ES338115A1 - Sulphanilamide Derivatives and Process for their Production - Google Patents

Abstract

Novel compounds of formula (wherein one of R 1 and R 2 is cyclopropyl and the other is H, Cl, C 1-3 alkyl, C 1-3 alkoxy or C 1-3 alkylthio, and R 3 is Cl, C 1-3 alkyl or C 1-3 alkoxy) and their pharmaceutically acceptable salts with bases, are prepared by reacting together compounds of the formul[mu] (wherein X is NH 2 or a nitrogen-containing group convertible thereto by hydrolysis or reduction one of A 1 and A 2 is NH while the other is a direct bond and Y and Z are reactive atoms or radicals which can be split off together), converting the group X (when other than NH 2 ) in the resulting product to NH 2 , and optionally salifying the thus-obtained product. Products wherein R 1 or R 2 is Cl may be converted to corresponding compounds wherein R 1 or R 2 is H, C 1-3 alkoxy or C 1-3 alkylthio by reduction or reaction with a metal derivative of an alkanol or alkane thiol. 4 - Chloro - 5 - methoxy - 6 - cyclopropyl - pyrimidine is obtained from [alpha]-diazo-#-oxo-#-cyclopropyl-propionic acid ethyl ester via ethyl [alpha]- methoxy - # - oxo - # - cyclopropyl - propionate, 2 - mercapto - 5 - methoxy - 6 - cyclopropyl - 4- pyrimidinol and 5 - methoxy - 6 - cyclopropyl - 4- pyrimidinol. N - (6 - Cyclopropyl - 5 - methoxy - 4 - pyrimidinyl) - N,N,N - trimethylammonium chloride is prepared from 6 - cyclopropyl - 5 - methoxy- 4-chloropyrimidine and trimethylamine. 4 - Chloro - 6 - cyclopropyl - 5 - methyl - pyrimidine is obtained from ethyl #-oxo-#-cyclopropyl-propionate via ethyl [alpha]-methyl-#-oxo-#- cyclopropyl - propionate, 2 - mercapto - 5 - methyl- 6 - cyclopropyl - 4 - pyrimidinol and 5 - methyl- 6-cyclopropyl-4-pyrimidinol. 4 - Chloro - 6 - cyclopropyl - 2,5 - dimethylpyrimidine is prepared from ethyl [alpha]-methyl-#- oxo - # - cyclopropyl - propionate + acetamidine hydrochloride via 6 - cyclopropyl - 2,5 - dimethyl-4-pyrimidinol. 4 - Chloro - 6 - cyclopropyl - 2 - methoxy - 5- methyl-pyrimidine is prepared from ethyl [alpha]- methyl - # - oxo - # - cyclopropyl - propionate + O-methyl-isourea hydrochloride via 6-cyclopropyl - 2 - methoxy - 5 - methyl - 4 - pyrimidinol. 6 - Cyclopropyl - 4,5 - dichloropyrimidine is prepared from 6-cyclopropyl-4-pyrimidinol via 5-chloro-6-cyclopropyl-4-pyrimidinol. 2 - Cyclopropyl - 4 - chloro - 5 - methyl - 6- methylthio-pyrimidine is prepared from cyclopropyl carboxamidine hydrochloride + methylmalonic acid diethyl ester via 2-cyclopropyl-5- methyl-pyrimidine - 4,6 - diol and 2 - cyclopropyl- 4,6-dichloro-5-methyl-pyrimidine. Compounds of Formula I and their pharmaceutically acceptable salts with inorganic and organic bases are said to possess antibacterial activity and may be made up with inert carriers into pharmaceutical compositions for oral or parenteral administration.