastereomer F20A (isomer 1) was collected at a retention
time of 4.13 min and possessed an optical rotation of
[.alpha.].sub.D.sup.25=+49.2 (c, 1.0% in CH.sub.2Cl.sub.2).
Diastereomer F20B was collected at 4.88 min and possessed an
optical rotation of [.alpha.].sub.D.sup.25=-38.8 (c, 1.0% in
CH.sub.2Cl.sub.2). Characterization data for these molecules are
listed in Table 2.
[1016] F20A and F20B Stereochemical Assignment
[1017] F20A and F20B were dissolved in CDCl.sub.3 and placed in a
100 .mu.m path length cell with BaF.sub.2 windows. IR and
vibrational circular dichroism (VCD) spectra were recorded on a
IR-2XTM VCD spectrometer (BioTools, Inc.) equipped with dual PEM
accessory, with 4 cm.sup.-1 resolution. The sample and CDCl.sub.3
spectra were acquired for 21 h on an instrument optimized at 1400
cm.sup.-1. The solvent-subtracted IR and VCD spectra were
collected.
[1018] Theoretical Calculations:
[1019] F20 with R,R- and S,R-configurations were built with Maestro
(Schrodinger, LLC. New York, N.Y.). The conformational search was
carried out with MacroModel (Schrodinger, LLC. New York, N.Y.) with
MMFF94x force field to generate low-energy conformers. Single point
calculation (SPE), geometry, frequency, and IR and VCD calculations
were performed at the DFT level (B3LYP/lacvp**) in Jaguar
(Schrodinger, LLC. New York, N.Y.). A scaling factor of 0.96 was
applied to the frequency calculation. Analysis: for F20 with R,R-
and S,R-configurations, the top 100 low-energy conformers generated
with MacroModel were selected for DFT SPE calculations. These
calculations resulted in the 8 and 4 conformers that have energies
within 1 kcal/mol higher than the lowest energy conformer for R,R-
and S,R-configurations, respectively. The frequency calculations
were performed on these conformers to determine the IR and VCD
spectra. The Boltzmann-weighted IR and VCD spectra of these
conformers were compared with the observed IR and VCD spectra.
Based on the overall agreement in VCD pattern between the observed
and calculated spectra, the absolute configuration of F20A is
assigned as R,R-configuration. The assignment was evaluated by
CompareVOA program (BioTools). The confidence level of the
assignment is 88% based on a database that includes 105 previous
correct assignments for different chiral structures. However, the
observed spectrum for F20B does not agree well with the calculated
spectrum for S,R-configuration with a confidence level of 65%. But
considering that the compound has only one chiral center, two
possible configurations and F20A is of R,R-configuration, F20B can
be with high confidence assigned as the S,R-configuration.
Example 134: Preparation of
(E)-2-Methyl-N-(2-methyl-1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-y-
l)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzothioamide
(F31)
##STR00415##
[1021] To a stirred solution of
(E)-2-methyl-N-(2-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-yl)--
4-(4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (400
mg, 0.68 mmol) in CH.sub.2Cl.sub.2 (50 mL) was added P.sub.2S.sub.5
(75 mg, 0.34 mmol) and HMDO (0.25 mL, 1.12 mmol) at room
temperature and the mixture was refluxed for 3 h. The reaction
mixture was cooled to room temperature and another portion of
P.sub.2S.sub.5 (75 mg, 0.34 mmol) was added and the resulting
mixture was refluxed for 18 h. The volatiles were evaporated and
the residue was purified by prep TLC to give the title compound as
pale yellow gum (47 mg, 11%). Characterization data for this
molecule is listed in Table 2.
Example 135: Preparation of
(E)-2-Bromo-N-(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-
-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
(F1)
##STR00416##
[1023] To
(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-
yl)benzoic acid (200 mg, 0.409 mmol) in MeCN (5 mL) was added
1H-benzo[d][1,2,3]triazol-1-ol hydrate (63 mg, 0.411 mmol), HBTU
(155 mg, 0.409 mmol), N-(2,2,2-trifluoroethyl)
1-amino-2-methyl-propanecarboxamide hydrochloride (180 mg, 0.816
mmol) and diisopropylethylamine (0.24 mL, 1.38 mmol). After 24 h
the material was concentrated in vacuo. The crude product was
purified by passing the crude reaction mixture through a silica
frit and eluting with EtOAc/hexane (1:2). The recovered material
was further purified by medium pressure chromatography on silica
with EtOAc/hexane as the eluent to afford the title as a white foam
(147 mg, 55%). Characterization data for this molecule is listed in
Table 2.
Example 136: Preparation of
1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanone
##STR00417##
[1025] Isopropyl magnesium chloride lithium chloride complex (22.0
mL, 28.02 mmol) was added dropwise to a stirred solution of
5-bromo-1,3-difluoro-2-methoxybenzene (5.0 g, 22.42 mmol) at
-5.degree. C. in THF (100 mL) and the reaction mixture was stirred
at same temperature for 30 min. Methyl trifluoroacetate (3.67 g,
28.69 mmol) was added dropwise and the reaction mixture was stirred
at ambient temperature for 2 h. A 2 N HCl solution (200 mL) was
added to quench the reaction and then it was extracted with
diethylether. The combined organic layers were washed with brine,
dried (Na.sub.2SO.sub.4) filtered and concentrated to afford the
title compound (5.4 g, crude) as a yellow liquid. The material was
taken to next step without further purification. .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.68-7.60 (m, 2H) 4.19 (s, 3H); ESIMS m/z
240.1 ([M].sup.+).
[1026] The following molecule was prepared in accordance with the
procedures disclosed in Example 136:
2,6-Difluoro-4-(2,2,2-trifluoroacetyl)benzonitrile
##STR00418##
[1028] .sup.1H NMR (400 MHz, CDCl3) .delta. 7.45 (d, J=8.4 Hz, 1H),
7.37 (d, J=8.4 Hz, 1H); EIMS m/z 235.1 ([M].sup.+).
Example 137: Preparation of
(E)-N-(1-((2-Fluoroethyl)amino)-1-oxopropan-2-yl)-4-(4,4,4-trifluoro-3-(3-
,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide
(P1618A)
##STR00419##
[1029] Step 1: (2R)-tert-Butyl
2-(4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluo-
romethyl)benzamido)propanoate
[1030] The title compound was prepared according to procedures
outlined in Example 15: .sup.1HNMR (400 MHz, DMSO d.sub.6) .delta.
8.73 (d, J=6.8 Hz, 1H), 7.92-7.90 (m, 3H), 7.61 (d, J=7.2 Hz, 1H),
7.36 (d, J=7.6 Hz, 1H), 6.99 (dd, J=15.2, 9.2 Hz, 1H), 6.77 (d,
J=15.2 Hz, 1H), 4.85-4.80 (m, 1H), 4.30-4.26 (m, 1H), 1.43 (s, 9H),
1.33 (d, J=6.8 Hz, 3H); ESIMS m/z 601.9 ([M-H].sup.-); IR (KBr)
3414, 1732, 1661, 1170, 748 cm.sup.-1.
Step 2:
(2R)-(4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)--
2-(trifluoromethyl)benzamido)propanoic acid
[1031] TFA (1 mL) was added to a stirred solution of tert-butyl
2-(2-bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)ben-
zamido)propanoate (1.0 g, 1.63 mmol) in CH.sub.2Cl.sub.2 (20 mL) at
0.degree. C. and the reaction mixture was stirred at ambient
temperature for 18 h. The volatiles were evaporated under vacuum
and the residue was triturated with pentane to afford the title
compound as brown solid (0.65 g, 67%): .sup.1HNMR (400 MHz,
DMSO-d.sub.6) .delta. 12.60 (bs, 1H), 8.82 (d, J=8.0 Hz, 1H), 7.99
(s, 1H), 7.92-7.89 (m, 3H), 7.51 (d, J=8.0 Hz, 1H), 7.08 (dd,
J=15.6, 8.8 Hz, 1H), 6.88 (d, J=15.6 Hz, 1H), 4.88-4.83 (m, 1H),
4.41-4.34 (m, 1H), 1.34 (d, J=7.2 Hz, 3H); ESIMS: m/z 545.7
([M-H].sup.+); IR (KBr) 3410, 3281, 2928, 1728, 1172, 744
cm.sup.-1.
Step 3.
(E)-N-(1-((2-Fluoroethyl)amino)-1-oxopropan-2-yl)-4-(4,4,4-trifluo-
ro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide
(P1618)
[1032] DIPEA (0.60 mL, 1.08 mmol), PyBOP (180 mg, 0.36 mmol)
2-(4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluo-
romethyl)benzamido)propanoic acid (35 mg, 0.36 mmol) were added to
a stirred solution of compound 1 (200 mg, 0.36 mmol) in
CH.sub.2Cl.sub.2 (10 mL) at ambient temperature and the reaction
mixture was stirred for 18 h. The reaction mixture was diluted
CH.sub.2Cl.sub.2, washed with 1N HCl, followed by a saturated
NaHCO.sub.3 solution, water and brine. The organic phase was dried
(Na.sub.2SO.sub.4), filtered, concentrated and the residue was
purified by column chromatography on silica (100-200 mesh) eluting
with 10% EtOAc in petroleum ether to afford the title compound as a
brown solid (85 mg, 39%).
[1033] The following molecule was prepared in accordance with the
procedures disclosed in Example 137, Step 1:
tert-Butyl
2-(2-bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but--
1-enyl)benzamido)propanoate
##STR00420##
[1035] .sup.1H NMR (400 MHz, DMSO-d.sub.6): .delta. 8.82 (d, J=7.6
Hz, 1H), 7.99 (s, 1H), 7.91-7.90 (m, 3H), 7.50 (d, J=7.6 Hz, 1H),
7.07 (dd, J=16.0, 8.8 Hz, 1H), 6.88 (d, J=15.2 Hz, 1H), 4.88-4.83
(m, 1H), 4.31-4.27 (m, 1H), 1.42 (s, 9H), 1.32 (d, J=7.6 Hz, 3H);
ESIMS m/z 611.7 ([M-H].sup.-); IR (KBr) 3296, 2932, 1732, 1162,
743, 556 cm.sup.-1.
(E)-tert-Butyl
2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzami-
do)acetate
##STR00421##
[1037] Isolated as a (620 mg, 72%) pale yellow solid. .sup.1H NMR
(400 MHz, DMSO-d.sub.6) .delta. 8.77 (t, J=6.0 Hz, 1H), 7.93-7.91
(m, 3H), 7.62 (d, J=6.8 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.00 (dd,
J=15.6, 9.2 Hz, 1H), 6.77 (d, J=16.0 Hz, 1H), 4.86-4.81 (m, 1H),
3.86-3.85 (m, 2H), 1.33 (s, 9H). ESIMS m/z 599.87
([M+H].sup.+).
[1038] The following molecule was prepared in accordance with the
procedures disclosed in Example 137, Step 2:
2-(2-Bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benz-
amido)propanoic acid
##STR00422##
[1040] .sup.1HNMR (400 MHz, DMSO-d.sub.6): .delta. 12.62 (bs, 1H),
8.73 (d, J=9.6 Hz, 1H), 7.93-7.91 (m, 3H), 7.61 (d, J=8.1 Hz, 1H),
7.37 (d, J=7.8 Hz, 1H), 7.01 (dd, J=15.6, 9.0 Hz, 1H), 6.78 (d,
J=15.9 Hz, 1H), 4.89-4.79 (m, 1H), 4.42-4.32 (m, 1H), 1.36 (d,
J=7.2 Hz, 3H); ESIMS: m/z 558.0 ([M+H].sup.+); IR (KBr) 3418, 1650,
1115, 747, 560 cm.sup.-1.
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benz-
amido)acetic acid
##STR00423##
[1042] Isolated as an (550 mg, 97%) off white solid. .sup.1H NMR
(300 MHz, DMSO-d6) .delta. 12.56 (bs, 1H), 8.73 (t, J=5.4 Hz, 1H),
7.93-7.91 (m, 3H), 7.62 (d, J=9.3 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H),
7.01 (dd, J=15.9, 9.0 Hz, 1H), 6.78 (d, J=15.9 Hz, 1H), 4.89-4.80
(m, 1H), 3.90-3.88 (m, 2H). ESIMS m/z 541.82 ([M-H].sup.-).
Example 138: Preparation of
(E)-2-Chloro-5-hydroxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(-
4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
##STR00424##
[1043] Step 1. Methyl 4-bromo-2-chloro-5-methoxybenzoate
[1044] A 25 mL round bottomed flask equipped with a magnetic stir
bar was charged with 4-bromo-2-chloro-5-methoxybenzoic acid (JACS,
1963, 730-2; 1.25 g, 4.72 mmol), 20% MeOH/EtOAc (25 mL) and cooled
in an ice-water bath. Trimethylsilyldiazomethane (TMSCHN.sub.2 2 M
in hexanes, 2.6 mL, 5.20 mmol) was added dropwise via an addition
funnel. The reaction continued to stir for 1 h then it was
concentrated to afford the title compound as a white solid (1.31 g,
100%): mp 78-79.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.65 (s, 1H), 7.36 (s, 1H), 3.94 (s, 3H), 3.93 (s, 3H);
EIMS m/z 280 ([M].sup.+).
Step 2. 2-Chloro-5-methoxy-4-vinylbenzoic acid
[1045] A 25 mL round bottomed flask was charged with methyl
4-bromo-2-chloro-5-methoxybenzoate (640 mg, 2.29 mmol),
K.sub.2CO.sub.3 (665 mg, 4.81 mmol), potassium
trifluoro(vinyl)borate (920 mg, 6.87 mmol), PdCl.sub.2(dppf) (84
mg, 0.11 mmol) and anhydrous DMSO (15 mL) and stirred at 80.degree.
C. for 2 h. The reaction was allowed to cool, water (150 mL) was
added and then extracted several times with Et.sub.2O. The organic
layer was washed with brine, dried over MgSO.sub.4, filtered and
concentrated to give a brown residue. The crude product was
purified via flash chromatography eluting with 15%
Et.sub.2O/hexanes to give methyl 2-chloro-5-methoxy-4-vinylbenzoate
as a yellow oil (440 mg, 85%). To a 25 mL round bottomed flask
containing methyl 2-chloro-5-methoxy-4-vinylbenzoate (440 mg, 1.94
mmol) and MeOH (10 mL) was added 1N NaOH (2 mL, 2.04 mmol) and
reaction stirred at ambient temperature for 18 h. The reaction
mixture was concentrated to give a solid residue. The residue was
dissolved in water and extracted 1.times. with 50%
Et.sub.2O/hexanes. The aqueous layer was made acidic with 2N HCl
and extracted 2.times. with CH.sub.2Cl.sub.2, dried over
MgSO.sub.4, filtered and concentrated to afford the title compound
as a white solid (0.39 g, 94%): .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.54 (d, J=0.5 Hz, 1H), 7.52 (s, 1H), 6.98 (ddd, J=17.7,
11.2, 0.6 Hz, 1H), 5.87 (dd, J=17.7, 1.1 Hz, 1H), 5.45 (dd, J=11.2,
1.1 Hz, 1H), 3.90 (s, 3H).
Step 3.
(E)-2-Chloro-5-methoxy-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl-
)but-1-en-1-yl)benzoic acid
[1046] A 50 mL 3 neck round bottomed flask was charged with
2-chloro-5-methoxy-4-vinylbenzoic acid (390 mg, 1.84 mmol)),
5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (754 mg,
2.20 mmol) and anhydrous N-methyl pyrrolidinone (10 mL). Nitrogen
was bubbled into the reaction mixture for 15 min. After which time,
2,2'-dipyridyl (57.3 mg, 0.37 mmol) and CuBr (11.7 mg, 0.18 mmol)
were added and reaction mixture stirred at 150.degree. C. for 1 h.
Reaction mixture was allowed to cool, water (300 mL) was added and
extracted several times with Et.sub.2O. Organic layer was washed
repeatedly with water, dried over MgSO.sub.4, filtered and
concentrated to afford--the title compound as a light brown foam
(870 mg, 100%). This material was 95% pure by LC/MS; ESIMS m/z 473
([M-H].sup.-). This material was used without further
purification.
Step 4.
(E)-2-Chloro-5-methoxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)eth-
yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
[1047] A 50 mL round bottomed flask was charged with
(E)-2-chloro-5-methoxy-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1--
en-1-yl)benzoic acid (780 mg, 1.65 mmol)),
di(1H-imidazol-1-yl)methanone (267 mg, 1.65 mmol) and anhydrous THF
(30 mL). The resulting mixture was heated at reflux until it ceased
giving off gas. 2-Amino-N-(2,2,2-trifluoroethyl)acetamide HCl (257
mg, 1.65 mmol) was added in one portion and the reaction mixture
continued to stir at reflux for 18 h. The reaction mixture was
concentrated to dryness and the residue was taken up in Et.sub.2O
(50 mL) and 0.1N HCl (10 mL). The layers were separated. The
aqueous layer was extracted 2.times. with Et.sub.2O. The Et.sub.2O
layers were combined and washed 1.times. with aqueous NaHCO.sub.3,
1.times. with brine, dried over MgSO.sub.4, filtered and
concentrated to give a brown oil. The crude product was purified
via flash chromatography eluting with 30-40% EtOAc/hexanes to
afford the title compound--as an off white foam (280 mg, 28%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.45 (s, 1H), 7.41 (s,
2H), 7.29 (s, 1H), 7.28 (s, 1H), 6.84 (m, 2H), 6.43 (dd, J=16.0,
8.3 Hz, 1H), 4.25 (d, J=5.4 Hz, 2H), 4.10 (m, 1H), 3.97 (qd, J=9.0,
6.4 Hz, 2H), 3.87 (s, 3H); ESIMS m/z 613.1 ([M+H].sup.+).
Step 5.
(E)-2-Chloro-5-hydroxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)eth-
yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
[1048] A 25 mL round bottomed flask was charged with
(E)-2-chloro-5-methoxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(-
4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
(57 mg, 0.093 mmol) and CH.sub.2Cl.sub.2 (3 mL). The reaction
mixture was cooled to -78.degree. C. and boron tribromide
(BBr.sub.3, 1.0M solution in CH.sub.2Cl.sub.2, 0.33 mL, 0.326 mmol)
was added slowly via syringe. The reaction allowed to warm to
ambient temperature and stirred for 18 h. An additional 0.3-0.4 mL
of BBr.sub.3 was added at ambient temperature and continued to stir
for 3 h. The reaction mixture was added to aqueous NaHCO.sub.3 and
extracted 3.times. with CH.sub.2Cl.sub.2. The CH.sub.2Cl.sub.2
layers were combined and dried over MgSO.sub.4, filtered and
concentrated to give an oil. The crude material was purified via
flash chromatography eluting with 50% EtOAc/hexanes to afford the
title compound as a white solid (18 mg, 33%): mp 190.degree. C.
(dec.); .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 9.81 (s, 1H),
8.06 (d, J=7.0 Hz, 1H), 7.71 (m, 1H), 7.44 (d, J=2.8 Hz, 2H), 7.37
(s, 1H), 7.20 (s, 1H), 6.82 (d, J=15.9 Hz, 1H), 6.50 (m, 1H), 4.14
(m, 3H), 3.89 (m, 2H); ESIMS m/z 599 ([M+H].sup.+).
Example 139: Preparation of
1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-one
##STR00425##
[1050] To a magnetically stirred solution of
4-bromo-1,2-dichlorobenzene (5.64 g, 24.98 mmol) in dry Et.sub.2O
(109 mL) was added n-BuLi (10.86 mL, 24.98 mmol) via an addition
funnel under a nitrogen atmosphere. The reaction mixture was
stirred at -78.degree. C. for 30 min, A solution of ethyl
2,2-difluoropropanoate (3.0 g, 21.7 mmol) in Et.sub.2O (10 mL) was
added dropwise over 15 min and allowed to stir for 1 h. The
reaction was then carefully quenched with 1 N HCl (4 mL) and
allowed to warm to 23.degree. C. The solution was dilute with
Et.sub.2O and washed with water. The combined organic layers were
dried over Na.sub.2SO.sub.4, concentrated under reduced pressure
and the resulting material was purified via flash column
chromatography using 100% hexanes to 5% acetone/95% hexanes as
eluent. The relevant fractions were concentrated under reduced
pressure to afford the title compound as a colorless oil (3.89 g,
71%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.21-8.18 (m, 1H),
7.99-7.93 (m, 1H), 7.59 (dd, J=8.4, 4.2 Hz, 1H), 1.89 (t, J=19.6
Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -92.08--93.21
(m); EISMS m/z 240 ([M-H].sup.+).
Example 140:
(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-vinylbenzoi-
c acid
##STR00426##
[1052] To a stirred solution of
(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoi-
c acid (600 mg, 1.23 mmol) in dry toluene (10 mL) was added
tributyl(vinyl)stannane (470 mg, 1.48 mmol) and the mixture was
degassed with argon for 15 min. Pd(PPh.sub.3).sub.4 (72 mg, 0.06
mmol) was added and the reaction mixture was refluxed for 2 h. The
reaction mixture was brought to ambient temperature, water was
added and the mixture extracted with EtOAc. The organic layer was
washed with 2N HCl and brine, dried (Na.sub.2SO.sub.4), filtered,
and concentrated. The residue was purified by column chromatography
on silica eluting with 30% EtOAc in petroleum ether to afford the
title compound as brown solid (295 mg, 55%): .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 13.05 (bs, 1H), 7.91 (s, 2H), 7.81-7.75 (m,
2H), 7.59 (d, J=8.1 Hz, 1H), 7.48 (dd, J=17.4, 10.8 Hz, 1H), 7.03
(dd, J=15.9, 8.7 Hz, 1H), 6.84 (d, J=15.6 Hz, 1H), 5.88 (d, J=16.5
Hz, 1H), 5.39 (d, J=12.3 Hz, 1H), 4.89-4.82 (m, 1H); ESIMS m/z
432.18 ([M-H].sup.-); IR (thinfilm) 3418, 1689, 1114, 747
cm.sup.-1.
Example 141:
(E)-2-Iodo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic
acid
##STR00427##
[1054] Per Buchwald, et al.; JACS, 2002, 124, 14844-14845,
potassium iodide (KI, 273 mg, 1.64 mmol), CuI (31 mg, 0.16 mmol)
and trans-N,N'-dimethylcyclohexane-1,2-diamine (catalytic amount)
were added to a solution of
(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoi-
c acid (400 mg, 0.82 mmol) in 1,4-dioxane (8 mL). The mixture in an
Ace pressure tube was heated at 100.degree. C. for 3 h. The
reaction mixture was brought to ambient temperature and filtered
through a Celite.RTM. pad. The filtrate was concentrated and
residue was diluted with EtOAc and washed with 1N HCl followed by
brine. The organic layer was dried (Na.sub.2SO.sub.4), filtered,
and concentrated. The residue was purified by column chromatography
on silica eluting with 25% EtOAc in petroleum ether to afford the
title compound as brown semi solid (240 mg, 55%): .sup.1H NMR (400
MHz, DMSO-d.sub.6) .delta. 13.3 (bs, 1H), 8.21 (s, 1H), 7.91 (s,
2H), 7.71-7.64 (m, 2H), 7.01 (dd, J=15.6, 9.2 Hz, 1H), 6.75 (d,
J=15.6 Hz, 1H), 4.85-4.81 (m, 1H); ESIMS m/z 532.8 ([M-H].sup.-);
IR (thinfilm) 3436, 1699, 1113, 750 cm.sup.-1.
Example 142: Preparation of
(E)-2-Bromo-N-(2-methyl-1-(neopentylamino)-1-oxopropan-2-yl)-4-(4,4,4-tri-
fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
##STR00428##
[1055] Step 1.
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
benzamido)-2-methylpropanoic acid
[1056] A 25 mL round bottomed flask equipped with a magnetic stir
bar and reflux condenser was charged with
(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)ben-
zoic acid (400 mg, 0.82 mmol) and 1,2-dichloroethane (DCE) (5 mL).
Thionyl chloride (0.12 mL, 1.64 mmol) was added neat in one portion
and the resulting reaction mixture was heated at reflux for 2 h.
After which time, reaction mixture was allowed to cool and
concentrated to give the crude acid chloride which was used without
further purification. To a solution containing NaHCO.sub.3 (68.8
mg, 0.82 mmol), 2-amino-2-methylpropanoic acid (84 mg, 0.82 mmol)
and dodecyltrimethylammonium bromide (2.52 mg, 8.19 .mu.mol) in 10
mL of THF was added to the acid chloride in THF (1 mL). The
resulting mixture was heated at reflux for 18 h. Reaction mixture
was allowed to cool and added to water, made acidic with 0.1N HCl,
extracted (3.times.) with Et.sub.2O, washed (1.times.) with brine,
dried over MgSO.sub.4, filtered and evaporated to afford the title
compound as a light brown foam (400 mg, 85%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.60 (d, J=1.6 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H),
7.40 (s, 2H), 7.37 (dd, J=8.1, 1.6 Hz, 1H), 6.63 (s, 1H), 6.53 (d,
J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.10 (p, J=8.3 Hz,
1H), 1.73 (s, 6H). This material is used without further
purification.
Step 2.
(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-e-
n-1-yl)phenyl)-4,4-dimethyloxazol-5(4H)-one
[1057] A 25 mL round bottomed flask was charged with
(E)-2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
benzamido)-2-methylpropanoic acid (400 mg, 0.70 mmol),
CH.sub.2Cl.sub.2 (10 mL) and stirred at 0.degree. C. EDC. HCl (134
mg, 0.70 mmol) was added in one portion as a solid and the reaction
mixture was allowed to warm toward ambient temperature and
continued to stir for 1 h. The reaction was diluted with
CH.sub.2Cl.sub.2, washed with brine, dried over MgSO.sub.4,
filtered and evaporated to give a dark oil. The crude product was
purified via flash chromatography eluting with 50%
hexanes/CH.sub.2Cl.sub.2 to afford the title compound as an off
white foam (220 mg, 57): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.76 (d, J=8.1 Hz, 1H), 7.73 (d, J=1.6 Hz, 1H), 7.42 (d, J=7.8 Hz,
3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.7 Hz, 1H), 4.12
(p, J=8.5 Hz, 1H), 1.57 (s, 6H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -68.55; ESIMS m/z 554 ([M-H].sup.-).
Step 3.
(E)-2-Bromo-N-(2-methyl-1-(neopentylamino)-1-oxopropan-2-yl)-4-(4,-
4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide
[1058] A 10 mL round bottomed flask was charged with
(E)-2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-
phenyl)-4,4-dimethyloxazol-5(4H)-one (90 mg, 0.16 mmol) and
CH.sub.2Cl.sub.2 (2 mL). 2,2-Dimethylpropan-1-amine (28.2 mg, 0.324
mmol) was added neat via pipette and the reaction stirred at
ambient temperature for 18 h. The reaction mixture was evaporated
to give an oil. The crude product was purified via flash
chromatography eluting with 20% EtOAc/hexanes to afford the title
compound as a white foam (90 mg, 86%): .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.60 (d, J=1.6 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H),
7.40 (s, 2H), 7.36 (dd, J=8.1, 1.6 Hz, 1H), 6.66 (d, J=10.0 Hz,
2H), 6.53 (d, J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.8 Hz, 1H), 4.11
(m, 1H), 3.12 (d, J=6.2 Hz, 2H), 1.72 (s, 6H), 0.93 (s, 9H); 19F
NMR (376 MHz, CDCl.sub.3) .delta. -68.62; ESIMS m/z 643.19
([M+H].sup.+).
Example 143: Preparation of 3,5-Dibromo-4-chlorobenzaldehyde
##STR00429##
[1059] Step 1. Methyl 4-amino-3,5-dibromobenzoate: conc
[1060] H.sub.2SO.sub.4 (1.35 mL, 25.48 mmol) was added dropwise to
a stirred solution of 4-amino-3,5-dibromobenzoic acid (5.0 g, 16.99
mmol) in MeOH (50 mL) at ambient temperature and the reaction
mixture was then stirred at 80.degree. C. for 8 h. The reaction
mixture was brought to ambient temperature, volatiles were
evaporated and ice cold water was added to the residue and which
was then extracted with EtOAc. The organic layer was washed with an
aqueous NaHCO.sub.3 solution followed by brine and water. The
solution was then dried (Na.sub.2SO.sub.4), filtered and
concentrated to afford the title compound as an off white solid
(5.0 g, 95%): .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 7.91 (s,
2H), 6.20 (bs, 2H), 3.78 (s, 3H); ESIMS m/z 307.0 ([M].sup.+); IR
(thin film) 3312, 2953, 1726, 595 cm.sup.-1.
Step 2. Methyl 3,5-dibromo-4-chlorobenzoate
[1061] CuCl.sub.2 (2.82 g, 21.0 mmol) in MeCN (30 mL) was stirred
at 80.degree. C. for 30 min. To this mixture tert-butylnitrite (2.7
mL, 23 mmol) was then added dropwise at same temperature and the
mixture was stirred for another 10 min. Methyl
4-amino-3,5-dibromobenzoate (5.0 g, 16 mmol) in MeCN (30 mL) was
added dropwise to the reaction mixture and then stirred at
80.degree. C. for 30 min. The reaction mixture was brought to
ambient temperature and an aqueous ammonia solution (20 mL) was
added to the reaction mixture and extracted with petroleum ether.
The organic layer was washed with brine followed by water, dried
(Na.sub.2SO.sub.4), filtered and concentrated to afford the title
compound as an off white solid (4.5 g, 84%). .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 8.21 (s, 2H), 3.94 (s, 3H); ESIMS m/z 326
([M].sup.+); IR (thin film) 1732, 746 cm.sup.-1.
Step 3. (3,5-Dibromo-4-chlorophenyl)methanol
[1062] NaBH.sub.4 (1.53 g, 40.65 mmol) was added portionwise to a
stirred solution of methyl 3,5-dibromo-4-chlorobenzoate (4.45 g,
13.6 mmol) in MeOH (50 mL) at 0.degree. C. The reaction mixture was
then stirred at ambient temperature for 8 h. The volatiles were
evaporated and the residue was diluted with CH.sub.2Cl.sub.2 and
washed with brine followed by water. The organic layer was dried
(Na.sub.2SO.sub.4), filtered and concentrated to afford the title
compound as an off white solid (3.3 g, 80%): .sup.1H NMR (300 MHz,
DMSO-d.sub.6) .delta. 7.71 (s, 2H), 5.49 (bs, 1H), 4.48 (d, J=4.5
Hz, 2H); ESIMS m/z 297.9 ([M].sup.+); IR (thin film) 3460, 747, 534
cm.sup.-1.
Step 4. 3,5-Dibromo-4-chlorobenzaldehyde
[1063] Pyridinium chlorochromate (PCC, 3.44 g, 15.9 mmol) was added
in one portion to a stirred solution of
(3,5-dibromo-4-chlorophenyl)methanol (3.2 g, 11.0 mmol) in
CHCl.sub.3 (40 mL) at ambient temperature and the reaction mixture
was stirred overnight. The reaction mixture was filtered through
Celite.RTM., the Celite.RTM. pad was washed with CHCl.sub.3 and the
filtrate was concentrated to afford the title compound as an off
white solid (2.0 g, 62%): mp 110-113.degree. C.; .sup.1H NMR (300
MHz, DMSO-d.sub.6) .delta. 9.93 (s, 1H), 8.27 (s, 2H); ESIMS m/z
297.0 ([M].sup.+).
Example 144: Preparation of 4-Bromo-3,5-dichlorobenzaldehyde
##STR00430##
[1064] Step 1. Methyl 4-amino-3, 5-dichlorobenzoate: conc
[1065] H.sub.2SO.sub.4 (2.5 mL, 97.04 mmol) was added drop wise to
a stirred solution of 4-amino-3,5-dichlorobenzoic acid (10.0 g,
48.54 mmol) in MeOH (150 mL) at 0.degree. C. and the reaction
mixture was then stirred at 80.degree. C. for 8 h. The volatiles
were evaporated; ice cold water was added to the residue and which
was then extracted with EtOAc. The combined organic layers were
washed with brine, dried (Na.sub.2SO.sub.4), filtered and
concentrated under reduced pressure to afford the title compound as
a white solid (7.5 g, 70%): .sup.1H NMR (300 MHz, DMSO-d.sub.6)
.delta. 8.05 (s, 2H), 3.96 (s, 3H); ESIMS m/z 282 ([M].sup.+); IR
(KBr): 1733, 762, 514 cm.sup.-1.
Step 2. Methyl 4-bromo-3, 5-dichlorobenzoate
[1066] CuBr.sub.2 (7.5 g, 34.08 mmol) in MeCN (50 mL) was stirred
at 80.degree. C. for 30 min. To this solution tert-butylnitrite
(6.5 mL, 54.55 mmol) was added dropwise at the same temperature and
the mixture was stirred for another 10 min. Methyl
4-amino-3,5-dichlorobenzoate in MeCN (30 mL) was added dropwise to
the reaction mixture which was then stirred at 80.degree. C. for 30
min. The reaction mixture was brought to ambient temperature.
Aqueous ammonia solution (20 mL) was added and extracted with
petroleum ether. The organic layer was washed with brine followed
by water. The organic solution was dried (Na.sub.2SO.sub.4),
filtered and concentrated to afford the title compound as an off
white solid (7.5 g, 77%): .sup.1H NMR (300 MHz, DMSO-d.sub.6)
.delta. 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z 282 ([M].sup.+); IR
(thin film) 1733, 762, 514 cm.sup.-1.
Step 3. (4-Bromo-3,5-dichlorophenyl)methanol
[1067] DIBAL-H (1M in toluene, 66 mL, and 66.0 mmol) was added
dropwise to a stirred solution of methyl 4-bromo-3,
5-dichlorobenzoate (7.5 g, 26.0 mmol) in THF (50 mL) at -78.degree.
C. The reaction mixture was brought to ambient temperature and
stirred for 6 h. The reaction mixture was poured into ice-water and
extracted with CH.sub.2Cl.sub.2. The organic layer was washed with
brine followed by water, dried (Na.sub.2SO.sub.4), filtered and
concentrated to afford a mixture of
(4-bromo-3,5-dichlorophenyl)methanol and
4-bromo-3,5-dichlorobenzaldehyde (6.0 g) as an off white solid
which was taken to next step without purification.
Step 4. 4-Bromo-3, 5-dichlorobenzaldehyde
[1068] PCC (7.5 g, 35.16 mmol) was added in one portion to a
stirred solution containing a mixture of
(4-bromo-3,5-dichlorophenyl)methanol and
4-bromo-3,5-dichlorobenzaldehyde (6.0 g) in CHCl.sub.3 (40 mL) at
ambient temperature and the reaction mixture was stirred overnight.
The reaction mixture was filtered through celite. The celite pad
was washed with CHCl.sub.3. The filtrate was concentrated to afford
the title compound as an off white solid (3.5 g, 67%): mp
125-128.degree. C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta.
9.96 (s, 1H), 8.10 (s, 2H); ESIMS m/z 252 ([M].sup.+).
Example 145: 3-Chloro-5-ethylbenzaldehyde
##STR00431##
[1070] PdCl.sub.2(dppf)(37 mg, 0.046 mmol), potassium phosphate
(1.93 g, 9.11 mmol) and triethylborane (1M in hexane, 0.45 g, 4.56
mmol) were added to a solution of 3-bromo-5-chloro-benzaldehyde
(1.0 g, 4.56 mmol) in THF (20 mL) at ambient temperature and the
mixture was refluxed for 12 h. The reaction mixture was brought to
ambient temperature, diluted with EtOAc and washed with water. The
organic layer was dried (Na.sub.2SO.sub.4), filtered, concentrated
and the residue was purified by column chromatography on silica
(100-200 mesh) eluting with 2% EtOAc in petroleum ether to afford
the title compound (330 mg, 41%) as a pale yellow liquid: .sup.1H
NMR (400 MHz, DMSO-d.sub.6) .delta. 9.97 (s, 1H), 7.75 (d, J=1.6 Hz
1H), 7.73 (s, 1H), 7.65 (s, 1H), 2.74-2.68 (m, 2H), 1.23 (t, J=7.6
Hz, 3H); ESIMS m/z 168.0 ([M].sup.+); IR (thin film) 3071, 1699,
692 cm.sup.-1.
Example 146:
(E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-
-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
##STR00432##
[1071] Step 1. (E)-Ethyl
4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenz-
oate
[1072]
5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.5
g, 10.8 mmol), CuCl (54 mg, 0.54 mmol) and 2,2-bipyridyl (169 mg,
1.08 mmol) were added to a stirred solution of ethyl
2-nitro-4-vinylbenzoate (1.2 g, 5.42 mmol) in 1,2-dichlorobenzene
(12 mL) at ambient temperature and the mixture was then stirred at
180.degree. C. for 18 h. The reaction mixture was then cooled to
ambient temperature, adsorbed on silica gel and purified by column
chromatography eluting with 10% EtOAc in petroleum ether to afford
the title compound (1.3 g, 53%) as a brown liquid: .sup.1H NMR
(DMSO-d.sub.6, 300 MHz) .delta. 8.31 (s, 1H), 8.02-7.95 (m, 1H),
7.88-7.85 (m, 3H), 7.20 (dd, J=15.9, 9.3 Hz, 1H), 6.91 (d, J=15.6
Hz, 1H), 4.91-4.85 (m, 1H), 4.34-4.27 (m, 2H), 1.27 (t, J=6.6 Hz,
3H); ESIMS m/z 463.8 ([M-H].sup.-); IR (KBr) 3439, 2985, 1731, 1251
cm.sup.-1.
Step 2.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)--
2-nitrobenzoic acid
[1073] Concentrated HCl (16.0 mL) was added dropwise to a stirred
solution of (E)-ethyl
4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenz-
oate (800 mg, 1.72 mmol) in 1,4-dioxane (8.0 mL) at 0.degree. C.
and the reaction mixture was refluxed for 36 h. The volatiles were
evaporated; the residue was diluted with EtOAc and washed with
brine and water. The organic layer was dried (Na.sub.2SO.sub.4),
filtered, concentrated and the residue was purified by column
chromatography on silica (100-200 mesh) eluting with 30% EtOAc in
petroleum ether to afford the title compound as a yellow solid (390
mg, 52%): .sup.1H NMR (400 MHz, DMSO-d.sub.6) .delta. 13.9 (bs,
1H), 8.22 (s, 1H), 7.93-7.91 (m, 1H), 7.86-7.84 (m, 3H), 7.16 (dd,
J=15.6, 9.2 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H), 4.89-4.85 (m, 1H).
ESIMS m/z 435.9 ([M-H].sup.-); IR (KBr) 3445, 2924, 1708, 1541, 817
cm.sup.-1.
Step 3.
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)--
2-nitro-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
[1074] 2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (96
mg, 0.35 mmol), PyBOP (165 mg, 0.32 mmol) and DIPEA (0.1 mL, 0.57
mmol) were added to a stirred solution of
(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitro-
benzoic acid (130 mg, 0.29 mmol) in CH.sub.2Cl.sub.2 (3 mL) and the
reaction mixture was stirred at ambient temperature for 8 h. Water
was added to reaction mixture and extracted with CH.sub.2Cl.sub.2.
The organic layer was washed with brine, dried (Na.sub.2SO.sub.4),
filtered, concentrated and the residue was purified by column
chromatography on silica (100-200 mesh) eluting with 30% EtOAc in
petroleum ether to afford the title compound as a yellow solid (120
mg, 74%): .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 9.04 (t,
J=5.7 Hz, 1H), 8.60 (t, J=6.0 Hz, 1H), 8.25 (s, 1H), 7.97-7.94 (m,
1H), 7.87 (d, J=6.3 Hz, 2H), 7.69 (d, J=7.5 Hz, 1H), 7.15 (dd,
J=15.9, 9.3 Hz, 1H), 6.89 (d, J=15.9 Hz, 1H), 4.88-4.83 (m, 1H),
3.98-3.89 (m, 4H); ESIMS m/z 575.87 ([M+H].sup.+); IR (KBr) 3430,
2925, 1663, 1168, 832 cm.sup.-1.
Step 4.
(E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut--
1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
[1075] Iron powder (81.8 mg, 1.46 mmol) and NH.sub.4Cl (104 mg,
1.94 mmol) was added to a stirred solution of
(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitro-
-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide (280 mg,
0.486 mmol) in EtOH: water (6 mL, 1:1) at ambient temperature and
the mixture was stirred at reflux for 90 min. The reaction mixture
was cooled to ambient temperature and filtered through celite. The
filtrate was concentrated and the residue was dissolved in EtOAc
and washed with saturated NaHCO.sub.3 solution, brine and water.
The organic layer was dried (Na.sub.2SO.sub.4), filtered,
concentrated and the residue was purified by column chromatography
on silica (10-200 mesh) eluting with 35% EtOAc in petroleum ether
to afford the titled compound as a yellow solid (215 mg, 81%).
Example 147:
(E)-2-Bromo-4-(3-(3,5-dichloro-4-hydroxyphenyl)-4,4,4-trifluorobut-1-enyl-
)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
##STR00433##
[1077] DIPEA (0.20 mL, 1.26 mmol), PyBOP (245 mg, 0.47 mmol) and
2-amino-N-(2,2,2-trifluoroethyl)acetamide (90 mg, 0.47 mmol) were
added to a stirred solution of
(E)-2-bromo-4-(3-(3,5-dichloro-4-hydroxyphenyl)-4,4,4-trifluorobut-1-enyl-
)benzoic acid (200 mg, 0.42 mmol, 66% purity) in CH.sub.2Cl.sub.2
(5 mL) at ambient temperature. The resulting mixture was then
stirred for 12 h. The reaction mixture was diluted with
CH.sub.2Cl.sub.2, washed with 1N HCl, followed by saturated sodium
bicarbonate solution, brine solution and water. The organic layer
was dried (Na.sub.2SO.sub.4), filtered, concentrated under vacuum.
The residue was purified by column chromatography on silica
(100-200 mesh) eluting with 30% EtOAc in petroleum ether to give
the title compound as light green solid (130 mg, 52%).
Example 148: Preparation of
(R)-2-Amino-3-methyl-N-(2,2,2-trifluoroethyl)butanamide
##STR00434##
[1079] A Parr shaker flask charged with (R)-benzyl
(3-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)-butan-2-yl)carbamate
(4.95 g, 14.9 mmol) in 100 mL of EtOAc and 25 mL of EtOH was
treated with 175 mg of 10% Pd/C. The mixture was placed under 40
psi of hydrogen and shaken for 6 h. An additional 65 mg of 10% Pd/C
was added to the reaction mixture which was then placed under 40
psi of hydrogen and shaken for 3.5 h. The reaction solution was
then filtered through a pad of celite, concentrated in vacuo and
purified by sublimation (75 to 85.degree. C., 200-230 millibar) to
afford the title compound as a white solid (1.92 g, 65%): mp
43-47.degree. C.; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.04-7.74 (m, 1H), 3.92 (ddd, J=16.0, 9.3, 6.8 Hz, 1H), 3.84-3.60
(m, 1H), 3.23 (d, J=3.8 Hz, 1H), 2.23 (ddd, J=10.7, 7.0, 3.5 Hz,
1H), 0.92 (d, J=7.0 Hz, 3H), 0.75 (d, J=6.9 Hz, 3H); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -72.70.
Example 149: Preparation of
(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(meth-
ylsulfonyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide
##STR00435##
[1081] Oxone (320 mg, 0.50 mmol) was added to a stirred solution of
(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(meth-
ylthio)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide (150
mg, 0.25 mmol) in acetone-water (10 mL, 1:1) at ambient temperature
and the reaction mixture was stirred for 18 h. The reaction mixture
was then extracted with CH.sub.2Cl.sub.2. The organic layer was
washed with brine and water, dried (Na.sub.2SO.sub.4), filtered,
concentrated and the residue was triturated with pentane-Et.sub.2O
(1:1) to afford the title compound as an off white solid (85 mg,
56%): .sup.1H NMR (300 MHz, DMSO-d.sub.6) .delta. 9.01 (t, J=6.0,
1H), 8.37 (t, J=6.4 Hz, 1H), 8.08 (s, 1H), 8.01-7.96 (m, 1H),
7.88-7.86 (m, 2H), 7.64 (d, J=7.6 Hz, 1H), 7.05 (dd, J=16.4, 8.8
Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.87-4.80 (m, 1H), 3.98-3.91 (m,
4H), 3.38 (s, 3H); ESIMS m/z 608.85 ([M+H].sup.+); IR (thin film)
337, 416, 721, 164, 768 cm.sup.-1.
