JPS5818391A - Substituted thiazolo(3,2-a)pyrimidines and manufacture - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to substituted thiazolo[3,2-a)pyrimidines, processes for their preparation, and pharmaceutical compositions containing them. The present invention provides a compound having the following general formula (I) 21-, where A is a bond, thereby forming a bond between the α- and β-carbon atoms. The number of double bonds to be formed is A is 20H.
2-group thereby forming a cyclopropane ring containing α- and β-carbon atoms, each of R1 and R2 being independently a) a hydrogen or halogen atom, b) 01-04 alkyl, cyano or trifluoromethyl; C) chenyl, pyridyl, biphenyl or naphthyl; d) unsubstituted or halogen; C1-C4 alkyl; hydroxy; e) a phenyl group substituted by 1 to 3 substituents selected from the group consisting of nitro, aminoformylamino and C2-C8 alkanoylamino; e) substituted by 1 or 2 01-C4 alkylenedioxy groups; represents a phenyl group (wherein the oxygen atom is bonded to two adjacent carbon atoms of the phenyl ring), or independently represents a hydrogen atom or a 01-C4 argyl group, and R3 is hydrogen or halogen atom, b')', c, ~C4 alkyl, C/) hydroxy, formyluo+7 or 02~C
B represents alkanoyloxy, or d') 01-C4 alkoxy or 05-C'4 alkenyloxy, R4 is a pyridyl group which may be unsubstituted or substituted by 01-04 alkyl, 5 alkyl (represents a group), and each of R8 is independently a hydrogen or halogen atom, a hibioxy group, an 01-C6 alkoxy group that is unsubstituted or substituted by a 01-C4 sialgylamino group, a 01-C4 alkyl group , formyloxy or 0
2-C8 alkanoyl group, -NO2 group is -<
R'p group (in the formula, R9 and R1'O are each Ftl.

independently represents a hydrogen atom, a 01-04 alkyl group, formyl or a 02-C8 alkanoyl group], or may be unsubstituted or substituted by a 1-a 4 alkyl represents a thiazolyl group.

The compounds of the invention also include pharmaceutically acceptable salts of compounds of formula (I), metabolites and metabolic precursors of compounds of formula (I), and all possible isomers (e.g., cis or trans). isomers and optical isomers) and mixtures thereof (R4 is as defined above) are in the trans configuration. Alkyl, alkoxy, alkenyloxy, alkanoyl and alkanoyloxy groups can be branched or straight-chain. When R1 and/or R2 are a 1-a 4 alkyl groups, these are 01-
C2 alkyl groups are preferred.

When R1 and/or R2 is a 25-substituted phenyl ring as described above, the phenyl ring is chlorine, fluorine, methyl, methoxy, hydroxy, C1-C2
Preferably it is substituted with one or two substituents selected from the group consisting of alkylenedioxy and amino.

When one or more of R1, R2 and R5 are halogen atoms, they are preferably chlorine or bromine.

When R3 is 01-C4 alkoxy, it is preferably methoxy or ethoxy.

When R3 is 01-C4 alkyl, it is preferably methyl, ethyl or propyl.

When one or both of R9 and Rj is an 02-C8 alkanoyl group, for example acetyl, propionyl, butyryl, valeryl and invaleryl, preferably acetyl and propionyl.

When R4 is substituted pyridyl, preferably -26- Substituted by a thyl group.

When R4 is substituted thiazolyl, it is preferably substituted by a methyl group.

When R5 is an 01-C4 alkyl group, it is preferably a methyl or ethyl group.

one or more of R3, R6, R7 and R8 is 0
When representing a 2-C8 alkanoyloxy group, for example acetoxy, propionyloxy and butyryloxy,
Preferably it is acetoxy.

R' and R# are preferably dihydrogen or 01-C2 alkyl groups.

R,! , one or more of R7 and R4 is 01-
When it is a C6 alkoxy group, it is preferably a methoxy or ethoxy group.

One or more of R6, R7 and R8 is 01-0
When it is a 4-alkyl group, it is preferably a methyl group.

When one or more of R6, R7 and R8 is a halogen atom, it is preferably chlorine, fluorine or iodine.

In a preferred compound of the present invention, A is the above-mentioned Toosho;
R1 is hydrogen, 01-C2 alkyl, trifluoromethyl, carboxymethyl, pyridyl, biphenyl, naphthyl or phenyl (the phenyl being unsubstituted or substituted as described above); R2 is hydrogen; chlorine, bromine, 01-02 alkyl, cyanide or phenyl (which is unsubstituted or substituted as described above) and R3 is hydrogen, chlorine, bromine, 0
1-C3 alkyl or auto-C2 alkoxy, and R4 is a' unsubstituted or pyridyl group substituted by a methyl group, b#s) unsubstituted or auto-C2 alkyl, chlorine, iodine, hydroxy s
a phenyl group substituted with one or two substituents selected from the group consisting of 01-03 alkoxy, amino, acetylamino and acetoxy; Compounds of formula (1) comprising a substituted thiazolyl group and pharmaceutically acceptable salts thereof.

Examples of pharmaceutically acceptable salts are salts with inorganic bases such as sodium, potassium, calcium and aluminum hydroxides or lysine, triethylamine, triethanolamine, dibenzylamine, methylvanzylamine, :) ( 2-ethylhexyl)amine, hybaridine, N-ethylpilysine, N,N-diethylaminoethylamine, N-ethylmorpholine, β-7enethylaξ
salts with organic bases such as N, N-benzyl-β-phenethylamine, N-benzyl-N,N-') methylamine and other acceptable organic amines, and inorganic acids such as hydrochloric acid, 29-hydrogen bromide. acids, salts with sulfuric and nitric acids and organic acids such as citric acid, tartaric acid, maleic acid, malic acid, fumaric acid,
Salts with methanesulfonic acid and ethanesulfonic acid.

Examples of particularly preferred compounds of the present invention are as follows.

7-trans-[2-(3-pyridyl)-ethynyl2-5H-thiazolo(3,2-a)pyrimidin-5-one, 7-trans-(2-(4-methyl-phenyl)-ethynyl2-5H-thiazolo[ 3,2-a) Pyrimidine-5
-one, 6-medoxy7-trans-(2-(3-pyridyl)
-ethynyl2-5H-thiazolo(3,2-a)pyrimidin-5-one, 2-cyano-7-trans-(2-(3-pyridyl)-
Ethynyl2-5H-thiazolo(3ez-a)30-pyrimidin-5-one, 2-chloro-7-trans-[2-(3-pyridyl)-
Ethynyl-5H-thiazolo[5,2-a)pyrimidin-5-one, 2-chloro-7-trans-[:2-(2-methyl-5
-thiazolyl)-ethynyl]-5H-thiazolo[3,2
-a) Pyrimidin-5-one, 2-chloro-6-medoxy7-trans-(2-(3-pyridyl)-ethynyl)-5H-thiazolo[3,2-a]]pyrimidin-5-one 2-chloro- 6-methyl-7-trans-(2
-(3-pyridyl)-ethynyl')-5H-thiazolo[
3,2-a) Pyrimidin-5-one, 6-methyl-7
-trans-[2-(3-pyridyl)-ethynyl25
H-thiazolo(S,2-a)pyrimidin-5-one, 3,6-dimethyl-7-trans-[2-(3-pyridyl)-ethynyl)-51-thiazolo[3,2-a)pyrimidine-5- on, 2.3.6-)limethyl-7-
trans-[2-(3-pyridyl)-ethynyl2-5H
-thiazolo[3,2-a)pyrimidin-5-one, 6
-Methyl-2-phenyl-7-trans-[2-(3-
pyridyl)-ethynyl)-5H-thiazolo[3,2-a
) pyrimidin-5-one, 6-nityl-7-trans-(2-(3-pyridyl)-ethynyl-5H-thiazolo(3,2-IL)pyrimidin-5-one, 6-methyl-7-trans-(2- (2-pyridyl)-
Ethynyl-5H-thiazolo(3,2-a]pyrimidin-5-one, 6-methyl-7-, trans-(2-(6-methyl-2
-pyridyl)-ethynyl2-5H-thiazolo[3,2-
a) Pyrimidin-5-one, 6-methyl-7-trans-[2-(4-methyl-phenyl)-ethynyl)-5H
-thiazolo[3,2-a'J pyrimidin-5-one,
6-Methyl-7-trans-[2-(6-methyl-2-
pyridyl)-cyclozolovir')-5H-thiazolo[3
, 2-a) pyrimidin-5-one.

6-methyl-7-trans-(2-(2-pyridyl)-
cyclopropyl]-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-methyl-7-trans-[2
-(3-pyridyl)-cyclopropyl)-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-chloro-7-trans-(2-phenyl-ethynyl)-5H-
Thiazolo[3,2-a)pyrimidin-5-one, 2.6-:)chloro-7-trans-[2-(3-pyridyl)-ethynyl2-5H-thiazolo33-(3,2-a)pyrimidine- 5-one, 6-chloro-
7-trans-(2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a:1pyrimidin-5-one, 6-chloro-6-methyl-7-trans-[2-(3-
pyridyl)-ethynyl2-5H-thiazoloC3,2-a
) pyrimidin-5-one, 6-chloro-2,3-dimethyl-7-trans-[2-(3-pyridyl)-ethynyl2-5H-thiazolo[3,2-& )pyrimidine-5
-one, 6-chloro-5-trifluoromethyl-7-trans-(2-(3-pyridyl)-ethynyl2-5H-
ThiazoloC3,2-a) pyrimidin-5-one, 6-chloro-3-phenyl-7-trans-(2-(3
-pyridyl)-ethynyl:]-]5H-thiazolo 5,
2-a) Pyrimidin-5-one, 34-6-chloro-3-(4-fluoro-phenyl)-7-trans-[2-(3-pyridyl)-denyl]
-'5H-'thiazolo[S,2-a)pyrimidin-5-one, 6-chloro-3-(4-chloroenyl)-7-trans-(2-(3-pyridyl)-ethynylcy5H- Thiazolo(!+,2-a)pyrimidin-5-one, 6-chloro-3-(4-methyl-phenyl)nia-trans-(2-(3-pyridyl)-ethynylcy5H-thiazoloC3+2-a') Pyrimidin-5-one, 6-chloro-3-(2-methoxy-phenyl)-7-trans-(2-(3-pyridyl)-ethynylcy5H-
Thiazolo[3,2-a)pyrimidin-5-one, 6-chloro-3-(3-methoxyphenyl)-7-trans-C2-(3-pyridyl)-ethynylcy5H-thiazoloC3,2-a)pyrimidine -5-one, 6-chloro-3-(4-methoxyphenyl)-7-trans-[2-(3-pyridyl)-ethynylcy5H-thiazolo(3,2-a)pyrimidin-5-one, 6- Chlor-3-(2-chenyl)-7”-trans-
t-2-(3-pyridyl)-ethynyl]-5H-thiazo0 [: 3.2- = )pyrimyrin-5-one, 6-chloro-3-(2-pyridyl)-7-) lance-(
2-(s-pyridyl)-ethynylcy5H-thiazolo[
3,2-a]]pyrimidin-5-one ・(6-chloro-3-(3-pyridyl)-7-trans-c
2-<3-pyridyl)-ethynylcy5H-thiazolo[3,2-a)pyrimidin-5-one, 6-chloro-3-(4-pyridyl)-7-1-lans-[2-(3-pyridyl) )-ethynylcy5H-thiazolo[3,2-a ]]pyrimidin-5-one 6-chloro-7-trans-[2-(3-pyridyl)-
ethynyl]-5-oxo5H-thiazolo[3,2-a
]] Pyrimidine-3-acetic acid 3-(4-amino-phenyl)-7-) lance-(2-('3-pyridyl)-ethynylcy5H-thiazolo(3,2-a)pyrimidine-
5-one, 3-phenyl-7-trans-[2-(3-
pyridyl)-ethynylcy5H-thiazolo[3,2-a
, 1pyrimidin-5-one, 3-(4-fluorophenyl)-7-trans-(2
'-(3-pyridyl)-ethynyl]-5H37- -thiazolo[3',2- a )pyrimidin-5-one, ro-(4-chloro-phenyl)-7L trans-[2
-(3-pyridyl)-ethynyl-5H-thiazolo[3
,2-a ]]pyrimidin-5-one 3-(4-methyl-phenyl)-7-1 lance-[2-(!l-pyridyl)-ethynyl2-5H-thiazoloshi3.2-a) pyrimidine-5- On, ro-(3-methoxy-phenyl)
-7-') trans-[2-<3-pyridyl)-thenyl]-5H-thiazolo[3,2-a]]pyrimidin-5-one 6-(4-methoxy-phenyl>-74 trans-[2
-(3-pyridyl)-ethynylcy5H-thiazolo[3
,2-a) Pyrimidin-5-one, 3-(3,4-dimethoyacyphenyl)-7-trans-C2-<5-pyridyl)-ethynyl]38- -5H-thiazoo [3,2- a) Pyrimidine-5-
on, 3-(3,4-ethylenedioxy-phenyl)-7-
trans-[2-(3-pyridyl)-ethynylcy 5H
-thiazolo[:3,2-a:]]pyrimidine-5
-one-(4-biphenylyl)-7-') lance-[2
-(3-pyridyl)-ethynyl-5H-thiazolo[3,
2-a ]]pyrimidine-5-ole3-(2-naphthyl)-7-) lance-[2-(3-pyridyl)-ethynyl-5H-thiazolo['3.2'-a]]pyrimidin-5-one 3-(2-pyridyl)17-) lance-
[2-(5-pyridyl)-ethynylcy 5H-thiazolo[3,2-a) pyrimidisilyl-5-one, 3-(3-pyridyl)-7-) lance-[2-(3-pyridyl)-ethynylcy 5H- Thiazolo[3,2-a]]pyrimidin-5-one 5-(4-pyridyl)-7-trans-[
2-(3-pyridyl)-ethynylcy 5H-thiazolo[
3,2-a) Pyrimidin-5-one, 2-methyl-3
-phenyl-7-trans-[2-(3-pyridyl)-
ethynyl)-5H-thiazolo[3,2-a]]pyrimidin-5-one 3-(4-N-acetyl-amino-phenyl)-7-trans-[2-(3-pyridyl)-ethynylcy5H-thiazolo[ 3,2-a) Pyrimidine-
5-one and 7-trans-[2-(3-pyridyl)-ethynyl)-
3-(2-chenyl)-5H-thiazolo(3,2-a
) Pyrimidin-5-ones and pharmaceutically acceptable salts thereof.

The compound of formula (1) can be obtained by any of the methods a) to d) below. That is, a) formula (■) (in the formula, R1, R2 and R6 are as described above)
or a salt thereof is reacted with an aldehyde of the formula (■) (in the formula, the person is a bond) ), or b) a compound of the formula (goods) in which R1, R2 and R5 are as defined above;
Q is aryl or C1-C6 alkyl and Y
←) represents an acid salt ion) is reacted with an aldehyde of the above formula (g) to obtain a compound of formula (I) (wherein A is a bond), or 41-C) a compound of formula (r) ) (wherein R1, R2 and R5 are as described above)
Compound 1 of the formula (b) ('')l-) (b) R4-OH2-P(Q, )5 (wherein R4s'Q and Y(-) are as described above) or Formula (A) (wherein, R4 is as described above and R11 is 01
~04 alkyl) to obtain in each case a compound of formula (■) in which A is a bond, or d) a compound of formula (■) 42- (wherein R1 , R2, R3 and R4 are as described above) by adding cyclobromone to form the formula (1) (
in which A is a -CH2- group and optionally converting the compound of formula (I) into other compounds of formula (I) and/or optionally converting the compound of formula (1) into a pharmaceutical compound. and/or optionally converting the salt to the free compound and/or optionally resolving the isomer mixture into the qt-isomers.

Acid anion Y in compounds of formulas (trans) and (b)
(-) is, for example, an acid anion derived from hydrologonic acid, preferably an acid anion derived from hydrochloric acid or hydrobromic acid.

When Q in the compounds of formulas (II) and (II) is aryl, it is preferably phenyl and Q is 0
When it is 1-C6 alkyl, it is preferably ethyl.

The reaction of the compound of Ql) or a salt thereof with the aldehyde of formula @) is preferably carried out in the presence of a basic condensing agent such as sodium ethoxide, sodium methoxide, sodium hydride, sodium amide or sodium hydroxide. It is preferably carried out at a temperature of about 0<0>C to 120<0>C in a solvent selected from the group consisting of, for example, methanol, ethanol, impropatol, dioxane, water and mixtures thereof.

