Patent ID: 6919449
Filing Date: 2005-07-19
Classification: A61P,C07C,C07D,C07F

Abstract:
1. A process for the preparation of a cephalosporin antibiotic of the formula (II) wherein R 1 represents CH 3 , CR a R b COOR c where R a and R b independently represent hydrogen or methyl and R c represents hydrogen or (C 1 -C 3 )alkyl; R 2 represents H, CH 3 , CH 2 OCH 3 , CH 2 OCOCH 3 , CH═CH 2 , and R 3 is carboxylate ion or COOR d , where R d is selected from the group consisting of hydrogen, esters which form a prodrug and a counter ion which forms a salt, said process comprising: (i) hydrolyzing and halogenating of the ester of formula (III) by photochemical irradiation in one pot using a halogenating agent in the absence or presence of a solvent at a temperature in a range of −20° C. to 30 ° C., to produce compound of formula (I) wherein R 1 represents CH 3 , CR a R b COOR c where R a and R b independently represent hydrogen or methyl and R c represents hydrogen or (C 1 -C 3 )alkyl, and X represents halogen such as chlorine or bromine, (ii) activating the 4-halogeno2-substitutedimino-3-oxo-butyric acid of formula (I) using conventional activation agents in the presence of a solvent at a temperature in a range of −50 ° C. to 10° C. to produce a compound of formula (IV) wherein X and R 1 are as defined earlier and X′ represents a halogen or activating group, (iii) condensing the activated compound of the formula (IV) with a 7-amino cephem derivative of formula (V) wherein R 4 is hydrogen or trimethylsilyl, and R 2 and R 3 are as defined above in the presence of a solvent at a temperature in a range of −50° C. to 10° C. to produce a compound of formula (VI) where all symbols are as defined above, (iv) cyclizig of the compound of formula (VI) with thiourea in the presence of water miscible solvents at room temperature to produce the cephalosporin antibiotic of the formula (II) where all symbols are as defined earlier, (v) optionally converting the compound of formula (II) to its pharmaceutically-acceptable salt.