[1082] The following prophetic molecules could be made in
accordance with the procedures disclosed in this application:
TABLE-US-00001 Compound Number Structure P1 ##STR00436## P2
##STR00437## P3 ##STR00438## P4 ##STR00439## P5 ##STR00440## P6
##STR00441## P7 ##STR00442## P8 ##STR00443## P9 ##STR00444## P10
##STR00445## P11 ##STR00446## P12 ##STR00447## P13 ##STR00448## P14
##STR00449## P15 ##STR00450## P16 ##STR00451## P17 ##STR00452## P18
##STR00453## P19 ##STR00454## P20 ##STR00455## P21 ##STR00456## P22
##STR00457## P23 ##STR00458## P24 ##STR00459## P25 ##STR00460## P26
##STR00461## P27 ##STR00462## P28 ##STR00463## P29 ##STR00464## P30
##STR00465## P31 ##STR00466## P32 ##STR00467## P33 ##STR00468## P34
##STR00469## P35 ##STR00470## P36 ##STR00471## P37 ##STR00472## P38
##STR00473## P39 ##STR00474## P40 ##STR00475## P41 ##STR00476## P42
##STR00477## P43 ##STR00478## P44 ##STR00479## P45 ##STR00480##
[1083] The following prophetic molecules could be made in
accordance with the procedures disclosed in this application:
##STR00481##
TABLE-US-00002 Cmpd No. R1 R2 R3 R4 R6 R8 R10 W1 (C1-C8) alkyl W2
R15 P46 F F F H CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P47 F F
F H CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P48 F F F H
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P49 F F F H
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P50 F F F H
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P51 F F F H CF.sub.3 H
Cl O CH.sub.2 S CH.sub.2CF.sub.3 P52 F F F H CF.sub.3 H CF.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P53 F F F H CF.sub.3 H CH.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P54 F F F H CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P55 F F F H CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P56 F F F H CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P57 F F F H CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P58 F F F H CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P59 F F F H CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P60 F F F H CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P61 F F F H CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P62 F F F H CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P63 F F F H CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P64 F F F H CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2
O CH.sub.2CF.sub.3 P65 F F F H CF.sub.3 CF.sub.3 CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P66 F F F H CF.sub.2CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CF.sub.3 P67 F F F H CF.sub.2CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P68 F F F H CF.sub.2CF.sub.3 H CF.sub.3
O CH.sub.2 O CH.sub.2CF.sub.3 P69 F F F H CF.sub.2CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P70 F F F H CF.sub.3 H Br O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P71 F F F H CF.sub.3 H Cl O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P72 F F F H CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P73 F F F H CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P74 F F F H CF.sub.3 CF.sub.3 Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P75 F F F H CF.sub.3 CF.sub.3 Cl O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P76 F F F H CF.sub.3 CF.sub.3
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P77 F F F H CF.sub.3
CF.sub.3 CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P78 F F F H
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P79 F F F H
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P80 F F F H
CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P81 F
F F H CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P82 F F F H CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P83 F F
F H CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P84 F F F H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P85 F F F H
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P86 F F F H
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P87 F F F H
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P88 F F F H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P89 F F F H
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P90 F F F H
CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P91 F F F H
CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P92 F F F H
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P93 F F F H
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P94 F F F H
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P95 F F F H
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P96 F F F H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P97 F F F H
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P98 F F F H
CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P99 F F F H
CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P100 F F F H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P101 F F
F H CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P102
F F F H CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P103 F F F H CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P104 F F F H CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P105 F F F H CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P106 F F F H
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P107 F F F
H CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P108 F F
F H CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P109 F F F H CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P110 F F F H CF.sub.3 H Br O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P111 F F F H CF.sub.3 H Cl O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P112 F F F H CF.sub.3 H CF.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P113 F F F H CF.sub.3 H
CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P114 F F F H
CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P115 F F F H
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P116 F F F H
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P117 F F
F H CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P118
Cl Cl H Cl CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P119 Cl Cl H
Cl CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P120 Cl Cl H Cl
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P121 Cl Cl H Cl
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P122 Cl Cl H Cl
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P123 Cl Cl H Cl
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P124 Cl Cl H Cl
CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P125 Cl Cl H Cl
CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P126 Cl Cl H Cl
CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P127 Cl Cl H Cl
CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P128 Cl Cl H Cl
CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P129 Cl Cl H Cl
CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P130 Cl Cl H Cl
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2 P131 Cl Cl H Cl
CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P132 Cl Cl H Cl
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P133 Cl Cl H Cl
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P134 Cl Cl H Cl
CF.sub.3 CF.sub.3 Br O CH.sub.2 O CH.sub.2CF.sub.3 P135 Cl Cl H Cl
CF.sub.3 CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P136 Cl Cl H Cl
CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P137 Cl Cl
H Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P138
Cl Cl H Cl CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P139
Cl Cl H Cl CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P140
Cl Cl H Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P141 Cl Cl H Cl CF.sub.2CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P142 Cl Cl H Cl CF.sub.3 H Br O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P143 Cl Cl H Cl CF.sub.3 H Cl O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P144 Cl Cl H Cl CF.sub.3 H CF.sub.3
O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P145 Cl Cl H Cl CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P146 Cl Cl H Cl CF.sub.3
CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P147 Cl Cl H Cl
CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P148 Cl Cl H
Cl CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P149 Cl Cl H Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P150 Cl Cl H Cl CF.sub.2CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P151 Cl Cl H Cl CF.sub.2CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P152 Cl Cl H Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P153
Cl Cl H Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P154 Cl Cl H Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P155 Cl Cl H Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P156 Cl Cl H Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P157 Cl Cl H Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P158 Cl Cl H Cl CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P159 Cl Cl H Cl CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P160 Cl Cl H Cl CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P161 Cl Cl H Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P162 Cl Cl H Cl CF.sub.3
H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P163 Cl Cl H Cl CF.sub.3 H
Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P164 Cl Cl H Cl CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P165 Cl Cl H Cl CF.sub.3
H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P166 Cl Cl H Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P167 Cl Cl H Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P168 Cl Cl H Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P169 Cl Cl H
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P170 Cl
Cl H Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P171 Cl
Cl H Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P172 Cl
Cl H Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P173 Cl Cl H Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P174 Cl Cl H Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P175 Cl Cl H Cl CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P176 Cl Cl H Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P177 Cl Cl H Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P178
Cl Cl H Cl CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P179 Cl Cl H Cl CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P180 Cl Cl H Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P181 Cl Cl H Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P182 Cl Cl H Cl
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P183 Cl Cl H
Cl CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P184 Cl Cl
H Cl CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P185 Cl Cl H Cl CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P186 Cl Cl H Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P187 Cl Cl H Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P188 Cl Cl H Cl CF.sub.3 H CF.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P189 Cl Cl H Cl CF.sub.3 H
CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P190 H H H OCF.sub.3
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P191 H H H OCF.sub.3
CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P192 H H H OCF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P193 H H H
OCF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P194 H
H H OCF.sub.3 CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P195 H H
H OCF.sub.3 CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P196 H H H
OCF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P197 H
H H OCF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3
P198 H H H OCF.sub.3 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3
P199 H H H OCF.sub.3 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3
P200 H H H OCF.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P201 H H H OCF.sub.3 CF.sub.3 H CH.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P202 H H H OCF.sub.3 CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CHF.sub.2 P203 H H H OCF.sub.3 CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CHF.sub.2 P204 H H H OCF.sub.3 CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P205 H H H OCF.sub.3
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P206 H H H
OCF.sub.3 CF.sub.3 CF.sub.3 Br O CH.sub.2 O CH.sub.2CF.sub.3 P207 H
H H OCF.sub.3 CF.sub.3 CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3
P208 H H H OCF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P209 H H H OCF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P210 H H H OCF.sub.3 CF.sub.2CF.sub.3 H
Br O CH.sub.2 O CH.sub.2CF.sub.3 P211 H H H OCF.sub.3
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P212 H H H
OCF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P213 H H H OCF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P214 H H H OCF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P215 H H H OCF.sub.3 CF.sub.3 H Cl O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P216 H H H OCF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P217 H H H OCF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P218 H H H OCF.sub.3
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P219 H H H
OCF.sub.3 CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P220 H H H OCF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P221 H H H OCF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P222 H H H OCF.sub.3
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P223 H H H
OCF.sub.3 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P224 H H H OCF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P225 H H H OCF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P226 H H H OCF.sub.3 CF.sub.3 H Br
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P227 H H H OCF.sub.3 CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P228 H H H OCF.sub.3 CF.sub.3
H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P229 H H H OCF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P230 H H H
OCF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P231 H H
H OCF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P232 H
H H OCF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P233 H H H OCF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P234 H H H OCF.sub.3 CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P235 H H H OCF.sub.3 CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P236 H H H OCF.sub.3 CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P237 H H H OCF.sub.3
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P238 H H H
OCF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P239 H H
H OCF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P240 H
H H OCF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P241 H H H OCF.sub.3 CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P242 H H H OCF.sub.3 CF.sub.3 H Br
O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P243 H H H OCF.sub.3 CF.sub.3
H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P244 H H H OCF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P245 H H
H OCF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
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CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P247 H H H OCF.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P248 H H H
OCF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P249 H H H OCF.sub.3 CF.sub.3 H CH.sub.3 O
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CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P251 H H H OCF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P252 H H H OCF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P253
H H H OCF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P254 H H H OCF.sub.3 CF.sub.3 H Br O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P255 H H H OCF.sub.3 CF.sub.3
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CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P257 H H
H OCF.sub.3 CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
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CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P259 H H H OCF.sub.3 CF.sub.3 H
Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P260 H H H OCF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P261 H H
H OCF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P262 H F H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P263 H F H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P264 H F H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P265 H F H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P266 H F H Br CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P267 H F H Br CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P268 H F H Br CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P269 H F H Br CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P270 H F H Br CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P271 H F H Br CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P272 H F H Br CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P273 H F H Br CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P274 H F H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P275 H F H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P276 H F H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P277 H F H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P278 H F H Br CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P279 H F H Br CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P280 H F H Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P281 H F H Br CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P282 H F H Br
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P283 H F H Br
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P284 H F H Br
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P285 H F
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H F H Br CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P287 H F H
Br CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P288 H F H Br
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P289 H F H Br
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P290 H F H Br
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P291 H F H
Br CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P292 H F
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CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P297 H F H Br
CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P298
H F H Br CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P299 H F H
Br CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P300 H F H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P301 H F H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P302 H F H Br
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P303 H F H Br
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P304 H F H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P305 H F H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P306 H F H Br
CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P307 H F H Br
CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P308 H F H Br
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P309 H F H Br
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P310 H F H Br
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P311 H F H Br
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P312 H F H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P313 H F H
Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P314 H F
H Br CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P315 H F H
Br CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P316 H F H
Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P317 H
F H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P318 H F H Br CF.sub.3 H Br O CH(CH.sub.3) O
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O CH.sub.2CH.sub.2CF.sub.3 P320 H F H Br CF.sub.3 H CF.sub.3 O
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CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P322 H F H Br
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P323 H F H
Br CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P324 H F
H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
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CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P331 H F H Br
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P332 H F H Br
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P333 H F
H Br CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P334
H CH.sub.3 Cl H CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P335 H
CH.sub.3 Cl H CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P336 H
CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P337 H CH.sub.3 Cl H CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P338 H CH.sub.3 Cl H CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P339 H CH.sub.3 Cl H CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P340 H CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P341 H CH.sub.3 Cl H CF.sub.3 H
CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P342 H CH.sub.3 Cl H
CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P343 H CH.sub.3 Cl H
CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P344 H CH.sub.3 Cl H
CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P345 H CH.sub.3
Cl H CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P346 H
CH.sub.3 Cl H CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2 P347 H
CH.sub.3 Cl H CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P348 H
CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2
P349 H CH.sub.3 Cl H CF.sub.3 H CH.sub.3 O CH.sub.2 O
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CH.sub.2 O CH.sub.2CF.sub.3 P351 H CH.sub.3 Cl H CF.sub.3 CF.sub.3
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CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P353 H CH.sub.3 Cl
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CH.sub.3 Cl H CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3
P355 H CH.sub.3 Cl H CF.sub.2CF.sub.3 H Cl O CH.sub.2 O
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CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P359 H CH.sub.3 Cl
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CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P373 H CH.sub.3 Cl H
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P374 H
CH.sub.3 Cl H CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P375
H CH.sub.3 Cl H CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3
P376 H CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P377 H CH.sub.3 Cl H CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P378 H CH.sub.3 Cl H CF.sub.3 H Br
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P379 H CH.sub.3 Cl H CF.sub.3 H
Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P380 H CH.sub.3 Cl H CF.sub.3
H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P381 H CH.sub.3 Cl H
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P382 H
CH.sub.3 Cl H CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P383
H CH.sub.3 Cl H CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P384 H CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P385 H CH.sub.3 Cl H CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P386 H CH.sub.3 Cl H CF.sub.3 H Br
O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P387 H CH.sub.3 Cl H CF.sub.3
H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P388 H CH.sub.3 Cl H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P389 H
CH.sub.3 Cl H CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P390 H CH.sub.3 Cl H CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P391 H CH.sub.3 Cl H
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P392 H
CH.sub.3 Cl H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
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CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P395 H
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CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P398
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P402 H CH.sub.3 Cl H CF.sub.3 H Br O CH.sub.2CH.sub.2 O
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CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P404 H CH.sub.3 Cl H CF.sub.3 H
CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P405 H CH.sub.3 Cl H
CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P406 H Cl
CH.sub.3 H CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P407 H Cl
CH.sub.3 H CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P408 H Cl
CH.sub.3 H CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P409 H
Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P410 H Cl CH.sub.3 H CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3
P411 H Cl CH.sub.3 H CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3
P412 H Cl CH.sub.3 H CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P413 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P414 H Cl CH.sub.3 H CF.sub.3 H Br S
CH.sub.2 O CH.sub.2CF.sub.3 P415 H Cl CH.sub.3 H CF.sub.3 H Cl S
CH.sub.2 O CH.sub.2CF.sub.3 P416 H Cl CH.sub.3 H CF.sub.3 H
CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P417 H Cl CH.sub.3 H
CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P418 H Cl
CH.sub.3 H CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2 P419 H Cl
CH.sub.3 H CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P420 H Cl
CH.sub.3 H CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P421
H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2
P422 H Cl CH.sub.3 H CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P423 H Cl CH.sub.3 H CF.sub.3 CF.sub.3 Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P424 H Cl CH.sub.3 H CF.sub.3 CF.sub.3
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P425 H Cl CH.sub.3 H
CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P426 H Cl
CH.sub.3 H CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P427
H Cl CH.sub.3 H CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3
P428 H Cl CH.sub.3 H CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P429 H Cl CH.sub.3 H CF.sub.2CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P430 H Cl CH.sub.3 H CF.sub.3 H Br O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P431 H Cl CH.sub.3 H CF.sub.3 H Cl
O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P432 H Cl CH.sub.3 H CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P433 H Cl CH.sub.3 H
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P434 H Cl
CH.sub.3 H CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P435 H Cl CH.sub.3 H CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P436 H Cl CH.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P437 H Cl CH.sub.3 H CF.sub.3
CF.sub.3 CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P438 H Cl
CH.sub.3 H CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3
P439 H Cl CH.sub.3 H CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P440 H Cl CH.sub.3 H CF.sub.2CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P441 H Cl CH.sub.3 H
CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P442
H Cl CH.sub.3 H CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P443 H Cl CH.sub.3 H CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P444 H Cl CH.sub.3 H CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P445 H Cl CH.sub.3 H CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P446 H Cl CH.sub.3 H
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P447 H Cl CH.sub.3
H CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P448 H Cl
CH.sub.3 H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P449 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P450 H Cl CH.sub.3 H CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P451 H Cl CH.sub.3 H CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P452 H Cl CH.sub.3 H CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P453 H Cl CH.sub.3 H
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P454 H Cl
CH.sub.3 H CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P455 H
Cl CH.sub.3 H CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P456
H Cl CH.sub.3 H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P457 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P458 H Cl CH.sub.3 H CF.sub.3 H Br
O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P459 H Cl CH.sub.3 H CF.sub.3
H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P460 H Cl CH.sub.3 H
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P461 H Cl
CH.sub.3 H CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P462 H Cl CH.sub.3 H CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P463 H Cl CH.sub.3 H
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P464 H Cl
CH.sub.3 H CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P465 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P466 H Cl CH.sub.3 H
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P467 H Cl
CH.sub.3 H CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P468 H Cl CH.sub.3 H CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P469 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P470 H Cl CH.sub.3 H
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P471 H Cl
CH.sub.3 H CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P472 H Cl CH.sub.3 H CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P473 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P474 H Cl CH.sub.3 H CF.sub.3
H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P475 H Cl CH.sub.3 H
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P476 H Cl
CH.sub.3 H CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P477 H Cl CH.sub.3 H CF.sub.3 H CH.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P478 H CH.sub.3 F CH.sub.3
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P479 H CH.sub.3 F
CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P480 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P481 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P482 H CH.sub.3 F CH.sub.3 CF.sub.3 H
Br O CH.sub.2 S CH.sub.2CF.sub.3 P483 H CH.sub.3 F CH.sub.3
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P484 H CH.sub.3 F
CH.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P485 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P486 H CH.sub.3 F CH.sub.3 CF.sub.3 H Br S
CH.sub.2 O CH.sub.2CF.sub.3 P487 H CH.sub.3 F CH.sub.3 CF.sub.3 H
Cl S CH.sub.2 O CH.sub.2CF.sub.3 P488 H CH.sub.3 F CH.sub.3
CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P489 H CH.sub.3 F
CH.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P490 H
CH.sub.3 F CH.sub.3 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2
P491 H CH.sub.3 F CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P492 H CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P493 H CH.sub.3 F CH.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P494 H CH.sub.3 F CH.sub.3
CF.sub.3 CF.sub.3 Br O CH.sub.2 O CH.sub.2CF.sub.3 P495 H CH.sub.3
F CH.sub.3 CF.sub.3 CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P496
H CH.sub.3 F CH.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P497 H CH.sub.3 F CH.sub.3 CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P498 H CH.sub.3 F CH.sub.3
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P499 H CH.sub.3
F CH.sub.3 CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P500
H CH.sub.3 F CH.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P501 H CH.sub.3 F CH.sub.3 CF.sub.2CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P502 H CH.sub.3 F CH.sub.3
CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P503 H CH.sub.3 F
CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P504 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P505 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3
O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P506 H CH.sub.3 F CH.sub.3
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P507 H
CH.sub.3 F CH.sub.3 CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P508 H CH.sub.3 F CH.sub.3 CF.sub.3 CF.sub.3
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P509 H CH.sub.3 F
CH.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P510 H CH.sub.3 F CH.sub.3 CF.sub.2CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P511 H CH.sub.3 F CH.sub.3
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P512 H
CH.sub.3 F CH.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P513 H CH.sub.3 F CH.sub.3 CF.sub.2CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P514 H CH.sub.3 F
CH.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P515 H
CH.sub.3 F CH.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P516 H CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P517 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P518 H CH.sub.3 F CH.sub.3 CF.sub.3
H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P519 H CH.sub.3 F CH.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P520 H CH.sub.3 F
CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P521
H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P522 H CH.sub.3 F CH.sub.3 CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P523 H CH.sub.3 F CH.sub.3 CF.sub.3
H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P524 H CH.sub.3 F CH.sub.3
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P525 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O
CH.sub.2CF.sub.3 P526 H CH.sub.3 F CH.sub.3 CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P527 H CH.sub.3 F CH.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P528 H CH.sub.3 F
CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P529 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P530 H CH.sub.3 F CH.sub.3 CF.sub.3 H Br O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P531 H CH.sub.3 F CH.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P532 H CH.sub.3
F CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P533 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3
O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P534 H CH.sub.3 F CH.sub.3
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P535 H
CH.sub.3 F CH.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P536 H CH.sub.3 F CH.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P537 H CH.sub.3
F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P538 H CH.sub.3 F CH.sub.3 CF.sub.3 H Br O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P539 H CH.sub.3 F CH.sub.3
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P540 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P541 H CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P542 H CH.sub.3 F CH.sub.3
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P543 H
CH.sub.3 F CH.sub.3 CF.sub.3 H Cl O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P544 H CH.sub.3 F CH.sub.3 CF.sub.3 H CF.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P545 H CH.sub.3 F CH.sub.3
CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P546 H
CH.sub.3 F CH.sub.3 CF.sub.3 H Br O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P547 H CH.sub.3 F CH.sub.3 CF.sub.3 H Cl O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P548 H CH.sub.3 F CH.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P549 H
CH.sub.3 F CH.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P550 H Cl H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P551 H Cl H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P552 H Cl H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P553 H Cl H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P554 H Cl H Br CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P555 H Cl H Br CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P556 H Cl H Br CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P557 H Cl H Br CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P558 H Cl H Br CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P559 H Cl H Br CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P560 H Cl H Br CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P561 H Cl H Br CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P562 H Cl H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P563 H Cl H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P564 H Cl H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P565 H Cl H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P566 H Cl H Br CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P567 H Cl H Br CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P568 H Cl H Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P569 H Cl H Br CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P570 H Cl H Br
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P571 H Cl H Br
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P572 H Cl H Br
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P573 H Cl
H Br CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P574
H Cl H Br CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P575 H Cl
H Br CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P576 H Cl H Br
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P577 H Cl H
Br CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P578 H Cl
H Br CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P579 H
Cl H Br CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P580
H Cl H Br CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P581 H Cl H Br CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P582 H Cl H Br CF.sub.2CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P583 H Cl H Br
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P584 H Cl H
Br CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P585 H Cl H Br CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P586 H Cl H Br CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P587 H Cl H Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P588 H Cl H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P589 H Cl H Br CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P590 H Cl H Br CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P591 H Cl H Br CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P592 H Cl H Br CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P593 H Cl H Br CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P594 H Cl H Br CF.sub.3
H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P595 H Cl H Br CF.sub.3 H Cl
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P596 H Cl H Br CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3
P597 H Cl H Br CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O
CH.sub.2CF.sub.3 P598 H Cl H Br CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P599 H Cl H Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P600 H Cl H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CHF.sub.2 P601 H Cl H Br CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P602 H Cl H Br CF.sub.3 H Br O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P603 H Cl H Br CF.sub.3 H Cl O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P604 H Cl H Br CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P605 H Cl H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P606 H Cl
H Br CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P607 H
Cl H Br CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P608 H Cl H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P609 H Cl H Br CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P610 H Cl H Br CF.sub.3 H
Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P611 H Cl H Br
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P612 H Cl H
Br CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P613 H Cl H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P614 H Cl H Br CF.sub.3 H Br O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P615 H Cl H Br CF.sub.3 H Cl O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P616 H Cl H Br CF.sub.3 H CF.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P617 H Cl H Br CF.sub.3 H
CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P618 H Cl H Br
CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P619 H Cl H Br
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P620 H Cl H Br
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P621 H Cl
H Br CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P622
H H Br Br CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P623 H H Br
Br CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P624 H H Br Br
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P625 H H Br Br
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P626 H H Br Br
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P627 H H Br Br CF.sub.3
H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P628 H H Br Br CF.sub.3 H
CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P629 H H Br Br CF.sub.3 H
CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P630 H H Br Br CF.sub.3 H Br
S CH.sub.2 O CH.sub.2CF.sub.3 P631 H H Br Br CF.sub.3 H Cl S
CH.sub.2 O CH.sub.2CF.sub.3 P632 H H Br Br CF.sub.3 H CF.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P633 H H Br Br CF.sub.3 H CH.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P634 H H Br Br CF.sub.3 H Br O CH.sub.2
O CH.sub.2CHF.sub.2 P635 H H Br Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P636 H H Br Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P637 H H Br Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P638 H H Br Br CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P639 H H Br Br CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P640 H H Br Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P641 H H Br Br CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P642 H H Br Br
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P643 H H Br Br
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P644 H H Br Br
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P645 H H
Br Br CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P646 H H Br Br CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P647
H H Br Br CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P648 H H
Br Br CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P649 H
H Br Br CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P650
H H Br Br CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P651 H H Br Br CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P652 H H Br Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P653 H H Br Br CF.sub.3 CF.sub.3
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P654 H H Br Br
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P655 H H Br
Br CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P656 H H
Br Br CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P657 H H Br Br CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P658 H H Br Br CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P659 H H Br Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P660 H H Br Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P661 H H Br Br CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P662 H H Br Br CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P663 H H Br Br CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P664 H H Br Br CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P665 H H Br Br CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P666 H H Br Br CF.sub.3
H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P667 H H Br Br CF.sub.3 H Cl
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P668 H H Br Br CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P669 H H Br Br CF.sub.3
H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P670 H H Br Br
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P671 H H Br Br
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P672 H H Br Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P673 H H Br
Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P674 H H
Br Br CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P675 H H
Br Br CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P676 H H
Br Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P677 H H Br Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P678 H H Br Br CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P679 H H Br Br CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P680 H H Br Br CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P681 H H Br Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P682
H H Br Br CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P683 H H Br Br CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P684 H H Br Br CF.sub.3 H CF.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P685 H H Br Br CF.sub.3 H
CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P686 H H Br Br
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P687 H H Br Br
CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P688 H H Br Br
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P689 H H
Br Br CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P690 H H Br Br CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P691 H H Br Br CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P692 H H Br Br CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P693 H H Br Br CF.sub.3 H CH.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P694 H H Cl NO.sub.2 CF.sub.3 H
Br O CH.sub.2 O CH.sub.2CF.sub.3 P695 H H Cl NO.sub.2 CF.sub.3 H Cl
O CH.sub.2 O CH.sub.2CF.sub.3 P696 H H Cl NO.sub.2 CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P697 H H Cl NO.sub.2
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P698 H H Cl
NO.sub.2 CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P699 H H Cl
NO.sub.2 CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P700 H H Cl
NO.sub.2 CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P701 H H
Cl NO.sub.2 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P702
H H Cl NO.sub.2 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P703 H
H Cl NO.sub.2 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P704 H H
Cl NO.sub.2 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P705
H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3
P706 H H Cl NO.sub.2 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2
P707 H H Cl NO.sub.2 CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2
P708 H H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P709 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P710 H H Cl NO.sub.2 CF.sub.3 CF.sub.3
Br O CH.sub.2 O CH.sub.2CF.sub.3 P711 H H Cl NO.sub.2 CF.sub.3
CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P712 H H Cl NO.sub.2
CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P713 H H
Cl NO.sub.2 CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P714 H H Cl NO.sub.2 CF.sub.2CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CF.sub.3 P715 H H Cl NO.sub.2 CF.sub.2CF.sub.3 H
Cl O CH.sub.2 O CH.sub.2CF.sub.3 P716 H H Cl NO.sub.2
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P717 H H
Cl NO.sub.2 CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P718 H H Cl NO.sub.2 CF.sub.3 H Br O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P719 H H Cl NO.sub.2 CF.sub.3 H Cl O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P720 H H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P721 H H Cl NO.sub.2 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P722 H H Cl NO.sub.2
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P723 H H Cl
NO.sub.2 CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P724 H H Cl NO.sub.2 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P725 H H Cl NO.sub.2 CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P726 H H Cl NO.sub.2
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P727 H H Cl
NO.sub.2 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P728 H H Cl NO.sub.2 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P729 H H Cl NO.sub.2 CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P730 H H Cl NO.sub.2 CF.sub.3 H Br
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P731 H H Cl NO.sub.2 CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P732 H H Cl NO.sub.2 CF.sub.3
H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P733 H H Cl NO.sub.2
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P734 H H Cl
NO.sub.2 CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P735 H H
Cl NO.sub.2 CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P736 H
H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P737 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P738 H H Cl NO.sub.2 CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P739 H H Cl NO.sub.2 CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P740 H H Cl NO.sub.2 CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P741 H H Cl NO.sub.2
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P742 H H Cl
NO.sub.2 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P743 H H
Cl NO.sub.2 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P744 H
H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P745 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P746 H H Cl NO.sub.2 CF.sub.3 H Br
O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P747 H H Cl NO.sub.2 CF.sub.3
H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P748 H H Cl NO.sub.2
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P749 H H
Cl NO.sub.2 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P750 H H Cl NO.sub.2 CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P751 H H Cl NO.sub.2
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P752 H H Cl
NO.sub.2 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P753 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P754 H H Cl NO.sub.2
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P755 H H Cl
NO.sub.2 CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P756 H H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P757 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P758 H H Cl NO.sub.2
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P759 H H Cl
NO.sub.2 CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P760
H H Cl NO.sub.2 CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P761 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P762 H H Cl NO.sub.2 CF.sub.3
H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P763 H H Cl NO.sub.2
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P764 H H Cl
NO.sub.2 CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P765 H H Cl NO.sub.2 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P766 H H F CN CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P767 H H F CN CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P768 H H F CN CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P769 H H F CN CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P770 H H F CN CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P771 H H F CN CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P772 H H F CN CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P773 H H F CN CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P774 H H F CN CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P775 H H F CN CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P776 H H F CN CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P777 H H F CN CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P778 H H F CN CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P779 H H F CN CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P780 H H F CN CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P781 H H F CN CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P782 H H F CN CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P783 H H F CN CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P784 H H F CN CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P785 H H F CN CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P786 H H F CN
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P787 H H F CN
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P788 H H F CN
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P789 H H
F CN CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P790
H H F CN CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P791 H H F
CN CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P792 H H F CN
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P793 H H F CN
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P794 H H F CN
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P795 H H F
CN CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P796 H H
F CN CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P797 H H F CN CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3
P798 H H F CN CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P799 H H F CN CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P800 H H F CN CF.sub.2CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P801 H H F CN CF.sub.2CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P802 H H F CN CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P803 H H F CN CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P804 H H F CN CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P805 H H F CN CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P806 H H F CN CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P807 H H F CN CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P808 H H F CN CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P809 H H F CN CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P810 H H F CN CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P811 H H F CN CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P812 H H F CN CF.sub.3 H CF.sub.3 S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P813 H H F CN CF.sub.3 H CH.sub.3 S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P814 H H F CN CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P815 H H F CN CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P816 H H F CN CF.sub.3 H CF.sub.3
O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P817 H H F CN CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P818 H H F CN CF.sub.3
H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P819 H H F CN CF.sub.3 H
Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P820 H H F CN CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P821 H H F CN
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P822 H H
F CN CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P823 H
H F CN CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P824
H H F CN CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P825 H H F CN CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P826 H H F CN CF.sub.3 H Br
O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P827 H H F CN CF.sub.3 H
Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P828 H H F CN CF.sub.3
H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P829 H H F CN
CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P830
H H F CN CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P831
H H F CN CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P832
H H F CN CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P833 H H F CN CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P834 H H F CN CF.sub.3 H Br O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P835 H H F CN CF.sub.3 H Cl O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P836 H H F CN CF.sub.3 H CF.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P837 H H F CN CF.sub.3 H
CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P838 H Cl OCF.sub.3
Cl CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P839 H Cl OCF.sub.3
Cl CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P840 H Cl OCF.sub.3
Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P841 H Cl
OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P842
H Cl OCF.sub.3 Cl CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P843
H Cl OCF.sub.3 Cl CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P844
H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3
P845 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P846 H Cl OCF.sub.3 Cl CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P847 H Cl OCF.sub.3 Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P848 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P849 H Cl OCF.sub.3 Cl CF.sub.3 H
CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P850 H Cl OCF.sub.3 Cl
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2 P851 H Cl OCF.sub.3 Cl
CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P852 H Cl OCF.sub.3 Cl
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P853 H Cl
OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2
P854 H Cl OCF.sub.3 Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P855 H Cl OCF.sub.3 Cl CF.sub.3 CF.sub.3 Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P856 H Cl OCF.sub.3 Cl CF.sub.3
CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P857 H Cl OCF.sub.3
Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P858 H
Cl OCF.sub.3 Cl CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3
P859 H Cl OCF.sub.3 Cl CF.sub.2CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P860 H Cl OCF.sub.3 Cl CF.sub.2CF.sub.3 H CF.sub.3
O CH.sub.2 O CH.sub.2CF.sub.3 P861 H Cl OCF.sub.3 Cl
CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P862 H Cl
OCF.sub.3 Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P863 H
Cl OCF.sub.3 Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P864 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P865 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P866 H Cl OCF.sub.3 Cl CF.sub.3
CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P867 H Cl OCF.sub.3
Cl CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P868 H Cl
OCF.sub.3 Cl CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P869 H Cl OCF.sub.3 Cl CF.sub.3 CF.sub.3 CH.sub.3
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P870 H Cl OCF.sub.3 Cl
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P871 H Cl
OCF.sub.3 Cl CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P872 H Cl OCF.sub.3 Cl CF.sub.2CF.sub.3 H CF.sub.3
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P873 H Cl OCF.sub.3 Cl
CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P874
H Cl OCF.sub.3 Cl CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P875 H Cl OCF.sub.3 Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P876 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P877 H Cl OCF.sub.3 Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P878 H Cl OCF.sub.3 Cl
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P879 H Cl OCF.sub.3
Cl CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P880 H Cl
OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P881 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P882 H Cl OCF.sub.3 Cl CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P883 H Cl OCF.sub.3 Cl CF.sub.3 H
Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P884 H Cl OCF.sub.3 Cl
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P885 H Cl
OCF.sub.3 Cl CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3
P886 H Cl OCF.sub.3 Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P887 H Cl OCF.sub.3 Cl CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P888 H Cl OCF.sub.3 Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P889 H Cl OCF.sub.3 Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P890 H Cl
OCF.sub.3 Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P891 H Cl OCF.sub.3 Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P892 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P893 H Cl OCF.sub.3 Cl CF.sub.3
H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P894 H Cl
OCF.sub.3 Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P895 H Cl OCF.sub.3 Cl CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P896 H Cl OCF.sub.3 Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P897
H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P898 H Cl OCF.sub.3 Cl CF.sub.3 H Br O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P899 H Cl OCF.sub.3 Cl
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P900 H Cl
OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P901 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P902 H Cl OCF.sub.3 Cl
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P903 H Cl
OCF.sub.3 Cl CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P904 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P905 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P906 H Cl OCF.sub.3 Cl
CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P907 H Cl
OCF.sub.3 Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P908 H Cl OCF.sub.3 Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P909 H Cl OCF.sub.3 Cl CF.sub.3 H CH.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P910 H Cl CN Cl CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CF.sub.3 P911 H Cl CN Cl CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P912 H Cl CN Cl CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P913 H Cl CN Cl CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P914 H Cl CN Cl CF.sub.3 H Br O
CH.sub.2 S CH.sub.2CF.sub.3 P915 H Cl CN Cl CF.sub.3 H Cl O
CH.sub.2 S CH.sub.2CF.sub.3 P916 H Cl CN Cl CF.sub.3 H CF.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P917 H Cl CN Cl CF.sub.3 H CH.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P918 H Cl CN Cl CF.sub.3 H Br S
CH.sub.2 O CH.sub.2CF.sub.3 P919 H Cl CN Cl CF.sub.3 H Cl S
CH.sub.2 O CH.sub.2CF.sub.3 P920 H Cl CN Cl CF.sub.3 H CF.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P921 H Cl CN Cl CF.sub.3 H CH.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P922 H Cl CN Cl CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CHF.sub.2 P923 H Cl CN Cl CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CHF.sub.2 P924 H Cl CN Cl CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P925 H Cl CN Cl CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P926 H Cl CN Cl CF.sub.3 CF.sub.3 Br O
CH.sub.2 O CH.sub.2CF.sub.3 P927 H Cl CN Cl CF.sub.3 CF.sub.3 Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P928 H Cl CN Cl CF.sub.3 CF.sub.3
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P929 H Cl CN Cl CF.sub.3
CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P930 H Cl CN Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P931 H Cl CN Cl
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P932 H Cl CN Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P933 H Cl
CN Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P934 H Cl CN Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P935 H Cl CN Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P936 H Cl CN Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P937 H Cl CN Cl CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P938 H Cl CN Cl CF.sub.3 CF.sub.3 Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P939 H Cl CN Cl CF.sub.3 CF.sub.3
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P940 H Cl CN Cl CF.sub.3
CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P941 H Cl CN Cl
CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P942 H
Cl CN Cl CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P943 H Cl CN Cl CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P944 H Cl CN Cl CF.sub.2CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P945 H Cl CN Cl CF.sub.2CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P946 H Cl CN Cl CF.sub.3
H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P947 H Cl CN Cl CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P948 H Cl CN Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P949 H Cl CN Cl CF.sub.3
H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P950 H Cl CN Cl
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P951 H Cl CN Cl
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P952 H Cl CN Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P953 H Cl CN
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P954 H Cl
CN Cl CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P955 H Cl CN
Cl CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P956 H Cl CN Cl
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P957 H Cl CN
Cl CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P958 H Cl
CN Cl CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P959 H Cl CN
Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P960 H Cl CN Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P961 H Cl CN
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P962 H Cl
CN Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P963 H Cl
CN Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P964 H Cl
CN Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P965 H Cl CN Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P966 H Cl CN Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P967 H Cl CN Cl CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P968 H Cl CN Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P969 H Cl CN Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P970
H Cl CN Cl CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P971 H Cl CN Cl CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P972 H Cl CN Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P973 H Cl CN Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P974 H Cl CN Cl
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P975 H Cl CN
Cl CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P976 H Cl
CN Cl CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P977 H Cl CN Cl CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P978 H Cl CN Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P979 H Cl CN Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P980 H Cl CN Cl CF.sub.3 H CF.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P981 H Cl CN Cl CF.sub.3 H
CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P982 H CH.sub.3 H Br
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P983 H CH.sub.3 H Br
CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P984 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P985 H CH.sub.3 H
Br CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P986 H
CH.sub.3 H Br CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P987 H
CH.sub.3 H Br CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P988 H
CH.sub.3 H Br CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3
P989 H CH.sub.3 H Br CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P990 H CH.sub.3 H Br CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P991 H CH.sub.3 H Br CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P992 H CH.sub.3 H Br CF.sub.3 H CF.sub.3 S
CH.sub.2 O CH.sub.2CF.sub.3 P993 H CH.sub.3 H Br CF.sub.3 H
CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P994 H CH.sub.3 H Br
CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2 P995 H CH.sub.3 H Br
CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P996 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P997 H CH.sub.3
H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P998 H
CH.sub.3 H Br CF.sub.3 CF.sub.3 Br O CH.sub.2 O CH.sub.2CF.sub.3
P999 H CH.sub.3 H Br CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1000 H CH.sub.3 H Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1001 H CH.sub.3 H Br CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1002 H CH.sub.3 H Br
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1003 H
CH.sub.3 H Br CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3
P1004 H CH.sub.3 H Br CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1005 H CH.sub.3 H Br CF.sub.2CF.sub.3 H CH.sub.3
O CH.sub.2 O CH.sub.2CF.sub.3 P1006 H CH.sub.3 H Br CF.sub.3 H Br O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1007 H CH.sub.3 H Br CF.sub.3 H Cl
O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1008 H CH.sub.3 H Br CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1009 H CH.sub.3 H Br
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1010 H
CH.sub.3 H Br CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1011 H CH.sub.3 H Br CF.sub.3 CF.sub.3 Cl O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1012 H CH.sub.3 H Br CF.sub.3
CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1013 H
CH.sub.3 H Br CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1014 H CH.sub.3 H Br CF.sub.2CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1015 H CH.sub.3 H Br
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1016 H
CH.sub.3 H Br CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1017 H CH.sub.3 H Br CF.sub.2CF.sub.3 H CH.sub.3
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1018 H CH.sub.3 H Br CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1019 H CH.sub.3 H Br CF.sub.3
H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1020 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1021 H
CH.sub.3 H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1022 H CH.sub.3 H Br CF.sub.3 H Br O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1023 H CH.sub.3 H Br CF.sub.3 H Cl O CH(CH.sub.3)
S CH.sub.2CF.sub.3 P1024 H CH.sub.3 H Br CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1025 H CH.sub.3 H Br CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1026 H CH.sub.3 H Br
CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1027 H CH.sub.3 H
Br CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1028 H CH.sub.3
H Br CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1029 H
CH.sub.3 H Br CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3
P1030 H CH.sub.3 H Br CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1031 H CH.sub.3 H Br CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1032 H CH.sub.3 H Br CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1033 H CH.sub.3 H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1034 H
CH.sub.3 H Br CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1035 H CH.sub.3 H Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1036 H CH.sub.3 H Br CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1037 H CH.sub.3 H Br CF.sub.3
H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1038 H CH.sub.3 H
Br CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1039 H
CH.sub.3 H Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1040 H CH.sub.3 H Br CF.sub.3 H CF.sub.3
O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1041 H CH.sub.3 H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1042
H CH.sub.3 H Br CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1043 H CH.sub.3 H Br CF.sub.3 H Cl O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1044 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1045
H CH.sub.3 H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1046 H CH.sub.3 H Br CF.sub.3 H Br O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1047 H CH.sub.3 H Br CF.sub.3
H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1048 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1049 H
CH.sub.3 H Br CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1050 H CH.sub.3 H Br CF.sub.3 H Br O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1051 H CH.sub.3 H Br CF.sub.3
H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1052 H CH.sub.3 H Br
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1053 H
CH.sub.3 H Br CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1054 H H F CH.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1055 H H F CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1056 H H F CH.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1057 H H F CH.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1058 H H F CH.sub.3
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P1059 H H F CH.sub.3
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P1060 H H F CH.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1061 H H F
CH.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1062 H
H F CH.sub.3 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P1063 H H
F CH.sub.3 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P1064 H H F
CH.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P1065 H
H F CH.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3
P1066 H H F CH.sub.3 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2
P1067 H H F CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2
P1068 H H F CH.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1069 H H F CH.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P1070 H H F CH.sub.3 CF.sub.3 CF.sub.3
Br O CH.sub.2 O CH.sub.2CF.sub.3 P1071 H H F CH.sub.3 CF.sub.3
CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1072 H H F CH.sub.3
CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1073 H H
F CH.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1074 H H F CH.sub.3 CF.sub.2CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1075 H H F CH.sub.3 CF.sub.2CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P1076 H H F CH.sub.3 CF.sub.2CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1077 H H F CH.sub.3
CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1078 H H
F CH.sub.3 CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1079 H
H F CH.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1080
H H F CH.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1081 H H F CH.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1082 H H F CH.sub.3 CF.sub.3
CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1083 H H F CH.sub.3
CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1084 H H F
CH.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1085 H H F CH.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1086 H H F CH.sub.3
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1087 H H F
CH.sub.3 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1088 H H F CH.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1089 H H F CH.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1090 H H F CH.sub.3 CF.sub.3 H Br
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1091 H H F CH.sub.3 CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1092 H H F CH.sub.3 CF.sub.3
H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1093 H H F CH.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1094 H H F
CH.sub.3 CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1095 H H
F CH.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1096 H
H F CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P1097 H H F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1098 H H F CH.sub.3 CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1099 H H F CH.sub.3 CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1100 H H F CH.sub.3 CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1101 H H F CH.sub.3
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1102 H H F
CH.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1103 H H
F CH.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1104 H
H F CH.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P1105 H H F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1106 H H F CH.sub.3 CF.sub.3 H Br O CH(CH.sub.3)
O CH(CH.sub.3)CF.sub.3 P1107 H H F CH.sub.3 CF.sub.3 H Cl O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1108 H H F CH.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1109 H H F CH.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1110 H H
F CH.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1111 H H F CH.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1112 H H F CH.sub.3 CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1113 H H F CH.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1114
H H F CH.sub.3 CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1115 H H F CH.sub.3 CF.sub.3 H Cl O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1116 H H F CH.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1117
H H F CH.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1118 H H F CH.sub.3 CF.sub.3 H Br O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1119 H H F CH.sub.3 CF.sub.3
H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1120 H H F CH.sub.3
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1121 H
H F CH.sub.3 CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1122 H H F CH.sub.3 CF.sub.3 H Br O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1123 H H F CH.sub.3 CF.sub.3 H
Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1124 H H F CH.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1125 H H
F CH.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1126 H H F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1127 H H F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1128 H H F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1129 H H F Cl CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1130 H H F Cl CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1131 H H F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1132 H H F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1133 H H F Cl CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1134 H H F Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1135 H H F Cl CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1136 H H F Cl CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1137 H H F Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1138 H H F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1139 H H F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1140 H H F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1141 H H F Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1142 H H F Cl CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1143 H H F Cl CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1144 H H F Cl CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1145 H H F Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1146 H H F Cl
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1147 H H F Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1148 H H
F Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1149 H H F Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1150 H H F Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1151 H H F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1152 H H F Cl CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P1153 H H F Cl CF.sub.3 CF.sub.3 Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1154 H H F Cl CF.sub.3 CF.sub.3 Cl
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1155 H H F Cl CF.sub.3 CF.sub.3
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1156 H H F Cl CF.sub.3
CF.sub.3 CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1157 H H F Cl
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1158 H H F
Cl CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1159 H
H F Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1160 H H F Cl CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1161 H H F Cl CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3
P1162 H H F Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1163 H H F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1164 H H F Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1165 H H F Cl CF.sub.3 H Br O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1166 H H F Cl CF.sub.3 H Cl O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1167 H H F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
S CH.sub.2CF.sub.3 P1168 H H F Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1169 H H F Cl CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1170 H H F Cl CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1171 H H F Cl CF.sub.3 H CF.sub.3
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1172 H H F Cl CF.sub.3 H
CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1173 H H F Cl CF.sub.3
H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1174 H H F Cl CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1175 H H F Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1176 H H F Cl CF.sub.3
H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1177 H H F Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1178 H H F Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1179 H H F Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1180 H H
F Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1181 H H F Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1182 H H F Cl CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1183 H H F Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1184 H H F Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1185
H H F Cl CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1186 H H F Cl CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1187 H H F Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1188 H H F Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1189 H H F Cl
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1190 H H F Cl
CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1191 H H F Cl
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1192 H
H F Cl CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3
P1193 H H F Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1194 H H F Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1195 H H F Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1196 H H F Cl CF.sub.3 H CH.sub.3 O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1197 H F F F CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CF.sub.3 P1198 H F F F CF.sub.3 H Cl O CH.sub.2
O CH.sub.2CF.sub.3 P1199 H F F F CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1200 H F F F CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1201 H F F F CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1202 H F F F CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1203 H F F F CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1204 H F F F CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1205 H F F F CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1206 H F F F CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1207 H F F F CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1208 H F F F CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1209 H F F F CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1210 H F F F CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1211 H F F F CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1212 H F F F CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1213 H F F F CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1214 H F F F CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1215 H F F F CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1216 H F F F CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1217 H F F F
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1218 H F F F
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1219 H F F F
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1220 H F
F F CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1221
H F F F CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1222 H F F
F CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1223 H F F F
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1224 H F F F
CF.sub.3 H CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1225 H F F F
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1226 H F F
F CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1227 H F
F F CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1228 H F F F CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1229 H F F F CF.sub.2CF.sub.3 H Br O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1230 H F F F CF.sub.2CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1231 H F F F CF.sub.2CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1232 H F F F
CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1233
H F F F CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1234 H F F
F CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1235 H F F F
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1236 H F F F
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1237 H F F F
CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1238 H F F F
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1239 H F F F
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1240 H F F F
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1241 H F F F
CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1242 H F F F
CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1243 H F F F
CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1244 H F F F
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1245 H F F F
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1246 H F F F
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1247 H F F F
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1248 H F F
F CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1249 H F
F F CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1250 H F F
F CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1251 H F F F
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1252 H F
F F CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1253
H F F F CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1254 H F F F CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1255 H F F F CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1256 H F F F CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1257 H F F F
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1258 H F F
F CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1259 H F
F F CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1260 H F F F CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1261 H F F F CF.sub.3 H Br O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1262 H F F F CF.sub.3 H Cl O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1263 H F F F CF.sub.3 H CF.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1264 H F F F CF.sub.3 H
CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1265 H F F F
CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1266 H F F F
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1267 H F F F
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1268 H F
F F CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1269
H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3
P1270 H CF.sub.3 H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1271 H CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1272 H CF.sub.3 H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1273 H CF.sub.3 H CF.sub.3
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P1274 H CF.sub.3 H
CF.sub.3 CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P1275 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1276 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 S CH.sub.2CF.sub.3 P1277 H CF.sub.3 H CF.sub.3 CF.sub.3 H
Br S CH.sub.2 O CH.sub.2CF.sub.3 P1278 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P1279 H CF.sub.3 H
CF.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P1280 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1281 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH.sub.2 O CH.sub.2CHF.sub.2 P1282 H CF.sub.3 H CF.sub.3 CF.sub.3 H
Cl O CH.sub.2 O CH.sub.2CHF.sub.2 P1283 H CF.sub.3 H CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P1284 H CF.sub.3
H CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P1285
H CF.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1286 H CF.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3 Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P1287 H CF.sub.3 H CF.sub.3 CF.sub.3
CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1288 H CF.sub.3 H
CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1289 H CF.sub.3 H CF.sub.3 CF.sub.2CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1290 H CF.sub.3 H CF.sub.3 CF.sub.2CF.sub.3 H Cl
O CH.sub.2 O CH.sub.2CF.sub.3 P1291 H CF.sub.3 H CF.sub.3
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1292 H
CF.sub.3 H CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1293 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1294 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1295 H CF.sub.3 H
CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1296 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1297 H CF.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1298 H CF.sub.3 H CF.sub.3
CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1299 H
CF.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1300 H CF.sub.3 H CF.sub.3 CF.sub.3 CF.sub.3
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1301 H CF.sub.3 H
CF.sub.3 CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1302 H CF.sub.3 H CF.sub.3 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1303 H CF.sub.3 H CF.sub.3 CF.sub.2CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1304 H CF.sub.3 H
CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1305 H CF.sub.3 H CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1306 H CF.sub.3 H CF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1307 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1308 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1309 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1310 H CF.sub.3 H
CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P1311 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1312 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1313 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1314 H CF.sub.3 H
CF.sub.3 CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3
P1315 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1316 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1317 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1318 H CF.sub.3 H
CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P1319 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1320 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1321 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1322 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1323 H CF.sub.3 H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1324 H CF.sub.3 H
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1325 H CF.sub.3 H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1326 H CF.sub.3 H CF.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1327 H CF.sub.3
H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1328 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br
O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1329 H CF.sub.3 H
CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1330 H CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1331 H CF.sub.3 H CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1332
H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1333 H CF.sub.3 H CF.sub.3 CF.sub.3 H Cl O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1334 H CF.sub.3 H CF.sub.3