The reaction between the compound of formula 2 and the aldehyde of formula (g) and the reaction of the compound of formula (b) with the compound of formula (b) or the compound of formula Organic solvents such as sulfoxide, dimethylformamide, dimethylacetamide or mixtures thereof at about 0°C
Treatment with dimethylsulfinyl carbanion or a base such as sodium methoxide or sodium hydride or potassium tert-butoxide or with an alkyllithium derivative preferably methyllithium butyllithium or phenyllithium at a temperature of 4100°C. It can be implemented by

The cyclobromone compound of 0 to the formula is preferably carried out in an inert organic solvent selected from the group consisting of, for example, dimethylformamide, dimethyl sulfoxide, dioxane and mixtures thereof and operated at a temperature of about 50°C to about 50°C. For example, dimethylsulfoxonium methylide (e.g. r:
r: ahθm.

Soc, J 1967, p. 2495). Formula (2)
Preferably 1 to 3 mol, especially 1 to 3 mol per mol of compound of
1.5 moles of reagent are used.

Compounds of formula (1) can be converted into other compounds of formula (1) by known methods as described above. For example, free hydroxy groups are preferably removed in a solvent selected from the group consisting of, for example, methanol, ethanol, dioxane, acetone, dimethylformamide, hexamethylphosphoric triamide, tetrahydrofuran, water and mixtures thereof, preferably at a temperature of about 150°C to about 150°C. , NaOH, KOH, Na2
00g, NaH.

NaNH2, sodium methoxide, x2ao5t
Alternatively, it can be etherified by reaction with a suitable alkyl halide in the presence of a base such as sodium ethoxide.

Furthermore, etherified hydroxy groups can be converted to free hydroxy groups, for example, by treatment with pyridine hydrochloride or with strong acids such as HCl, HBr or Lewis acids such as AβCλ3 or BBr5.

Formula (■) [In the formula, R1 and/or R2 are independently 46
- tH-Coo 01-04 alkyl group (where 1' is as defined above)] is preferably operated at temperatures from room temperature to about 150°C in the presence of an organic solvent such as acetic acid or dioxane. and can be converted into a compound of formula (■) (in which R1 and/or R1) by hydrolysis, for example, by acid hydrolysis using Hen, HBr% HI in water.

The same reaction can also be carried out, for example, by treatment with lithium bromide in dimethylformamide at temperatures above 50°C.

Compounds of formula (I), in which R1 and/or R2 independently represent Other compounds of formula (I) (wherein R1 and/or R
2 can be converted into a seed compound.

Alternatively, the esterification of the compound of formula (I) in which R1 and W or For example, the desired acid halides such as oxalyl chloride, thionyl chloride,
The carboxylic acid is converted into the corresponding halocarbonyl derivative, preferably a chlorocarbonyl derivative, by reaction with po13, poJ25 or poai3, and then the resulting halocarbonyl visiting conductor is benzene, toluene, xylene, dioxane, dichloroethane, in an inert solvent such as methylene chloride or tetrahydrofuran at a temperature of from about 0°C to about 120°C, preferably in the presence of a base such as triethylamine or pyridine.
This can be accomplished by reacting H (wherein R' is an 01-C4 alkyl group) with a suitable alcohol.

A hydroxy group or an amino group as a substituent on the phenyl ring in a compound of formula (1) can be converted into an 02-C8 alkanoyloxy or an 02-C8 alkanoylamino group, respectively, using known conventional methods in organic chemistry.

The nitro group as a substituent on the phenyl ring in the compound of formula (1) can be replaced with, for example, 49-concentrated hydrochloric acid at a temperature of from room temperature to about 100°C using an organic co-solvent such as acetic acid, dioxane, tetrahydrofuran, if necessary. can be converted to an amino group by treatment with stannous chloride in

The salt formation which may be carried out in the case of the compounds of formula (1) as well as the conversion of the salts into the free compounds and the resolution of isomer mixtures into single isomers can also be carried out by customary methods.

For example, resolution of an optical isomer mixture into individual isomers can be carried out by salt formation with an optically active base followed by fractional crystallization.

Thus, resolution of geometric isomer mixtures can be carried out, for example, by fractional crystallization.

The compound of the formula (■) (in which R3 is different from hydroxy and bromine) is, for example, a compound of the formula lead (in the formula, R1 and R2 are as described above) or a salt thereof. in which R3 is as defined above but unlike hydroxy and bromine and R13 is preferably 01-C
4 alkyl).

The reaction between the compound of formula (2) and the compound of formula (a) can be carried out, for example, by polyphosphoric acid (polyphosphoric acid is a mixture of approximately equal weights of PO4 and P2O5), sulfuric acid, methanesulfone e' It can be conveniently carried out in the presence of an acid condensing agent such as t*Kel-)luenesulfonic acid at a temperature of about 50<0>C to 150<0>C. The reaction is dimethylformamide, dimethylacetamide, vinegar L9Je, benzene, toluene,
xylene, ethylene glycol monomethymethether,
It can be carried out in an organic solvent such as dichloroethane or without the use of a solvent.

Alternatively, a compound of formula (II) (wherein R3 is alkoxy or alkenyloxy) can be prepared, for example, by a compound of formula (2) (wherein R1 and R2 are as defined above) in acetone, dioxane, dimethylformamide at a temperature from room temperature to about 120°C in the presence of a basic reagent such as sodium hydride, sodium methoxide, sodium or potassium carbonate in a solvent such as
4-alkyl or C3-C4 alkenyl halogenation
It can be prepared by reacting with chloride, preferably chloride, bromide or iodite.

Compounds of the formula (wherein R3 is halogen, e.g. bromine or chlorine) can be prepared by, for example, 2ω) (wherein R3 is hydrogen) in a solvent such as benzene or carbon tetrachloride at 20°C to It can be obtained by reacting with a suitable rosuccinimide, such as N-bromsuccinimide or 5o2c, Q2, operating at a temperature of about 100 DEG C.

The compound of 2ω is a compound of the formula x+b (wherein Y is a group convertible to the above-mentioned anion Y(-), and R1, R2 and R3 are as described above) in benzene, toluene, xylene or ( It is particularly prepared by reacting with P(Q,)5 (where Q is 9 as above) in a solvent such as acetonitrile at temperatures from room temperature to reflux temperature.

The compound of formula (V) is, for example, a compound of formula (Xlll)〇53- (wherein R1, R2 and R3 are as defined above) in a solvent such as benzene, toluene or dimethyl sulfoxide at 0°C to 50°C. It can be prepared by oxidation with dimethyl sulfoxide in the presence of dicyclohexylcarbodiimide and phosphoric acid or pyri, di-ram trifluoroacetate at a temperature of 0.degree. C. [Moffat reaction].

Alternatively, compounds of formula (V) may be of formula CX+V)
(In the formula, R1, R2 and R3 are as described above, and R14 is a halogen, especially chlorine, odor or hydrogen.
It can be prepared by hydrolyzing a compound (representing a 6-alkoxy group). Hydrolysis of a compound of formula ω is carried out at room temperature to about
HOI, HBr, HI, H2SO at a temperature of 20 °C
This can be carried out by treatment with an aqueous mineral acid such as 4.

Compounds of formula S can be prepared, for example, by reacting a compound of formula (If) with an aldehyde of formula 41 [) using the same experimental conditions as described above.

For example, when a compound of formula (XV) (wherein R1 and R2 are as described above and R15 represents formyl or f size 0.+ to C8 alkanoyl group) is hydrolyzed, , and 1 make it more ff+4.

Hydrolysis can be carried out, for example, in an aqueous medium in the presence of an organic co-solvent such as dioxane, acetone, methanol, ethanol, tetrahydrofuran, dimethylformamide at room temperature to reflux temperature with NaHCO2, KHC! 03,
Na2003. 2003, bases such as NaOH, KOH or HO2, HBr, HI.

This can be carried out by treatment with mineral acids such as H2SO4, a5po4.

The compound of 2〇lll1 (wherein Y is halogen and R3 is hydrogen) can be prepared, for example, by the same experiment as described above for the reaction of a compound of formula □□□ or a salt thereof with a compound of formula ω and a compound of 2ω. Expression (XVI) using the condition 000Rj 5 ? H2(XVI) in which R13 is as defined above and Y represents a halogen atom, preferably chlorine.

A compound of formula (6) (wherein R5 is different from hydrogen and Y is a halogen, e.g. N-halosuccinimide, preferably 7 N, in a solvent such as a,, ap 4 at room temperature to reflux temperature
- can be prepared by reacting with bromsuccinimide.

Alternatively, a compound of formula (Xl (in which R3 is chlorine or bromine)) can be prepared by operating a compound of formula (Xl (in which R3 is chlorine or bromine) at a temperature of 0°C to 100°C, e.g. 5o20 as a solvent. (1,) using acQ4 or dichloroethane in the reaction with pyridinium bromide perbromide, pyridine in the reaction with pyridinium bromide perbromide and benzene in the reaction with halosuccinimide, 57- can be prepared by reacting with a suitable halogenating agent such as

A compound of formula (XII[) can be, for example, a compound of ⑐〇@ (wherein Y is a readily leaving group such as an or Br) reacted with potassium or sodium acetate in dimethylformamide at room temperature to 100°C, and thus The corresponding acetoxy derivatives can be prepared by hydrolysis to the corresponding alcohols, for example by treating the extract with 37% Heμ in dioxane at room temperature to reflux temperature.

For example, a compound of formula (A) may be prepared at 50°C to about 170°C, preferably in an inert solvent such as dioxane, toluene, xylene, dimethylformamide, dimethylacetamide, or without the use of a solvent. 20℃～
At a temperature of about 150°C, the formula ■ 58-C00Rj :5 1 (wherein R3, R13 and R14 are as described above and R16 is amino and 01-c6 alkoximata represents tri(01-G+1)alkylsilyloxy )
can be prepared by reacting with a compound of

The compound of formula (XV) is a compound of formula
Xvll) 00R13 (wherein R15 and R15 are as defined above).

The reaction of Ofuna's compound with the formula (leg compound) is, for example, polyphosphoric acid (polyphosphoric acid means a mixture of approximately equal weights of 99% H3PO4 and p2o5), sulfuric acid, methanesulfonic acid or Rp-h luenesulfonic acid. The reaction may be carried out preferably at a temperature of about 50°C to 150°C in the presence of an acid binder such as dimethylformamide, dimethylacetamide, benzene, toluene, xylene, ethylene glycol monomethyl ether or dichloroethane. It is carried out in an organic solution ζλ, but it can also be carried out in the absence of a solvent.

The compounds of ■, lead, ■, @1) and (Shu) to 200% are known compounds and may be prepared by conventional methods. In some cases they are commercially available materials.

The compounds of the invention are active on the gastrointestinal system.

In particular, they have anti-ulcerogenic and gastric secretion-inhibiting effects and are therefore useful, for example, in the prevention and treatment of peptic ulcers, such as duodenal ulcers, gastric ulcers and externally erosive ulcers, and in the inhibition of gastric acid secretion. The compounds of the invention are also useful in reducing undesirable gastrointestinal side effects resulting from systemic administration of anti-inflammatory prostaglandin synthase inhibitors and may therefore be used in combination with these for this purpose. .

The anti-ulcerogenic activity of the compounds of the invention can be demonstrated by, for example, BOnfil
Mr. S et al.'s method [rTherapieJ Vol. 5 No. 1096
(1960), “Jap, J. Pharma.
aJ Vol. 43, p. 5 (1945)] by the fact that they are active in the rat restraint ulcer inhibition test by K. Six Sprague-Dawley male rats (body weight 100-12(1)) fasted for 24 hours were used in the experiment. A square flexible small mesh wire mesh was used for immobilization. After 4 hours of immobilization, the rats were sacrificed, their stomachs were removed and the lesions were calculated under a dissecting microscope.The test compound was administered orally (p-+) 1 hour before immobilization. The table shows, for example, the approximate F!D5Q values of anti-ulcerogenic activity obtained in the above test in rats after oral administration for two compounds of the invention.

Table 1 Compounds of the invention can also be prepared, for example, by the method of H. 8hay et al. [
[Gaatroenter, J Vol. 43, p. 5 (19
45)] in suppressing gastric secretion in rats, 62
- They also have an inhibitory effect on gastric juice secretion, as shown by the fact that they are active after intraduodenal administration. The inhibitory effect on gastric juice secretion was evaluated using the pylorus ligation technique in rats. 6 male spray gootle rats (weight 110-130
F) was used per group. Twenty-four hours before the start of the test, rats were removed from food but provided only water. On the day of surgery, the pylorus was ligated under light ether anesthesia, and the round compound was injected into the duodenum (1, a, ) at the time of ligation. Four hours after ligation, rats were sacrificed, gastric secretions were collected, and 35
Centrifugation was performed for 10 minutes at 00 r, p-m, and a relatively small volume of sediment was measured. The amount of free hydrochloric acid in gastric juice can be measured using an electric pH meter (p)! It was measured by titrating with α01N sodium hydroxide until it reached 7.0. One of the preferred compounds of the present invention having gastric juice secretion suppressing activity is, for example, 6-medoxy7-trans-(2-(3-pyridyl)-ethynyl)-5H-thiazolo(3,2-a)pyrimidin-5-one. , which corresponds to an ED5 of approximately 30+v/9 in the above study in rats after intraduodenal administration.
It has a Q value.

Compounds of the invention may also be used, for example, after their oral administration.
A) O.A. Winter et al.'s method [(J.

Pharmac, Eip, Therap,) No. 14
1, p. 369 (1963)] and P. Lenc.
Mr. e's method 1: rArch.

nt, Pharmacodyn, J Vol. 156, p. 237 (1962)] in the rat hind limbs in response to the injection of carrageenin; and B) reverse passive arthus formation in the rat forelimbs induced by the interaction of antigen and antibody. Reaction (Revereθd Pa5sive
ArthusReaction) (r RPAR
This results in precipitation of immune complexes, followed by fixation of complement and accumulation of polymorphonuclear leukocytes in the focus (r Agents and Actions J No. 9).
1, p. 107 (1979)].

The compounds of the invention also possess analgesic properties. The analgesic effect can be determined by, for example, the phenylquinone-induced writhing test in mice by Siegmund rProc;
Soc, Kxper, Biol Med, J No. 9
Vol. 5, p. 729 (1957)].

The compounds of the invention may therefore be used to treat pain and inflammatory processes such as rheumatoid arthritis and osteoarthritis.

Tables 1 and 2 show the approximate ED25 values of anti-inflammatory activity in the above test after oral administration to rats, for example, for some compounds of the present invention.

65- Table 1 Table 1 Regarding the analgesic effect, one of the preferred compounds of the present invention is, for example, 2-chloro-7-dransu66-[2=(3-pyridyl)-ethynyl)-5H-thiazolo[312-a ) pyrimidin-5-one, which has an approximate ED25 value of 25 /
Has a smell.

Furthermore, the compounds of the present invention are effective in inhibiting TXA2 synthase in vivo and are therefore useful for use in the prevention and treatment of, for example, all types of thrombosis, peripheral vascular disease, and coronary artery disease.

Activity against TXA2 synthase, for example, can be determined by administering a single oral dose of rat K compound at 1o++v/9 ml and 7
Animals were killed 2 hours after drug administration, and TXA in their serum was analyzed.
2 concentration was evaluated.

A preferred example of a compound having a TXA2 synthase inhibitory effect is 6-methyl-7-trans-[2-(5-pyridyl)-ethynyl2-5H-thiazoloC3,2-a
) pyrimidin-5-one.

The □compounds of the present invention can be safely used in medicine due to their high therapeutic index. For example, 7-trans-[2-(3-pyridyl)-ethynyl]-5H-thiazolo[5,2-a] determined in mice by administering a single dose of increasing doses and measuring on day 7 of treatment: ]]pyrimidine-5-o and 2-chloro-7-trans-[:2-
(3-pyridyl)-ethynyl-5H-thiazoloC3,
2-a) Approximate acute toxicity of pyrimidin-5-one (
LDso) is greater than 800111/odor orally. Similar toxicity data are found for other compounds of the invention.

The compounds of the invention may be administered orally in various dosage forms, e.g. in the form of tablets, capsules, dragees or film-coated tablets, liquid solutions or suspensions, or rectally in the form of herbal medicines, or parenterally, e.g. intramuscularly. , or can be administered by intravenous injection or infusion.

