U.S. patent application number 16/146644 was filed with the patent office on 2019-01-31 for imidazopyrimidine and imidazotriazine derivative, and pharmaceutical composition comprising the same.
This patent application is currently assigned to SK BIOPHARMACEUTICALS CO., LTD.. The applicant listed for this patent is SK BIOPHARMACEUTICALS CO., LTD.. Invention is credited to Soo Bong CHA, Nahm Ryune CHO, Eun Ju CHOI, Jin Yong CHUNG, Seung Mo HAM, Seung Nam HAN, Young Koo JANG, Chan Mi JOUNG, Hyo Jun JUNG, Ji Yeon KIM, Yong Gil KIM, Ji Won LEE, Ju Young LEE, Cheol Young MAENG, Hye Kyung MIN, Chun Eung PARK, Jong Sil PARK, Eun Ju RYU, Yong Je SHIN.
Application Number | 20190031669 16/146644 |
Document ID | / |
Family ID | 56788906 |
Filed Date | 2019-01-31 |
View All Diagrams
United States Patent
Application |
20190031669 |
Kind Code |
A1 |
PARK; Chun Eung ; et
al. |
January 31, 2019 |
IMIDAZOPYRIMIDINE AND IMIDAZOTRIAZINE DERIVATIVE, AND
PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
Abstract
The present disclosure provides a compound of Chemical Formula
(1) or a pharmaceutically acceptable salt thereof, and a
pharmaceutical composition comprising the same: ##STR00001##
wherein X, Z, R.sub.1 and R.sub.2 are as defined in the
specification. The compound of Chemical Formula (1) or
pharmaceutically acceptable salt thereof acts as a positive
allosteric modulator of metabotropic glutamate receptor subtype 5
(mGluR5), thereby being useful in the prevention or treatment of
disorder mediated by glutamate dysfunction and mGluR5.
Inventors: |
PARK; Chun Eung; (Daejeon,
KR) ; JANG; Young Koo; (Daejeon, KR) ; SHIN;
Yong Je; (Daejeon, KR) ; KIM; Ji Yeon;
(Daejeon, KR) ; HAM; Seung Mo; (Daejeon, KR)
; KIM; Yong Gil; (Daejeon, KR) ; MIN; Hye
Kyung; (Daejeon, KR) ; CHA; Soo Bong;
(Daejeon, KR) ; JUNG; Hyo Jun; (Daejeon, KR)
; LEE; Ju Young; (Daejeon, KR) ; HAN; Seung
Nam; (Daejeon, KR) ; CHUNG; Jin Yong;
(Daejeon, KR) ; CHOI; Eun Ju; (Daejeon, KR)
; JOUNG; Chan Mi; (Daejeon, KR) ; PARK; Jong
Sil; (Daejeon, KR) ; LEE; Ji Won; (Daejeon,
KR) ; CHO; Nahm Ryune; (Daejeon, KR) ; RYU;
Eun Ju; (Daejeon, KR) ; MAENG; Cheol Young;
(Daejeon, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SK BIOPHARMACEUTICALS CO., LTD. |
Seoul |
|
KR |
|
|
Assignee: |
SK BIOPHARMACEUTICALS CO.,
LTD.
|
Family ID: |
56788906 |
Appl. No.: |
16/146644 |
Filed: |
September 28, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15664633 |
Jul 31, 2017 |
10100057 |
|
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16146644 |
|
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15053569 |
Feb 25, 2016 |
9745310 |
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15664633 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 43/00 20180101;
C07D 487/04 20130101; A61P 25/18 20180101 |
International
Class: |
C07D 487/04 20060101
C07D487/04 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 26, 2016 |
KR |
10-2015-0027395 |
Claims
1.-19. (canceled)
20. A method for treating a disorder mediated by glutamate
dysfunction and metabotropic glutamate receptor subtype 5 (mGluR5),
comprising: administering to a subject in need thereof a
therapeutically effective amount of a compound of Chemical Formula
(1) or pharmaceutically acceptable salt thereof: ##STR00208##
wherein X is CH or N; Z is O or S; R.sub.1 is aryl optionally
substituted with one or more substituents selected from the group
consisting of halo, hydroxy, alkyl, alkoxy, alkylthio, amino,
dialkylamino, cyano, formyl, haloalkyl, hydroxyalkyl, alkoxyalkyl,
carbamoyloxy alkyl, alkyl-C(O)O-alkyl, dialkylaminoalkyl and 5- or
6-membered heterocycloalkylalkyl; or 5- to 12-membered, unsaturated
heterocyclyl optionally substituted with one or more substituents
selected from the group consisting of halo, hydroxy, alkyl, alkoxy
and haloalkyl; and R.sub.2 is aryl optionally substituted with one
or more substituents selected from the group consisting of halo,
deuterium, hydroxy and alkyl; or 5- to 12-membered, unsaturated
heterocyclyl optionally substituted with one or more substituents
selected from the group consisting of halo and alkyl.
21. (canceled)
22. The method of claim 20, wherein R.sub.1 is C.sub.6-C.sub.12
aryl optionally substituted with one or more substituents selected
from the group consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5 alkylthio, amino,
di(C.sub.1-C.sub.5 alkyl)amino, cyano, formyl, halo-C.sub.1-C.sub.5
alkyl, hydroxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl, carbamoyloxy-C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkyl-C(O)O--C.sub.1-C.sub.5 alkyl,
di(C.sub.1-C.sub.5 alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or
6-membered heterocycloalkyl-C.sub.1-C.sub.5 alkyl in which the
heterocycloalkyl has 1-3 heteroatoms selected from the group
consisting of N, O and S; or 5- to 12-membered, unsaturated
heterocyclyl having 1-5 heteroatoms selected from the group
consisting of N, O and S, which is optionally substituted with one
or more substituents selected from the group consisting of halo,
hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy and
halo-C.sub.1-C.sub.5 alkyl; and R.sub.2 is C.sub.6-C.sub.12 aryl
optionally substituted with one or more substituents selected from
the group consisting of halo, deuterium, hydroxy and
C.sub.1-C.sub.5 alkyl; or 5- to 12-membered, unsaturated
heterocyclyl having 1-3 heteroatoms selected from the group
consisting of N, O and S, which is optionally substituted with one
or more substituents selected from the group consisting of halo and
C.sub.1-C.sub.5 alkyl.
23. The method of claim 20, wherein R.sub.1 is selected from the
group consisting of the group consisting of: ##STR00209## wherein n
is 0, 1, 2, 3 or 4; each R.sub.3 is selected from the group
consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy, C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5
alkyl)amino, cyano, formyl, halo-C.sub.1-C.sub.5 alkyl,
hydroxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl, carbamoyloxy-C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkyl-C(O)O--C.sub.1-C.sub.5 alkyl,
di(C.sub.1-C.sub.5 alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or
6-membered heterocycloalkyl-C.sub.1-C.sub.5 alkyl; and each R.sub.4
is selected from the group consisting of halo, hydroxy,
C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy and
halo-C.sub.1-C.sub.5 alkyl; and R.sub.2 is selected from the group
consisting of: ##STR00210## wherein m is 0, 1, 2, 3 or 4; R.sub.5
is selected from the group consisting of halo, deuterium, hydroxy
and C.sub.1-C.sub.5 alkyl; and Re is selected from the group
consisting of halo and C.sub.1-C.sub.5 alkyl.
24. The method of claim 20, wherein R.sub.1 is phenyl optionally
substituted with 1 to 3 substituents selected from the group
consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy, C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5
alkyl)amino, cyano, formyl, halo-C.sub.1-C.sub.5 alkyl,
hydroxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl, carbamoyloxy-C.sub.1-C.sub.5 alkyl
and C.sub.1-C.sub.5 alkyl-C(O)O--C.sub.1-C.sub.5 alkyl; or 5- to
10-membered, unsaturated heterocyclyl having 1-3 heteroatoms
selected from the group consisting of N, O and S, which is
optionally substituted with 1 to 3 substituents selected from the
group consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl.
25. The method of claim 20, wherein R.sub.2 is phenyl optionally
substituted with 1 to 5 substituents selected from the group
consisting of halo, deuterium, hydroxy and C.sub.1-C.sub.5 alkyl;
or 5- or 6-membered heteroaryl having 1 to 3 heteroatoms selected
from the group consisting of N, O and S, which is optionally
substituted with 1 to 3 substituents selected from the group
consisting of halo and C.sub.1-C.sub.5 alkyl.
26. The method of claim 20, wherein X is CH or N; Z is O; R.sub.1
is phenyl optionally substituted with 1 to 3 substituents selected
from the group consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5 alkylthio, amino,
di(C.sub.1-C.sub.5 alkyl)amino, cyano, formyl, halo-C.sub.1-C.sub.5
alkyl, hydroxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl, carbamoyloxy-C.sub.1-C.sub.5 alkyl
and C.sub.1-C.sub.5 alkyl-C(O)O--C.sub.1-C.sub.5 alkyl; or 5- to
9-membered, unsaturated heterocyclyl having 1 or 2 heteroatoms
selected from the group consisting of N, O and S, which is
optionally substituted with 1 or 2 substituents selected from the
group consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl; and R.sub.2
is phenyl optionally substituted with 1 to 5 substituents selected
from the group consisting of halo, deuterium, hydroxy and
C.sub.1-C.sub.5 alkyl; or 6-membered heteroaryl having 1 or 2
nitrogen atoms, which is optionally substituted with 1 or 2
substituents selected from the group consisting of halo and
C.sub.1-C.sub.5 alkyl.
27. The method of claim 20, wherein R.sub.1 is phenyl optionally
substituted with 1 to 3 substituents selected from the group
consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy, C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5
alkyl)amino, cyano, formyl, halo-C.sub.1-C.sub.5 alkyl,
hydroxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl, carbamoyloxy-C.sub.1-C.sub.5 alkyl
and C.sub.1-C.sub.5 alkyl-C(O)O--C.sub.1-C.sub.5 alkyl;
1,3-benzodioxolyl which is unsubstituted or substituted with 1 or 2
halo; or pyridyl or pyrimidinyl which is optionally substituted
with 1 or 2 substituents selected from the group consisting of
halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy and
halo-C.sub.1-C.sub.5 alkyl; and R.sub.2 is phenyl optionally
substituted with 1 to 5 substituents selected from the group
consisting of halo, deuterium, hydroxy and C.sub.1-C.sub.5 alkyl;
or pyridyl optionally substituted with 1 or 2 substituents selected
from the group consisting of halo and C.sub.1-C.sub.5 alkyl.
28. The method of claim 20, wherein X is CH; Z is O; R.sub.1 is
phenyl optionally substituted with 1 to 3 substituents selected
from the group consisting of halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5 alkylthio, amino,
halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5 alkyl and
C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl; and R.sub.2 is
pyridyl optionally substituted with 1 or 2 substituents selected
from the group consisting of halo and C.sub.1-C.sub.5 alkyl.
29. The method of claim 20, wherein the compound is selected from
the group consisting of:
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimid-
ine;
6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine-
;
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne;
6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e;
6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-3-hydroxyphenyl)-2-(3fluorophenoxymethyl)-imidazo[1,2-a-
]pyrimidine;
6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e;
6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]py-
rimidine;
6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]-
pyrimidine;
6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
2-[(4-fluorophenoxy)methyl]-6-(6fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine-
; 4-[[6-(4fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol;
2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l; 2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l;
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phe-
nol;
6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[-
1,2-a]pyrimidine;
2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine;
2-[(4-fluorophenoxy)methyl]-6-(2fluoro-4-pyridyl)imidazo[1,2-a]py-
rimidine;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l;
6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]p-
yrimidine;
2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]im-
idazo[1,2-a]pyrimidine;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine;
4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-met-
hoxy-benzonitrile;
6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]py-
rimidine;
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-
-yl]aniline;
6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methy-
l-aniline;
4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimi-
din-6-yl]aniline;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-anil-
ine;
5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-meth-
yl-aniline;
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne;
2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimi-
dine;
2-[(3-fluorophenoxy)methyl]-6-(2fluoro-4-pyridyl)imidazo[1,2-a]pyrim-
idine;
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidaz-
o[1,2-a]pyrimidine;
2-[(3-fluorophenoxy)methyl]-6-(6fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine-
;
2-[(3-fluorophenoxy)methyl]-6-(2fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e;
6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-m
ethoxy-aniline;
2-[(4-fluorophenoxy)methyl]-6-(5fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine-
;
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine;
6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine;
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]-
pyrimidine;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyridin-2-ol;
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine;
2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyim
idine;
2-[(3-fluorophenoxy)methyl]-6-(5fluoro-2-pyridyl)imidazo[1,2-a]pyr-
imidine;
2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl-
]imidazo[1,2-a]pyrimidine;
4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-m
ethoxy-benzonitrile;
[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol;
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol;
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine;
2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidi-
ne;
2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-a-
niline;
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]aniline;
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidin-
e;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine;
6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]p-
yrimidine;
6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)-
imidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine;
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)im-
idazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidi-
ne;
6-(4-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)imidazo[-
1,2-a]pyrimidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(3-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)imi-
dazo[1,2-a]pyrimidine;
6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluorophenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]-
pyrimidine;
2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyr-
imidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridy-
l]imidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline;
2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]a-
niline;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]ph-
enyl]methanol;
3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitr-
ile;
4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-m-
ethoxy-benzonitrile;
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine;
[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol;
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;
6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine;
[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethy-
l)phenyl]methanol;
6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl-
)benzaldehyde;
6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)
imidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]-
pyrimidine;
6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(5fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo-
[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imid-
azo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imid-
azo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo-
[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]py-
rimidine;
6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymet-
hyl)imidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-[(5fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidi-
ne;
2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyri-
midine;
2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)p-
henyl]imidazo[1,2-a]pyrimidine;
2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline;
5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrim-
idin-6-yl]aniline;
[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol;
2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine;
2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine;
2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1-
,2,4]triazine;
2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne;
2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]tri-
azine;
2-(2,4-difluorophenyl)-6-((2fluoropyridin-4-yloxy)methyl)imidazo[1,-
2-b][1,2,4]triazine;
2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,-
2-b][1,2,4]triazine;
2-(2-methylphenyl)-6-((2fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4-
]triazine;
2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)im-
idazo[1,2-b][1,2,4]triazine;
2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine;
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b]-
[1,2,4]triazine;
2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)
imidazo[1,2-b][1,2,4]triazine;
2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine;
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b]-
[1,2,4]triazine;
2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-
-b][1,2,4]triazine;
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methyl carbamate;
[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl
carbamate;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl carbamate;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl acetate;
6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1-
,2-a]pyrimidine;
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine; and
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine.
30. The method of claim 20, wherein the compound is selected from
the group consisting of:
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e;
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]p-
yrimidine;
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)im-
idazo[1,2-a]pyrimidine;
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine;
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-
;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]m-
ethanol;
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imid-
azo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2-
,4]triazine; and
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine.
31. The method of claim 20, wherein the compound is selected from
the group consisting of:
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimid-
ine;
6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine-
;
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne;
6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e;
6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-3-hydroxyphenyl)-2-(3fluorophenoxymethyl)-imidazo[1,2-a-
]pyrimidine;
6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimi-
dine;
6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimi-
dine;
4-[[6-(4fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol;
2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l; 2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l;
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phe-
nol;
6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[-
1,2-a]pyrimidine;
2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol-
;
6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]py-
rimidine;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne;
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine;
4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile;
6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidaz-
o[1,2-a]pyrimidine;
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-a-
niline;
4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
-6-yl]aniline;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-anil-
ine;
5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline;
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-meth-
yl-aniline;
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy--
aniline;
2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl-
]imidazo[1,2-a]pyrimidine;
4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile;
[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
-6-yl]phenyl]methanol;
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol;
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine;
2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-anil-
ine;
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline;
2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triaz-
ine;
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-
phenyl]methyl carbamate;
[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl
carbamate
6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl-
)imidazo[1,2-a]pyrimidine; and
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine.
32. The method of claim 20, wherein the compound is selected from
the group consisting of:
6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e;
6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrim-
idine;
2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyr-
imidine;
2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]p-
yrimidine;
2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]im-
idazo[1,2-a]pyrimidine;
6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine;
2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pynridyl)imidazo[1,2-a]py-
rimidine;
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]-
pyrimidine;
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2--
a]pyrimidine;
2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e;
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimid-
ine;
6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]p-
yrimidine;
2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a-
]pyrimidine;
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidi-
ne;
6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimi-
dine;
6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyri-
midine;
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]p-
yrimidine;
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyri-
din-2-ol;
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imida-
zo[1,2-a]pyrimidine;
2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e;
2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimid-
ine; and
2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]-
pyrimidine.
33. The method of claim 20, wherein the compound is selected from
the group consisting of:
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]-
pyrimidine;
6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine;
6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]p-
yrimidine;
6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)-
imidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine;
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)im-
idazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidi-
ne;
6-(4-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)imidazo[-
1,2-a]pyrimidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(3-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)imi-
dazo[1,2-a]pyrimidine;
6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;
6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluorophenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]-
pyrimidine;
2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline;
2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]a-
niline;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]ph-
enyl]methanol;
3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitr-
ile;
4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-m-
ethoxy-benzonitrile;
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine;
[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol;
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;
6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine;
[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethy-
l)phenyl]methanol;
6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl-
)benzaldehyde;
6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)
imidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]-
pyrimidine;
6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine;
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(5fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo-
[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imid-
azo[1,2-a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine;
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imid-
azo[1,2-a]pyrimidine;
6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a-
]pyrimidine;
6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo-
[1,2-a]pyrimidine;
6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine;
6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]py-
rimidine;
6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymet-
hyl)imidazo[1,2-a]pyrimidine;
6-(4-fluorophenyl)-2-[(5fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidi-
ne;
2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyri-
midine;
2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)p-
henyl]imidazo[1,2-a]pyrimidine;
2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine;
5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline;
5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrim-
idin-6-yl]aniline;
[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol;
2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine;
2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1-
,2,4]triazine; 2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)
imidazo[1,2-b][1,2,4]triazine;
2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne;
2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2--
b][1,2,4]triazine;
2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,-
2-b][1,2,4]triazine;
2-(2-methylphenyl)-6-((2fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4-
]triazine;
2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)im-
idazo[1,2-b][1,2,4]triazine;
2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine;
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b]-
[1,2,4]triazine;
2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)
imidazo[1,2-b][1,2,4]triazine;
2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine;
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b]-
[1,2,4]triazine;
2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-
-b][1,2,4]triazine;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl carbamate;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl acetate; and
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine.