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1335 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1336 H CF.sub.3 H CF.sub.3 CF.sub.3 H Br O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1337 H CF.sub.3 H CF.sub.3
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1338 H
CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3
P1339 H CF.sub.3 H CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2
O CH.sub.2CF.sub.3 P1340 H F H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1341 H F H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1342 H F H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1343 H F H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1344 H F H CF.sub.3
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P1345 H F H CF.sub.3
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P1346 H F H CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1347 H F H
CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1348 H
F H CF.sub.3 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P1349 H F
H CF.sub.3 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P1350 H F H
CF.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P1351 H
F H CF.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3
P1352 H F H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2
P1353 H F H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2
P1354 H F H CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1355 H F H CF.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P1356 H F H CF.sub.3 CF.sub.3 CF.sub.3
Br O CH.sub.2 O CH.sub.2CF.sub.3 P1357 H F H CF.sub.3 CF.sub.3
CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1358 H F H CF.sub.3
CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1359 H F
H CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1360 H F H CF.sub.3 CF.sub.2CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1361 H F H CF.sub.3 CF.sub.2CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P1362 H F H CF.sub.3 CF.sub.2CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1363 H F H CF.sub.3
CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1364 H F
H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1365 H
F H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1366
H F H CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1367 H F H CF.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1368 H F H CF.sub.3 CF.sub.3
CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1369 H F H CF.sub.3
CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1370 H F H
CF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1371 H F H CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1372 H F H CF.sub.3
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1373 H F H
CF.sub.3 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1374 H F H CF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1375 H F H CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1376 H F H CF.sub.3 CF.sub.3 H Cl
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1377 H F H CF.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1378 H F H CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1379 H F H
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1380 H F
H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1381 H
F H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P1382 H F H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1383 H F H CF.sub.3 CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1384 H F H CF.sub.3 CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1385 H F H CF.sub.3 CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1386 H F H CF.sub.3
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1387 H F H
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1388 H F
H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1389 H
F H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P1390 H F H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1391 H F H CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3)
O CH(CH.sub.3)CF.sub.3 P1392 H F H CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1393 H F H CF.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1394 H F H CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1395 H F
H CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1396 H F H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1397 H F H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1398 H F H CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1399
H F H CF.sub.3 CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1400 H F H CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1401 H F H CF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1402
H F H CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1403 H F H CF.sub.3 CF.sub.3 H Br O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1404 H F H CF.sub.3 CF.sub.3
H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1405 H F H CF.sub.3
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1406 H
F H CF.sub.3 CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1407 H F H CF.sub.3 CF.sub.3 H Br O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1408 H F H CF.sub.3 CF.sub.3 H
Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1409 H F H CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1410 H F
H CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1411 H Cl H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1412 H Cl H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1413 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1414 H Cl H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1415 H Cl H CF.sub.3
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P1416 H Cl H CF.sub.3
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P1417 H Cl H CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1418 H Cl H
CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1419 H
Cl H CF.sub.3 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P1420 H
Cl H CF.sub.3 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P1421 H
Cl H CF.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3
P1422 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1423 H Cl H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1424 H Cl H CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1425 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P1426 H Cl H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CHF.sub.2 P1427 H Cl H CF.sub.3
CF.sub.3 CF.sub.3 Br O CH.sub.2 O CH.sub.2CF.sub.3 P1428 H Cl H
CF.sub.3 CF.sub.3 CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1429 H
Cl H CF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1430 H Cl H CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1431 H Cl H CF.sub.3 CF.sub.2CF.sub.3
H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1432 H Cl H CF.sub.3
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1433 H Cl H
CF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1434 H Cl H CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1435 H Cl H CF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1436 H Cl H CF.sub.3 CF.sub.3 H Cl O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P1437 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1438 H Cl H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1439 H Cl H CF.sub.3
CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1440 H Cl H
CF.sub.3 CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1441 H Cl H CF.sub.3 CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1442 H Cl H CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1443 H Cl H CF.sub.3
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1444 H Cl
H CF.sub.3 CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1445 H Cl H CF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1446 H Cl H CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1447 H Cl H CF.sub.3 CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1448 H Cl H CF.sub.3 CF.sub.3
H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1449 H Cl H CF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1450 H Cl H
CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1451 H Cl H CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1452 H Cl H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3)
S CH.sub.2CF.sub.3 P1453 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1454 H Cl H CF.sub.3 CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1455 H Cl H CF.sub.3
CF.sub.3 H Br S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1456 H Cl H
CF.sub.3 CF.sub.3 H Cl S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1457 H Cl
H CF.sub.3 CF.sub.3 H CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3
P1458 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1459 H Cl H CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3)
O CH.sub.2CHF.sub.2 P1460 H Cl H CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1461 H Cl H CF.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1462 H Cl H CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1463 H Cl H
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1464
H Cl H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1465 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1466 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1467 H Cl H CF.sub.3 CF.sub.3
H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1468 H Cl H
CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1469 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1470 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3
O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1471 H Cl H CF.sub.3
CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1472 H Cl
H CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1473 H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1474 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1475 H Cl H CF.sub.3
CF.sub.3 H Br O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1476 H Cl H
CF.sub.3 CF.sub.3 H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1477
H Cl H CF.sub.3 CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1478 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1479 H Cl H CF.sub.3 CF.sub.3
H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1480 H Cl H CF.sub.3
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1481 H Cl H
CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1482 H Cl H CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1483 H H F CF.sub.3 CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1484 H H F CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1485 H H F CF.sub.3 CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1486 H H F CF.sub.3 CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1487 H H F CF.sub.3
CF.sub.3 H Br O CH.sub.2 S CH.sub.2CF.sub.3 P1488 H H F CF.sub.3
CF.sub.3 H Cl O CH.sub.2 S CH.sub.2CF.sub.3 P1489 H H F CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1490 H H F
CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 S CH.sub.2CF.sub.3 P1491 H
H F CF.sub.3 CF.sub.3 H Br S CH.sub.2 O CH.sub.2CF.sub.3 P1492 H H
F CF.sub.3 CF.sub.3 H Cl S CH.sub.2 O CH.sub.2CF.sub.3 P1493 H H F
CF.sub.3 CF.sub.3 H CF.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3 P1494 H
H F CF.sub.3 CF.sub.3 H CH.sub.3 S CH.sub.2 O CH.sub.2CF.sub.3
P1495 H H F CF.sub.3 CF.sub.3 H Br O CH.sub.2 O CH.sub.2CHF.sub.2
P1496 H H F CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CHF.sub.2
P1497 H H F CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1498 H H F CF.sub.3 CF.sub.3 H CH.sub.3 O
CH.sub.2 O CH.sub.2CHF.sub.2 P1499 H H F CF.sub.3 CF.sub.3 CF.sub.3
Br O CH.sub.2 O CH.sub.2CF.sub.3 P1500 H H F CF.sub.3 CF.sub.3
CF.sub.3 Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1501 H H F CF.sub.3
CF.sub.3 CF.sub.3 CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1502 H H
F CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1503 H H F CF.sub.3 CF.sub.2CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1504 H H F CF.sub.3 CF.sub.2CF.sub.3 H Cl O
CH.sub.2 O CH.sub.2CF.sub.3 P1505 H H F CF.sub.3 CF.sub.2CF.sub.3 H
CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1506 H H F CF.sub.3
CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1507 H H
F CF.sub.3 CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1508 H
H F CF.sub.3 CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1509
H H F CF.sub.3 CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3
P1510 H H F CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1511 H H F CF.sub.3 CF.sub.3 CF.sub.3 Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1512 H H F CF.sub.3 CF.sub.3
CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1513 H H F CF.sub.3
CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1514
H H F CF.sub.3 CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1515 H H F CF.sub.3 CF.sub.2CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1516 H H F CF.sub.3
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1517 H H F
CF.sub.3 CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1518 H H F CF.sub.3 CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1519 H H F CF.sub.3 CF.sub.3 H Br
O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1520 H H F CF.sub.3 CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1521 H H F CF.sub.3 CF.sub.3
H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1522 H H F CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1523 H H F
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1524 H H
F CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1525 H
H F CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3
P1526 H H F CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P1527 H H F CF.sub.3 CF.sub.3 H Br S CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1528 H H F CF.sub.3 CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1529 H H F CF.sub.3 CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1530 H H F CF.sub.3
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1531 H H F
CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1532 H H
F CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1533 H
H F CF.sub.3 CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P1534 H H F CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1535 H H F CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3)
O CH(CH.sub.3)CF.sub.3 P1536 H H F CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1537 H H F CF.sub.3 CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1538 H H F CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1539 H H
F CF.sub.3 CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1540 H H F CF.sub.3 CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1541 H H F CF.sub.3 CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1542 H H F CF.sub.3
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1543
H H F CF.sub.3 CF.sub.3 H Br O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1544 H H F CF.sub.3 CF.sub.3 H Cl O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1545 H H F CF.sub.3
CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1546
H H F CF.sub.3 CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1547 H H F CF.sub.3 CF.sub.3 H Br O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1548 H H F CF.sub.3 CF.sub.3
H Cl O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1549 H H F CF.sub.3
CF.sub.3 H CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1550 H
H F CF.sub.3 CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1551 H H F CF.sub.3 CF.sub.3 H Br O
CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1552 H H F CF.sub.3 CF.sub.3 H
Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1553 H H F CF.sub.3
CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1554 H H
F CF.sub.3 CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1555 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CF.sub.3 P1556 H Cl Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1557 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 S
CH.sub.2CF.sub.3 P1558 H Cl Cl Cl CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1559 H Cl Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1560 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1561 H Cl Cl Cl CF.sub.3 H H S CH.sub.2 O
CH.sub.2CF.sub.3 P1562 H Cl Cl Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1563 H Cl Cl Cl CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1564 H Cl Cl Cl CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1565 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CHF.sub.2 P1566 H Cl Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1567 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1568 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.2F P1569 H Cl Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.2F P1570 H Cl Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.2F P1571 H Cl Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1572 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1573 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.3 P1574 H Cl Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.3 P1575 H Cl Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.3 P1576 H Cl Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1577 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1578 H Cl Cl Cl CF.sub.3 CF.sub.3 H O CH.sub.2 O
CH.sub.2CF.sub.3 P1579 H Cl Cl Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1580 H Cl Cl Cl CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1581 H Cl Cl Cl CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1582 H Cl Cl Cl CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1583 H Cl Cl Cl
CF.sub.2CF.sub.3 H H O CH.sub.2 O CH.sub.2CF.sub.3 P1584 H Cl Cl Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1585 H Cl Cl
Cl CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1586 H Cl
Cl Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1587 H Cl Cl Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1588 H Cl Cl Cl CF.sub.3 H H O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1589 H Cl Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1590 H Cl Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1591 H Cl Cl Cl CF.sub.3 H CF.sub.3 O
CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1592 H Cl Cl Cl CF.sub.3 H
CH.sub.3 O CH.sub.2 O CH(CH.sub.3)CF.sub.3 P1593 H Cl Cl Cl
CF.sub.3 CF.sub.3 H O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1594 H Cl Cl
Cl CF.sub.3 CF.sub.3 Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1595 H
Cl Cl Cl CF.sub.3 CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1596 H Cl Cl Cl CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1597 H Cl Cl Cl CF.sub.3 CF.sub.3 CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1598 H Cl Cl Cl CF.sub.2CF.sub.3 H
H O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1599 H Cl Cl Cl
CF.sub.2CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1600 H Cl
Cl Cl CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1601
H Cl Cl Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1602 H Cl Cl Cl CF.sub.2CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1603 H Cl Cl Cl CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1604 H Cl Cl Cl CF.sub.3 H H O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1605 H Cl Cl Cl CF.sub.3 H H S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1606 H Cl Cl Cl CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1607 H Cl Cl Cl CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1608 H Cl Cl Cl CF.sub.3 H
CF.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1609 H Cl Cl Cl
CF.sub.3 H CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1610 H Cl Cl
Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1611 H Cl Cl Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1612 H Cl Cl Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1613 H Cl Cl Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1614 H Cl
Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1615
H Cl Cl Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1616 H
Cl Cl Cl CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1617 H
Cl Cl Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1618 H
Cl Cl Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F
P1619 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2F P1620 H Cl Cl Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.3 P1621 H Cl Cl Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.3 P1622 H Cl Cl Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.3 P1623 H Cl Cl Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.3 P1624 H Cl Cl Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1625 H Cl Cl Cl
CF.sub.3 H H O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1626 H Cl Cl Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1627 H Cl Cl
Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1628 H Cl
Cl Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1629 H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1630 H Cl Cl Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1631 H Cl Cl Cl CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1632 H Cl Cl Cl CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1633 H Cl Cl Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1634
H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1635 H Cl Cl Cl CF.sub.3 H H O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1636 H Cl Cl Cl CF.sub.3 H
H O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1637 H Cl Cl Cl CF.sub.3
H H O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1638 H Cl Cl Cl CF.sub.3
H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1639 H Cl Cl Cl
CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1640 H Cl Cl
Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1641
H Cl Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1642 H Cl H Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CF.sub.3 P1643 H Cl H Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1644 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1645 H Cl H Cl CF.sub.3 H H O CH.sub.2 S
CH.sub.2CF.sub.3 P1646 H Cl H Cl CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1647 H Cl H Cl CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1648 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1649 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1650 H Cl H Cl CF.sub.3 H H S CH.sub.2 O
CH.sub.2CF.sub.3 P1651 H Cl H Cl CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1652 H Cl H Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1653 H Cl H Cl CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1654 H Cl H Cl CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1655 H Cl H Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CHF.sub.2 P1656 H Cl H Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1657 H Cl H Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1658 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1659 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1660 H Cl H Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.2F P1661 H Cl H Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.2F P1662 H Cl H Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.2F P1663 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1664 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1665 H Cl H Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.3 P1666 H Cl H Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.3 P1667 H Cl H Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.3 P1668 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1669 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1670 H Cl H Cl CF.sub.3 CF.sub.3 H O CH.sub.2 O
CH.sub.2CF.sub.3 P1671 H Cl H Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1672 H Cl H Cl CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1673 H Cl H Cl CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1674 H Cl H Cl CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1675 H Cl H Cl
CF.sub.2CF.sub.3 H H O CH.sub.2 O CH.sub.2CF.sub.3 P1676 H Cl H Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1677 H Cl H Cl
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1678 H Cl H Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1679 H
Cl H Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1680 H Cl H Cl CF.sub.3 H H O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1681 H Cl H Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1682 H Cl H Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1683 H Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1684 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P1685 H Cl H Cl CF.sub.3 CF.sub.3 H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1686 H Cl H Cl CF.sub.3 CF.sub.3
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1687 H Cl H Cl CF.sub.3
CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1688 H Cl H Cl
CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1689
H Cl H Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1690 H Cl H Cl CF.sub.2CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1691 H Cl H Cl CF.sub.2CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1692 H Cl H Cl
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1693 H Cl
H Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1694 H Cl H Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1695 H Cl H Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1696 H Cl H Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1697 H Cl H Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1698 H Cl H Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1699 H Cl H Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1700 H Cl H Cl CF.sub.3 H H O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1701 H Cl H Cl CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1702 H Cl H Cl CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1703 H Cl H Cl CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1704 H Cl H Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1705 H Cl H Cl CF.sub.3
H H S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1706 H Cl H Cl CF.sub.3 H Br
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1707 H Cl H Cl CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1708 H Cl H Cl CF.sub.3 H CF.sub.3
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1709 H Cl H Cl CF.sub.3 H
CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1710 H Cl H Cl CF.sub.3
H H O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1711 H Cl H Cl CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1712 H Cl H Cl CF.sub.3 H Cl
O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1713 H Cl H Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2
P1714 H Cl H Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CHF.sub.2 P1715 H Cl H Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.2F P1716 H Cl H Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CH.sub.2F P1717 H Cl H Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CH.sub.2F P1718 H Cl H Cl CF.sub.3 H CF.sub.3 O
CH(CH.sub.3) O CH.sub.2CH.sub.2F P1719 H Cl H Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1720 H Cl H Cl
CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1721 H Cl H Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1722 H Cl H Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1723 H Cl H Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1724 H Cl H
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1725 H Cl
H Cl CF.sub.3 H H O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1726 H Cl
H Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1727 H Cl
H Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1728 H Cl
H Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1729 H Cl H Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1730 H Cl H Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1731 H Cl H Cl CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1732 H Cl H Cl CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1733 H Cl H Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1734
H Cl H Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1735 H Cl H Cl CF.sub.3 H H O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1736 H Cl H Cl CF.sub.3 H
Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1737 H Cl H Cl
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1738 H Cl
H Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1739 H Cl H Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1740 H Cl H Cl CF.sub.3 H H O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1741 H Cl H Cl CF.sub.3 H Br O C(CH.sub.3).sub.2
O CH.sub.2CF.sub.3 P1742 H Cl H Cl CF.sub.3 H Cl O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1743 H Cl H Cl CF.sub.3 H
CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1744 H Cl H Cl
CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1745 H
Cl H Cl CF.sub.3 H H O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1746 H
Cl H Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1747 H
Cl H Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1748 H
Cl H Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1749 H Cl H Cl CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1750 H H Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CF.sub.3 P1751 H H Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1752 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1753 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1754 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1755 H H Cl Cl CF.sub.3 H H O CH.sub.2 S
CH.sub.2CF.sub.3 P1756 H H Cl Cl CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1757 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1758 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1759 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1760 H H Cl Cl CF.sub.3 H H S CH.sub.2 O
CH.sub.2CF.sub.3 P1761 H H Cl Cl CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1762 H H Cl Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1763 H H Cl Cl CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1764 H H Cl Cl CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1765 H H Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CHF.sub.2 P1766 H H Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1767 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1768 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1769 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1770 H H Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.2F P1771 H H Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.2F P1772 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.2F P1773 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1774 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1775 H H Cl Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.3 P1776 H H Cl Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.3 P1777 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.3 P1778 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1779 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1780 H H Cl Cl CF.sub.3 CF.sub.3 H O CH.sub.2 O
CH.sub.2CF.sub.3 P1781 H H Cl Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1782 H H Cl Cl CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1783 H H Cl Cl CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1784 H H Cl Cl CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1785 H H Cl Cl
CF.sub.2CF.sub.3 H H O CH.sub.2 O CH.sub.2CF.sub.3 P1786 H H Cl Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1787 H H Cl Cl
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1788 H H Cl Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1789 H H
Cl Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1790 H H Cl Cl CF.sub.3 H H O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1791 H H Cl Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1792 H H Cl Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1793 H H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1794 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P1795 H H Cl Cl CF.sub.3 CF.sub.3 H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1796 H H Cl Cl CF.sub.3 CF.sub.3
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1797 H H Cl Cl CF.sub.3
CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1798 H H Cl Cl
CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1799
H H Cl Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1800 H H Cl Cl CF.sub.2CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1801 H H Cl Cl CF.sub.2CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1802 H H Cl Cl
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1803 H H
Cl Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1804 H H Cl Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1805 H H Cl Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1806 H H Cl Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1807 H H Cl Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1808 H H Cl Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1809 H H Cl Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1810 H H Cl Cl CF.sub.3 H H O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1811 H H Cl Cl CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1812 H H Cl Cl CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1813 H H Cl Cl CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1814 H H Cl Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1815 H H Cl Cl CF.sub.3
H H S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1816 H H Cl Cl CF.sub.3 H Br
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1817 H H Cl Cl CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1818 H H Cl Cl CF.sub.3 H CF.sub.3
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1819 H H Cl Cl CF.sub.3 H
CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1820 H H Cl Cl CF.sub.3
H H O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1821 H H Cl Cl CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1822 H H Cl Cl CF.sub.3 H Cl
O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1823 H H Cl Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1824 H H Cl Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1825 H H Cl
Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1826 H H Cl Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1827 H H Cl Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1828 H H Cl Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1829 H H Cl
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1830 H H
Cl Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1831 H H Cl
Cl CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1832 H H Cl Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1833 H H Cl Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1834 H H Cl
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1835 H H
Cl Cl CF.sub.3 H H O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1836 H H
Cl Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1837 H H
Cl Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1838 H H
Cl Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1839 H H Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1840 H H Cl Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1841 H H Cl Cl CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1842 H H Cl Cl CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1843 H H Cl Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1844
H H Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1845 H H Cl Cl CF.sub.3 H H O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1846 H H Cl Cl CF.sub.3 H
Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1847 H H Cl Cl
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1848 H H
Cl Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1849 H H Cl Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1850 v H Cl Cl CF.sub.3 H H O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1851 H H Cl Cl CF.sub.3 H Br O C(CH.sub.3).sub.2
O CH.sub.2CF.sub.3 P1852 H H Cl Cl CF.sub.3 H Cl O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1853 H H Cl Cl CF.sub.3 H
CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1854 H H Cl Cl
CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1855 H
H Cl Cl CF.sub.3 H H O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1856 H
H Cl Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1857 H
H Cl Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1858 H
H Cl Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1859 H H Cl Cl CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1860 H Cl F Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CF.sub.3 P1861 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1862 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1863 H Cl F Cl CF.sub.3 H H O CH.sub.2 S
CH.sub.2CF.sub.3 P1864 H Cl F Cl CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1865 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1866 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1867 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1868 H Cl F Cl CF.sub.3 H H S CH.sub.2 O
CH.sub.2CF.sub.3 P1869 H Cl F Cl CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1870 H Cl F Cl CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1871 H Cl F Cl CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1872 H Cl F Cl CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1873 H Cl F Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CHF.sub.2 P1874 H Cl F Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1875 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1876 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1877 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1878 H Cl F Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.2F P1879 H Cl F Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.2F P1880 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.2F P1881 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1882 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1883 H Cl F Cl CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.3 P1884 H Cl F Cl CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.3 P1885 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.3 P1886 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1887 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1888 H Cl F Cl CF.sub.3 CF.sub.3 H O CH.sub.2 O
CH.sub.2CF.sub.3 P1889 H Cl F Cl CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1890 H Cl F Cl CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1891 H Cl F Cl CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P1892 H Cl F Cl CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1893 H Cl F Cl
CF.sub.2CF.sub.3 H H O CH.sub.2 O CH.sub.2CF.sub.3 P1894 H Cl F Cl
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P1895 H Cl F Cl
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P1896 H Cl F Cl
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P1897 H
Cl F Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P1898 H Cl F Cl CF.sub.3 H H O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1899 H Cl F Cl CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1900 H Cl F Cl CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P1901 H Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P1902 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P1903 H Cl F Cl CF.sub.3 CF.sub.3 H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1904 H Cl F Cl CF.sub.3 CF.sub.3
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1905 H Cl F Cl CF.sub.3
CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1906 H Cl F Cl
CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1907
H Cl F Cl CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1908 H Cl F Cl CF.sub.2CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1909 H Cl F Cl CF.sub.2CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1910 H Cl F Cl
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P1911 H Cl
F Cl CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P1912 H Cl F Cl CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1913 H Cl F Cl CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1914 H Cl F Cl CF.sub.3 H Br O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1915 H Cl F Cl CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P1916 H Cl F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
O CH.sub.2CF.sub.3 P1917 H Cl F Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1918 H Cl F Cl CF.sub.3 H H O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1919 H Cl F Cl CF.sub.3 H Br O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1920 H Cl F Cl CF.sub.3 H Cl O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P1921 H Cl F Cl CF.sub.3 H CF.sub.3
O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1922 H Cl F Cl CF.sub.3 H
CH.sub.3 O CH(CH.sub.3) S CH.sub.2CF.sub.3 P1923 H Cl F Cl CF.sub.3
H H S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1924 H Cl F Cl CF.sub.3 H Br
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1925 H Cl F Cl CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P1926 H Cl F Cl CF.sub.3 H CF.sub.3
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1927 H Cl F Cl CF.sub.3 H
CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P1928 H Cl F Cl CF.sub.3
H H O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1929 H Cl F Cl CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1930 H Cl F Cl CF.sub.3 H Cl
O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1931 H Cl F Cl CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1932 H Cl F Cl
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P1933 H Cl F
Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1934 H Cl F Cl
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1935 H Cl F Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1936 H Cl F Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1937 H Cl F
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P1938 H
Cl F Cl CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1939 H Cl F
Cl CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1940 H Cl F Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1941 H Cl F Cl
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1942 H Cl F
Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P1943 H Cl
F Cl CF.sub.3 H H O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1944 H Cl
F Cl CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1945 H Cl F Cl CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P1946 H Cl F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P1947 H Cl F Cl CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P1948 H Cl F Cl CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1949 H Cl F Cl CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1950 H Cl F Cl
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P1951 H Cl
F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3
P1952 H Cl F Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P1953 H Cl F Cl CF.sub.3 H H O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1954 H Cl F Cl CF.sub.3 H
Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1955 H Cl F Cl
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P1956 H Cl
F Cl CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P1957 H Cl F Cl CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P1958 H Cl F Cl CF.sub.3 H H O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P1959 H Cl F Cl CF.sub.3 H Br O C(CH.sub.3).sub.2
O CH.sub.2CF.sub.3 P1960 H Cl F Cl CF.sub.3 H Cl O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1961 H Cl F Cl CF.sub.3 H
CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1962 H Cl F Cl
CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P1963 H
Cl F Cl CF.sub.3 H H O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1964 H
Cl F Cl CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1965 H
Cl F Cl CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P1966 H
Cl F Cl CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P1967 H Cl F Cl CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3 P1968 H Br H Br CF.sub.3 H H O CH.sub.2 O
CH.sub.2CF.sub.3 P1969 H Br H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CF.sub.3 P1970 H Br H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P1971 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1972 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CF.sub.3 P1973 H Br H Br CF.sub.3 H H O CH.sub.2 S
CH.sub.2CF.sub.3 P1974 H Br H Br CF.sub.3 H Br O CH.sub.2 S
CH.sub.2CF.sub.3 P1975 H Br H Br CF.sub.3 H Cl O CH.sub.2 S
CH.sub.2CF.sub.3 P1976 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1977 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2 S
CH.sub.2CF.sub.3 P1978 H Br H Br CF.sub.3 H H S CH.sub.2 O
CH.sub.2CF.sub.3 P1979 H Br H Br CF.sub.3 H Br S CH.sub.2 O
CH.sub.2CF.sub.3 P1980 H Br H Br CF.sub.3 H Cl S CH.sub.2 O
CH.sub.2CF.sub.3 P1981 H Br H Br CF.sub.3 H CF.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1982 H Br H Br CF.sub.3 H CH.sub.3 S CH.sub.2 O
CH.sub.2CF.sub.3 P1983 H Br H Br CF.sub.3 H H O CH.sub.2 O
CH.sub.2CHF.sub.2 P1984 H Br H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CHF.sub.2 P1985 H Br H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CHF.sub.2 P1986 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1987 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CHF.sub.2 P1988 H Br H Br CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.2F P1989 H Br H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.2F P1990 H Br H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.2F P1991 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1992 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.2F P1993 H Br H Br CF.sub.3 H H O CH.sub.2 O
CH.sub.2CH.sub.3 P1994 H Br H Br CF.sub.3 H Br O CH.sub.2 O
CH.sub.2CH.sub.3 P1995 H Br H Br CF.sub.3 H Cl O CH.sub.2 O
CH.sub.2CH.sub.3 P1996 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1997 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2 O
CH.sub.2CH.sub.3 P1998 H Br H Br CF.sub.3 CF.sub.3 H O CH.sub.2 O
CH.sub.2CF.sub.3 P1999 H Br H Br CF.sub.3 CF.sub.3 Br O CH.sub.2 O
CH.sub.2CF.sub.3 P2000 H Br H Br CF.sub.3 CF.sub.3 Cl O CH.sub.2 O
CH.sub.2CF.sub.3 P2001 H Br H Br CF.sub.3 CF.sub.3 CF.sub.3 O
CH.sub.2 O CH.sub.2CF.sub.3 P2002 H Br H Br CF.sub.3 CF.sub.3
CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P2003 H Br H Br
CF.sub.2CF.sub.3 H H O CH.sub.2 O CH.sub.2CF.sub.3 P2004 H Br H Br
CF.sub.2CF.sub.3 H Br O CH.sub.2 O CH.sub.2CF.sub.3 P2005 H Br H Br
CF.sub.2CF.sub.3 H Cl O CH.sub.2 O CH.sub.2CF.sub.3 P2006 H Br H Br
CF.sub.2CF.sub.3 H CF.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3 P2007 H
Br H Br CF.sub.2CF.sub.3 H CH.sub.3 O CH.sub.2 O CH.sub.2CF.sub.3
P2008 H Br H Br CF.sub.3 H H O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P2009 H Br H Br CF.sub.3 H Br O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P2010 H Br H Br CF.sub.3 H Cl O CH.sub.2 O CH(CH.sub.3)CF.sub.3
P2011 H Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2 O
CH(CH.sub.3)CF.sub.3 P2012 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2
O CH(CH.sub.3)CF.sub.3 P2013 H Br H Br CF.sub.3 CF.sub.3 H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P2014 H Br H Br CF.sub.3 CF.sub.3
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P2015 H Br H Br CF.sub.3
CF.sub.3 Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P2016 H Br H Br
CF.sub.3 CF.sub.3 CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3 P2017
H Br H Br CF.sub.3 CF.sub.3 CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P2018 H Br H Br CF.sub.2CF.sub.3 H H O
CH(CH.sub.3) O CH.sub.2CF.sub.3 P2019 H Br H Br CF.sub.2CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CF.sub.3 P2020 H Br H Br
CF.sub.2CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CF.sub.3 P2021 H Br
H Br CF.sub.2CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CF.sub.3
P2022 H Br H Br CF.sub.2CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P2023 H Br H Br CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P2024 H Br H Br CF.sub.3 H Cl O CH(CH.sub.3) O
CH.sub.2CF.sub.3 P2025 H Br H Br CF.sub.3 H H O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P2026 H Br H Br CF.sub.3 H Br O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P2027 H Br H Br CF.sub.3 H Cl O CH(CH.sub.3) S
CH.sub.2CF.sub.3 P2028 H Br H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3)
S CH.sub.2CF.sub.3 P2029 H Br H Br CF.sub.3 H CH.sub.3 O
CH(CH.sub.3) S CH.sub.2CF.sub.3 P2030 H Br H Br CF.sub.3 H H S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P2031 H Br H Br CF.sub.3 H Br S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P2032 H Br H Br CF.sub.3 H Cl S
CH(CH.sub.3) O CH.sub.2CF.sub.3 P2033 H Br H Br CF.sub.3 H CF.sub.3
S CH(CH.sub.3) O CH.sub.2CF.sub.3 P2034 H Br H Br CF.sub.3 H
CH.sub.3 S CH(CH.sub.3) O CH.sub.2CF.sub.3 P2035 H Br H Br CF.sub.3
H H O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P2036 H Br H Br CF.sub.3 H
Br O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P2037 H Br H Br CF.sub.3 H Cl
O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P2038 H Br H Br CF.sub.3 H
CF.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P2039 H Br H Br
CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CHF.sub.2 P2040 H Br H
Br CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.2F P2041 H Br H Br
CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.2F P2042 H Br H Br
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2F P2043 H Br H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P2044 H Br H
Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2F P2045 H
Br H Br CF.sub.3 H H O CH(CH.sub.3) O CH.sub.2CH.sub.3 P2046 H Br H
Br CF.sub.3 H Br O CH(CH.sub.3) O CH.sub.2CH.sub.3 P2047 H Br H Br
CF.sub.3 H Cl O CH(CH.sub.3) O CH.sub.2CH.sub.3 P2048 H Br H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P2049 H Br H
Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.3 P2050 H Br
H Br CF.sub.3 H H O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P2051 H Br
H Br CF.sub.3 H Br O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P2052 H Br
H Br CF.sub.3 H Cl O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3 P2053 H Br
H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH(CH.sub.3)CF.sub.3
P2054 H Br H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH(CH.sub.3)CF.sub.3 P2055 H Br H Br CF.sub.3 H H O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P2056 H Br H Br CF.sub.3 H Br O
CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P2057 H Br H Br CF.sub.3 H
Cl O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P2058 H Br H Br
CF.sub.3 H CF.sub.3 O CH(CH.sub.3) O CH.sub.2CH.sub.2CF.sub.3 P2059
H Br H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.3) O
CH.sub.2CH.sub.2CF.sub.3 P2060 H Br H Br CF.sub.3 H H O
CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P2061 H Br H Br CF.sub.3 H
Br O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P2062 H Br H Br
CF.sub.3 H Cl O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3 P2063 H Br
H Br CF.sub.3 H CF.sub.3 O CH(CH.sub.2CH.sub.3) O CH.sub.2CF.sub.3
P2064 H Br H Br CF.sub.3 H CH.sub.3 O CH(CH.sub.2CH.sub.3) O
CH.sub.2CF.sub.3 P2065 H Br H Br CF.sub.3 H H O C(CH.sub.3).sub.2 O
CH.sub.2CF.sub.3 P2066 H Br H Br CF.sub.3 H Br O C(CH.sub.3).sub.2
O CH.sub.2CF.sub.3 P2067 H Br H Br CF.sub.3 H Cl O
C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P2068 H Br H Br CF.sub.3 H
CF.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P2069 H Br H Br
CF.sub.3 H CH.sub.3 O C(CH.sub.3).sub.2 O CH.sub.2CF.sub.3 P2070 H
Br H Br CF.sub.3 H H O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P2071 H
Br H Br CF.sub.3 H Br O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P2072 H
Br H Br CF.sub.3 H Cl O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3 P2073 H
Br H Br CF.sub.3 H CF.sub.3 O CH.sub.2CH.sub.2 O CH.sub.2CF.sub.3
P2074 H Br H Br CF.sub.3 H CH.sub.3 O CH.sub.2CH.sub.2 O
CH.sub.2CF.sub.3
Example A: Bioassays on Beet Armyworm ("BAW") and Corn Earworm
("CEW") and Cabbage Looper ("CL")
[1084] BAW has few effective parasites, diseases, or predators to
lower its population. BAW infests many weeds, trees, grasses,
legumes, and field crops. In various places, it is of economic
concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa,
sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers,
and citrus, among other plants. CEW is known to attack corn and
tomatoes, but it also attacks artichoke, asparagus, cabbage,
cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima
beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans,
spinach, squash, sweet potatoes, and watermelon, among other
plants. CEW is also known to be resistant to certain insecticides.
CL is also known to be resistant to certain insecticides.
Consequently, because of the above factors control of these pests
is important. Furthermore, molecules that control these pests are
useful in controlling other pests.
[1085] Certain molecules disclosed in this document were tested
against BAW, CEW and CL using procedures described in the following
examples. In the reporting of the results, the "BAW & CEW &
CL Rating Table" was used (See Table Section).
Bioassays on BAW (Spodoptera exigua)
[1086] Bioassays on BAW were conducted using a 128-well diet tray
assay. One to five second instar BAW larvae were placed in each
well (3 mL) of the diet tray that had been previously filled with 1
mL of artificial diet to which 50 .mu.g/cm.sup.2 of the test
compound (dissolved in 50 .mu.L of 90:10 acetone-water mixture) had
been applied (to each of eight wells) and then allowed to dry.
Trays were covered with a clear self-adhesive cover, and held at
25.degree. C., 14:10 light-dark for five to seven days. Percent
mortality was recorded for the larvae in each well; activity in the
eight wells was then averaged. The results are indicated in the
tables entitled "Table 3: Assay Results Part 1" and "Table 4: Assay
Results Part 2" (See Table Section).
Bioassays on CEW (Helicoverpa zea)
[1087] Bioassays on CEW were conducted using a 128-well diet tray
assay. One to five second instar CEW larvae were placed in each
well (3 mL) of the diet tray that had been previously filled with 1
mL of artificial diet to which 50 .mu.g/cm.sup.2 of the test
compound (dissolved in 50 .mu.L of 90:10 acetone-water mixture) had
been applied (to each of eight wells) and then allowed to dry.
Trays were covered with a clear self-adhesive cover, and held at
25.degree. C., 14:10 light-dark for five to seven days. Percent
mortality was recorded for the larvae in each well; activity in the
eight wells was then averaged. The results are indicated in the
table entitled "Table 3: Assay Results Part 1" (See Table
Section).
Bioassays on CL (Trichoplusia ni)
[1088] Bioassays on CL were conducted using a 128-well diet tray
assay. One to five second instar CL larvae were placed in each well
(3 mL) of the diet tray that had been previously filled with 1 mL
of artificial diet to which 50 .mu.g/cm.sup.2 of the test compound
(dissolved in 50 .mu.L of 90:10 acetone-water mixture) had been
applied (to each of eight wells) and then allowed to dry. Trays
were covered with a clear self-adhesive cover, and held at
25.degree. C., 14:10 light-dark for five to seven days. Percent
mortality was recorded for the larvae in each well; activity in the
eight wells was then averaged. The results are indicated in the
table entitled "Table 4: Assay Results Part 2" (See Table
Section).
Example B: Bioassays on Green Peach Aphid ("GPA") (Myzus
persicae)
[1089] GPA is the most significant aphid pest of peach trees,
causing decreased growth, shriveling of the leaves, and the death
of various tissues. It is also hazardous because it acts as a
vector for the transport of plant viruses, such as potato virus Y
and potato leafroll virus to members of the nightshade/potato
family Solanaceae, and various mosaic viruses to many other food
crops. GPA attacks such plants as broccoli, burdock, cabbage,
carrot, cauliflower, daikon, eggplant, green beans, lettuce,
macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress,
and zucchini, among other plants. GPA also attacks many ornamental
crops such as carnation, chrysanthemum, flowering white cabbage,
poinsettia, and roses. GPA has developed resistance to many
pesticides.
[1090] Certain molecules disclosed in this document were tested
against GPA using procedures described in the following example. In
the reporting of the results, the "GPA Rating Table" was used (See
Table Section).
[1091] Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5
cm) true leaves, were used as test substrate. The seedlings were
infested with 20-50 GPA (wingless adult and nymph stages) one day
prior to chemical application. Four pots with individual seedlings
were used for each treatment. Test compounds (2 mg) were dissolved
in 2 mL of acetone/MeOH (1:1) solvent, forming stock solutions of
1000 ppm test compound. The stock solutions were diluted 5.times.
with 0.025% Tween 20 in water to obtain the solution at 200 ppm
test compound. A hand-held aspirator-type sprayer was used for
spraying a solution to both sides of cabbage leaves until runoff.
Reference plants (solvent check) were sprayed with the diluent only
containing 20% by volume of acetone/MeOH (1:1) solvent. Treated
plants were held in a holding room for three days at approximately
25.degree. C. and ambient relative humidity (RH) prior to grading.
Evaluation was conducted by counting the number of live aphids per
plant under a microscope. Percent Control was measured by using
Abbott's correction formula (W. S. Abbott, "A Method of Computing
the Effectiveness of an Insecticide" J. Econ. Entomol. 18 (1925),
pp. 265-267) as follows.
Corrected % Control=100*(X-Y)/X [1092] where [1093] X=No. of live
aphids on solvent check plants and [1094] Y=No. of live aphids on
treated plants
[1095] The results are indicated in the tables entitled "Table 3:
Assay Results Part 1" and "Table 4: Assay Results Part 2" (See
Table Section).
Pesticidally Acceptable Acid Addition Salts, Salt Derivatives,
Solvates, Ester Derivatives, Polymorphs, Isotopes and
Radionuclides
[1096] Molecules of Formula One may be formulated into pesticidally
acceptable acid addition salts. By way of a non-limiting example,
an amine function can form salts with hydrochloric, hydrobromic,
sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic,
malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic,
ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic,
ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic
acids. Additionally, by way of a non-limiting example, an acid
function can form salts including those derived from alkali or
alkaline earth metals and those derived from ammonia and amines.
Examples of preferred cations include sodium, potassium, and
magnesium.
[1097] Molecules of Formula One may be formulated into salt
derivatives. By way of a non-limiting example, a salt derivative
can be prepared by contacting a free base with a sufficient amount
of the desired acid to produce a salt. A free base may be
regenerated by treating the salt with a suitable dilute aqueous
base solution such as dilute aqueous NaOH, potassium carbonate,
ammonia, and sodium bicarbonate. As an example, in many cases, a
pesticide, such as 2,4-D, is made more water-soluble by converting
it to its dimethylamine salt.
[1098] Molecules of Formula One may be formulated into stable
complexes with a solvent, such that the complex remains intact
after the non-complexed solvent is removed. These complexes are
often referred to as "solvates." However, it is particularly
desirable to form stable hydrates with water as the solvent.
[1099] Molecules of Formula One may be made into ester derivatives.
These ester derivatives can then be applied in the same manner as
the invention disclosed in this document is applied.
[1100] Molecules of Formula One may be made as various crystal
polymorphs. Polymorphism is important in the development of
agrochemicals since different crystal polymorphs or structures of
the same molecule can have vastly different physical properties and
biological performances.
[1101] Molecules of Formula One may be made with different
isotopes. Of particular importance are molecules having .sup.2H
(also known as deuterium) in place of .sup.1H.
[1102] Molecules of Formula One may be made with different
radionuclides. Of particular importance are molecules having
.sup.14C.
Stereoisomers
[1103] Molecules of Formula One may exist as one or more
stereoisomers. Thus, certain molecules can be produced as racemic
mixtures. It will be appreciated by those skilled in the art that
one stereoisomer may be more active than the other stereoisomers.
Individual stereoisomers may be obtained by known selective
synthetic procedures, by conventional synthetic procedures using
resolved starting materials, or by conventional resolution
procedures. Certain molecules disclosed in this document can exist
as two or more isomers. The various isomers include geometric
isomers, diastereomers, and enantiomers. Thus, the molecules
disclosed in this document include geometric isomers, racemic
mixtures, individual stereoisomers, and optically active mixtures.
It will be appreciated by those skilled in the art that one isomer
may be more active than the others. The structures disclosed in the
present disclosure are drawn in only one geometric form for
clarity, but are intended to represent all geometric forms of the
molecule.
Combinations
[1104] Molecules of Formula One may also be used in combination
(such as, in a compositional mixture, or a simultaneous or
sequential application) with one or more compounds having
acaricidal, algicidal, avicidal, bactericidal, fungicidal,
herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal,
or virucidal properties. Additionally, the molecules of Formula One
may also be used in combination (such as, in a compositional
mixture, or a simultaneous or sequential application) with
compounds that are antifeedants, bird repellents, chemosterilants,
herbicide safeners, insect attractants, insect repellents, mammal
repellents, mating disrupters, plant activators, plant growth
regulators, or synergists. Examples of such compounds in the above
groups that may be used with the Molecules of Formula One are
-(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,
1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol,
2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,
2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,
2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl,
2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB,
2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl,
2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,
2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,
2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,
2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,
2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,
2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,
2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,
2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP,
2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl,
2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium,
2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl,
2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl,
2,4-D-tetradecylammonium, 2,4-D-triethylammonium,
2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,
2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB,
3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium,
4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline
sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid,
ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor,
acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl,
acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen,
acrep, acrinathrin, acrolein, acrylonitrile, acypetacs,
acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole,
aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin,
allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl
alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan,
ametoctradin, ametridione, ametryn, amibuzin, amicarbazone,
amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb,
aminocyclopyrachlor, aminocyclopyrachlor-methyl,
aminocyclopyrachlor-potassium, aminopyralid,
aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium,
amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate,
amitraz, amitrole, ammonium sulfamate, ammonium
.alpha.-naphthaleneacetate, amobam, ampropylfos, anabasine,
ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu,
apholate, aramite, arsenous oxide, asomate, aspirin, asulam,
asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,
aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,
azadirachtin, azafenidin, azamethiphos, azimsulfuron,
azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram,
azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh,
barban, barium hexafluorosilicate, barium polysulfide, barthrin,
BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin,
benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium,
bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb,
benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox,
bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron,
bentazone, bentazone-sodium, benthiavalicarb,
benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,
benzadox-ammonium, benzalkonium chloride, benzamacril,
benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,
benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,
benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl
benzoate, benzyladenine, berberine, berberine chloride,
beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone,
bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos,
bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin,
bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir,
bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron,
bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux
mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl,
brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil,
bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin,
bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide,
bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl,
bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate,
bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,
brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb,
buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan,
butacarb, butachlor, butafenacil, butamifos, butathiofos,
butenachlor, butethrin, buthidazole, buthiobate, buthiuron,
butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,
butroxydim, buturon, butylamine, butylate, cacodylic acid,
cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium
cyanamide, calcium polysulfide, calvinphos, cambendichlor,
camphechlor, camphor, captafol, captan, carbamorph, carbanolate,
carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate,
carbendazim sulfite, carbetamide, carbofuran, carbon disulfide,
carbon tetrachloride, carbophenothion, carbosulfan, carboxazole,
carboxide, carboxin, carfentrazone, carfentrazone-ethyl,
carpropamid, cartap, cartap hydrochloride, carvacrol, carvone,
CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat,
chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben,
chloramben-ammonium, chloramben-diolamine, chloramben-methyl,
chloramben-methylammonium, chloramben-sodium, chloramine
phosphorus, chloramphenicol, chloraniformethan, chloranil,
chloranocryl, chlorantraniliprole, chlorazifop,
chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron,
chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone,
chlordimeform, chlordimeform hydrochloride, chlorempenthrin,
chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium,
chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol,
chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos,
chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl,
chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron,
chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride,
chlornidine, chlornitrofen, chlorobenzilate,
chlorodinitronaphthalenes, chloroform, chloromebuform,
chloromethiuron, chloroneb, chlorophacinone,
chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate,
chlorothalonil, chlorotoluron, chloroxuron, chloroxynil,
chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos,
chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl,
chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl,
chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate,
choline chloride, chromafenozide, cinerin I, cinerin II, cinerins,
cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide,
cismethrin, clethodim, climbazole, cliodinate, clodinafop,
clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,
clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,
clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,
clopyralid-olamine, clopyralid-potassium,
clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,
cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,
clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,
codlelure, colophonate, copper acetate, copper acetoarsenite,
copper arsenate, copper carbonate, basic, copper hydroxide, copper
naphthenate, copper oleate, copper oxychloride, copper silicate,
copper sulfate, copper zinc chromate, coumachlor, coumafuryl,
coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF,
CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos,
crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam,
cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine,
cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid,
cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate,
cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron,
cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid,
cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin,
cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil,
cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat
chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole,
cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine,
cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium,
dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium,
DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin,
decarbofuran, dehydroacetic acid, delachlor, deltamethrin,
demephion, demephion-O, demephion-S, demeton, demeton-methyl,
demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl,
demeton-S-methylsulphon, desmedipham, desmetryn,
d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate,
diamidafos, diatomaceous earth, diazinon, dibutyl phthalate,
dibutyl succinate, dicamba, dicamba-diglycolamine,
dicamba-dimethylammonium, dicamba-diolamine,
dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine,
dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon,
dichlobenil, dichlofenthion, dichlofluanid, dichlone,
dichloralurea, dichlorbenzuron, dichlorflurenol,
dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen,
dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl,
dichlorprop-dimethylammonium, dichlorprop-ethylammonium,
dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,
dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,
dichlorprop-potassium, dichlorprop-sodium, dichlorvos,
dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl,
diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol,
dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon,
dieldrin, dienochlor, diethamquat, diethamquat dichloride,
diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl
pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,
difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat,
difenzoquat metilsulfate, difethialone, diflovidazin,
diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,
diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif,
dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone,
dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid,
dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph,
dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos,
dimetilan, dimexano, dimidazon, dimoxystrobin, dinex,
dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M,
dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton,
dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb
acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,
dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb
acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb,
dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl
sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione,
diquat, diquat dibromide, disparlure, disul, disulfiram,
disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos,
dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC,
DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph
acetate, dodemorph benzoate, dodicin, dodicin hydrochloride,
dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin,
drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos,
eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC,
empenthrin, endosulfan, endothal, endothal-diammonium,
endothal-dipotassium, endothal-disodium, endothion, endrin,
enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,
eprinomectin, epronaz, EPTC, erbon, ergocalciferol,
erlujixiancaoan, esdepallthrine, esfenvalerate, esprocarb,
etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor,
ethalfluralin, ethametsulfuron, ethametsulfuron-methyl,
ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate,
ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl,
ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,
ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl
formate, ethyl .alpha.-naphthaleneacetate, ethyl-DDD, ethylene,
ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin,
ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate,
ethylmercury bromide, ethylmercury chloride, ethylmercury
phosphate, etinofen, etnipromid, etobenzanid, etofenprox,
etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone,
famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil,
fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,
fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,
fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid,
fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop,
fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl,
fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl,
fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil,
fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl,
fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin,
fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,
fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,
fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,
fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,
fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,
fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil,
flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl,
flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron,
flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim,
fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P,
fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide,
flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron,
fluchloralin, flucofuron, flucycloxuron, flucythrinate,
fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,
flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,
flufiprole, flumethrin, flumetover, flumetralin, flumetsulam,
flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin,
flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram,
fluorbenside, fluoridamid, fluoroacetamide, fluorodifen,
fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine,
fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin,
flupoxam, flupropacil, flupropadine, flupropanate,
flupropanate-sodium, flupyradifurone, flupyrsulfuron,
flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium,
fluquinconazole, flurazole, flurenol, flurenol-butyl,
flurenol-methyl, fluridone, flurochloridone, fluroxypyr,
fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid,
flurtamone, flusilazole, flusulfamide, fluthiacet,
fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate,
fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium,
fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,
formetanate hydrochloride, formothion, formparanate, formparanate
hydrochloride, fosamine, fosamine-ammonium, fosetyl,
fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,
frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,
fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,
furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,
furfural, furilazole, furmecyclox, furophanate, furyloxyfen,
gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid,
gibberellins, gliftor, glufosinate, glufosinate-ammonium,
glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium,
glyodin, glyoxime, glyphosate, glyphosate-diammonium,
glyphosate-dimethylammonium, glyphosate-isopropylammonium,
glyphosate-monoammonium, glyphosate-potassium,
glyphosate-sesquisodium, glyphosate-trimesium, glyphosine,
gossyplure, grandlure, griseofulvin, guazatine, guazatine
acetates, halacrinate, halfenprox, halofenozide, halosafen,
halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,
haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P,
haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH,
hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil,
heterophos, hexachloroacetone, hexachlorobenzene,
hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron,
hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos,
hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,
hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,
hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,
imazalil nitrate, imazalil sulfate, imazamethabenz,
imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,
imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,
imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium,
imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole,
imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine
triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide,
indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb,
iodomethane, iodosulfuron, iodosulfuron-methyl,
iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium,
ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium,
ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione,
iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos,
isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin,
isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron,
isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon,
isopyrazam, isopyrimol, isothioate, isotianil, isouron,
isovaledione, isoxaben, isoxachlortole, isoxadifen,
isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion,
ivermectin, izopamfos, j aponilure, j apothrins, j asmolin I, j
asmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin,
jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone
I, juvenile hormone II, juvenile hormone III, kadethrin,
karbutilate, karetazan, karetazan-potassium, kasugamycin,
kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,
ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl,
kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate,
lenacil, lepimectin, leptophos, lindane, lineatin, linuron,
lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin,
lythidathion, MAA, malathion, maleic hydrazide, malonoben,
maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb,
matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl,
MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl,
MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl,
MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,
MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium,
mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop,
mecoprop-2-ethylhexyl, mecoprop-dimethylammonium,
mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl,
mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,
mecoprop-P-dimethylammonium, mecoprop-P-isobutyl,
mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium,
mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate,
medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide,
mefluidide-diolamine, mefluidide-potassium, megatomoic acid,
menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan,
mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil,
meptyldinocap, mercuric chloride, mercuric oxide, mercurous
chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl,
mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl,
metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,
metamitron, metam-potassium, metam-sodium, metazachlor,
metazosulfuron, metazoxolon, metconazole, metepa, metflurazon,
methabenzthiazuron, methacrifos, methalpropalin, methamidophos,
methasulfocarb, methazole, methfuroxam, methidathion,
methiobencarb, methiocarb, methiopyrisulfuron, methiotepa,
methiozolin, methiuron, methocrotophos, methometon, methomyl,
methoprene, methoprotryne, methoquin-butyl, methothrin,
methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate,
methyl bromide, methyl eugenol, methyl iodide, methyl
isothiocyanate, methylacetophos, methylchloroform, methyldymron,
methylene chloride, methylmercury benzoate, methylmercury
dicyandiamide, methylmercury pentachlorophenoxide,
methylneodecanamide, metiram, metobenzuron, metobromuron,
metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam,
metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax,
metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan,
milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF,
moguchun, molinate, molosultap, monalide, monisouron,
monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,
monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat
dichloride, moroxydine, moroxydine hydrochloride, morphothion,
morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin,
N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,
naphthalene, naphthaleneacetamide, naphthalic anhydride,
naphthoxyacetic acids, naproanilide, napropamide, naptalam,
naptalam-sodium, natamycin, neburon, niclosamide,
niclosamide-olamine, nicosulfuron, nicotine, nifluridide,
nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,
nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene,
nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron,
novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether,
octhilinone, ofurace, omethoate, orbencarb, orfralure,
ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin,
oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon,
oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine,
oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper,
oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin,
oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,
oxymatrine, oxytetracycline, oxytetracycline hydrochloride,
paclobutrazol, paichongding, para-dichlorobenzene, parafluron,
paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,
parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,
penconazole, pencycuron, pendimethalin, penflufen, penfluron,
penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad,
pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid,
phenamacril, phenazine oxide, phenisopham, phenkapton,
phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin,
phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate,
phenylmercury chloride, phenylmercury derivative of pyrocatechol,
phenylmercury nitrate, phenylmercury salicylate, phorate,
phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,
phosglycin, phosmet, phosnichlor, phosphamidon, phosphine,
phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide,
picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,
picloram-olamine, picloram-potassium, picloram-triethylammonium,
picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,
pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,
piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,
piprotal, pirimetaphos, pirimicarb, pirimioxyphos,
pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate,
polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium
arsenite, potassium azide, potassium cyanate, potassium
gibberellate, potassium naphthenate, potassium polysulfide,
potassium thiocyanate, potassium .alpha.-naphthaleneacetate,
pp'-DDT, prallethrin, precocene I, precocene II, precocene III,
pretilachlor, primidophos, primisulfuron, primisulfuron-methyl,
probenazole, prochloraz, prochloraz-manganese, proclonol,
procyazine, procymidone, prodiamine, profenofos, profluazol,
profluralin, profluthrin, profoxydim, proglinazine,
proglinazine-ethyl, prohexadione, prohexadione-calcium,
prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit,
propachlor, propamidine, propamidine dihydrochloride, propamocarb,
propamocarb hydrochloride, propanil, propaphos, propaquizafop,
propargite, proparthrin, propazine, propetamphos, propham,
propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,
propoxycarbazone-sodium, propyl isome, propyrisulfuron,
propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb,
prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride,
prothioconazole, prothiofos, prothoate, protrifenbute, proxan,
proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,
pyraclofos, pyraclonil, pyraclostrobin, pyraflufen,
pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin,
pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos,
pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen,
pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins,
pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,
pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol,
pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox,
pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen,
pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate,
pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen,
pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon,
pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,
quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,
quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,
quinonamid, quinothion, quinoxyfen, quintiofos, quintozene,
quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,
quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole,
rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III,
ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao,
saisentong, salicylanilide, sanguinarine, santonin, schradan,
scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,
semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim,
shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica
gel, silthiofam, simazine, simeconazole, simeton, simetryn,
sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium
chlorate, sodium fluoride, sodium fluoroacetate, sodium
hexafluorosilicate, sodium naphthenate, sodium
orthophenylphenoxide, sodium pentachlorophenoxide, sodium
polysulfide, sodium thiocyanate, sodium .alpha.-naphthaleneacetate,
sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,
spirotetramat, spiroxamine, streptomycin, streptomycin
sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium,
sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid,
sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep,
sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl
fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate,
tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl,
TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,
tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,
tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,
tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,
terallethrin, terbacil, terbucarb, terbuchlor, terbufos,
terbumeton, terbuthylazine, terbutryn, tetcyclacis,
tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon,
tetrafluron, tetramethrin, tetramethylfluthrin, tetramine,
tetranactin, tetrasul, thallium sulfate, thenylchlor,
theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor,
thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos,
thicyofen, thidiazimin, thidiazuron, thiencarbazone,
thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl,
thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim,
thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate,
thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,
thiohempa, thiomersal, thiometon, thionazin, thiophanate,
thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,
thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,
thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,
tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,
tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,
tralocythrin, tralomethrin, tralopyril, transfluthrin,
transpermethrin, tretamine, triacontanol, triadimefon, triadimenol,
triafamone, tri-allate, triamiphos, triapenthenol, triarathene,
triarimol, triasulfuron, triazamate, triazbutil, triaziflam,
triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos,
tributyltin oxide, tricamba, trichlamide, trichlorfon,
trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl,
triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole,
tridemorph, tridiphane, trietazine, trifenmorph, trifenofos,
trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium,
triflumizole, triflumuron, trifluralin, triflusulfuron,
triflusulfuron-methyl, trifop, trifop-methyl, trifopsime,
triforine, trihydroxytriazine, trimedlure, trimethacarb,
trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,
triptolide, tritac, triticonazole, tritosulfuron, trunc-call,
uniconazole, uniconazole-P, urbacide, uredepa, valerate,
validamycin, valifenalate, valone, vamidothion, vangard,
vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium,
warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC,
xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin,
zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide,
zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong,
.alpha.-chlorohydrin, .alpha.-ecdysone, .alpha.-multistriatin, and
.alpha.-naphthaleneacetic acid. For more information consult the
"COMPENDIUM OF PESTICIDE COMMON NAMES" located at
http://www.alanwood.net/pesticides/index.html. Also consult "THE
PESTICIDE MANUAL" 14th Edition, edited by C D S Tomlin, copyright
2006 by British Crop Production Council, or its prior or more
recent editions.
