Syntheses of 2-Disubstituted-amino-4-arylthiazol-5-ylalkanoic Acids

抄録

A novel method of synthesizing 2-disubstituted-amino-4-arylthiazol-5-ylalkanoic acids (3) was studied. Dehydration of S-(α-benzoyl-β-ethoxycarbonyl) ethyl 1-piperidinethiocarbonate (5a) in the presence of aqueous perchloric acid-acetic anhydride yielded 4-ethoxycarbonyl-methyl-5-phenyl-2-piperidino-1, 3-oxathiolium perchlorate (1a). Nucleophilic reaction of ammonia with 1a afforded 5-ethoxycarbonylmethyl-4-phenyl-2-piperidinothiazole (2a). Acid-catalyzed hydrolysis of 2a gave 3a as a hydrochloride. The acids (3) were also synthesized by the classical Hantzsch method. These alkanoic acids were evaluated as antiinflammatory agents on carrageenin-induced abscess in rat.