34. The method of claim 20, wherein the compound is selected from
the group consisting of:
2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyr-
imidine;
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridy-
l]imidazo[1,2-a]pyrimidine; and
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
35. The method of claim 20, wherein the compound is a compound of
Formula (2): ##STR00211## wherein n is 0, 1, 2 or 3; each R.sub.3
is independently selected from the group consisting of halo,
hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy,
C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino,
cyano, formyl, halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5
alkyl, C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl, di(C.sub.1-C.sub.5
alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or 6-membered
heterocycloalkyl-C.sub.1-C.sub.5 alkyl wherein the heterocycloalkyl
has 1-3 heteroatoms selected from the group consisting of N, O and
S; m is 0, 1, 2 or 3; and each R.sub.6 is independently selected
from the group consisting of halo and C.sub.1-C.sub.5 alkyl.
36. The method of claim 35, wherein n is 0, 1 or 2; each R.sub.3 is
selected from the group consisting of halo, halo-C.sub.1-C.sub.5
alkyl, C.sub.1-C.sub.5 alkyl, and hydroxy-C.sub.1-C.sub.5 alkyl; m
is 0 or 1; and R.sub.6 is halo.
37. The method of claim 35, wherein n is 1 or 2; each R.sub.3 is
selected from the group consisting of fluoro, fluoromethyl,
trifluoromethyl, methyl, and hydroxymethyl; m is 0 or 1; and
R.sub.6 is fluoro.
38. The method of claim 35, wherein the compound is selected from
the group consisting of:
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine;
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine;
6-(4-fluorophenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidi-
ne;
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl-
]methanol; and
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a non-provisional application claiming
priority to Korean Patent Application No. 10-2015-0027395, filed on
26 Feb. 2015. The entire disclosure of the application identified
in this paragraph is incorporated herein by reference.
FIELD
[0002] The present disclosure generally relates to a compound
modulating receptor activity, pharmaceutical compositions
comprising the compound, and methods useful for treating diseases.
The present disclosure relates to a compound useful as a positive
allosteric modulator (PAM) of metabotropic glutamate receptor
subtype 5 (mGluR5) or a pharmaceutically acceptable salt thereof,
and a pharmaceutical composition for the prevention and/or
treatment of disorders mediated by glutamate dysfunction and mGluR5
comprising a therapeutically effective amount of the same.
BACKGROUND
[0003] Glutamate is the most prevalent excitatory neurotransmitter
in the central nervous system (CNS) of mammals. Glutamate plays an
important role in numerous physiological functions such as
cardiovascular regulation, perception and recognition, and
synaptogenesis as well as learning and memory. As such, in the
occurrence of imbalance in glutamate neurotransmission, various
nervous and mental diseases such as schizophrenia may be caused,
and thus glutamate plays an important role in physiology.
[0004] Glutamate mediates synaptic neurotransmission via ionotropic
glutamate receptors (iGluR)--i.e., the activation of NMDA
receptors, AMPA receptors and kainate receptors involved in rapid
excitatory transmission (Nakanishi S. et al., Brain Res. Rev.,
(1998) 26: 230-235). In addition, glutamate plays a role in subtly
regulating excitatory synaptic neurotransmission via the activation
of metabotropic glutamate receptor (mGluR).
[0005] Metabotropic glutamate receptors (mGluR) consist of eight
(8) subtypes and are sub-divided into three groups (Groups I, II
and III) according to arrangement, homology and pharmacological
property. mGluR5 belongs to Group I, and it is known that mGluR5
interacts with NMDA receptors via various proteins and
neurotransmission pathways. Therefore, because the balance of
deficiency or hyperactivity of physiological function by NMDA
receptors can be regulated via the modulation of mGluR5, to
modulate mGluR5 is very important.
[0006] Since a variety of pathophysiological processes and disease
states affecting the CNS are thought to be related to abnormal
glutamate neurotransmission and NMDA receptor malfunction,
modulators of mGluR5 receptors could be therapeutically beneficial
in the treatment of various CNS diseases. Moreover, because mGluR5
receptor modulators which act through allosteric binding site have
some advantages such as subtype selectivity, brain penetration and
safety potential, many studies have reported that the mGluR5
positive allosteric modulators were useful for the treatment of
schizophrenia and CNS diseases.
[0007] International Publication Nos. WO 2008/151184 and WO
2011/035324 disclose benzamide and O-benzyl nicotinamide
derivatives as an mGluR5 positive allosteric modulator,
respectively. International Publication No. WO 2010/124055
discloses 2-alkyl piperidine derivatives as an mGluR5 positive
allosteric modulator, and International Publication No. WO
2011/082010 discloses tetrahydrotriazolopyridine derivative
compounds. International Publication Nos. WO 2012/078817 and WO
2012/083224 disclose bicyclic pyrazole and bicyclic triazole
compounds as an mGluR5 positive allosteric modulator,
respectively.
SUMMARY
[0008] In an embodiment, there is provided imidazopyrimidine and
imidazotriazine derivative compound as a positive allosteric
modulator of metabotropic glutamate receptor subtype 5 (mGluR5) or
a pharmaceutically acceptable salt thereof.
[0009] In another embodiment, there is provided a pharmaceutical
composition comprising the above imidazopyrimidine and
imidazotriazine derivative compound or a pharmaceutically
acceptable salt thereof as an active ingredient.
[0010] The present inventors have synthesized imidazopyrimidine and
imidazotriazine derivative compounds of Chemical Formula (1) and
confirmed that said compounds show effective and selective effects
as a positive allosteric modulator of metabotropic glutamate
receptor subtype 5 (mGluR5), thereby being useful in the treatment
of disorders mediated by glutamate dysfunction and mGluR5 such as
schizophrenia.
DETAILED DESCRIPTION
[0011] The following description is merely exemplary in nature and
is not intended to limit the present disclosure, application, or
uses.
[0012] The present disclosure provides a compound of Chemical
Formula (1) and a pharmaceutically acceptable salt thereof:
##STR00002##
wherein
[0013] X represents CH or N;
[0014] Z represents O or S;
[0015] R.sub.1 represents aryl which is unsubstituted or
substituted with one or more substituents selected from halo,
hydroxy, alkyl, alkoxy, alkylthio, amino, dialkylamino, cyano,
formyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carbamoyloxy alkyl,
alkyl-C(O)O-alkyl, dialkylaminoalkyl and 5- or 6-membered
heterocycloalkylalkyl in which the heterocycloalkyl has 1-3
heteroatoms selected from N, O and S; or 5- to 12-membered,
unsaturated heterocyclyl having 1-5 heteroatoms selected from N, O
and S, which is unsubstituted or substituted with one or more
substituents selected from halo, hydroxy, alkyl, alkoxy and
haloalkyl; and
[0016] R.sub.2 represents aryl which is unsubstituted or
substituted with one or more substituents selected from halo,
deuterium, hydroxy and alkyl; or 5- to 12-membered, unsaturated
heterocyclyl having 1-3 heteroatoms selected from N, O and S, which
is unsubstituted or substituted with one or more substituents
selected from halo and alkyl.
[0017] In a particular embodiment, R.sub.1 represents aryl which is
unsubstituted or substituted with one or more substituents selected
from halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy,
C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino,
cyano, formyl, halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5
alkyl, C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl, di(C.sub.1-C.sub.5
alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or 6-membered
heterocycloalkyl-C.sub.1-C.sub.5 alkyl wherein the heterocycloalkyl
has 1-3 heteroatoms selected from N, O and S; or 5- to 12-membered,
unsaturated heterocyclyl having 1-5 heteroatoms selected from N, O
and S, which is unsubstituted or substituted with one or more
substituents selected from halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl; and R.sub.2
represents aryl which is unsubstituted or substituted with one or
more substituents selected from halo, deuterium, hydroxy and
C.sub.1-C.sub.5 alkyl; or 5- to 12-membered, unsaturated
heterocyclyl having 1-3 heteroatoms selected from N, O and S, which
is unsubstituted or substituted with one or more substituents
selected from halo and C.sub.1-C.sub.5 alkyl.
[0018] Unless stated otherwise, herein the term "alkyl," either
alone or in combination with further terms (for example,
haloalkyl), means a radical of saturated aliphatic hydrocarbyl
group having 1 to 5 carbon atoms, which may be linear or branched.
Examples of representative alkyl group include, but are not limited
to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,
sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl,
1-methylbutyl, 2-methylbutyl, 1-ethylpropyl and
1,2-dimethylpropyl.
[0019] Unless stated otherwise, herein the term "halo," either
alone or in combination with further terms (for example,
haloalkyl), means a radical of F, Cl, Br or I.
[0020] Unless stated otherwise, herein the term "heterocycloalkyl"
means a 5- or 6-membered, saturated monocyclic ring having 1 to 3
heteroatoms selected from N, O and S, and preferably a 5- or
6-membered, saturated monocyclic ring having 1 or 2 heteroatoms
selected from N and O. Concrete examples of heterocycloalkyl
include, but are not limited to, pyrrolidinyl, piperidinyl,
tetrahydrofuranyl, tetrahydropyranyl and morpholinyl.
[0021] Unless stated otherwise, herein the term "aryl" means an
aromatic radical having 6 to 12 carbon atoms. Concrete examples of
aryl include, but are not limited to, phenyl and naphthyl.
[0022] Unless stated otherwise, herein the term "unsaturated
heterocyclyl" means a 5- or 12-membered, unsaturated monocyclic or
bicyclic ring having 1 to 5 heteroatoms selected from N, O and S.
Concrete examples of unsaturated heterocyclyl include, but are not
limited to, 1,3-benzodioxolyl, or heteroaryl such as pyridyl,
pyrimidinyl, thienyl, pyrazinyl, quinolinyl and isoquinolinyl.
[0023] According to one aspect of the present disclosure, R.sub.1
is selected from the group consisting of:
##STR00003##
wherein n is 0, 1, 2, 3 or 4; each R.sub.3 is selected from halo,
hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy,
C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino,
cyano, formyl, halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5
alkyl, C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl, di(C.sub.1-C.sub.5
alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or 6-membered
heterocycloalkyl-C.sub.1-C.sub.5 alkyl; and each R.sub.4 is
selected from halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkoxy and halo-C.sub.1-C.sub.5 alkyl; and
[0024] R.sub.2 is selected from the group consisting of:
##STR00004##
wherein m is 0, 1, 2, 3 or 4; R.sub.5 is selected from halo,
deuterium, hydroxy and C.sub.1-C.sub.5 alkyl; and R.sub.5 is
selected from halo and C.sub.1-C.sub.5 alkyl.
[0025] According to one aspect of the present disclosure, in
Chemical Formula (1), R.sub.1 represents phenyl which is
unsubstituted or substituted with 1 to 3 substituents selected from
halo, hydroxy, C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy,
C.sub.1-C.sub.5 alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino,
cyano, formyl, halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5
alkyl, C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl and C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl; or 5- to 10-membered,
unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O
and S, which is unsubstituted or substituted with 1 to 3
substituents selected from halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl.
[0026] According to another aspect of the present disclosure, in
Chemical Formula (1), R.sub.2 represents phenyl unsubstituted or
substituted with 1 to 5 substituents selected from halo, deuterium,
hydroxy and C.sub.1-C.sub.5 alkyl; or 5- or 6-membered heteroaryl
having 1 to 3 heteroatoms selected from N, O and S, which is
unsubstituted or substituted with 1 to 3 substituents selected from
halo and C.sub.1-C.sub.5 alkyl.
[0027] According to still another aspect of the present disclosure,
in Chemical Formula (1),
[0028] X represents CH or N;
[0029] Z represents O;
[0030] R.sub.1 represents phenyl which is unsubstituted or
substituted with 1 to 3 substituents selected from halo, hydroxy,
C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5
alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino, cyano, formyl,
halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl and C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl; or 5- to 9-membered,
unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N,
O and S, which is unsubstituted or substituted with 1 or 2
substituents selected from halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl; and
[0031] R.sub.2 represents phenyl which is unsubstituted or
substituted with 1 to 5 substituents selected from halo, deuterium,
hydroxy and C.sub.1-C.sub.5 alkyl; or 6-membered heteroaryl having
1 or 2 nitrogen atoms, which is unsubstituted or substituted with 1
or 2 substituents selected from halo and C.sub.1-C.sub.5 alkyl.
[0032] According to still another aspect of the present disclosure,
in Chemical Formula (1),
[0033] R.sub.1 represents phenyl which is unsubstituted or
substituted with 1 to 3 substituents selected from halo, hydroxy,
C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5
alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino, cyano, formyl,
halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl and C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl; 1,3-benzodioxolyl which is
unsubstituted or substituted with 1 or 2 halo; or pyridyl or
pyrimidinyl which is unsubstituted or substituted with 1 or 2
substituents selected from halo, hydroxy, C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy and halo-C.sub.1-C.sub.5 alkyl; and
[0034] R.sub.2 represents phenyl which is unsubstituted or
substituted with 1 to 5 substituents selected from halo, deuterium,
hydroxy and C.sub.1-C.sub.5 alkyl; or pyridyl which is
unsubstituted or substituted with 1 or 2 substituents selected from
halo and C.sub.1-C.sub.5 alkyl.
[0035] According to still another aspect of the present disclosure,
in Chemical Formula (1),
[0036] X represents CH;
[0037] Z represents O;
[0038] R.sub.1 represents phenyl which is unsubstituted or
substituted with 1 to 3 substituents selected from halo, hydroxy,
C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5
alkylthio, amino, halo-C.sub.1-C.sub.5 alkyl,
hydroxy-C.sub.1-C.sub.5 alkyl and C.sub.1-C.sub.5
alkoxy-C.sub.1-C.sub.5 alkyl; and
[0039] R.sub.2 represents pyridyl which is unsubstituted or
substituted with 1 or 2 substituents selected from halo and
C.sub.1-C.sub.5 alkyl.
[0040] In an embodiment, there is provided a compound of Chemical
Formula (2) or a pharmaceutically acceptable salt thereof:
##STR00005##
[0041] wherein n is 0, 1, 2 or 3;
[0042] each R.sub.3 is independently selected from halo, hydroxy,
C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5
alkylthio, amino, di(C.sub.1-C.sub.5 alkyl)amino, cyano, formyl,
halo-C.sub.1-C.sub.5 alkyl, hydroxy-C.sub.1-C.sub.5 alkyl,
C.sub.1-C.sub.5 alkoxy-C.sub.1-C.sub.5 alkyl,
carbamoyloxy-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkyl-C(O)O--C.sub.1-C.sub.5 alkyl, di(C.sub.1-C.sub.5
alkyl)amino-C.sub.1-C.sub.5 alkyl and 5- or 6-membered
heterocycloalkyl-C.sub.1-C.sub.5 alkyl wherein the heterocycloalkyl
has 1-3 heteroatoms selected from N, O and S;
[0043] m is 0, 1, 2 or 3; and
[0044] each R.sub.6 is independently selected from halo and
C.sub.1-C.sub.5 alkyl.
[0045] In various embodiments, n is 0, 1 or 2; each R.sub.3 is
selected from halo, halo-C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5
alkyl, and hydroxy-C.sub.1-C.sub.5 alkyl; m is 0 or 1; and R.sub.6
is halo. In a particular embodiment, n is 1 or 2; each R.sub.3 is
selected from fluoro, fluoromethyl, trifluoromethyl, methyl, and
hydroxymethyl; m is O or 1; and R.sub.6 is fluoro.
[0046] The compounds of Chemical Formula (1) according to the
present disclosure include, but are not limited to, the following
compounds: [0047]
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0048]
2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine; [0049]
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0050] 6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0051] 6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0052]
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0053]
6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0054] 6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0055] 6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0056] 6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0057]
6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0058]
6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine-
; [0059]
6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0060]
6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0061]
6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimi-
dine; [0062]
6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0063]
6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0064]
6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]-
pyrimidine; [0065]
6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0066]
6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0067]
6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0068]
6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrim-
idine; [0069]
6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0070]
6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyr-
imidine; [0071]
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e; [0072]
6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyr-
imidine; [0073]
6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0074]
6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyri-
midine; [0075]
6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0076]
6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0077]
6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0078]
6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0079]
6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0080]
6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0081]
6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0082]
6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0083] 6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0084]
6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0085]
6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrim-
idine; [0086]
6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0087]
6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
[0088]
6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2--
a]pyrimidine; [0089]
6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyri-
midine; [0090]
6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
[0091]
6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]py-
rimidine; [0092]
6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e; [0093]
6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]py-
rimidine; [0094]
6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimi-
dine; [0095]
6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e; [0096]
6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]py-
rimidine; [0097]
2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0098]
4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]pheno-
l; [0099]
2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyri-
midine; [0100]
2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
[0101]
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenol; [0102]
2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;
[0103]
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l; [0104]
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-
-yl]phenol; [0105]
6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2--
a]pyrimidine; [0106]
2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;
[0107]
6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine; [0108]
2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0109]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l; [0110]
6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[-
1,2-a]pyrimidine; [0111]
2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2--
a]pyrimidine; [0112]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;
[0113]
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine; [0114]
4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile; [0115]
6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]py-
rimidine; [0116]
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0117]
6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine; [0118]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-anil-
ine; [0119]
4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline; [0120]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-anil-
ine; [0121]
5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0122]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-m-
ethyl-aniline; [0123]
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0124]
2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a-
]pyrimidine; [0125]
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0126]
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imi-
dazo[1,2-a]pyrimidine; [0127]
2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0128]
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]-
pyrimidine; [0129]
6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine; [0130]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy-ani-
line; [0131]
2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0132]
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a-
]pyrimidine; [0133]
6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
e; [0134]
6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine; [0135]
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidi-
ne; [0136]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyri-
din-2-ol; [0137]
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine; [0138]
2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0139]
2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]-
pyrimidine; [0140]
2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo-
[1,2-a]pyrimidine; [0141]
4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile; [0142]
[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol; [0143]
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol; [0144]
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine; [0145]
2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidi-
ne; [0146]
2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-m-
ethyl-aniline; [0147]
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0148]
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0149]
6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0150]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0151]
6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0152]
6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0153]
6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0154]
6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0155]
6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine; [0156]
6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,-
2-a]pyrimidine; [0157]
6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0158]
6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0159]
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine; [0160]
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0161]
6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
[0162]
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0163]
6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0164]
6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)-
imidazo[1,2-a]pyrimidine; [0165]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0166]
6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine; [0167]
6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,-
2-a]pyrimidine; [0168]
6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine; [0169]
6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine; [0170]
6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0171]
2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0172]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;
[0173]
6-(4-chloro-2-methyl-phenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imida-
zo[1,2-a]pyrimidine; [0174]
6-(2,4-dimethylphenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyri-
midine; [0175]
6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine; [0176]
2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyr-
imidine; [0177]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidaz-
o[1,2-a]pyrimidine; [0178]
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)
imidazo[1,2-a]pyrimidine; [0179]
2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline; [0180]
2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline;
[0181]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]ph-
enyl]methanol; [0182]
3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitr-
ile; [0183]
4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-metho-
xy-benzonitrile; [0184]
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)
imidazo[1,2-a]pyrimidine; [0185]
[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol; [0186]
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;
[0187]
6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo-
[1,2-a]pyrimidine; [0188]
[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethy-
l)phenyl]methanol; [0189]
6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
[0190]
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluor-
omethyl)benzaldehyde; [0191]
6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine; [0192]
6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0193]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0194]
6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0195]
6-4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]-
pyrimidine; [0196]
6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0197]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0198]
6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0199]
6-(2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0200]
6-(4-fluoro-2-methylphenyl)-2-(5fluoro-pyridin-3-yloxymethyl)
imidazo[1,2-a]pyrimidine; [0201]
6-(4-fluoro-2-methoxyphenyl)-2-(5fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0202]
6-(4-fluoro-2-hydroxyphenyl)-2-(5fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0203]
6-(2,4-difluorophenyl)-2-(6fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyri-
midine; [0204]
6-(4-fluoro-2-methylphenyl)-2-(6fluoropyridin-3-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0205]
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0206]
6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0207]
6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine; [0208]
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0209]
6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0210]
6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0211]
6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine; [0212]
6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0213]
6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0214]
6-(2-methylphenyl)-2-(2fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0215]
6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,-
2-a]pyrimidine; [0216]
6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imida-
zo[1,2-a]pyrimidine; [0217]
6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine; [0218]
2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimid-
ine; [0219]
2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0220]
2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0221]
5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline; [0222]
5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline; [0223]
[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol;
[0224]
2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triaz-
ine; [0225]
2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine; [0226]
2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine; [0227]
2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne; [0228]
2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,-
2,4]triazine; [0229]
2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][-
1,2,4]triazine; [0230]
2-(4-fluoro-2-methylphenyl)-6-((2fluoropyridin-4-yloxy)methyl)imidazo[1,2-
-b][1,2,4]triazine; [0231]
2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,-
4]triazine; [0232]
2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine; [0233]
2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)
imidazo[1,2-b][1,2,4]triazine; [0234]
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)
imidazo[1,2-b][1,2,4]triazine; [0235]
2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine; [0236]
2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine; [0237] 2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)
imidazo[1,2-b][1,2,4]triazine; [0238]
2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-
-b][1,2,4]triazine; [0239]
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methyl carbamate; [0240]
[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl
carbamate; [0241]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl carbamate; [0242]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl acetate; [0243]
6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1-
,2-a]pyrimidine; [0244]
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine; and [0245]
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine.