The dosage depends on the patient's age, weight, situation and route of administration. For example, the medicinal dosage used for oral administration to adults is about 50 to about 200'9°, 1 to 5 times a day.

The invention also encompasses pharmaceutical compositions consisting of a compound of the invention in combination with a pharmaceutically acceptable excipient, which may be a carrier or diluent.

Pharmaceutical compositions containing the compounds of the invention are usually prepared according to conventional methods and administered in a pharmaceutically suitable form.

For example, solid oral forms may contain the active compound together with diluents such as lactose, glucose, sucrose, cellulose, corn or potato starch, lubricants such as silica, talc, stearic acid, magnesium or calcium stearate, and/or polyethylene glycols. , binders such as starch, gum arabic, gelatin, methylcellulose, carboxymethylcellulose or polyvinylpyrolene, disintegrants such as starch, alginic acid, alginate or sodium starch glycolate, effervescent mixtures, dyes, sweeteners, humectants such as It may contain lecithin, polysorbate, lauryl sulfate, and other non-toxic and pharmacologically inert substances commonly used in pharmaceutical formulations. The pharmaceutical formulations may be prepared by known methods such as mixing, granulating, tabletting, dragee coating, or film coating processes. Liquid dispersions for oral administration can be, for example, syrups, emulsions and suspensions.

The syrup may contain as carrier, for example sucrose or a combination of sucrose and glycerin, and/or mannitol and/or sorbitol. In particular, syrups administered to diabetic patients may contain as carrier only substances that cannot be metabolized to glucose or are metabolized only to a very small extent, such as sorbitol.

Suspensions and emulsions may contain as carrier, for example natural gum, agar, sodium alginate, cactin, methylcellulose, carboxymethylcellulose or polyvinyl alcohol.

Intramuscular injection suspensions or solutions may contain the active compound together with a pharmaceutically acceptable carrier such as sterile water, olive oil, ethyl oleate, glycols such as propylene glycol, and, if desired, a suitable amount of gluedocaine hydrochloride. .

Intravenous or infusion solutions may contain as carrier, for example, M. bacterium water, or preferably they may be in the form of sterile aqueous isotonic saline solutions.

Herbal medicines may contain the active compound together with pharmaceutically acceptable carriers such as cocoa butter, polyethylene glycol, polyoxyethylene sorbitan fatty acid ester surfactants or lecithin.

The invention is illustrated by the following examples, but the invention is not limited thereto.

Example 1 2-amino-thiazole1. o6r) at 100℃ for 2 hours
with ethyl 2-methylacetoacetate (6,4y) in polyphosphoric acid (15,3S', 7.1 f of P2O5 and 8.22 of 99% H3PO4) with stirring. After cooling, diluting with ice water and neutralizing, the precipitate was filtered, washed with water, and crystallized from isopropyl ether.
a) Pyrimidin-5-one (melting point 112-113°C)
5.049 was obtained, which was reacted with 3-pyridine-carboxaldehyde (5,99f) in methanol (130++I) in the presence of sodium methoxide (4,5sy) with stirring at reflux temperature for 12 hours. After cooling, the precipitate was filtered and washed with water until neutral, and crystallized from methanol to give 3.21 6-methyl-7-trans-[2-(3-pyridyl)-ethe75-nylku 5H-thiazolo (3,2-a), pyrimidin-5-one was obtained.

Melting point 192-194°C, NMR (CDC13) δppm
: 2.36 (B) (RoH, CI (3), 6.97 (a
) (H, c -2 proton), 7.68 (dd) (
IH, C-5 pyridyl proton), 7.38 (a)
(IT(.

β-ethynylfloton), 7.91(a) (IH, α
-ethynyl proton), z, 97(a) (IH, c-3
proton), a OO(m) (IT(.

C-4 pyridyl proton), 8. /II 2 (aa)
(1'H, c-6 pyridyl proton), 8.88
(d) (IH, C-2 pyridyl proton), JHctH
β-16Hz0 The following compound was prepared by the same operation using the appropriate aldehyde.

6-methyl-7-trans-(2-(4-pyridyl)-
Ethynyl2-5H-thiazolo[3,2-a)pyrimidin-5-one (melting point 252-253°C), 6-methyl-7-trans-C2-C6-methyl-2-pyridyl)-ethynyl ml-5H -thiazolo(3,2-a)pyrimidin-5-one (melting point 198~
199°C), 6-methyl-7-trans-[:2-(1-methyl-2
-pyrrolyl)-ethynyl:]-]5H-thiazoloC3,
2-a]]pyrimidin-5-one 6-methyl-7-trans-(2-(2-pyridyl)-ethynyl2-5H-
Thiazolo[6,2-a)pyrimidin-5-one (melting point 1
89-190°C), 6-methyl-7-trans-(2-phenyl-ethynyl)-5H-thiazolo[3,2-a]]pyrimidine-5
-on melting point 173-175°C), 6-methyl-7-trans-(2-(4-chloro-phenyl)-ethynyl)-
5H-thiazolo[3,2-a)pyrimidin-5-one (melting point 223-224°C), 6-methyl-7-trans-(: 2-(2,6-dichloro-phenyl)-ethynyl)-,5H -f Azolo C
3,2-a ]]pyrimidine-5-one melting point 202-2
04°C), 2-cyano-6-methyl-7-trans-[2-(3-
pyridyl)-ethynyl2-5H-thiazoloC3,2-a
) Pyrimidin-5-one, 6-methyl-7-trans-[2-(3-methyl-phenyl)-ethynyl)-5H
-thiazolo(3,2-a)pyrimidin-5-one, 6
-Methyl-7-trans-C2-C4-methyl-phenyl)-ethynyl)-5H-thiazolo(3,2-a ]]
Pyrimidin-5-one (melting point 190-192°C), 6-methyl-7,-trans-(2-(2-meth)oxy-
3-4)*Ciphenyl)-ethynyl2-5H-thiazoo (3,2'-a)pyrimidin-5-one and 6-methyl-2-phenyl-7-trans-1:2-(
3-pyridyl)-ethynyl)-5H-thiazoloC3,2
-a) Pyrimidin-5-one (melting point 274-277°C
).

Example 2 The following compounds were prepared by operating according to Example 1 using ethyl 2-alkyl-acetoacetate as appropriate.

6-Nityru-7-trans-[:2-(3-pyridyl)
-ethynyl-5H-thiazolo[3,2-a)pyrimidin-5-one (melting point 176-177°C), 6-propyl-futrans-(2-(3-pyridyl)
-ethynyl)-5T(-1-7so[3,2-a)pyrimidin-5-one (melting point 190-191°C], 1'7'7-6-nityl-7-trans-(2-(4-pyridyl) )−
Ethynyl-5H-thiazolo[3,2-a')pyrimidin-5-one, 6-propyl-futrans-(2-(2-pyridyl)
-ethynyl)-5I(-thiazolo[3,2-a)pyrimidin-5-one, 6-nityl-7-trans-(2-(2-pyridyl)-
Ethynyl-5H-thiazolo[3,2-8]pyrimidin-5-one and 6-nityl-'7-trans-C2-(6-methyl-2
-pyridyl)-ethynyl)-5H--F-azolo(3,
2-a]]Pyrimidin-5-one Example 3 The following compound was prepared by operating according to Example 1 using ethyl 2-chloro-acetoacetate.

6-chloro-7-trans-[2-(3-pia 8-lysyl)-ethynyl-5H-thiazolo[3,2-a)
Pyrimidin-5-one (melting point 235-237°C), 6-chloro-7-trans-(2-phenyl-ethynyl)-5H-thiazoloC3,2-a ]]pyrimidine-5
-on melting point 230-232°C), 6-chloro-7-trans-[2-(4-chloro-phenyl)-ethynyl]-
5H-fazoloC3,2-a)pyrimidin-5-one (melting point 271-272°C) and 6-chloro-7-trans-[2-(2,6-dichloro-phenyl)-ethynyl2-5H-thiazolo(3 ,2-
a]] Pyrimidin-5-one Example 4 2-Amino-thiazole (5t) was dissolved in polyphosphoric acid (2sr) with stirring at 100°C for 8 hours with 4-chloro-
Reacted with ethyl acetoacetate (10,85'). After cooling, diluting with ice water and neutralizing, the precipitate was filtered and washed with water to obtain 7-chloromethyl-5H-thiazoloC.
3,2-a) Pyrimidin-5-one (melting point 136-1
38° C.) was obtained, which was reacted with triphenylphosphine (12.8 f) in acetonitrile (130 ml) while stirring at reflux temperature for 30 hours. After cooling, the precipitate was filtered and washed with isopropyl ether. (511(-thiazoloC3,2-a:Ipyrimidine-
5-one-7-yl)-methylto I7 Phenylphosphonium chloride (melting point 295-299°C) 20.6
9, which was dissolved at 50% in dimethyl sulfoxide (300 m/) and dichloroethane (200)
A suspension of NaH (2,61?) was stirred and then reacted with 3-pyridine-carboxaldehyde (Z152) at room temperature for 6 hours. After evaporation of the dichloroethane in vacuo, the solution was diluted with water and the precipitate was filtered, washed with water and then crystallized from isopropyl alcohol to give 7-trans[2-(3-pyridyl)-ethynyl] of 6.22. 5H-thiazoloC3,2-a]
] Pyrimidine-5-o was obtained.

Melting point 206-207℃, NMR (DM80 a6) δp
pm: 6.41 (El) (IH, c-6 proton), 7.36 (d) (IH, β-ethynyl proton), 7.45 (da) (IT (, C-5 pyridyl proton), 7 , 58 (d) (IH, C, -2 proton), 7.82 (d) (IH, α-ethynyl proton), s, o 6 ((1) (IH, c -3 proton), 8.17 (tit) (IH, C-4 pyridyl proton), a60 (ad) (IH.

C-6 pyridyl proton), 8.91 (a) (IH
, c -2 pyridyl proton), JH,yH79-16
The following compound was prepared by similar operation using a suitable aldehyde.

7-trans-[2-(2-pyridyl)-ethynyl2-5H-thiazoloC3,2-a)pyrimi81-zin-5-one (melting point 231-232°C), 7-trans-(2-(4-pyridyl) )-ethynyl2-5H-thiazoloC3,2-a)pyrimidin-5-one (melting point 24
6-247°C), 7-trans-C2-(6-methyl-
2-pyridyl)-ethynyl-5H-thiazolo[3,2
-a) Pyrimidin-5-one (melting point 213-216°C)
, 7-trans-[2-(2-pyrrolyl)-ethynyl-5H-thiazolo-(,!+,2-a']pyrimidine-5
-one (melting point 209-211°C), 7-trans-(2
-(1-methyl-2-pyrrolyl)-ethynyl2-5H-
Thiazolo[3,2-a]pyrimidin-5-one (melting point 2
11-212°C), 7-trans-[2'-(1-ethyl-2-pyrrolyl)
-ethynyl2-5H-thiazolo[3,282- -a)pyrimidin-5-one, 7-trans-(2-phenyl-ethynyl)-5T(-
Thiazo o (3,2-a:]]pyrimidin-5-one melting point 198-200°C) 1. 7-trans-[2-(3-chloro-phenyl)-ethynyl-5H-thiazoloC3,2-a)pyrimidine-
5-one (melting point 230-236°C), 7-trans-C
2-(4-chloro-phenyl)-ethynyl-5H-thiazolo[3,2-a:1pyrimidin-5-one (melting point 2
08-209°C), 7-trans-C2-(2,6-dichloro-phenyl)-ethynyl2-5H-thiazolo[3
,2-a]pyrimidin-5-one (melting point 175-177
), 7-trans-[2-(3-methoxy-phenyl)-ethynyl-5H-thiazolo[3,2-a]pyrimidine-
5-one (melting point 185-186°C), 7-trans-C
2-(5-hydroxy-phenyl)-ethynyl-5H
-thiazolo[3,2-a)pyrimidin-5-one (melting point 226-229°C), 7-trans-(2-(4-hydroxy-3-iodo-
phenyl)-ethynyl)-5H-thiazoloC3,2-a
) Pyrimidin-5-one [melting point 250-270°C (decomposition)], 7-trans-C2-(4-N,N-dimethylamino-
phenyl)-ethynyl]-5H-thiazolo(3,2-a
) pyrimidin-5-one (melting point 233-234°C), 7-trans-(2-(2-nitro-phenyl)-ethynyl2-5H-thiazolo[3,2-a)pyrimidine-5
-1one [melting point 280-290°C (decomposed)], 7-trans-(2-(3-N,N-dimethylamine)
-Floboxyphenyl]-ethynyl)-5H-thiazolo[3,2-a,]]pyrimidin-5-one7-trans-C2-,(4-methyl-phenyl)-ethynyl2-5H-thiazolo[3,2-, a: 1-pyrimidin-5-one (melting point 214-216°C), 7-trans-(2-(3-methyl-phenyl)-ethynyl2-5H)
-thiazolo[:3,2-a:]]pyrimidin-5-one and 7-trans-[2-,(2-methoxy-3-ethoxy-phenyl)-ethynyl)-5H-thiazolo[3,2-
a) Pyrimidin-5-one.

Example 5 The 2-amino-5-chloro-thiazolo-hydrochloric acid layer 82) was reacted with 4-chloroacetoacetate (15,89) in polyphosphoric acid (409) with stirring at 110° C. for 1 hour. After cooling, diluting with 85° of water and neutralizing with 3596 NaOH, the precipitate was filtered and washed with water. 2-chloro-7-chloromethyl-5H-thiazolo[3,2-a]]pyrimidin-5-one crystallized from isopropyl ether, melting point 12
(3-125°C) Z45 was obtained which was stirred at reflux temperature for 10 hours and then reacted with triphenylphosphine (9,429) in acetonate (100-). After cooling this, the precipitate was filtered and then acetonate) I
Wash with Jul.
2=a)pyrimidin-5-one-7-yl)-methyl-
Triphenylphosphonium chloride (melting point 300-3
(10°C (decomposed)) IC1 was obtained which was suspended in dimethylsulfoxide (40m) and then potassium tert-butoxide (2,48? ) was processed. Dimethyl sulfoxide (2
3-pyridine-carboxaldehyde (M) dissolved in
2.4 sg) was added and the reaction mixture was kept under stirring for 15 minutes at room temperature, diluted with ice water and diluted with NaH.
After neutralization with 2P O4, the precipitate was filtered and CH2C
4.3 by crystallization from l2/isopropyl alcohol
2-chloro-7-trans-(2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a,)pyrimidin-5-one (melting point 189-190°C) was obtained.

NMR (CDC13) δppm: 6.24 (s
) (IH, C-6 proton), 6.91 (d'l (
IH, β-ethynyl proton), 7.3o(aa)(I
H, C-5 pyridyl proton), 7.7.1 (cl)
(IH, α-ethynyl proton), 7.82(s)
(IH, C-3 proton), 7.87 (dacl)
(1) I, C-4 pyridyl proton), 8.5
5 (dd) (IH, C-6 pyridyl proton),
8.77(d) (IT(, C-2 pyridyl proton),
JHaHp-16Hz 0 The following compound was produced by the same operation.

2-chloro-7-trans-(2-(4-pyridyl)-
Ethynylcou 5H-thiazolo[3,2-a]pyrimidin-5-one, 2-chloro-7-trans-[2-(1-methyl-2-
pyrrolyl)-ethynyl)-5H-thiazoloC3,2-a
]]Pyrimidin-5-one 3-methyl-7-trans-[:2-(3-pyridyl)-ethynylcou 5H-thiazolo[3,2-a]pyrimidin-5-one (melting point 191
~193°C), 2,3-dimethyl-7-trans-C2'-(3-pyridyl)-ethynylcou 5H-thiazolo(3,2-a)
Pyrimidin-5-one (melting point 179-180°C),
□ 3-trifluoromethyl-7-trans-[2-(3-
pyridyl)-ethynylcou 5H-thiazolo(3,2-a
) pyrimidin-5-one (melting point 224-226°C), 2-promo7-trans-(2-(3-pyridyl)-
Ethynyl 5H-thiazolo[3,2-a]pyrimidin-5-one (melting point 211-213°C), 3-tert-butyl-7-trans-[2-(3-pyridyl)-ethynyl)-5H-thiazolo C3,2-a]]
Pyrimidin-5-one 2-cyano-7-trans-['
2-(3-pyridyl)-ethynylcou 5H-thiazolo[3,2-a)pyrimidin-5-one [melting point 248-2
50°C, NMR (DMSOa6) δppm: 6.4
0 (s) (IH, C-6 proton), 7.32 (
a) (IH, β-ethynyl proton), 7.44 (a
a) (IH, C-5 pyridyl proton), 7.72 (
d) (IH.

