IMPROVEMENTS RELATING TO PENICILLINS

1292603 Penicillins; thiazole and oxazole intermediates therefor JOHN WYETH & BROTHER Ltd 5 Jan 1970 [7 Jan 1969 (2)] 924/69 and 925/69 Headings C2A and C2C Novel penicillins of Formula I and salts thereof, wherein A is C 1 -C 4 alkylene, R1 is an optionally substituted aryl or heterocyclic radical or a cycloalkyl radical, R2 is hydrogen, amino, C 1 to C 6 alkyl or an optionally substituted aryl or heterocyclic radical and X is oxygen or sulphur, with the proviso that when A is methylene, R2 is an aryl or heterocyclic radical are prepared by acylating 6-aminopenicillanic acid or a salt or silyl derivative there. of with an acid of Formula II or an acylating derivative thereof. Substituents of R1 and R2 may be halogen, C 1 to C 6 alkyl or alkoxy, CF 3 , or NO 2 . When heterocyclic, R1 and R2 may be thienyl, furyl or pyridyl. Acylating derivatives of the acid are preferably the chloride, or an anhydride or mixed anhydride. The reaction is preferably carried out in the presence of a base, e.g. sodium bicarbonate, or triethylamine. The penicillins may be converted to their salts, e.g. of Na, K, ammonium, amines or diamines, or the hydrochloride, sulphate or fumarate. 3 - [2 - Amino - 4 - phenylthiazol - 5 - yl] propionic acid is prepared by cyclizing 4-bromo-4- benzoylbutyric acid and thiourea (see Example 2). 4 - Phenylthiazol - 5 - yl propionic acid is prepared by treating formamide with phosphorus pentasulphide followed by 4-bromobenzoylbutyric acid (Example 4). Ethyl - 6 - bromo - 5 - oxohexanoate and p - chlorothio - benzamide are reacted to give ethyl - 2 - p - chlorophenylthiazol - 4 - yl butyrate which is hydrolysed to the corresponding acid (Example 11). 2 - Ethyl-; 2 - propyl-; and 2 - butyl - 4- phenylthiazol - 5 - yl propionic acids are prepared by reacting respectively, thiopropamide, thiobutyramide and thiovaleramide with 4- benzoyl - 4-bromobutyric acid. These acids and others of Formula II above are converted to the corresponding acid chlorides by treatment with thionyl chloride. Pharmaceutical compositions comprise a penicillin of Formula I above together with a pharmaceutical carrier.