[0246] In various embodiments, R.sub.1 and R.sub.2 are optionally
substituted phenyl and such compounds include, but are not limited
to, the following compounds: [0247]
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0248]
phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine; [0249]
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0250] 6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0251] 6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0252]
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0253]
6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0254] 6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0255] 6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0256] 6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0257]
6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0258]
6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine-
; [0259]
6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0260]
6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0261]
6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimi-
dine; [0262]
6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0263]
6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0264]
6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]-
pyrimidine; [0265]
6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0266]
6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0267]
6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidi-
ne; [0268]
6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrim-
idine; [0269]
6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0270]
6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyr-
imidine; [0271]
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e; [0272]
6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyr-
imidine; [0273]
6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0274]
6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyri-
midine; [0275]
6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; [0276]
6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyri-
midine; [0277]
6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrim-
idine; [0278]
6-(4-fluoro-3-hydroxyphenyl)-2-(3fluorophenoxymethyl)-imidazo[1,2-a]pyrim-
idine; [0279]
6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
[0280]
6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyri-
midine; [0281]
6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimi-
dine; [0282]
6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;
[0283]
4-[[6-(4fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol;
[0284]
2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimi-
dine; [0285]
2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;
[0286]
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenol; [0287]
2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;
[0288]
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l; [0289]
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-
-yl]phenol; [0290]
6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2--
a]pyrimidine; [0291]
2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;
[0292]
6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine; [0293]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;
[0294]
6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine; [0295]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;
[0296]
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine; [0297]
4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-m
ethoxy-benzonitrile; [0298]
6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]py-
rimidine; [0299]
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0300]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-m-
ethyl-aniline; [0301]
4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline; [0302]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-anil-
ine; [0303]
5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0304]
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-m-
ethyl-aniline; [0305]
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0306]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-m
ethoxy-aniline; [0307]
2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo-
[1,2-a]pyrimidine; [0308]
4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-m
ethoxy-benzonitrile; [0309]
[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol; [0310]
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol; [0311]
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine; [0312]
2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-anil-
ine; [0313]
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne; [0314]
2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]tr-
iazine; [0315]
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methyl carbamate; [0316]
[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl
carbamate [0317]
6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1-
,2-a]pyrimidine; and [0318]
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine.
[0319] In various embodiments, R.sub.1 is optionally substituted
pyridinyl and R.sub.2 is optionally substituted phenyl, and such
compounds include, but are not limited to, the following compounds:
[0320]
6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0321]
6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0322]
6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0323]
6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0324]
6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0325]
6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0326]
6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0327]
6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0328]
6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrim-
idine; [0329]
6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0330]
6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;
[0331]
6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]py-
rimidine; [0332]
6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e; [0333]
6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]-
pyrimidine; [0334]
2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0335]
2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]-
pyrimidine; [0336]
2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2--
a]pyrimidine; [0337]
6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine; [0338]
2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0339]
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]-
pyrimidine; [0340]
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2--
a]pyrimidine; [0341]
2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0342]
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]-
pyrimidine; [0343]
6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine; [0344]
2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0345]
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a-
]pyrimidine; [0346]
6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
e; [0347]
6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine; [0348]
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidi-
ne; [0349]
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyri-
din-2-ol; [0350]
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine; [0351]
2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e; [0352]
2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]-
pyrimidine; and [0353]
2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidi-
ne.
[0354] In various embodiments, R.sub.1 is optionally substituted
phenyl and R.sub.2 is optionally substituted pyridinyl, and such
compounds include, but are not limited to, the following compounds:
[0355]
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0356]
6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0357]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1-
,2-a]pyrimidine; [0358]
6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0359]
6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0360]
6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0361]
6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0362]
6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine; [0363]
6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,-
2-a]pyrimidine; [0364]
6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0365]
6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0366]
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine; [0367]
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0368]
6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
[0369]
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0370]
6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0371]
6-(4-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)i-
midazo[1,2-a]pyrimidine; [0372]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0373]
6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine; [0374]
6-(3-fluoro-2-methoxy-phenyl)-2-[(4fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0375]
6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine; [0376]
6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine; [0377]
6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine; [0378]
2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0379]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;
[0380]
6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imid-
azo[1,2-a]pyrimidine; [0381]
6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine; [0382]
6-(4-fluorophenyl)-2-[(5fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0383]
2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyri-
midin-6-yl]aniline; [0384]
2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline;
[0385]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]ph-
enyl]methanol; [0386]
3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitr-
ile; [0387]
4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-metho-
xy-benzonitrile; [0388]
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine; [0389]
[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol; [0390]
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;
[0391]
6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo-
[1,2-a]pyrimidine; [0392]
[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethy-
l)phenyl]methanol; [0393]
6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;
[0394]
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluor-
omethyl)benzaldehyde; [0395]
6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine; [0396]
6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0397]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0398]
6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0399]
6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a-
]pyrimidine; [0400]
6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0401]
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrim-
idine; [0402]
6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;
[0403]
6-(2-methylphenyl)-2-(5fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]-
pyrimidine; [0404]
6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0405]
6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0406]
6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0407]
6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyr-
imidine; [0408]
6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0409]
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0410]
6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0411]
6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine; [0412]
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2--
a]pyrimidine; [0413]
6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0414]
6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0415]
6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine; [0416]
6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0417]
6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine; [0418]
6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine; [0419]
6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimi-
dine; [0420]
6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imida-
zo[1,2-a]pyrimidine; [0421]
6-(4-fluorophenyl)-2-[(5fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidi-
ne; [0422]
2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-
-a]pyrimidine; [0423]
2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0424]
2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine; [0425]
5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline; [0426]
5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline; [0427]
[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol; [0428]
2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)
imidazo[1,2-b][1,2,4]triazine; [0429]
2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine; [0430]
2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne; [0431]
2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,-
2,4]triazine; [0432]
2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][-
1,2,4]triazine; [0433]
2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,-
2-b][1,2,4]triazine; [0434]
2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,-
4]triazine; [0435]
2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine; [0436]
2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine; [0437]
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine; [0438]
2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine; [0439]
2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine; [0440]
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine; [0441]
2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-
-b][1,2,4]triazine; [0442]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl carbamate; [0443]
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl acetate; and [0444]
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine.
[0445] In various embodiments, both R.sub.1 and R.sub.2 are
optionally substituted pyridinyl, and such compounds include, but
are not limited to, the following compounds: [0446]
2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyr-
imidine; [0447]
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidaz-
o[1,2-a]pyrimidine; and [0448]
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
[0449] As described herein, it is confirmed that the compounds of
Chemical Formula (1) are effective as a positive allosteric
modulator of metabotropic glutamate receptor subtype 5 (mGluR5
PAM). Also, they have selective activity as a positive allosteric
modulator of mGluR5 PAM. Such medicinal effects of the compounds of
Chemical Formula (1) can be maintained in the form of
pharmaceutically acceptable salts.
[0450] Therefore, in still another aspect of the present
disclosure, there is provided a pharmaceutical composition for the
prevention or treatment of disorder mediated by glutamate
dysfunction and metabotropic glutamate receptor subtype 5 (mGluR5)
comprising a therapeutically effective amount of the compound of
Chemical Formula (1) or a pharmaceutically acceptable salt thereof
as an active ingredient, together with a pharmaceutically
acceptable carrier or excipient. The pharmaceutical composition may
further comprise one or more additives selected from the group
consisting of a pharmaceutically acceptable carrier, diluent and
adjuvant.
[0451] Specifically, the pharmaceutical composition may be a
composition for a positive allosteric modulator of mGluR5.
[0452] In addition, the pharmaceutical composition may be a
composition for the prevention and/or treatment of disorders
mediated by glutamate dysfunction and mGluR5. The disorders
mediated by glutamate dysfunction and mGluR5 may be, for example,
schizophrenia, and include any disorders known as being related to
glutamate dysfunction and mGluR5. In this regard, the article (N.
Matosin et al., Schizophrenia Research, 2013, Vol. 146, pp.
170-176) reported the relation between a positive allosteric
modulator of mGluR5 and the treatment of schizophrenia.
[0453] The pharmaceutically acceptable salt includes any acid or
base addition salts, and any stereochemical isomer thereof. These
salts are not specifically limited and may be any salt that is able
to retain activity of a parent compound thereof in a target subject
and does not cause any undesirable effect. Examples of these salts
are both inorganic and organic salts, such as acetic acid, nitric
acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid,
glutamic acid, formic acid, succinic acid, phosphoric acid,
phthalic acid, tannic acid, tartaric acid, hydrobromic acid,
propionic acid, benzenesulfonic acid, benzoic acid, stearic acid,
cresylic acid, lactic acid, bicarbonic acid, bisulfuric acid,
bitartaric acid, oxalic acid, butylic acid, calcium edatate,
camsylic acid, carbonic acid, chlorobenzoic acid, citric acid,
edetic acid, toluenesulfonic acid, edicylinic acid, ecylinic acid,
fumaric acid, gluceptic acid, pamoic acid, gluconic acid,
glycollarsanylic acid, methyl nitrate, polygalactronic acid,
hexyllisorcynonic acid, malonic acid, hydrobamic acid,
hydrochlorinic acid, hydroiodic acid, hydroxynaphtholic acid,
isethionic acid, lactobionic acid, mandelic acid, estolinic acid,
mucic acid, muconic acid, p-nitromethanesulfonic acid, hexamic
acid, phantothenic acid, monohydrogen phosphoric acid, dihydrogen
phosphoric acid, salicylic acid, sulfamine acid, sulfanilic acid,
methanesulfonic acid and theoclic acid. In addition, examples of a
basic salt are an ammonium salt, a salt of an alkali or alkali
earth metal such as lithium, sodium, potassium, magnesium, or
calcium, a salt containing an organic base such as benzathine,
N-methyl-D-glucamine, or hydrabamine, and a salt containing an
amino acid such as arginine or lysine. These salts may be converted
into a free form by treatment with appropriate acid or base. The
term "addition salt" may be taken to include solvates obtainable
from any of the compounds of Chemical Formula (1) and salts
thereof. Examples of these solvates are hydrates and
alcoholates.
[0454] The pharmaceutical composition may be formulated into
various types for oral or parenteral administration. For example,
it may be formulated into any dosage form for oral administration
such as tablets, pills, soft/hard capsules, solutions, suspensions,
emulsions, syrups, granules and elixirs. Besides the effective
ingredient, such a dosage form for oral administration may further
include any pharmaceutically acceptable carriers depending on a
typical construction of each formulation--for example, diluents
such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose
and/or glycine, or lubricants such as silica, talc, steric acid and
its magnesium or calcium salt, and/or polyethylene glycol.
[0455] In addition, in case the formulation for oral administration
is in a tablet form, it may also comprise binding agents such
magnesium aluminum silicate, starch paste, gelatin, gum tragacanth,
methyl cellulose, sodium carboxymethyl cellulose, and/or polyvinyl
pyrrolidone, and if desired, it may also include disintegrating
agents such as starch, agar, or alginic acid or its sodium salt, or
a boiling mixture, and/or an absorbing agent, a colorant, a
flavoring agent, or a sweetening agent.
[0456] The pharmaceutical composition may be formulated into a form
of parenteral administration. In this case, it may be administered
by means of parenteral administration methods such as a hypodermic
injection, an intravenous injection, an intramuscular injection or
an intrathoracic injection. In order for the pharmaceutical
composition of the present disclosure to be formulated into a
dosage form for parenteral administration, the effective ingredient
(i.e., the compound of Chemical Formula (1) or a pharmaceutically
acceptable salt thereof) may be mixed with a stabilizer or a
buffering agent in water to prepare as a solution or a suspension,
and this solution or suspension may then be produced as a unit
dosage form such as an ampoule or a vial.
[0457] In addition, the pharmaceutical composition may be
sterilized or may further comprise an adjuvant such as a
preservative, a stabilizing agent, a hydrating agent, an
emulsifying agent, or a salt for controlling osmotic pressure
and/or a buffering agent, and it may further include other
therapeutically beneficial substances and may be formulated in
accordance with conventional methods of mixing, granulation or
coating.
[0458] The pharmaceutical composition may comprise the effective
ingredient--i.e., the compound of Chemical Formula (1) or a
pharmaceutically acceptable salt thereof in an effective amount of
0.1 to 500 mg/kg (body weight), preferably 0.5 to 100 mg/kg (body
weight) per day in case of mammals including a human, and such a
pharmaceutical composition may be divided into one, or two or more
doses per day and administered via an oral or parenteral route.
[0459] In still another aspect, the present disclosure also
provides a role as a positive allosteric modulator of metabotropic
glutamate receptor subtype 5 (mGluR5), comprising the step of
administering a therapeutically effective amount of the compound of
Chemical Formula (1) or a pharmaceutically acceptable salt thereof
to a patient in need thereof. The modulation method may further
comprise a step of identifying the patient who is in need of
positive allosteric modulation of mGluR5 prior to the step of
administration.
[0460] In addition, the present disclosure provides a method for
the prevention and/or treatment of disorders mediated by glutamate
dysfunction and mGluR5, comprising the step of administering a
therapeutically effective amount of the compound of Chemical
Formula (1) or a pharmaceutically acceptable salt thereof to a
patient in need thereof. The method for the prevention and/or
treatment may further comprise a step of identifying the patient
who is in need of the prevention and/or treatment of disorders
mediated by glutamate dysfunction and mGluR5 prior to the step of
administration.
[0461] The disorders mediated by glutamate dysfunction and mGluR5
may be--for example, schizophrenia, and include any disorders known
as being related to glutamate dysfunction and the modulation of
mGluR5. The patient may be a mammal, preferably a human.
[0462] In addition, a person skilled in the art may easily select a
specific administration method and a therapeutically effective
amount of the compound of Chemical Formula (1) or a
pharmaceutically acceptable salt thereof with no particular
limitations, taking the type of the mammals to be administered and
the disorder, and the specific type of the compound of Chemical
Formula (1) and its activity on positive allosteric modulation of
mGluR5.
[0463] According to still another aspect, the present disclosure
provides a method of preparing the compound of Chemical Formula
(1). The preparation of the compound of Chemical Formula (1) may be
conducted by using a known compound or a compound easily prepared
therefrom in the perspective of a person skilled in the art
regarding a chemical synthesis. Therefore, the following
explanations about the method of preparing the compound of Chemical
Formula (1) merely present exemplary methods and if necessary, the
order of the unit operation may be selectively altered and does not
limit the scope of the disclosure.
##STR00006##
[0464] In a general synthesis method, from compound (2) as a
starting material a heterocycle synthesis reaction is carried out
with dichloroacetone to obtain imidazopyrimidine or imidazotriazine
derivative (3). From this compound, a nucleophilic reaction is
carried out to obtain compound (4), and then the final compound (1)
can be obtained via Suzuki coupling reaction.
##STR00007##
[0465] In another synthesis method, from compound (2) as a starting
material Suzuki coupling reaction is carried out to obtain compound
(5) in which aryl or heteroaryl is substituted. Then, a heterocycle
synthesis reaction is carried out with the obtained compound and
dichloroacetone to obtain imidazopyrimidine or imidazotriazine
derivative (6). From this compound, a nucleophilic reaction is
carried out to obtain the final compound (1).
##STR00008##
[0466] A heterocycle synthesis reaction is carried out with
compound (5) obtained in Reaction Scheme 2 and
1-acetoxy-3-chloroacetone to obtain compound (7), and the obtained
compound is then hydrolyzed to obtain compound (8). An aromatic
nucleophilic reaction of compound (8) is carried out to obtain the
final compound (9).
[0467] According to the present disclosure, a novel
imidazopyrimidine and imidazotriazine derivative, and a
pharmaceutically acceptable salt thereof showing excellent effect
on positive allosteric modulation of metabotropic glutamate
receptor subtype 5 (mGluR5) are provided. Therefore, such
imidazopyrimidine and imidazotriazine derivative, and a
pharmaceutically acceptable salt thereof can be effectively used in
the prevention or treatment of disorders mediated by glutamate
dysfunction and mGluR5 such as schizophrenia.
[0468] In addition, according to the present disclosure, a method
of preparing the novel imidazopyrimidine and imidazotriazine
derivative, a pharmaceutical composition comprising the same and a
method of positive allosteric modulation of mGluR5 by using the
same, and a method for the treatment of disorders mediated by
glutamate dysfunction and mGluR5 are provided.
EXAMPLES
[0469] Hereinafter, the present disclosure is explained in more
detail with the following examples. However, it must be understood
that the protection scope of the present disclosure is not limited
to the examples.