α-ethynyl proton), 8.1'1 (dda)
(IH, C-4 pyridyl proton), 8.52 (m)
(IH, C-6 pyridyl proton), 89- 8.84 (aa) (IT(, c-2 pyridyl proton), 9. O0(e) (IH, C'-3 proton)
, JHaHp-16Hz 0 Example 6 7-chloromethyl-6 prepared according to Example 5
-Phenyl-5H-thiazo, [3,2-alpyrimidin-5-one (melting point 194-195°C) 7.8 t was stirred at reflux temperature for 24 hours and then acetonitrile (25
o-) with triphenylphosphine (8v). After cooling, the solution was concentrated in vacuo to a small volume, diluted with isopropyl ether and the precipitate was filtered to give 117 [3-phenyl-5H-thiazoloC3,'2-
a]Pyrimidin-5-one-7-yl]-methyl-triphenylphosphonium chloride was obtained, which was suspended in dimethylsulfoxide (50d) and then dissolved in dimethylsulfoxide (so-) with stirring at room temperature. Treated with potassium 390-butoxide (2,469). The solution of the ylide thus obtained was reacted with 6-pyridine-carboxaldehyde (2,369) for 60 min at room temperature, then the reaction mixture was diluted with ice water and NaHPO
Neutralized with 4. The precipitate was filtered and washed with water, CH2C4
Crystallization from 2/methanol gave 2.82 of 3-phenyl-7-trans-[2-(3-pyridyl)-ethynylcou 5H-thiazolo(3,2-a)pyrimidin-5-one.

Melting point 270-272°C, NMR (CDC15) δppm
: 6.17(s) (IH, C-6 proton), l
, 7 Q (s) (IH, C-2 proton), 6.
97 (a) (IH, β-ethynyl proton), 7.
34 (4t1) (IT (, C-'5 pyridyl proton), 6.39 (S) (5H, phenyl proton),
7.77 (a) (IH, α-engineered proton), Z
87 (→ (IH, C-4 pyridyl proton), a54
(m) (IH, C-6 pyridyl proton), a80 (
ad) (IH, C-2biI)U proton), JHaH
β-j6Hz0 The following compounds were produced by similar operations.

2-phenyl-7-trans-(2-(3-pyridyl)
-ethynylcou 5H-thiazolo[3,2-a)pyrimidin-5-one, 3-[4-fluoro-phenyl)-7-)lanse-(2
-(3-pyridyl)-ethynyl-5H-thiazoo C
3,2-a 3pyrimidin-5-one (melting point 241-2
43°C), 3-(2-chloro-phenyl)-7-) lance-C2-
(5-pyridyl)-ethynylcou 5H-thiazoloC3,
2-a) Pyrimidin-5-one, 3-(3-chloro-
phenyl)-7-) lance-C2-C3-pyridyl)-
Ethynylcou 5H-thiazoloC3,2-a) pyrimidin-5-one, 3-[4-chloro-phenyl)-7-)
Lance-(2-(3-pyridyl)-ethynylcou 5H-
Thiazolo[3,2-a)pyrimidin-5-one (melting point 282-283°C), 3-(3-)IJfluoromethyl-phenyl)-7
-trans-[2-(3-pyridyl)-ethynylcou 5
H-thiazolo[3,2-a)pyrimidin-5-one, 3-(2-methyl-phenyl)-7-trans-[2-
(3-pyridyl)-ethynylcou 5H-thiazoloC3,
2-a ]]pyrimidin-5-one 3-(3-methyl-
phenyl)-7-) lance-[:2-(3-pyridyl)
-ethynylcou 5H-thiazolo(3,2-a)pyrimidin-5-o,n,3-(4-methyl-phenyl)-7
-) lance-[2-(3-pyridyl)-ethynyl2-5
H-thiazolo[3,2-a)pyrimidin-5-one (
melting point 254-255°C), 3-(2-methoxy-phenyl)-7-trans-(2
-(3-pyridyl)-ethynyl]-93- 5H-thiazolo[3,2-a)pyrimidin-5-one, 3-(3-methoxy-phenyl)-7-) lance-[2
-(3-pyridyl)-ethynyl-5H-thiazoo (
3,2-a) Pyrimidin-5-one (melting point 209-2
100), 3-(4-methoxy-phenyl)-7-) lance-(2
-(3-pyridyl)-ethynyl-5H-thiazoa (
3,2-a) Pyrimidin-5-one (melting point 241-2
42°C), 3-(2,4-dimethoxy-phenyl)-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazoo(3,2-a)pyrimidin-5-one, 3-( 3,4-dimethoxy-phenyl)-7-trans-C2-C5-pyridyl)-ethynyl-5H-thiazolo[3,2-a)pyrimidin-594--one, 3-(3,4-ethylenedioxy-phenyl )-7-
trans-[2-(3-pyridyl)-ethynylcou 5H
-thiazoloC3,2-a ]]pyrimidin-5-one melting point 232-266°C), 3-(3,4-methylenedioxy-phenyl)-7-trans-(2-(3-pyridyl)-ethynylcou 5H- ThiazoloC3,2-a)pyrimidin-5-one, 3-(3,4-dihydroxy-phenyl)-7-trans-(2-(3-pyridyl)-ethynylcou 5H-thiazolo(3,2-a]) Pyrimidin-5-one 3-(4-hydroxy-phenyl)-7-trans-[
2-(3-biIJdyl)-ethynyl-5H-thiazoo
(3,2-a:lpyrimidin-5-one, 2-methyl-3-phenyl-7-trans-(2-(3
-pyridyl)-ethynyl)-51(-thiazolo[3,2
-a) Pyrimidin-5-one (melting point 234-237°C
), 2-ethyl-3-phenyl-7-trans-[2-(3
-pyridyl)-ethynyl:]-57(-thiazoloC3,
2-a) Pyrimidin-5-one, 3-(4-biphenylyl)-7-) lance-[2-(3-pyridyl)-ethynyl)-5H-thiazolo(3,2-a ]]pyrimidin-5-one (melting point 239-240°C), 3-(2-naphthyl)-7-trans-[2-(3-pyridyl)-ethynylcou 5H-thiazolo(3,2-a
) Pyrimidin-5-one (melting point 308-310°C), 3-(3-hydroxy-phenyl)-7-tran x-C
2-(3-HylJul)-ethynyl-5H-thiazolo[3,2-a)pyrimidin-5-one, 4-(4-acetoxy-phenyl)-7-thyl-7-su
(2-(3-piIJdyl)-ethynyl2-5H-thiazoo (3,2-a ]]pyrimidin-5-one 3-(2-nitro-phenyl)-7-) lance-[2-
(3-pyridyl)-ethynylcou-5H-thiazolo[3,
2-a) Pyrimidin-5-one (melting point 264-266
°C), 3-(4-nitro-phenyl)-7-trans-[2-
(3-pyridyl)-ethynylcou-5H-thiazolo(3,
2-a) Pyrimidin-5-one, 6-[2-amino-
phenyl)-71 lance-[2-(3-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one, 3-(3-amino-phenyl)-7-tran97-su[: 2-(3-pyridyl]-ethynyl]-5H-thiazolo[3,2-a)pyrimidin-5-one, 5-(
4-amino-phenyl)-7-) lance-[2-(3-
pyridyl)-ethynylcou 5H-thiazoloC3,2-a
]]Pyrimidin-5-one and 2,3-diphenyl-7-trans-C2-C3-pyridyl)-ethynylcou 5H-thiazolo[3,2-a]pyrimidin-5-one (melting point 249-250°C).

Example 7 7-chloromethyl-6 prepared according to Example 6
-(3-pyridyl)-5H-thiazolo(3,2-a)
Pyrimidin-5-one, [melting point 280-290°C (decomposition): 15.3Of] was stirred at reflux temperature for 40 hours and then neatly prepared in acetonitrile (500 m/), triphenylphosphine (!M),! [98- I responded. After cooling, the solution was concentrated in vacuo to a small volume, diluted with isopropyl ether and the precipitate was filtered to give 8 g of C3-,(3-pyridyl)-5H-thiazolo(3,2-a)pyrimidine. -5-one-7-yl]methyl-triphenylphosphonium chloride, which was suspended in dimethyl sulfoxide (C100 ml) and stirred at room temperature before dimethyl sulfoxide (50 ml) was obtained.
) dissolved in potassium tert-butoxide (1,662)
Processed with. The solution of the ylide thus obtained was heated at room temperature for 60 minutes with 6-pyridine-carboxaldehyde (1
;749) and the reaction mixture was then diluted with ice water and neutralized with NaT (2PO4). The precipitate was filtered, washed with water and crystallized from cH2cz2/methanol to give 6-(3- pyridyl)-7-trans-
C2-C5-pyridyl)-ethynyl-5H-thiazolo[5,2-a)pyrimidin-5-one was obtained.

Melting point 270-272℃, NMR (CF3COOD+CI
) C45) δppm: 6.82 (s) (IH, C
-6 proton), 7.51 (a) (IH, β-ethynyl proton), 7.76 (e) (1H, C-2 proton), 796 (d, ) (IH, α-ethynyl proton), a , o 1-8.36 (m) (2H.

C-5 pyridyl proton), 8.70-900 (→(4
H, C-4 and C-6 pyridyl protons), 9.11
(bs) (2H, C-2 pyridyl proton), J
HaHp-16T (z0) The following compound was produced by the same operation.

7-trans-[2-(3-pyridyl)-ethynyl)-
3-(2-chenyl)-5H-thiazolo(3,2-a
) pyrimidin-5-one (melting point 121-125°C), 3-(2-pyridyl)-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a
:]]Pyrimidine-5-o and 6-(4-pyridyl)
-7-) Lance-[2-(6-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one.

Example 8 2-Amino-5-chloro-thiazole hydrochloride (82) was reacted with 4-chloro-acetoacetate-) (15, El) in polyphosphoric acid (4 fl) with stirring at 110<0>C for 1 hour. This was cooled and diluted with water to 35%
After neutralization with NaOH, the precipitate was filtered and washed with water.

This was crystallized from isopropyl ether to give 2-chloro-7-chloromethyl-5H-thiazoloC3,2-a)
Pyrimidin-5-one (melting point 123-125°C) 745
y was obtained, which was reacted with triphenylphosphine (9,421) in acetonitrile (100 m/) with stirring at reflux temperature for 10 hours. After cooling, the precipitate was filtered and washed with acetonitrile (2-rioo-5H
-thiazolo[3,2-a:1401-pyrimidin-5-one-7-yl)-methyl-triphenylphosphonium chloride [melting point 300-310°C (
Dimethyl sulfoxide (decomposition)]
0-) and treated at room temperature with stirring for 10 minutes with potassium tert-butoxide (2,4El) dissolved in dimethyl sulfoxide (40 m/ml). Sulfoxide (2
5-Forkyl-2-methyl-thiazole (3,1F) dissolved in 2-methyl-thiazole (3,1F) was added and the reaction mixture was kept under stirring at room temperature for 15 min, diluted with ice water and then neutralized with NaH2PO4. After that, filter the precipitate and c
n2cz2 / crystallized from methanol to give 2 of 6.42
-chloro-7-trans-C2-(2-methyl-5-thiazolyl)-ethynyl2-5H-thiazolo[3,2-a
) Pyrimidin-5-one (melting point 224-226°C) was obtained.

102-NMR (CD'C/1.3) δppm: 2.9
7 (s) (3H, -CN3), 6.61 (E+)
(IT (, C-6 proton), 6.78 (a) (IH
, β-ethynyl proton), 7.82 (a) (IT
(, α-ethynyl proton), 7.88(s) (IH
, :c-3 proton), 8. [l 2 (e) (iH,
c-4 thiazolyl proton), JHaHβ=16H2
The following compounds were prepared by starting from the appropriate 2-amino-thiazole and proceeding in a similar manner.

7-trans-C2-C2-methyl-5-thiazolyl)
-ethynyl)-5H-thiazolo-C3,2-a) pyrimidin-5-one (melting point 245-248°C), 2-cyano-7-trans-[2-(2-methyl-5-
Thiazolyl)-ethynyl)-5H-thiazoloC3,2-
a) Pyrimidin-5-one, 2,3-diphenyl-7
-Torarasu-C2-(2-methyl-5-thiazolyl)-
ethynyl]-5H-thiazoloC3,2=a' :]]pyrimidin-5-one7-trans-C2-(2-methyl-5-thiazolyl)-ethynyl]-3-phenyl-゛5
H-thiazoloC3,2-a]]pyrimidin-5-one7-trans-C"2-(2-methyl-5-thiazolyl)-ethynylcou 3-trifluoromethyl-5H-thiazolo(3,2-a)] Pyrimidin-5-one and 7-trans-C2-(2-methyl-5-thiazolyl)
-ethynyl]-3-(3-pyridyl)-5)[-thiazol:3',2-a]]pyrimidin-5-one Example 9 7-Chloromethyl-5 prepared according to Example 4
H-thiazolo[3,2-a)pyri-midin-5-one (
10f) was dissolved in dimethylformamide (200+7ml) and reacted with anhydrous potassium acetate (.102) with stirring at room temperature for 20 hours. After diluting it with ice water, the precipitate was filtered and washed with water and extracted from methanol. 7-Acedoxymethyl-5H-thousandazolo[3,
2-a,) Pyrimidin-5-one (melting point 144-145
°C) Z57 was obtained, which was dissolved in dioxane (1(]Om/) at 7% Hc't(
Hydrolyzed by treatment with 50-). The reaction mixture was diluted with acetone and the precipitate was filtered and washed with anhydrous N.
Treated with a 2 HPO4, filtered and washed with neutral water to give 7-hydroxymethyl-5H-thiazo o[3
,2-Fl, :]]pyrimidin-5-one melting point 189
~191 °C) 4.89 was obtained, which was dissolved in benzene (8'01 nl) in the presence of trifluoroacetic acid (0,9-) and pyridine (1,53-) while stirring at room temperature for 24 h.
) and dicyclohexylcarpodi-105-imide (12,6r) in dimethyl sulfoxide (36rn1.). After treatment with oxalic acid dihydrate (2,89) at room temperature, the precipitate of dicyclohexylurea was evaporated and the organic solution was concentrated to dryness in vacuo, and the residue was eluted with chloroform/ethyl acetate. Purified on a 51o2 column using This was crystallized from ethyl acetate to give 7-formyl-5H-thiazolo[3,2-a)pyrimidin-5-one (melting point 184~
186°C), which was treated with 50% NaH (0,274S') in dimethyl sulfoxide (6 ml pieces and 4 pieces of dichloroethane) at room temperature for 16 hours to give phenylphosphonium benzyl chloride (IJ).
ts7r). After evaporating the solvent in vacuo, the solution was diluted with ice water and the precipitate was filtered and washed with water and crystallized from isopropyl ether to give 1.22 of the 7-
Trans-(2-phenyl-ethynyl)-5H-thiazolo[:3,2-a]106-pyrimidin-5-one was obtained.

Melting point 198-2.00℃, NM'R(DMSOd6)δ
ppm: 6.40 (θ) (IH, C-6 proton)
, 7.22 (d) (IH, β-ethynyl proton)
, Z3-7.867I) (5H, phenyl proton)
, 7.54(d) (IH, C-2 proton), 7.8
0 (d) (IH, α-ethynyl proton), a, o
4 (a) (IH, c -3 proton), JHaH
β-6H20 Example 10 2-amino-4,5-dimethyl-chia sheets L (21)
of ethyl 3-amino-4,4 in dimethylacetamide (15 taJ) with stirring at 140°C for 15 hours.
-Jethoxy-2-methyl-crotonate (5,42)
I reacted. After cooling, the reaction mixture was diluted with ice water and extracted with ethyl acetate, and the organic phase was diluted with 0.1 N HC.
1 and water and decolorized with charcoal. After evaporation to dryness in vacuo, the residue was purified on a flash column using hexane/ethyl acetate (3=2) as eluent to give 0.9f of 7-dinitoxymethyl-2.3. 6-)
Riftyl-5H-thiazolo(5,2-a)pyrimidin-5-one (melting point 84-85 °C) was obtained, which was dissolved in dioxane (10rd) and stirred at 50 °C for 30 min with 5% HC1 ( 15td).

