GB1229670A - - Google Patents

Abstract

1,229,670. Esters of α - carboxyarylmethylpenicillins. CHAS. PFIZER & CO. Inc. 21 Nov., 1968 [3 Sept., 1968], No. 55386/68. Headings C2A and C2C. Penicillins of the formula wherein M is hydrogen, sodium, potassium or tri - (C 1-4 alkyl)amine; R 1 is thienyl, furyl, pyridyl, phenyl or substituted phenyl wherein the substituent is C 1-4 alkyl, chloro, bromo, C 1-4 alkoxy, di(C 1-4 alkyl) amino, or trifluoromethyl; R 2 is isopropylphenyl, wherein X 1 is chloro, bromo, fluoro, C 1-4 alkyl or C 1-4 alkoxy; X 2 is C 1-4 alkyl or chloro; X 3 is hydrogen or methyl; and X 4 is nitro or di(C 1-4 alkyl)amino; ac indanyl and substituted derivatives thereof, wherein the substituent is methyl, chloro or bromo; ac tetrahydronaphthyl and substituted derivatives thereof wherein the substituent is methyl, chloro or bromo; 1- C 1-4 alkoxy - 2,2,2 - trichloroethyl, 1 - C 1-4 alkoxy - 2,2,2 - trifluoroethyl, [carbo C 1-4 alkoxy] C 1-4 alkoxymethyl, [dicarbo C 1-4 alkoxy] C 1-4 alkoxymethyl wherein m is 2 or 3; -NR 5 R 6 is wherein the lower alkyl groups are C 1-4 and may be alike or different, and -N-(C 1-4 alkyl)anilino; and Y 1 is azetidino, aziridino, pyrrolidino, piperidino, morpholino, thiomorpholino, N- (C 1-4 alkyl) piperazino, pyrrolo, imidazolino, 2,5 - dimethylpyrrolidino, 1,4,5,6 - tetrahydropyrimidino, 4 - methylpiperidino and 2,6- dimethylpiperidino and substituted derivatives thereof, wherein Z is alkylene and is -(CH 2 ) 3 - or -(CH 2 ) 4 -, and wherein the substituent is methyl, chloro or bromo; are prepared by reacting a compound of the formula with an acylating agent of the formula wherein X is chloro, bromo or -OCOR 4 wherein R 4 is benzyl or C 1-4 alkyl, in a reaction inert solvent system at 0‹ to 50‹ C. at a pH of 5 to 8. The penicillins may be isolated by solvent extraction, precipitation by addition of a non- solvent and/or precipitation as an amine or alkali-metal salt thereof. The penicillins are effective against grampositive and gram-negative bacteria and may be administered orally or parenterally. Compounds R 1 CH(COOH) 2 are produced by hydrolysis of the appropriate esters. Compounds R 1 C(COCl)=C=O are produced by reaction of R 1 CH(COOH) 2 with PCl 5 . Compounds CH 3 .CH(OH).CH 2 NR 5 R 6 are produced by reaction of propylene oxide with the appropriate amine. Compounds HOCH 2 CH(CH 3 )-NR 5 R 6 are produced by reduction with LiAlH 4 of compounds C 2 H 5 OOCCH(CH 3 )NR 5 R 6 .