Example 1: Synthesis of
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00009##
[0470] Example 1-1: Synthesis of
6-bromo-2-chloromethylimidazo[1,2-a]pyrimidine
[0471] 5-Bromopyrimidin-2-amine (2 g, 11.5 mmol) and
1,3-dichloropropan-2-one (2.9 g, 23 mmol) were dissolved in DMF (20
ml), and then agitated at 110.degree. C. for 2 hours. After
confirmation of the reaction termination by liquid chromatography,
the reaction solution was diluted with ethyl acetate and washed
three times with water. Then, the solution was dried with magnesium
sulfate and filtrated. This was under reduced pressure, and the
resulting solids were washed with ethyl acetate to obtain the title
compound (amount: 0.85 g, yield: 30%).
Example 1-2: Synthesis of
6-bromo-2-phenoxymethylimidazo[1,2-a]pyrimidine
[0472] 6-Bromo-2-chloromethylimidazo[1,2-a]pyrimidine (2 g, 8.11
mmol) and phenol (1.5 g, 16.23 mmol) were dissolved in DMF (40 ml),
and potassium carbonate (3.4 g, 24.34 mmol) was added thereto at
room temperature. Then, the reaction solution was agitated at
60.degree. C. for 15 hours. After confirmation of the reaction
termination by liquid chromatography, the reaction solution was
diluted with ethyl acetate and washed three times with water. Then,
the solution was dried with magnesium sulfate and filtrated. This
was under reduced pressure, and the resulting solids were washed
with ethyl acetate to obtain the title compound (amount: 0.9 g,
yield: 38%).
Example 1-3: Synthesis of
6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
synthesis
[0473] 6-Bromo-2-phenoxymethylimidazo[1,2-a]pyrimidine (0.3 g, 0.99
mmol) obtained in Example 1-2 and 2-fluorophenylboronic acid (0.2
g, 1.43 mmol) were dissolved in 1,2-dimethoxyethane (8 ml), and
[1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) complex
dichloromethane (0.2 g, 0.24 mmol) and 2N sodium carbonate aqueous
solution (1.8 ml, 3.6 mmol) were then added thereto at room
temperature. Then, the reaction solution was agitated under reflux
at 90.degree. C. for 6 hours. After confirmation of the reaction
termination by liquid chromatography, the reaction solution was
diluted with methylene chloride and filtrated by the use of
Cellite.TM.. The solution was washed twice with water, and then
dried with magnesium sulfate and filtrated. This was under reduced
pressure and purified by column chromatography (methylene
chloride:methanol=50:1) to obtain the title compound (amount: 0.1
g, yield: 32%).
[0474] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.74 (s, 1H), 8.59 (s,
1H), 7.64 (s, 1H), 7.50 (m, 1H), 7.45 (m, 1H), 7.32 (m, 3H), 7.23
(m, 1H), 7.03 (m, 2H), 6.98 (m, 1H), 5.39 (s, 2H)
Example 2: Synthesis of
2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine
##STR00010##
[0476] Phenylboronic acid as a starting material was used in the
same manner as in Example 1-3 to obtain the title compound.
[0477] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.80 (s, 1H), 8.51 (s,
1H), 7.64 (s, 1H), 7.52 (m, 3H), 7.45 (m, 2H), 7.31 (m, 2H), 7.04
(m, 2H), 6.97 (m, 1H), 5.38 (s, 2H)
Example 3: Synthesis of
6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00011##
[0479] 2,4-Difluoro phenylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0480] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.20 (s, 1H), 8.72 (s,
1H), 8.00 (s, 1H), 7.76 (m, 1H), 7.49 (m, 1H), 7.30 (m, 3H), 7.07
(d, 2H), 6.95 (t, 1H), 5.27 (s, 2H)
Example 4: Synthesis of
6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00012##
[0482] 2-Methoxyphenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0483] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.74 (s, 1H), 8.55 (s,
1H), 7.61 (s, 1H), 7.42 (m, 2H), 7.37 (m, 1H), 7.29 (m, 1H), 7.13
(m, 1H), 7.05 (m, 3H), 6.95 (m, 1H), 5.40 (s, 2H), 3.87 (s, 3H)
Example 5: Synthesis of
6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00013##
[0485] 2-Methylphenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0486] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.58 (s, 1H), 8.33 (s,
1H), 7.64 (s, 1H), 7.35 (m, 5H), 7.25 (m, 1H), 7.06 (d, 2H), 7.00
(m, 1H), 5.42 (s, 2H), 2.33 (s, 3H)
Example 6: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00014##
[0488] 4-Fluoro-2-methylphenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0489] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.52 (s, 1H), 8.29 (s,
1H), 7.63 (s, 1H), 7.33 (m, 2H), 7.21 (m, 1H), 7.06 (m, 3H), 6.99
(m, 2H), 5.41 (s, 2H), 2.31 (s, 3H)
Example 7: Synthesis of
6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00015##
[0491] 2,3-Difluorophenylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0492] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.73 (s, 1H), 8.62 (s,
1H), 7.67 (s, 1H), 7.30 (m, 3H), 7.27 (m, 2H), 7.06 (m, 2H), 6.99
(m, 1H), 5.40 (s, 2H)
Example 8: Synthesis of
6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00016##
[0494] 4-Fluorophenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0495] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.75 (s, 1H), 8.54 (s,
1H), 7.66 (d, 1H), 7.51 (m, 1H), 7.31 (m, 3H), 7.26 (m, 1H), 7.15
(m, 1H), 7.05 (m, 2H), 6.98 (m, 1H), 5.38 (s, 2H)
Example 9: Synthesis of
6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00017##
[0497] 3-Aminophenylboronic acid as a starting material was used in
the same manner as in Example 1-3 to obtain the title compound.
[0498] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.15 (s, 1H), 8.77 (s,
1H), 7.95 (s, 1H), 7.31 (t, 2H), 7.15 (t, 1H), 7.07 (d, 2H), 6.95
(t, 1H), 6.86 (s, 1H), 6.83 (d, 1H), 6.64 (d, 1H), 5.27 (s, 2H),
5.25 (s, 2H)
Example 10: Synthesis of
6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00018##
[0500] 2-Aminophenylboronic acid as a starting material was used in
the same manner as in Example 1-3 to obtain the title compound.
[0501] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.67 (s, 1H), 8.48 (s,
1H), 7.62 (s, 1H), 7.33 (m, 2H), 7.20 (m, 1H), 7.13 (m, 1H), 7.05
(m, 2H), 6.99 (m, 1H), 6.90 (m, 1H), 6.83 (m, 1H), 5.40 (s, 2H)
Example 11: Synthesis of
6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00019##
[0503] 3-Amino-6-methylphenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0504] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.93 (s, 1H), 8.50 (s,
1H), 7.94 (s, 1H), 7.31 (t, 2H), 7.07 (d, 2H), 7.00 (m, 1H), 6.96
(m, 1H), 6.58 (d, 1H), 6.53 (s, 1H), 5.25 (s, 2H), 5.03 (s, 2H),
2.10 (s, 3H)
Example 12: Synthesis of
6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00020##
[0506] 3-Amino-4-fluorophenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0507] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.14 (s, 1H), 8.75 (s,
1H), 7.95 (s, 1H), 7.54 (m, 2H), 7.30 (m, 2H), 7.15 (m, 1H), 7.11
(m, 2H), 6.95 (m, 1H), 5.35 (s, 2H), 5.24 (s, 2H)
Example 13: Synthesis of
6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00021##
[0509] 3-Chloro-4-fluorophenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0510] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.73 (s, 1H), 8.50 (s,
1H), 7.66 (s, 1H), 7.61 (m, 1H), 7.44 (m, 1H), 7.32 (m, 3H), 7.05
(m, 2H), 7.00 (m, 1H), 5.40 (s, 2H)
Example 14: Synthesis of
6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00022##
[0512] 2-Dimethylaminophenylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0513] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.04 (s, 1H), 8.73 (s,
1H), 7.95 (s, 1H), 7.39 (m, 1H), 7.32 (m, 3H), 7.21 (m, 1H), 7.19
(m, 2H), 6.96 (m, 2H), 5.23 (s, 2H), 2.51 (s, 6H)
Example 15: Synthesis of
6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00023##
[0515] 2-Chloro-4-fluorophenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0516] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.08 (s, 1H), 8.59 (s,
1H), 7.98 (s, 1H), 7.65 (m, 2H), 7.40 (m, 1H), 7.31 (m, 2H), 7.06
(m, 2H), 6.95 (m, 1H), 5.25 (s, 2H)
Example 16: Synthesis of
6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00024##
[0518] 2-Hydroxyphenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0519] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.64 (s, 1H), 8.55 (s,
1H), 7.45 (s, 1H), 7.25 (m, 4H), 7.05 (m, 1H), 6.98 (m, 1H), 6.92
(m, 3H), 5.21 (s, 2H)
Example 17: Synthesis of
6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00025##
[0521] 3-Hydroxyphenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0522] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.77 (s, 1H), 8.46 (s,
1H), 7.59 (s, 1H), 7.35 (m, 1H), 7.26 (m, 2H), 7.07 (m, 2H), 6.99
(m, 2H), 6.90 (m, 2H), 5.35 (s, 2H)
Example 18: Synthesis of
6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethyllmidazo[1,2-a]pyrimid-
ine
##STR00026##
[0524] 4-Fluoro-2-trifluoromethylphenylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0525] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.05 (s, 1H), 8.49 (s,
1H), 8.00 (s, 1H), 7.85 (m, 1H), 7.71 (m, 2H), 7.32 (m, 2H), 7.09
(m, 2H), 6.95 (m, 1H), 5.28 (s, 2H)
Example 19: Synthesis of
6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00027##
[0527] 3,4-Difluorophenylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0528] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.33 (s, 1H), 8.91 (s,
1H), 7.94 (m, 2H), 7.64 (m, 2H), 7.32 (m, 2H), 7.08 (m, 2H), 6.96
(m, 1H), 5.26 (s, 2H)
Example 20: Synthesis of
6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00028##
[0530] 2-Methoxy-4-fluorophenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0531] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.06 (s, 1H), 8.64 (s,
1H), 7.95 (s, 1H), 7.51 (t, 1H), 7.31 (t, 2H), 7.12 (m, 1H), 7.06
(d, 2H), 6.95 (m, 2H), 5.26 (s, 2H), 3.84 (s, 3H)
Example 21: Synthesis of
6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00029##
[0533] 4-Fluoro-3-methoxyphenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0534] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.30 (s, 1H), 8.93 (s,
1H), 7.94 (s, 1H), 7.56 (m, 1H), 7.35 (m, 4H), 7.08 (m, 2H), 6.95
(m, 1H), 5.26 (s, 2H), 3.94 (s, 3H)
Example 22: Synthesis of
6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00030##
[0536] 4-Chloro-2-methoxyphenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0537] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.66 (s, 1H), 8.54 (s,
1H), 7.62 (s, 1H), 7.29 (m, 3H), 7.05 (m, 5H), 5.37 (s, 2H), 3.86
(s, 3H)
Example 23: Synthesis of
6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00031##
[0539] 4-Cyano-2-methoxyphenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0540] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.70 (s, 1H), 8.63 (s,
1H), 7.66 (s, 1H), 7.49 (d, 2H), 7.32 (m, 3H), 7.06 (m, 2H), 7.01
(m, 1H), 5.40 (s, 2H), 3.93 (s, 3H)
Example 24: Synthesis of
6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00032##
[0542] 7-Fluorobenzo[1,3]dioxol-4-ylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0543] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.29 (s, 1H), 8.89 (s,
1H), 8.02 (s, 1H), 7.30 (m, 3H), 7.06 (m, 3H), 6.95 (m, 1H), 6.26
(s, 2H), 5.25 (s, 2H)
Example 25: Synthesis of
6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidin-
e
##STR00033##
[0545] 4-Fluoro-2-hydroxymethylphenylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0546] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.99 (s, 1H), 8.56 (s,
1H), 7.95 (s, 1H), 7.43 (m, 2H), 7.32 (m, 2H), 7.27 (m, 1H), 7.06
(m, 2H), 6.95 (m, 1H), 5.44 (s, 1H), 5.27 (s, 2H), 4.47 (s, 2H)
Example 26: Synthesis of
6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00034##
[0548] 4-Fluoro-2-methylthiophenylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0549] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.01 (s, 1H), 8.51 (s,
1H), 7.96 (s, 1H), 7.42 (m, 1H), 7.35 (m, 3H), 7.15 (m, 1H), 7.06
(d, 2H), 6.95 (m, 1H), 5.27 (s, 2H), 2.47 (s, 3H)
Example 27: Synthesis of
6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00035##
[0551] 2-Amino-4-fluorophenylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0552] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.59 (s, 1H), 8.39 (s,
1H), 7.58 (s, 1H), 7.29 (m, 2H), 7.05 (m, 4H), 6.55 (m, 2H), 5.39
(s, 2H), 3.89 (s, 2H)
Example 28: Synthesis of
6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00036##
[0554] 2,4-Difluoro-5-methoxyphenylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0555] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.14 (s, 1H), 8.69 (s,
1H), 7.95 (s, 1H), 7.43 (m, 1H), 7.32 (m, 3H), 7.06 (m, 2H), 6.96
(m, 1H), 5.26 (s, 2H), 3.81 (s, 3H)
Example 29: Synthesis of
6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00037##
[0557] (2-Fluoropyridin-3-yl)boronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0558] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.75 (d, 1H), 8.70 (s,
1H), 8.33 (d, 1H), 7.99 (m, 1H), 7.69 (s, 1H), 7.41 (m, 1H), 7.32
(m, 2H), 7.05 (m, 2H), 6.95 (m, 1H), 5.41 (s, 2H)
Example 30: Synthesis of
6-(6-methoxypyridin-3-yl)-2-phenoxymethyllmidazo[1,2-a]pyrimidine
##STR00038##
[0560] 6-Methoxypyridin-3-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0561] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.89 (s,
1H), 8.57 (s, 1H), 8.10 (m, 1H), 7.94 (s, 1H), 7.30 (m, 2H), 7.08
(m, 2H), 7.00 (m, 1H), 6.96 (t, 1H), 5.26 (s, 2H), 3.90 (s, 3H)
Example 31: Synthesis of
6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00039##
[0563] 6-Fluoropyridin-3-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0564] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.36 (s, 1H), 8.93 (s,
1H), 8.65 (s, 1H), 8.41 (m, 1H), 7.97 (s, 1H), 7.40 (m, 1H), 7.31
(t, 2H), 7.08 (m, 2H), 6.95 (t, 1H), 5.27 (s, 2H)
Example 32: Synthesis of
6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00040##
[0566] 4-Methylpyridin-3-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0567] 1H-NMR (CD3OD, 500 MHz) .delta. 9.47 (s, 1H), 9.15 (s, 1H),
8.95 (m, 1H), 8.88 (m, 1H), 8.39 (s, 1H), 8.15 (s, 1H), 7.35 (m,
2H), 7.12 (m, 2H), 7.04 (m, 1H), 5.48 (s, 2H), 2.69 (s, 3H)
Example 33: Synthesis of
6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00041##
[0569] 2,6-Difluoropyridin-3-ylboronic acid as a starting material
was used in the same manner as in Example 1-3 to obtain the title
compound.
[0570] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.28 (s, 1H), 8.78 (s,
1H), 8.49 (q, 1H), 8.03 (s, 1H), 7.40 (d, 1H), 7.30 (t, 2H), 7.07
(d, 2H), 6.95 (t, 1H), 5.27 (s, 2H)
Example 34: Synthesis of
6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00042##
[0572] 6-Chloropyridin-3-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0573] 1H-NMR (CD3OD, 500 MHz) .delta. 9.58 (s, 1H), 9.37 (s, 1H),
8.82 (s, 1H), 8.32 (s, 1H), 8.25 (d, 1H), 7.71 (m, 1H), 7.35 (m,
2H), 7.11 (m, 2H), 7.04 (m, 1H), 5.46 (s, 2H)
Example 35: Synthesis of
6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00043##
[0575] 2-Fluoropyridin-4-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0576] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.57 (s, 1H), 9.06 (s,
1H), 8.38 (m, 1H), 7.99 (s, 1H), 7.82 (d, 1H), 7.69 (d, 1H), 7.31
(t, 2H), 7.08 (d, 2H), 6.95 (t, 1H), 5.28 (s, 2H)
Example 36: Synthesis of
6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00044##
[0578] 3-Chloropyridin-4-ylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0579] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.42 (s, 1H), 8.91 (s,
1H), 8.85 (s, 1H), 8.71 (d, 1H), 8.18 (s, 1H), 7.70 (s, 1H), 7.32
(m, 2H), 7.09 (m, 2H), 6.97 (m, 1H), 5.35 (s, 2H)
Example 37: Synthesis of
6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00045##
[0581] 4-Chlorophenylboronic acid as a starting material was used
in the same manner as in Example 1-3 to obtain the title
compound.
[0582] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.33 (s, 1H), 8.91 (s,
1H), 7.96 (s, 1H), 7.81 (d, 2H), 7.60 (d, 2H), 7.31 (t, 2H), 7.09
(d, 2H), 6.95 (t, 1H), 5.27 (s, 2H)
Example 38: Synthesis of
6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00046##
[0584] 6-Fluoro-4-methyl-3-pyridylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0585] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.49 (s, 1H), 8.35 (s,
1H), 8.09 (s, 1H), 7.66 (s, 1H), 7.30 (m, 2H), 7.03 (m, 2H), 6.97
(m, 2H), 5.39 (s, 2H), 2.36 (s, 3H)
Example 39: Synthesis of
6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00047##
[0587] 6-Fluoro-5-methyl-3-pyridylboronic acid as a starting
material was used in the same manner as in Example 1-3 to obtain
the title compound.
[0588] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.35 (s, 1H), 8.89 (s,
1H), 8.42 (s, 1H), 8.22 (d, 1H), 7.94 (s, 1H), 7.29 (m, 2H), 7.05
(m, 2H), 6.94 (m, 1H), 5.27 (s, 2H), 2.35 (s, 3H)
Example 40: Synthesis of
6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine
##STR00048##
[0590] 5-Fluoro-2-pyridylboronic acid as a starting material was
used in the same manner as in Example 1-3 to obtain the title
compound.