After cooling, the solution was neutralized with 10% NaOH, diluted with ice water and extracted with ethyl acetate, the organic solution was evaporated to dryness in vacuo and the residue was crystallized from hexane to give 0.
6f 7-formyl-2,3,6-drimethyl-5H-
Thiazolo[3,2-a)pyrimidin-5-one (melting point 170-173°C) was obtained, which was dissolved in (3-pyridyl)methyltriphenylphosphonium chloride (tosl to potassium tert. The reaction mixture was reacted with the ylide obtained by treatment with butoxide (0,3f) for 1 h at room temperature.
Diluted with ice water containing aH2PO4 and extracted with ethyl acetate, the organic solution was evaporated to dryness in vacuo and the residue was crystallized from isopropyl alcohol/hexane to 0.
．． 257 of 2.3.6-)limethyl-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo(3,,2-a)pyrimidin-5-one was obtained.

Melting point 193-195°C, NMR, (CDC7,3)δp
pm: 2.22(S) (3T(, CT(5), 2
．． 24 (s) (3)T, CH3), 2.70 (
s) (3H.

CH3), 7.22 (a) (IH, β-ethynyl proton), 7.28 (aaa) (IH, C-5 pyridyl proton), 7.74 (a) (IH.

α-ethynyl proton), 7.86 (aaa) (I
H, c-4 pyridyl proton), 8.49 (d) (
IH, C-6 pyridyl proton), s, 7s (aa)
(IH, C-, 2 pyridyl proton), JHaT (β
-6H20 The following compounds were produced by similar operations.

2-chloro-6-methyl-7-trans-[2109--(3-pyridyl)-ethynyl2-5H-thiazo0 [
3,2-a) Pyrimidine-5-off (NMR (cD
ct3) δppm: 2.2 B CB”) (3H
, CH3), 6.94 ((1) (1!(.

β-ethynyl proton), 7.19 (da) (IT
(, C-5 pyridylprotoy), 7.80 (s) (
IH, C-3 proton), Z75←) (1H9α-ethynyl proton), 7.78 (bd) (IT(, C-
4 pyridyl proton), a56 (m) (IT(, C
-6 pyridyl proton), a77 (a) (IH, c
-2pyridyl proton), JHttHp16Hz0 3.6-dimethyl-7-trans-[2-(3-hyricyl)-ethynyl)-sH-thiazolo(3,2-a)pyrimidin-5-one [melting point 211-214°C, NMR (
CDCl2) δppm: 2.24 (s) (3H
.

c-b methyl), 2.80 (d) (3H, C-3 methyl), 6.30 (to) (IT (, C-2 proton),
7.24 (a) (1) (, β-ethynyl proton)
, 7.29 (dd) (IH, C-5 pyridyl proton), 7, 78 (tl) (1) (, α-ethynyl proton), 7.85 (4dd,) 110- (1H, C-4 pyridyl proton), 8.51 (a
d) (IH, C-6 pyridyl proton), 8.77 (
d) (IH, C-2 pyridyl proton), JHaHp
”= 16 H2.

Example 11 2-amino-thiazole (1oy) at 100°C for 24 hours
Ethyl 2-acetoxyacetoacetate (37,5j)a was reacted in dimethylacetamide containing polyphosphoric acid (71,5F, 42.57% P2O5 and 20% H5po4) with stirring at . After cooling, diluting with ice water and neutralizing with Na2HPO4,
The precipitate was extracted with ethyl acetate, the organic solution was evaporated to dryness in vacuo and the residue was purified on an 8102 column using CHCl 5 as eluent. The residue was crystallized from isopropyl ether to obtain 8t of 6-acedoxy 7.
-Methyl-5H-thiazolo[3,2-a)pyrimidin-5-one (mp 118-119 °C) was obtained which was treated with NaHCO3 (169) in methanol (8 omt) with stirring at 60 °C for 4 hours. and hydrolyzed.

After cooling, the solution was evaporated to a small volume in vacuo and the residue was dissolved in ethyl acetate and extracted repeatedly with aqueous NaOH. The aqueous phase was neutralized with 37% HCl and the precipitate was extracted with chloroform and the organic solution was evaporated to dryness in vacuo. This was crystallized from ethyl acetate to give 5.3f 6-hydroxy7-methyl-5H-thiazoloC3,2-a)pyrimidin-5-one (melting point 225
~227°C), which was dissolved in dimethylformamide (50°C).
mt and reacted with methyl iodide (asp) in the presence of anhydrous 2CO3 (8,1?) with stirring at room temperature for 16 hours. The reaction mixture was diluted with ice water, extracted with ethyl acetate, and the organic solution was purified with gaseous HC.
1. The precipitate was filtered and washed with ethyl acetate to give 6-medoxy7-methyl-5H-thiazolo[3,2
-a] Pyrimidin-5-one hydrochloride [melting point 185-19
5°C (decomposition)) was obtained which was dissolved in methanol (14M) in the presence of sodium methoxide (3,32) with stirring at reflux temperature for 24 hours. ) was reacted. After concentrating this in vacuo to a small volume and diluting with isopropyl ether, the precipitate was filtered and washed with isopropyl ether and then water. This was crystallized from 50% ethanol to obtain 6.29 6-medoxy7-trans-[2-(3-pyridyl)-ethynyl]-5H-thiazolo(3,2-a)pyrimidin-5-one. .

Melting point 186-187℃ NMB (CDC65) 499m
: 4-0263) (5H, -OC'H3), 6.9
6 (d) (IH, C-2 proton), Z52 ((
1(1) (IH, C-5 pyridyl proton), 7.50
(a) (IH, β-ethynyl proton), 113-7, 80 (a) (IH, a-ethynyl proton),
7.89 ((1) (IH.

C-3 proton), 7.96 (dt) (IH, C-
4 pyridyl proton), as3 (aa) (1H, C-
6 pyridyl protons), 8.81 (bs) (IH
.

6-medoxy7-trans-C2-(2-pyridyl)
-ethynyl) -'5)(-thiazolo(3,2-a
) Pyrimidin-5-one, 6-medoxy7-trans-C2-C6-methyl-2
-hil)9l)-ethynyl)-5H-thiazolo(3,
2-a) Pyrimidin-5-one, 6-hydroxyloxy7
-trans-[2-(3++Hyl)-ethynyl)-5H-thiazolo(3,2-a]]pyrimidin-5-one-114,-6-nitoxy7-trans-[2,-(3-pyridyl) -ethynyl2-5H-thiazolo[5,2-a)pyrimidin-5-one (melting point 166-165°C), 6-medoxy17-trans-[2-(,4-pyridyl)-ethynyl2-5H-thiazolo[3,2 -, a) Pyrimidin-5-one, 6-methoxy7-trans-(2-phenyl-ethynyl)-5H-thiazolo[3,2-a,)pyrimidine-
5-one, 6-methoxy7-trans-(2-(2,6-dico
lophenyl)-ethynyl,] -]5H-thiazoloC
3,2-a, , ) pyrimidin-5-one, and 6-propoxy-futrans-[: 2-(3-pyridyl)-ethynyl)+5H-thiazolo[6,2-a) pyrimidin-5-one.

Example 12″ 2-amino-5-chloro-thiazole hydrochloride (109)
Polyphosphoric acid (719,2
Ethyl 2-acetoxy-acetoacetate-) (22S') in dimethylacetamide (400 Tnl) containing 95' H3PO4 and 427 P2O3)
I reacted. Cool this, dilute it with ice water, and then
After neutralization with % NaOH, the precipitate was extracted with ethyl acetate and the organic solution was evaporated to dryness in vacuo. The residue was hydrolyzed by treatment with 35% HCl in dioxane (10'[]-') at reflux temperature for 2 hours, and after cooling the reaction mixture was diluted with ice water and then neutralized with 37% Na0)T. The precipitate was then extracted with ethyl acetate. The organic solution was evaporated to dryness in vacuo and the residue was crystallized from methanol to yield 5.85t of 2-chloro-6-hydroxy-7-
Methyl-5H-thiazolo(3,2=a]pyrimidine-5
-one (melting point 214-217 °C), which was dissolved in dimethylformamide (100 ml) and treated with anhydrous 2CO3 (:j 5 t) with stirring at 60 °C for 3 h.
) was reacted with methyl iodide (15,41i'). After cooling, the reaction mixture was diluted with ice water and N
a Neutralized with H2PO4, filtered the precipitate and extracted the aqueous phase with ethyl acetate for complete recovery of the product. A total of 5.17 2-chloro-6-medoxy-7-,methyl-5H-teazolo[3,2-a]pyrimidin-5-one (hard point 138-141°C) was obtained, which was kept at reflux temperature for 400 hours. was reacted with N-bromosuccinimide (172 drops added) in benzene (150 ml). After cooling, the reaction mixture was diluted with ethyl acetate and treated with aqueous NaHCO3 and then water, and the organic solution was separated and purified in vacuo. and the residue was crystallized from ethyl acetate to yield 2.8
2 of 7-P-1.1'7-lomomethyl-2-chloro-6''meth*cy-5H-thiazoloi'[3,2-a]]pyrimidin-5-one (melting point 160-162°C) was obtained, and this was Reacted with triphenylphosphine (2,'6t) in acetonitrile (5'Omg) at reflux temperature for an hour - After cooling and evaporating the solvent in vacuo, the residue was purified with ethyl acetate. and 6.82 (2-chloro-6-medoxy-5H-thiazolo[: 3,2'-a]pyridine-5
-one-7-''yl)-methyltributenylphosphonium bromide was obtained, and dimethyl sulfur oxide (
45 ml)' and stirred for 10 minutes at room temperature with potassium tert-butoxide (0,75P) dissolved in dimethyl sulfoxide (20 mg).

The solution of ylide thus obtained was reacted with 3-pyridine-carboxaldehyde (0,'94 f') for 1 hour at room temperature. The reaction mixture was diluted with ice water and diluted with NaT (2P
Neutralization with O4118- and crystallization of the precipitate from p.
-trans-[2-(3-pyridyl)-ethynylcou 5
H-thiazolo[3,2-a ml pyrimidin-5-one was obtained.

Melting point 205-207℃, NMR (CDCl2-CF, C
00D) δppm: 3.9 9 (8)
(3H,0CT(3), 7.6 9 (d)
(IH, β-ethynyl proton), 7.9! l (
a) (It(, α-ethynyl proton), 7.99(8
) (IH, C-3 proton), a, o, s (m)
(II-T, C-5 pyridyl proton), a 75
(m) (2H, c -4 and C-6 pyridyl protons), 9.02 (be) (IH, C-2 pyridyl protons), JH (YHβ = 16H20 The following compounds were produced by similar operations. .

6-methoxy7-trans-(,2= (,2-methyl-5-thiazolyl)-ethynyl)-5T(-thiazolo[:3,2-a]pyrimidin-5-one, 2-chloro-
6-nitoxy7-thorax-[2-(3-pyridyl)
-ethynyl: l-'5H-thiazolo[3,.2-a]pyrimidin-5-one, 6-methoxy7-trans-(
2 = '(1''-methyl-2-pyrrolyl)-ethynyl'
] -'5 H'-thiazoloC3,2-a: l pyrimidin-5-one, 6-medoxy 3-(2-chenyl)
-7-trans-[2-(3-pyridyl)-ethynyl]
-5) (-Thiazo01: 3.2-a]pyrimidine-5
-one, 2-chloro-6-methoxy7-trans-[2-'(
2-Methyl-5-thiazolyl)-ethynylcou 5H-thiazolo(3,'2,-a)pyrimidin-5-one [
Melting point 225-227°C, NMR (CDCl2) δppm
:2. ．． 71 (El) (3H,-CHg), 5.
98 (s) (3T(,0CH3), Z02(d)(
1H1β-ethynyl proton), 7.68' (S)
(IH; C-4 thiazolyl proton), 7.76 (s
) (IH, C-3 proton), 7.8 t (a)
CIH, α-ethynyl proton), JHaHβ-6H2
0 6-Medoxy 3-trifluoromethyl-7-trans-[2-(3-pyridyl)-ethynylcou 5H-thiazolo(3,ja-a ]]pyrimidin-5-one 6-Medoxy 3-(6-pyridyl)- 7-trans-
[2-(3-pyridyl)-ethynyl]-5H-thiazoloC3,2-a')pyrimidin-5-one, 6-medoxy 3-(2-pyridyl)-7-tran, X
, -, [27(3-pyridyl)-ethynyl]-5T(-
ThiazoloC3,2-a) pyrimidin-5-one, 6-medoxy 3-(4-pyridyl)-7-trans-
[:27C3-pyridi,l)-ethynyl]-5. H-thiazolo(3,2m,,4)pyrimidin-5-one, 121-6-medoxy3-(4-biphenylyl)-7-trans-(2-(3-pyridyl)-ethynylcou 5H-thiazolo[3, 2-a) Pyrimidin-5-one, 3-methyl-6-methoxy7-trans-(2-(5
-pyridyl)-ethynyl: l -5H-thiazolo[,3
,2-a:]]pyrimidin-5-one 2,3-dimethyl-6-medoxy7-trans-C2-(3-pyridyl)-ethynylcou 5H-thiazolo[3,2-a)pyrimidin-5-one,6- Medoxy 3-(3-methoxy-phenyl)-7-) lance-(2-(3-pyridyl)
-ethynylcou 5H-thiazolo(3,2-a)pyrimidin-5-one, 6-methoxy3-'(4-methoxy-phenyl)-
7-) lance-[:2-(3-pyridyl)-ethynyl-5H-thiazolo(3,2-a]pi=122-rimidin-5-one, 6-medoxy-3-(4-chlorophenynoly7-trans- (2-(3-pyridyl)-ethynyl-5H-
Thiazolo(3,2-a ]]pyrimidin-5-one 6-medoxy3-(4-methyl-phenyl)-7-trans-(2-(3-pyridyl)-ethynyl2-5H-
Thiazolo(3,2-a)pyrimidin-5-one, and 6-medoxy3-phenyl-7-trans-[2'-
(3-pyridyl)-ethynyl-5H-thiazolo(3,
2-a]]Pyrimidin-5-one Example 16 Using ethyl 2-methylacetoacetate, Example 1
The following compounds were prepared by operating according to 2.

6-methyl-3-trifluoromethyl-7-trans-
[2-(3-pyridyl)-ethynyl]-5I'(-thiazolo[3,2-a)pyrimidin-5-one, 6-methyl-3-(3-pyridyl)-7-trans-(
:2-(3-biIJdyl)-ethynyl2-5H-thiazoo C3,2-a)pyrimidin-5-one, 6-methyl-3-(2-pyridyl)-7-trans-[
2-<3-pyridyl-ethynyl]-57(-thiazolo[3,2-a ]]pyrimidin-5-one 6-methyl-3-(4-pyridyl)-7-) lance-[
2-(3-pyridyl)-ethynyl-5H-thiazolo(
3,2-a) Pyrimidin-5-one, -6-methyl-3-(4-biphenyl)-7-trans-
C2-C5-pyridyl)-ethynyl]-5) T-thiazoo C3,2-a) pyrimidin-5-one, 2-chloro-6-methyl-7-trans-[2-(3-
pyridyl)-ethynyl-5H-thiazolo(ri, 2-
a ]]pyrimidin-5-one 6-methyl-3-phenyl-7-trans-[2-(3-pyridyl)-ethynyl) -5H-thiazolo[3,2-a ]]pyrimidin-5-one 6-methyl- 6-(4-chloro-phenyl)-
7-trans-C2-(5-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-methyl-3-(4-methyl-phenyl)-7-trans-(2- (3-pyridyl)-ethynyl-5H-thiazolo(5,2-a)pyrimidin-5-one, 6-methyl-3-(4-methoxy-phenyl)125--7-trans-(2-(3-pyridyl) )-ethynyl2-5H-thiazolo(3,2-a)pyrimidin-5-one, and 6-methyl-3-(2-chenyl)-7-)lance-C
2-(3-Hiry')-ethynyl]-5T(-thiazolo(5,2-a')pyrimidin-5-one.

