7-METHOXYCEPHALOSPORIN DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF

摘要

1508113 7-Methoxycephalosporin derivatives and their preparation SANKYO CO Ltd 26 April 1976 [30 April 1975 7 May 1975] 16768/76 Heading C2C Compounds of the formula wherein Y represents a 2-carboxyethylthio group or a trifluoromethylthio group, and non- toxic pharmaceutically acceptable salts thereof, may be obtained (a) by reacting a compound of the formula wherein X1 represents a halogen atom, with a compound of the formula Y-H (III) or with an alkali metal, alkaline earth metal or silver salt thereof, suitably in the presence of a solvent and a base, (b) by reacting a compound of the formula wherein R represents a protected carbonyl group with a compound of the formula Y1-CH 2 COX11 (V) where X11 represents halogen and Y1 represents an optionally protected 2-carboxyethylthio group or a trifluoromethylthio group, suitably in a solvent in the presence of an acid binding agent at or below ambient temperature, or (c) by reacting a compound of the formula wherein A represents an acetoxy or carbamoyloxy group, with 5-mercapto-1-methyl-1H-tetrazole or an alkali metal salt thereof, suitably in a solvent in the presence of an alkaline substance at or above room temperature. The compound of Formula (II) may be prepared by condensing an ester of the corresponding 7-amino compound with 4 - hydroxy - 3,5 - di - t - butylbenzaldehyde, oxidizing the product and then reacting it with methanol to give a corresponding ester of 7# - (4 - hydroxy - 3,5 - di - t - butylbenzylideneamino) - 7α- methoxy - 3 - (1 - methyl - 1H- tetrazol - 5 - yl)thiomethyl - 3 - cephem - 4 - carboxylic acid, eliminating the benzylidene group, reacting the free amine with a haloacetic acid halide, and saponifying the product to give the free acid. The compounds of Formula VI may be prepared by a similar method. The removal of protecting groups and the conversion of the free acids to salts may be carried out by known methods. The products possess antibacterial properties and may be formulated and applied in a conventional manner.