[0591] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.60 (s, 1H), 9.20 (s,
1H), 8.71 (s, 1H), 8.13 (d, 1H), 8.02 (s, 1H), 7.94 (t, 1H), 7.28
(t, 2H), 7.07 (d, 2H), 6.92 (t, 1H), 5.24 (s, 2H)
Example 41: Synthesis of
6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
##STR00049##
[0593] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0594] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.20 (s, 1H), 8.72 (s,
1H), 8.02 (s, 1H), 7.76 (m, 1H), 7.49 (m, 1H), 7.33 (m, 2H), 6.98
(m, 1H), 6.90 (m, 1H), 6.76 (m, 1H) 5.28 (s, 2H)
Example 42: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00050##
[0596] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0597] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.68 (s, 1H), 8.52 (s,
1H), 7.61 (s, 1H), 7.30 (m, 1H), 7.23 (m, 1H), 6.82 (m, 2H), 6.76
(m, 2H), 6.68 (m, 1H), 5.35 (s, 2H), 3.85 (s, 3H)
Example 43: Synthesis of
6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyri-
midine
##STR00051##
[0599] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-3-hydroxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0600] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.20 (s, 1H), 8.81 (s,
1H), 7.98 (s, 1H), 7.33 (m, 3H), 7.18 (m, 1H), 6.99 (m, 1H), 6.93
(m, 1H), 6.78 (m, 1H), 5.28 (s, 2H)
Example 44: Synthesis of
6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
##STR00052##
[0602] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 2-aminophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0603] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.93 (s, 1H), 8.54 (s,
1H), 7.95 (s, 1H), 7.31 (m, 1H), 7.10 (m, 2H), 6.98 (m, 1H), 6.92
(m, 1H), 6.79 (m, 2H), 6.63 (m, 1H), 5.27 (s, 2H), 5.14 (s, 2H)
Example 45: Synthesis of
6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e
##STR00053##
[0605] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine
and 3-chloropyridin-4-ylboronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0606] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.81 (s,
1H), 8.72 (s, 1H), 8.67 (s, 1H), 8.06 (s, 1H), 7.69 (m, 1H), 7.32
(m, 1H), 6.99 (m, 1H), 6.92 (m, 1H), 6.79 (m, 1H), 5.30 (s, 2H)
Example 46: Synthesis of
6-(4-methylpyridin-3-y)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
##STR00054##
[0608] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-methylpyridin-3-ylboronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0609] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 9.34 (s, 1H), 9.00 (s,
2H), 8.78 (s, 1H), 8.62 (s, 1H), 7.73 (s, 1H), 7.32 (m, 2H), 7.06
(m, 2H), 7.01 (m, 1H), 5.42 (s, 2H)
Example 47: Synthesis of
6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
##STR00055##
[0611] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethylimidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethylimidazo[1,2-a]pyrimidine
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0612] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.70 (s, 1H), 8.57 (s,
1H), 7.64 (s, 1H), 7.47 (m, 1H), 6.99 (m, 6H), 5.35 (s, 2H)
Example 48: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00056##
[0614] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0615] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.53 (s, 1H), 8.31 (s,
1H), 7.62 (s, 1H), 7.22 (m, 2H), 7.09 (m, 1H), 6.99 (m, 4H), 5.36
(s, 2H), 2.32 (s, 3H)
Example 49: Synthesis of
6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidin-
e
##STR00057##
[0617] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 3-chloropyridin-4-ylboronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0618] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.79 (s, 1H), 8.68 (m,
2H), 8.62 (m, 1H), 7.69 (s, 1H), 7.38 (m, 1H), 6.99 (m, 4H), 5.37
(s, 2H)
Example 50: Synthesis of
6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
##STR00058##
[0620] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 2,6-dimethylphenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0621] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.88 (s, 1H), 8.38 (s,
1H), 7.92 (s, 1H), 7.26 (m, 1H), 7.20 (m, 2H), 7.10 (m, 4H), 5.25
(s, 2H), 2.07 (s, 6H)
Example 51: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00059##
[0623] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (6-fluoro-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0624] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.74 (s, 1H), 8.55 (s,
1H), 8.44 (s, 1H), 7.99 (m, 1H), 7.67 (s, 1H), 7.13 (m, 1H), 6.98
(m, 4H), 5.35 (s, 2H)
Example 52: Synthesis of
4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol
##STR00060##
[0626] Benzene-1,4-diol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-hydroxyphenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-hydroxyphenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0627] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.95 (s,
1H), 8.88 (s, 1H), 7.90 (s, 1H), 7.82 (m, 2H), 7.38 (t, 2H), 6.89
(d, 2H), 6.68 (d, 2H), 5.14 (s, 2H)
Example 53: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine
##STR00061##
[0629] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0630] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.28 (s, 1H), 8.89 (s,
1H), 7.94 (s, 1H), 7.81 (s, 2H), 7.38 (s, 2H), 7.12 (m, 4H), 5.25
(s, 2H)
Example 54: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine
##STR00062##
[0632] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0633] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.78 (s, 1H), 8.50 (s,
1H), 7.64 (s, 1H), 7.53 (m, 2H), 7.25 (m, 2H), 6.84 (m, 1H), 6.77
(m, 1H), 6.68 (m, 1H), 5.37 (s, 2H)
Example 55: Synthesis of
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l
##STR00063##
[0635] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluoro-3-hydroxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0636] 1H-NMR (DMSO-d6, 500 MHz) .delta. 10.21 (s, 1H), 9.21 (s,
1H), 8.80 (s, 1H), 7.95 (s, 1H), 7.28 (m, 2H), 7.11 (m, 5H), 5.24
(s, 2H)
Example 56: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine
##STR00064##
[0638] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and phenylboronic acid were used in the same manner as in Example
1-3 to obtain the title compound.
[0639] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.30 (s, 1H), 8.91 (s,
1H), 7.95 (s, 1H), 7.78 (d, 2H), 7.55 (t, 2H), 7.46 (m, 1H), 7.12
(m, 4H), 5.25 (s, 2H)
Example 57: Synthesis of
5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l
##STR00065##
[0641] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluoro-2-hydroxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0642] 1H-NMR (DMSO-d6, 500 MHz) .delta. 10.5 (s, 1H), 9.10 (s,
1H), 8.70 (s, 1H), 7.99 (s, 1H), 7.48 (m, 1H), 7.35 (m, 1H), 7.00
(m, 1H), 6.93 (m, 1H), 6.80 (m, 2H), 5.28 (s, 2H)
Example 58: Synthesis of
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pheno-
l
##STR00066##
[0644] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluoro-2-hydroxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0645] 1H-NMR (DMSO-d6, 500 MHz) .delta. 10.5 (s, 1H), 9.07 (s,
1H), 8.68 (s, 1H), 7.94 (s, 1H), 7.45 (m, 1H), 7.08 (m, 4H), 6.78
(m, 2H), 5.22 (s, 2H)
Example 59: Synthesis of
6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2--
a]pyrimidine
##STR00067##
[0647] 2,3,4,5,6-Pentadeuteriophenol as a starting material was
used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2,3,4,5,6-pentadeuteriophenoxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2,3,4,5,6-pentadeuteriophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluorophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0648] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.29 (d, 1H), 8.89 (d,
1H), 7.95 (s, 1H), 7.82 (t, 2H), 7.39 (t, 2H), 5.27 (s, 2H)
Example 60: Synthesis of
2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine
##STR00068##
[0650] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and o-tolylboronic acid were used in the same manner as in Example
1-3 to obtain the title compound.
[0651] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.00 (s, 1H), 8.58 (s,
1H), 7.93 (s, 1H), 7.35 (m, 4H), 7.12 (m, 4H), 5.25 (s, 2H), 2.30
(s, 3H)
Example 61: Synthesis of
6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine
##STR00069##
[0653] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-fluoro-2-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0654] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.04 (s, 1H), 8.59 (s,
1H), 7.94 (s, 1H), 7.40 (t, 1H), 7.28 (m, 1H), 7.22 (m, 1H), 7.12
(m, 4H), 5.25 (s, 2H), 2.27 (s, 3H)
Example 62: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00070##
[0656] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-fluoro-4-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0657] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.57 (s, 1H), 9.05 (s,
1H), 8.38 (d, 1H), 7.98 (s, 1H), 7.82 (m, 1H), 7.70 (s, 1H), 7.12
(m, 4H), 5.25 (s, 2H)
Example 63: Synthesis of
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol
##STR00071##
[0659] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-hydroxyphenyl)boronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0660] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.97 (s, 1H), 9.11 (s,
1H), 8.73 (s, 1H), 7.96 (s, 1H), 7.42 (d, 1H), 7.25 (m, 1H), 7.11
(m, 4H), 7.00 (m, 2H), 5.23 (s, 2H)
Example 64: Synthesis of
6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine
##STR00072##
[0662] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-fluoro-4-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0663] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.88 (s,
1H), 7.93 (s, 1H), 7.63 (t, 1H), 7.15 (m, 6H), 5.24 (s, 2H), 2.32
(s, 3H)
Example 65: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2--
a]pyrimidine
##STR00073##
[0665] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and [6-(trifluoromethyl)-3-pyridyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0666] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.48 (s, 1H), 9.17 (s,
1H), 9.00 (d, 1H), 8.48 (d, 1H), 8.07 (m, 1H), 7.98 (s, 1H), 7.10
(m, 4H), 5.25 (s, 2H)
Example 66: Synthesis of
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline
##STR00074##
[0668] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-aminophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0669] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.92 (s, 1H), 8.48 (s,
1H), 7.90 (s, 1H), 7.08 (m, 6H), 6.76 (d, 1H), 6.65 (t, 1H), 5.22
(s, 2H), 5.13 (s, 1H), 3.15 (s, 1H)
Example 67: Synthesis of
6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyr-
imidine
##STR00075##
[0671] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-chloro-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0672] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.09 (s, 1H), 8.59 (s,
1H), 7.96 (s, 1H), 7.67 (m, 2H), 7.40 (m, 1H), 7.12 (m, 4H), 5.24
(s, 2H)
Example 68: Synthesis of
4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile
##STR00076##
[0674] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-cyano-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0675] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.18 (s, 1H), 8.71 (s,
1H), 7.97 (s, 1H), 7.70 (s, 2H), 7.58 (m, 1H), 7.10 (m, 4H), 5.25
(s, 2H)
Example 69: Synthesis of
6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]py-
rimidine
##STR00077##
[0677] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-chloro-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0678] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.08 (s, 1H), 8.64 (s,
1H), 7.94 (s, 1H), 7.48 (d, 1H), 7.26 (d, 1H), 7.14 (m, 5H), 5.23
(s, 2H), 3.83 (s, 3H)
Example 70: Synthesis of
2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne
##STR00078##
[0680] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (3-amino-4-fluoro-phenyl)boronic acid as a starting material
were used in the same manner as in Example 1-3 to obtain the title
compound.
[0681] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.15 (s, 1H), 8.75 (s,
1H), 7.94 (s, 1H), 7.09 (m, 6H), 6.85 (m, 1H), 5.36 (m, 2H), 5.23
(s, 2H)
Example 71: Synthesis of
6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine
##STR00079##
[0683] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2,6-difluoro-3-pyridyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0684] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.69 (m, 2H), 8.09 (m,
1H), 7.69 (s, 1H), 7.27 (m, 1H), 7.06 (m, 1H), 6.82 (s, 1H), 6.75
(m, 2H), 5.37 (s, 2H)
Example 72: Synthesis of
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-anil-
ine
##STR00080##
[0686] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (3-amino-4-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0687] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.12 (s, 1H), 8.74 (s,
1H), 7.93 (s, 1H), 7.08 (m, 5H), 6.90 (s, 1H), 6.80 (m, 1H), 5.22
(s, 2H), 5.03 (m, 2H), 2.08 (s, 3H)
Example 73: Synthesis of
4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]a-
niline
##STR00081##
[0689] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-4,5-difluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0690] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.96 (s, 1H), 8.48 (s,
1H), 7.94 (s, 1H), 7.27 (m, 1H), 7.15 (m, 4H), 6.74 (m, 1H), 5.35
(s, 2H), 5.24 (s, 2H)
Example 74: Synthesis of
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-anil-
ine
##STR00082##
[0692] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-4-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0693] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.88 (s, 1H), 8.46 (s,
1H), 7.90 (s, 1H), 7.10 (m, 4H), 6.95 (m, 1H), 6.57 (s, 1H), 6.47
(m, 1H), 5.22 (s, 2H), 5.06 (s, 2H), 2.19 (s, 3H)
Example 75: Synthesis of
5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne
##STR00083##
[0695] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-4-chloro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0696] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.93 (s, 1H), 8.44 (s,
1H), 7.93 (s, 1H), 7.10 (m, 5H), 6.80 (s, 1H), 6.64 (d, 1H), 5.48
(s, 2H), 5.24 (s, 2H)
Example 76: Synthesis of
2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-anil-
ine
##STR00084##
[0698] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-5-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0699] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.92 (s, 1H), 8.50 (s,
1H), 7.91 (s, 1H), 7.11 (m, 4H), 6.92 (m, 2H), 6.67 (d, 1H), 5.24
(s, 2H), 4.93 (s, 2H), 2.17 (s, 3H)
Example 77: Synthesis of
5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]anili-
ne
##STR00085##
[0701] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0702] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.90 (s, 1H), 8.43 (s,
1H), 7.93 (s, 1H), 7.10 (m, 5H), 6.53 (m, 1H), 6.42 (m, 1H), 5.46
(s, 2H), 5.23 (s, 2H)
Example 78: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00086##
[0704] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-methyl-3-pyridyl)boronic acid as were used in the same
manner as in Example 1-3 to obtain the title compound.
[0705] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.07 (s, 1H), 8.62 (s,
1H), 8.50 (t, 2H), 7.94 (s, 1H), 7.40 (m, 1H), 7.09 (m, 4H), 5.25
(s, 2H), 2.33 (s, 3H)
Example 79: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00087##
[0707] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-fluoro-4-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0708] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.84 (s, 1H), 8.70 (s,
1H), 8.41 (d, 1H), 7.73 (s, 1H), 7.44 (d, 1H), 7.26 (m, 1H), 7.18
(s, 1H), 6.85 (d, 1H), 6.76 (m, 2H), 5.39 (s, 2H)
Example 80: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2--
a]pyrimidine
##STR00088##
[0710] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and [6-(trifluoromethyl)-3-pyridyl)boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0711] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.98 (s, 1H), 8.82 (s,
1H), 8.66 (s, 1H), 8.12 (d, 1H), 7.90 (m, 1H), 7.74 (s, 1H), 6.86
(m, 1H), 6.72 (m, 2H), 5.41 (s, 2H)
Example 81: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00089##
[0713] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (6-fluoro-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0714] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.74 (s, 1H), 8.54 (s,
1H), 8.44 (s, 1H), 8.00 (m, 1H), 7.67 (s, 1H), 7.13 (m, 1H), 6.83
(m, 1H), 6.76 (d, 1H), 6.71 (m, 1H), 5.37 (s, 2H)
Example 82: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00090##
[0716] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-fluoro-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0717] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.75 (s, 1H), 8.70 (s,
1H), 8.32 (d, 1H), 7.98 (t, 1H), 7.67 (s, 1H), 7.39 (t, 1H), 6.83
(m, 1H), 6.76 (d, 1H), 6.69 (m, 1H), 5.37 (s, 2H)
Example 83: Synthesis of
6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrim-
idine
##STR00091##
[0719] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5,6-difluoro-3-pyridyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0720] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.40 (s, 1H), 8.94 (s,
1H), 8.55 (m, 1H), 8.48 (s, 1H), 7.96 (s, 1H), 7.09 (m, 4H), 5.25
(s, 2H)
Example 84: Synthesis of
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy-ani-
line
##STR00092##
[0722] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (3-amino-4-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0723] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.08 (s, 1H), 8.74 (s,
1H), 7.91 (s, 1H), 7.10 (m, 4H), 6.91 (m, 3H), 5.21 (s, 2H), 4.90
(s, 2H), 3.79 (s, 3H)
Example 85: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00093##
[0725] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-fluoro-2-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0726] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 9.07 (m, 2H), 8.56 (s,
1H), 7.78 (s, 1H), 7.66 (s, 1H), 7.59 (m, 1H), 6.98 (m, 4H), 5.35
(s, 2H)
Example 86: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidi-
ne
##STR00094##
[0728] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-methoxy-2-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0729] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.54 (s, 1H), 9.17 (s,
1H), 8.40 (s, 1H), 8.00 (m, 2H), 7.56 (d, 1H), 7.10 (m, 4H), 5.22
(s, 2H), 3.88 (s, 3H)
Example 87: Synthesis of
6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
e
##STR00095##
[0731] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-chloro-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0732] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.22 (s, 1H), 8.77 (s,
1H), 8.71 (s, 1H), 8.64 (d, 1H), 8.02 (s, 1H), 7.77 (d, 1H), 7.12
(m, 4H), 5.28 (s, 2H)
Example 88: Synthesis of
6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-
e
##STR00096##
[0734] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-chloro-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0735] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.46 (s, 1H), 8.99 (d,
2H), 8.70 (s, 1H), 8.42 (s, 1H), 7.97 (s, 1H), 7.11 (m, 4H), 5.26
(s, 2H)
Example 89: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidi-
ne
##STR00097##
[0737] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-methoxy-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0738] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.38 (s, 1H), 8.96 (s,
1H), 8.55 (s, 1H), 8.34 (s, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.09
(m, 4H), 5.24 (s, 2H), 3.90 (s, 3H)
Example 90: Synthesis of
5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyridin-2-ol
##STR00098##
[0740] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (6-hydroxy-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0741] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.35 (s, 1H), 8.91 (s,
1H), 8.62 (s, 1H), 8.39 (m, 1H), 7.95 (s, 1H), 7.38 (d, 1H), 7.11
(m, 4H), 5.22 (s, 2H)
Example 91: Synthesis of
6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]-
pyrimidine
##STR00099##
[0743] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (6-fluoro-5-methyl-3-pyridyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0744] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.34 (s, 1H), 8.92 (s,
1H), 8.44 (s, 1H), 8.25 (d, 1H), 7.95 (s, 1H), 7.10 (m, 4H), 5.25
(s, 2H), 2.32 (s, 3H)
Example 92: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00100##
[0746] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (6-methyl-3-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0747] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.34 (s, 1H), 8.92 (s,
1H), 8.84 (s, 1H), 8.06 (d, 1H), 7.95 (s, 1H), 7.41 (d, 1H), 7.10
(m, 4H), 5.25 (s, 2H), 2.32 (s, 3H)
Example 93: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidin-
e
##STR00101##
[0749] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (5-fluoro-2-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0750] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.61 (s, 1H), 9.18 (s,
1H), 8.69 (s, 1H), 8.12 (t, 1H), 8.03 (s, 1H), 7.92 (t, 1H), 7.30
(m, 1H), 6.95 (d, 1H), 6.88 (d, 1H), 6.75 (t, 1H), 5.24 (s, 2H)
Example 94: Synthesis of
2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo-
[1,2-a]pyrimidine
##STR00102##
[0752] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0753] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.77 (s,
1H), 8.23 (s, 1H), 7.89 (t, 1H), 7.76 (t, 1H), 7.68 (t, 1H), 7.35
(m, 1H), 7.01 (d, 1H), 6.93 (d, 1H), 6.81 (t, 1H), 5.38 (s, 2H)
Example 95: Synthesis of
4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-ben-
zonitrile
##STR00103##
[0755] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-cyano-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0756] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.18 (s, 1H), 8.70 (s,
1H), 7.99 (s, 1H), 7.67 (m, 2H), 7.58 (m, 1H), 7.32 (m, 1H), 6.98
(m, 1H), 6.91 (m, 1H), 6.78 (m, 1H), 5.28 (s, 2H), 3.88 (s, 3H)
Example 96: Synthesis of
[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol
##STR00104##
[0758] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(hydroxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0759] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.98 (s, 1H), 8.55 (s,
1H), 7.95 (s, 1H), 7.42 (m, 2H), 7.33 (m, 1H), 7.24 (m, 1H), 6.97
(d, 1H), 6.91 (d, 1H), 6.76 (t, 1H), 5.41 (s, 1H), 5.28 (s, 2H)
4.45 (d, 2H)
Example 97: Synthesis of
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methanol
##STR00105##
[0761] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(hydroxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0762] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.97 (s, 1H), 8.54 (s,
1H), 7.93 (s, 1H), 7.41 (m, 2H), 7.24 (m, 1H), 7.10 (m, 4H), 5.74
(s, 1H), 5.23 (s, 2H) 4.45 (d, 2H)
Example 98: Synthesis of
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1-
,2-a]pyrimidine
##STR00106##
[0764] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluoro-2-methylsulfanyl-phenyl)boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0765] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.01 (s, 1H), 8.51 (s,
1H), 7.98 (s, 1H), 7.43 (t, 1H), 7.28 (d, 1H), 7.12 (m, 5H), 5.26
(s, 2H), 2.48 (s, 3H)
Example 99: Synthesis of
2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidi-
ne
##STR00107##
[0767] 4-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-methoxy-4-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0768] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.80 (s, 1H), 8.60 (s,
1H), 8.30 (s, 1H), 7.66 (s, 1H), 6.98 (m, 6H), 5.34 (s, 2H), 4.01
(s, 3H)
Example 100: Synthesis of
2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-anil-
ine
##STR00108##
[0770] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-5-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0771] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.95 (s, 1H), 8.51 (s,
1H), 7.94 (s, 1H), 7.33 (m, 1H), 6.98 (m, 1H), 6.93 (m, 3H), 6.79
(t, 1H), 6.68 (d, 1H), 5.41 (s, 2H), 4.95 (s, 2H), 2.21 (s, 3H)
Example 101: Synthesis of
5-fluoro-2-[2-[(3-fluorophenoxymethyl]imidazo[1,2-a]pyrimidin-6-yl]anilin-
e
##STR00109##
[0773] 3-Fluorophenol as a starting material was used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine
and (2-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0774] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.91 (s, 1H), 8.44 (s,
1H), 7.93 (s, 1H), 7.31 (m, 1H), 7.08 (t, 1H), 6.97 (d, 1H), 6.90
(d, 1H), 6.77 (t, 1H), 6.52 (t, 1H), 5.48 (s, 2H), 5.27 (s, 2H)
Example 102: Synthesis of
6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00110##
[0776] 2-Hydroxypyridine and silver carbonate were used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0777] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.77 (s, 1H), 8.51 (s,
1H), 8.22 (s, 1H), 7.63 (m, 4H), 7.25 (m, 2H), 6.83 (m, 2H), 5.67
(s, 2H)
Example 103: Synthesis of
6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00111##
[0779] 2-Hydroxypyridine and silver carbonate were used in the same
manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 2-methylphenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0780] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.58 (s, 1H), 8.33 (s,
1H), 8.23 (s, 1H), 7.65 (m, 2H), 7.37 (m, 3H), 7.11 (m, 1H), 6.93
(m, 2H), 5.68 (s, 2H), 2.34 (s, 3H)
Example 104: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00112##
[0782] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0783] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.65 (s, 1H), 8.52 (s,
1H), 8.20 (s, 1H), 7.61 (s, 1H), 7.58 (t, 1H), 7.31 (t, 1H), 6.91
(t, 1H), 6.85 (d, 1H), 6.77 (m, 2H), 5.63 (s, 2H), 3.84 (s, 3H)
Example 105: Synthesis of
6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00113##
[0785] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0786] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.59 (s, 1H), 9.19 (s,
1H), 8.35 (s, 1H), 8.23 (s, 1H), 7.82 (m, 2H), 7.59 (m, 1H), 7.39
(m, 1H), 7.09 (t, 1H), 6.98 (d, 1H), 5.65 (s, 2H)
Example 106: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00114##
[0788] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0789] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.53 (s, 1H), 8.31 (s,
1H), 8.22 (s, 1H), 7.66 (m, 2H), 7.24 (m, 1H), 7.05 (m, 2H), 6.90
(m, 2H), 5.68 (s, 2H), 2.32 (s, 3H)
Example 107: Synthesis of
6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00115##
[0791] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 2,3-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0792] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.69 (d, 2H), 8.19 (s,
1H), 7.70 (s, 1H), 7.61 (s, 1H), 7.28 (m, 3H), 6.90 (m, 2H), 5.65
(s, 2H)
Example 108: Synthesis of
6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00116##
[0794] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 5-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0795] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.55 (s, 1H), 8.35 (s,
1H), 8.22 (s, 1H), 7.69 (s, 1H), 7.62 (m, 1H), 7.30 (m, 1H), 7.10
(m, 1H), 6.99 (d, 1H), 6.92 (t, 1H), 6.87 (m, 1H), 5.68 (s, 2H),
2.29 (s, 3H)
Example 109: Synthesis of
6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00117##
[0797] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 3-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0798] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.53 (s, 1H), 8.36 (s,
1H), 8.21 (s, 1H), 7.68 (s, 1H), 7.61 (m, 1H), 7.28 (m, 1H), 7.15
(t, 1H), 7.08 (t, 1H), 6.91 (t, 1H), 6.85 (d, 1H), 5.67 (s, 2H),
2.23 (s, 3H)
Example 110: Synthesis of
6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,-
2-a]pyrimidine
##STR00118##
[0800] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and
2-(7-fluoro-2H-1,3-benzodioxol-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborol-
ane were used in the same manner as in Example 1-3 to obtain the
title compound.