Example 14 2-Chloro-7-chloromethyl-5H-thiazoloC3,2-a]pyrimidine- prepared according to Example 5
5-off (6,079) was reacted with sulfuryl chloride (3, El) in dichloroethane (15M) with stirring at room temperature for 4 hours. The reaction mixture was diluted with 5% NaH.
After treatment with aqueous CO3 solution, the organic phase was then separated and evaporated to dryness in vacuo. This was crystallized from methanol and 5.6f of 2,6-dichloro-7-chloromethyl 12
6- -5H-Thiazoo (3,2-a)pyrimidine-5-
On [melting point 117-119℃ (decomposition)] was obtained, and the temperature was 2.
Reacted with triphenylphosphine (5,959) in acetonitrile (115yd) at reflux temperature for 0 hours. The solution was evaporated to dryness in vacuo and the residue was purified with inpropyl ether 10. , In [2,6
-dichloro-5H-thiazolo[3,2-a)pyrimidin-5-one-7-yl]-methyl-triphenylphosphonium chloride was obtained, which was suspended in dimethyl sulfoxide (50-) and dimethyl Treated with potassium tert-butoxide (2,419) dissolved in sulfoxide (45 m/). The solution of the ylide thus obtained was reacted with 6-pyridine-carboxaldehyde (2,369) at room temperature for 20 hours. The reaction mixture was diluted with ice water, neutralized with NaH2PO4 and the precipitate was filtered and crystallized from methanol to give 3.45 f of 2,6-dichloro-7-trans-(2-(3-pyridyl)-ethynyl2). 5H-thiazolo[3,2-a)pyrimidin-5-one (melting point 242-243°C) was obtained.

NM'R(CDCl2) δ ppm: 7.33
(da) (IH, C-5 pyridyl proton), 7.
51 (d) (IT(, β-ethynyl proton), 7
．． 83(8) (IH, c'-3 proton), 7.88
(d) (IH, a-x tenyl proton), 7.91
(at) (IH, c-4 pyridyl proton), a5
a (ba)clH,' c-6 pyridyl proton),
8.80 (bs) (ITJ, C-2 pyridyl proton), JHaHp-6Hz0 By similar operation) the following compound was produced.

6-chloro-3-methyl-7-trans-[2-(3-
pyridyl)-ethynyl2-5H-thiazolo[3,2-a
) Pyrimidin-5-one (melting point 219-220°C, )
, 6-chloro-2,3-')methyl-7-trans-(2
-(3-pyridyl)-ethynyl-5H-thiazoloC3
, 2-a) Pyrimidin-5-one (melting point 226-22
8°C), 6-10rho-3-phenyl-7-5nsC2-C5
-pyridyl)-ethynyl)-5H-thiazoloC3,2-
a]]pyrimidine-5-one melting point 203-204°C)
, 6-chloro-3-(4-chloro-phenyl)-7-trans-[2-(3-pyridyl)-ethynyl]-5■-thiazolo[3,2-a)pyrimidin-5-one (melting point 2
78-280℃), 6-chloro-3-(4-methoxy-
phenyl)-7-trans-[2-(3-pyridyl)-
Ethynyl-5H-thiazoloC3,2-a pyrimidin-5-one (melting point 264-265°C), 6-chloro-3-(4-fluoro-phenyl)-7-trans-
(2-(3-pyridyl)-ethyl)-5H-thiazoloC3,2-a pyrimidin-5-one (melting point 268-269°C), 6-chloro-
3-(4-methyl-phenyl)-7-trans-C2-
C5-pyridyl)-ethynyl-5H-thiazolo(3,
2-a) Pyrimidin-5-one (melting point 258-259
°C), 6-1oO-3-(3-methoxy-phenyl)-
7-trans-C2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a]]pyrimidin-5-one 6-chloro-3-(2-methoxy-phenyl)-7-trans-[2-( 3-pyridyl)-ethynyl-5H-
ThiazoloC3,2-a ]]pyrimidin-5-one 6-chloro-3-(2-thenyl)-7-) lance-C
2-(3-hir')-ethynyl-5H-thiazoO
C3,2-a) Pyrimidine-5-1,30-naso,6-chloro-6-tert-butyl-7-trans-(2-
(3-pyridyl)-ethynyl-5T(-thiazoloC-,
3,2-, a) Pyrimidin-5-one, 6,,-ri0
Rho 37, lJ fluoromethyl-7-trans-[
2,-(3,-pyridyl)-ethynyl]-one (melting point 247-249°C), 6-chloro-3-(3,4-ethylenedioxy-ester), , 7. ,, =, ) Lance 2 [27(3
-pyridyl)-ethynyl2-5H-thiazolo[3,2-
a,,) pyrimidien-5-one, 6-chloro-3-(3,4-dimethoxy-phenyl)-
7-trans-[:,2-(3-pyridyl)-ethenyl]-5H-thiazolo[3,2-a)pyrimidine-5-
6-chloro-3,,-(,2,4-,dimethoxy-phenyl)-7-trans-(2-(3-pyridyl)-ethynyl2-5H-thiazoloC3,2-a]]pyrimidin-5-one 6-chloro-2-methyl-3-phenyl-7-trans-(2-(3-pyridyl)-ethemole)-5!-thiazolo[3,2-a)pyrimidin-5-one (melting point 229
~232°C), 6-chloro-2-cyano-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2,-a:]]pyrimidin-5-one 6-chloro-3- (6-pyridyl)-7-) lance-(,27,
(3-,)-'lysyl)-ethyl]-5F(-thiazoloC3,2-,a,)pyrimidin-5-one (melting point 2
74-275°C), 6-chloro-3-(2-pyridyl)-7-) lance-(
j-(3,-pyridyl)-ethynyl]-5H-thia,zoo,c,3. ,2-a) pyrimidin-5-one, 6-chloro-6-(4-pyridyl)-77) lance-[
2-, (3-pyridyl)-, ethynyl-5H-thiazolo[ro, 2-a) pyrimidine-5-sun-6-chloro-3-(4-biphenylyl)-77-[2-(3,7-pyridyl) )-ethynyl2-5H-thiazolo[3,2-4]pyrimidin-5-one, 6-chloro-3-(2-naphthyl)=,'77) lance7[2-,(3-pyridyl)-ethynyl]75 H-Thiazoo C3,,2-a']pyrimidin-5-one, 6-chloro-6-(2-nitro□-phenyl)-7-to, lance-(2,7(,3-pyridyl)-ethynyl2) 5H-thiazolo(”+2- a, ]]pyrimidine-5
-one-,133- 6-chloro-3-(2-amino-phenyl)-7-trans-(2-(3-pyridyl)-ethynyl2-5H-thiazolo[3,2,-a)pyrimidin-5-one , 6-chloro-5-(3-amino-phenyl)-7-trans-[,,2-(3-pyridyl)-ethynyl25H
-thiazolo(5,,27,a, :lpyrimidine-5-
on, 6-chloro-3-(4-amino-phenyl)-7-trans-[2-(3-pyridyl)-ethynyl2-5H-thiazolo[3,2=, a)pyrimidin-5-one, 6-chloro -7-trans-[2-(2-methyl-5-
thiazolyl)-ethynyl)-5H-thiazolo(,3,2
7a, 1 pyrimidin-5-one (melting point 230-233
°C), 2,6-dichloro-7-trans-C2-C2134- -methyl-5-thiazolyl)-ethynyl) -5H-thiazolo(3,2-al)pyrimidin-5-one, 6-
Chloro-3-methyl-7-trans-[2-C2-,I
f syl--thiazolyl]-ethynyl]-5H-thiazoloC3,2-a]]pyrimidin-5-one 6-chloro-2,3-dimethyl-7-trans-C2-
(2-Methyl-5-thiazolyl)-ethynyl]-5H-
ThiazoloC3,2-a ]]pyrimidin-5-one 6-chloro-7-trans-['2-(2-methyl-5
-thiazolyl)-ethynyl]-3-phenyl-5H-thiazoloC3,2-a)pyrimidin-5-one (melting point 1
90-192°C), 6-chloro-7-trans-C2-
C2-methyl-5-thiazolyl)-ethynyl) -3-
) Lifluoromethyl-5H-thiazolo[3,2-a
] Pyrimidin-5-one, and 6-chloro-7-trans-C2-C2-methyl-5-
thiazolyl)-ethynyl ml -3-(3-biridyl)
-5H-thiazolo[:3.2-'a)pyrimidine-5-
Example 15 4-carbethoxymethyl-2-amino-thiazole (
149) was reacted with ethyl 4-chloro-acetoacetate (1,39) in polyphosphoric acid (70f) with stirring at 100° C. for 2.5 hours. After cooling, diluting with ice water and neutralizing, the precipitate was filtered and washed with water.
-carbethoxymethyl-7-chloromethyl-5H-thiazoloC3,2-a)pyrimidin-5-one (melting point 9
4-95[deg.]C) 19,r was obtained, which was stirred at reflux for 200 hours and then reacted with triphenylphosphine (19,1') in acetonitrile (100 m/). After cooling, the precipitate was filtered and washed with isopropyl ether (3-carbuethoxymethyl-5H-thiazoloC3,2-a)pyrimidin-5-one-7-yl).
-Methyl-triphenylphosphonium chloride (melting point 295°C (min M)) 1 sy was obtained, which was mixed with dichloroethane (11]Om/) and dimethyl sulfoxide (75% N in 100 ml) with stirring.
aH(1,312) and 25°C for 6 hours.
3-pyridine-carboxaldehyde (5,7
62). The reaction mixture was diluted with ice water and Na
After neutralization to pH 6 with H2PO4 and extraction with dichloroethane and evaporation to dryness in vacuo, the residue was crystallized from methanol to give 7-trans-[2-(3-pyridyl)
-ethynylcu-5-okine-5H-thiazoo (3,2
-a) Pyrimidine-3-acetic acid ethyl ester (melting point 1
85-187℃)-13'7-5.352 was obtained, and this was heated at reflux temperature for 1 hour to 37) IC.
/, (6 [3 mg)] and acetic acid (60 g), cooled the sample, diluted with ice water, and then diluted with 35 g of NaOH.
After neutralization to pH 6 with pH 6, the precipitate was stirred and crystallized from dimethylformamide/water to give 3.32 of 7-trans-(2-(3-pyridyl)-ethynyl]-5-oxo5H-thiazolo[3 ,2-a]pyrimidine-3-acetic acid[
A melting point of 300°C (decomposition) was obtained.

NMR (CF3C'0OD) δppm: 4.61
'(bs) (2H, CH2C00H), 7.07(8
) (IH, c-6 proton), 7.66 (d) (I
H, β-ethynyl proton), 7.68 (s) (1H
, C-2 proton), a06(d) (IH, α-ethynyl proton), 8.40 (dtl) (1H.

C-5 pyridyl proton), 9.09(m) (2T(
, c-4 and C-6 pyridyl protons), 9.37
(bs) (IH, C-2 pyridyl proton), JHa
Hp-16Hz.

138- operated similarly using the appropriate aldehyde. As a result, the following compounds were produced.

7-trans-[2-(2-hylysyl)-ethynyl]
-5-okine-5H-thiazolo[5,2-a]pyrimidine-3-acetic acid, 7-trans-C2-C4-pyridyl)-ethynyl-5-oxo-5H-thiazolo[6,2-a)pyrimidine-6- Acetic acid, 7-trans-[:2-C6-methyl-2-pyridyl)
-ethynyl-5-oxo-5H-thiazolo(3,2-
a) Pyrimidine-3-acetic acid, 7-trans-C2-(
2-Methyl-5-thiazolyl)-ethynyl-5-auxo 5H-thiazoloC3,2-a) pyrimidine-3
-acetic acid, 7-trans-[2-(1-methyl-2-pyrrolyl)-ethynyl]-macro-okine-5H-thiazolo[3
,2-a ]]pyrimidine-3-acetic acid 7-trans-(
2-phenyl-ethynyl)-5-oxo-5H-thiazoo C3,2-a) pyrimidine-3-acetic acid (melting point 25
2-255°C), 7-trans-C2-C4-methoxyphenyl)-ethynyl]-5-oxo5H-thiazoloC3,2-a]]pyrimidine-3-acetic acid 7-trans-(2-(4- Chloro-phenyl)-ethynyl-5
-oxo-5H-thiazolo(3,2-a)pyrimidine-3-acetic acid, 7-trans-C2-(2,6-dichloro-phenyl)-ethynyl m1-5-ox:/-5'H-
Thiazolo[3,2-a)pyrimidine-3-acetic acid, and 7-trans-(2-(2,4-:)chloro-phenyl)-ethynyl]-5-4xo5H-thiazoloC3,2
-a]]pyrimidine-3-acetic acid Example 16 The following compound was prepared by operating according to Example 9 starting from the appropriate 6-substituted-5H-thiazolo[3,2-alpyrimidin-5-one. Ta.

6-Methyl-7-trans-[2-(3-pyridyl)-
ethynyl]-5-ogiso5H-thiazoloC3,2-a
) Pyrimidine-3-acetic acid, 6-chloro-7-trans-[2-(2-pyridyl)-ethynyl-5-oxo-
5H-thiazolo[3,2-a)pyrimidine-3-acetic acid, 6-chloro-7-trans-(2-(4-pyridyl)
-ethynyl-5-oxo-5H-thiazolo(3,2-
a ]] Pyrimidine-3-acetic acid 6-chloro-7-trans-[2-6-methyl-2-HJ yl)-ethynyl)-5-oxo-thiazolo(5,2-a)pyrimidine-3-acetic acid, 6-chloro-7-trans-(2-(2-
Methyl-5-thiazolyl)-ethynyl]-5-o141
- Nakaso-5H-thiazoloC3,2-a ]] Pyrimidine-3-acetic acid 6-chloro-7-trans-(2-(1-methyl-2-
pyrrolyl)-ethynyl)-5-oxo-5H-thiazolo(3,2-a)pyrimidine-3-acetic acid, 6-methyl-7-trans-C2-C4-methoxy-phenyl)-ethynyl)-5-o* /-5H-thiazo0
(3,2-a]]pyrimidine-3-acetic acid 6-methyl-7-trans-C2-C4-rioo-phenyl)-ethynyl)-5-, :t#/-5H-thiazoo
C3,2-a') pyrimidine-6-acetic acid, 6-methyl-7-trans-(2-phenyl-ethynyl)-5-oxo-5H-thiazolo-C3,2-a ]]
Pyrimidine-3-acetic acid 142-6-chloro-7-trans-C2-(2,6-dichloro-phenyl)-ethynyl)-5-,t*so5H-thiazolo(3,2-a)pyrimidine-3-acetic acid , 6-chloro-7-trans-[2-(3-pyridyl)-
ethynyl]-5-oxo5H-thiazolo[3,2-a
]] Pyrimidine-3-acetic acid melting point 320-330°C (decomposition), NMR (CDC6-CH2COOD) δ ppm
: 4.3 o (8) (2T(, -CH2
COO-) , :, 1 1 (s) (IT
(.

C-2 proton), 7.73 (d,) (IH, β-
ethynyl proton), 7,98 (d) (IT(,a
-ethynyl proton), 8.0'9 (m) (1)T
.

C-5 pyridyl proton), 8.80 (IT+) (
2H, C-4 and C-6 pyridyl protons), 9.0
8 (bs) (IH, C-2 pyridyl proton), JH
6Hp = 1.6 H2O6-rioo-7-) lance-(2-phenyl-ethynyl)-5-oxo-5H-thiazolo-C3,2-a) pyrimidine-3-acetic acid (melting point 301-303 °C) and 6-Chloro-7-trans-C2-C4-methoxy-phenyl)-ethynyl]-5-oxo-5) T-thiazoo
C3,2-a ]]Pyrimidine-3-acetic acid Example 17 7-Methyl-5H-thiazolo[3,2-a] prepared according to Example 1 using ethyl acetoacetyltra
]]Pyrimidine-5-one melting point 127-129℃)4
2 was dissolved in benzene (10M) and stirred for 1 hour at room temperature before dissolving N'-bromo-succinimide (4,7
9).

The precipitate was dissolved by adding chloroform, the solution was washed with water, evaporated to dryness in vacuo and the residue was crystallized from methanol to give 6-promorph-methyl-5H-
ThiazoC1 [3,2-a ml pyrimidin-5-one (
5.12 (melting point 263-234°C) was obtained, which was heated under reflux temperature for 2 hours with sodium methoxide (2,25°C).
6 in methanol (190 m/) in the presence of
-pyridine-carboxaldehyde (3,4 g).