Biopesticides
[1105] Molecules of Formula One may also be used in combination
(such as in a compositional mixture, or a simultaneous or
sequential application) with one or more biopesticides. The term
"biopesticide" is used for microbial biological pest control agents
that are applied in a similar manner to chemical pesticides.
Commonly these are bacterial, but there are also examples of fungal
control agents, including Trichoderma spp. and Ampelomyces
quisqualis (a control agent for grape powdery mildew). Bacillus
subtilis are used to control plant pathogens. Weeds and rodents
have also been controlled with microbial agents. One well-known
insecticide example is Bacillus thuringiensis, a bacterial disease
of Lepidoptera, Coleoptera, and Diptera. Because it has little
effect on other organisms, it is considered more environmentally
friendly than synthetic pesticides. Biological insecticides include
products based on:
[1106] 1. entomopathogenic fungi (e.g. Metarhizium anisopliae);
[1107] 2. entomopathogenic nematodes (e.g. Steinernema feltiae);
and
[1108] 3. entomopathogenic viruses (e.g. Cydia pomonella
granulovirus).
[1109] Other examples of entomopathogenic organisms include, but
are not limited to, baculoviruses, bacteria and other prokaryotic
organisms, fungi, protozoa and Microsproridia. Biologically derived
insecticides include, but not limited to, rotenone, veratridine, as
well as microbial toxins; insect tolerant or resistant plant
varieties; and organisms modified by recombinant DNA technology to
either produce insecticides or to convey an insect resistant
property to the genetically modified organism. In one embodiment,
the molecules of Formula One may be used with one or more
biopesticides in the area of seed treatments and soil amendments.
The Manual of Biocontrol Agents gives a review of the available
biological insecticide (and other biology-based control) products.
Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents
(formerly the Biopesticide Manual) 3rd Edition. British Crop
Production Council (BCPC), Farnham, Surrey UK.
Other Active Compounds
[1110] Molecules of Formula One may also be used in combination
(such as in a compositional mixture, or a simultaneous or
sequential application) with one or more of the following: [1111]
1.
3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-
-one; [1112] 2.
3-(4'-chloro-2,4-dimethyl[1,1'-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro-
[4,5]dec-3-en-2-one; [1113] 3.
4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;
[1114] 4.
4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;
[1115] 5.
3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,-
2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamid-
e; [1116] 6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;
[1117] 7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; [1118] 8.
2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;
[1119] 9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;
[1120] 10.
2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; [1121]
11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;
[1122] 12.
2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; [1123]
13.
3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-
-carboxamide; [1124] 14.
N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-.alpha.,.alpha.,.alpha.--
trifluoro-p-tolyl) hydrazone; [1125] 15.
N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-.al-
pha.,.alpha.,.alpha.-trifluoro-p-tolyl) hydrazone nicotine; [1126]
16.
O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-
-methyl thiocarbonate; [1127] 17.
(E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;
[1128] 18.
1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imi-
dazo[1,2-a]pyridin-5-ol; [1129] 19.
4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate;
and [1130] 20.
N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alph-
a,alpha,alpha-trifluoro-p-tolyl)hydrazone.
Synergistic Mixtures
[1131] Molecules of Formula One may be used with certain active
compounds to form synergistic mixtures where the mode of action of
such compounds compared to the mode of action of the molecules of
Formula One are the same, similar, or different. Examples of modes
of action include, but are not limited to: acetylcholinesterase
inhibitor; sodium channel modulator; chitin biosynthesis inhibitor;
GABA and glutamate-gated chloride channel antagonist; GABA and
glutamate-gated chloride channel agonist; acetylcholine receptor
agonist; acetylcholine receptor antagonist; MET I inhibitor;
Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor;
Midgut membrane disrupter; oxidative phosphorylation disrupter, and
ryanodine receptor (RyRs). Generally, weight ratios of the
molecules of Formula One in a synergistic mixture with another
compound are from about 10:1 to about 1:10, in another embodiment
from about 5:1 to about 1:5, and in another embodiment from about
3:1, and in another embodiment about 1:1.
Formulations
[1132] A pesticide is rarely suitable for application in its pure
form. It is usually necessary to add other substances so that the
pesticide can be used at the required concentration and in an
appropriate form, permitting ease of application, handling,
transportation, storage, and maximum pesticide activity. Thus,
pesticides are formulated into, for example, baits, concentrated
emulsions, dusts, emulsifiable concentrates, fumigants, gels,
granules, microencapsulations, seed treatments, suspension
concentrates, suspoemulsions, tablets, water soluble liquids, water
dispersible granules or dry flowables, wettable powders, and
ultra-low volume solutions. For further information on formulation
types see "Catalogue of Pesticide Formulation Types and
International Coding System" Technical Monograph no 2, 5th Edition
by CropLife International (2002).
[1133] Pesticides are applied most often as aqueous suspensions or
emulsions prepared from concentrated formulations of such
pesticides. Such water-soluble, water-suspendable, or emulsifiable
formulations are either solids, usually known as wettable powders,
or water dispersible granules, or liquids usually known as
emulsifiable concentrates, or aqueous suspensions. Wettable
powders, which may be compacted to form water dispersible granules,
comprise an intimate mixture of the pesticide, a carrier, and
surfactants. The concentration of the pesticide is usually from
about 10% to about 90% by weight. The carrier is usually selected
from among the attapulgite clays, the montmorillonite clays, the
diatomaceous earths, or the purified silicates. Effective
surfactants, comprising from about 0.5% to about 10% of the
wettable powder, are found among sulfonated lignins, condensed
naphthalenesulfonates, naphthalenesulfonates,
alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants
such as ethylene oxide adducts of alkyl phenols.
[1134] Emulsifiable concentrates of pesticides comprise a
convenient concentration of a pesticide, such as from about 50 to
about 500 grams per liter of liquid dissolved in a carrier that is
either a water miscible solvent or a mixture of water-immiscible
organic solvent and emulsifiers. Useful organic solvents include
aromatics, especially xylenes and petroleum fractions, especially
the high-boiling naphthalenic and olefinic portions of petroleum
such as heavy aromatic naphtha. Other organic solvents may also be
used, such as the terpenic solvents including rosin derivatives,
aliphatic ketones such as cyclohexanone, and complex alcohols such
as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable
concentrates are selected from conventional anionic and non-ionic
surfactants.
[1135] Aqueous suspensions comprise suspensions of water-insoluble
pesticides dispersed in an aqueous carrier at a concentration in
the range from about 5% to about 50% by weight. Suspensions are
prepared by finely grinding the pesticide and vigorously mixing it
into a carrier comprised of water and surfactants. Ingredients,
such as inorganic salts and synthetic or natural gums may also be
added, to increase the density and viscosity of the aqueous
carrier. It is often most effective to grind and mix the pesticide
at the same time by preparing the aqueous mixture and homogenizing
it in an implement such as a sand mill, ball mill, or piston-type
homogenizer.
[1136] Pesticides may also be applied as granular compositions that
are particularly useful for applications to the soil. Granular
compositions usually contain from about 0.5% to about 10% by weight
of the pesticide, dispersed in a carrier that comprises clay or a
similar substance. Such compositions are usually prepared by
dissolving the pesticide in a suitable solvent and applying it to a
granular carrier which has been pre-formed to the appropriate
particle size, in the range of from about 0.5 to about 3 mm. Such
compositions may also be formulated by making a dough or paste of
the carrier and compound and crushing and drying to obtain the
desired granular particle size.
[1137] Dusts containing a pesticide are prepared by intimately
mixing the pesticide in powdered form with a suitable dusty
agricultural carrier, such as kaolin clay, ground volcanic rock,
and the like. Dusts can suitably contain from about 1% to about 10%
of the pesticide. They can be applied as a seed dressing or as a
foliage application with a dust blower machine.
[1138] It is equally practical to apply a pesticide in the form of
a solution in an appropriate organic solvent, usually petroleum
oil, such as the spray oils, which are widely used in agricultural
chemistry.
[1139] Pesticides can also be applied in the form of an aerosol
composition. In such compositions the pesticide is dissolved or
dispersed in a carrier, which is a pressure-generating propellant
mixture. The aerosol composition is packaged in a container from
which the mixture is dispensed through an atomizing valve.
[1140] Pesticide baits are formed when the pesticide is mixed with
food or an attractant or both. When the pests eat the bait they
also consume the pesticide. Baits may take the form of granules,
gels, flowable powders, liquids, or solids. They can be used in
pest harborages.
[1141] Fumigants are pesticides that have a relatively high vapor
pressure and hence can exist as a gas in sufficient concentrations
to kill pests in soil or enclosed spaces. The toxicity of the
fumigant is proportional to its concentration and the exposure
time. They are characterized by a good capacity for diffusion and
act by penetrating the pest's respiratory system or being absorbed
through the pest's cuticle. Fumigants are applied to control stored
product pests under gas proof sheets, in gas sealed rooms or
buildings or in special chambers.
[1142] Pesticides can be microencapsulated by suspending the
pesticide particles or droplets in plastic polymers of various
types. By altering the chemistry of the polymer or by changing
factors in the processing, microcapsules can be formed of various
sizes, solubility, wall thicknesses, and degrees of penetrability.
These factors govern the speed with which the active ingredient
within is released, which in turn, affects the residual
performance, speed of action, and odor of the product.
[1143] Oil solution concentrates are made by dissolving pesticide
in a solvent that will hold the pesticide in solution. Oil
solutions of a pesticide usually provide faster knockdown and kill
of pests than other formulations due to the solvents themselves
having pesticidal action and the dissolution of the waxy covering
of the integument increasing the speed of uptake of the pesticide.
Other advantages of oil solutions include better storage stability,
better penetration of crevices, and better adhesion to greasy
surfaces.
[1144] Another embodiment is an oil-in-water emulsion, wherein the
emulsion comprises oily globules which are each provided with a
lamellar liquid crystal coating and are dispersed in an aqueous
phase, wherein each oily globule comprises at least one compound
which is agriculturally active, and is individually coated with a
monolamellar or oligolamellar layer comprising: (1) at least one
non-ionic lipophilic surface-active agent, (2) at least one
non-ionic hydrophilic surface-active agent and (3) at least one
ionic surface-active agent, wherein the globules having a mean
particle diameter of less than 800 nanometers. Further information
on the embodiment is disclosed in U.S. patent publication
20070027034 published Feb. 1, 2007, having patent application Ser.
No. 11/495,228. For ease of use, this embodiment will be referred
to as "OIWE".
[1145] For further information consult "Insect Pest Management" 2nd
Edition by D. Dent, copyright CAB International (2000).
Additionally, for more detailed information consult "Handbook of
Pest Control--The Behavior, Life History, and Control of Household
Pests" by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media
Inc.
Other Formulation Components
[1146] Generally, when the molecules disclosed in Formula One are
used in a formulation, such formulation can also contain other
components. These components include, but are not limited to, (this
is a non-exhaustive and non-mutually exclusive list) wetters,
spreaders, stickers, penetrants, buffers, sequestering agents,
drift reduction agents, compatibility agents, anti-foam agents,
cleaning agents, and emulsifiers. A few components are described
forthwith.
[1147] A wetting agent is a substance that when added to a liquid
increases the spreading or penetration power of the liquid by
reducing the interfacial tension between the liquid and the surface
on which it is spreading. Wetting agents are used for two main
functions in agrochemical formulations: during processing and
manufacture to increase the rate of wetting of powders in water to
make concentrates for soluble liquids or suspension concentrates;
and during mixing of a product with water in a spray tank to reduce
the wetting time of wettable powders and to improve the penetration
of water into water-dispersible granules. Examples of wetting
agents used in wettable powder, suspension concentrate, and
water-dispersible granule formulations are: sodium lauryl sulfate;
sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and
aliphatic alcohol ethoxylates.
[1148] A dispersing agent is a substance which adsorbs onto the
surface of particles and helps to preserve the state of dispersion
of the particles and prevents them from reaggregating. Dispersing
agents are added to agrochemical formulations to facilitate
dispersion and suspension during manufacture, and to ensure the
particles redisperse into water in a spray tank. They are widely
used in wettable powders, suspension concentrates and
water-dispersible granules. Surfactants that are used as dispersing
agents have the ability to adsorb strongly onto a particle surface
and provide a charged or steric barrier to reaggregation of
particles. The most commonly used surfactants are anionic,
non-ionic, or mixtures of the two types. For wettable powder
formulations, the most common dispersing agents are sodium
lignosulfonates. For suspension concentrates, very good adsorption
and stabilization are obtained using polyelectrolytes, such as
sodium naphthalene sulfonate formaldehyde condensates.
Tristyrylphenol ethoxylate phosphate esters are also used.
Non-ionics such as alkylarylethylene oxide condensates and EO-PO
block copolymers are sometimes combined with anionics as dispersing
agents for suspension concentrates. In recent years, new types of
very high molecular weight polymeric surfactants have been
developed as dispersing agents. These have very long hydrophobic
`backbones` and a large number of ethylene oxide chains forming the
`teeth` of a `comb` surfactant. These high molecular weight
polymers can give very good long-term stability to suspension
concentrates because the hydrophobic backbones have many anchoring
points onto the particle surfaces. Examples of dispersing agents
used in agrochemical formulations are: sodium lignosulfonates;
sodium naphthalene sulfonate formaldehyde condensates;
tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol
ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft
copolymers.
[1149] An emulsifying agent is a substance which stabilizes a
suspension of droplets of one liquid phase in another liquid phase.
Without the emulsifying agent the two liquids would separate into
two immiscible liquid phases. The most commonly used emulsifier
blends contain alkylphenol or aliphatic alcohol with twelve or more
ethylene oxide units and the oil-soluble calcium salt of
dodecylbenzenesulfonic acid. A range of hydrophile-lipophile
balance ("HLB") values from 8 to 18 will normally provide good
stable emulsions. Emulsion stability can sometimes be improved by
the addition of a small amount of an EO-PO block copolymer
surfactant.
[1150] A solubilizing agent is a surfactant which will form
micelles in water at concentrations above the critical micelle
concentration. The micelles are then able to dissolve or solubilize
water-insoluble materials inside the hydrophobic part of the
micelle. The types of surfactants usually used for solubilization
are non-ionics, sorbitan monooleates, sorbitan monooleate
ethoxylates, and methyl oleate esters.
[1151] Surfactants are sometimes used, either alone or with other
additives such as mineral or vegetable oils as adjuvants to
spray-tank mixes to improve the biological performance of the
pesticide on the target. The types of surfactants used for
bioenhancement depend generally on the nature and mode of action of
the pesticide. However, they are often non-ionics such as: alkyl
ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine
ethoxylates.
[1152] A carrier or diluent in an agricultural formulation is a
material added to the pesticide to give a product of the required
strength. Carriers are usually materials with high absorptive
capacities, while diluents are usually materials with low
absorptive capacities. Carriers and diluents are used in the
formulation of dusts, wettable powders, granules and
water-dispersible granules.
[1153] Organic solvents are used mainly in the formulation of
emulsifiable concentrates, oil-in-water emulsions, suspoemulsions,
and ultra-low volume formulations, and to a lesser extent, granular
formulations. Sometimes mixtures of solvents are used. The first
main groups of solvents are aliphatic paraffinic oils such as
kerosene or refined paraffins. The second main group (and the most
common) comprises the aromatic solvents such as xylene and higher
molecular weight fractions of C.sub.9 and C.sub.10 aromatic
solvents. Chlorinated hydrocarbons are useful as cosolvents to
prevent crystallization of pesticides when the formulation is
emulsified into water. Alcohols are sometimes used as cosolvents to
increase solvent power. Other solvents may include vegetable oils,
seed oils, and esters of vegetable and seed oils.
[1154] Thickeners or gelling agents are used mainly in the
formulation of suspension concentrates, emulsions and
suspoemulsions to modify the rheology or flow properties of the
liquid and to prevent separation and settling of the dispersed
particles or droplets. Thickening, gelling, and anti-settling
agents generally fall into two categories, namely water-insoluble
particulates and water-soluble polymers. It is possible to produce
suspension concentrate formulations using clays and silicas.
Examples of these types of materials, include, but are not limited
to, montmorillonite, bentonite, magnesium aluminum silicate, and
attapulgite. Water-soluble polysaccharides have been used as
thickening-gelling agents for many years. The types of
polysaccharides most commonly used are natural extracts of seeds
and seaweeds or are synthetic derivatives of cellulose. Examples of
these types of materials include, but are not limited to, guar gum;
locust bean gum; carrageenam; alginates; methyl cellulose; sodium
carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other
types of anti-settling agents are based on modified starches,
polyacrylates, polyvinyl alcohol and polyethylene oxide. Another
good anti-settling agent is xanthan gum.
[1155] Microorganisms can cause spoilage of formulated products.
Therefore preservation agents are used to eliminate or reduce their
effect. Examples of such agents include, but are not limited to:
propionic acid and its sodium salt; sorbic acid and its sodium or
potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic
acid sodium salt; methyl p-hydroxybenzoate; and
1,2-benzisothiazolin-3-one (BIT).
[1156] The presence of surfactants often causes water-based
formulations to foam during mixing operations in production and in
application through a spray tank. In order to reduce the tendency
to foam, anti-foam agents are often added either during the
production stage or before filling into bottles. Generally, there
are two types of anti-foam agents, namely silicones and
non-silicones. Silicones are usually aqueous emulsions of dimethyl
polysiloxane, while the non-silicone anti-foam agents are
water-insoluble oils, such as octanol and nonanol, or silica. In
both cases, the function of the anti-foam agent is to displace the
surfactant from the air-water interface.
[1157] "Green" agents (e.g., adjuvants, surfactants, solvents) can
reduce the overall environmental footprint of crop protection
formulations. Green agents are biodegradable and generally derived
from natural and/or sustainable sources, e.g. plant and animal
sources. Specific examples are: vegetable oils, seed oils, and
esters thereof, also alkoxylated alkyl polyglucosides.
[1158] For further information, see "Chemistry and Technology of
Agrochemical Formulations" edited by D. A. Knowles, copyright 1998
by Kluwer Academic Publishers. Also see "Insecticides in
Agriculture and Environment--Retrospects and Prospects" by A. S.
Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by
Springer-Verlag.
Pests
[1159] In general, the molecules of Formula One may be used to
control pests e.g. beetles, earwigs, cockroaches, flies. aphids,
scales, whiteflies, leafhoppers, ants, wasps, termites, moths,
butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips,
bristletails, mites, ticks, nematodes, and symphylans.
[1160] In another embodiment, the molecules of Formula One may be
used to control pests in the Phyla Nematoda and/or Arthropoda.
[1161] In another embodiment, the molecules of Formula One may be
used to control pests in the Subphyla Chelicerata, Myriapoda,
and/or Hexapoda.
[1162] In another embodiment, the molecules of Formula One may be
used to control pests in the Classes of Arachnida, Symphyla, and/or
Insecta.
[1163] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Anoplura. A non-exhaustive list
of particular genera includes, but is not limited to, Haematopinus
spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and
Polyplax spp. A non-exhaustive list of particular species includes,
but is not limited to, Haematopinus asini, Haematopinus suis,
Linognathus setosus, Linognathus ovillus, Pediculus humanus
capitis, Pediculus humanus humanus, and Pthirus pubis.
[1164] In another embodiment, the molecules of Formula One may be
used to control pests in the Order Coleoptera. A non-exhaustive
list of particular genera includes, but is not limited to,
Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp.,
Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp.,
Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp.,
Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp.,
Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes
spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp.,
Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus
spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and
Tribolium spp. A non-exhaustive list of particular species
includes, but is not limited to, Acanthoscelides obtectus, Agrilus
planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius
spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus
pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida
vittata, Cerotoma trifurcata, Ceutorhynchus assimilis,
Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus,
Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi,
Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes
turcicus, Cylindrocopturus adspersus, Deporaus marginatus,
Dermestes lardarius, Dermestes maculatus, Epilachna varivestis,
Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus
hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys
fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis
joliveti, Melanotus communis, Meligethes aeneus, Melolontha
melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros,
Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,
Oulema oryzae, Phyllophaga cuyabana, Popillia japonica,
Prostephanus truncatus, Rhyzopertha dominica, Sitona lineatus,
Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais,
Stegobium paniceum, Tribolium castaneum, Tribolium confusum,
Trogoderma variabile, and Zabrus tenebrioides.
[1165] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Dermaptera.
[1166] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Blattaria. A non-exhaustive list
of particular species includes, but is not limited to, Blattella
germanica, Blatta orientalis, Parcoblatta pennsylvanica,
Periplaneta americana, Periplaneta australasiae, Periplaneta
brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and
Supella longipalpa.
[1167] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Diptera. A non-exhaustive list
of particular genera includes, but is not limited to, Aedes spp.,
Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp.,
Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp.,
Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia
spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp.,
Tabanus spp., and Tipula spp. A non-exhaustive list of particular
species includes, but is not limited to, Agromyza frontella,
Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa,
Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens,
Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia
platura, Fannia canicularis, Fannia scalaris, Gasterophilus
intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma
lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis,
Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila
rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax,
Sitodiplosis mosellana, and Stomoxys calcitrans.
[1168] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Hemiptera. A non-exhaustive list
of particular genera includes, but is not limited to, Adelges spp.,
Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp.,
Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp.,
Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp.,
Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp.,
Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus
spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp.,
Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp.
and Unaspis spp. A non-exhaustive list of particular species
includes, but is not limited to, Acrosternum hilare, Acyrthosiphon
pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus
floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis
gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia
argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella
asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris
norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex
lectularius, Dagbertusfasciatus, Dichelopsfurcatus, Diuraphis
noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus
suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster
maura, Euschistus heros, Euschistus servus, Helopeltis antonii,
Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus,
Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa
varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum
euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles
quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum,
Mictis longicornis, Myzus persicae, Nephotettix cinctipes,
Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens,
Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis,
Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus,
Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus,
Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes,
Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum
padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum,
Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum,
Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia
entrerriana.
[1169] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Hymenoptera. A non-exhaustive
list of particular genera includes, but is not limited to,
Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica
spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes
spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A
non-exhaustive list of particular species includes, but is not
limited to, Athalia rosae, Atta texana, Iridomyrmex humilis,
Monomorium minimum, Monomorium pharaonis, Solenopsis invicta,
Solenopsis geminata, Solenopsis molesta, Solenopsis richtery,
Solenopsis xyloni, and Tapinoma sessile.
[1170] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Isoptera. A non-exhaustive list
of particular genera includes, but is not limited to, Coptotermes
spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp.,
Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes
spp., Microcerotermes spp., Procornitermes spp., Reticulitermes
spp., Schedorhinotermes spp., and Zootermopsis spp. A
non-exhaustive list of particular species includes, but is not
limited to, Coptotermes curvignathus, Coptotermes frenchi,
Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,
Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes
flavipes, Reticulitermes hageni, Reticulitermes hesperus,
Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes
tibialis, and Reticulitermes virginicus.
[1171] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Lepidoptera. A non-exhaustive
list of particular genera includes, but is not limited to,
Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp.,
Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp.,
Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia
spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp.,
Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis
spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp.,
Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp.,
and Yponomeuta spp. A non-exhaustive list of particular species
includes, but is not limited to, Achaea janata, Adoxophyes orana,
Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois
transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis
sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips
rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes,
Borbo cinnara, Bucculatrix thurberiella, Capua reticulana,
Carposina niponensis, Chlumetia transversa, Choristoneura
rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella,
Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia
nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis,
Diatraea grandiosella, Earias insulana, Earias vittella,
Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia
cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema,
Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa
auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa
armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis,
Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera
coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis
albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,
Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna
unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis,
Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis
cerasana, Pandemis heparana, Papilio demodocus, Pectinophora
gossypiella, Peridroma saucia, Perileucoptera coffeella,
Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae,
Plathypena scabra, Plodia interpunctella, Plutella xylostella,
Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia
unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga
incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens,
Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua,
Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,
Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera
coffeae, and Zeuzera pyrina.
[1172] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Mallophaga. A non-exhaustive
list of particular genera includes, but is not limited to,
Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp.,
Menacanthus spp., and Trichodectes spp. A non-exhaustive list of
particular species includes, but is not limited to, Bovicola bovis,
Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes
dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon
gallinae, and Trichodectes canis.
[1173] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Orthoptera. A non-exhaustive
list of particular genera includes, but is not limited to,
Melanoplus spp., and Pterophylla spp. A non-exhaustive list of
particular species includes, but is not limited to, Anabrus
simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa
brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,
Microcentrum retinerve, Schistocerca gregaria, and Scudderia
furcata.
[1174] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Siphonaptera. A non-exhaustive
list of particular species includes, but is not limited to,
Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis,
Ctenocephalides felis, and Pulex irritans.
[1175] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Thysanoptera. A non-exhaustive
list of particular genera includes, but is not limited to,
Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips
spp. A non-exhaustive list of particular sp. includes, but is not
limited to, Frankliniella fusca, Frankliniella occidentalis,
Frankliniella schultzei, Frankliniella williamsi, Heliothrips
haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri,
Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips
hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips
tabaci.
[1176] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Thysanura. A non-exhaustive list
of particular genera includes, but is not limited to, Lepisma spp.
and Thermobia spp.
[1177] In another embodiment, the molecules of Formula One may be
used to control pests of the Order Acarina. A non-exhaustive list
of particular genera includes, but is not limited to, Acarus spp.,
Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp.,
Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp.,
Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A
non-exhaustive list of particular species includes, but is not
limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops
lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma
americanum, Brevipalpus obovatus, Brevipalpus phoenicis,
Dermacentor variabilis, Dermatophagoides pteronyssinus,
Eotetranychus carpini, Notoedres cati, Oligonychus coffeae,
Oligonychus ilicis, Panonychus citri, Panonychus ulmi,
Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus
sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus
urticae, and Varroa destructor.
[1178] In another embodiment, the molecules of Formula One may be
used to control pest of the Order Symphyla. A non-exhaustive list
of particular sp. includes, but is not limited to, Scutigerella
immaculata.
[1179] In another embodiment, the molecules of Formula One may be
used to control pests of the Phylum Nematoda. A non-exhaustive list
of particular genera includes, but is not limited to,
Aphelenchoides spp., Belonolaimus spp., Criconemella spp.,
Ditylenchus spp., Heterodera spp., Hirschmanniella spp.,
Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and
Radopholus spp. A non-exhaustive list of particular sp. includes,
but is not limited to, Dirofilaria immitis, Heterodera zeae,
Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus,
Radopholus similis, and Rotylenchulus reniformis.
[1180] For additional information consult "HANDBOOK OF PEST
CONTROL--THE BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD
PESTS" by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media
Inc.
Applications
[1181] Molecules of Formula One are generally used in amounts from
about 0.01 grams per hectare to about 5000 grams per hectare to
provide control. Amounts from about 0.1 grams per hectare to about
500 grams per hectare are generally preferred, and amounts from
about 1 gram per hectare to about 50 grams per hectare are
generally more preferred.
[1182] The area to which a molecule of Formula One is applied can
be any area inhabited (or maybe inhabited, or traversed by) a pest,
for example: where crops, trees, fruits, cereals, fodder species,
vines, turf and ornamental plants, are growing; where domesticated
animals are residing; the interior or exterior surfaces of
buildings (such as places where grains are stored), the materials
of construction used in building (such as impregnated wood), and
the soil around buildings. Particular crop areas to use a molecule
of Formula One include areas where apples, corn, sunflowers,
cotton, soybeans, canola, wheat, rice, sorghum, barley, oats,
potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes,
peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and
other valuable crops are growing or the seeds thereof are going to
be planted. It is also advantageous to use ammonium sulfate with a
molecule of Formula One when growing various plants.
[1183] Controlling pests generally means that pest populations,
pest activity, or both, are reduced in an area. This can come about
when: pest populations are repulsed from an area; when pests are
incapacitated in or around an area; or pests are exterminated, in
whole, or in part, in or around an area. Of course, a combination
of these results can occur. Generally, pest populations, activity,
or both are desirably reduced more than fifty percent, preferably
more than 90 percent. Generally, the area is not in or on a human;
consequently, the locus is generally a non-human area.
[1184] The molecules of Formula One may be used in mixtures,
applied simultaneously or sequentially, alone or with other
compounds to enhance plant vigor (e.g. to grow a better root
system, to better withstand stressful growing conditions). Such
other compounds are, for example, compounds that modulate plant
ethylene receptors, most notably 1-methylcyclopropene (also known
as 1-MCP). Furthermore, such molecules may be used during times
when pest activity is low, such as before the plants that are
growing begin to produce valuable agricultural commodities. Such
times include the early planting season when pest pressure is
usually low.
[1185] The molecules of Formula One can be applied to the foliar
and fruiting portions of plants to control pests. The molecules
will either come in direct contact with the pest, or the pest will
consume the pesticide when eating leaf, fruit mass, or extracting
sap, that contains the pesticide. The molecules of Formula One can
also be applied to the soil, and when applied in this manner, root
and stem feeding pests can be controlled. The roots can absorb a
molecule taking it up into the foliar portions of the plant to
control above ground chewing and sap feeding pests.
[1186] Generally, with baits, the baits are placed in the ground
where, for example, termites can come into contact with, and/or be
attracted to, the bait. Baits can also be applied to a surface of a
building, (horizontal, vertical, or slant surface) where, for
example, ants, termites, cockroaches, and flies, can come into
contact with, and/or be attracted to, the bait. Baits can comprise
a molecule of Formula One.
[1187] The molecules of Formula One can be encapsulated inside, or
placed on the surface of a capsule. The size of the capsules can
range from nanometer size (about 100-900 nanometers in diameter) to
micrometer size (about 10-900 microns in diameter).
[1188] Because of the unique ability of the eggs of some pests to
resist certain pesticides, repeated applications of the molecules
of Formula One may be desirable to control newly emerged
larvae.
[1189] Systemic movement of pesticides in plants may be utilized to
control pests on one portion of the plant by applying (for example
by spraying an area) the molecules of Formula One to a different
portion of the plant. For example, control of foliar-feeding
insects can be achieved by drip irrigation or furrow application,
by treating the soil with for example pre- or post-planting soil
drench, or by treating the seeds of a plant before planting.
[1190] Seed treatment can be applied to all types of seeds,
including those from which plants genetically modified to express
specialized traits will germinate. Representative examples include
those expressing proteins toxic to invertebrate pests, such as
Bacillus thuringiensis or other insecticidal toxins, those
expressing herbicide resistance, such as "Roundup Ready" seed, or
those with "stacked" foreign genes expressing insecticidal toxins,
herbicide resistance, nutrition-enhancement, drought resistance, or
any other beneficial traits. Furthermore, such seed treatments with
the molecules of Formula One may further enhance the ability of a
plant to better withstand stressful growing conditions. This
results in a healthier, more vigorous plant, which can lead to
higher yields at harvest time. Generally, about 1 gram of the
molecules of Formula One to about 500 grams per 100,000 seeds is
expected to provide good benefits, amounts from about 10 grams to
about 100 grams per 100,000 seeds is expected to provide better
benefits, and amounts from about 25 grams to about 75 grams per
100,000 seeds is expected to provide even better benefits.
[1191] It should be readily apparent that the molecules of Formula
One may be used on, in, or around plants genetically modified to
express specialized traits, such as Bacillus thuringiensis or other
insecticidal toxins, or those expressing herbicide resistance, or
those with "stacked" foreign genes expressing insecticidal toxins,
herbicide resistance, nutrition-enhancement, or any other
beneficial traits.
[1192] The molecules of Formula One may be used for controlling
endoparasites and ectoparasites in the veterinary medicine sector
or in the field of non-human animal keeping. The molecules of
Formula One are applied, such as by oral administration in the form
of, for example, tablets, capsules, drinks, granules, by dermal
application in the form of, for example, dipping, spraying, pouring
on, spotting on, and dusting, and by parenteral administration in
the form of, for example, an injection.
[1193] The molecules of Formula One may also be employed
advantageously in livestock keeping, for example, cattle, sheep,
pigs, chickens, and geese. They may also be employed advantageously
in pets such as, horses, dogs, and cats. Particular pests to
control would be fleas and ticks that are bothersome to such
animals. Suitable formulations are administered orally to the
animals with the drinking water or feed. The dosages and
formulations that are suitable depend on the species.
[1194] The molecules of Formula One may also be used for
controlling parasitic worms, especially of the intestine, in the
animals listed above.
[1195] The molecules of Formula One may also be employed in
therapeutic methods for human health care. Such methods include,
but are limited to, oral administration in the form of, for
example, tablets, capsules, drinks, granules, and by dermal
application.
[1196] Pests around the world have been migrating to new
environments (for such pest) and thereafter becoming a new invasive
species in such new environment. The molecules of Formula One may
also be used on such new invasive species to control them in such
new environment.
[1197] The molecules of Formula One may also be used in an area
where plants, such as crops, are growing (e.g. pre-planting,
planting, pre-harvesting) and where there are low levels (even no
actual presence) of pests that can commercially damage such plants.
The use of such molecules in such area is to benefit the plants
being grown in the area. Such benefits, may include, but are not
limited to, improving the health of a plant, improving the yield of
a plant (e.g. increased biomass and/or increased content of
valuable ingredients), improving the vigor of a plant (e.g.
improved plant growth and/or greener leaves), improving the quality
of a plant (e.g. improved content or composition of certain
ingredients), and improving the tolerance to abiotic and/or biotic
stress of the plant.
[1198] Before a pesticide can be used or sold commercially, such
pesticide undergoes lengthy evaluation processes by various
governmental authorities (local, regional, state, national, and
international). Voluminous data requirements are specified by
regulatory authorities and must be addressed through data
generation and submission by the product registrant or by a third
party on the product registrant's behalf, often using a computer
with a connection to the World Wide Web. These governmental
authorities then review such data and if a determination of safety
is concluded, provide the potential user or seller with product
registration approval. Thereafter, in that locality where the
product registration is granted and supported, such user or seller
may use or sell such pesticide.
[1199] A molecule according to Formula One can be tested to
determine its efficacy against pests. Furthermore, mode of action
studies can be conducted to determine if said molecule has a
different mode of action than other pesticides. Thereafter, such
acquired data can be disseminated, such as by the internet, to
third parties.
[1200] The headings in this document are for convenience only and
must not be used to interpret any portion hereof.
Table Section
TABLE-US-00003 [1201] % Control (or Mortality) Rating BAW, CEW
& CL Rating Table 50-100 A More than 0-Less than 50 B Not
Tested C No activity noticed in this bioassay D GPA Rating Table
80-100 A More than 0-Less than 80 B Not Tested C No activity
noticed in this bioassay D
TABLE-US-00004 TABLE 1 Structures for Compounds Compound Number
Structure AI34 ##STR00482## AI36 ##STR00483## AI37 ##STR00484##
AI38 ##STR00485## AI39 ##STR00486## AI40 ##STR00487## AI41
##STR00488## AI44 ##STR00489## AI45 ##STR00490## AC1 ##STR00491##
AC2 ##STR00492## AC3 ##STR00493## AC4 ##STR00494## AC5 ##STR00495##
AC6 ##STR00496## AC7 ##STR00497## AC8 ##STR00498## AC9 ##STR00499##
AC10 ##STR00500## AC11 ##STR00501## AC12 ##STR00502## AC13
##STR00503## AC14 ##STR00504## AC15 ##STR00505## AC16 ##STR00506##
AC17 ##STR00507## AC18 ##STR00508## AC19 ##STR00509## AC20
##STR00510## AC21 ##STR00511## AC22 ##STR00512## AC23 ##STR00513##
AC24 ##STR00514## AC25 ##STR00515## AC26 ##STR00516## AC27
##STR00517## AC28 ##STR00518## AC29 ##STR00519## AC30 ##STR00520##
AC31 ##STR00521## AC32 ##STR00522## AC33 ##STR00523## AC34
##STR00524## AC35 ##STR00525## AC36 ##STR00526## AC37 ##STR00527##
AC38 ##STR00528## AC39 ##STR00529## AC40 ##STR00530## AC41
##STR00531## AC42 ##STR00532## AC43 ##STR00533## AC44 ##STR00534##
AC45 ##STR00535## AC46 ##STR00536## AC47 ##STR00537## AC48
##STR00538## AC49 ##STR00539## AC50 ##STR00540## AC51 ##STR00541##
AC52 ##STR00542## AC53 ##STR00543## AC54 ##STR00544## AC57
##STR00545## AC58 ##STR00546## AC59 ##STR00547## AC60 ##STR00548##
AC61 ##STR00549## AC62 ##STR00550## AC63 ##STR00551## AC64
##STR00552## AC65 ##STR00553## AC66 ##STR00554## AC67 ##STR00555##
AC68 ##STR00556## AC69 ##STR00557## AC70 ##STR00558## AC71
##STR00559## AC72 ##STR00560## AC75 ##STR00561## AC76 ##STR00562##
AC77 ##STR00563## AC78 ##STR00564## AC79 ##STR00565## AC80
##STR00566## AC81 ##STR00567## AC82 ##STR00568## AC83 ##STR00569##
AC84 ##STR00570## AC85 ##STR00571## AC86 ##STR00572## AC87
##STR00573## AC89 ##STR00574## AC90 ##STR00575## AC91 ##STR00576##
AC92 ##STR00577## AC93 ##STR00578## AC94 ##STR00579## AC95
##STR00580## AC96 ##STR00581## AC97 ##STR00582## AC98 ##STR00583##
AC99 ##STR00584## AC100 ##STR00585## AC101 ##STR00586## AC102
##STR00587## AC103 ##STR00588## AC104 ##STR00589## AC105
##STR00590## AC106 ##STR00591## AC107 ##STR00592## AC108
##STR00593## AC109 ##STR00594## AC110 ##STR00595## AC111
##STR00596## AC112 ##STR00597## AC113 ##STR00598## AC114
##STR00599## AC115 ##STR00600## AC116 ##STR00601## AC117
##STR00602## AC118 ##STR00603##
BC1 ##STR00604## BC2 ##STR00605## BC3 ##STR00606## BC4 ##STR00607##
BC5 ##STR00608## BC6 ##STR00609## BC7 ##STR00610## BC8 ##STR00611##
BC9 ##STR00612## BC10 ##STR00613## BC11 ##STR00614## BC12
##STR00615## BC13 ##STR00616## BC14 ##STR00617## CI4 ##STR00618##
CI5 ##STR00619## CI8 ##STR00620## CI9 ##STR00621## CI34
##STR00622## CI35 ##STR00623## CI36 ##STR00624## CI37 ##STR00625##
CI38 ##STR00626## CI39 ##STR00627## CI40 ##STR00628## CI41
##STR00629## CI49 ##STR00630## CI50 ##STR00631## CI51 ##STR00632##
CI52 ##STR00633## CI53 ##STR00634## CI54 ##STR00635## CI55
##STR00636## CI56 ##STR00637## CI57 ##STR00638## CC1 ##STR00639##
CC2 ##STR00640## CC3 ##STR00641## CC4 ##STR00642## CC5 ##STR00643##
CC6 ##STR00644## CC7 ##STR00645## CC8 ##STR00646## CC9 ##STR00647##
CC10 ##STR00648## CC11 ##STR00649## CC12 ##STR00650## CC13
##STR00651## CC14 ##STR00652## CC15 ##STR00653## CC16 ##STR00654##
CC17 ##STR00655## CC18 ##STR00656## CC19 ##STR00657## CC20
##STR00658## CC21 ##STR00659## CC22 ##STR00660## CC23 ##STR00661##
CC24 ##STR00662## CC25 ##STR00663## CC26 ##STR00664## CC27
##STR00665## CC28 ##STR00666## CC29 ##STR00667## CC30 ##STR00668##
CC31 ##STR00669## CC32 ##STR00670## CC33 ##STR00671## CC34
##STR00672## CC35 ##STR00673## CC36 ##STR00674## CC37 ##STR00675##
CC38 ##STR00676## CC39 ##STR00677## CC40 ##STR00678## CC41
##STR00679## CC42 ##STR00680## CC43 ##STR00681## CC44 ##STR00682##
CC45 ##STR00683## CC46 ##STR00684## CC47 ##STR00685## CC48
##STR00686## CC49 ##STR00687## CC50 ##STR00688## CC51 ##STR00689##
CC52 ##STR00690## CC53 ##STR00691## CC54 ##STR00692## DC1
##STR00693## DC2 ##STR00694## DC3 ##STR00695## DC4 ##STR00696## DC5
##STR00697## DC6 ##STR00698## DC7 ##STR00699## DC8 ##STR00700## DC9
##STR00701## DC10 ##STR00702## DC11 ##STR00703## DC12 ##STR00704##
DC13 ##STR00705## DC14 ##STR00706## DC15 ##STR00707## DC16
##STR00708## DC17 ##STR00709## DC18 ##STR00710## DC19 ##STR00711##
DC20 ##STR00712## DC21 ##STR00713## DC22 ##STR00714## DC23
##STR00715## DC24 ##STR00716## DC25 ##STR00717## DC26 ##STR00718##
DC27 ##STR00719## DC28 ##STR00720## DC29 ##STR00721## DC30
##STR00722## DC31 ##STR00723## DC32 ##STR00724## DC33 ##STR00725##
DC34 ##STR00726## DC35 ##STR00727## DC36 ##STR00728## DC37
##STR00729##
DC38 ##STR00730## DC39 ##STR00731## DC40 ##STR00732## DC41
##STR00733## DC42 ##STR00734## DC43 ##STR00735## DC44 ##STR00736##
DC45 ##STR00737## DC46 ##STR00738## DC47 ##STR00739## DC48
##STR00740## DC49 ##STR00741## DC50 ##STR00742## DC51 ##STR00743##
DC52 ##STR00744## DC53 ##STR00745## DC54 ##STR00746## DC55
##STR00747## DC56 ##STR00748## DC57 ##STR00749## DC58 ##STR00750##
DC59 ##STR00751## DC60 ##STR00752## DC61 ##STR00753## DC62
##STR00754## DC63 ##STR00755## DC64 ##STR00756## DC65 ##STR00757##
DC66 ##STR00758## DC67 ##STR00759## DC68 ##STR00760## DC69
##STR00761## DC70 ##STR00762##
TABLE-US-00005 TABLE 1A Structures for F Compounds Compound
Prepared as Number Structure Appearance in Example: F1 ##STR00763##
white foam 135 F2 ##STR00764## brown gum 15 F3 ##STR00765## pale
yellow gum 15 F4 ##STR00766## yellow solid 15 F5 ##STR00767## 108
F6 ##STR00768## 108 F7 ##STR00769## yellow solid 15 F8 ##STR00770##
off-white solid 15 F8A ##STR00771## pale yellow solid 15 F9
##STR00772## yellow solid 15 F10 ##STR00773## off-white solid 132
F11 ##STR00774## off-white solid 132 F12 ##STR00775## off-white
solid 133 F13 ##STR00776## off-white solid 133 F14 ##STR00777##
pale yellow solid 15 F15 ##STR00778## yellow solid 15 F15A
##STR00779## yellow solid 15 F16 ##STR00780## pale yellow solid 15
F16A ##STR00781## yellow solid 15 F17 ##STR00782## off-white solid
15 F18 ##STR00783## yellow solid 15 F19 ##STR00784## yellow gum 15
F20 ##STR00785## yellow solid 15 F20A ##STR00786## off-white solid
133 F20B ##STR00787## off-white solid 133 F20C ##STR00788## white
solid 88 F21 ##STR00789## yellow gum 15 F22 ##STR00790## light
brown gum 15 F23 ##STR00791## pale yellow liquid 15 F23A
##STR00792## yellow solid 15 F24 ##STR00793## pale yellow liquid 15
F25 ##STR00794## yellow solid 15 F26 ##STR00795## brown gum 15 F27
##STR00796## pale yellow gum 15 F28 ##STR00797## brown gum 15 F29
##STR00798## pale yellow gum 15 F30 ##STR00799## brown gum 15 F31
##STR00800## pale yellow gum 134
TABLE-US-00006 TABLE 1B Structures of Prophetic Compounds
Subsequently Exemplified Compound Prepared as Number Structure
Appearance in Example: P1 ##STR00801## Yellow solid 15 P2
##STR00802## Brown gum 15 P12 ##STR00803## Off white solid 15 P14
##STR00804## Light yellow gum 19 P15 ##STR00805## Light yellow gum
19 P82 ##STR00806## Brown semi solid 15 P84 ##STR00807## Pale
yellow solid 15 P156 ##STR00808## Green liquid 15 P226 ##STR00809##
Brown semi solid 15 P228 ##STR00810## Brown semi solid 15 P298
##STR00811## Yellow solid 15 P300 ##STR00812## Brown gum 15 P442
##STR00813## Pale yellow solid 15 P444 ##STR00814## Pale yellow
solid 15 P514 ##STR00815## Off white solid 15 P516 ##STR00816##
Brown solid 15 P568 ##STR00817## Brown semi solid 15 P586
##STR00818## Brown semi solid 15 P588 ##STR00819## Brown semi solid
15 P660 ##STR00820## Pale yellow solid 15 P730 ##STR00821## Yellow
solid 15 P732 ##STR00822## Brown semi solid 15 P802 ##STR00823##
Brown gum 15 P804 ##STR00824## Brown gum 15 P1090 ##STR00825##
Light brown solid 15 P1092 ##STR00826## Brown semi solid 15 P1197
##STR00827## Off white solid 15 P1269 ##STR00828## Pale yellow
solid 15 P1340 ##STR00829## Pale yellow solid 15 P1411 ##STR00830##
Pale yellow solid 15 P1483 ##STR00831## Off white solid 15 P1556
##STR00832## Brown solid 15 P1558 ##STR00833## Brown solid 134
P1559 ##STR00834## Brown gum 134 P1560 ##STR00835## Off white solid
19 P1564 ##STR00836## Yellow solid 19 P1566 ##STR00837## Brown
solid 15 P1589 ##STR00838## Pale yellow gum 15 P1591 ##STR00839##
Brown gum 15 P1592 ##STR00840## Pale yellow gum 15 P1599
##STR00841## Brown semi solid 12 P1601 ##STR00842## Brown viscous
liquid 15 P1603 ##STR00843## Off white solid 135 P1611A
##STR00844## Pale yellow solid 137 P1613A ##STR00845## Brown solid
137 P1616 ##STR00846## Brown gum 15 P1616A ##STR00847## Pale yellow
semi solid 137 P1618A ##STR00848## Brown solid 137 P1621
##STR00849## Brown viscous liquid 12 P1623 ##STR00850## Brown
liquid 12 P1624 ##STR00851## Brown semi solid 12 P1631A
##STR00852## Brown viscous liquid 137 P1633A ##STR00853## Brown
solid 137 P1636 ##STR00854## Off white solid 135 P1638 ##STR00855##
Pale yellow solid 15 P1640 ##STR00856## Brown semi solid 15 P1641
##STR00857## Brown solid 15 P1691 ##STR00858## Brown gum 15 P1693
##STR00859## Pale yellow semi solid 15 P1696 ##STR00860## Yellow
solid 15 P1698 ##STR00861## Yellow semi solid 15 P1776 ##STR00862##
White solid 15 P1781 ##STR00863## White solid 15 P1806 ##STR00864##
Brown gum 15 P1808 ##STR00865## Pale yellow gum 15 P1862
##STR00866## Off white gum 15 P1864 ##STR00867## Brown gum 19 P1866
##STR00868## Brown liquid 19 P1969 ##STR00869## Brown solid 15
P1970 ##STR00870## Brown gum 15 P1971 ##STR00871## Pale yellow
solid 15 P1972 ##STR00872## Light brown solid 15 P2009 ##STR00873##
Yellow solid 15 P2010 ##STR00874## Yellow gum 15 P2011 ##STR00875##
Yellow solid 15 P2012 ##STR00876## Off white solid 15 P2036
##STR00877## Brown solid 15 P2038 ##STR00878## Yellow liquid 15
P2041 ##STR00879## Brown solid 15 P2043 ##STR00880## Dark green
solid 15 P2056 ##STR00881## Brown solid 15 P2058 ##STR00882## Pale
yellow semi solid 15
TABLE-US-00007 TABLE 1C Structures for FA Compounds Prepared as
Compound in Number Structure Appearance Example: FA1 ##STR00883##
Pale yellow gum 15 FA2 ##STR00884## Light green liquid 15 FA3
##STR00885## Brown gum 15 FA4 ##STR00886## White foam 138 FA5
##STR00887## White foam 138 FA6 ##STR00888## Yellow solid 146 FA7
##STR00889## Pale yellow solid 137 FA8 ##STR00890## Pale yellow gum
15 FA9 ##STR00891## Yellow gum 134 FA10 ##STR00892## Yellow gum 134
FA11 ##STR00893## Brown semi solid 134 FA12 ##STR00894## Brown semi
solid 134 FA13 ##STR00895## Light green solid 147 FA14 ##STR00896##
White foam 142 FA15 ##STR00897## White foam 142 FA16 ##STR00898##
Pale yellow solid 15 FA17 ##STR00899## Off white solid 15 FA18
##STR00900## Yellow semi solid 15 FA19 ##STR00901## Pale yellow
solid 15 FA20 ##STR00902## Pale yellow solid 15 FA21 ##STR00903##
Brown gum 15 FA22 ##STR00904## Yellow gum 15 FA23 ##STR00905##
Light yellow oil 142 FA24 ##STR00906## Off white solid 15 FA25
##STR00907## Yellow solid 15 FA26 ##STR00908## Light green solid 12
FA27 ##STR00909## Pale green solid 12 FA28 ##STR00910## Brown solid
15 FA29 ##STR00911## Brown liquid 15 FA30 ##STR00912## Brown gum 12
FA31 ##STR00913## Pale yellow solid 12 FA32 ##STR00914## Yellow
solid 15 FA33 ##STR00915## Yellow solid 135 FA34 ##STR00916## Off
white solid 149
TABLE-US-00008 TABLE 2 Analytical Data for Compounds in Table 1.
