Preparation of 5-Aminothiazole-4-carboxylic Acid Derivatives

Abstract

Cyclization of 2-acylamino-2-thiocarbamoylacetamides (Va, b) with acetic formic anhydride gave good yields of 5-formamidothiazole-4-carboxamides (VIa, b) which were converted to 5-aminothiazole-4-carboxamides (VIIa, b) by hydrolysis. For the purpose of the preparation of the free base (VIIa), however, cyclization of Va with polyphosphoric acid was proved to give better result, that is, heating of Va-c and ethyl 2-acylamino-2-thiocarbamoylacetates (Vd-f) in polyphosphoric acid gave VIIa-c and ethyl 5-aminothiazole-4-carboxylates (VIId-f) in excellent yields. 5-Aminothiazole-4-carbonitriles (VIIg, h) were prepared by treatment of Va, b with phosphorus oxychloride.