After cooling, the precipitate is filtered and washed with water in a neutral trench, c.
Crystallization from H2ct2/methanol yielded 5.182 6-bromo-trans-(2-(3-pyridyl)-
Ethynyl-5H-thiazolo[3,2-a]pyrimidin-5-one was obtained.

Melting point 208-209℃, NMR (CDCl2) δppm
:6.99 ((1) (IH, C-2 proton), 7.
33 (dd) (IH, C-5 pyridyl proton),
7. s q (a) (IH, β-ethynyl proton), 7,95 (d) (IH, a-ethynyl proton), 7.96 (a) (IH.

C-3 proton), 7. '? 8(m) (IH, c-4 pyridyl proton), 8.58 CM) (IH, C-6
pyridyl proton), 8.82 (bs)' (IH,
C-2 pyridyl proton), JHaI (β-1'6H2
0 145- The following compound was produced by a similar operation.

6-promoardransuC2-C2-pyridyl)-
Ethynyl-5H-thiazolo[3,2-a]pyrimidin-5-one, 6-bromo-trans-[2-(4-pyridyl)-
Ethynyl-5H-thiazolo[3,2-a)pyrimidin-5-one and 6-bromo-trans-[2-(6-methyl-2-a)
pyridyl)-ethynyl] -5H-thiazolo[3,2-
a) Pyrimidin-5-one.

Example 18 7-trans-(2-(
2-nitro-phenyl)-ethynyl-5H-thiazolo[3,2-a)pyrimidin-5-one (10f)
37 HC1 (45 yd) while stirring at 60℃ for 4 hours
and 5nC42・2H2 in acetic acid (1ss-)
0(74f). After cooling, pour the precipitate into a P pot, wash with water in a neutral trench, and add 2-5% NaHCO7 aqueous solution (300++) while pressing with your fingers.
+A). The precipitate was filtered and washed with water until neutral, and after purification with hot chloroform, the 7-
trans-[2-(2-amino-phenyl)-ethynyl-5H-thiazolo(,3,2-a]pyrimidine-5-
(melting point 246-248°C) was obtained.

NMR (CDC1, -DMSOd6-CF5 C00
D) δppm: 6.62 (S) (IH, c -6
proton), 7.10 (a) (IH, β-ethynyl proton), 7.48 (d) (II (, C-2 proton), 7. s 5 (m) (3H, C-3, C- 4 and C-5 phenyl protons), 7.88 (m) (I
T(,C-,6Fe,=,luproton), 8.16(a
) (IH.

α-ethynyl proton), 8.18(a) (IH, c-
3 protons), JHaHβ=16H20 The following compounds were produced by similar operations.

3-[4-amino-phenyl)-7-) lance-(2-
(3-pyridyl)-ethynylcou-5H-thiazolo(3,
2-a ]]pyrimidin-5-one 6-(3-amino-
phenyl)-7-trans-[2-(3-pyridyl)-
Ethynylku 5H-thiazoloC3,2-a :]]pyrimidin-5-one Example 19 7-trans-C2- prepared according to Example 4
C4-Hydroxy-3-iodo-phenyl)-ethynylcou 5H-thiazolo[3,2-a]pyrimidin-5-one (1,4f) was dissolved in pyridine (1,4f) with stirring at room temperature for 2 hours.
5,6ml) and dimethylacetamide (3omg)
After diluting with ice water, the precipitate was filtered and washed with water until neutral, and crystallized from dioxane to give 1.22 7-trans-[2 -(4-acetoxy-3-iodo-phenyl)
-ethynylcou 5H-thiazolo[3,2-a]pyrimidin-5-one was obtained.

Melting point 272-275°C, NMR, (CDCA3-CF3
COOD) δppm: 2.52 (s) (3H, -
0cOCT(3), 6.91 (s) (11(,C-
6 protons), 7.03 Ca”+ (IT(, β-ethynyl proton), 7.22(d) (11(, C-5
phenyl proton), 7.66 (a) (IH.

α-ethynyl proton), 7.67(d) (11-I
, C-2 proton), 7, 67 (dd) (IH,
C-6 phenyl proton), 8.13 (d) (1H,
, C-2 phenyl proton), 8.37 (d) (I
H, C-3 proton), JH, yHβ-16H20 The following compounds were produced by operating in the same manner.

7-trans-(2-(2-N-acetylamino-phenyl)-ethynyl)-5H-thiazolo[,3,2-a:
I pyrimidin-5-one (melting point 240-242°C), 3-(4-N-acetylamino-phenyl)149- -7-trans-[:2-(3-pyridyl)-ethynylcou 5H-thiazoloC3,2 -a) Pyrimidine-5-
one, 3-(3-N-acetylamino-phenyl)-7-trans-(2-(3-pyridyl)-ethynyl-5H-thiazoloC3,2-a ]]pyrimidin-5-one and 3-(2-N -acetylamino-phenyl)-7-trans-[:2-(3-pyridyl)-ethynylcou 5H-
Thiazolo[3,2-a]]pyrimidin-5-one Example 20 Trimethyl-sulfoxonium iodite (10,4F
) was stirred at room temperature for 1 hour, then dimethylformamide (
50% sodium hydride (2,2s
5H-thiazolo[3,2-a,)pyrimidin-5-one (6f) in dimethylformamide (50 mL).
The solution and solution were added. The mixture was allowed to react for 20 hours with stirring at room temperature, then it was diluted with ice water and diluted with NaH2.
Neutralized with PO4 and extracted with chloroform. After evaporation in vacuo, the crude residue was purified on 5102 using ethyl acetate as eluent and crystallized from ethyl acetate to give 2.357 7-trans-(2-(3-pyridine) treecyclopropyl]-5H-thiazolo[3,2-a]pyrimidin-5-one was obtained.

Melting point 115-117°C, NMR (CDC73) δppm
:1.507.1-7.5(m) C2H, C-4 and C-5 pyridyl protons), aOo (a) (1H
, c-3 proton), 8. '5 (m) (2H,c
-2 and C-6 pyridyl protons).

The following compounds were produced by similarly crushing.

-6-methyl-7-trans-C2-C4-pyridyl)-
Cyclopropyl-5H-thiazoloC3,2-a ]]
Pyrimidin-5-one 6-methyl-7-trans-[2
-(3-pyridyl)-cyclopropyl-5H-thiazolo(3,2-a ]]pyrimidin-5-one Melting point 151
~152°C), 6-Nity-7-trans-[2-(3-pyridyl)-
cyclopropyl)-5H-thiazolo[3,2-a)pyrimidin-5-one, 2-phenyl-7-trans-1
:2-(3-pyridyl)-cyclopropyl-5H-thiazolo[3,2-a ]]pyrimidin-5-one 6-methyl-7-trans-C2-C4-methyl-phenyl)
-cyclopropyl] -5H-thiazolo(3,2-a
) pyrimidin-5-one (melting point 153-155°C), 6-methyl-7-trans-C2-(2-methoxy-3
-ethoxy-phenyl)-cyclopropyl-5H-thiazoloC3,2-a]]pyrimidin-5-one7-trans-1':2-(1-methyl-2-pyrrolyl)-cyclopropyl]-5)T- Thiazolo (3,2-a
]]Pyrimidin-5-one 3-methyl-7-trans-(2-(3-pyridyl)-cyclopropyl-5H-
Thiazolo(3,2-a:]]pyrimidin-5-one 3
．． 6-dimethyl-7-trans-[2-(3-pyridyl)-cyclopropyl-5H-thiazolo[3,2-a
]] Pyrimidin-5-one 2-chloro-7 citrans-(2'-(3-bi153-lysyl)-cyclopropyl-5H-thiazolo(3,2
-a,) pyrimidin-5-one, 7-trans-(2-
(3-pyridyl)-cyclopropylcy5-oxo-5
H-thiazolo[3,2-a)pyrimidine-3-acetic acid,
7-) Lance-(2-phenyl-cyclopropyl)-5
-oxo-5H-thiazolo[3,2-a]pyrimidine-
5-acetic acid, 6-chloro-7-trans-C2-C3-pyridyl)-
[cyclopropyl]-5-oxo5H-thiazoloC3,
2-a ]]pyrimidine-3-acetate 6-methyl-7-trans-[2-(3-pyridyl)-cyclopropyl]-
5-oxo5H-thiazolo(3,2-a ]]pyrimidine-6-acetic acid 2.3.b -trimethyl-7-trans-[:2-(3-pyridyl)-cyclopropyl]-
5H-thiazoloC3,2-a) pyrimidin-5-one [melting point 154-120°C (decomposition)], 6-chloro-7-trans-(2-(3-pyridyl)-
Cyclopropyl': l-5H-thiazolo(3,2-a
]]pyrimidine-5-one melting point 159-161°C), 6-chloro-3-phenyl-7-) lance-[:2-(
3-pyridyl)-cyclopropyl-5H-thiazo
[:3,2-a]]pyrimidine-5-one melting point 1
66-138°C), 6-chloro-7-trans-(2-(2-methyl-5-
thiazolyl)-cyclopropylio5H-thiazolo(3
,2-a:l pyrimidin-5-one (acid 11 points 174
~175°C), 6-methyl-2-phenyl-7-trans-(2-(3
-H')-cyclopropyl-5H-thiazoo
(5,2-a)pyrimidin-5-one (melting point 210
~216°C), 6-medoxy7-trans-C2-(3-pyridyl)
-cyclopropylio5H-thiazolo[3,2-a]
]pyrimidine-5-one (melting point 92-95°C), 2-chloro-6-methoxy7-trans-C2-(3
-HiIJ sil)-cyclopropylio5H-thiazoloC3,2-a)pyrimidin-5-one, 6-methyl-7-trans-[2-(2-pyridyl)-
Cyclopropyl:]-]5H-thiazoloC3,2-a
:]]Pyrimidin-5-one 6-methyl-7-trans-[2-(6-methyl-2-pyridyl)-cyclopropyl 11-5H-thiazoloC3,2-a)pyrimidine-
5-one, 6-chloro-7-trans-[:2-(3-
pyridyl)-cyclopropyl-3-trifluoromethyl-5H-thiazoloC3,2-a]]pyrimidine-5
-one 6-chloro-7-trans-[:2-(3-pyridyl]
-cyclopropyl]-3-)lifluoromethyl-5H-
ThiazoloC3,2=a]]pyrimidin-5-one 6-chloro-7-trans-[2-(3-pyridyl)-
cyclopropyl)-3-(2-chenyl)-5H-thiazoloC3,2-a)pyrimidin-5-one, 6-chloro-3-(3-pyridyl)-7-trans-[
2-(3-pyridyl)-cyclopropylio5H-thiazolo(3,2-a)pyrimidin-5-one, 6-chloro-3-(2-pyridyl)-7-trans-[
2-(3-pyridyl)-cyclopropylio5H-thiazolo(3,2-a)pyrimidin-5-one, -15'i'-6-chloro-3-(4-pyridyl)-7-trans-[
2-(3-pyridyl)-cyclopropylio5H-thiazoloC3,2-a)pyrimidin-5-one, 6-chloro-6-(4-biphenylyl)-7-trans-[2-(3-pyridyl) -Cyclopropylyo 5H-
Thiazolo[3,2-a)pyrimidin-5-one, 6-chloro-3-phenyl-7-trans-(2-(3
-pyridyl)-cyclozolovir]=5H-thiazolo(3
,2-a ]]pyrimidin-5-one 6-chloro-3-(4-chloro-phenyl)-7-trans-C2-(3-bi-ridyl)-cyclopropyl-5H-thiazolo[3,2 -a]Pyrimidin-5-one, 6-chloro-3-(4-methyl-phenyl)158- -7-1.Lance-[2-(3-pyridyl)-cyclopropyl]-5H-thiazoloC3,2 -a:]]pyrimidin-5-one and 6-chloro-3-(4-methoxyphenynoly7-trans-[2-(3-pyridyl)-cyclopropyl]-
5H-thiazolo(3,2-a]]pyrimidin-5-one Example 21 7-)Lance-(2-phenyl-ethynyl)-5-oxo-5H-thiazoOC3,2-a Tlpyrimidine-3
- Acetic acid (1,29) was heated at reflux temperature for 2 hours to dioxane (1,29).
It was reacted with thionyl chloride (0.6 m/ml) in a 2 m/ml solution and the mixture was then evaporated to dryness in vacuo.

The residue was reacted with excess ethanol for 30 minutes at 50°C, then the solution was concentrated in vacuo and the residue was diluted with ice water. Filter the precipitate, wash with water, and add cH2
cz2/0,8 crystallized from isopropyl ether
5 r7-trans-(2-phenyl-ethynyl)-
5-oxo-5H-thiazoloC3,2-a]pyrimidine-3-acetic acid ethyl ester was obtained.

Melting point 252-255℃, NMR (CDC't3) δpp
m: 1.29(t) (3H, -CH2CH3),
4.12 (be) (2H, -CH2COO-), 4
．． 22 ((1) (2H, -ca2cu3), 6.13
(8) (1H, c L 6 protons), 6.62
(be) (II(, C-2 proton), 6.85
((1) (1H2β-ethynyl proton), 7.2~
7.7 (→ (5H, phenyl proton), 7.7 s
(a) (IH, α-ethynyl proton), JHnHp
-1'6 H20 The following compounds were produced by operating in the same manner.

6'-rioo-7-) lance-(2-phenyl-ethynyl)-5-oxo-5H-thiazolo(3,2-a)
Pyrimidine-3-acetic acid ethyl ester (melting point 214-2
17℃).

Example 22 7-trans-[2-(3-pyridyl)-ethynyl-5-oxo-5H-thiazolo[6,2-a]pyrimidine-3-acetic acid ([ ], El) was stirred at room temperature for 6 hours. in dimethylformamide (7me) from ethyl iodide (0,6!M) and anhydrous x2co3 (0,652)
I reacted. After dilution with ice water, the precipitate was filtered and washed with water until neutral, then crystallized from methanol to give 0.5 Fl of 7-trans-(2-(3-pyridyl)
-ethynyl]-5-okine-5H-thiazoo (3,2
-a) Pyrimidine-3-acetic acid ethyl ester was obtained.

Melting point 185-187℃, NMR (CDCl2) δppm
: 1.29(t) (3H, -CH2CH5), 4
．． 14 (8) (2H, -CH2-Coo-), 4,
33 (q) (2I(,-42CH3), 6.16
(s) (IH, C-6 proton), 6.66 (s)
(IH, C-2 proton), 6.90 (d) (I
H.

161-β-ethynyl proton), 7.30 (da) (1T
(, C-5 pyridyl proton), 7.75 (d) (I
I-T, C-4 pyridyl proton), 7, 89 (d
d, d) (IT(, C-6 pyridyl proton), 8.
54 (Jad) (IT(, C-2 pyridyl proton)
, 8.87 (aa) (1H1α-ethynyl proton),
−'H, Hβ=16Hz.

The following compounds were produced by similar operations.

6-chloro-7-trans-C2-C6-pyridyl)-
Ethynyl-5-oxo-5H-thiazoloC5,2-a
]]Pyrimidine-6-acetic acid ethyl ester melting point 242
~243°C).

Example 23 6-Hydroxyl 7-trans-(2-(3-H+7')) dissolved in dimethylformamide (40-)
-Ethynyl:]-5H~Thiaso0[:3,2-a]pyrimidin-5-one (2,7p) was added to 2CO3(2,[]7t) in anhydrous solution with stirring at 50°C for 5 hours.
2- Reacted with methyl iodide (2, 12g) in the lower right. After cooling, the reaction mixture was diluted with ice water and the precipitate was filtered, washed with water and crystallized from 50% ethanol.
05P 6-methoxy7-trans-[2-(3-pyridyl)-ethynyl]-5T(-thiazoo (3,2-
a]]pyrimidine-5-one melting point 186-187°C)
I got it.

Example 24 Isopropyl and n-butyl esters of the following compounds were prepared by operating according to Examples 21 and 22.

7-trans-(2-phenyl-ethynyl)-5-oxo-5H-thiazo0 [3,2-a)pyrimidine-3
-acetic acid, 7-trans-C2-('3-pyridyl)-ethynyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-acetic acid, 6-chloro-7-trans-(2-phenyl- ethynyl)-5-oxo-5H-thiazoloC3,2-a:) pyrimidine-3-acetic acid, and 6-chloro-7-trans-(2-(3-pyridyl)-ethynyl-5-oxo-
5H-thiazolo(3,2-a)pyrimidine-6-acetic acid.