Compound Number mp (.degree. C.) ESIMS .sup.1H NMR (.delta.).sup.a
IR (cm.sup.-1) AC1 156-161 386.09 7.83 (m, 2H), 7.68-7.63 ([M -
H].sup.-) (m, 5H), 6.93 (dd, J = 15.6, 8.0 Hz, 1H), 6.81 (d J =
15.6 Hz, 1H,), 4.15 (m, 1H), 2.80 (s, 3H) AC2 110-112 374 7.80 (d,
J = 8.4 Hz, 2H), ([M + H].sup.+) 7.48 (d, J = 8.0 Hz, 2H), 7.38 (m,
1H), 7.30 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0,
8.0 Hz, 1H), 4.15 (m, 1H) AC3 162-166 402.24 7.42 (m, 4H), 7.37 (t,
J = ([M + H].sup.+) 1.8 Hz, 1H), 7.28 (s, 2H), 6.63 (d, J = 16.0
Hz, 1H), 6.41 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H), 3.20 (s,
3H), 3.00 (s, 3H) AC4 122-126 454 7.79 (d, J = 1.2 Hz, 2H), ([M -
H].sup.-) 7.48 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.30
(s, 2H), 6.64 (d, J = 15.6 Hz, 1H), 6.40 (dd, J = 15.6, 8.0 Hz,
1H), 6.30 (m, 1H), 4.15 (m, 3H) AC5 444.12 7.67 (s, 3H), 7.64 (d, J
= ([M + H].sup.+) 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 6.91 (dd,
J = 15.6, 8.0 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.80 (m, 1H),
3.60 (br s, 8H) AC6 468.40 7.40 (m, 2H), 7.26 (m, 1657, 1113, ([M -
H].sup.-) 3H), 6.56 (d, J = 16.0 804 Hz, 1H), 6.48 (dd, J = 16.0,
8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H) AC7 511.02
8.39 (s, 1H), 7.74 (m, 3276, 1645, ([M - H].sup.-) 1H), 7.39 (m,
3H), 7.24 1111, 801 (m, 4H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J
= 16.0, 8.0 Hz, 1H), 6.16 (br s, 1H), 4.63 (m, 2H), 4.12 (m, 1H),
2.41 (s, 3H) AC8 454.11 7.39 (s, 1H), 7.22 (m, 1748, 1112, ([M -
H].sup.-) 2H), 7.19 (m, 3H), 6.53 801 (d, J = 16.0 Hz, 1H),
6.39-6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H), 3.95 (t, J =
7.0 Hz, 2H), 2.62 (t, J = 8.0 Hz, 2H), 2.30 (s, 3H), 2.18 (m, 2H)
AC9 494.02 7.45 (t, J = 7.6 Hz, 1H), 3276, 1645, ([M - H].sup.-)
7.36 (m, 2H), 7.21 (m, 1112, 801 3H), 7.15 (m, 4H), 6.56 (d, J =
16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.4 Hz, 1H), 6.08 (br s, 1H),
4.68 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.44 (s, 3H) A10 140-143
458.00 7.38 (t, J = 1.6 Hz, 1H), ([M - H].sup.-) 7.34 (d, J = 7.6
Hz, 1H), 7.27 (m, 2H), 7.24 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H),
6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (m 1H), 5.44 (m, 1H), 4.12
(m, 1H), 3.51 (m, 2H), 3.40 (m, 2H), 2.44 (s, 3H) AC11 476.17
7.39-7.29 (m, 9H), 7.24 3287, 1644, ([M - H].sup.-) (m, 2H), 6.56
(d, J = 1112, 801 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H),
5.99 (br s, 1H), 4.63 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H), 2.47 (s,
3H) AC12 479.30 8.63 (d, J = 4.4 Hz, 1H), 3293, 1653, ([M +
H].sup.+) 7.71 (m, 1H), 7.47 (d, J = 1112, 800 8.4 Hz, 1H), 7.37
(m, 2H), 7.32 (m, 2H), 7.23 (m, 2H), 7.13 (m, 1H), 6.58 (d, J =
16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.75 (d, J = 4.8 Hz,
2H), 4.12 (m, 1H), 2.49 (s, 3H) AC13 75-78 490.04 7.38 (m, 2H),
7.27 (m, ([M - H].sup.-) 3H), 7.23 (br s, 1H), 6.58 (d, J = 16.0
Hz, 1H), 6.45 (m 1H), 6.42 (dd, J = 16.0, 8.4 Hz, 1H), 4.91 (m 1H),
4.64 (m, 2H), 4.14 (m, 1H), 4.04 (m, 2H), 2.46 (s, 3H) AC14 480.99
8.63 (s, 2H), 7.76 (d, J = 3293, 1645, ([M + 2H].sup.+) 8.0 Hz,
1H), 7.36 (m, 1113, 800 3H), 7.22 (m, 1H), 7.13 (m, 2H), 6.57 (d, J
= 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H),
4.66 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC15 59-61
516.86 7.45 (s, 1H), 7.37 (m, 3246, 1635, ([M - H].sup.-) 1H), 7.34
(m, 1H), 7.26 1112, 801 (m, 3H), 7.22 (m, 1H), 6.57 (d, J = 16.0
Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.71 (d, J
= 6.4 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC16 506.93 8.47 (m, 1H),
8.19 (s, 1657, 1113, ([M + H].sup.+) 1H), 7.76 (m, 1H), 7.47 801
(m, 2H), 7.37 (m, 1H), 7.28 (m, 2H), 7.24 (m, 1H), 7.21 (m, 1H),
6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.4 Hz, 1H), 4.12
(m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC17 70-73 494.98 7.49 (m, 2H),
7.38 (m, ([M - H].sup.-) 1H), 7.29 (m, 4H), 7.08 (m, 3H), 6.91 (m,
1H), 6.61 (d, J = 16.0 Hz, 1H), 6.48 (m, 1H), 6.43 (dd, J = 16.0,
8.0 Hz, 1H), 4.13 (m, 1H), 2.49 (s, 3H) AC18 155-158 480.44 8.73
(d, J = 4.8 Hz, 2H), ([M + H].sup.+) 7.53 (d, J = 8.4 Hz, 1H), 7.37
(m, 1H), 7.27 (m, 4H), 7.23 (m, 1H), 7.11 (m, 1H), 6.60 (d, J =
16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (d, J = 4.8 Hz,
2H), 4.13 (m, 1H), 2.52 (s, 3H) AC19 55-57 471.66 7.37 (m, 1H),
7.33 (d, J = ([M + H].sup.+) 7.6 Hz, 1H), 7.27 (m, 2H), 7.22 (m,
2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H),
6.10 (brs, 1H), 4.13 (m, 2H), 3.94 (m, 1H), 3.79 (m, 2H), 3.35 (m,
1H), 2.45 (s, 3H), 2.14 (m, 1H), 1.71 (m, 2H), 1.65 (m, 1H). AC20
467.68 7.37 (m, 2H), 7.27 (m, 3437, 1664, ([M + H].sup.+) 2H), 7.23
(m, 2H), 6.57 1265, 1114, (d, J = 16.0 Hz, 1H), 746 6.38 (m, 3H),
6.01 (m, 1H), 4.63 (d, J = 5.6 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H)
AC21 61-64 528.78 8.44 (s, 1H), 8.18 (s, ([M + H].sup.+) 1H), 7.83
(br s, 1H), 7.38 (m, 2H), 7.27 (m, 2H), 7.25 (m, 2H), 7.21 (m, 1H),
6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.01
(s, 2H), 4.11 (m, 1H), 2.43 (s, 3H) AC22 545.08 8.39 (s, 1H), 7.73
(m, 3270, 1642, ([M - H].sup.-) 1H), 7.40 (s, 1H), 7.35 1111, 809
(m, 2H), 7.22 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.38 (dd, J =
16.0, 7.6 Hz, 1H), 6.14 (br s, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13
(m, 1H), 2.45 (s, 3H) AC23 492.35 7.42 (s, 2H), 7.36 (m, 3273,
1641, ([M - H].sup.-) 1H), 7.24 (m, 2H), 6.59 1250, 1113, (d, J =
16.0 Hz, 1H), 807 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.20 (br s, 1H),
5.46 (m, 1H), 4.15 (m, 1H), 3.52 (m, 2H), 3.41 (m, 2H), 2.45 (s,
3H) AC24 129-132 526.98 7.40 (m, 2H), 7.27 (m, 3298, 1664, ([M +
H].sup.+) 2H), 7.25 (m, 2H), 6.92 1113, 803 (br s, 2H), 6.60 (m,
1H), 6.48(dd, J = 16.0, 8.0 Hz, 1H), 4.19 (d, J = 5.2, 2H), 4.08
(m, 1H), 3.99 (m, 2H), 2.46 (s, 3H) AC25 542.24 7.41 (m, 3H), 7.27
(m, 3257, 1652, ([M - H].sup.-) 2H), 6.58 (d, J = 15.6 1316, 1109,
Hz, 1H), 6.42 (m, 2H), 807 4.92 (m, 1H), 4.65 (m, 2H), 4.14 (m,
1H), 4.09 (m, 2H), 2.46 (s, 3H) AC26 550.69 7.45 (s, 1H), 7.40 (s,
3255, 1638, ([M - H].sup.-) 2H), 7.34 (d, J = 8.0 Hz, 1113, 809
1H), 7.22 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0,
8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H)
AC27 541.00 8.46 (d, J = 4.0 Hz, 1H), 1653, 1113, ([M - H].sup.-)
8.20 (s, 1H), 7.76 (m, 809 1H), 7.47 (m, 2H), 7.41 (s, 2H), 7.23
(m, 2H), 7.21 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.37 (dd, J =
16.0, 8.4 Hz, 1H), 4.11 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC28
65-67 564.84 8.40 (s, 1H), 7.74 (m, 3267, 1650, ([M - H].sup.-)
2H), 7.42 (m, 3H), 7.36 1112, 809 (m, 2H), 6.72 (br s, 1H), 6.52
(d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J =
6.4 Hz, 2H), 4.12 (m, 1H) AC29 75-78 511.78 7.71 (d, J = 8.4 Hz,
1H), ([M - H].sup.-) 7.42 (m, 3H), 7.35 (m, 1H), 6.75 (br s, 1H),
6.56 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 5.49
(m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC30 110-113 543.72 7.42 (d, J
= 8.4 Hz, 1H), ([M - H].sup.-) 7.44 (s, 1H), 7.40 (s, 1H), 7.38 (m,
1H), 7.06 (br s, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.45 (dd, J =
15.6, 8.0 Hz, 1H), 4.93 (m, 1H), 4.65 (m, 2H), 4.13 (m, 3H) AC31
68-70 610.73 8.42 (s, 1H), 7.76 (m, ([M + H].sup.+) 1H), 7.61 (m,
2H), 7.39 (m, 4H), 6.54-6.39 (m, 3H), 4.66 (d, J = 6.0 Hz,
2H), 4.12 (m, 1H) AC32 78-80 555.89 7.61 (m, 2H), 7.40 (m, ([M -
H].sup.-) 3H), 6.54 (m, 2H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.46
(m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC33 182-184 587.68 7.62 (s,
1H), 7.58 (d, J = ([M - H].sup.-) 8.0 Hz, 1H), 7.40 (m, 3H), 6.84
(br s, 1H), 6.55 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 7.6 Hz,
1H), 4.93 (m 1H), 4.65 (m, 2H), 4.13 (m, 4H) AC34 151-153 545.83
7.67 (s, 1H), 7.61 (d, J = ([M - H].sup.-) 6.0 Hz, 1H), 7.53 (m,
1H), 7.41 (s, 2H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0,
8.0 Hz, 1H), 6.18 (br s, 1H), 5.44 (m, 1H), 4.14 (m, 1H), 3.50 (m,
2H), 3.40 (m, 2H) AC35 100-102 577.71 7.70 (s, 1H), 7.63 (m, 3257,
1655, ([M - H].sup.-) 1H), 7.53 (d, J = 7.6 Hz, 1113, 808 1H), 7.41
(s, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.49 (m, 2H), 4.93 (m, 1H),
4.64 (m, 2H), 4.13 (m, 1H), 4.03 (m, 2H) AC36 81-83 600.83 8.40 (s,
1H), 7.73 (m, ([M + H].sup.+) 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.52
(d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.35 (d, J = 8.0 Hz, 1H), 6.63
(d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (m,
1H), 4.63 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H) AC37 512.68 8.39 (s,
1H), 7.73 (m, 3268, 1644, ([M + H].sup.+) 1H), 7.48 (m, 2H), 7.34
1109, 820 (d, J = 7.6 Hz, 1H), 7.24 (m, 3H), 6.55 (d, J = 16.0 Hz,
1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 6.12 (m, 1H), 4.62 (d, J =
6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC38 79-80 528.85 8.46 (m,
1H), 7.73 (m, ([M - H].sup.-) 1H), 7.35 (m, 4H), 7.22 (m, 2H), 6.56
(d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.62 (d, J =
6.0 Hz, 2H), 4.10 (m, 1H), 2.45 (s, 3H) AC39 141-144 477.83 9.19
(s, 1H), 8.79 (s, ([M - H].sup.-) 2H), 7.37 (m, 2H), 7.23 (m, 2H),
7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz
1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC40
69-72 484.67 8.33 (t, J = 5.6 Hz, 1H), ([M + H].sup.+) 8.61 (m,
1H), 7.68 (m, 3H), 7.48 (m, 2H), 6.86 (dd, J = 15.6, 8.2 Hz 1H),
6.74 (d, J = 15.6 Hz, 1H), 4.44 (m, 1H), 3.76 (d, J = 6.0 Hz, 2H),
2.54 (m, 1H), 2.67 (s, 3H), 0.59 (m, 2H), 0.54 (m, 2H) AC41 196-199
515.00 8.66 (d, J = 7.6 Hz, 1H), ([M - H].sup.-) 8.39 (t, J = 5.6
Hz, 1H), 7.65 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 15.6, 8.8 Hz,
1H), 6.74 (d, J = 15.6 Hz, 1H), 5.01 (m, 1H), 4.99 (m, 1H), 3.78
(d, J = 6.0 Hz, 2H), 3.40 (m, 2H), 3.22 (m, 2H), 2.37 (m, 3H) AC42
79-82 534.72 7.99 (d, J = 8.0 Hz, ([M + H].sup.+) 1H), 7.89 (d, J =
8.0 Hz, 1H), 7.51 (m, 2H), 7.44 (m, 2H), 7.27 (m, 4H), 6.71 (t, J =
5.2 Hz, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz,
1H), 5.05 (d, J = 1.6 Hz, 2H), 4.12 (m, 1H), 2.52 (m, 3H) AC43
481.75 8.69 (s, 1H), 8.52 (s, 1663, 1608, ([M + H].sup.+) 2H), 7.45
(d, J = 7.6 Hz, 1168, 1114, 1H), 7.37 (d, J = 2.0 Hz, 801 1H), 7.26
(m, 2H), 7.21 (m, 1H), 6.83 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H),
6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.81 (d, J = 5.6 Hz, 2H), 4.12 (t,
J = 8.4 Hz 1H), 2.45 (s, 3H) AC44 528.01 8.44 (d, J = 2.4 Hz, 1H),
1640, 1166, ([M + H].sup.+) 7.69 (d, J = 2.4 Hz, 1H), 1112, 800
7.37 (m, 1H), 7.33 (s, 1H), 7.31 (s, 1H), 7.26 (m, 1H), 7.24 (m,
3H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H),
5.96 (d, J = 7.2 Hz, 1H), 5.32 (t, J = 7.2 Hz, 1H), 4.11 (t, J =
8.4 Hz, 1H), 2.41 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H) AC45 512.88
7.66 (s, 1H), 7.37 (d, J = 1657, 1167, ([M + H].sup.+) 6.8 Hz, 2H),
7.26 (m, 1106, 800 3H), 7.18 (m, 1H), 7.11 (m, 2H), 6.99 (m, 1H),
6.57 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.11
(t, J = 8.4 Hz, 1H), 3.36 (s, 3H), 2.43 (s, 3H) AC46 61-64 575.93
8.42 (d, J = 2.0 Hz, 1H), ([M + H].sup.+) 7.76 (d, J = 2.4 Hz, 1H),
7.61 (m, 2H), 7.39 (m, 3H), 7.26 (s, 2H), 6.54 (d, J = 16.0 Hz,
1H), 6.42 (dd, J = 16.0, 7.6 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H),
4.14 (m, 1H) AC47 525.89 10.02 (s, 1H), 9.87 (s, 3280, 1640 ([M -
H].sup.-) 1H), 8.47 (t, J = 6.0 Hz, 1H), 7.66 (s, 3H), 7.44 (s,
1H), 7.40 (d, J = 3.6 Hz, 2H), 6.86 (dd, J = 15.6, 9.2 Hz, 1H),
6.74 (d, J = 15.6 Hz, 1H), 4.82 (t, J = 9.6 Hz, 2H), 3.88 (d, J =
6.0 Hz, 2H), 2.36 (s, 3H), 1.63 (m, 1H), 0.76 (m, 4H) AC48 509.96
7.37 (m, 7H), 7.34 (m, 3275, 1642 ([M - H].sup.-) 3H), , 6.57 (d, J
= 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.01 (m, 1H), 4.60
(d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.46 (s, 3H) AC49 518.85 8.39
(d, J = 2.0 Hz, 1H), 1658, 1112, ([M + H].sup.+) 8.11 (m, 1H), 7.71
(d, 1025, 2219 J = 2.4 Hz, 1H), 7.41 (m, 3H), 7.17 (m, 3H), 6.59
(d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J =
5.6 Hz, 2H), 4.14 (m, 1H) AC50 481.88 8.72 (m, 1H), 7.67 (s, 1654,
1112, ([M + H].sup.+) 3H), 7.46 (s, 1H), 7.40 800, 3069 (m, 2H),
7.08 (s, 1H), 6.82 (m, 2H), 6.55 (d, J = 7.6 Hz, 1H), 4.82 (m, 1H),
4.48 (s, 2H), 3.65 (s, 3H), 2.38 (s, 3H) AC51 540.83 7.45 (d, J =
7.6 Hz, 1H), 1652, 1571, ([M + H].sup.+) 7.38 (m, 1H), 7.27 (m,
802, 1114, 2H), 7.22 (m, 2H), 6.85 2926 (m, 1H), 6.58 (d, J = 16.0
Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.33 (m, 2H), 4.14 (m,
3H), 3.18 (s, 3H), 2.48 (s, 3H) AC52 488.29 7.33 (m, 2H), 7.25 (m,
1635, 11134, ([M - H].sup.-) 3H), 6.56 (d, J = 15.6 813, 2927 Hz,
1H), 6.37 (dd, J = 15.6, 8.0 Hz, 1H), 5.61 (d, J = 8.0 Hz, 1H),
4.21 (m, 1H), 4.01 (m, 1H), 4.08 (m, 2H), 3.56 (t, J = 10.0 Hz,
2H), 2.48 (m, 2H), 2.08 (m, 2H), 1.5 (m, 3H) AC53 532.92 8.49 (d, J
= 2.0 Hz, 1H), 1651, 3027, ([M + H].sup.+) 7.69 (d, J = 2.4 Hz,
1H), 815, 1113 7.43 (d, J = 8.0 Hz, 1H), 7.34 (m, 3H), 7.26 (m,
2H), 6.95 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0,
8.0 Hz, 1H), 4.72 (d, J = 5.2 Hz, 2H), 4.09 (m, 1H), 2.47 (s, 3H)
AC54 529.06 8.37 (d, J = 5.2 Hz, 1H), 1654, 3434, ([M - H].sup.-)
7.41 (d, J = 8.0 Hz, 1H), 814, 1112 7.36 (m, 3H), 7.31 (m, 1H),
7.26 (m, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6
Hz, 1H), 5.20 (t, J = 5.6 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.13
(m, 1H), 2.18 (s, 3H) AC57 464.96 8.69 (t, J = 6.0 Hz, 1H), 3417,
1658, ([M + H].sup.+) 8.58 (t, J = 6.0 Hz, 1H), 1165, 817 7.92 (s,
1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J
= 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H), 6.76 (dd, J
= 15.6, 8.0 Hz, 1H), 4.01 (m, J = 8.0 Hz, 1H), 3.71 (m, 2H), 3.49
(m, 2H) AC58 124.4-126.9 599.76 7.62 (m, 2H), 7.40 (s, ([M +
H].sup.+) 2H), 7.37 (d, J = 1.6 Hz, 1H), 6.61 (t, J = 4.8 Hz, 1H),
6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.16
(d, J = 6.0 Hz, 2H), 4.01 (m, 1H), 1.56 (s, 9H) AC59 80-83 497.40
8.42 (d, J = 2.1 Hz, 1H), ([M - H].sup.-) 8.29 (d, J = 7.5 Hz, 1H),
7.51 (m, 2H), 7.39 (m, 1H), 7.36 (m, 4H), 7.28 (m, 1H), 6.61 (d, J
= 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8 Hz 1H), 4.14 (t, J = 8.4
Hz, 1H), 2.51 (s, 3H) AC60 515.09 8.52 (s, 1H), 8.39 (d, J = 1668,
1589, ([M + H]-) 1.8 Hz, 2H), 7.70 (d, J = 1167, 1113, 2.1 Hz, 1H),
7.62 (s, 802 1H), 7.43 (s, 1H), 7.35 (m, 3H), 6.62 (d, J = 16.2 Hz,
1H), 6.52 (dd, J = 16.2, 7.5 Hz, 1H), 4.62 (d, J = 6.3 Hz, 2H),
4.19 (m, 1H), 2.76 (s, 3H) AC61 461.90 8.07 (t, J = 8.0 Hz, 1H),
1658, 1114, ([M - H].sup.-) 7.39 (t, J = 2.0 Hz, 1H), 801 7.28 (d,
J = 1.2 Hz, 3H), 7.17 (d, J = 1.6 Hz, 1H), 7.11 (m, 1H), 6.59 (d, J
= 15.6 Hz, 1H), 6.47 (dd, J = 15.6, 7.6 Hz,
1H), 5.49 (m, 1H), 4.14 (t, J = 8.4 Hz, 1H), 3.48 (m, 4H) AC62
105-108 528.88 8.62 (t, J = 6.4 Hz, 1H), ([M - H].sup.-) 8.46 (m,
1H), 7.73 (m, 5H), 7.48 (d, J = 7.6 Hz, 1H), 7.03 (dd, J = 15.6,
9.2 Hz, 1H), 6.81 (d, J = 15.6 Hz, 1H), 4.86 (m, 1H), 3.97 (m, 4H)
AC63 77-80 594.67 8.43 (s, 1H), 7.76 (d, J = 3257, 1653 ([M +
H].sup.+) 2.4 Hz, 1H), 7.60 (m, 2H), 7.38 (d, J = 7.6 Hz, 1H), 7.33
(d, J = 6.4 Hz, 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.46 (m, 1H), 6.41
(dd, J = 16.0 8.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H)
AC64 83-85 580.72 7.72 (d, J = 8.0 Hz, 1H), ([M - H].sup.-) 7.44
(s, 1H), 7.40 (s, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.05 (t, J = 5.2
Hz, 1H), 6.70 (t, J = 5.2 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.44
(dd, J = 15.6, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.15 (m, 1H),
4.01 (m, 2H) AC65 534.72 8.39 (d, J = 2.0 Hz, 1H), 1658, 1113, ([M
- H].sup.-) 8.12 (t, J = 8.4 Hz, 1H), 817, 2925 7.71 (d, J = 2.4
Hz, 1H), 7.34 (m, 3H), 7.26 (m, 1H), 7.11 (m, 2H), 6.59 (d, J =
16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.2 Hz,
2H), 4.13 (m, 1H) AC66 73-75 624.61 7.88 (s, 1H), 7.63 (d, J = ([M
- H].sup.-) 1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.40 (m, 2H),
6.80 (t, J = 5.6 Hz, 1H), 6.70 (t, J = 5.6 Hz, 1H), 6.56 (d, J =
16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 2H), 4.12
(m, 1H), 4.01 (m, 2H) AC67 479.82 8.07 (t, J = 8.0 Hz, 1H), 3272,
1644 ([M - H].sup.-) 7.34 (d, J = 6.0 Hz, 2H), 7.28 (s, 1H),
7.17(s, 2H), 6.59 (d, J = 15.6 Hz, 1H), 6.46 (dd, J = 15.6, 8.0 Hz,
1H), 5.49 (m, 1H), , 4.12 (m, 1H), 3.49 (m, 4H). AC68 90-93 546.80
8.6 (t, J = 6.4 Hz, 1H), 3315, 1684 ([M - H].sup.-) 8.45 (m, 1H),
7.86 (d, J = 6.4 Hz, 2H), 7.75 (t, J = 8.0 Hz, 1H), 7.63 (d, J =
12.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz,
1H), 6.80 (d, J = 15.6 Hz, 1H), 4.88 (m, 1H), 3.96 (m, 4H) AC69
542.82 7.41 (d, J = 8.0 Hz, 1H), 3294, 1685 ([M - H].sup.-) 7.34
(d, J = 5.6 Hz, 2H), 7.26 (m, 1H), 7.23 (m, 1H), 6.81 (s, 1H), 6.57
(d, J = 15.6 Hz, 1H), 6.55 (s, 1H), 6.39 (dd, J = 15.6, 8.0 Hz,
1H), 4.18 (m, 2H), 4.13 (m, 1H), 3.97 (m, 2H), 2.46 (s, 3H) AC70
176-178 545.23 8.38 (d, J = 2.4 Hz, 1H), ([M - H].sup.-) 8.22 (d, J
= 6.8 Hz, 2H), 7.71 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 6.0 Hz, 2H),
7.30 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 1.6 Hz, 1H), 6.93 (d, J =
1.2 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.6, 7.6 Hz,
1H), 4.66 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 3.98 (s, 3H) AC71
492.20 8.24 (d, J = 7.6 Hz, 1H), 1639, 3079, ([M - H].sup.-) 8.15
(d, J = 8.4 Hz, 1H), 858 7.35 (d, J = 6.0 Hz, 2H), 7.13 (d, J = 1.2
Hz, 1H), 6.92 (s, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.43 (dd, J =
16.0, 7.6 Hz, 1H), 5.48 (m, 1H), 4.13 (m, 1H), 4.03 (s, 3H), 3.48
(m, 4H) AC72 543.05 8.42 (d, J = 2.4 Hz, 1H), 1642, 3246, ([M -
H].sup.-) 7.75 (d, J = 2.4 Hz, 1H), 814, 1113 7.34 (m, 4H), 7.20
(m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz,
1H), 6.12 (t, J = 5.6 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.20 (m,
1H), 2.82 (m, 2H), 1.45 (t, J = 5.6 Hz, 3H) AC75 644.78 8.72 (s,
1H), 7.97 (d, J = 3431, 1652, ([M + H].sup.+) 7.2 Hz, 1H), 7.70 (d,
J = 1171, 809 8.4 Hz, 1H), 7.61 (m, 2H), 7.40 (m, 2H), 6.55 (m,
2H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.76 (d, J = 6.0 Hz, 2H),
4.12 (m, 1H) AC76 531.34 8.87 (t, J = 6.0 Hz, 1H), 3120, 1708, ([M
+ H].sup.+) 8.34 (d, J = 2.1 Hz, 1H), 1171 7.85 (d, J = 6.3 Hz,
3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6,
9.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.82 (m, 2H),
2.36 (t, J = 5.6 Hz, 3H) AC77 531.1 8.87 (t, J = 6.0 Hz, 1H), 3444,
1648, ([M + H].sup.+) 8.34 (d, J = 2.1 Hz, 1H), 1114, 814 7.85 (d,
J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd,
J = 15.6, 8.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.36
(s, 3H) AC78 561.06 8.59 (t, J = 6.4 Hz, 1H), 3432, 1631, ([M +
H].sup.+) 8.47 (t, J = 5.6 Hz, 1H), 1161, 840 7.89 (s, 2H), 7.45
(m, 3H), 6.87 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (t, J = 8.0
Hz 1H), 3.98 (m, 4H), 2.58 (s, 3H) AC79 610.97 8.69 (t, J = 6.0 Hz,
1H), 3303, 1658, ([M + H].sup.+) 8.58 (t, J = 6.0 Hz, 1H), 1166,
817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz,
1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz,
1H) 4.83 (t, J = 8.0 Hz, 1H), 3.98 (m, 4H) AC80 561.06 7.37 (m,
3H), 7.26 (m, 3412, 1624, ([M + H].sup.+) 1H), 7.24 (m, 1H), 6.59
1157, 825 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H),
4.24 (m, 4H), 3.90 (m, 1H), 2.83 (m, 2H), 1.26 (m, 3H) AC81 9-92
546.93 8.73 (d, J = 5.6 Hz, 1H), ([M - H].sup.-) 8.45 (t, J = 6.0
Hz, 1H), 7.76 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 16.0, 9.2 Hz,
1H), 4.83 (m, 1H), 4.56 (m, 2H), 4.51 (m, 1H), 4.10 (m, 2H), 3.85
(d, J = 6.0 Hz, 2H), 2.50 (m, 3H) AC82 477.69 7.38 (d, J = 1.8 Hz,
2H), 1646, 1353, ([M + H].sup.+) 7.33 (s, 1H), 7.27 (s, 3H), 1196,
1112, 6.58 (d, J = 16.0 800 Hz, 1H), 6.42 (d, J = 8.1 Hz, 1H), 6.36
(dd, J = 16.0, 7.8 Hz, 1H), 4.71 (m, 1H), 4.23 (m, 3H), 3.26 (m,
2H), 2.45 (s, 3H) AC83 493.83 8.07 (t, J = 8.4 Hz, 1H), 1527, 1113,
([M - H].sup.-) 7.39 (t, J = 1.6 Hz, 1H), 801, 1167, 7.31 (d, J =
1.2 Hz, 1H), 1321 7.26 (m, 2H), 7.23 (m, 1H), 7.19 (d, J = 1.6 Hz,
1H), 6.60 (d, J = 16.8 Hz, 1H), 6.49 (dd, J = 16.8, 7.6 Hz, 1H),
4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H), 4.10 (m, 1H) AC84 511.75
8.07 (t, J = 8.0 Hz, 1H), 1645, 1113, ([M - H].sup.-) 7.34 (m, 3H),
7.19 (d, J = 804, 3030, 13.2 Hz, 1H), 6.60 (d, J = 1245 16.4 Hz,
1H), 6.48 (dd, J = 16.4, 8.0 Hz, 1H), 4.88 (m, 1H), 4.62 (m, 2H),
4.12 (m, 3H) AC85 523.83 8.60 (d, J = 6.8 Hz, 1H), 1652, 3039, ([M
- H].sup.-) 8.15 (d, J = 8.4 Hz, 1H), 802, 1114 7.35 (d, J = 6.0
Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.94 (s, 1H), 6.60 (d, J = 15.6
Hz, 1H), 6.44 (dd, J = 7.6, 7.6 Hz, 1H), 4.93 (m, 1H), 4.62 (m,
2H), 4.13 (m, 6H) AC86 524.36 7.35 (d, J = 6.3 Hz, 3H), 3333, 1651,
([M + H].sup.+) 7.26 (m, 2H), 7.20 (m, 815 1H), 6.60 (d, J = 15.9
Hz, 1H), 6.47 (dd, J = 15.9, 6.6 Hz, 1H), 4.86 (m, 1H), 4.65 (m,
2H), 4.13 (m, 3H), 2.84 (q, 2.8 Hz, 2H), 1.26 (m, 3H) AC87 495.82
8.07 (t, J = 8.0 Hz, 1H), 1623, 1114, ([M - H].sup.-) 7.52 (m, 3H),
7.19 (d, 816 J = 13.2 Hz, 1H), 6.59 (d, J = 16.4 Hz, 1H), 6.47 (dd,
J = 16.4, 8.0 Hz, 1H), 4.69 (m, 1H), 4.23 (m, 3H), 3.29 (m, 2H)
AC89 509.89 7.43 (m, 2H), 7.27 (m, 1666, 1166, ([M + H].sup.+) 2H),
7.23 (m, 2H), 6.58 1112, 800 (d, J = 16.0 Hz, 1H), 6.41 (dd, J =
16.0, 7.6 Hz, 1H), 4.79 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s,
3H), 2.18 (m, 1H), 1.16 (m, 4H) AC90 656.9 8.34 (m, 1H), 8.27 (m,
([M - H].sup.-) 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.0 Hz,
2H), 7.40 (s, 2H), 7.36 (dd, J = 8.2, 1.7 Hz, 1H), 6.53 (d, J =
16.0 Hz, 1H), 6.38 (dd, J = 15.9, 7.9 Hz, 1H), 4.89 (d, J = 8.4 Hz,
2H), 4.48 (d, J = 9.0 Hz, 2H), 4.11 (m, 1H) AC91 640.9 8.18 (t, J =
5.0 Hz, 1H), ([M - H].sup.-) 7.58 (d, J = 1.6 Hz, 1H), 7.47 (d, J =
8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J = 8.1, 1.6 Hz, 1H), 6.52 (m,
2H), 6.37 (dd, J = 15.9, 7.9 Hz, 1H), 4.54 (d, J = 4.9 Hz, 2H),
4.12 (m, 1H), 3.99 (qd, J = 8.9, 6.5 Hz, 2H) AC92 640.9 9.16 (d, J
= 6.1 Hz, 1H), ([M - H].sup.-) 7.65 (d, J = 1.6 Hz, 1H), 7.57 (d, J
= 8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J = 5.6 Hz, 1H), 6.55 (d, J
=
15.9 Hz, 1H), 6.41 (dd, J = 15.9, 7.8 Hz, 1H), 4.59 (d, J = 5.6 Hz,
2H), 4.45 (qd, J = 9.0, 6.0 Hz, 2H), 4.12 (q, J = 7.2 Hz, 1H) AC93
485.5 7.52-7.41 (d, J = 8.2 Hz, .sup.13C NMR (.delta.).sup.3 ([M +
H].sup.+) 1H), 7.39-7.34 (m, 1H), 169.91, 169.84, 7.24-7.17 (d, J =
1.8 Hz, 138.23, 137.41, 2H), 7.02-6.92 (m, 2H), 136.84, 134.79,
6.90-6.83 (d, J = 11.4 134.69, 131.07, Hz, 1H), 6.71 (br s, 1H),
128.69, 127.49, 6.17 (br s, 1H), 6.12- 127.43, 126.72, 6.01 (dd, J
= 11.4, 10.3 126.61 (q, J = Hz, 1H), 4.44-4.38 (d, 212.10 Hz), J =
4.2 Hz, 1H), 4.35-4.27 125.61, (m, 1H), 4.10-3.99 (d, J = 123.76,
47.89 5.1 Hz, 2H), 2.78-2.67 (q, J = 28.28 (m, 1H), 2.44 (s, 3H),
Hz), 43.46, 0.88-0.78 (m, 2H), 0.60- 22.65, 19.97, 0.45 (m, 2H)
8.21 AC94 511.6 8.36-8.24 (d, J = 2.4 3262, 1607, ([M].sup.-) Hz,
1H), 7.75-7.64 (m, 1247, 1164, 1H), 7.38-7.24 (m, 3H), 1111
7.24-7.09 (d, J = 1.8 Hz, 2H), 6.99-6.90 (m, 2H), 6.89-6.74 (d, J =
11.4 Hz, 1H), 6.63- 6.43 (m, 1H), 6.14- 5.98 (m, 1H), 4.69- 4.51
(d, J = 6.1 Hz, 2H), 4.37-4.20 (m, 1H), 2.46-2.31 (s, 3H) AC95
48-61 626.9 7.58 (d, J = 7.9 Hz, 1H), ([M + H].sup.+) 7.44-7.29 (m,
3H), 7.14 (dd, J = 7.9, 1.6 Hz, 1H), 6.86 (d, J = 11.4 Hz, 1H),
6.76 (t, J = 5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23
(d, J = 5.5 Hz, 1H), 3.98 (qd, J = 9.0, 6.5 Hz, 2H) AC96 619.6 8.83
(s, 1H), 8.06 (br, 1616, 1114 ([M + H].sup.+) 1H), 7.90 (s, 2H),
7.63 (d, J = 8.1 Hz, 2H), 7.53 (m, 1H), 6.94 (m, 1H), 6.77 (d, J =
15.3 Hz, 1H), 6.63 (d, J = 9.3 Hz, 1H), 4.84 (m, 1H), 4.30 (d, J =
5.6 Hz, 2H), 2.99 (s, 6H) AC97 606.6 8.20 (d, J = 2.1 Hz, 1H),
1644, 1113 ([M + H].sup.+) 7.73 (d, J = 2.7 Hz, 1H), 7.60 (m, 2H),
7.39 (s, 2H), 7.29 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.55 (d, J =
15.9 Hz, 1H), 6.40 (m, 2H), 4.60 (d, J = 2.7 Hz, 2H), 4.13 (m, 1H),
3.95 (s, 3H) AC98 577.87 9.04 (t, J = 6.0 Hz, 1H), 1663, 1168 ([M +
H].sup.+) 8.60 (t, J = 6.6 Hz, 1H), 8.25 (s, 1H), 7.97 (d, J = 8.1
Hz, 1H), 7.87 (d, J = 6.3 Hz, 2H), 7.69 (d, J = 7.5 Hz, 1H), 7.15
(dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.86 (m,
1H), 3.98 (m, 4H). AC99 574.81 8.69 (t, J = 6.0 Hz, 1H), 1650, 1164
([M + H].sup.+) 8.58 (t, J = 6.6 Hz, 1H), 7.91 (s, 1H), 7.85 (m,
1H), 7.61 (m, 2H), 7.52 (m, 2H), 6.98 (dd, J = 15.3, 9.0 Hz, 1H),
6.76 (d, J = 15.3 Hz, 1H), 4.81 (m, 1H), 4.01 (m, 4H) AC100 673.80
8.29 (s, 1H), 8.22 (d, J = 3403, 1659 ([M + H].sup.+) 8.1 Hz, 1H),
7.93 (d, J = 7.8 Hz, 1H), 7.72 (m, 1H), 7.65 (m, 2H), 7.40 (s, 2H),
7.18 (br, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6
Hz, 1H), 5.02 (d, J = 1.2 Hz, 2H), 4.12 (m, 1H) AC101 636.83 7.56
(d, J = 9.0 Hz, 1H), 1637, 1113 ([M + H].sup.+) 7.39 (d, J = 6.0
Hz, 2H), 7.26 (m, 2H), 6.54 (d, J = 15.9 Hz, 1H), 6.37 (dd, J =
8.0, 15.9 Hz, 1H), 4.01 (m, 1H), 3.84 (m, 2H), 3.33 (m, 2H), 3.04
(m, 2H), 2.84 (m, 3H), 2.62 (m, 1H) AC102 592.84 7.60 (m, 2H), 7.32
(m, 1H), 1668, 1167 ([M + H].sup.+) 7.03 (d, J = 7.2 Hz, 2H), 6.74
(br, 1H), 6.62 (br, 1H), 6.56 (d, J = 16.2 Hz, 1H), 6.41 (dd, J =
16.2, 7.8 Hz, 1H), 4.22 (d, J = 5.4 Hz, 2H), 4.14 (m, 1H), 4.01 (m,
2H) AC103 99.2-105.0 612.7 8.40 (d, J = 8.0 Hz, 1H), 1634, 1113,
([M + H].sup.+) 7.92 (d, J = 5.2 Hz, 1H), 809 7.59 (d, J = 8.0 Hz,
1H), 7.35 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0, 7.6 Hz, 1H),
6.76 (d, J = 16.0 Hz, 1H), 4.84 (m, 1H), 4.23 (d, J = 13.2 Hz, 1H),
3.97 (m, 1H), 3.79 (d, J = 13.6 Hz, 1H), 3.16 (t, J = 11.2 Hz, 1H),
2.77 (t, J = 11.2 Hz, 1H), 1.99 (s, 3H), 1.88 (m, 2H), 1.45 (m, 2H)
AC104 680.97 7.60 (m, 2H), 7.40 (m 3437, 1644, ([M + H].sup.+) 3H),
6.55 (d, J = 15.6 1113, 807, Hz, 1H), 6.41 (dd, J = 511 15.6, 7.8
Hz, 1H), 4.24 (m, 1H), 3.34 (m, 2H), 2.90 (m, 1H), 2.24 (m, 2H),
1.52(m, 2H), 1.34 (m, 4H) AC105 609.9 7.59 (s, 1H), 7.55 (m, 3303,
1649, ([M + H].sup.+) 1H), 7.50 (m, 1H), 7.40 1115, 2242, (m, 2H),
6.54(d, J = 809, 506 16.0 Hz, 1H), 6.50 (J = 16.0, 8.0 Hz, 1H),
4.14 (m, 2H), 3.08 (m, 4H), 2.67 (m, 2H), 2.12 (m, 2H), 1.70 (m,
2H). AC106 584.95 7.59 (s, 1H), 7.51 (d, J = 3417, 1648, ([M +
H].sup.+) 8.4 Hz, 1H), 7.40 (s, 2H), 1112, 805, 7.36 (d, J = 6.8
Hz, 1H), 555 6.54 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz,
1H), 6.03 (d, J = 8.0 Hz, 1H), 4.11 (m, 2H), 3.10 (m, 2H), 2.50 (m,
2H), 2.50 (s, 3H) (m, 2H), 1.94 (m, 2H) AC107 609.9 8.41 (d, J =
7.8 Hz, 1H), 3303, 1645, ([M + H].sup.+) 7.90 (s, 2H), 7.62 (m,
1115, 2243, 2H), 7.51(m, 1H), 6.92 810, 507 (dd, J = 15.9, 9.0 Hz,
1H), 6.77 (d, J = 15.9 Hz, 1H), 4.81 (m, 1H), 3.73 (s, 2H), 3.31
(m, 1H), 3.28 (m, 1H), 2.82 (t, J = 11.4 Hz, 2H), 2.82 (m, 2H),
2.30 (m, 2H), 1.88 (m, 2H), 1.57 (m, 2H) AC108 626.9 7.60 (m, 2H)
7.39 (s, 3420, 1649, ([M + H].sup.+) 2H), 7.28 (m, 1H), 6.56 1113,
809, (d, J = 15.6 Hz, 1H), 554 6.40 (dd, J = 15.6, 7.8 Hz, 1H),
5.91 (m, 1H), 4.65 (m, 2H), 4.10 (m, 1H), 4.07 (m, 2H), 3.59 (m,
1H), 2.74 (m, 2H), 2.13 (m, 4H), 2.07 (m, 1H) AC109 614.6 7.56 (m,
2H), 7.39 (s, 1647, 1113 ([M + H].sup.+) 2H), 7.29 (s, 1H), 6.50
(d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 8.0 Hz 1H), 4.09 (m, 1H),
3.88 (m, 2H), 3.49 (m, 2H), 2.92 (m, 2H), 2.81 (m, 1H), 2.74 (m,
2H), 2.25 (m, 4H) AC110 572.6 11.20 (s, 1H), 8.66 (br, 3412, 1690,
([M + H].sup.+) 1H), 7.92 (m, 3H), 7.62 1114, 846, (d, J = 8.0 Hz,
1H), 7.45 559 (d, J = 8.0 Hz, 1H), 6.77 (dd, J = 15.6, 9.2 Hz, 1H),
6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.74 (d, J = 5.2 Hz, 2H),
3.61 (s, 3H) AC111 582.79 8.63 (t, J = 6.0 Hz, 1H), 3419, 1659, ([M
+ H].sup.+) 8.04 (t, J = 6.0 Hz, 1H), 843, 557 7.92 (m, 3H), 7.62
(d, J = 1.2 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.00 (dd, J = 15.6,
8.8 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 5.19 (d, J = 1.6 Hz, 1H),
5.01 (d, J = 1.2 Hz, 1H), 4.85 (m, 1H), 3.86 (d, J = 5.6 Hz, 2H),
3.75 (t, J = 5.6 Hz, 2H) AC112 582.79 8.84 (br, 1H), 8.58 (m, 3399,
1662, ([M + H].sup.+) 1H), 8.30 (m, 1H), 7.91 1114, 807, (s, 2H),
7.61 (d, J = 8.1 582 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J
= 15.6, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 4.11
(d, J = 5.6 Hz, 1H), 3.73 (d, J = 5.6 Hz, 1H), 3.04 (s, 6H) AC113
626.88 8.48 (t, J = 5.2 Hz, 1H), 3431, 1651, ([M + H].sup.+) 8.3
(s, 1H), 7.90 (s, 2H), 1113, 808, 7.79 (dd, J = 2.0, 2.0 Hz 554
2H), 7.58 (d, J = 8.4 Hz, 1H) 7.46 (d, J = 7.6 Hz, 1H) 7.26 (d, J =
7.6 Hz, 1H), 6.98 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H),
3.49 (d, J = 6.4 Hz, 2H) 2.87 (t, J = 6.4 Hz, 2H) AC114 113.7-117.5
570.7 8.77 (s, 1H), 8.58 (d, J = ([M + H].sup.+) 7.2 Hz, 2H), 7.93
(d, J = 7.2 Hz, 2H), 7.60 (dd, J = 1.2, 0.8 Hz, 1H), 7.37 (d, J =
7.6 Hz, 1H), 6.99 (m, 1H), 6.77 (d, J = 16 Hz, 1H), 4.85 (m, 1H),
4.10 (m, 1H) 3.29 (m, 2H), 3.05 (m, 2H), 2.0 (m, 2H), 1.76 (m, 2H)
AC115 529.00 8.43 (s, 1H), 7.79 (d, J = 1589, 3459, ([M + H].sup.+)
8.0 Hz, 1H), 7.51 (m, 1H), 801, 1110 7.36 (d, J = 8.4 Hz, 3H), 7.21
(m, 3H), 6.55 (d, J = 15.6 Hz, 1H), 6.36 (dd, J = 15.6, 8.0 Hz,
1H), 5.04 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 2.35 (s, 3H) AC116
614.87 7.99 (d, J = 8.4 Hz, 1H), 3424, 1657, ([M + H].sup.+) 7.46
(d, J = 1.6 Hz, 1H), 1165 7.34 (d, J = 6.4 Hz, 2H), 7.28 (m, 2H),
6.62 (m, 2H), 6.47 (dd, J = 16.0, 7.2 Hz, 1H), 4.23 (m, 2H), 4.12
(m, 1H), 4.00 (m, 2H) AC117 525.42 8.39 (br, 1H), 7.85 (br, 3401,
1636, ([M - H].sup.-) 1H), 7.62 (m, 3H), 7.53 1113, 750 (d, J = 8.0
Hz, 1H), 7.46 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.17 (m, 1H), 6.78
(dd, J = 16.0, 8.8
Hz, 1H), 6.70 (m, 1H), 4.77 (m, 1H), 4.66 (s, 1H), 4.32 (s, 1H),
2.97 (s, 3H), 2.16 (s, 3H) AC118 471.79 7.36 (d, J = 8.0 Hz, 2H),
3437, 1655, ([M + H].sup.+) 7.27 (m, 2H), 7.22 (m, 1262, 1105, 2H),
6.57 (d, J = 16.0 802 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H),
6.10 (br, 1H), 4.15 (m, 2H), 3.89 (m, 1H), 3.80 (m, 2H), 3.35 (m,
1H), 2.46 (s, 3H), 2.06 (s, 1H), 1.96 (m, 2H), 1.65 (m, 1H) BC1
492.17 7.39 (s, 2H), 7.25-7.18 3211, 1569, ([M + H].sup.+) (m, 3H),
6.58 (d, J = 1113, 806 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 8.4 Hz,
1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05- 2.80 (m, 6H), 2.70 (m,
1H), 1.81 (m, 1H) BC2 506.4 8.80 (s, 1H), 8.20 (s, 2923, 1542, ([M
+ H].sup.+) 1H), 7.82 (m, 3H), 7.4 1033, 805 (s, 2H), 6.62 (d, J =
16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18(m, 1H), 3.38
(m, 2H), 2.98 (m, 2H), 2.71 (m, 1H), 2.04 (m, 2H), 1.54 (s, 3H).