[0801] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.84 (s, 1H), 8.75 (s,
1H), 8.21 (d, 1H), 7.62 (m, 2H), 7.06 (m, 1H), 6.93 (m, 1H), 6.85
(m, 2H), 6.16 (s, 2H), 5.65 (s, 2H)
Example 111: Synthesis of
6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00119##
[0803] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-chloro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0804] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.64 (s, 1H), 8.54 (s,
1H), 8.18 (d, 1H), 7.59 (m, 2H), 7.28 (m, 1H), 7.07 (m, 2H), 6.88
(m, 2H), 5.62 (s, 2H), 3.84 (s, 3H)
Example 112: Synthesis of
6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00120##
[0806] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (3-fluoro-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0807] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.73 (d, 1H), 8.62 (d,
1H), 8.22 (t, 1H), 7.67 (s, 1H), 7.64 (m, 1H), 7.19 (m, 3H), 6.94
(t, 1H), 6.88 (m, 1H), 5.85 (s, 2H), 3.85 (s, 3H)
Example 113: Synthesis of
6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00121##
[0809] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0810] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.47 (s, 1H), 8.38 (s,
1H), 8.22 (d, 1H), 7.67 (s, 1H), 7.64 (m, 1H), 7.57 (m, 1H), 7.43
(m, 2H), 6.93 (m, 1H), 6.87 (m, 1H), 5.67 (s, 2H)
Example 114: Synthesis of
6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00122##
[0812] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluoro-2-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0813] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.51 (s, 1H), 8.35 (s,
1H), 8.03 (s, 1H), 7.67 (s, 1H), 7.38 (m, 1H), 7.22 (t, 1H), 7.04
(m, 2H), 6.83 (m, 1H), 5.61 (s, 2H), 2.31 (s, 3H)
Example 115: Synthesis of
6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine
##STR00123##
[0815] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (2-ethylphenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0816] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.55 (s, 1H), 8.34 (s,
1H), 8.21 (d, 1H), 7.67 (s, 1H), 7.62 (m, 1H), 7.42 (m, 2H), 7.32
(m, 1H), 7.23 (d, 1H), 6.93 (t, 1H), 6.87 (d, 1H), 5.67 (s, 2H),
2.63 (q, 2H), 1.15 (t, 3H)
Example 116: Synthesis of
6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00124##
[0818] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluoro-2-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0819] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.64 (s, 1H), 8.08 (d,
1H), 8.05 (d, 1H), 7.48 (t, 2H), 7.40 (m, 2H), 6.91 (m, 1H), 6.59
(s, 1H), 5.47 (s, 2H), 2.47 (s, 3H)
Example 117: Synthesis of
6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidi-
ne
##STR00125##
[0821] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (2-fluoro-4-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0822] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.64 (s, 1H), 8.08 (d,
1H), 8.05 (d, 1H), 7.48 (t, 2H), 7.40 (m, 2H), 6.91 (m, 1H), 6.59
(s, 1H), 5.47 (s, 2H), 2.47 (s, 3H)
Example 118: Synthesis of
6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,-
2-a]pyrimidine
##STR00126##
[0824] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluoro-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0825] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.67 (s, 1H), 8.49 (s,
1H), 8.16 (d, 1H), 7.61 (s, 1H), 7.31 (m, 1H), 6.78 (m, 2H), 6.69
(m, 1H), 6.55 (d, 1H), 5.65 (s, 2H), 3.85 (s, 3H)
Example 119: Synthesis of
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine
##STR00127##
[0827] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0828] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.48 (s, 1H), 8.35 (s,
1H), 8.02 (s, 1H), 7.63 (s, 1H), 7.55 (d, 1H), 7.39 (m, 3H), 6.83
(m, 1H), 5.60 (s, 2H)
Example 120: Synthesis of
6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00128##
[0830] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (2,4-difluorophenyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0831] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.71 (s, 1H), 8.59 (s,
1H), 8.17 (d, 1H), 7.68 (s, 1H), 7.50 (m, 1H), 7.08 (m, 2H), 6.73
(m, 1H), 6.58 (m, 1H), 5.69 (s, 2H)
Example 121: Synthesis of
6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,-
2-a]pyrimidine
##STR00129##
[0833] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (3-fluoro-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0834] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.72 (s, 1H), 8.61 (s,
1H), 8.16 (s, 1H), 7.64 (s, 1H), 7.17 (m, 3H), 6.70 (m, 1H), 6.55
(m, 1H), 5.66 (s, 2H), 3.84 (s, 3H)
Example 122: Synthesis of
6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00130##
[0836] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (2,3-difluorophenyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0837] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.77 (s, 1H), 8.68 (s,
1H), 8.19 (s, 1H), 7.72 (s, 1H), 7.30 (m, 3H), 6.74 (m, 1H), 6.59
(m, 1H), 5.70 (s, 2H)
Example 123: Synthesis of
6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00131##
[0839] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluorophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0840] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.81 (s, 1H), 8.53 (s,
1H), 8.19 (s, 1H), 7.69 (m, 1H), 7.57 (m, 2H), 7.29 (m, 2H), 6.74
(m, 1H), 6.59 (m, 1H), 5.70 (s, 2H)
Example 124: Synthesis of
6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00132##
[0842] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (3-fluoro-2-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0843] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.50 (s, 1H), 8.41 (s,
1H), 8.00 (s, 1H), 7.68 (s, 1H), 7.37 (m, 1H), 7.29 (m, 1H), 7.16
(m, 1H), 7.04 (m, 1H), 6.81 (m, 1H), 5.58 (s, 2H), 2.21 (s, 3H)
Example 125: Synthesis of
2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine
##STR00133##
[0845] 4-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0846] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.48 (s, 1H), 8.36 (s,
1H), 8.17 (m, 1H), 7.65 (m, 1H), 7.57 (m, 1H), 7.41 (m, 2H), 6.72
(m, 1H), 6.56 (m, 1H), 5.67 (s, 2H)
Example 126: Synthesis of
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine
##STR00134##
[0848] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and o-tolylboronic acid were used in the same manner as in Example
1-3 to obtain the title compound.
[0849] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.56 (s, 1H), 8.30 (s,
1H), 8.02 (s, 1H), 7.62 (m, 1H), 7.37 (m, 3H), 7.25 (m, 2H), 6.83
(m, 1H), 5.60 (s, 2H), 2.31 (s, 3H)
Example 127: Synthesis of
6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00135##
[0851] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-chloro-2-methyl-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0852] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.49 (s, 1H), 8.29 (s,
1H), 8.01 (s, 1H), 7.62 (s, 1H), 7.37 (m, 2H), 7.28 (m, 1H), 7.17
(m, 1H), 6.80 (m, 1H), 5.59 (s, 2H), 2.27 (s, 3H)
Example 128: Synthesis of
6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00136##
[0854] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (2,4-dimethylphenyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0855] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.54 (s, 1H), 8.29 (s,
1H), 8.03 (s, 1H), 7.62 (s, 1H), 7.38 (m, 1H), 7.16 (s, 1H), 7.13
(m, 2H), 6.82 (m, 1H), 5.60 (s, 2H), 2.39 (s, 3H), 2.28 (s, 3H)
Example 129: Synthesis of
6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00137##
[0857] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluorophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0858] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.27 (s, 1H), 8.88 (d,
1H), 8.20 (d, 1H), 7.91 (s, 1H), 7.83 (m, 2H), 7.74 (m, 1H), 7.38
(m, 2H), 6.97 (m, 1H), 5.47 (s, 2H)
Example 130: Synthesis of
2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyr-
imidine
##STR00138##
[0860] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [6-(trifluoromethyl)-3-pyridyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0861] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.95 (s, 1H), 8.77 (s,
1H), 8.63 (s, 1H), 8.19 (s, 1H), 8.09 (d, 1H), 7.86 (s, 1H), 7.73
(s, 1H), 7.61 (s, 1H), 6.86 (m, 2H), 5.67 (s, 2H)
Example 131: Synthesis of
2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidaz-
o[1,2-a]pyrimidine
##STR00139##
[0863] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and [6-(trifluoromethyl)-3-pyridyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0864] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.96 (s, 1H), 8.80 (s,
1H), 8.64 (s, 1H), 8.10 (m, 1H), 7.88 (m, 1H), 7.73 (s, 1H), 7.61
(m, 1H), 7.51 (m, 1H), 6.85 (m, 1H), 5.64 (s, 2H)
Example 132: Synthesis of
6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine
##STR00140##
[0866] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (5-fluoro-2-pyridyl)boronic acid were used in the same manner
as in Example 1-3 to obtain the title compound.
[0867] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.58 (s, 1H), 9.17 (s,
1H), 8.69 (s, 1H), 8.20 (s, 1H), 8.12 (t, 1H), 7.98 (s, 1H), 7.92
(t, 1H), 7.71 (t, 1H), 6.99 (t, 1H), 6.87 (d, 1H), 5.47 (s, 2H)
Example 133: Synthesis of
2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline
##STR00141##
[0869] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (3-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0870] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.74 (s, 1H), 8.45 (s,
1H), 8.03 (s, 1H), 7.63 (s, 1H), 7.38 (t, 1H), 7.12 (m, 1H), 6.95
(m, 1H), 6.84 (m, 2H), 5.64 (s, 2H), 3.92 (s, 2H)
Example 134: Synthesis of
2-fluoro-5-[2-2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline
##STR00142##
[0872] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (3-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0873] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.73 (s, 1H), 8.44 (s,
1H), 8.21 (s, 1H), 7.62 (m, 2H), 7.11 (m, 1H), 6.92 (m, 4H), 5.65
(s, 2H), 3.92 (s, 2H)
Example 135: Synthesis of
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thanol
##STR00143##
[0875] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(hydroxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0876] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.96 (s, 1H), 8.54 (s,
1H), 8.20 (d, 1H), 7.89 (s, 1H), 7.75 (t, 1H), 7.40 (m, 2H), 7.24
(m, 1H), 7.00 (m, 1H), 6.89 (d, 1H), 5.49 (s, 2H), 5.40 (m, 1H),
4.45 (d, 2H)
Example 136: Synthesis of
3-methoxy-4-[2-2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitri-
le
##STR00144##
[0878] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (4-cyano-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0879] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.66 (s, 1H), 8.60 (s,
1H), 8.18 (d, 1H), 7.64 (s, 1H), 7.60 (m, 1H), 7.47 (d, 1H), 7.40
(d, 1H), 7.26 (d, 1H), 6.90 (m, 1H), 6.84 (m, 1H), 5.63 (s, 1H),
3.89 (s, 3H)
Example 137: Synthesis of
4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-metho-
xy-benzonitrile
##STR00145##
[0881] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-cyano-2-methoxy-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0882] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.16 (s, 1H), 8.69 (s,
1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.72 (m, 3H), 7.58 (m, 1H), 6.95
(m, 1H), 5.45 (s, 2H), 3.88 (s, 3H)
Example 138: Synthesis of
6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine
##STR00146##
[0884] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (4-fluoro-2-methylsulfanyl-phenyl)boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0885] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.99 (s, 1H), 8.51 (s,
1H), 8.22 (d, 1H), 7.94 (s, 1H), 7.76 (m, 1H), 7.41 (m, 1H), 7.28
(d, 1H), 7.15 (t, 1H), 7.01 (t, 1H), 6.90 (d, 1H), 5.51 (s, 2H),
2.48 (s, 3H)
Example 139: Synthesis of
[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol
##STR00147##
[0887] 5-Fluoropyridin-2-ol as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(hydroxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0888] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.99 (s, 1H), 8.54 (s,
1H), 8.21 (s, 1H), 7.89 (s, 1H), 7.71 (t, 1H), 7.43 (m, 2H), 7.22
(t, 1H), 6.97 (d, 1H), 5.46 (s, 2H), 5.41 (s, 1H), 4.45 (s, 2H)
Example 140: Synthesis of
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile
##STR00148##
[0890] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (4-cyanophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0891] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.81 (s, 1H), 8.60 (s,
1H), 8.22 (s, 1H), 7.85 (d, 2H), 7.71 (t, 3H), 7.63 (m, 1H), 6.95
(m, 1H), 6.89 (m, 1H), 5.69 (s, 2H)
Example 141: Synthesis of
6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]-
pyrimidine
##STR00149##
[0893] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [4-fluoro-2-(methoxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0894] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.95 (s, 1H), 8.52 (s,
1H), 8.20 (t, 1H), 7.91 (s, 1H), 7.74 (m, 1H), 7.48 (m, 1H), 7.36
(m, 1H), 7.31 (m, 1H), 7.02 (m, 1H), 6.88 (d, 1H), 5.49 (s, 2H),
4.37 (s, 2H), 3.23 (s, 3H)
Example 142: Synthesis of
[2-[22-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethyl)-
phenyl]methanol
##STR00150##
[0896] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [2-(hydroxymethyl)-4-(trifluoromethyl)phenyl]boronic acid were
used in the same manner as in Example 1-3 to obtain the title
compound.