Example 25 6-medoxy7-trans-C2-(3-pyridyl)
-ethynyl]-5H-thiazolo[6,2-a)pyrimidin-5-one (2,35') was dissolved in ethyl acetate and treated with a stoichiometric amount of gaseous HCt in ether to precipitate. Filter and wash with ethyl acetate 2.1
7 of 6-methoxy 7-trans-(2-(3-pyridyl)-ethynyl)-5H lower thiaso-C3,2-a]
] Pyrimidine-5-one hydrochloride Melting point 205-210℃ (
decomposition)] was obtained.

The following compounds were produced by similar operations.

2-chloro-6-methoxy7-trans-[2-(3
-pyridyl)-ethynyl]-5H-thiazolo(3,2-
a) Pyrimidin-5-one hydrochloride, 2-chloro-7-trans-(2-(3-pyridyl)-
Ethynyl-5H-thiazolo[3,2-a)pyrimidin-5-one hydrochloride, and 6-methyl-7-trans-
[2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a) pyrimidin-5-one hydrochloride.

Example 26 Pyrimidine-3-vinegar was dissolved in a stoichiometric amount of NaT ( The solution was concentrated to dryness in vacuo and diluted with acetone. The precipitate was filtered and washed with acetone (7).
Lance-(2-phenyl-ethynyl)-5-oxo-5
H-thiazo o[3,2-a]]pyrimidine-3-sodium acetate salt (melting point>300°C) was obtained.

The following compounds were produced by similar operations.

7-trans-[2-(3-pyridyl)-ethynyl-5-oxo-5H-thiazolo[3,2-a) pyrimidine-3-acetic acid sodium salt, 6-chloro-7-trans-
(:2-(5-pyridyl)-ethynyl-5-oxo-
5H-thiazoloC3,2-a)pyrimidine-3-acetic acid sodium salt and 6-chloro-7-trans-(2-phenyl-ethynyl)-5-oxo-5H-thiazolo(3,2-a)pyrimidine-3 - Sodium acetate salt.

166- Example 27 Each contains iomg of active substance and weighs 200 kg [4°]. Tablets are manufactured as follows.

Composition (per 10,000 tablets) C3,2-a,
) Pyrimidin-5-one 1ooo it
'Lactose 7107 Corn starch 237.59 Talc powder 37.517' Magnesium stearate 15 f2-chloro-7-trans-(2-(5-pyridyl)-ethynyl)
-5H-thiazolo[3,2-a]pyrimidin-5-one, lactose and half the corn starch are mixed and the mixture is forced through a 0.5 inch sieve.

Cornstarch NsB is suspended in warm water (180g). The resulting R-st is used to granulate the powder. The granules were dried and ground on a sieve with a mesh size of 1.4 mm, then the remaining amounts of starch, talc and magnesium stearate were added, carefully mixed and tableted using an 8 barrel diameter punch. Process it into

Patent applicant: Farmitalia Calguchi Erba,
Continuing from page 1 of Società R. Le Azioni Priority claim ■During January 20, 1982) United Kingdom (G
B) ■8201621 @April 29, 1982■United Kingdom (GB)■8212430 (C Inventor Giuliana Alcali, Milan, Italy, ViasisMondei4 @Inventor: Ada Buttinoni, Milan, Italy, Viamontes Etsuro 18

Claims (1)

[Scope of Claims] 1) Compounds having the following general formula (1) and pharmaceutically acceptable salts thereof [wherein A is a bond and thereby α- and β-
- a double bond is formed between the carbon atoms, or A is a 10H2- group thereby forming a cyclopropane ring containing α- and β-carbon atoms, and each of R1 and R2 is independently a) hydrogen or halogen atom; b) 01-04 alkyl, cyano or trifluoromethyl; C) chenyl, pyridyl, biphenyl or naphthyl; d) unsubstituted or halogen; C4 alkoxy, formyloxys C2~CB alkanoyloxy, trifluoromethyl, nitro, aminoformylamino and 02~C
1 to 3 selected from the group consisting of 8 alkanoylamino
e) a phenyl group substituted by one or two C1-C4 alkylenedioxy groups, where the oxygen atom is bonded to two adjacent carbon atoms of the phenyl ring; ), or each independently a hydrogen atom or C1-c! 4 represents an alkyl group), and R3 is ′ a hydrogen or a syn atom. b'), ,, (', 1~04 A, Lukiru, C/)
human 90xy, formyloxy or C2(8alkanoyloxy, 4 or (1')01''(34alkoxy or 03~C
4alkenyloxy, R4 is a pyridyl group which is unsubstituted or optionally substituted by 01-C4 alkyl, and R4 is a halogen atom, a hydroxy group, unsubstituted or C1-C4 alkyl 6-alkoxy group substituted by amino, 01-C4 Al, K, R group, formyloxy, 02-CB Alkanoyloxy group, -NO2 group or -N group IQ (in the formula, each of R9 and RlQ is independently represents a hydrogen atom, a 01-C4 alkyl group, formyl or a 02-C8 alkanoyl group], or a thiazolyl group which may be unsubstituted or still substituted by 01-04'alkyl; ]. 2) A is as described in claim 1, and R1 is hydrogen, 01-02 alkyl, trifluorolythyl, carboxymethyl, pyridyl, biphenyl,
naphthyl or phenyl, the phenyl being unsubstituted or substituted as described above, and R
2 is hydrogen, chlorine, bromine, 01-02 alkyl, cyano or phenyl (which is unsubstituted or substituted as described above); R3 is hydrogen, chlorine, bromine, 01-02 C3 alkyl spans C1-02 alkoxy, and R4 is a#') pyridyl group unsubstituted or substituted by methyl, b1#l)
unsubstituted or substituted with one or two substituents selected from the group consisting of 01-02 alkyl, chlorine, iodine, hydroxy, 01-02 alkoxy, amino, acetylamino and acetoxy phenyl group,
ft
8. A compound having formula (I) according to claim 1 and a pharmaceutically acceptable salt thereof. 3) The following: 7-trans-[2-(3-pyridyl)-5 = ethynyl-5H-thiazolo[-3,2-a)pyrimidin-5-one, 7-trans-7-1: 2- (4-methyl-phenyl)
-ethynyl2-5H-thiazolo[3,2-a)pyrimidin-5-one, 6-medoxy7-trans-(2-(3-pyridyl)
-ethynyl2-5H-thiazolo[3,2-a ]]pyrimidin-5-one 2-cyano-7-trans L [:'
2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a″ll pyrimidin-one, “2-chloro-7-trans-(’2-(3-pyridyl)-ethynyl]-5H- [3,'2-a]pyrimidin-5-one, 2-chloro-7-trans-[2-(2-
Methyl-5-thiazolyl)-ethynyl2-5H-thiazolo(3;2-a]pyrimidin-5-one 6-one 2-chloror)7-/, -methoxy-7-trans-[2
-1,-pyridyl)-ethynyl]-5n-thiazolo(3
,2L',a :]]pyrimidin-5-one 1-chloro-6-methyl-7-trans-[2=(3-
pyridyl)-ethynyl]-5H-thiazolo[3,2-a
) l rimidin-5-one, 6-methyl-7-trans-C2” (3-pyridyl)
-ethynyl':] -s H-thiazolo[3,2-a
) Pyrimidin-5-one, 3.6-dimethyl-7-trans-(2-(3-pyridyl)-gotenyl]-5H-thiazoloC3,2-a) Pyrimidin-5-one, 2.3
,6-trimethyl-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-methyl-2-phenyl-7-
trans-(2-(3-pyridyl)-ethynyl-5H)
-thiazoloC3,2-a) pyrimidin-5-one, 6-nityl-7-trans-[2-(3-pyridyl)-
Ethynyl j-sa-thiazolo(3,2-a)pyrimidin-5-one, 6-methyl-7-trans-[2-(2
-pyridyl)-ethynyl2-5H-thiazolo(3,2-
a) Pyrimidin-5-one, 6-methyl-7-trans-C2-C6-methyl-2-pyridyl)-ethynyl)
-5M-thiazolo('3.2-'a)pyrimidin-5-one, 6-methyl-7-trans-C,27(4,-methyl-
phenyl)-ethenyl/I/]-5H-thiazolo[3
,2-a) Pyrimidin-5-one, 6-methyl-7-
trans-(2-'(6-methyl-2-pyridyl)-cyclozolobyl]-5)I-thiazoloC3,2-a ]]
Pyrimidin-5-one 6-methyl-7-trans-(2-(2-pyridyl)-
cyclozolovir) -5H-thiazolo(' 3.2-
a) Pyrimidin-5-one, 6-methyl-7-trans-C2-(3-pyridyl)-cyclopropyl-5H
-thiazolo[5t2-':]]pyrimidin-5-one 6-chloro-7-trans-(2-phenyl-ethynyl)-5H-thiazolo[3,2-a]pyrimidine-5-
2.6-') chloro-7-trans-(2-(3-hyridyl)-ethynyl')-5H-thiazoloC3,2-a
) pyrimidin-5-one, 9-6-chloro-7-thanosu[・2-, ('3'-pyridyl)-ethynyl)"-5H-thiazolo['3.'2
-'a) Pyrimidin-5-one, 6-chloro-6-methyl-7-trans-(2-(3-pyridyl)-ethynyl-5H-thiazolo(s, 2-'al pyridine-5
-one 1 6-chloro-2,3-dimethyl-7-trans-[2-
(3-pyridyl)-ethynyl]-5H-thiazotetraC3'
+2- a]pyrimidin-5-one, 6-chloro-3-trifluoromethyl-7-trans-
1:2-(3-pyridyl)-ethynyl2-5H-thiazolo(312-a)pyrimidin-5-one, 6-chloro-3-phenyl-7-trans-1:2-(
'3-pyridyl)-ethynyl]-5H-1〇--thiazolo[3,2-a)pyrimidin-5-one 1 6-chloro-3-(4-fluorophenyl)-7-trans-[2- (3-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-chloro-6-(4-chloro-phenyl)-7-trans-(2-(3-pyridyl)- Ethynyl2-5H-thiazolo[3,2-a)pyrimidin-5-one 6-chloro-3-(4-methyl-phenyl)-7-trans-[2-(3-pyridyl)-ethynyl25H-thiazoloC312-a ) Pyrimidin-5-one 6-chloro-3-(2-methoxy-phenyl)-7-trans-[
2-(3-pyridyl)-ethynyl-5H-thiazolo[
3,2-a]]pyrimidin-5-one-chloro-3-(3-methoxy-phenyl)-7-trans-(2-(3-pyridyl)-ethynyl-5H-
Thiazolo[3,2-a]]pyrimidin-5-one 6-chloro-3-(,4-methoxy-phenyl)-7-
)2-(2-(3-pyridyl)-ethynyl-5H)
-thiazolo(3,2-a)pyrimidin-5-one, 6-chloro-3-(2-chenyl)-7-trans-(
2-(3-pyridyl)-ethynyl-5H-thiazolo(
3,2-a) Pyrimidin-5-one, 6-chloro-3-(2-pyridyl)-7-trans-[
2-(3-pyridyl)-ethynyl-5H-thiazolo(
3,2-a) Pyrimidin-5-one, 6-chloro-3-(3-pyridyl)-7-trans-1
:2-1(3-pyridyl)-ethynyl-5H-thiazolo(3,2-a)pyrimidin-5-one, 6-chloro-3-(4-pyridyl)-7-trans-[
2-(3-pyridyl)-ethynyl-5H-thiazolo[
3,2-a ]]pyrimidin-5-one 6-chloro-7-trans-[2,-(3-pyridyl)
-ethynyltwo-5-oxo-5H-thiazolo(3+2-
a) Pyrimidine-6-acetic acid, 3-(4-amino-phenyl)-7-) lance-[2-
(3-pyridyl)-ethynyl-5H-thiazolo[3,
2-a) Pyrimidin-5-one, 3-phenyl-7-trans-(2-(3-pyridyl)
-ethynyl) -s H-thiazoloC3*2- a ]
]Pyrimidin-5-one 6-(4-fluorophenyl)
-7-trans-(2-(5-pyridyl)-ethynyl)
13--5H-thiazolo(3,2-a)pyrimidin-5-one, 3-(4-chlorophenyl)-7-)lans-(2-(
3-pyridyl)-ethynyl]-5H-thiazo0 (3,
2-a) Pyrimidin-5-one, 3-(4-methyl-phenyl)-7-trans-(2-
(3-pyridyl)-ethynyl]-51(-thiazolo L
3+2- a]pyrimidin-5-one, 3-(3-methoxy-phenyl)-7-) lance-1:
2-(3-pyridyl)-ethynyl-51'l-thiazolo(3,2-a)pyrimidin-5-one, 3-(4-methoxy-phenyl)-7-)ginsu c2
-<s-pylvvl)-ethynyl2-5H-thiazoloC3
,2-a′)pyrimidin-14-5-one, 3-(5,4-dimethoxyeneenyl)-7-trans-[2-(3-pyridyl)-ethynyl)-5H-thiazolo[3,2 -a ]]pyrimidin-5-one -(3,4-ethylenedioxyphenyl)-7-
trans-(2-(3-pyridyl)-ethynyl-5H)
-thiazolo[3,2-a:]]pyrimidin-5-one-(4-vinenylyl)-7-)lanse-[2-(3
-pyridyl)-ethynyl2-5H-thiazolo[3,2-
a) Pyrimidin-5-one, 3-(2-su7tyl)-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo(3,2-a
) pyrimidin-5-one, 3-(2-pyridyl)-7-
) lance-[2-(3-pyridyl)-ethynyl2 5H
-thiazolo [ro, 2-a) pyrimidin-5-one 3
-(3-pyridyl)-7-) lance-[2-(3-pyridyl)-ethynyl2-5H-thiazoloC3*2-a
']pyrimidin-5-one 3-(4-pyridyl)-7-
) lance-[2-(5-pyridyl)-ethynyl2 5H
-thiazoloC3,2-a) pyrimidin-5-one 2-
Methyl-3-phenyl-7-trans-[2-(3-pyridyl)-ethynyl-5H-thiazolo[3,2-a
) pyrimidin-5-one, 3-(4-IJ-acetyl-aminophenyl)-7-
trans-(2-(3-pyridyl)-ethynyl)-5F
-thiazolo(3,2-a)pyrimidin-5-one, and 7-trans-(2-(3-pyridyl)-ethynyl)-
3-(,2-chenyl) -s H-thiazolo[3,2
A compound selected from the group consisting of -a]]pyrimidine-5-o and a pharmaceutically acceptable salt thereof. 4) In producing a compound having the formula (1) as set forth in claim 1, the following formula (a) formula value) (wherein R1, R2 and R3 are as defined in claim 1) or a salt thereof with an aldehyde having the formula @) R4-OHO@), where R4 is as described in claim 1 above. , formula (I)
or 11-b) wherein R1, R2 and R3 are as described in claim 1, Q is aryl or 01~
C6 alkyl and Y (-) represents an acid anion) is reacted with an aldehyde having the formula (a) to obtain a compound having the formula (1) (wherein the human is a bond) or C) 18- having the formula (b) in which R1, R2 and R5 are as described in claim 1, where R4 is as defined in claim 1. or react with a compound having h, Q, and Y (→ is as defined above) in the reaction described in claim 1; and R11 is C1-C4 alkyl) in each case to give the formula (
I) obtain a compound having the formula (wherein is a bond);
or d) cyclopropanation of a compound having the formula (in which R1, R2, R3 and R4 are as described in claim 1) to form a compound of formula (I) (in the formula is a -cn2- group), and optionally a compound having the formula (1) is converted into a compound having the formula (1)
) and/or optionally converted into a compound of formula (1)
converting the compound into a pharmaceutically acceptable salt thereof and/or converting the desired salt into the free compound and/or
Or, if desired, a process for producing a compound of formula (1), characterized in that a mixture of isomers is resolved into single isomers. 5) A pharmaceutical composition containing a suitable carrier and/or diluent and a compound having the formula (1) according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. 6) A compound according to claim 1 or a pharmaceutically acceptable salt thereof for use in the treatment of a human or animal body by surgery or therapy or in diagnosis performed on a human or animal body. 7) Used for administration to human patients for the prevention or treatment of gastrointestinal ulcer formation, treatment of pain and inflammatory processes and prevention or treatment of all types of thrombosis, peripheral vascular disease and coronary artery disease. or a pharmaceutically acceptable salt thereof;
Or the pharmaceutical composition according to claim 5.