BC3 518.04 7.40 (s, 2H), 7.33-7.22 3120, 1592, ([M - H].sup.-) (m,
3H), 6.61 (d, J = 1146, 895 16.0 Hz, 1H), 6.34- 6.28 (dd, J = 16.0,
8.0 Hz, 1H), 5.96-5.80 (m, 3H), 5.22 (m, 4H), 4.01 (m, 2H),
2.84-2.99 (m, 2H), 2.71 (m, 1H), 1.86 (m, 1H) BC4 529.02 7.39 (s,
2H), 7.25-7.20 3283, 1652, ([M + H].sup.+) (m, 3H), 6.34 (d, J =
1241, 811 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 8.0 Hz, 1H), 5.81 (br,
1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H),
2.86 (m, 1H), 1.81 (m, 1H); BC5 544.25 7.40 (s, 2H), 7.21 (s, 3489,
3291, ([M - H].sup.-) 1H), 7.12 (m, 1H), 6.56 1655, 1112, (d, J =
16.0 Hz, 1H), 808 6.32 (dd, J = 16.0, 8.4 Hz, 1H), 5.85 (br s, 1H),
5.23 (br s, 1H), 4.12 (m, 1H), 3.18 (m, 3H), 2.80 (m, 3H), 2.08 (m,
2H), 1.83 (m, 5H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC6
485.96 7.40 (s, 2H), 7.31-7.18 3429, 1114, ([M - H].sup.-) (m, 3H),
6.58 (d, J = 804 16.0 Hz, 1H), 6.24- 6.28 (dd, J = 16.0, 8.0 Hz,
1H), 5.40 (br, 1H), 4.01 (m, 2H), 2.78- 3.01 (m, 2H), 2.51 (s, 1H),
1.86 (m, 1H), 1.20 (m, 2H), 1.01 (m, 2H), 0.78 (m, 2H) BC7 500.01
7.40 (s, 2H), 7.31 (s, 1H), 3296, 1115, ([M - H].sup.-) 7.18 (m,
1H), 7.18 806 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (dd, J =
16.0, 8.0 Hz, 1H), 5.78 (br s, 1H), 5.21 (br s, 1H), 4.01 (m, 1H),
2.78 (m, 2H), 2.01 (m, 1H), 1.86 (m, 4H), 1.25 (m, 2H), 1.01 (m,
3H), 0.78 (m, 2H) BC8 511.88 7.38-7.20 (m, 5H), 6.62 1657, 1113,
([M - H].sup.-) (d, J = 16.0 Hz, 1H), 855 6.34 (dd, J = 16.0, 8.0
Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.12 (m, 2H),
3.06- 2.82 (m, 2H), 2.75 (m, 1H), 1.85 (m, 1H) BC9 179-181 556.83
8.30 (s, 1H), 7.68 (d, J = ([M - H].sup.-) 6.4 Hz, 1H), 7.38-7.20
(m, 5H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz,
1H), 5.63 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.56 (s, 2H),
3.06-2.82 (m, 2H), 2.70 (m, 1H), 1.82 (m, 1H) BC10 497.98 7.38-7.20
(m, 5H), 6.62 3027, 1654, ([M - H].sup.-) (d, J = 16.0 Hz, 1H), 815
6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12
(m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 3H), 1.82 (m, 1H),
1.42 (m, 1H) BC11 530.09 7.80 (m, 1H), 7.48 (m, 1715, 1113, ([M -
H].sup.-) 2H), 7.32 6.65 (d, J = 816 16.0 Hz, 1H), 6.54 (dd, J =
16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32
(m, 1H), 2.86 (m, 1H), 1.81 (m, 1H) BC12 514.86 7.32, (d, J = 6.0
Hz, 2H) 3428, 1112, ([M + H].sup.+) 7.28 (m, 1H), 7.20 (d, J = 857
8.0, 1H), 7.14 (d, J = 8.8, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.60 (m,
2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19
(m, 2H); BC13 121-126 553.06 8.33 (br, 1H), 7.59 (s, ([M -
H].sup.-) 1H), 7.45 (m, 3H), 6.72 (d, J = 3.6, 1H), 6.39 (m, 1H),
4.71 (t, J = 7.2 Hz, 2H), 4.15 (m, 2H) BC14 172-175 554.0 8.83 (t,
J = 6.6 Hz, 1H), ([M - H].sup.-) 8.42 (t, J = 14.7 Hz, 1H), 8.22
(d, J = 8.1 Hz, 1H), 8.13 (t, J = 6.3 Hz, 1H), 7.98-7.86 (m, 2H),
7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88
(m, 2H) CC1 107-109 402.00 7.37 (m, 3H), 7.28 (m, ([M + H].sup.+)
4H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H),
5.75 (br s, 1H), 4.46 (d, J = 6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H)
CC2 118-120 428.11 7.37 (m, 3H), 7.28 (m, ([M + H].sup.+) 4H), 6.60
(d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br s,
1H), 4.46 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 1.40 (m, 1H), 1.02 (m,
2H), 0.77 (m, 2H) CC3 119-122 468.20 7.38 (m, 3H), 7.27 (m, ([M -
H].sup.-) 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.4
Hz, 1H), 5.00 (br s, 1H), 4.48 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H),
3.15 (q, J = 10.4 Hz, 2H) CC4 414.16 7.37 (m, 3H), 7.28 (m, ([M -
H].sup.-) 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0
Hz, 1H), 5.69 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H),
2.29 (q, J = 5.8 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H) CC5 460.28 7.40
(m, 3H), 7.28 (m, ([M - H].sup.-) 2H), 6.60 (d, J = 15.6 Hz, 1H),
6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.84 (br s, 1H), 4.46 (d, J = 5.6
Hz, 2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC6
106-108 504.08 7.40 (m, 3H), 7.26 (m, ([M - H].sup.-) 1H), 6.60 (d,
J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.96 (br s, 1H),
4.49 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 3.15 (q, J = 10.8 Hz, 2H)
CC7 127-128 436.03 7.42 (m, 4H), 7.24 (m, ([M + H].sup.+) 2H), 6.53
(d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.86 (br s,
1H), 4.51 (d, J = 6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H) CC8
129-131 462.15 8.58 (t, J = 5.6 Hz, 1H), ([M + H].sup.+) 7.72 (m,
1H), 7.66 (m, 3H), 7.49 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz,
1H), 6.90 (dd, J = 16.0, 8.0 Hz, 1H), 6.73 (d, J = 16 Hz, 1H), 4.81
(m, 1H), 4.33 (d, J = 6.0 Hz, 1H), 1.64 (m, 1H), 0.68 (m, 4H) CC9
132-134 504.25 7.41 (m, 3H), 7.26 (m, ([M + H].sup.+) 3H), 6.54 (d,
J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H),
4.56 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 3.13 (m, 2H) CC10 538.03
7.38 (m, 4H), 6.56 (d, 1651, 1112, ([M + 2H].sup.+) J = 16.0 Hz,
1H), 6.38 807 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.58 (m,
2H), 4.08 (m, 1H), 3.08 (m, 2H) CC11 111-112 494.12 7.42 (m, 3H),
7.24 (m, ([M - H].sup.-) 1H), 6.54 (d, J = 15.6 Hz, 1H), 6.34 (dd,
J = 16.0, 8.0 Hz, 1H), 6.03 (m, 1H), 4.53 (d, J = 6.0 Hz, 1H), 4.10
(m, 1H), 1.39 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC12 76-78 510.07
7.39 (s, 4H), 7.34 (d, J = ([M - H].sup.-) 8.0 Hz, 1H), 7.26 (m,
1H), 6.57 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H),
6.10 (br s, 1H), 4.49 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.20 (s,
9H) CC13 73-76 563.37 8.51 (d, J = 5.2 Hz, 1H), ([M - H].sup.-)
7.63 (s, 1H), 7.51 (m, 1H), 7.45 (m, 2H), 7.39 (s, 2H), 7.28 (m,
1H), 6.58 (m, 2H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (d, J =
6.0 Hz, 1H), 4.11 (m, 1H) CC14 581.45 8.51 (m, 1H), 8.30 (d, 3430,
1656, ([M + 1H].sup.+) J = 2.4 Hz, 1H), 7.73 (m, 1109, 806 1H),
7.61 (s, 2H), 7.51 (s, 1H), 7.32 (m, 3H), 6.66 (d, J = 16.0 Hz,
1H), 6.56 (dd, J = 16.0, 8.4 Hz, 1H), 4.50 (m, 1H), 4.45 (d, J =
5.6 Hz, 1H), 3.56 (s, 2H) CC15 480.24 7.40 (m, 3H), 7.33 (m, 3293,
1651, ([M + H].sup.+) 1H), 7.22 (m, 2H), 6.54 1543, 1114,
(d, J = 15.6 Hz, 1H), 812 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (br
s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 1.41 (m, 1H), 1.00
(m, 2H), 0.77 (m, 2H) CC16 520.33 7.42 (s, 1H), 7.37 (m, 3307,
1665, ([M - H].sup.-) 3H), 7.22 (m, 1H), 6.54 1114, 813 (d, J =
16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.19 (br s, 1H),
4.51 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 3.33 (m, 2H) CC17 117-119
459.83 7.51 (m, 2H), 7.39 (m, 3293, 1633, ([M - H].sup.-) 2H), 7.24
(m, 2H), 6.52 1110, 820 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6,
7.6 Hz, 1H), 6.02 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.14 (m,
1H), 1.38 (m, 1H)), 1.00 (m, 2H), 0.77 (m, 2H) CC18 119-123 501.88
7.48 (m, 2H), 7.41 (s, 3435, 1644, ([M - H].sup.-) 1H), 7.36 (d, J
= 8.0 Hz, 1111, 817 1H), 7.23 (m, 2H), 6.52 (d, J = 16.0 Hz, 1H),
6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0
Hz, 2H), 4.15 (m, 1H), 3.13 (m, 2H) CC19 530 7.41 (m, 2H), 7.24 (m,
3435, 1644, ([M + H].sup.+) 1H), 6.53 (d, J = 16.0 1111, 817 Hz,
1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.53 (m, 2H), 4.10 (m, 1H),
3.42 (m, 2H), 2.97 (s, 3H), 2.78 (m, 2H) CC20 512 7.42 (m, 3H),
7.24 (m, 3293, 1633, ([M + H].sup.+) 1H), 6.54 (d, J = 15.6 1110,
820 Hz, 1H), 6.34 (dd, J = 15.6, 8.0 Hz, 1H), 6.03 (m 1H), 4.53 (d,
J = 6.0 Hz, 1H), 4.10 (m, 1H), 1.19 (m, 1H), 1.00 (m, 2H), 0.77 (m,
2H) CC21 55-58 493.99 (DMSO-d.sub.6) 8.62 (m, ([M - H].sup.-) 1H),
7.95 (s, 1H), 7.85 (m, 1H), 7.66 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H),
6.98 (dd, J = 16.0, 8.0 Hz, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.83
(m, 1H), 4.44 (s, 2H), 1.68 (m, 1H), 0.71 (m, 4H) CC22 67-69 530.01
8.62 (m, 1H), 7.90 (s, ([M + H].sup.+) 3H), 7.82 (m, 1H), 7.45 (m,
1H), 6.98 (m, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.82 (m, 1H), 4.4 (s,
2H), 1.66 (m, 1H), 0.72 (m, 4H) CC23 69-71 564.99 9.02 (br s, 1H),
8.54 (br ([M - H].sup.-) s, 1H), 8.26 (br s, 1H), 7.48-7.54 (m,
3H), 7.22-7.42 (m, 3H), 6.59-6.62 (m, 2H), 6.38-6.42 (m, 1H), 4.82
(m, 2H), 4.19 (s, 1H) CC24 125-127 570.26 7.64 (s, 1H), 7.54 (s,
([M - H].sup.-) 2H), 7.46 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.41
(dd, J = 16.0, 8.4 Hz, 1H), 6.03 (m, 1H), 4.65 (d, J = 6.4 Hz, 2H),
4.14 (m, 1H,), 3.13 (q, J = 10.6 Hz, 2H) CC25 579.86 7.60 (s, 1H),
7.40 (s, 3297, 1663, ([M - H].sup.-) 2H), 7.37 (d, J = 8.0 Hz,
1114, 809 1H), 7.31 (d, J = 8.0 Hz, 1H), 6.53 (d, 1H, J = 16.0 Hz),
6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 4.56 (d, J = 6.4
Hz, 2H), 4.12 (m, 1H), 3.15 (q, J = 10.6 Hz, 2H) CC26 129-131
539.89 7.59 (s, 1H), 7.39 (m, ([M + H].sup.+) 2H), 7.30 (s, 1H),
6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.06
(br s, 1H), 4.42 (d, J = 4.4 Hz, 2H), 4.12 (m, 1H), 1.35 (br s,
1H), 0.95 (br s, 2H), 0.75 (m, 2H) CC27 519.95 7.39 (s, 2H), 7.33
(t, J = 3306, 1786 ([M - H].sup.-) 7.6 Hz, 1H), 7.14 (m, 2H), 6.56
(d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 7.6 Hz, 1H), 6.06 (br s,
1H), 4.52 (d, J = 16.0 Hz, 2H), 4.08 (m, 1H), 3.90 (s, 2H), 3.13
(m, 2H) CC28 477.93 7.39 (s, 2H), 7.35 (m, 3625, 1747 ([M -
H].sup.-) 1H), 7.14 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.33 (dd, J
= 15.6, 8.0 Hz, 1H), 5.93 (br s, 1H), 4.49 (d, J = 16.0 Hz, 2H),
4.10 (m, 1H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC29 620.86
8.58 (d, J = 4.6 Hz, 1H), 1645, 1115, ([M - H].sup.-) 7.74 (m, 1H),
7.62 (m, 2H), 808 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m,
2H), 6.60 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H),
5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J = 10 Hz, 2H), 4.10 (m, 1H),
1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H) CC30 101-104 559.75 7.41 (m,
4H), 7.24 (m, ([M - H].sup.-) 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35
(dd, J = 16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m,
1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H) CC31 177-178 463 7.58
(m, 2H), 7.41 (m, ([M - H].sup.-) 3H), 7.24 (m, 1H), 6.53 (d, J =
16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.70 (br s, 1H),
4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); CC32
141-142 532.99 7.66 (m, 2H), 7.54 (m, ([M + H].sup.+) 1H), 7.41 (s,
2H), 6.62 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H),
4.59 (s, 3H), 4.19 (m, 1H), 3.25 (m, 2H), 1.15 (m, 2H) CC33 540.88
7.57 (s, 1H), 7.40 (m, 2H), 3338, 1631, ([M - H].sup.-) 7.30 (s,
1H), 7.20 1578, 1114, (br s, 1H), 6.53 (d, J = 809 16.0 Hz, 1H),
6.33 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s, 1H), 4.75 (br s, 1H),
4.42 (s, 2H), 4.20 (br s, 1H), 4.15 (m, 2H), 3.20 (m, 2H), 1.15 (m,
3H) CC34 118-120 541.40 7.42 (m, 3H), 7.28 (m, ([M + H].sup.+) 2H),
6.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 4.96
(m, 1H), 4.51 (d, J = 5.6 Hz, 2H), 4.12 (m, 1H), 3.69 (t, J = 4.8
Hz, 4H), 3.35 (t, J = 4.8 Hz, 1H) CC35 78-79 547.82 9.95 (br s,
1H), 8.17 (d, ([M + H].sup.+) J = 4.8 Hz, 1H), 7.61 (d, J = 6.4
Hz), 7.43 (m, 3H), 7.24 (m, 2H), 6.90 (t, J = 5.6 Hz, 1H), 6.66 (d,
J = 8.4 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 8.0
Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.09 (m, 1H) CC36 497 7.39 (m,
4H), 7.28 (m, 3350, 1705, ([M - H].sup.-) 1H), 6.54 (d, J = 16.0
1114, 808 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s,
1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s,
3H) CC37 88-91 515.01 7.49 (d, J = 8 Hz, 1H), ([M + H].sup.+) 7.41
(d, J = 7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J = 16 Hz, 1H), 6.35
(dd, J = 16.0, 8.0 Hz, 1H), 6.0 (brs, 1H), 5.73 (br s, 1H), 4.80
(br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H) CC38 63-66 526.97 7.48 (d, J
= 8 Hz, 1H), ([M + H].sup.+) 7.39 (m, 3H), 7.27 (m, 1H), 6.54 (d, J
= 16 Hz, 1H), 6.33 (dd, J = 6.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 5.92
(br s, 1H), 5.83 (m, 2H), 5.29 (t, J = 15.4 Hz, 2H), 4.80 (br s,
2H), 4.12 (m, 1H), 4.02 (br s, 2H) CC39 526.09 7.39 (m, 4H), 7.28
(m, 3350, 1705, ([M - H].sup.-) 1H), 6.54 (d, J = 16.0 1114, 808
Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d,
J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H) CC40 159-160 580.25
7.46 (m, 5H), 7.29 (m, ([M - H].sup.-) 1H), 7.20 (m, 3H), 6.55 (d,
J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 5.62 (br s, 1H),
4.55 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC41 512.22 7.48 (m, 1H),
7.43 (m, 1740, 1701, ([M - H].sup.-) 3H), 7.38 (m, 1H), 7.23 1114,
808 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H),
4.60 (d, 2H), 4.18 (m, 1H), 3.85 (s, 3H) CC42 161-163 578.96
(DMSO-d.sub.6) 9.45 (br s, ([M - H].sup.-) 2H), 7.90 (s, 2H), 7.75
(s, 1H), 7.46 (br s, 1H), 7.28 (br s, 1H), 6.93 (m, 1H), 6.75 (br
s, 1H), 4.80 (m, 1H), 4.40 (br s, 2H), 3.90 (br s, 2H) CC43 140-142
505.39 8.11 (d, J = 4.0 Hz, 1H), ([M + H].sup.+) 7.40 (m, 5H), 7.22
(m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H) 4.61 (d, J =
6.4 Hz, 2H), 4.11 (m, 1H) CC44 536.88 8.41 (s, 1H), 7.77 (s, 3320,
1674, ([M - H].sup.-) 1H), 7.47 (br s, 1H), 1114, 808 7.40 (s, 2H),
6.58 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.68
(d, J = 4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J = 10.8 Hz, 2H) CC45
494.88 8.41 (s, 1H), 7.76 (s, 3309, 1659, ([M - H].sup.-) 1H), 7.40
(s, 2H), 7.15 1115, 808 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.44
(dd, J = 16.0, 8.0 Hz, 1H), 4.67 (d, J = 4.4 Hz, 2H), 4.16 (m, 1H),
1.57 (m,
1H), 1.04 (m, 2H), 0.87 (m, 2H) CC46 151-153 554.04 8.06 (m, 1H),
7.61 (m, ([M - H].sup.-) 4H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz,
1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H),
4.24 (m, 1H), 3.12 (m, 2H) CC47 478.09 8.06 (m, 2H), 7.61 (m, 3309,
1659, ([M + H].sup.+) 4H), 7.48 (s, 2H), 7.44 1115, 808 (d, J = 8.0
Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H),
1.00 (m, 2H), 0.77 (m, 2H) CC48 511.05 8.06 (m, 2H), 7.61 (m, 3309,
1659, ([M + H].sup.+) 3H), 7.48 (s, 2H), 7.44 1115, 808 (d, J = 8.0
Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H),
1.00 (m, 2H), 0.77 (m, 2H) CC49 84-87 515.33 8.06 (m, 1H), 7.98 (m,
([M + H].sup.+). 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J = 8.0
Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H),
4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J = 4.6 Hz, 3H) CC50 138-140
461.32 9.81 (s, 1H), 7.90 (s, ([M - 1H].sup.-)) 1H), 7.84 (s, 2H),
7.34 (d, J = 8.4 Hz, 2H), 6.65 (d, J = 15.6 Hz, 1H), 6.61 (m, 1H),
6.57 (s, 1H), 6.48 (dd, J = 15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64
(m, 1H), 0.75 (m, 4H); CC51 149-150 505.31 7.56 (br s, 1H), 7.4 (s,
([M - H].sup.-) 3H), 7.3 (m, 3H), 7.05 (br s, 1H), 6.8 (d, J = 6
Hz, 2H), 6.57 (m, 2H), 6.20 (m, 2H), 4.05 (m, 1H), 3.2 (q, J = 10.4
Hz, 2H) CC52 464.87 7.40 (s, 2H), 7.18 (s, 3309, 1659, ([M -
H].sup.-) 1H), 7.08 (s, 1H), 6.85 1115, 808 (m, 1H), 6.45 (m, 1H),
6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.30-1.10 (m, 4H), 1.90
(m, 1H) CC53 506 7.40 (s, 2H), 7.18 (s, 3309, 1659, ([M + H].sup.+)
1H), 7.08 (s, 1H), 6.85 1115, 808 (m, 1H), 6.45 (m, 1H), 6.20 (m,
1H), 5.55 (s, 1H), 4.08 (m, 1H), 3.21 (m, 2H) CC54 504 7.28 (s,
2H), 7.25 (m, ([M + H].sup.+) 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.89
(d, J = 11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J =
5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J = 7.5 Hz, 2H) DC1 93-97
398.05 8.56 (s, 1H), 8.11 (s, ([M + H].sup.+) 1H), 7.68 (d, J = 8.4
Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.29
(s, 2H), 6.62 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.2 Hz,
1H), 4.15 (m, 1H) DC2 363.0746 8.59 (s, 1H), 8.13 (s, 3121, 1524,
(363.075) 1H), 7.69 (d, J = 8.5 Hz, 1251, 1165, 2H), 7.55 (d, J =
8.5 Hz, 1119 2H), 7.41-7.29 (m, 4H), 6.64 (d, J = 15.7 Hz, 1H),
6.47 (dd, J = 15.9, 8.0 Hz, 1H), 4.17 (m, 1H) DC3 329.1144 8.56 (s,
1H), 8.11 (s, 1521, 1246, (329.114) 1H), 7.65 (d, J = 8.4 Hz, 1219,
1162, 2H), 7.52 (d, J = 8.3 Hz, 1152, 1107 2H), 7.40 (m, 5H), 6.61
(d, J = 15.8 Hz, 1H), 6.51 (dd, J = 15.9, 7.7 Hz, 1H), 4.18 (m, 1H)
DC4 364.11 8.56 (s, 1H), 8.10 (s, 1H), 3147, 1528, ([M + H].sup.+)
7.66 (d, J = 2.0 Hz, 2H), 1494, 1246, 7.52 (d, J = 8.8 Hz, 2H),
1165, 1108 7.38 (d, J = 2.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.61
(d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H)
DC5 344.25 8.54 (s, 1H), 8.10 (s, 1H), 3122, 3047, ([M + H].sup.+)
7.62 (d, J = 8.3 Hz, 2H), 1523, 1252, 7.50 (d, J = 8.4 Hz, 2H),
1160, 1107 7.25 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.60
(d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m,
1H), 2.37 (s, 3H) DC6 360.28 8.55 (s, 1H), 8.10 (s, 1H), 3124,
2936, ([M + H].sup.+) 7.65 (d, J = 8.8 Hz, 2H), 1522, 1249, 7.52
(d, J = 8.8 Hz, 2H), 1160 7.32 (d, J = 8.8 Hz, 2H), 6.95 (d, J =
8.8 Hz, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0, 7.4 Hz,
1H), 4.15 (m, 1H), 3.82 (s, 3H) DC7 348 8.55 (s, 1H), 8.10 (s, 1H),
3141, 1512, ([M + H].sup.+) 7.62 (d, J = 8.8 Hz, 2H), 1246, 1118
7.5 (d, J = 8.4 Hz, 2H), 7.38 (m, 2H), 7.12 (m, 2H), 6.61 (d, J =
16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H) DC8
366.13 8.57 (s, 1H), 8.11 (s, 1H), 3116, 1628, ([M + H].sup.+) 7.65
(d, J = 7.2 Hz, 2H), 1524, 1252, 7.52 (d, J = 8.0 Hz, 2H), 1168,
1118 6.95 (m, 2H), 6.82 (m, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.50
(dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC9 348.11 8.71 (s, 1H),
8.20 (s, 1H), 3115, 1525, ([M + H].sup.+) 7.70 (d, J = 8.0 Hz, 2H),
1248, 1174 7.57 (d, J = 8.0 Hz, 2H), 7.40 (m, 1H), 7.19 (m, 3H),
6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.15
(m, 1H) DC10 348.11 8.75 (s, 1H), 8.20 (s, 1H), 3114, 1526, ([M +
H].sup.+) 7.72 (d, J = 8.4 Hz, 2H), 1259, 1238, 7.6 (d, J = 8.4 Hz,
2H), 1193, 1114 7.20-7.40 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.40
(dd, J = 16.0, 8.0 Hz, 1H,), 4.60 (m, 1H) DC11 75.5-78.5 358.14
8.55 (s, 1H), 8.10 (s, ([M + H].sup.+) 1H), 7.65 (d, J = 8.8 Hz,
2H), 7.52 (d, J = 8.4 Hz, 2H), 7.01 (s, 3H), 6.60 (d, J = 16.0 Hz,
1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.15 (m, 1H), 2.34 (s, 6H)
DC12 398.05 8.58 (s, 1H), 8.10 (s, 3055, 2930, ([M + H].sup.+) 1H),
7.68 (d, J = 8.4 Hz, 1523, 1250, 2H), 7.53 (m, 4H), 7.2 1165 (s,
1H) 6.62 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H),
4.15 (m, 1H) DC13 396.16 8.58 (s, 1H), 8.10 (s, 3108, 1523, ([M +
H].sup.+) 1H), 7.62 (d, J = 8.4 Hz, 1249, 1166, 2H), 7.55 (m, 4H),
7.25 1127 (m, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0,
8.0 Hz, 1H), 4.90 (m, 1H) DC14 398.05 8.58 (s, 1H), 8.10 (s, 1H),
3117, 2925, ([M + H].sup.+) 7.62 (d, J = 8.4 Hz, 2H), 1526, 1246,
7.55 (m, 4H), 7.25 1172, 1117 (m, 1H), 6.67 (d, J = 16.0 Hz, 1H),
6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.00 (m, 1H) DC15 397.95 8.58 (s,
1H), 8.10 (s, 1H), 3120, 1524, ([M + H].sup.+) 7.66 (d, J = 8.0 Hz,
2H), 1267, 1176, 7.52 (m, 3H), 7.40 1112 (d, J = 8.0 Hz, 1H), 7.30
(dd, J = 8.4, 2.9 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J =
16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC16 466 8.61 (s, 1H), 8.13 (s, ([M
+ H].sup.+) 1H), 7.92 (s, 1H), 7.86 (s, 2H), 7.70 (d, J = 7.0 Hz,
2H), 7.54 (d, J = 7.0 Hz, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.46 (dd,
J = 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC17 430.06 8.58 (s, 1H), 8.1
(s, 1H), 3122, 3076, ([M + H].sup.+) 7.68 (d, J = 8.4 Hz, 2H),
2929, 1523, 7.54 (d, J = 8.4 Hz, 2H), 1250, 1168, 7.51 (s, 1H),
7.42 (s, 1H), 1114 6.68 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0,
8.0, Hz, 1H), 4.98 (m, 1H) DC18 92-95 429.91 8.57 (s, 1H), 8.11 (s,
1H), ([M + H].sup.+) 7.69 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.4 Hz,
2H), 7.42 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0,
8.0 Hz, 1H), 4.10 (m, 1H) DC19 97-99 430.321 8.58 (s, 1H), 8.12 (s,
1H), ([M + H].sup.+) 7.68 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.59
(s, 1H), 7.55 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J =
16.0, 8.0 Hz, 1H), 4.22 (m, 1H) DC20 427.0463 8.58 (s, 1H), 8.15
(s, 1H), 2937, 1524, (427.0466) 7.70 (d, J = 8.4 Hz, 2H), 1482,
1278, 7.58 (d, J = 8.4 Hz, 2H), 1249, 1166, 7.36 (s, 2H), 6.62 1112
(d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m,
1H), 3.88 (s, 3H) DC21 412.04 8.42 (s, 1H), 7.60 (d, J = 3108,
1572, ([M + H].sup.+) 8.0 Hz, 2H), 7.50 (d, J = 1531, 1242, 8.0 Hz,
2H), 7.40 (s, 1172, 1104 1H), 7.22 (s, 2H), 6.60 (d, J = 16.0 Hz,
1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.5 (s, 3H)
DC22 147-149 441.01 8.62 (s, 1H), 7.78 (d, J = ([M - H].sup.-) 8.0
Hz, 2H), 7.60 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.67
(d, J = 16.0 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H)
DC23 412.05 7.95 (s, 1H), 7.35 (d, J = 1112, 799 ([M + H].sup.+)
8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.39 (s, 1H), 7.29 (s, 2H),
6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.12
(m, 1H), 2.51 (s, 3H) DC24 133-134 440.03 8.10 (s, 1H), 7.52 (d, J
= ([M + H].sup.+) 8.0 Hz, 2H), 7.42-7.38
(m, 3H), 7.28 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J =
16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.79 (s, 3H) DC25 442.02 7.97 (s,
1H), 7.59 (d, J = 1167, 1114, ([M - H].sup.-) 8.0 Hz, 2H), 7.53 (d,
J = 800 8.0 Hz, 2H), 7.38 (m, 1H), 7.29 (s, 2H), 6.65 (d, J = 16.0
Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.17 (m, 1H), 2.74 (s,
3H) DC26 464.03 8.12 (s, 1H), 7.49 (d, J = 1689, 1253, ([M -
H].sup.-) 8.0 Hz, 2H), 7.40-7.37 1166, 1114, (m 3H), 7.28 (s, 2H),
979, 964 6.66 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz,
1H), 4.14 (m, 1H), 3.22 (m, 1H), 1.09-1.16 (m, 4H) DC27 473.94 8.19
(s, 1H), 7.64 (d, J = 1571, 1331, ([M - H].sup.-) 7.2 Hz, 2H), 7.55
(d, 7.2 1170, 1113, Hz, 2H), 7.39 (s, 1H), 764 7.30 (s, 2H), 6.62
(d, J = 16.0 Hz, 1H), 6.42 (dd, J = 8.0, 16.0 Hz, 1H), 4.18 (m,
1H), 3.58 (s, 3H) DC28 421.22 8.79 (s, 1H), 8.18 (s, 3126, 2233,
([M + H].sup.+) 1H), 7.80 (m, 3H), 7.52 1516, 1250, (m, 2H), 7.24
(m, 1H), 1165, 1109 6.63 (d, J = 16.0 Hz, 1H), 6.54 (d, J = 16.0,
7.6 Hz, 1H), 4.19 (m, 1H) DC29 421.22 8.80 (s, 1H), 8.2 (s, 1H),
3005, 1716, ([M + H].sup.+) 7.75-7.82 (m, 3H), 1363, 1223 7.41 (t,
J = 2 Hz, 1H), 7.26 (m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.52 (dd, J
= 16.0, 7.6 Hz, 1H), 4.16 (m, 1H) DC30 489.17 8.81 (s, 1H), 8.20
(s, 2964, 2234, ([M + H].sup.+) 1H), 7.94 (s, 1H), 7.85 1289, 1166,
(m, 3H), 7.79 (m, 2H), 1136 6.70 (d, J = 16.0 Hz, 1H), 6.58 (dd, J
= 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC31 117-118 455.27 8.80 (s, 1H),
8.20 (s, ([M + H].sup.+) 1H), 7.82 (m, 3H), 7.4 (s, 2H), 6.62 (d, J
= 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC32
388.0705 8.82 (s, 1H), 8.22 (s, 3126, 2234, (388.0703) 1H),
7.82-7.78 (m, 3H), 1520, 1280, 7.38-7.30 (m, 3H), 6.62 1164, 1112
(d, J = 16.1 Hz, 1H), 6.56 (dd, J = 16.1, 6.8 Hz, 1H), 4.18 (m, 1H)
DC33 455.22 8.80 (s, 1H), 8.20 (s, 3122, 3086, ([M - H].sup.-) 1H),
7.82-7.80 (m, 3H), 2234, 1517, 7.70-7.50 (m, 3H), 6.65 1327, 1168,
(d, J = 16.9 Hz, 1H), 1113 6.54 (dd, J = 16.9, 6.8 Hz, 1H), 4.25
(m, 1H) DC34 452.0412 8.85 (s, 1H), 8.23 (br s, 3122, 2934,
(452.0419) 1H), 7.83-7.78 (m, 3H), 2231, 1516, 7.33 (s, 2H), 6.69
(d, J = 1480, 1248, 14.9 Hz, 1H), 6.50 (dd, 1211, 1165, J = 14.9,
7.2 Hz, 1H), 1111 4.15 (m, 1H), 3.90 (s, 3H) DC35 439.01 8.60 (s,
1H), 8.20 (s, 2233, 1518, ([M - H].sup.-) 1H), 7.82 (m, 3H), 7.28
1250, 1169, (m, 2H), 6.65 (d, J = 1035, 817 16.0 Hz, 1H), 6.48 (dd,
J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC36 437.25 8.70 (s, 1H), 7.80
(m, 2927, 2233, ([M + H].sup.+) 3H), 7.40 (s, 1H), 7.28 1572, 1531,
(s, 2H), 6.63 (d, J = 16.0 1248, 1166, Hz, 1H), 6.50 (dd, J = 1112
16.0, 8.0 Hz, 1H), 4.18 (m, 1H), 2.50 (s, 1H) DC37 109-111 466.10
8.86 (s, 1H), 7.89 (m, ([M - H].sup.-) 3H), 7.40 (s, 1H), 7.30 (s,
2H), 6.68 (d, J = 16.0 Hz, 1H), 6.57 (dd, J = 16.0, 8.0 Hz, 1H),
4.18 (m, 1H) DC38 96-98 436.11 8.58 (s, 1H), 7.75 (m, ([M -
H].sup.-) 3H), 7.40 (s, 1H), 7.28 (s, 2H), 6.61 (d, J = 16.0 Hz,
1H), 6.42 (dd, J = 16.0, 8.2 Hz, 1H), 4.40 (br s, 2H), 4.15 (m, 1H)
DC39 224-226 480.30 8.65 (s, 1H), 8.18 (br s, 3352, 2237, ([M +
H].sup.+) 1H), 7.80-7.70 (m, 3H), 1707, 1163, 7.40 (s, 1H), 7.27
(s, 841 2H), 7.36 (m, 1H), 7.28 (m, 2H), 6.60 (d, J = 16.8 Hz, 1H),
6.47 (m, 1H), 4.16 (m, 1H), 2.40 (br s, 3H) DC40 70-73 436.11 8.86
(s, 1H), 7.88 (m, ([M - 2H].sup.-) 3H), 7.44 (s, 2H), 6.67 (d, J =
16.0 Hz, 1H), 6.56 (dd, J = 16.0 7.6 Hz, 1H), 4.19 (m, 1H) DC41
72-75 469.95 (DMSO-d.sub.6) 8.72 (s, ([M - H].sup.-) 1H), 8.26 (s,
1H), 8.01 (d, J = 8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J = 8.4 Hz,
1H), 6.42 (dd, J = 15.6, 9.2 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H),
5.87 (s, 2H), 4.89 (m, 1H) DC42 104-107 609.98 8.78 (s, 2H), 7.83
(s, 2234, 1714, ([M + H].sup.+) 1H), 7.80 (m, 2H), 7.42 1114, 807
(s, 2H), 6.65 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.8 Hz,
1H), 4.17 (m, 1H), 4 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H), DC43
109-112 540.04 (DMSO-d.sub.6) 10.94 (br s, 3233, 2233, ([M +
H].sup.+) 1H), 8.36 (s, 1H), 8.08 1699, 1114, (m, J = 8.4 Hz, 1H),
807 7.91 (s, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 15.6, 9.2
Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H),
0.82 (s, 4H) DC44 435.26 8.33 (s, 1H), 8.23 (s, 2236, 1510, [M -
H].sup.- 1H), 7.66 (s, 1H), 7.60 1114, 801 (s, 1H), 7.41 (m, 1H),
7.28 (m, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8
Hz, 1H), 4.16 (m, 1H), 2.20 (s, 3H) DC45 75-78 468.87 8.36 (s, 1H),
8.23 (s, [M - H].sup.- 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.41 (s,
2H), 6.62 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.6 Hz, 1H),
4.16 (m, 1H), 2.20 (s, 3H) DC46 411.4 8.83 (s, 1H), 8.21 (s, 1H),
.sup.13C NMR (.delta.).sup.3 ([M].sup.+) 7.83 (d, J = 8.5 Hz, 1H),
155.63, 153.27, 7.61 (d, J = 1.9 Hz, 1H), 153.12, 143.01, 7.52 (dd,
J = 8.4, 137.89, 136.25, 1.9 Hz, 1H), 7.28 (d, J = 134.03, 133.88,
3.8 Hz, 2H), 6.93 (d, J = 132.23, 131.23, 11.5 Hz, 1H), 6.26-6.20
(m, 131.18, 129.20, 1H), 4.22 (m, 1H) 126.17, 125.04, 124.99 DC47
139-141 474.16 8.51 (s, 1H), 8.14 (s, ([M - H].sup.-) 1H), 7.75 (s,
1H), 7.5 (m, 2H), 7.4 (s, 1H), 7.30 (m, 2H), 6.60 (d, J = 16.0 Hz,
1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC48 124-126
414.05 8.69 (s, 1H), 8.14 (s, [M - H].sup.- 1H), 7.96 (d, J = 4.8
Hz, 1H), 7.39-7.27 (m, 5H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J
= 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC49 81-83 463.96 8.57 (s, 1H),
8.14 (s, [M - H].sup.- 1H), 7.60 (m, 2H), 7.44 (m, 3H), 6.95 (d, J
= 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC50
140-143 430.07 8.56 (s, 1H), 8.13 (s, 1110, 803 [M - H].sup.-) 1H),
7.59 (d, J = 1.2 Hz, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 6.61 (d, J =
16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC51
118-121 464.22 8.32 (s, 1H), 8.15 (s, ([M - H].sup.-) 1H), 7.82 (s,
1H), 7.73 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (s,
1H), 7.29 (s, 2H), 6.70 (d, J = 15.6 Hz, 1H), 6.50 (dd, J = 15.6,
8.0 Hz, 1H), 4.20 (m, 1H) DC52 9.99 (s, 1H), 8.42 (s, 3123, 3079,
1H), 8.12 (s, 1H), 8.01 2925, 1692, (s, 1H), 7.68 (m, 1H), 1571,
1512, 7.44 (m, 1H), 7.33 (m, 1253, 1164, 1H), 7.22 (s, 2H), 6.62
1111 (d, J = 16.7 Hz, 1H), 6.45 (dd, J = 16.7, 9.3 Hz, 1H), 4.10
(m, 1H) DC53 8.30 (m, 1H), 8.00 (br s, 3250, 3043, 1H), 7.75 (m,
1H), 7.68 1683, 1116 (m, 1H), 7.55 (m, 1H), 7.36 (m, 1H), 7.28 (m,
2H), 6.70 (m, 1H), 6.58 (br s, 1H), 6.33 (m, 1H), 5.88 (m, 2H),
4.10 (m, 1H) DC54 56-58 441.07 8.40 (s, 1H), 8.13 (s, ([M -
H].sup.-) 1H), 8.02 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (d, J =
8.0 Hz, 1H), 7.4 (s, 1H), 7.29 (m, 2H), 6.69 (d, J = 15.6 Hz, 1H),
6.57 (dd, J = 15.6, 7.8 Hz, 1H), 4.15 (m, 1H) DC55 412.97 8.37 (s,
1H), 8.18 (s, ([M + H].sup.+) 1H), 7.39 (s, 1H), 7.30 (m, 2H), 7.19
(d, J = 8.0 Hz, 1H), 6.90 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.38
(dd, J = 15.6, 8.2 Hz, 1H), 4.20 (m, 1H), 2.50 (br s, 2H) DC56
175-177 453 9.59 (br s, 1H), 8.55 (s, ([M - H].sup.-) 1H), 8.47 (s,
2H), 8.23 (s, 1H), 7.30 (m, 4H), 6.62 (d, J = 16.0 Hz, 1H), 6.40
(dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.20 (s, 3H) DC57
426.0627 8.33 (s, 1H), 8.16 (s, 3342, 3112, (426.0626) 1H), 7.38
(s, 1H), 7.29 2931, 1606, (s, 2H), 7.15 (d, J = 7.6 1583, 1574, Hz,
1H), 6.80 (d, J = 7.6 1528, 1153 Hz, 1H), 6.74 (m, 1H), 6.60 (d, J
= 15.6 Hz, 1H), 6.35 (dd, J = 15.6, 8.4 Hz, 1H), 5.40 (br s, 1H),
4.15 (m, 1H), 2.90 (s, 3H) DC58 94-97 440.0424 (DMSO-d.sub.6) 8.76
(s, 3403, 3304, (440.0419) 1H), 8.16 (s, 1H), 7.90 3178, 1674, (br
s, 1H), 7.83 (s, 1H), 1571, 1169, 7.70 (d, J = 7.9 Hz, 1H), 1108
7.71-7.67 (m, 3H), 7.58 (d, J = 7.9 Hz, 1H), 7.52 (br s, 1H), 7.00
(dd, J = 15.8, 8.7 Hz, 1H), 6.85 (d, J = 15.8 Hz, 1H), 4.85 (m, 1H)
DC59 87-90 (DMSO-d.sub.6) 9.00 (s, 1H), 8.63 (s, 1H), 8.17 (s, 1H),
7.70-7.59 (m, 5H), 7.00 (dd, J = 16.2,
9.7 Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 5.90 (br s 2H), 4.83 (m,
1H) DC60 469.0577 8.32 (s, 1H), 8.10 (s, 2987, 1725, (469.0572)
1H), 7.97 (s, 1H), 7.65 1518, 1275, (d, J = 8.1 Hz, 1H), 7.47 1166,
1113 (d, J = 8.1 Hz, 1H), 7.40 (m, 1H), 7.28 (s, 2H), 6.62 (d, J =
16.5 Hz, 1H), 6.49 (dd, J = 16.5, 7.7 Hz, 1H), 4.23-4.04 (m, 3H),
1.15 (t, J = 8.0 Hz, 3H) DC61 130-132 442.15 (DMSO-d.sub.6) 9.90
(s, ([M + H].sup.+) 1H), 8.17 (s, 1H), 8.15 (m, 1H), 7.90 (m, 1H),
7.71 (m, 2H), 7.67 (m, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.03 (dd, J =
16.5, 8.3 Hz, 1H), 6.62 (d, J = 16.5 Hz, 1H), 4.87 (m, 1H) DC62
412.10 8.27 (s, 1H), 8.23 (s, 1513, 1252, ([M + H].sup.+) 1H), 7.40
(m, 3H), 7.30 1166, 1112, (m, 3H), 6.64 (d, J = 801 16.0 Hz, 1H),
6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.19 (m, 1H), 2.21 (s, 3H) DC63
446.01 8.26 (s, 1H), 8.12 (s, 2928, 2525, ([M + H].sup.+) 1H), 7.42
(s, 2H), 7.18- 1249, 1169, 7.28 (m, 3H), 6.62 (d, 1114, 809 J =
15.6 Hz, 1H), 6.39 (dd, J = 15.6, 9.4 Hz, 1H), 4.10 (m, 1H), 2.25
(s, 3H) DC64 475.03 8.84 (d, J = 5.8 Hz, 2H), 1683, 1167, ([M +
H].sup.+) 8.33 (s, 1H), 8.20 (s, 650, 479 1H), 7.75 (m, 1H), 7.60
(d, J = 28.6 Hz, 1H), 7.58-7.48 (m, 3H), 7.42 (m, 1H), 7.28 (s,
2H), 6.71 (d, J = 16.9 Hz, 1H), 6.39 (dd, J = 16.9, 8.2 Hz, 1H),
4.15 (m, 1H) DC65 412.05 8.55 (s, 1H), 8.12 (s, 722, 111 ([M +
H].sup.+) 1H), 7.55 (m, 3H), 7.39 (m, 1H), 7.30 (d, J = 1.6 Hz,
1H), 6.85 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H),
4.17 (m, 1H), 2.40 (s, 3H) DC66 60-61 468.26 8.59 (s, 1H), 8.14 (s,
([M + H].sup.+) 1H), 7.94 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.61
(d, J = 8.0 Hz, 1H), 7.43 (s, 2H), 7.23 (d, J = 16.0 Hz, 1H), 6.41
(dd, J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC67 133-134 432.30 8.59
(s, 1H), 8.12 (s, 800, 114 ([M + H].sup.+) 1H), 7.78 (br s, 1H),
7.71 (m, 1H), 7.62 (m, 1H), 7.39 (s, 1H), 7.32 (s, 2H), 7.03 (d, J
= 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 0.21 (m, 1H) DC68
412.03 8.71 (s, 1H), 8.18 (s, ([M + H].sup.+) 1H), 7.71 (d, J = 8.0
Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.28 (m, 2H), 6.08
(d, J = 16.0 Hz, 1H), 4.26 (m, 1H), 2.05 (s, 3H) DC69 162-168
414.03 8.56 (s, 1H), 8.11 (s, 1H), ([M + H].sup.+) 7.70 (d, J = 8.5
Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54 (m, 2H), 7.40 (m, 1H), 6.91
(d, J = 16.5 Hz, 1H), 6.66 (d, J = 16.5 Hz, 1H) DC70 99-103 428.05
8.58 (s, 1H), 8.13 (s, ([M + H].sup.+) 1H), 7.73 (d, J = 8.7 Hz,
2H), 7.60 (d, J = 8.7 Hz, 2H), 7.46 (m, 2H), 7.42 (m, 1H), 6.85 (d,
J = 16.2 Hz, 1H), 6.40 (d, J = 16.2 Hz, 1H), 3.42 (s, 3H) .sup.a1H
NMR spectral data were acquired using a 400 MHz instrument in
CDCl.sub.3 except where noted. HRMS data are noted observed value
(theoretical value).
TABLE-US-00009 TABLE 2A Analytical Data for Compounds in Table 1A.