[0897] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.63 (s, 1H), 8.55 (d,
1H), 8.20 (d, 1H), 7.89 (s, 1H), 7.72 (d, 1H), 7.63 (m, 2H), 7.49
(d, 1H), 6.93 (t, 1H), 6.85 (d, 1H), 5.63 (s, 2H), 4.72 (s, 2H)
Example 143: Synthesis of
6-(2-Isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine
##STR00151##
[0899] 2-hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and (2-isopropylphenyl)boronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0900] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.92 (s, 1H), 8.46 (s,
1H), 8.20 (s, 1H), 7.90 (s, 1H), 7.73 (t, 1H), 7.45 (m, 2H), 7.28
(t, 2H), 7.02 (t, 1H), 6.89 (d, 1H), 5.50 (s, 2H), 2.93 (m, 1H),
1.14 (d, 6H)
Example 144: Synthesis of
4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl-
)benzaldehyde
##STR00152##
[0902] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [4-formyl-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0903] 1H-NMR (DMSO-d6, 500 MHz) .delta. 10.18 (s, 1H), 9.10 (s,
1H), 8.53 (s, 1H), 8.40 (s, 1H), 8.29 (d, 1H), 8.19 (d, 1H), 7.95
(s, 1H), 7.87 (d, 1H), 7.74 (t, 1H), 7.02 (t, 1H), 6.90 (d, 1H),
5.51 (s, 2H)
Example 145: Synthesis of
6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00153##
[0905] 2-Hydroxypyridine as a starting material and silver
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and [4-chloro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0906] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.38 (s, 1H), 8.91 (s,
1H), 8.31 (s, 1H), 8.23 (d, 1H), 8.07 (s, 1H), 7.98 (d, 1H), 7.80
(t, 1H), 7.65 (d, 1H), 7.09 (t, 1H), 6.95 (d, 1H), 5.63 (s, 2H)
Example 146: Synthesis of
6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00154##
[0908] 3-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0909] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.79 (s, 1H), 8.53 (s,
1H), 8.46 (s, 1H), 8.25 (s, 1H), 7.68 (s, 1H), 7.55 (m, 2H), 7.39
(m, 1H), 7.25 (m, 3H), 5.43 (s, 2H)
Example 147: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00155##
[0911] 3-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0912] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.70 (s, 1H), 8.52 (s,
1H), 8.46 (s, 1H), 8.27 (s, 1H), 7.63 (s, 1H), 7.35 (m, 2H), 7.24
(m, 1H), 6.84 (m, 2H), 5.43 (s, 2H), 3.87 (s, 3H)
Example 148: Synthesis of
6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00156##
[0914] 3-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0915] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.71 (s, 1H), 8.60 (s,
1H), 8.46 (s, 1H), 8.27 (s, 1H), 7.68 (s, 1H), 7.50 (m, 1H), 7.38
(m, 1H), 7.26 (m, 1H), 7.08 (m, 2H), 5.43 (s, 2H)
Example 149: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00157##
[0917] 3-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0918] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.50 (s, 1H), 8.38 (d,
2H), 8.23 (s, 1H), 7.67 (s, 1H), 7.36 (m, 1H), 7.21 (m, 2H), 7.03
(m, 2H), 5.39 (s, 2H), 2.30 (s, 3H)
Example 150: Synthesis of
6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00158##
[0920] 3-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-hydroxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0921] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.21 (s, 1H), 8.75 (s,
1H), 8.45 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.55 (m, 1H), 7.45
(m, 1H), 7.34 (m, 1H), 6.62 (s, 2H), 5.34 (s, 2H), 4.05 (m, 1H)
Example 151: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrim-
idine
##STR00159##
[0923] 4-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0924] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.68 (s, 1H), 8.54 (s,
1H), 8.43 (s, 2H), 7.61 (s, 1H), 7.29 (m, 1H), 6.95 (d, 2H), 6.79
(m, 2H), 5.39 (s, 2H), 3.84 (s, 3H)
Example 152: Synthesis of
6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine
##STR00160##
[0926] 4-Hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine. The
obtained 6-bromo-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0927] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.68 (s, 1H), 8.62 (s,
1H), 8.45 (m, 2H), 7.67 (s, 1H), 7.47 (m, 1H), 7.06 (m, 1H), 7.02
(m, 1H), 6.95 (m, 2H), 5.39 (s, 2H)
Example 153: Synthesis of
6-(2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00161##
[0929] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2-methylphenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0930] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.62 (s, 1H), 8.36 (s,
1H), 8.31 (s, 1H), 8.16 (s, 1H), 7.66 (s, 1H), 7.38 (m, 4H), 7.19
(m, 1H), 5.44 (s, 2H), 2.35 (s, 3H)
Example 154: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00162##
[0932] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0933] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.55 (s, 1H), 8.36 (s,
1H), 8.29 (s, 1H), 8.14 (s, 1H), 7.67 (s, 1H), 7.23 (m, 1H), 7.17
(m, 1H), 7.04 (m, 2H), 5.42 (s, 2H), 3.32 (s, 3H)
Example 155: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00163##
[0935] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0936] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.71 (s, 1H), 8.52 (s,
1H), 8.29 (s, 1H), 8.14 (s, 1H), 7.62 (s, 1H), 7.33 (m, 1H), 7.16
(m, 1H), 6.82 (m, 2H), 5.41 (s, 2H), 3.87 (s, 3H)
Example 156: Synthesis of
6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00164##
[0938] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-hydroxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0939] 1H-NMR (DMSO-d6, 500 MHz) .delta. 10.52 (s, 1H), 9.10 (s,
1H), 8.71 (s, 1H), 8.31 (s, 1H), 8.20 (s, 1H), 8.03 (s, 1H), 7.65
(m, 1H), 7.47 (m, 1H), 6.80 (m, 2H), 5.38 (s, 2H)
Example 157: Synthesis of
6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00165##
[0941] 6-Fluoro-3-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0942] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.73 (s, 1H), 8.59 (s,
1H), 7.99 (s, 1H), 7.67 (s, 1H), 7.50 (m, 2H), 7.07 (m, 2H), 6.90
(m, 1H), 5.40 (s, 2H)
Example 158: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00166##
[0944] 2-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0945] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.56 (s, 1H), 8.34 (s,
1H), 7.99 (s, 1H), 7.65 (s, 1H), 7.53 (m, 1H), 7.25 (m, 1H), 7.11
(m, 1H), 7.07 (m, 1H), 6.89 (m, 1H), 5.41 (s, 2H), 2.33 (s, 3H)
Example 159: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00167##
[0947] 2-Fluoro-3-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0948] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.17 (s, 1H), 8.79 (s,
1H), 8.17 (s, 1H), 7.94 (m, 1H), 7.80 (s, 1H), 7.44 (t, 1H), 7.38
(m, 1H), 7.30 (m, 1H), 7.21 (m, 1H), 5.50 (s, 2H), 2.34 (s, 3H)
Example 160: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00168##
[0950] 5-Chloro-3-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0951] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.56 (d, 1H), 8.35 (s,
2H), 8.24 (s, 1H), 7.66 (s, 1H), 7.40 (s, 1H), 7.25 (m, 1H), 7.05
(m, 2H), 5.42 (s, 2H), 2.33 (s, 3H)
Example 161: Synthesis of
6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00169##
[0953] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2,4-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0954] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.20 (s, 1H), 8.73 (s,
1H), 8.04 (s, 1H), 7.99 (d, 1H), 7.68 (m, 1H), 7.41 (m, 1H), 7.22
(m, 1H), 6.97 (m, 1H), 6.86 (s, 1H), 5.35 (s, 2H)
Example 162: Synthesis of
6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2--
a]pyrimidine
##STR00170##
[0956] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methylphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0957] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.53 (s, 1H), 8.29 (s,
1H), 8.04 (d, 1H), 7.60 (s, 1H), 7.20 (t, 1H), 7.03 (d, 1H), 7.00
(t, 1H), 6.86 (m, 1H), 6.54 (s, 1H), 5.40 (s, 2H), 2.29 (s, 3H)
Example 163: Synthesis of
6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00171##
[0959] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-methoxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0960] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.69 (s, 1H), 8.54 (s,
1H), 8.04 (s, 1H), 7.62 (s, 1H), 7.32 (m, 1H), 6.87 (d, 1H), 6.78
(m, 2H), 6.55 (s, 1H), 5.40 (s, 2H), 3.85 (s, 3H)
Example 164: Synthesis of
6-(4-fluorophenyl)-2-2fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin-
e
##STR00172##
[0962] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0963] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.80 (s, 1H), 8.51 (s,
1H), 8.07 (d, 1H), 7.65 (s, 1H), 7.54 (m, 2H), 7.24 (m, 2H), 6.88
(s, 1H), 6.57 (s, 1H), 5.43 (s, 2H)
Example 165: Synthesis of
6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyr-
imidine
##STR00173##
[0965] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2,3-difluorophenylboronic acid were used in the same manner as
in Example 1-3 to obtain the title compound.
[0966] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.78 (s, 1H), 8.68 (s,
1H), 8.08 (s, 1H), 7.70 (s, 1H), 7.29 (s, 3H), 6.89 (s, 1H), 6.58
(s, 1H), 5.44 (s, 2H)
Example 166: Synthesis of
6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00174##
[0968] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2-fluorophenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0969] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.79 (s, 1H), 8.64 (s,
1H), 8.07 (s, 1H), 7.65 (s, 1H), 7.51 (m, 1H), 7.47 (m, 1H), 7.34
(m, 2H), 6.88 (s, 1H), 6.57 (s, 1H), 5.43 (s, 2H)
Example 167: Synthesis of
6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-
-a]pyrimidine
##STR00175##
[0971] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-hydroxyphenylboronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0972] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.53 (s, 1H), 9.19 (s,
1H), 8.42 (s, 1H), 8.13 (s, 1H), 7.55 (m, 2H), 7.10 (s, 1H), 7.01
(m, 2H), 6.86 (m, 1H), 5.59 (s, 2H)
Example 168: Synthesis of
6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00176##
[0974] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2-methylphenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0975] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.61 (s, 1H), 8.35 (s,
1H), 8.07 (s, 1H), 7.63 (s, 1H), 7.39 (m, 4H), 6.88 (s, 1H), 6.58
(s, 1H), 5.44 (s, 2H), 2.34 (s, 3H)
Example 169: Synthesis of
6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimi-
dine
##STR00177##
[0977] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 2-hydroxyphenylboronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0978] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.14 (s, 1H), 8.76 (s,
1H), 8.07 (m, 2H), 7.43 (m, 1H), 7.25 (m, 1H), 7.06 (m, 1H), 7.00
(m, 1H), 6.95 (m, 2H), 5.40 (s, 2H)
Example 170: Synthesis of
6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imida-
zo[1,2-a]pyrimidine
##STR00178##
[0980] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and 4-fluoro-2-hydroxymethylphenylboronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[0981] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.03 (s, 1H), 8.60 (s,
1H), 8.09 (s, 1H), 8.04 (s, 1H), 7.42 (m, 2H), 7.26 (m, 1H), 7.07
(d, 1H), 6.97 (s, 1H), 5.43 (s, 2H), 4.48 (m, 2H), 4.11 (m, 1H)
Example 171: Synthesis of
6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimid-
ine
##STR00179##
[0983] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluorophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0984] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.30 (s, 1H), 8.91 (s,
1H), 8.32 (s, 1H), 8.20 (s, 1H), 8.02 (s, 1H), 7.82 (t, 2H), 7.66
(d, 1H), 7.39 (t, 2H), 5.39 (s, 2H)
Example 172: Synthesis of
2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimid-
ine
##STR00180##
[0986] 2-Chloro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-chloropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-chloropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and (4-fluorophenyl)boronic acid were used in the same manner as in
Example 1-3 to obtain the title compound.
[0987] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.30 (s, 1H), 8.91 (s,
1H), 8.24 (d, 1H), 8.01 (s, 1H), 7.83 (m, 2H), 7.39 (t, 2H), 7.30
(s, 1H), 7.15 (m, 1H), 5.42 (s, 2H)
Example 173: Synthesis of
2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine
##STR00181##
[0989] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0990] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.08 (s, 1H), 8.51 (s,
1H), 8.32 (m, 1H), 8.21 (m, 1H), 7.98 (m, 1H), 7.88 (m, 1H), 7.70
(m, 2H), 7.65 (m, 1H), 5.40 (s, 2H)
Example 174: Synthesis of
2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]i-
midazo[1,2-a]pyrimidine
##STR00182##
[0992] 2-Fluoro-4-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(trifluoromethyl)phenyl]boronic acid were used in
the same manner as in Example 1-3 to obtain the title compound.
[0993] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.35 (s, 1H), 8.83 (s,
1H), 8.33 (s, 1H), 8.09 (d, 1H), 7.88 (m, 1H), 7.77 (m, 1H), 7.67
(m, 1H), 7.07 (d, 1H), 6.98 (s, 1H), 5.59 (s, 2H)
Example 175: Synthesis of
5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline
##STR00183##
[0995] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and (2-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0996] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.92 (s, 1H), 8.45 (s,
1H), 8.29 (s, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.64 (d, 1H), 7.08
(t, 1H), 6.52 (d, 1H), 6.43 (m, 1H), 5.47 (s, 2H), 5.37 (s, 2H)
Example 176: Synthesis of
5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl-
]aniline
##STR00184##
[0998] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and (2-amino-4-fluoro-phenyl)boronic acid were used in the same
manner as in Example 1-3 to obtain the title compound.
[0999] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.92 (s, 1H), 8.45 (s,
1H), 8.05 (d, 1H), 7.98 (s, 1H), 7.06 (m, 2H), 6.93 (s, 1H), 6.52
(d, 1H), 6.42 (t, 1H), 5.47 (m, 2H), 5.40 (s, 2H)
Example 177: Synthesis of
[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol
##STR00185##
[1001] 3-Fluoro-5-hydroxypyridine as a starting material and cesium
carbonate were used in the same manner as in Example 1-2 to obtain
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine.
The obtained
6-bromo-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidin- e
and [4-fluoro-2-(hydroxymethyl)phenyl]boronic acid were used in the
same manner as in Example 1-3 to obtain the title compound.
[1002] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.01 (s, 1H), 8.56 (s,
1H), 8.30 (s, 1H), 8.21 (s, 1H), 8.02 (s, 1H), 7.64 (d, 1H), 7.40
(m, 2H), 7.22 (t, 1H), 5.41 (s, 1H), 5.40 (s, 2H), 4.46 (s, 2H)
Example 178: Synthesis of
2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine
##STR00186##
[1003] Example 178-1: Synthesis of
6-bromo-1,2,4-triazine-3-amine
[1004] 1,2,4-Triazine-3-amine (2 g, 20.814 mmol) was dissolved in
acetonitrile (20.8 ml) and water (31.5 ml). After the reaction
temperature was cooled to 0.degree. C., N-bromosuccinimide (3.89 g,
20.855 mmol) was added thereto. The resulting mixture was agitated
for 10 minutes, and then heated to room temperature and
agitated.
[1005] After the reaction termination, the resulting mixture was
diluted with ethyl acetate and cooled to 0.degree. C. Sodium
carbonate was added thereto, agitated for 10 minutes, and washed
with saturated sodium bicarbonate and brine. After drying with
anhydrous magnesium sulfate and filtration, the solvent was
concentrated under reduced pressure to obtain
6-bromo-1,2,4-triazine-3-amine (amount: 2.4 g, yield: 67%).
Example 178-2: Synthesis of
6-(2,4-difluorophenyl)-1,2,4-triazine-3-amine
[1006] 6-Bromo-1,2,4-triazine-3-amine (0.5 g, 2.857 mmol),
2,4-difluorophenylboronic acid (0.68 g, 4.286 mmol), 2N sodium
carbonate and
[1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) complex
with dichloromethane (0.28 g, 0.343 mmol) were added to
1,2-dimethoxyethane (28.6 ml) and agitated at 90.degree. C.
overnight. After the temperature of the reaction mixture was cooled
to room temperature, the reaction mixture was filtrated with
Cellite.TM. pad, and the solvent was concentrated under reduced
pressure, and then washed with ethyl acetate and filtrated to
obtain yellow solid, 6-(2,4-difluorophenyl)-1,2,4-triazine-3-amine
(amount: 0.82 g, yield: 46%).
Example 178-3: Synthesis of
6-(chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazine
[1007] 6-(2,4-Difluorophenyl)-1,2,4-triazine-3-amine (0.2 g, 0.961
mmol) was dissolved in dimethylformamide (4.8 ml), and
1,3-dichloroacetone (0.24 g, 1.922 mmol) was added thereto and
agitated at 110.degree. C. for 2 hours. After the reaction
termination, water and ethyl acetate were added thereto and
extracted. After drying with anhydrous magnesium sulfate and
filtration, the solvent was concentrated under reduced pressure.
Flash column chromatography was carried out to obtain yellow solid,
6-(chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazi-
ne (amount: 80 mg, yield: 30%).
Example 178-4: Synthesis of
2-(2,4-difluorophenyl)-6-phenoxymethylimidazo[1,2-b][1,2,4]triazine
[1008]
6-(Chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazin-
e (20 mg, 0.071 mmol) was dissolved in dimethylformamide (1 ml),
and phenol (14 mg, 0.143 mmol) and potassium carbonate (69 mg,
0.213 mmol) were added thereto and agitated at 60.degree. C. for 2
hours. After the reaction termination, the resulting mixture was
filtrated and the solvent was concentrated under reduced pressure.
Flash column chromatography was carried out to obtain white solid,
2-(2,4-difluorophenyl)-6-phenoxymethylimidazo[1,2-b][1,2,4]triazine
(amount: 12 mg, yield: 50%).
[1009] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.86 (s, 1H), 8.06 (s,
1H), 7.90 (m, 1H), 7.33 (m, 2H), 7.12 (m, 1H), 7.05 (m, 3H), 7.00
(m, 1H), 5.43 (s, 2H)
Example 179: Synthesis of
2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine
##STR00187##
[1011]
6-(Chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazin-
e (66 mg, 0.235 mmol) obtained in Example 178-3 was dissolved in
dimethylformamide (2.35 ml), and 4-hydroxypyridine (27 mg, 0.282
mmol) and cesium carbonate (0.23 g, 0.705 mmol) were added thereto
and agitated at 40.degree. C. for 2 hours. After the reaction
termination, the resulting mixture was filtrated with Cellite.TM.
pad, and the solvent was concentrated under reduced pressure.
Column chromatography was carried out to obtain the title compound
(amount: 10 mg, yield: 11%).
[1012] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.88 (s, 1H), 8.50 (m,
2H), 8.05 (s, 1H), 7.89 (m, 1H), 7.09 (m, 2H), 6.99 (s, 2H), 5.49
(s, 2H)
Example 180: Synthesis of
2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]tr-
iazine
##STR00188##
[1014]
6-(Chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazin-
e (90 mg, 0.321 mmol) obtained in Example 178-3 was dissolved in
dimethylformamide (3.2 ml), and 2-hydroxypyridine (37 mg, 0.385
mmol) and silver carbonate were added thereto and agitated at
40.degree. C. for 2 hours. After the reaction termination, the
resulting mixture was filtrated with Cellite.TM. pad, and the
solvent was concentrated under reduced pressure. Column
chromatography was carried out to obtain the title compound
(amount: 23 mg, yield: 19%).
