PROCESS FOR PREPARING 4-(ISOXAZOLYL)-THIAZOLE-2- OXAMIC ACID DERIVATIVES

摘要

Process for preparing 4-(isoxazolyl)-thiazole-2-oxamic acid derivatives and intermediate compounds. Said compounds possess antiarthritic activity; compositions for pharmaceutical use containing said compounds as the active ingredients are also described. More particularly, this invention relates to the preparation of the compounds of formula: (I) wherein R and R1 which may be the same or different represent a hydroxy group; a hydrogen or halogen atom; a C1-C6 alkyl or alkoxy group optionally substituted by from one to three substituents selected from the group consisting of halogen, hydroxy, alkoxy, amino, carboxy, alkoxycarbonyl, alkoxalyloxy and phenyl, the latter in turn optionally substituted by from one to three substituents selected from the group consisting of halogen, hydroxy, alkoxy, amino and trifluoroalkyl; a phenyl group optionally substituted by from one to three substituents selected from the group consisting of halogen, hydroxy, alkoxy, amino and trifluoromethyl; R2 is a hydroxy group, an OR3 group or an NR4R5 group; R3 is a C1-C6 alkyl group optionally substituted with from one to three substituents selected from the group consisting of hydroxy, alkoxy, amino, carboxy and alkoxycarbonyl; a C5-6 cycloalkyl group optionally substituted by from one to three alkyl groups; a C7-C9 phenylalkyl group optionally substituted on the phenyl ring by from one to three substituents selected from the group consisting of halogen, methyl and methoxy group; a group of the formula -(CH2-CH2-O)n-R6 wherein n is an integer number from 2 to 4 and R6 is a hydrogen atom or an alkyl group; R4 and R5 which may be the same or different are a hydrogen atom, an alkyl, a C5-C6 cycloalkyl, a C7-C9 phenylalkyl, or a phenyl group; or R4 and R5 together with the nitrogen atom to which they are linked, form a 1-piperidyl, 1-piperazinyl, 4-methyl-1-piperazinyl, pirazolyl, thiazolyl or imidazolyl radical; or either R4 or R5 is a hydrogen atom and the other a group of the formula wherein R and R1 have the above indicated meanings. R7 is a hydrogen atom or a C1-C3 alkyl radical and of the salts of the compounds of formula I in which R2 is a hydroxy group with pharmaceutically acceptable organic and inorganic bases and the salts of the compounds of formula I in which R2 contains a basic function with pharmaceutically acceptable organic and inorganic acids.