Compound mp (.degree. C.); IR (cm.sup.-1); Number
[.alpha.].sub.D.sup.25 ESIMS .sup.1H NMR (.delta.).sup.a .sup.19F
NMR (.delta.) F1 53-64 655 rotomers .delta. 7.61 (d, J = ([M +
H].sup.+) 1.6 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 6.4,
3.0 Hz, 0.5H), 7.41 (s, 2H), 7.37 (dd, J = 8.0, 1.6 Hz, 1H), 7.33
(t, J = 6.2 Hz, 0.5H), 6.53 (d, J = 15.9 Hz, 1H), 6.45 (s, 1H),
6.39 (dd, J = 15.9, 7.8 Hz, 1H), 4.21-4.01 (m, 1H), 3.96 (qd, J =
9.1, 6.4 Hz, 1.5H), 3.85 (td, J = 9.2, 6.5 Hz, 0.5 H) 1.69 (s, 6H)
F2 608.92 (300 MHz, CDCl.sub.3) .delta. 3368, 1682, ([M + H].sup.+)
7.65 (d, J = 7.6 Hz, 1162, 808 1H), 7.43-7.40 (m, 2H), 7.36 (d, J =
8.4 Hz, 1H), 7.29 (m, 1H), 6.56 (d, J = 15.6 Hz, 1H), 6.43 (dd, J =
15.6, 7.2 Hz, 1H), 4.12-4.08 (m, 1H), 3.97-3.94 (m, 2H), 1.70 (s,
6H) F3 588.90 (300 MHz, DMSO-d.sub.6) 3394, 1678, ([M + H].sup.+)
.delta. 8.23 (s, 1H), 8.17 (broad s, 1163, 807 1H), 7.89 (s, 2H),
7.48- 7.38 (m, 3H), 6.82 (dd, J = 15.6, 7.8 Hz, 1H), 6.74 (d, J =
15.6 Hz, 1H), 4.90-4.80 (m, 1H), 3.89-3.84 (m, 2H), 2.30 (s, 3H),
1.42 (s, 6H) F4 642.99 (300 MHz, DMSO-d.sub.6) 3460, 1677, ([M +
H].sup.+) .delta. 8.58 (s, 1H), 8.20 (t, J = 1165, 557 6.6 Hz, 1H),
7.98- 7.89 (m, 4H), 7.80 (d, J = 8.1 Hz, 1H), 7.04 (dd, J = 15.6,
8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.78 (m, 1H),
3.89-3.82 (m, 2H), 1.40 (s, 6H) F5 640.9 7.62 (d, J = 1.7 Hz, 3288,
1644, ([M + H].sup.+) 1H), 7.53 (d, J = 7.8 1162 Hz, 1H), 7.42-7.29
(m, 3H), 6.91 (t, J = 6.7 Hz, 1H), 6.54 (bs, 1H) 6.53 (d, J = 15.9
Hz, 1H), 6.39 (dd, J = 15.9, 7.8 Hz, 1H), 4.74 (q, J = 7.1 Hz, 1H),
4.10 (m, 1H), 4.05-3.72 (m, 2H), 1.53 (d, J = 7.0 Hz, 3H) F6 640.9
7.62 (d, J = 1.6 Hz, 3288, 1645, ([M + H].sup.+) 1H), 7.53 (d, J =
8.0 1164 Hz, 1H), 7.41 (s, 2H), 7.38 (dd, J = 8.0, 1.7 Hz, 1H),
6.86 (t, J = 6.2 Hz, 1H), 6.57-6.49 (m, 2H), 6.40 (dd, J = 15.9,
7.8 Hz, 1H), 4.74 (m, 1H), 4.15-4.04 (m, 1H), 4.00-3.81 (m, 2H),
1.53 (d, J = 7.1 Hz, 3H) F7 574.92 (300 MHz, DMSO-d.sub.6) 3412,
1685, ([M + H].sup.+) .delta. 8.56 (t, J = 6.3 Hz, 1163, 809 1H),
8.43 (d, J = 4.5 Hz, 1H), 7.89 (s, 2H), 7.44.7.34 (m, 3H), 6.88
(dd, J = 15.6, 8.4 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85-4.79
(m, 1H), 4.49-4.44 (m, 1H), 3.99-3.83 (m, 2H), 2.33 (s, 3H), 1.34
(d, J = 7.2 Hz, 3H) F8 652.95 (400 MHz, DMSO-d.sub.6) 3291, 1647,
([M + H].sup.+) .delta. 8.62 (t, J = 6.0 Hz, 1165, 808, 1H), 8.59
(d, J = 7.6 565 Hz, 1H), 7.92-7.91 (m, 3H), 7.60 (d, J = 7.6 Hz,
1H), 7.38 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 15.6, 9.2 Hz, 1H),
6.77 (d, J = 15.6 Hz, 1H), 4.85-4.80 (m, 1H), 4.41-4.36 (m, 1H),
4.05-3.99 (m, 1H), 3.91-3.84 (m, 1H), 1.73-1.63 (m, 2H), 0.99 (t, J
= 7.6 Hz, 3H) F8A 650.99 (300 MHz, DMSO-d.sub.6) 3289, 1646, ([M -
H].sup.-) .delta. 8.64-8.57 (m, 2H), 1164, 808. 7.92-7.91 (m, 3H),
7.60 725, 649 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.01
(dd, J = 15.6, 9.0 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.86- 4.80
(m, 1H), 4.42-4.35 (m, 1H), 4.06-3.84 (m, 2H), 1.76-1.62 (m, 2H),
0.93 (t, J = 7.2 Hz, 3H). F9 575.04 (400 MHz, DMSO-d.sub.6) 3407,
1685, ([M + H].sup.+) .delta. 8.56 (t, J = 6.0 Hz, 1161, 808 1H),
8.44 (d, J = 7.2 Hz, 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.41-7.35 (m,
2H), 6.87 (dd, J = 16.0, 9.2 Hz, 1H), 6.74 (d, J = 15.2 Hz, 1H),
4.85-4.80 (m, 1H), 4.48-4.44 (m, 1H), 4.03-3.85 (m, 2H), 2.33 (s,
3H), 1.31 (d, J = 7.2 Hz, 3H) F10 638.84 (400 MHz, DMSO-d.sub.6)
3415, 1652, ([M + H].sup.+) .delta. 8.61 (d, J = 7.2 Hz, 1162, 807,
1H), 8.52 (t, J = 6.0 Hz, 561 1H), 7.88-7.87 (m, 3H), 7.56 (d, J =
7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.96 (dd, J = 16.6, 9.2 Hz,
1H), 6.73 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m, 1H), 4.46-4.42 (m,
1H), 4.00-3.81 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) F11 638.90 (400
MHz, DMSO-d.sub.6) 3415, 1652, ([M + H].sup.+) .delta. 8.61 (d, J =
7.2 Hz, 1162, 807, 1H), 8.52 (t, J = 6.0 Hz, 561 1H), 7.88-7.87 (m,
3H), 7.56 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.96 (dd,
J = 16.6, 9.2 Hz, 1H), 6.73 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m,
1H), 4.46-4.42 (m, 1H), 4.00-3.81 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H)
F12 638.90 (400 MHz, DMSO-d.sub.6) 3418, 1646, ([M + H].sup.+)
.delta. 8.65 (d, J = 7.2 Hz, 1163, 808, 1H), 8.56 (t, J = 8.0 Hz,
564 1H), 7.92 (s, 1H), 7.91 (s, 2H), 7.60-7.58 (m, 1H), 7.42 (d, J
= 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 8.0 Hz, 1H), 6.77 (d, J = 15.6
Hz, 1H), 4.83-4.76 (m, 1H), 4.52-4.45 (m, 1H), 4.06-3.82 (m, 2H),
1.33 (d, J = 8.0 Hz, 3H) F13 638.96 (400 MHz, DMSO-d.sub.6) 3418,
1646, ([M + H].sup.+) .delta. 8.65 (d, J = 7.2 Hz, 1163, 808, 1H),
8.56 (t, J = 8.0 Hz, 564 1H), 7.92 (s, 1H), 7.91 (s, 2H), 7.60-7.58
(m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 8.0 Hz, 1H),
6.77 (d, J = 15.6 Hz, 1H), 4.83-4.76 (m, 1H), 4.52-4.45 (m, 1H),
4.06-3.82 (m, 2H), 1.33 (d, J = 8.0 Hz, 3H) F14 673.31 (300 MHz,
CDCl.sub.3) .delta. 3422, 1640, ([M + H].sup.+) 7.91 (s, 1H), 7.82
(s, 1169, 528 2H), 7.62 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.40 (d,
J = 8.1 Hz, 1H), 6.80 (bs, 1H), 6.62 (s, 1H), 6.55 (d, J = 16.0 Hz,
1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.73- 4.70 (m, 1H), 4.40-
4.25 (m, 1H), 3.95-3.92 (m, 2H), 1.56 (d, J = 7.5 Hz, 3H) F15
589.00 (400 MHz, DMSO-d.sub.6) 3295, 1682, ([M + H].sup.+) .delta.
8.58 (t. J = 8.8 Hz, 1164, 80 1H), 8.32 (d, J = 8.0 Hz, 1H), 7.85
(s, 2H), 7.42 (s, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 7.6
Hz, 1H), 6.83 (dd, J = 15.6 Hz, 8.8 Hz, 1H), 6.71 (d, J = 15.6 Hz,
1H), 4.77-4.81 (m, 1H), 4.30-4.35 (m, 1H), 3.94-4.00 (m, 1H),
3.80-3.86 (m, 1H), 2.29 (s, 3H), 1.71-1.60 (m, 2H), 0.88 (t, J =
7.6 Hz, 3H) F15A 588.9 (300 MHz, DMSO-d.sub.6) 3290, 1646, ([M +
H].sup.+) .delta. 8.61 (t, J = 6.0 Hz, 1165, 808. 1H), 8.35 (d, J =
7.5 725, 651 Hz, 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.41 (d, J = 8.4
Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 6.88 (dd, J = 15.9, 8.7 Hz, 1H),
6.75 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 4.40-4.32 (m, 1H),
4.04-3.82 (m, 2H), 2.33 (s, 3H), 1.76-1.62 (m, 2H), 0.91 (t, J =
7.5 Hz, 3H) F16 643.06 (400 MHz, DMSO-d.sub.6) 3292, 1652, ([M +
H].sup.+) .delta. 8.65-8.60 (m, 2H), 1167, 809 7.95 (s, 1H),
7.89-7.82 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 7.04 (dd, J = 15.6,
9.2 Hz, 1H), 6.85 (d, J = 15.9 Hz, 1H), 4.85-4.80 (m, 1H),
4.38-4.33 (m, 1H), 4.01 (m, 2H), 1.72-1.58 (m, 2H), 0.86 (t, J =
7.6 Hz, 3H) F16A 640.9 (300 MHz, DMSO-d.sub.6) 3290, 1651, ([M -
H].sup.-) .delta. 8.66-8.62 (m, 2H), 1166, 809 7.98 (s, 1H),
7.92-7.87 (m, 3H), 7.51 (d, J = 7.8 Hz, 1H), 7.04 (dd, J = 15.6,
9.0 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H),
4.41-4.37 (m, 1H), 4.05-3.87 (m, 2H), 1.72-1.63 (m, 2H), 0.90 (t, J
= 6.9 Hz, 3H) F17 628.95 (400 MHz, DMSO-d.sub.6) 3299, 1686, ([M +
H].sup.+) .delta. 8.55 (t, J = 6.4 Hz, 1165, 568 1H), 8.42 (d, J =
7.6
Hz, 1H), 7.89 (s, 1H), 7.82 (s, 2H), 7.45 (s, 1H), 7.41-7.35 (m,
2H), 6.85 (dd, J = 16.0 Hz, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H),
4.81- 4.76 (m, 1H), 4.48-4.44 (m, 1H), 3.99-3.84 (m, 2H), 2.33 (s,
3H), 1.30 (d, J = 7.6 Hz, 3H) F18 629.0 (300 MHz, DMSO-d.sub.6)
3407, 1713, ([M + H].sup.+) .delta. 8.76 (d, J = 7.8 Hz, 1160, 807
1H), 8.61 (t, J = 12.9 Hz, 1H), 7.98 (s, 1 H), 7.92-7.88 (m, 3H),
7.56 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 16.2, 9.3 Hz, 1H), 6.89 (d,
J = 16.0 Hz, 1H), 4.89-4.83 (m, 1H), 4.51-4.47 (m, 1H), 4.01-3.88
(m, 2H), 1.29 (d, J = 7.2 Hz, 3H) F19 692.88 (400 MHz,
DMSO-d.sub.6) 3404, 1646, ([M + H].sup.+) .delta. 8.61 (d, J = 7.2
Hz, 1165, 565 1H), 8.52 (t, J = 12.8 Hz, 1H), 7.88 (s, 1H), 7.85
(s, 1H), 7.80 (s, 2H), 7.56 (d, J = 6.8 Hz, 1H), 7.38 (d, J = 8.0
Hz, 1H), 6.95 (dd, J = 15.6, 9.2 Hz, 1H), 6.72 (d, J = 15.6 Hz,
1H), 4.77-4.72 (m, 1H), 4.46-4.42 (m, 1H), 3.98-3.82 (m, 2H), 1.27
(d, J = 6.8 Hz, 3H) F20 629.29 (400 MHz, DMSO-d.sub.6) 3407, 1679,
([M + H].sup.+) .delta. 8.75 (d, J = 7.8 Hz, 1165, 808 1H), 8.59
(t, J = 6.6 Hz, 1H), 7.98-7.88 (m, 4H), 7.56 (d, J = 8.1 Hz, 1H),
7.09 (dd, J = 15.6, 8.7 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-
4.83 (m, 1H), 4.52-4.47 (m, 1H), 4.01-3.88 (m, 2H), 1.30 (d, J =
6.9 Hz, 3H) F20A [.alpha.].sub.D.sup.25 = +49.2 628.89 (400 MHz,
DMSO-d.sub.6) 3315, 1657, (c, 1% in ([M + H].sup.+) .delta. 8.74
(d, J = 7.6 Hz, 1167, 700 CH.sub.2Cl.sub.2) 1H), 7.98 (s, 1H),
7.92- 7.89 (m, 3H), 7.56 (d, J = 8.4 Hz, 1H), 7.08 (dd, J = 15.6,
8.8 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.83 (m, 1H),
4.51-4.48 (m, 1H), 3.99-3.86 (m, 2H), 1.49 (d, J = 6.8 Hz, 3H) F20B
[.alpha.].sub.D.sup.25 = -38.8 628.89 (400 MHz, DMSO-d.sub.6) 3315,
1657, (c, 1% in ([M + H].sup.+) .delta. 8.74 (d, J = 7.6 Hz, 1167,
700 CH.sub.2Cl.sub.2) 1H), 7.98 (s, 1H), 7.92- 7.89 (m, 3H), 7.56
(d, J = 8.4 Hz, 1H), 7.08 (dd, J = 15.6, 8.8 Hz, 1H), 6.88 (d, J =
15.6 Hz, 1H), 4.88-4.83 (m, 1H), 4.51-4.48 (m, 1H), 3.99-3.86 (m,
2H), 1.49 (d, J = 6.8 Hz, 3H) F20C 61-70 629 7.64 (t, J = 6.4 Hz,
.sup.19F NMR ([M + H].sup.+) 1H), 7.52 (d, J = 7.9 (376 MHz, CDCl3)
Hz, 1H), 7.42 (s, 1H), .delta. -59.22, amide 7.34 (d, J = 2.9 Hz,
rotamers -69.43 3H), 6.64 (m, 1H), 6.91 and -69.45, -72.60 (d, J =
11.4 Hz, 1H), 6.19 (dd, J = 11.4, 10.3 Hz, 1H), 4.94 (p, J = 7.1
Hz, 1H), 4.18 (q, J = 8.8 Hz, 1H), 3.95- 3.71 (m, 2H), 1.52 (d, J =
6.9 Hz, 3H) F21 682.98 (400 MHz, DMSO-d.sub.6) 3302, 1656, ([M +
H].sup.+) .delta. 8.70 (d, J = 7.2 Hz, 1166, 557 1H), 8.55 (t, J =
6.4 Hz, 1H), 7.94 (s, 1H), 7.87- 7.81 (m, 4H), 7.52 (d, J = 8.4 Hz,
1H), 7.04 (dd, J = 15.6, 9.2 Hz, 1H), 6.84 (d, J = 15.6 Hz, 1H),
4.80-4.75 (m, 1H), 4.47-4.44 (m, 1H), 3.97-3.78 (m, 2H), 1.29 (d, J
= 7.6 Hz, 3H) F22 605.32 (300 MHz, DMSO-d.sub.6) 3412, 1645, ([M +
H].sup.+) .delta. 8.65 (d, J = 7.5 Hz, 1164, 597 1H), 8.55 (t, J =
8.1 Hz, 1H), 7.93-7.87 (m, 3H), 7.78 (d, J = 8.1 Hz, 1H), 7.71-7.66
(m, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 6.0 Hz, 1H), 7.03
(dd, J = 15.6, 9.2 Hz, 1H), 6.79 (d, J = 15.9 Hz, 1H), 4.93-4.86
(m, 1H), 4.50-4.45 (m, 1H), 4.00-3.85 (m, 2H), 1.33 (d, J = 7.2 Hz,
3H) F23 609.00 7.66 (d, J = 8.4 Hz, 3291, 1645, ([M + H].sup.+)
1H), 7.43 (s, 1H), 7.40 1165, 749 (s, 2H), 7.34 (d, J = 7.6 Hz,
1H), 6.79 (s, 1H), 6.73 (s, 1H), 6.56 (d, J = 16.4 Hz, 1H), 6.43
(dd, J = 16.4, 8.0 Hz, 1H), 4.64-4.60 (m, 1H), 4.13-4.06 (m, 1H),
4.00-3.85 (m, 2H), 2.09 (m, 1H), 1.87-1.78 (m, 2H), 1.37 (t, J =
7.2 Hz, 3H) F23A 608.99 (400 MHz, DMSO-d.sub.6) 3292, 1646, ([M +
H].sup.+) .delta. 8.63 (t, J = 6.4 Hz, 1165, 808 1H), 8.59 (d, J =
8.0 Hz, 1H), 7.91 (s, 2H), 7.77 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H),
7.42 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.6, 9.2 Hz, 1H), 6.78 (d,
J = 15.6 Hz, 1H), 4.86-4.81 (m, 1H), 4.42-4.37 (m, 1H), 4.05-3.84
(m, 2H), 1.75-1.61 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H) F24 622.97
(300 MHz, DMSO-d.sub.6) 3421, 1646, ([M + H].sup.+) .delta. 8.65
(d, J = 7.5 Hz, 1168 1H), 8.56 (bs, 1H), 7.92-7.85 (m, 3H),
7.76-7.73 (m, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz,
1H), 7.04 (dd, J = 15.6, 9.0 Hz, 1H), 6.08 (d, J = 15.9 Hz, 1H),
4.98- 4.92 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (d,
J = 7.2 Hz, 3H) F25 594.94 (300 MHz, DMSO-d.sub.6) 3299, 1687, ([M
+ H].sup.+) .delta. 8.66 (d, J = 7.2 Hz, 1164, 808 1H), 8.57 (t, J
= 6.0 Hz, 1H), 7.91 (s, 2H), 7.77 (s, 1H), 7.57 (d, J = 6.9 Hz,
1H), 7.46 (d, J = 7.8 Hz, 1H), 7.02 (dd, J = 15.6, 9.0 Hz, 1H),
6.78 (d, J = 15.6 Hz, 1H), 4.87-4.80 (m, 1H), 4.51-4.47 (m, 1H),
4.04-3.88 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) F26 588.96 (300 MHz,
DMSO-d.sub.6) 3429, 1645, ([M - H].sup.-) .delta. 10.54 (bs, 1H),
8.53 1165, 750 (d, J = 6.9 Hz, 1H), 7.89 (s, 2H), 7.45-7.38 (m,
3H), 6.88 (dd, J = 15.9, 8.4 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H),
4.87-4.79 (m, 2H), 4.67-4.65 (m, 1H), 4.53-4.50 (m, 1H), 2.33 (s,
3H), 1.37 (d, J = 6.9 Hz, 3H) F27 655.27 (300 MHz, DMSO-d.sub.6)
3422, 1657, ([M + H].sup.+) .delta. 10.52 (bs, 1H), 8.74 1161, 806,
(d, J = 5.7 Hz, 1H), 557 7.93-7.91 (m, 3H), 7.62 (d, J = 8.7 Hz,
1H), 7.48 (d, J = 7.8 Hz, 1H), 6.98 (dd, J = 15.0, 6.3 Hz, 1H),
6.77 (d, J = 15.6 Hz, 1H), 4.88- 4.80 (m, 2H), 4.52-4.43 (m, 2H),
1.37 (d, J = 6.9 Hz, 3H) F28 644.94 (300 MHz, DMSO-d.sub.6) 3257,
1663, ([M + H].sup.+) .delta. 10.57 (bs, 1H), 8.85 1170, 809, (d, J
= 7.5 Hz, 1H), 552 7.99-7.70 (m, 4H), 7.65 (d, J = 8.1 Hz, 1H),
7.07 (dd, J = 15.9, 6.9 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H),
4.88-4.84 (m, 2H), 4.67-4.50 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H) F29
602.94 (300 MHz, DMSO-d.sub.6) 3420, 1645, ([M - H].sup.-) .delta.
9.87 (bs, 1H), 8.40 1164, 750 (bs, 1H), 7.89 (s, 2H), 7.54 (d, J =
8.1 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 7.8 Hz, 1H), 6.88 (dd, J =
15.9, 8.7 Hz, 1H), 6.75 (d, J = 15.3 Hz, 1H), 4.85-4.79 (m, 1H),
4.55-4.50 (m, 2H), 2.32 (s, 3H), 1.60 (s, 6H) F30 611.0 (300 MHz,
DMSO-d.sub.6) 3432, 1651, ([M + H].sup.+) .delta. 10.65 (bs, 1H),
8.75 1259, 750 (d, J = 6.9 Hz, 1H), 7.90 (s, 2H), 7.78 (s, 1H),
7.58-7.49 (m, 2H), 6.98 (dd, J = 14.7 Hz, 8.0 Hz, 1H), 6.78 (d, J =
15.3 Hz, 1H), 4.89- 4.84 (m, 2H), 4.78-4.60 (m, 1H), 4.59-4.49 (m,
1H), 1.37 (d, J = 6.9 Hz, 3H) F31 618.87 (300 MHz, DMSO-d.sub.6)
3436, 1261, ([M - H].sup.-) .delta. 10.14 (s, 1H), 9.72 750 (broad
s, 1H), 7.88 (s, 2H), 7.40-7.34 (m, 2H), 7.24 (d, J = 7.8 Hz, 1H),
6.81 (dd, J = 16.0, 8.0 Hz, 1H) 6.69 (d, J = 16.0 Hz, 1H),
4.84-4.78 (m, 1H), 4.55-4.50 (m, 2H), 2.29 (s, 3H), 1.76 (s, 6H)
.sup.a.sup.1H NMR spectral data were acquired using a 400 MHz
instrument in CDCl.sub.3 except where noted. HRMS data are noted
observed value (theoretical value).
TABLE-US-00010 TABLE 2B Analytical Data for Compounds in Table 1B.
Compound IR (cm.sup.-1); Number mp (.degree. C.) ESIMS .sup.1H NMR
(.delta.).sup.a .sup.19F NMR (.delta.) P1 590.91 (400 MHz,
DMSO-d.sub.6) .delta. 3327, 1703, ([M + H].sup.+) 8.69 (t, J = 5.6
Hz, 1H), 1164, 595 8.56 (t, J = 6.4 Hz, 1H), 7.93-7.88 (m, 3H),
7.77- 7.75 (m, 1H), 7.70-7.66 (m, 1H), 7.62-7.60 (m, 1H), 7.45 (d,
J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 8.8 Hz, 1H), 6.78 (d, J = 15.6
Hz, 1H), 4.92-4.87 (m, 1H), 3.97- 3.90 (m, 4H) P2 581.91 7.63-7.62
(m, 1H), 7.58 3280, 2243, ([M - H].sup.-) (d, J = 8.4 Hz, 1H),
1637, 1166 7.39-7.37 (m, 1H), 7.12 (d, J = 8.0 Hz, 2H), 6.78 (t, J
= 4.8 Hz, 1H), 6.65 (bs, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd,
J = 15.6, 7.6 Hz, 1H), 4.24-4.20 (m, 3H), 4.00- 3.92 (m, 2H) P12
577.07 (400 MHz, DMSO-d.sub.6) .delta. 3311, 1646, ([M + H].sup.+)
8.61-8.54 (m, 2H), 7.86 1164, 714 (d, J = 6.4 Hz, 2H), 7.53 (d, J =
8.0 Hz, 1H), 7.45-7.42 (m, 2H), 6.95 (dd, J = 15.6, 9.6 Hz, 1H),
6.80 (d, J = 15.6 Hz, 1H), 4.86-4.76 (m, 1H), 3.98-3.89 (m, 4H),
2.43 (s, 3H) P14 638.80 (300 MHz, DMSO-d.sub.6) .delta. 3435, 1166,
([M - H].sup.-) 10.55 (t, J = 6.0 Hz, 749, 597 1H), 10.53 (t, J =
5.2 Hz, 1H), 7.90 (s, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.59-7.56 (m,
1H), 7.37- 7.35 (m, 1H), 6.98 (dd, J = 15.6, 9.0 Hz, 1H), 6.76 (d,
J = 15.9 Hz, 1H), 4.84-4.77 (m, 1H), 4.70-4.58 (m, 4H) P15 590.8
(400 MHz, DMSO-d.sub.6) .delta. 3243, 2923, ([M - H].sup.-) 10.62
(t, J = 6.0 Hz, 1106, 614 1H), 10.54 (t, J = 5.2 Hz, 1H), 7.89 (s,
2H), 7.42 (s, 1H), 7.39-7.37 (m, 1H), 7.24 (d, J = 7.6 Hz, 1H),
6.84 (dd, J = 15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6, 1H), 4.84- 4.80
(m, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.65-4.56 (m, 2H), 2.35 (s, 3H)
P82 590.9 (300 MHz, DMSO-d.sub.6) .delta. 3298, 1643, ([M +
H].sup.+) 8.65 (d, J = 7.2 Hz, 1162 1H), 8.56 (t, J = 6.6 Hz, 1H),
7.88 (s, 1H), 7.59- 7.56 (m, 2H), 7.47- 7.40 (m, 2H), 6.90- 6.88
(m, 2H), 4.97-4.94 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H),
1.31 (d, J = 7.2 Hz, 3H) P84 82-85 581.1 (300 MHz, DMSO-d.sub.6)
.delta. ([M + H].sup.+) 8.74 (d, J = 7.2 Hz, 1H), 8.59 (t, J = 6.6
Hz, 1H), 7.96 (s, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.61-7.44 (m, 3H)
6.99 (m, 2H), 4.98-4.95 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.88 (m,
2H), 1.29 (d, J = 6.8 Hz, 3H) P156 639.0 (400 MHz, DMSO-d.sub.6)
.delta. 3436, 2924, ([M + H].sup.+) 8.66 (d, J = 8.0 Hz, 1H), 1662,
1162, 8.56 (t, J = 5.6 Hz, 1H), 750 7.95-7.93 (m, 2H), 7.60 (d, J =
7.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 8.8 Hz,
1H), 6.94 (d, J = 15.6 Hz, 1H), 5.09- 5.04 (m, 1H), 4.53- 4.43 (m,
1H), 4.02- 3.86 (m, 2H), 1.31 (t, J = 6.8 Hz, 3H) P226 620.95 (300
MHz, DMSO-d.sub.6) .delta. 3413, 1668, ([M + H].sup.+) 8.65 (d, J =
7.5 Hz 1H), 1161 8.57 (t, J = 6.3 Hz, 1H), 7.90 (s, 1H), 7.60-7.55
(m, 4H), 7.41 (d, J = 7.8 Hz, 2H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H),
6.78 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 4.50- 4.43 (m, 1H),
4.00-3.85 (m, 2H), 1.33 (d, J = 7.8 Hz, 3H) P228 610.94 (300 MHz,
DMSO-d.sub.6) .delta. 3413, 1668, ([M + H].sup.+) 8.74 (d, J = 7.5
Hz, 1H), 1161, 564 8.61 (t, J = 6.6 Hz, 1H), 7.96 (s, 1H), 7.91 (d,
J = 8.1 Hz, 1H), 7.63-7.53 (m, 4H), 7.41 (d, J = 7.5 Hz, 1H), 7.08
(dd, J = 15.6, 8.7 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.84-4.81
(m, 1H), 4.51-4.43 (m, 1H), 3.99-3.85 (m, 2H), 1.29 (d, J = 7.5 Hz,
3H) P298 634.8 (400 MHz, DMSO-d.sub.6) .delta. 3307, 2925, ([M +
H].sup.+) 8.65 (d, J = 7.6 Hz, 1H), 1652, 1164 8.55 (t, J = 6.4 Hz,
1H), 7.92-7.91 (d, J = 1.6 Hz, 1H), 7.67 (s, 1H), 7.62-7.58 (m,
2H), 7.54 (d, J = 9.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 6.97 (dd,
J = 15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.82- 4.77 (m,
1H), 4.50- 4.46 (m, 1H), 4.00- 3.82 (m, 2H), 1.31 (t, J = 7.2 Hz,
3H) P300 623.2 (400 MHz, DMSO-d.sub.6) .delta. 3296, 1652, ([M +
H].sup.+) 8.74 (d, J = 7.6 Hz, 1H), 1167 8.60 (d, J = 16.0 Hz, 1H),
7.97 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.62-7.59 (m,
1H), 7.56-7.53 (m, 2H), 7.06 (dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J
= 15.6 Hz, 1H), 4.84- 4.80 (m, 1H), 4.51- 4.47 (m, 1H), 4.03- 3.85
(m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P442 584.87 (400 MHz,
DMSO-d.sub.6) .delta. 3410, 1692, ([M + H].sup.+) 8.64 (d, J = 7.2
Hz, 1H), 1163, 769, 8.57 (t, J = 12.8 Hz, 565 1H), 7.87 (d, J = 1.2
Hz, 1H), 7.58-7.52 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.41-7.37 (m,
2H), 6.90 (dd, J = 16.0, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H),
4.68- 4.63 (m, 1H), 4.49- 4.46 (m, 1H), 3.99- 3.86 (m, 2H), 2.35
(s, 3H), 1.28 (d, J = 7.2 Hz, 3H) P444 574.98 (400 MHz,
DMSO-d.sub.6) .delta. 3292, 1661, ([M + H].sup.+) 8.73 (d, J = 8.0
Hz, 1H), 1158, 741 8.60 (t, J = 6.0 Hz, 1H), 7.92 (s, 1H), 7.88 (d,
J = 8.4 Hz, 1H), 7.55-7.53 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.40
(d, J = 8.4 Hz, 1H), 6.98 (dd, J = 15.6, 8.8 Hz, 1H), 6.86 (d, J =
15.6 Hz, 1H), 4.70-4.66 (m, 1H), 4.50-4.47 (m, 1H), 3.99-3.82 (m,
2H), 2.35 (s, 3H), 1.27 (d, J = 7.2 Hz, 3H) P514 583.0 (300 MHz,
DMSO-d.sub.6) .delta. 3276, 1638, ([M + H].sup.+) 8.64 (d, J = 7.2
Hz, 1H), 1167, 598 8.57 (t, J = 6.3 Hz, 1H), 7.86 (s, 1H), 7.58 (d,
J = 7.5 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.26 (d, J = 6.6 Hz,
2H), 6.88 (dd, J = 15.9, 8.4 Hz, 1H), 6.73 (d, J = 15.9 Hz, 1H),
4.58-4.46 (m, 2H), 4.00-3.85 (m, 2H), 2.24 (s, 6H), 1.31 (d, J =
7.5 Hz, 3H) P516 573.37 (300 MHz, DMSO-d.sub.6) .delta. 3299, 1654,
([M + H].sup.+) 8.73 (d, J = 7.8 Hz, 1H), 1165 8.61 (t, J = 6.3 Hz,
1H), 7.88 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.1 Hz, 1H), 7.27 (d, J
= 6.9 Hz, 2H), 6.98 (dd, J = 15.6, 8.4 Hz, 1H), 6.85 (d, J = 15.6
Hz, 1H), 4.57- 4.46 (m, 2H), 3.99- 3.85 (m, 2H), 2.24 (s, 6H), 1.29
(d, J = 7.2 Hz, 3H) P568 692.88 (300 MHz, DMSO-d.sub.6) .delta.
3306, 1646, ([M + H].sup.+) 8.65 (d, J = 7.8 Hz, 1H), 1164 8.55 (t,
J = 7.8 Hz, 1H), 7.98 (s, 1H), 7.90 (s, 1H), 7.85 (d, J = 8.7 Hz,
1H), 7.60-7.57 (m, 1H), 7.51-7.48 (m, 1H), 7.41-7.39 (m, 1H), 6.96
(dd, J = 15.6, 8.7 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.81- 4.72
(m, 1H), 4.50- 4.46 (m, 1H), 4.01- 3.82 (m, 2H), 1.31 (d, J = 6.9
Hz, 3H) P586 646.9 7.64 (s, 1H), 7.56-7.54 3384, 1647, ([M -
H].sup.-) (m, 2H), 7.43-7.39 (m, 1164, 749, 2H), 7.33 (s, 1H), 6.81
566 (bs, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H),
6.45 (dd, J = 16.0, 7.6 Hz, 1H), 4.75-4.72 (m, 1H), 4.14-4.10 (m,
1H), 4.00-3.90 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P588 638.84 (300
MHz, CDCl.sub.3) .delta. 3304, 2928, ([M + H].sup.+) 7.69 (s, 1H),
7.62-7.59 1650, 1165, (m, 1H), 7.55-7.49 (m, 673, 558 2H), 7.42 (s,
1H), 7.32 (s, 1H), 6.88 (bs, 1H), 6.65 (d, J = 16.2 Hz, 1H), 6.49
(dd, J = 16.2, 8.1 Hz, 1H), 6.34 (d, J = 7.2 Hz, 1H), 4.76-4.71 (m,
1H), 4.15-4.12 (m, 1H), 3.96-3.89 (m, 2H), 1.49 (d, J = 7.3 Hz, 3H)
P660 682.8 (400 MHz, DMSO-d.sub.6) .delta. 3310, 1650, ([M +
H].sup.+) 8.74 (d, J = 8.0 Hz, 1H), 1166, 558 8.60 (t, J = 8.8 Hz,
1H), 7.99-7.96 (m, 2H), 7.90 (d, J = 8.3 Hz, 1H),
7.85 (d, J = 8.3 Hz, 1H), 7.55-7.50 (m, 2H), 7.04 (dd, J = 15.6,
8.8 Hz, 1H), 6.86 (d, J = 16.0 Hz, 1H), 4.83-4.78 (m, 1H),
4.51-4.47 (m, 1H), 3.99-3.86 (m, 2H), 1.29 (d, J = 5.1 Hz, 3H) P730
615.85 (300 MHz, DMSO-d.sub.6) .delta. 3299, 1651, ([M + H].sup.+)
8.67 (d, J = 7.8 Hz, 1H), 1166, 739 8.55 (t, J = 6.6 Hz, 1H), 8.31
(s, 1H), 7.90-7.86 (m, 3H), 7.60 (d, J = 9.2 Hz, 1H), 7.42 (d, J =
8.1 Hz, 1H), 6.98 (dd, J = 15.6, 8.7 Hz, 1H), 6.79 (d, J = 15.6 Hz,
1H), 4.96-4.95 (m, 1H), 4.50-4.45 (m, 1H), 3.96-3.88 (m, 2H), 1.31
(d, J = 9.3 Hz, 3H) P732 605.96 (300 MHz, CDCl.sub.3) .delta. 3297,
1651, ([M + H].sup.+) 7.91 (s, 1H), 7.69 (s, 1167, 749 1H),
7.64-7.50 (m, 4H), 6.71 (bs, 1H), 6.67 (d, J = 16.2 Hz, 1H), 6.52
(dd, J = 15.9, 7.8 Hz, 1H), 6.30 (d, J = 6.9 Hz, 1H), 4.73-4.69 (m,
1H), 4.30-4.24 (m, 1H), 3.96-3.91 (m, 2H), 1.49 (d, J = 7.2 Hz, 3H)
P802 578.1 (300 MHz, DMSO-d.sub.6) 3307, 2927, ([M - H].sup.-)
.delta. 8.65 (d, J = 7.2 Hz, 2238, 1659, 1H), 8.56 (t, J = 6.3 Hz,
1166 1H), 8.20-8.18 (m, 1H), 8.00-7.90 (m, 2H), 7.66-7.54 (m, 2H),
7.42 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d,
J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.51-4.46 (m, 1H), 4.00-3.88
(m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P804 570.3 (300 MHz,
DMSO-d.sub.6) 3301, 3078, ([M + H].sup.+) .delta. 8.74 (d, J = 7.8
Hz, 2239, 1657, 1H), 8.59 (t, J = 6.6 Hz, 1167 1H), 8.21-8.19 (m,
1H), 8.01-7.96 (m, 2H), 7.90 (d, J = 8.1 Hz, 1H), 7.66-7.60 (m,
1H), 7.56 (d, J = 8.1 Hz, 1H), 7.08 (dd, J = 15.9, 8.7 Hz, 1H),
6.88 (d, J = 15.6 Hz, 1H), 4.91-4.85 (m, 1H), 4.52-4.47 (m, 1H),
3.99-3.88 (m, 2H), 1.29 (d, J = 6.9 Hz, 3H) P1090 569.89 (300 MHz,
DMSO-d.sub.6) .delta. 3277, 1698, ([M + H].sup.+) 8.64 (d, J = 7.5
Hz, 1H), 1167, 518 8.55 (t, J = 6.3 Hz, 1H), 7.86 (s, 1H), 7.58 (d,
J = 7.2 Hz, 1H), 7.47 (d, J = 6.9 Hz, 1H), 7.41-7.36 (m, 3H),
7.21-7.15 (m, 1H), 6.91 (dd, J = 15.6, 8.7 Hz, 1H), 6.74 (d, J =
15.9 Hz, 1H), 4.66- 4.60 (m, 1H), 4.50-4.45 (m, 1H), 4.03-3.85 (m,
2H), 2.26 (s, 3H), 1.31 (d, J = 7.2 Hz, 3H) P1092 559.05 (300 MHz,
DMSO-d.sub.6) .delta. 3437, 1643, ([M + H].sup.+) 8.74 (d, J = 7.8
Hz, 1H), 1165 8.59 (t, J = 6.3 Hz, 1H), 7.92 (s, 1H), 7.89 (d, J =
8.1 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H),
7.42-7.38 (m, 1H), 7.19 (t, J = 9.3 Hz, 1H), 7.00 (dd, J = 15.9,
8.7 Hz, 1H), 6.85 (d, J = 15.9 Hz, 1H), 4.69-4.62 (m, 1H),
4.51-4.47 (m, 1H), 4.02-3.85 (m, 2H), 2.26 (s, 3H), 1.29 (d, J =
7.2 Hz, 3H) P1197 576.83 (300 MHz, CDCl.sub.3) .delta. 3311, 1655,
([M + H].sup.+) 7.62-7.56 (m, 2H), 7.40- 1166 7.37 (m, 1H),
7.05-7.00 (m, 2H), 6.72 (bs, 1H), 6.56 (bs, 1H), 6.51 (d, J = 16.2
Hz, 1H), 6.52 (dd, J = 15.9, 7.5 Hz, 1H), 4.21 (d, J = 5.4 Hz, 2H),
4.13-4.08 (m, 1H), 4.02-3.91 (m, 2H) P1269 659.07 (300 MHz,
CDCl.sub.3) .delta. 3317, 1706, ([M + H].sup.+) 7.91 (s, 1H), 7.83
(s, 1175, 559 2H), 7.64-7.56 (m, 2H), 7.42-7.39 (m, 1H), 6.74 (bs,
1H), 6.62 (bs, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.50 (dd, J = 15.7,
7.8 Hz, 1H), 4.35-4.30 (m, 1H), 4.21 (d, J = 6.0 Hz, 2H), 4.02-3.90
(m, 2H) P1340 607.00 (300 MHz, DMSO-d.sub.6) .delta. 3411, 1652,
([M - H].sup.-) 8.68 (t, J = 5.7 Hz, 1H), 1166 8.56 (t, J = 6.3 Hz,
1H), 7.93 (s, 1H), 7.87-7.83 (m, 2H), 7.76-7.75 (m, 1H), 7.62-7.55
(m, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.05 (dd, J = 15.6, 9.0 Hz, 1H),
6.88 (d, J = 15.3 Hz, 1H), 4.99-4.92 (m, 1H), 4.01-3.90 (m, 4H)
P1411 624.92 (300 MHz, CDCl.sub.3) .delta. 3098, 1721, ([M +
H].sup.+) 7.64 (s, 1H), 7.58-7.55 1214, 723, (m, 3H), 7.51 (s, 1H),
513 7.41-7.38 (m, 1H), 6.77 (bs, 1H), 6.72 (bs, 1H), 6.59 (d, J =
15.9 Hz, 1H), 6.48 (dd, J = 15.9, 7.5 Hz, 1H), 4.24-4.19 (m, 4H),
4.01-3.90 (m, 1H) P1483 608.78 (300 MHz, CDCl.sub.3) .delta. 3300,
1657, ([M + H].sup.+) 7.62-7.54 (m, 3H), 7.39 1164, 560 (d, J = 8.1
Hz, 1H), 7.29-7.24 (m, 1H), 6.84- 6.82 (m, 1H), 6.56 (d, J = 15.6
Hz, 1H), 6.49 (dd, J = 15.6, 6.6 Hz, 1H), 4.23-4.19 (m, 2H),
4.01-3.93 (m, 3H) P1556 614.84 7.70 (s, 1H), 7.63-7.61 3369, 1719,
([M + H].sup.+) (m, 1H), 7.56-7.51 (m, 1164, 807. 1H), 7.41 (s,
2H), 6.65 (d, J = 15.6 Hz, 1H), 6.60 (bs, 2H), 6.50 (dd, J = 15.2,
6.8 Hz, 1H), 4.19-4.13 (m, 3H), 3.98-3.94 (m, 2H) P1558 595.00 (300
MHz, CDCl.sub.3) .delta. 3351, 1660, ([M - H].sup.-) 8.89 (bs, 1H),
7.72-7.69 1161, 700 (d, J = 8.1 Hz, 1H), 7.45-7.35 (m, 4H), 7.25-
7.19 (m, 1H), 6.58 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8
Hz, 1H), 4.57 (d, J = 5.7 Hz, 2H), 4.49-4.38 (m, 2H), 4.16-4.03 (m,
1H) P1559 628.95 (300 MHz, DMSO-d.sub.6) .delta. 3398, 1664, ([M -
H].sup.-) 10.45 (t, J = 6.4 Hz, 1163, 808 1H), 8.97 (t, J = 6.0 Hz,
1H), 8.02-7.92 (m, 4H), 7.77 (d, J = 7.5 Hz, 1H), 7.10 (dd, J =
15.6, 9.0 Hz, 1H), 6.90 (d, J = 15.6 Hz, 1H), 4.90-4.82 (m, 1H),
4.63-4.58 (m, 2H), 4.23 (d, J = 6.0 Hz, 2H) P1560 574.88 (400 MHz,
DMSO-d.sub.6) .delta. 3246, 1646, ([M - H].sup.-) 10.38 (t, J = 6.0
Hz, 1161, 808 1H), 8.65 (t, J = 5.6 Hz, 1H), 7.88 (s, 2H), 7.50-
7.42 (m, 3H), 6.88 (dd, J = 15.6, 8.8 Hz, 1H), 6.75 (d, J = 15.6
Hz, 1H), 4.85-4.81 (m, 1H), 4.63-4.54 (m, 2H), 4.24 (d, J = 6.2 Hz,
2H), 2.36 (s, 3H) P1564 576.6 (400 MHz, DMSO-d.sub.6) .delta. 3351,
1684, ([M + H].sup.+) 10.48 (t, J = 6.0 Hz, 1163, 808 1H), 8.74 (t,
J = 6.2 Hz, 1H), 7.89 (s, 2H), 7.41- 7.36 (m, 2H), 7.19 (d, J = 8.0
Hz, 1H), 6.84 (dd, J = 15.6, 8.8 Hz, 1H), 6.73 (d, J = 15.6 Hz,
1H), 4.84-4.79 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 3.98-3.92 (m,
2H), 2.32 (s, 3H) P1566 597.00 (400 MHz, DMSO-d.sub.6) .delta.
3323, 1654, ([M + H].sup.+) 8.74 (t, J = 5.6 Hz, 1H), 1115, 808
8.30 (t, J = 6.0 Hz, 1H), 8.03-7.84 (m, 4H), 7.61 (d, J = 8.4 Hz,
1H), 7.09 (dd, J = 15.6, 8.8 Hz, 1H), 6.89 (d, J = 16.4 Hz, 1H),
4.88-4.81 (m, 1H), 3.89 (d, J = 5.6 Hz, 2H), 3.59-3.48 (m, 3H)
P1589 638.9 (300 MHz, DMSO-d.sub.6) .delta. 3412, 1657, ([M +
H].sup.+) 8.63 (t, J = 5.7 Hz, 1H), 1169, 749, 8.50 (d, J = 9.0 Hz,
1H), 565 7.93-7.91 (m, 3H), 7.62- 7.60 (m, 1H), 7.42 (d, J = 7.8
Hz, 1H), 7.01 (dd, J = 15.6, 9.6 Hz, 1H), 6.77 (d, J = 15.6 Hz,
1H), 4.88-4.80 (m, 1H), 4.66-4.60 (m, 1H), 4.00- 3.97 (m, 1H),
3.87-3.80 (m, 1H), 1.27 (d, J = 6.9 Hz, 3H) P1591 628.95 (300 MHz,
DMSO-d.sub.6) .delta. 3436, 1667, ([M + H].sup.+) 8.74 (t, J = 6.0
Hz, 1H), 1261, 749 8.51 (d, J = 8.7 Hz, 1H), 7.99 (s, 1H),
7.92-7.90 (m, 3H), 7.58 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 15.6,
8.7 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.86 (m, 1H), 4.66-
4.58 (m, 1H), 4.00-3.92 (m, 1H), 3.88-3.80 (m, 1H), 1.27 (d, J =
7.2 Hz, 3H) P1592 574.98 (300 MHz, DMSO-d.sub.6) .delta. 3418,
1651, ([M + H].sup.+) 8.51 (d, J = 8.7 Hz, 1H), 1163, 748 8.41 (t,
J = 6.0 Hz, 1H), 7.89 (s, 2H), 7.45-7.35 (m, 3H), 6.83 (dd, J =
15.6, 8.5 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H),
4.65- 4.60 (m, 1H), 3.98-3.91 (m, 1H), 3.85-3.78 (m, 1H), 2.36 (s,
3H), 1.26 (d, J = 6.9 Hz, 3H) P1599 689.9 (300 MHz, DMSO-d.sub.6)
3415, 1599, ([M + H].sup.+) .delta. 8.67 (bs, 1H), 8.60 (t, 1162,
748 J = 6.0 Hz, 1H), 7.95 (d, J = 9.9 Hz, 2H), 7.91 (s, 1H), 7.78
(d, J = 6.6 Hz,
1H), 7.42 (d, J = 7.8 Hz, 1H) 7.12 (dd, J = 15.6, 9.9 Hz, 1H), 6.78
(d, J = 15.3 Hz, 1H), 4.94- 4.91 (m, 1H), 4.52- 4.45 (m, 1H), 4.00-
3.85 (m, 2H), 1.33 (d, J = 6.9 Hz, 3H) P1601 678.6 (300 MHz,
DMSO-d.sub.6) 3423, 1646, ([M + H].sup.+) .delta. 8.73 (bs, 1H),
8.59 (t, 1141, 807 J = 6.0 Hz, 1H), 7.95 (d, J = 9.9 Hz, 2H), 7.88-
7.83 (m, 2H), 7.56 (d, J = 7.2 Hz, 1H), 7.12 (dd, J = 15.6, 10.5
Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.94-4.91 (m, 1H), 4.51-4.43
(m, 1H), 3.99-3.88 (m, 2H), 1.31 (d, J = 6.9 Hz, 3H) P1603 113-117
563 7.80-7.72 (m, 2H), .sup.19F NMR ([M + H].sup.+) 7.48-7.44 (m,
2H), (376 MHz, CDCl.sub.3) 7.42 (s, 2H), 6.92 (t, J = .delta.
-68.66, -72.52 6.4 Hz, 1H), 6.62 (m, 1H), 6.42 (dd, J = 15.9, 8.0
Hz, 1H), 4.75 (p, J = 7.1 Hz, 1H), 4.11 (p, J = 8.5 Hz, 1H),
4.07-3.79 (m, 2H), 1.54 (d, J = 7.0 Hz, 3H) P1611A 621.0 (300 MHz,
DMSO-d.sub.6) .delta. 3410, 2925, ([M + H].sup.+) 8.60 (d, J = 7.8
Hz, 1H), 1645, 1115, 8.28 (t, J = 5.7 Hz, 1H), 748, 561 7.91 (s,
3H), 7.61-7.58 (m, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.01 (dd, J =
15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.86-4.79 (m, 1H),
4.49-4.44 (m, 1H), 3.55-3.31 (m, 2H), 1.30 (d, J = 6.9 Hz, 3H)
P1613A 611.1 (300 MHz, DMSO-d.sub.6) .delta. 3297, 1651, ([M +
H].sup.+) 8.70 (d, J = 7.8 Hz, 1H), 1115, 808 8.31 (t, J = 5.7 Hz,
1H), 7.98 (s, 1H), 7.92-7.88 (m, 3H), 7.57-7.55 (m, 1H),), 7.09
(dd, J = 15.3, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.82
(m, 1H), 4.52-4.43 (m, 1H), 3.57-3.47 (m, 2H), 1.29 (d, J = 7.5 Hz,
3H) P1616 602.8 (300 MHz, DMSO-d.sub.6) .delta. 3305, 1650, ([M +
H].sup.+) 8.64 (d, J = 7.5 Hz, 1H), 1169, 749, 8.11 (t, J = 5.4 Hz,
1H), 559 7.91 (s, 3H), 7.60-7.58 (m, 1H), 7.43 (d, J = 8.2 Hz, 1H),
7.00 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H),
4.86-4.53 (m, 1H), 4.51-4.42 (m, 2H), 4.35 (t, J = 5.1 Hz, 1H),
3.45-3.31 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) P1616A 602.8 (400 MHz,
DMSO-d.sub.6) .delta. 3407, 1651, ([M + H].sup.+) 8.53 (d, J = 7.60
Hz, 1169, 744, 1H), 8.08 (t, J = 6.0 Hz, 559 1H), 7.91-7.90 (m 3H),
7.59 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 6.98 (dd, J =
16.0, 9.2 Hz, 1H), 6.77 (d, J = 16.0 Hz, 1H), 4.84- 4.80 (m, 1H),
4.50- 4.36 (m, 3H), 3.44- 3.24 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H)
P1618A 593.1 (300 MHz, DMSO-d.sub.6) .delta. 3411, 1651, ([M +
H].sup.+) 8.64 (d, J = 7.8 Hz, 1H), 1115, 809 8.17 (t, J = 5.4 Hz,
1H), 8.03-7.87 (m, 3H), 7.60 (d, J = 7.8 Hz, 1H), 7.09 (dd, J =
15.9, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89- 4.53 (m, 1H),
4.53- 4.42 (m, 2H), 4.35 (t, J = 5.1 Hz, 1H), 3.44- 3.42 (m, 2H),
1.28 (d, J = 6.9 Hz, 3H) P1621 585.0 (300 MHz, DMSO-d.sub.6)
.delta. 3411, 1649, ([M + H].sup.+) 8.50 (bs, 1H), 7.91 (s, 1168,
806, 3H), 7.83-7.81 (m, 559 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.43.