[1015] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.85 (s, 1H), 8.22 (s,
1H), 8.08 (s, 1H), 7.91 (m, 1H), 7.64 (m, 1H), 7.10 (m, 2H), 6.93
(m, 2H), 5.72 (s, 2H)
Example 181: Synthesis of
2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne
##STR00189##
[1017] (4-Fluorophenyl)boronic acid as a starting material was used
in the same manner as in Example 178-2 and Example 178-3 to obtain
6-(chloromethyl)-2-(4-fluorophenyl)imidazo[1,2-b][1,2,4]triazine.
The obtained
6-(chloromethyl)-2-(4-fluorophenyl)imidazo[1,2-b][1,2,4]triazine
was used in the same manner as in Example 180 to obtain the title
compound.
[1018] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.85 (s, 1H), 8.20 (s,
1H), 8.04 (S, 1H), 7.98 (m, 2H), 7.62 (t, 1H), 7.28 (m, 2H), 6.92
(m, 1H), 6.86 (m, 1H), 5.69 (s, 2H)
Example 182: Synthesis of
2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazi-
ne
##STR00190##
[1020] (2-Methylphenyl)boronic acid as a starting material was used
in the same manner as in Example 178-2 and Example 178-3 to obtain
6-(chloromethyl)-2-(2-methylphenyl)imidazo[1,2,-b][1,2,4]triazine.
The obtained
6-(chloromethyl)-2-(2-methylphenyl)imidazo[1,2,-b][1,2,4]triazin- e
was used in the same manner as in Example 180 to obtain the title
compound.
[1021] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.56 (s, 1H), 8.20 (s,
1H), 8.04 (s, 1H), 7.62 (m, 1H), 7.46 (m, 2H), 7.36 (m, 2H), 6.91
(m, 1H), 6.86 (m, 1H), 5.70 (s, 2H), 2.43 (s, 3H)
Example 183: Synthesis of
2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][-
1,2,4]triazine
##STR00191##
[1023]
6-(Chloromethyl)-2-(2,4-difluorophenyl)imidazo[1,2-b][1,2,4]triazin-
e obtained in Example 178-3 as a starting material and
2-fluoro-4-hydroxypyridine were used in the same manner as in
Example 179 to obtain the title compound.
[1024] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.89 (s, 1H), 8.07 (m,
2H), 7.91 (m, 1H), 7.12 (m, 1H), 7.06 (m, 1H), 6.89 (s, 1H), 6.57
(s, 1H), 5.46 (s, 2H)
Example 184: Synthesis of
2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,-
2-b][1,2,4]triazine
##STR00192##
[1026] (4-Fluoro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 2-fluoro-4-hydroxypyridine were used in the same manner as in
Example 179 to obtain the title compound.
[1027] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.59 (s, 1H), 8.09 (t,
1H), 8.02 (d, 1H), 7.45 (m, 1H), 7.10 (m, 2H), 6.89 (m, 1H), 6.58
(d, 1H), 5.44 (s, 2H), 2.47 (s, 3H)
Example 185: Synthesis of
2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,-
4]triazine
##STR00193##
[1029] (2-Methylphenyl)boronic acid as a starting material was used
in the same manner as in Example 178-2 and Example 178-3 to obtain
6-(chloromethyl)-2-(o-tolyl)imidazo[1,2-b][1,2,4]triazine. The
obtained 6-(chloromethyl)-2-(o-tolyl)imidazo[1,2-b][1,2,4]triazine
and 2-fluoro-4-hydroxypyridine were used in the same manner as in
Example 179 to obtain the title compound.
[1030] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.64 (s, 1H), 8.08 (d,
1H), 8.05 (d, 1H), 7.48 (t, 2H), 7.40 (m, 2H), 6.91 (m, 1H), 6.59
(s, 1H), 5.47 (s, 2H), 2.47 (s, 3H)
Example 186: Synthesis of
2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine
##STR00194##
[1032] [4-Fluoro-2-(trifluoromethyl)phenyl]boronic acid as a
starting material was used in the same manner as in Example 178-2
and Example 178-3 to obtain
6-(chloromethyl)-2-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-b][1,2-
,4]triazine. The obtained
6-(chloromethyl)-2-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-b][1,2-
,4]triazine and 2-hydroxypyridine were used in the same manner as
in Example 180 to obtain the title compound.
[1033] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.52 (s, 1H), 8.21 (d,
1H), 8.07 (s, 1H), 7.61 (m, 3H), 7.46 (m, 1H), 6.94 (m, 1H), 6.89
(d, 1H), 5.73 (s, 2H)
Example 187: Synthesis of
2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine
##STR00195##
[1035] (3-Fluoro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(3-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(3-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 2-hydroxypyridine were used in the same manner as in Example
180 to obtain the title compound.
[1036] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.78 (s, 1H), 8.41 (s,
1H), 8.22 (d, 1H), 7.76 (t, 1H), 7.44 (s, 2H), 7.40 (m, 1H), 7.03
(t, 1H), 6.91 (t, 1H), 5.55 (s, 2H), 2.30 (s, 3H)
Example 188: Synthesis of
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine
##STR00196##
[1038] (4-Fluoro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 2-hydroxypyridine were used in the same manner as in Example
180 to obtain the title compound.
[1039] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.77 (s, 1H), 8.39 (s,
1H), 8.22 (d, 1H), 7.76 (m, 1H), 7.64 (m, 1H), 7.30 (m, 1H), 7.24
(t, 1H), 7.03 (t, 1H), 6.91 (d, 1H), 5.55 (s, 2H), 2.43 (s, 3H)
Example 189: Synthesis of
2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2--
b][1,2,4]triazine
##STR00197##
[1041] [4-Chloro-2-(trifluoromethyl)phenyl]boronic acid as a
starting material was used in the same manner as in Example 178-2
and Example 178-3 to obtain
6-(chloromethyl)-2-[4-chloro-2-(trifluoromethyl)phenyl]imidazo[1,2-b][1,2-
,4]triazine. The obtained
6-(chloromethyl)-2-[4-chloro-2-(trifluoromethyl)phenyl]imidazo[1,2-b][1,2-
,4]triazine and 2-hydroxypyridine were used in the same manner as
in Example 180 to obtain the title compound.
[1042] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.51 (s, 1H), 8.21 (d,
1H), 8.06 (s, 1H), 7.87 (s, 1H), 7.73 (d, 1H), 7.63 (t, 1H), 7.53
(d, 1H), 6.94 (t, 1H), 6.88 (d, 1H), 5.72 (s, 2H)
Example 190: Synthesis of
2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine
##STR00198##
[1044] (4-Chloro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(4-chloro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(4-chloro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 2-hydroxypyridine were used in the same manner as in Example
180 to obtain the title compound.
[1045] 1H-NMR (CDCl.sub.3, 500 MHz) .delta. 8.55 (s, 1H), 8.22 (d,
1H), 8.07 (s, 1H), 7.65 (m, 1H), 7.41 (m, 3H), 6.95 (m, 1H), 6.89
(m, 1H), 5.72 (s, 2H), 2.45 (s, 3H)
Example 191: Synthesis of
2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]t-
riazine
##STR00199##
[1047] (4-Fluoro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 6-fluoropyridin-2-ol were used in the same manner as in
Example 180 to obtain the title compound.
[1048] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.78 (s, 1H), 8.42 (s,
1H), 7.93 (t, 1H), 7.65 (t, 1H), 7.30 (m, 1H), 7.24 (m, 1H), 6.87
(m, 1H), 6.77 (m, 1H), 5.50 (s, 2H), 2.42 (s, 3H)
Example 192: Synthesis of
2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-
-b][1,2,4]trazine
##STR00200##
[1050] (4-Fluoro-2-methyl-phenyl)boronic acid as a starting
material was used in the same manner as in Example 178-2 and
Example 178-3 to obtain
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e. The obtained
6-(chloromethyl)-2-(4-fluoro-2-methyl-phenyl)imidazo[1,2-b][1,2,4]triazin-
e and 5-fluoropyridin-2-ol were used in the same manner as in
Example 180 to obtain the title compound.
[1051] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.77 (s, 1H), 8.39 (s,
1H), 8.19 (s, 1H), 7.74 (m, 1H), 7.63 (m, 1H), 7.31 (m, 1H), 7.24
(m, 1H), 6.98 (m, 1H), 5.52 (s, 2H), 2.42 (s, 3H)
Example 193: Synthesis of
[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phen-
yl]methyl carbamate
##STR00201##
[1053]
[5-Fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol (100 mg, 0.27 mmol) obtained in Example 97 was
dissolved in dimethylformamide (5 ml), and 1,1'-carbonyldiimidazole
(88 mg, 0.54 mmol) was added thereto and agitated at room
temperature for 30 minutes. Ammonia water (5 ml) was added to this
solution and agitated at room temperature for 4 hours. Ethyl
acetate was added to the reaction solution and extracted. After
drying with anhydrous magnesium sulfate and filtration, the solvent
was concentrated under reduced pressure. Flash column
chromatography was carried out to obtain the title compound
(amount: 88 mg, yield: 80%).
[1054] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.00 (s, 1H), 8.55 (s,
1H), 7.94 (s, 1H), 7.49 (t, 1H), 7.36 (m, 2H), 7.09 (m, 4H), 6.70
(m, 2H), 5.25 (s, 2H), 4.94 (s, 2H), 3.32 (s, 3H)
Example 194: Synthesis of
[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl
carbamate
##STR00202##
[1056]
[5-Fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]m-
ethanol obtained in Example 25 was used in the same manner as in
Example 193 to obtain the title compound.
[1057] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.01 (s, 1H), 8.56 (s,
1H), 7.96 (s, 2H), 7.52 (m, 1H), 7.37 (m, 4H), 7.09 (m, 2H), 6.98
(m, 1H), 6.67 (m, 1H), 6.56 (m, 1H), 5.29 (s, 2H), 4.95 (s, 1H)
Example 195: Synthesis of
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl carbamate
##STR00203##
[1059]
[5-Fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phe-
nyl]methanol obtained in Example 135 was used in the same manner as
in Example 193 to obtain the title compound.
[1060] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.99 (s, 1H), 8.55 (s,
1H), 8.22 (d, 1H), 7.91 (s, 1H), 7.77 (m, 1H), 7.50 (m, 1H), 7.37
(m, 2H), 7.04 (m, 1H), 6.92 (m, 1H), 6.68 (m, 1H), 6.57 (m, 1H),
5.52 (s, 2H), 4.95 (s, 2H)
Example 196: Synthesis of
[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]me-
thyl acetate
##STR00204##
[1062]
[5-Fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phe-
nyl]methanol (100 mg, 0.29 mmol) obtained in Example 135 was
dissolved in dimethylformamide (5 ml), and trimethylamine (58 mg,
0.57 mmol) and acetyl chloride (31 mg, 0.4 mmol) were added thereto
at 0.degree. C. and agitated at room temperature for 2 hours. After
the reaction termination, water and ethyl acetate were added to the
reaction solution and extracted. After drying ethyl acetate
solution with anhydrous magnesium sulfate and filtration, the
solvent was concentrated under reduced pressure. Flash column
chromatography was carried out to obtain the title compound
(amount: 57 mg, yield: 50%).
[1063] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.96 (s, 1H), 8.51 (s,
1H), 8.20 (t, 1H), 7.90 (s, 1H), 7.73 (t, 1H), 7.48 (t, 1H), 7.41
(m, 1H), 7.36 (m, 1H), 7.01 (t, 1H), 6.89 (d, 1H), 5.49 (s, 2H),
5.03 (s, 2H), 1.98 (s, 3H)
Example 197: Synthesis of
6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1-
,2-a]pyrimidine
##STR00205##
[1065]
[5-Fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol (100 mg, 0.27 mmol) obtained in Example 97 was
dissolved in dimethylformamide (5 ml), and trimethylamine (58 mg,
0.57 mmol) and methanesulfonyl chloride (65 mg, 0.57 mmol) were
added thereto at 0.degree. C. and agitated at room temperature for
2 hours. Ethyl acetate and water were added to the reaction
solution and extracted. The ethyl acetate solution was dried with
anhydrous magnesium sulfate and filtrated, and the solvent was
concentrated under reduced pressure. Flash column chromatography
was carried out to obtain the title compound (amount: 73 mg, yield:
70%).
[1066] 1H-NMR (DMSO-d6, 500 MHz) .delta. 9.00 (s, 1H), 8.54 (s,
1H), 7.95 (s, 1H), 7.50 (m, 2H), 7.38 (m, 1H), 7.12 (m, 4H), 5.24
(s, 2H), 4.74 (s, 2H)
Example 198: Synthesis of
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]p-
yrimidine
##STR00206##
[1068]
[5-Fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phe-
nyl]methanol (100 mg, 0.29 mmol) obtained in Example 135 was
dissolved in methylene chloride (10 ml), and diethylaminosulfur
trifluoride (70 mg, 0.44 mmol) was added thereto at 0.degree. C.
and agitated at room temperature for 30 minutes. Saturated ammonium
chloride aqueous solution was added to the reaction solution and
extracted by the use of methylene chloride and water. The methylene
chloride extract solution was dried with anhydrous magnesium
sulfate and filtrated, and the solvent was concentrated under
reduced pressure. Flash column chromatography was carried out to
obtain the title compound (amount: 92 mg, yield: 90%).
[1069] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.97 (s, 1H), 8.52 (s,
1H), 8.21 (m, 1H), 7.93 (s, 1H), 7.77 (m, 1H), 7.54 (m, 2H), 7.45
(m, 1H), 7.05 (m, 1H), 6.89 (m, 1H), 5.51 (s, 2H), 5.48 (s, 1H),
5.39 (s, 1H)
Example 199: Synthesis of
6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,-
2-a]pyrimidine
##STR00207##
[1071]
[5-Fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-y-
l]phenyl]methanol obtained in Example 97 as a starting material was
used in the same manner as in Example 198 to obtain the title
compound.
[1072] 1H-NMR (DMSO-d6, 500 MHz) .delta. 8.98 (s, 1H), 8.54 (s,
1H), 7.97 (s, 1H), 7.57 (m, 2H), 7.44 (m, 1H), 7.12 (m, 4H), 5.49
(s, 1H), 5.39 (s, 1H), 5.26 (s, 2H)
Experimental Example: Pharmacological Activity Test
[1073] Efficacy as a positive allosteric modulator (PAM) of mGluR5
of the compounds of the Examples was tested as follows:
[1074] Calcium Influx Assay Based on Fluorescence
[1075] Ca.sup.2+ (calcium) influx assay is an experiment for
measuring the activity of a positive allosteric modulator of mGluR5
receptor in which human mGluR5 receptor-overexpressed HEK293 cell
line is used. The day before the experiment, cells were prepared in
a cell culture medium (DMEM, 5% FBS) with the density of
80,000/well, and 100 .mu.l of cells were dispensed into each well
of a poly-D-lysine-coated 96-well plate. Cells were incubated in a
5% CO.sub.2, 37.degree. C. incubator. The next day, the cell
culture medium was removed from the plate, and 100 .mu.l of
1.times. Fluo-4 calcium indicator diluted with a buffer (1.times.
Hank's balanced salt solution, 20 mM HEPES, 2.5 mM probenecid) were
added to each well and incubated at 37.degree. C. for 1 hour. The
compound stock solutions were prepared in 100% DMSO, and the
compounds were serially diluted with a 1/4 dilution to 6 or 7
concentrations (final concentration was 10 .mu.M to 10 nM). The
diluted compound solutions were added to the plate with 0.1 to 0.2%
of final DMSO concentration. 1 hour after the addition of Fluo-4
calcium indicator, L-glutamate (EC.sub.20 concentration) and the
test compound solutions were added to the plate, and Ca.sup.2+
reaction was then measured by FLIPR at room temperature. The
activity of the compounds was standardized on the basis of the
results of maximum value-minimum value of fluorescent reaction, and
the activity value was calculated on the basis that no activity on
glutamate EC.sub.20 is 0% and the reaction to glutamate maximum
value is 100%.
[1076] In the same manner as in the above assay, the efficacy of
the test compounds as a human mGluR5 positive allosteric modulator
was calculated to EC.sub.50 and is represented in Table 1 (+:
500-1,000 nM, ++: 100-500 nM, +++: 100 nM or less).
TABLE-US-00001 TABLE 1 Human mGluR5 Example PAM EC.sub.50 (nM) 1 ++
2 ++ 3 +++ 4 ++ 5 +++ 6 +++ 7 ++ 8 ++ 9 + 10 ++ 11 ++ 12 + 13 + 14
++ 15 ++ 16 + 17 + 18 ++ 19 + 20 ++ 21 + 22 + 23 ++ 24 ++ 25 +++ 26
++ 27 ++ 28 + 29 ++ 30 + 31 ++ 32 ++ 33 ++ 34 ++ 35 ++ 36 ++ 37 +
38 ++ 39 ++ 40 ++ 41 ++ 42 + 43 ++ 44 ++ 45 ++ 46 ++ 47 ++ 48 ++ 49
+ 50 + 51 ++ 52 ++ 53 ++ 54 ++ 55 ++ 56 ++ 57 ++ 58 ++ 59 ++ 60 ++
61 + 62 + 63 ++ 64 + 65 ++ 66 ++ 67 +++ 68 ++ 69 ++ 70 ++ 71 ++ 72
++ 73 + 74 ++ 75 ++ 76 ++ 77 ++ 78 ++ 79 ++ 80 +++ 81 ++ 82 ++ 83
++ 84 + 85 ++ 86 ++ 87 + 88 ++ 89 + 90 ++ 91 +++ 92 ++ 93 ++ 94 ++
95 ++ 96 ++ 97 ++ 98 ++ 99 + 100 + 101 ++ 102 ++ 103 ++ 104 ++ 105
++ 106 ++ 107 + 108 + 109 ++ 110 ++ 111 ++ 112 ++ 113 ++ 114 ++ 115
++ 116 +++ 117 ++ 118 ++ 119 ++ 120 ++ 121 ++ 122 + 123 ++ 124 ++
125 ++ 126 ++ 127 ++ 128 + 129 + 130 ++ 131 ++ 132 +++ 133 + 134 ++
135 ++ 136 + 137 ++ 138 ++ 139 + 140 ++ 141 ++ 142 ++ 143 + 144 +
145 ++ 146 + 147 + 148 + 149 ++ 150 + 151 ++ 152 ++ 153 ++ 154 ++
155 ++ 156 ++ 157 + 158 ++ 159 + 160 + 161 ++ 162 +++ 163 ++ 164 ++
165 ++ 166 ++ 167 ++ 168 +++ 169 ++ 170 ++ 171 ++ 172 ++ 173 + 174
++ 175 + 176 ++ 177 + 178 ++ 179 ++ 180 ++ 181 + 182 ++ 183 ++ 184
++ 185 ++ 186 ++ 187 ++ 188 +++ 189 + 190 ++ 191 + 192 ++ 193 ++
194 ++ 195 ++ 196 ++ 197 ++ 198 +++ 199 ++
* * * * *