(d, J = 8.1 Hz, 1H), 7.00 (dd, J = 15.9, 9.9 Hz, 1H), 6.77 (d, J =
15.9 Hz, 1H), 4.86-4.80 (m, 1H), 4.40-4.36 (m, 1H), 3.14-3.06 (m,
2H), 1.28 (d, J = 6.9 Hz, 3H), 1.03 (t, J = 6.0 Hz, 3H) P1623 575.1
(300 MHz, DMSO-d.sub.6) 3412, 1645, ([M + H].sup.+) .delta. 8.59
(bs, 1H), 7.97 (s, 1115, 749 1H), 7.92-7.85 (m, 4H), 7.57 (d, J =
7.8 Hz, 1H), 7.09 (dd, J = 16.2, 9.3 Hz, 1H), 6.88 (d, J = 15.9 Hz,
1H), 4.89- 4.82 (m, 1H), 4.43- 4.36 (m, 1H), 3.12- 3.05 (m, 2H),
1.26 (d, J = 7.2 Hz, 3H), 1.05 (t, J = 7.5 Hz, 3H) P1624 521.2 (300
MHz, DMSO-d.sub.6) .delta. 3307, 1642, ([M + H].sup.+) 8.26 (bs,
1H), 7.89 (s, 1114, 749 1H), 7.85-7.81 (m, 2H), 7.47-7.37 (m, 2H),
7.34 (d, J = 7.5 Hz, 1H), 6.88 (dd, J = 15.9, 8.7 Hz, 1H), 6.75 (d,
J = 15.9 Hz, 1H), 4.85- 4.79 (m, 1H), 4.39- 4.34 (m, 1H), 3.13-
3.04 (m, 2H), 2.48 (s, 3H), 1.28 (d, J = 7.5 Hz, 3H), 1.04 (t, J =
7.5 Hz, 3H) P1631A 652.8 (400 MHz, DMSO-d.sub.6) .delta. 3297,
1646, ([M + H].sup.+) 8.54 (d, J = 7.60 Hz, 1161, 742, 1H), 8.07
(t, J = 5.4 Hz, 555 1H), 7.91-7.90 (m 3H), 7.60 (d, J = 9.2 Hz,
1H), 7.43 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 9.0 Hz, 1H),
6.77 (d, J = 16.0 Hz, 1H), 4.85- 4.80 (m, 1H), 4.41- 4.37 (m, 1H),
3.40- 3.26 (m, 2H), 2.50- 2.38 (m, 2H), 1.28 (d, J = 7.6 Hz, 3H)
P1633A 640.7 (300 MHz, DMSO-d.sub.6) .delta. 3299, 1651, ([M -
H].sup.-) 8.66 (d, J = 7.2 Hz, 1H), 1139, 808 8.13 (t, J = 5.4 Hz,
1H), 7.97 (s, 1H), 7.92-7.88 (m, 3H), 7.58 (d, J = 8.2 Hz, 1H),
7.09 (dd, J = 16.3, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H),
4.89-4.82 (m, 1H), 4.42-4.37 (m, 1H), 3.38-3.24 (m, 2H), 2.44-2.36
(m, 2H), 1.27 (d, J = 7.2 Hz, 3H) P1636 176-184 575 7.76-7.72 (m,
2H), .sup.19F NMR ([M - H].sup.-) 7.48-7.44 (m, 2H), (376 MHz,
CDCl.sub.3) 7.42 (s, 2H), 6.62 (d, J = rotomers 15.9 Hz, 1H), 6.54
(s, .delta. -68.65, -72.57, -73.24 1H), 6.42 (dd, J = 15.9, 7.9 Hz,
1H), 4.89 (s, 1H), 4.11 (p, J = 8.7 Hz, 1H), 3.92 (dqd, J = 22.9,
9.0, 6.5 Hz, 2H), 1.71 (s, 6H) P1638 638.64 (300 MHz, DMSO-d.sub.6)
.delta. 3427, 2924, ([M + H].sup.+) 8.60 (bs, 1H), 8.44 (t, J =
1651, 1162, 6.0 Hz, 1H), 7.90 (s, 680 3H), 7.59 (d, J = 6.9 Hz,
1H), 7.33 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 16.2, 9.6 Hz, 1H),
6.76 (d, J = 15.3 Hz, 1H), 4.88-4.4.80 (m, 1H), 3.92-3.87 (m, 2H),
3.42-3.40 (m, 2H), 2.50-2.49 (m, 2H) P1640 628.9 (300 MHz,
DMSO-d.sub.6) .delta. 3445, 1644, ([M + H].sup.+) 8.61 (bs, 1H),
8.53 (t, J = 1163, 749 6.0 Hz, 1H), 7.96 (s, 1H), 7.92-7.86 (m,
3H), 7.47 (d, J = 9.0 Hz, 1H), 7.18 (dd, J = 15.6, 8.1 Hz, 1H),
6.88 (d, J = 15.6 Hz, 1H), 4.91- 4.78 (m, 1H), 3.96- 3.84 (m, 2H),
3.45- 3.38 (m, 2H), 2.50- 2.43 (m, 2H) P1641 574.8 (300 MHz,
DMSO-d.sub.6) .delta. 3427, 2926, ([M + H].sup.+) 8.61 (bs, 1H),
8.27 (t, J = 1645, 1162, 5.4 Hz, 1H), 7.89 (s, 809 2H), 7.47-7.37
(m, 2H), 7.28 (d, J = 8.1 Hz, 1H), 6.88 (dd, J = 15.6, 9.0 Hz, 1H),
6.74 (d, J = 15.9 Hz, 1H), 4.88- 4.81 (m, 1H), 3.92- 3.86 (m, 2H),
3.45-3.38 (m, 2H), 2.51-2.44 (m, 2H), 2.32 (s, 3H) P1691 654.8 (300
MHz, DMSO-d.sub.6) .delta. 3301, 1647, ([M + H].sup.+) 8.64 (d, J =
7.2 Hz, 1H), 1164, 746 8.57 (t, J = 6.3 Hz, 1H), 7.91 (s, 1H), 7.71
(s, 2H), 7.66 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 7.5
Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz, 1H), 6.78 (d, J = 15.6 Hz,
1H), 4.91-4.71 (m, 1H), 4.50-4.45 (m, 1H), 4.02-3.82 (m, 2H), 1.30
(d, J = 7.2 Hz, 3H) P1693 645.1 (300 MHz, DMSO-d.sub.6) .delta.
3309, 1650, ([M + H].sup.+) 8.73 (d, J = 7.2 Hz, 1H), 1165, 677
8.61 (d, J = 6.3 Hz, 1H), 7.96 (s, 1H), 7.86-7.80 (m, 1H), 7.71 (s,
2H), 7.67 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.00 (dd,
J = 15.6, 9.3 Hz, 1H), 6.90 (d, J = 15.9 Hz, 1H), 4.92- 4.71 (m,
1H), 4.51- 4.49 (m, 1H), 3.99- 3.85 (m, 2H), 1.29 (d, J = 7.2 Hz,
3H) P1696 604.2 (300 MHz, DMSO-d.sub.6) .delta. 3418, 1645, ([M +
H].sup.+) 8.65 (d, J = 7.2 Hz, 1H), 1165, 750, 8.55 (t, J = 6.0 Hz,
1H), 562 7.92 (d, J = 1.5 Hz, 1H), 7.68 (t, J = 3.3 Hz, 3H), 7.60
(d, J = 6.9 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.3,
8.7 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.83 (t, J = 7.2 Hz, 1H),
4.51 (t, J = 7.2 Hz, 1H), 4.01- 3.88 (m, 2H), 1.29 (d, J = 7.2 Hz,
3H) P1698 595.1 (300 MHz, DMSO-d.sub.6) .delta. 3294, 2928, ([M +
H].sup.+) 8.74 (d J = 7.5 Hz, 1H), 1646, 1166, 8.59 (t, J = 6.6 Hz,
1H), 750
7.98 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.69-7.62 (m, 2H), 7.56 (d,
J = 7.5 Hz, 1H), 7.09 (dd, J = 15.3, 8.7 Hz, 1H), 6.88 (d, J = 15.6
Hz, 1H), 4.83-4.80 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.86 (m, 2H),
1.29 (d, J = 7.2 Hz, 3H) P1776 593.2 (400 MHz, DMSO-d.sub.6)
.delta. .sup.19F NMR ([M + H].sup.+) 8.69 (t, J = 6.0 Hz, 1H), (376
MHz, DMSO-d.sub.6) 8.57 (t, J = 6.4 Hz, 1H), .delta. -67.98, -70.71
7.90 (dd, J = 13.3, 1.8 Hz, 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.58
(ddd, J = 18.0, 8.2, 1.8 Hz, 2H), 7.44 (d, J = 7.9 Hz, 1H), 6.94
(dd, J = 15.7, 9.0 Hz, 1H), 6.74 (d, J = 15.7 Hz, 1H), 4.81 (p, J =
9.4 Hz, 1H), 4.02- 3.87 (m, 4H) P1781 513.2 7.85-7.74 (m, 2H),
.sup.19F NMR ([M + H].sup.+) 7.53-7.41 (m, 4H), (376 MHz,
CDCl.sub.3) 7.30 (t, J = 6.2 Hz, 1H), .delta. -68.78, -72.44 7.23
(dd, J = 8.4, 2.0 Hz, 1H), 7.19 (t, J = 5.2 Hz, 1H), 6.61 (d, J =
15.9 Hz, 1H), 6.46 (dd, J = 15.9, 7.8 Hz, 1H), 4.26 (d, J = 5.1 Hz,
2H), 4.21-4.07 (m, 1H), 3.95 (qd, J = 9.1, 6.4 Hz, 2H) P1806 605.0
(300 MHz, DMSO-d.sub.6) .delta. 3411, 2925, ([M + H].sup.+) 8.67
(d, J = 7.2 Hz, 1H), 1650, 1163, 8.57 (t, J = 6.3 Hz, 1H), 747
7.91-7.88 (m, 2H), 7.74 (d, J = 8.7 Hz, 1H), 7.64-7.59 (m, 2H),
7.41 (d, J = 8.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.76 (d,
J = 15.9 Hz, 1H), 4.83- 4.77 (m, 1H), 4.52- 4.43 (m, 1H), 4.05-
3.83 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P1808 695.1 (400 MHz,
DMSO-d.sub.6) .delta. 3297, 1652, ([M + H].sup.+) 8.74 (d, J = 7.2
Hz, 1H), 1165, 745 8.59 (s, 1H), 7.96-7.89 (m, 3H), 7.73 (d, J =
8.4 Hz, 1H), 7.55 (t, J = 8.8 Hz, 2H), 7.05 (dd, J = 16.0, 8.8 Hz,
1H), 6.87 (d, J = 16.0 Hz, 1H), 4.85-4.80 (m, 1H), 4.51-4.47 (m,
1H), 3.99-3.88 (m, 2H), 1.28 (d, J = 6.8 Hz, 3H) P1862 598.89 7.70
(s, 1H), 7.62-7.60 3324, 1673, ([M + H].sup.+) (m, 1H), 7.55-7.53
(m, 1164, 772 1H), 7.35 (d, J = 5.6 Hz, 2H), 7.89 (t, J = 6.0 Hz,
1H), 6.67 (t, J = 5.6 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.48 (dd,
J = 16.4, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.17-4.08 (m, 1H),
3.97- 3.89 (m, 2H) P1864 622.88 (400 MHz, DMSO-d.sub.6) .delta.
3256, 1657, ([M - H].sup.-) 10.39 (bs, 1H), 8.85 (t, J = 1166, 749,
6.0 Hz, 1H), 7.94 (s, 591 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.64 (d, J
= 8.4 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.6, 8.8
Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.81-4.79 (m, 1H), 4.63-4.59
(m, 2H), 4.24 (d, J = 6.0 Hz, 2H) P1866 614.91 (400 MHz,
DMSO-d.sub.6) .delta. 3447, 1655, ([M + H].sup.+) 10.43 (bs, 1H),
8.96 (t, J = 1167, 816 6.0 Hz, 1H), 8.00 (s, 1H), 7.94 (d, J = 7.6
Hz, 1H), 7.88 (d, J = 6.4 Hz, 2H), 7.76 (d, J = 8.0 Hz, 1H), 7.09
(dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J = 16.0 Hz, 1H), 4.86-4.78
(m, 1H), 4.62-4.58 (m, 2H), 4.23 (d, J = 5.6 Hz, 2H) P1969 678.77
(300 MHz, DMSO-d.sub.6) .delta. 3296, 1697, ([M + H].sup.+) 8.65
(t, J = 5.4 Hz, 1H), 1164, 596 8.54 (t, J = 6.3 Hz, 1H), 7.90-7.86
(m, 2H), 7.82 (s, 2H), 7.60 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 7.8
Hz, 1H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H), 6.75 (d, J = 15.6 Hz,
1H), 4.83-4.76 (m, 1H), 4.01- 3.91 (m, 4H) P1970 634.87 (300 MHz,
DMSO-d.sub.6) .delta. 3299, 1658, ([M + H].sup.+) 8.68 (t, J = 6.0
Hz, 1H), 1164, 745, 8.57 (t, J = 6.0 Hz, 1H), 543 7.89-7.78 (m,
4H), 7.59-7.56 (m, 1H), 7.49-7.46 (m, 1H), 7.02 (dd, J = 15.9, 8.1
Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.83- 4.76 (m, 1H), 4.01- 3.91
(m, 4H) P1971 668.87 (300 MHz, DMSO-d.sub.6) .delta. 3351, 1705,
([M + H].sup.+) 8.77 (t, J = 6.0 Hz, 1H), 1165, 551 8.59 (t, J =
6.3 Hz, 1H), 7.99 (s, 1H), 7.93-7.85 (m, 4H), 7.60 (d, J = 8.1 Hz,
1H), 7.10 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H),
4.85-4.79 (m, 1H), 3.98- 3.90 (m, 4H) P1972 614.84 (400 MHz,
DMSO-d.sub.6) .delta. 3311, 1650, ([M + H].sup.+) 8.57 (t, J = 6.4
Hz, 1H), 1163, 543 8.47 (t, J = 6.0 Hz, 1H), 7.88-7.80 (m, 3H),
7.45 (s, 1H), 7.43-7.37 (m, 2H), 6.86 (dd, J = 15.6, 8.8 Hz, 1H),
6.74 (d, J = 15.6 Hz, 1H), 4.83-4.74 (m, 1H), 3.98-3.88 (m, 4H),
2.37 (s, 3H) P2009 692.88 (300 MHz, DMSO-d.sub.6) .delta. 3402,
1659, ([M + H].sup.+) 8.62 (t, J = 5.7 Hz, 1H), 1165, 560 8.50 (d,
J = 8.7 Hz, 1H), 7.93-7.92 (m, 1H), 7.89-7.88 (m, 1H), 7.84 (s,
2H), 7.62-7.59 (m, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.01 (dd, J =
15.9, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.82-4.76 (m, 1H),
4.65-4.58 (m, 1H), 4.00- 3.92 (m, 1H), 3.87- 3.80 (m, 1H), 1.27 (d,
J = 6.9 Hz, 3H) P2010 646.84 (300 MHz, DMSO-d.sub.6) .delta. 3406,
1658, ([M - H].sup.-) 8.63 (t, J = 6.0 Hz, 1H), 1165, 746, 8.50 (d,
J = 8.7 Hz, 1H), 583 7.89-7.88 (m, 1H), 7.84 (s, 2H), 7.78 (s, 1H),
7.59-7.56 (m, 1H), 7.46 (d, J = 7.5 Hz, 1H), 7.00 (dd, J = 15.6,
9.0 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.79- 4.76 (m, 1H), 4.63-
4.60 (m, 1H), 3.95- 3.86 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) P2011
682.93 (400 MHz, DMSO-d.sub.6) .delta. 3417, 1666, ([M + H].sup.+)
8.73 (t, J = 5.6 Hz, 1H), 1115, 558 8.50 (d, J = 8.8 Hz, 1H), 7.98
(s, 1H), 7.90-7.89 (m, 2H), 7.85 (s, 2H), 7.57 (d, J = 8.4 Hz, 1H),
7.09 (dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.84-
4.79 (m, 1H), 4.65- 4.59 (m, 1H), 4.03- 3.95 (m, 1H), 3.87- 3.81
(m, 1H), 1.25 (d, J = 6.0 Hz, 3H) P2012 628.89 (300 MHz,
DMSO-d.sub.6) .delta. 3406, 1643, ([M + H].sup.+) 8.51 (d, J = 8.7
Hz, 1H), 1163, 583 8.41 (t, J = 6.0 Hz, 1H), 7.88 (s, 1H), 7.82 (s,
1H), 7.45-7.34 (m, 3H), 6.87 (dd, J = 15.9, 8.7 Hz, 1H), 6.74 (d, J
= 15.6 Hz, 1H), 4.82-4.75 (m, 1H), 4.65-4.57 (m, 1H), 3.98-3.78 (m,
2H), 2.36 (s, 3H), 1.26 (d, J = 7.2 Hz, 3H) P2036 674.7 (300 MHz,
DMSO-d.sub.6) .delta. 3296, 1651, ([M + H].sup.+) 8.61 (d, J = 7.8
Hz, 1H), 1113, 534 8.26 (t, J = 5.7 Hz, 1H), 7.92-7.88 (m, 2H),
7.84 (s, 2H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H),
7.00 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H),
6.20-5.80 (m, 1H), 4.83-4.74 (m, 1H), 4.51-4.42 (m, 1H), 3.61-3.31
(m, 2H), 1.31 (d, J = 7.5 Hz, 3H) P2038 662.7 (300 MHz,
DMSO-d.sub.6) .delta. 3292, 1650, ([M - H].sup.+) 8.69 (d, J = 7.2
Hz, 1H), 1115, 747, 8.30 (bs, 1H), 7.98 (s, 681 1H), 7.89-7.85 (m,
4H), 7.57 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.09 (dd,
J = 15.9, 9.6 Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 6.18- 5.81 (m,
1H), 4.84- 4.78 (m, 1H), 4.50- 4.45 (m, 1H), 3.50- 3.45 (m, 2H),
1.29 (d, J = 7.2 Hz, 3H) P2041 656.6 (400 MHz, DMSO-d.sub.6)
.delta. 3305, 1645, ([M + H].sup.+) 8.56 (d, J = 7.2 Hz, 1H), 1167,
559 8.10 (t, J = 5.2 Hz, 1H), 7.92-7.88 (m, 2H), 7.84 (s, 2H), 7.60
(d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0,
9.6 Hz, 1H), 6.76 (d, J = 16.0 Hz, 1H), 4.81-4.74 (m, 1H),
4.50-4.36 (m, 3H), 3.56-3.36 (m, 2H), 1.29 (d, J = 6.8 Hz, 3H)
P2043 646.9 (300 MHz, DMSO-d.sub.6) .delta. 3291, 1651, ([M +
H].sup.+) 8.64 (d, J = 7.8 Hz, 1H), 1115, 588 8.15 (t, J = 5.7 Hz,
1H), 7.97 (s, 1H) 7.90-7.85 (m, 4H), 7.57 (d, J = 8.0 Hz, 1H), 7.09
(dd, J = 15.9, 9.3 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.84-4.78
(m, 1H), 4.51-4.42 (m, 2H), 4.37- 4.33 (m, 1H), 3.45- 3.42 (m, 2H),
1.28 (d, J = 7.8 Hz, 3H) P2056 91-94 706.8 (400 MHz, DMSO-d.sub.6)
.delta. ([M + H].sup.+) 8.57 (d, J = 7.2 Hz, 1H),
8.09 (t, J = 5.2 Hz, 1H), 7.92-7.88 (m, 2H), 7.84 (s, 2H), 7.60 (d,
J = 7.6 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 9.1
Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m, 1H), 4.40-4.36
(m, 1H), 3.40-3.25 (m, 2H) 2.44-2.32 (m, 2H), 1.28 (d, J = 6.8 Hz,
3H) P2058 696.8 (300 MHz, DMSO-d.sub.6) .delta. 3309, 1650, ([M +
H].sup.+) 8.66 (s, 1H), 8.14 (s, 1141 2H), 7.97 (s, 1H), 7.89- 7.85
(m, 3H) 7.57 (d, J = 8.1 1H), 7.06 (dd, J = 16.2, 9.0 Hz, 1H), 6.88
(d, J = 16.2 Hz, 1H), 4.82-4.81 (m, 1H), 4.41-4.37 (m, 1H) 3.38-
2.99 (m, 2H), 2.44- 2.36 (m, 2H) 1.27 (d, J = 7.2 Hz, 3H)
.sup.a.sup.1H NMR spectral data were acquired using a 400 MHz
instrument in CDCl.sub.3 except where noted. HRMS data are noted
observed value (theoretical value).
TABLE-US-00011 TABLE 2C Analytical Data for Compounds in Table 1C.
Compound IR (cm.sup.-1); Number mp (.degree. C.) ESIMS .sup.1H NMR
(.delta.).sup.a .sup.19F NMR (.delta.) FA1 562.89 (400 MHz,
DMSO-d.sub.6) 3418, 1658, ([M + H].sup.+) .delta. 8.65 (t, J = 5.2
Hz, 1114, 749 1H), 8.28 (t, J = 6.0 Hz, 1H), 7.91 (s, 2H), 7.78 (s,
1H), 7.58 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.01 (dd,
J = 15.6, 9.2 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m,
1H), 3.90 (d, J = 6.0 Hz, 2H), 3.59-3.48 (m, 3H) FA2 542.93 (400
MHz, DMSO-d.sub.6) 3430, 1646, ([M + H].sup.+) .delta. 8.45 (t, J =
6.0 Hz, 1113, 749 1H), 8.29 (t, J = 4.5 Hz, 1H), 7.89 (s, 2H),
7.45-7.34 (m, 3H), 6.87 (dd, J = 15.7, 6.9 Hz, 1H), 6.75 (d, J =
15.8 Hz, 1H), 4.85-4.80 (m, 1H), 3.87 (d, J = 4.8 Hz, 2H),
3.57-3.47 (m, 3H), 2.42 (s, 3H) FA3 606.78 (400 MHz, DMSO-d.sub.6)
3420, 1654, ([M + H].sup.+) .delta. 8.65 (t, J = 5.6 Hz, 114, 749,
558 1H), 8.27 (t, J = 5.6 Hz, 1H), 7.93-7.91 (m, 2H), 7.62-7.58 (m,
2H), 7.46 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.2, 9.2 Hz, 1H),
6.77 (d, J = 15.6 Hz, 1H), 4.85-4.81 (m, 1H), 3.89 (d, J = 6.0 Hz,
1H), 3.59-3.48 (m, 2H), 3.17-3.08 (m, 2H) FA4 599.00 (400 MHz,
CDCl.sub.3) .delta. ([M + H].sup.+) 9.81 (s, 1H), 8.06 (d, J = 7.1
Hz, 1H), 7.70 (d, J = 5.5 Hz, 1H), 7.44 (s, 1H), 7.37 (t, J = 2.7
Hz, 2H), 7.20 (s, 1H), 6.82 (d, J = 15.9 Hz, 1H), 6.50 (dd, J =
16.0, 8.5 Hz, 1H), 4.14 (m, 3H), 3.89 (m, 2H) FA5 613.10 (400 MHz,
CDCl.sub.3) .delta. ([M + H].sup.+) 7.45 (s, 1H), 7.41 (s, 2H),
7.29 (s, 1H), 7.28 (s, 1H), 6.84 (m, 2H), 6.43 (dd, J = 16.0, 8.3
Hz, 1H), 4.25 (d, J = 5.4 Hz, 2H), 4.10 (m, 1H), 3.97 (qd, J = 9.0,
6.4 Hz, 2H), 3.87 (s, 3H) FA6 545.92 (400 MHz, DMSO-d.sub.6) 3369,
1694, ([M + H].sup.+) .delta. 8.56 (t, J = 6.4 Hz, 1164, 713 1H),
8.51 (t, J = 5.6 Hz, 1H), 7.82 (d, J = 6.4 Hz, 2H), 7.56 (d, J =
8.0 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.75 (s, 1H), 6.72 (dd, J =
15.6, 6.8 Hz, 1H), 6.62 (d, J = 15.6 Hz, 1H), 6.51 (bs, 2H),
4.82-4.78 (m, 1H), 3.96-3.85 (m, 4H) FA7 638.78 (300 MHz,
CDCl.sub.3) .delta. 3284, 1667, ([M + H].sup.+) 7.62-7.56 (m, 2H),
1166, 744, 7.46-7.37 (m, 2H), 591 6.77-6.76 (m, 1H), 6.56 (d, J =
14.1 Hz, 1H), 6.43 (dd, J = 15.9, 7.8 Hz, 1H), 4.14-4.07 (m, 3H),
3.61-3.54 (m, 2H), 2.42-2.34 (m, 2H) FA8 588.87 (300 MHz,
DMSO-d.sub.6) .delta. 3297, 1658, ([M + H].sup.+) 8.68 (t, J = 5.7
Hz, 1H), 1165 8.56 (t, J = 6.6 Hz, 1H), 7.91 (s, 1H), 7.61-7.58 (m,
1H), 7.45-7.39 (m, 3H), 6.95 (dd, J = 15.9, 9.3 Hz, 1H), 6.75 (d, J
= 15.9 Hz, 1H), 4.76-4.64 (m, 1H), 4.06-3.92 (m, 4H), 3.90 (s, 3H)
FA9 624.92 (300 MHz, DMSO-d.sub.6) 3430, 1651, ([M + H].sup.+)
.delta. 9.81 (bs, 1H), 8.69 (s, 1166, 750 1H), 7.90 (s, 2H), 7.78
(s, 1H), 7.59-7.58 (m, 2H), 7.02 (dd, J = 15.8, 9.3 Hz, 1H), 6.78
(d, J = 15.8 Hz, 1H), 4.86-4.79 (m, 1H), 4.57-4.52 (m, 2H), 1.60
(s, 6H) FA10 640.9 (300 MHz, DMSO-d.sub.6) 3434, 1260, ([M +
H].sup.+) .delta. 10.41 (s, 1H), 750 9.68 (bs, 1H), 7.90 (s, 2H),
7.76-7.67 (m, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.8 Hz,
1H), 6.97 (dd, J = 15.6, 8.7 Hz, 1H), 6.77 (d, J = 15.6, 1H), 4.86
(t, J = 9.3 Hz, 1H), 4.55-4.47 (m, 2H), 1.75 (s, 6H) FA11 668.8
(300 MHz, DMSO-d.sub.6) 3425, 1651, ([M + H].sup.+) .delta. 9.80
(bs, 1H), 8.69 (s, 1261, 750 1H), 7.92-7.90 (m, 3H), 7.60-7.55 (m,
2H), 7.01 (dd, J = 15.5, 9.1 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H),
4.84-4.30 (m, 1H), 4.57-4.52 (m, 2H), 1.60 (s, 6H) FA12 660.8 (300
MHz, DMSO-d.sub.6) 3430, 1651, ([M + 2H].sup.+) .delta. 9.87 (bs,
1H), 1261, 750 8.76 (bs, 1H), 7.98 (s, 1H), 7.95-7.91 (m, 3H), 7.83
(d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J =
15.9, 1H), 4.89 (t, J = 9.6 Hz, 1H), 4.57-4.51 (m, 2H), 1.58 (s,
6H) FA13 606.8 (300 MHz, DMSO-d.sub.6) 3418, 1651, ([M + H].sup.+)
.delta. 10.36 (s, 1H), 1164, 749 8.67 (bs, 1H), 8.56 (bs, 1H), 7.92
(s, 1H), 7.61-7.58 (m, 3H), 7.44 (d, J = 7.8 Hz, 1H), 6.96 (dd, J =
15.4, 8.8 Hz, 1H), 6.74 (d, J = 15.7 Hz, 1H), 4.61-4.70 (m, 1H),
4.04-3.90 (m, 4H) FA14 611.9 (400 MHz, CDCl.sub.3) .delta. .sup.19F
NMR ([M + H].sup.+) 7.69 (s, 1H), 7.62 (d, J = 1.6 Hz, (376 MHz,
1H), 7.53 (d, CDCl.sub.3) .delta. -68.59 J = 8.0 Hz, 1H), 7.39 (m,
3H), 6.54 (d, J = 15.9 Hz, 1H), 6.40 (dd, J = 15.9, 7.8 Hz, 1H),
6.28 (s, 1H), 4.21 (d, J = 5.7 Hz, 2H), 4.12 (m, 1H), 1.69 (s, 6H)
FA15 643.19 (400 MHz, CDCl.sub.3) .delta. .sup.19F NMR ([M +
H].sup.+) 7.60 (d, J = 1.6 Hz, (376 MHz, 1H), 7.51 (d, J = 8.0 Hz,
CDCl.sub.3) .delta. -68.62 1H), 7.40 (s, 2H), 7.36 (dd, J = 8.1,
1.6 Hz, 1H), 6.66 (d, J = 10.0 Hz, 2H), 6.53 (d, J = 15.9 Hz, 1H),
6.38 (dd, J = 15.9, 7.8 Hz, 1H), 4.11 (m, 1H), 3.12 (d, J = 6.2 Hz,
2H), 1.72 (s, 6H), 0.93 (s, 9H) FA16 687.0 (300 MHz, DMSO-d.sub.6)
3433, 1640, ([M + H].sup.+) .delta. 8.61-8.53 (m, 2H), 1163, 749
8.11 (s, 1H), 7.91 (s, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.36 (d, J =
8.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.74 (d, J = 15.9 Hz,
1H), 4.85-4.82 (m, 1H), 4.50-4.45 (m, 1H), 4.00-3.88 (m, 2H), 1.36
(d, J = 7.5 Hz, 3H) FA17 587.1 (300 MHz, DMSO-d.sub.6) 3419, 1644,
([M + H].sup.+) .delta. 8.60-8.53 (m, 2H), 1162, 748 7.91-7.85 (m,
3H), 7.54 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.02 (dd,
J = 17.4, 11.1 Hz, 1H), 6.92 (dd, J = 15.9, 9.0 Hz, 1H), 6.81 (d, J
= 15.9 Hz, 1H), 5.95 (d, J = 17.1 Hz, 1H), 5.33 (d, J = 11.7 Hz,
1H), 4.87-4.80 (m, 1H), 4.47-4.43 (m, 1H), 4.01-3.87 (m, 2H), 1.31
(d, J = 6.9 Hz, 3H) FA18 573.2 (300 MHz, DMSO-d.sub.6) 3422, 1649,
([M + H].sup.+) .delta. 8.62-8.56 (m, 2H), 1164, 809 7.91-7.86 (m,
3H), 7.56 (d, J = 9.3 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.11 (dd,
J = 17.4, 11.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.82 (d, J
= 15.9 Hz, 1H), 5.96 (d, J = 16.8 Hz, 1H), 5.34 (d, J = 12.0 Hz,
1H), 4.87-4.81 (m, 1H), 4.01-3.89 (m, 4H) FA19 667.0 (300 MHz,
DMSO-d.sub.6) 3288, 1645, ([M + H].sup.+) .delta. 8.64-8.58 (m,
2H), 1164, 743, 7.92-7.89 (m, 3H), 563 7.60 (d, J = 8.1 Hz, 1H),
7.37 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.3, 8.7 Hz, 1H), 6.77 (d,
J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H), 4.49-4.42 (m, 1H), 4.07-3.81
(m, 2H), 1.65-1.59 (m, 2H), 1.40-1.30 (m, 2H), 0.89 (t, J = 6.9 Hz,
3H) FA20 609.1 (400 MHz, DMSO-d.sub.6) 3422, 2926, ([M + H].sup.+)
.delta. 8.74 (d J = 7.6 Hz, 1651, 1165, 1H), 8.59 (t, J = 6.4 Hz,
783 1H), 7.95 (s, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.72 (s, 1H), 7.55
(d, J = 7.2 Hz, 2H), 7.02 (dd, J = 16.0, 8.8 Hz, 1H), 6.87 (d, J =
15.6 Hz, 1H), 4.76-4.72 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.88 (m,
2H), 2.42 (s, 3H), 1.29 (d, J = 7.2 Hz, 3H) FA21 673.0 (300 MHz,
DMSO-d.sub.6) 3429, 1650, ([M + H].sup.+) .delta. 8.74 (d, J = 7.5
Hz, 1165, 804 1H), 8.59 (t, J = 6.3 Hz, 1H), 7.98 (s, 1H),
7.91-7.85 (m, 3H), 7.56 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.9,
9.3 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.81 (m, 1H),
4.52-4.57 (m, 1H), 4.04-3.85 (m, 2H), 1.29 (t, J = 6.9 Hz, 3H) FA22
681.0 (300 MHz, DMSO-d.sub.6) 3298, 1651, ([M - H].sup.-) .delta.
8.65 (d, J = 7.5 Hz, 1164, 689, 1H), 8.55 (t, J = 5.7 Hz, 536 1H),
7.91-7.85 (m, 2H), 7.48-7.39 (m, 2H), 7.31-7.26 (m, 1H), 7.00 (dd,
J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.86-4.82 (m,
1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H)
FA23 651.2 (400 MHz, CDCl.sub.3) .delta. .sup.19F NMR ([M +
H].sup.+) 7.61 (d, J = 1.6 Hz, (376 MHz, 1H), 7.51 (d, J = 8.0 Hz,
CDCl.sub.3) .delta. -68.61, 1H), 7.40 (s, 2H), -96.22 7.37 (dd, J =
8.1, 1.6 Hz, 1H), 6.85 (t, J = 6.2 Hz, 1H), 6.53 (d, J = 15.9 Hz,
1H), 6.42 (s, 1H), 6.38 (dd, J = 15.9, 7.8 Hz, 1H), 4.11 (m, 1H),
3.70 (td, J = 13.3, 6.3 Hz, 2H), 1.67 (m, 9H) FA24 672.9 (400 MHz,
DMSO-d.sub.6) 3410, 1653, ([M + H].sup.+) .delta. 8.49 (t, J = 6.0
Hz, 1164, 812 1H), 8.42 (t, J = 6.4 Hz, 1H), 7.98 (s, 1H), 7.76 (s,
2H), 7.49-7.47 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.82 (dd, J =
15.6, 9.2 Hz, 1H), 6.59 (d, J = 16.4 Hz, 1H), 4.70-4.65 (m, 1H),
3.89-3.75 (m, 4H) FA25 603.0 (400 MHz, DMSO-d.sub.6) 3288, 1676,
([M + H].sup.+) .delta. 8.61 (t, J = 6.4 Hz, 1164, 809 1H), 8.37
(d, J = 8.0 Hz, 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.40 (d, J = 8.4
Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.86 (dd, J = 16.0, 8.8 Hz, 1H),
6.75 (d, J = 15.6 Hz, 1H), 4.85-4.80 (m, 1H), 4.47-4.41 (m, 1H),
4.02-3.96 (m, 1H), 3.90-3.83 (m, 1H), 2.32 (s, 3H), 1.67-1.61 (m,
2H), 1.42-1.28 (m, 2H), 0.89 (t, J = 7.6 Hz, 3H) FA26 108-111 726.9
(300 MHz, DMSO-d.sub.6) ([M + H].sup.+) .delta. 8.65 (d, J = 7.2
Hz, 1H), 8.55 (t, J = 6.3 Hz, 1H), 8.04 (s, 1H), 7.92 (s, 1H),
7.84-7.76 (m, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz,
1H), 7.01 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H),
4.84-4.78 (m, 1H), 4.51-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (d, J
= 7.5 Hz, 3H) FA27 103-107 717.1 (300 MHz, DMSO-d.sub.6) ([M +
H].sup.+) .delta. 8.74 (d, J = 6.9 Hz, 1H), 8.59 (t, J = 6.0 Hz,
1H), 8.06 (s, 1H), 7.91-7.79 (m, 3H), 7.56 (d, J = 8.1 Hz, 1H),
7.09 (dd, J = 15.9, 8.6 Hz, 1H), 6.88 (d, J = 15.3 Hz, 1H),
4.84-4.81 (m, 1H), 4.52-4.47 (m, 1H), 3.99-3.88 (m, 2H), 1.29 (d, J
= 6.9 Hz, 3H) FA28 588.9 (300 MHz, DMSO-d.sub.6) 3361, 2960, ([M +
H].sup.+) .delta. 8.59 (t, J = 6.6 Hz, 1690, 1166, 1H), 8.51 (d, J
= 6.9 Hz, 819 1H), 7.88 (s, 2H), 7.22 (s, 2H), 6.75-6.63 (m, 2H),
4.83-4.77 (m, 1H), 4.50-4.49 (m, 1H), 4.00-3.87 (m, 2H), 2.21 (s,
6H), 1.33-1.22 (m, 3H) FA29 600.8 (400 MHz, DMSO-d.sub.6) 3288,
1687, ([M + H].sup.+) .delta. 8.63 (d, J = 7.2 Hz, 1164, 748, 1H),
8.55 (t, J = 6.4 Hz, 568 1H), 7.86 (s, 2H), 7.77 (d, J = 2.0 Hz,
1H), 7.66 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.47 (dd,
J = 10.0, 8.0 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 6.94 (dd, J =
15.6, 9.3 Hz, 1H), 6.63 (d, J = 15.6 Hz, 1H), 4.48-4.43 (m, 1H),
4.05-3.92 (m, 2H), 1.64 (t, J = 19.2 Hz, 3H), 1.30 (d, J = 6.8 Hz,
3H) FA30 655.0 (300 MHz, DMSO-d.sub.6) 3418, 1717, ([M + H].sup.+)
.delta. 8.64 (d, J = 7.5 Hz, 1165, 748, 1H), 8.58 (t, J = 6.3 Hz,
525 1H), 7.95-7.91 (m, 2H), 7.66 (s, 2H), 7.60 (d, J = 8.1 Hz, 1H),
7.42 (d, J = 7.8 Hz, 1H), 6.99 (dd, J = 15.9, 9.3 Hz, 1H), 6.78 (d,
J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.85
(m, 2H), 1.31 (d, J = 7.5 Hz, 3H) FA31 598.9 (300 MHz,
DMSO-d.sub.6) 3406, 1645, ([M + H].sup.+) .delta. 8.65 (d, J = 7.5
Hz, 1163, 749, 1H), 8.55 (t, J = 5.7 Hz, 597 1H), 7.89 (s, 1H),
7.60 (d, J = 8.1 Hz, 1H), 7.46 (s, 1H), 7.41 (d, J = 7.8 Hz, 2H),
7.31 (s, 1H), 6.96 (dd, J = 15.9, 8.7 Hz, 1H), 6.76 (d, J = 15.9
Hz, 1H), 4.71 (t, J = 9.3 Hz, 1H), 4.50 (t, J = 7.5 Hz, 1H),
4.00-3.88 (m, 2H), 2.67-2.60 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H),
1.21 (t, J = 7.5 Hz, 3H) FA32 666.9 (300 MHz, DMSO-d.sub.6) 3288,
1645, ([M + H].sup.+) .delta. 8.68 (s, 1H), 8.54 (d, 1165, 750 J =
8.4 Hz, 1H), 7.96-7.91 (m, 3H), 7.59 (d, J = 8.1 Hz, 1H), 7.33 (d,
J = 6.6 Hz, 1H), 6.98 (dd, J = 15.6, 8.0 Hz, 1H), 6.77 (d, J =
15.9, 1H), 4.88-4.72 (m, 1H), 4.36-4.31 (m, 1H), 4.07-3.81 (m, 2H),
2.06-1.99 (m, 1H), 0.95-0.85 (m, 6H) FA33 656.9 (300 MHz,
DMSO-d.sub.6) 3294, 1650, ([M + H].sup.+) .delta. 8.71 (d, J = 6.3
Hz 1165, 810 1H), 8.65 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.92-7.87
(m, 3H), 7.45 (d, J = 8.1 Hz, 1H), 7.03 (dd, J = 1 6 Hz, 8.0 Hz,
1H), 6.89 (d, J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.35-4.10 (m,
1H), 4.07-3.81 (m, 2H), 2.06-1.99 (m, 1H), 0.95-0.85 (m, 6H) FA34
608.85 (300 MHz, DMSO-d.sub.6) 768, 721, [(M + H).sup.+] .delta.
9.01 (t, J = 6.0, 1H), 416, 337, 164 8.37 (t, J = 6.4 Hz, 1H), 8.08
(s, 1H), 8.01-7.96 (m, 1H), 7.88-7.86 (m, 2H), 7.64 (d, J = 7.6 Hz,
1H), 7.05 (dd, J = 16.4, 8.8 Hz, 1H), 6.91 (d, J = 15.6 Hz, 1H),
4.87-4.80 (m, 1H), 3.98-3.91 (m, 4H), 3.38 (s, 3H) .sup.a.sup.1H
NMR spectral data were acquired using a 400 MHz instrument in
CDCl.sub.3 except where noted. HRMS data are noted observed value
(theoretical value).
TABLE-US-00012 TABLE 3 Assays Results Part 1 Compound BAW CEW GPA
Number Rating Rating Rating AC1 D D B AC2 C C C AC3 D D B AC4 D A B
AC5 D D B AC6 D A B AC7 A A B AC8 D B B AC9 A A B AC10 A A B AC11 A
A D AC12 A A D AC13 A A B AC14 A B D AC15 A A B AC16 A A C AC17 A A
B AC18 A A B AC19 D D B AC20 A A C AC21 D D C AC22 A A D AC23 A A B
AC24 A A D AC25 A A D AC26 A A B AC27 A A B AC28 A A B AC29 A A B
AC30 A A B AC31 A A B AC32 A A B AC33 A A B AC34 A A B AC35 A A C
AC36 A A B AC37 A A B AC38 A A C AC39 A A C AC40 A A D AC41 A D D
AC42 A D D AC43 A A B AC44 A A B AC45 A A D AC46 A A D AC47 D D B
AC48 A A B AC49 A A B AC50 A D B AC51 A A B AC52 A A B AC53 A A B
AC54 A A B AC57 A A B AC58 A A B AC59 A A B AC60 A A B AC61 A A B
AC62 A A D AC63 A A B AC64 A A B AC65 A A B AC66 A A B AC67 A A B
AC68 A A D AC69 A A A AC70 D D B AC71 A A B AC72 A A B AC75 A A B
AC76 A A D AC77 A A B AC78 A A A AC79 A A A AC80 A A B AC81 A D D
AC82 A A B AC83 A A B AC84 A A D AC85 A A B AC86 A A D AC87 A A B
AC89 A A B AC90 A A C AC91 A A C AC92 A A C AC93 A D C AC94 D B B
AC95 A A C AC96 D D C AC97 D D C AC98 A A C AC99 A A C AC100 C C C
AC101 D D C AC102 D A C AC103 A A D AC104 A A B AC105 A A D AC106 A
A B AC107 B A D AC108 B D D AC109 D D C AC110 A A C AC111 A A C
AC112 A A C AC113 B A D AC114 A B D AC115 A A D AC116 C C C AC117 A
D B AC118 A D D BC1 A A D BC2 A A D BC3 A A D BC4 A A B BC5 A A B
BC6 A A D BC7 A A D BC8 A A B BC9 A A D BC10 A A B BC11 C C C BC12
C C C BC13 A A D BC14 A D D CC1 D D D CC2 A A B CC3 A A D CC4 A B B
CC5 A A B CC6 A A B CC7 A A B CC8 A A D CC9 A A B CC10 A A B CC11 A
A B CC12 D D B CC13 A A B CC14 A D D CC15 A A B CC16 A A B CC17 A A
B CC18 A A B CC19 A A B CC20 A A D CC21 A A D CC22 A A B CC23 A A B
CC24 A A D CC25 A A B CC26 A D B CC27 A A D CC28 A A D CC29 A A B
CC30 A A D CC31 B D C CC32 A A B CC33 A A B CC34 A A B CC35 D D D
CC36 A A D CC37 A A D CC38 A A D CC39 D D B CC40 D A D CC41 D D B
CC42 D D D CC43 A B B CC44 A A B CC45 A A D CC46 D A C CC47 D D C
CC48 D D C CC49 D D D CC50 A A D CC51 A A D CC52 A D D CC53 D D B
CC54 A A C DC1 A A D DC2 D D C DC3 B D C DC4 A D C DC5 D D C DC6 D
D C DC7 A D C DC8 A D C DC9 D D C DC10 D D C DC11 A D C DC12 A A B
DC13 A A C DC14 D D C DC15 D D C DC16 A A C DC17 A A C DC18 A A C
DC19 A A C DC20 A D C DC21 D D C DC22 D D C DC23 D A C DC24 D D C
DC25 D D C DC26 D D C DC27 D D C DC28 A A B DC29 A A C DC30 A A C
DC31 A A B DC32 D D C DC33 A A C DC34 A A B DC35 A A B DC36 D D C
DC37 A A C DC38 A A C DC39 A A C DC40 A A C DC41 A A C DC42 A A C
DC43 A A C DC44 A A C DC45 A A C DC46 A A C DC47 A A C DC48 A A C
DC49 A A C DC50 A A C DC51 A A C DC52 D D C DC53 D A C DC54 D D C
DC55 D D C DC56 D D C DC57 A A C DC58 D D C DC59 D D C DC60 A A C
DC61 D D C DC62 A A C DC63 A A C
DC64 D D C DC65 D A C DC66 A A C DC67 A A C DC68 A A C DC69 D D C
DC70 A A C
TABLE-US-00013 TABLE 4 Assays Results F Compounds Compound BAW CL
GPA Number Rating Rating Rating F1 A A B F2 A A C F3 A A C F4 A A C
F5 A A C F6 C C C F7 A A C F8 A A C F8A A A C F9 A A C F10 A A C
F11 A A C F12 A A C F13 A A C F14 A A C F15 A A C F15A A A C F16 A
A C F16A A A C F17 A A C F18 A A C F19 A A C F20 A A C F20A A A A
F20B A A C F20C A A C F21 A A C F22 A A C F23 D A C F23A A A C F24
A A C F25 A A C F26 A A C F27 A A C F28 A A C F29 A A C F30 A A C
F31 A A C
TABLE-US-00014 TABLE 5 Assay Results Prophetic Compounds
Subsequently Exemplified Compound BAW CL GPA Number Rating Rating
Rating P1 A A C P2 D A C P12 A A C P14 B A C P15 A A C P82 A A C
P84 A A C P156 A A C P226 A A C P228 A A C P298 D A B P300 A A C
P442 A A C P444 A A C P514 A A C P516 A A C P568 A A C P586 A A C
P588 A A C P660 A A C P730 A A C P732 A A C P802 A A C P804 A A C
P1090 A A C P1092 A A C P1197 A A C P1269 A A C P1340 A A C P1411 A
A B P1483 A A C P1556 A A C P1558 A A C P1559 A A C P1560 A A C
P1564 A A C P1566 A A A P1589 A A C P1591 A A C P1592 A A C P1599 A
A C P1601 A A B P1603 A A C P1611A A A C P1613A A A C P1616 A A C
P1616A A A C P1618A A A C P1621 A A C P1623 A A C P1624 A A A
P1631A A A B P1633A A A C P1636 A A C P1638 A A C P1640 D A D P1641
A A C P1691 A A C P1693 A A C P1696 A A C P1698 A A C P1776 A A C
P1781 A A C P1806 A A C P1808 A A C P1862 A A C P1864 A A C P1866 A
A C P1969* A A C P1970 A A C P1971 A A C P1972 A A C P2009 A A C
P2010 A A C P2011 A A C P2012 A A C P2036 A A C P2038 A A C P2041 A
A C P2043 A A C P2056 A A C P2058 A A C *Performed at 12.5
ug/cm.sup.2
TABLE-US-00015 TABLE 6 Assay Results FA Compounds Compound BAW CL
GPA Number Rating Rating Rating FA1 A A C FA2 A A C FA3 A A C FA4 A
A C FA5 A A C FA6 A A C FA7 A A C FA8 B A C FA9 A A C FA10 B B C
FA11 B A D FA12 A A C FA13 D A C FA14 A A C FA15 A A C FA16 A A A
FA17 A A C FA18 A A C FA19 A A C FA20 A A C FA21 A A C FA22 A A C
FA23 A A C FA24 A A C FA25 A A C FA26 A A C FA27 A A C FA28 A A C
FA29 A A C FA30 A A C FA31 A A C FA32 A A C FA33 A A C FA34 D A
C
* * * * *
References