Synthesis of an imidazo[1,2-c]pyrimidine analog of a thiamine antagonist coccidiostat and a comparison of several methods for the preparation of imidazo[1,2-c]pyrimidines

Several methods for the preparation of imidazo1,2-c]pyrimidines are presented. Compound 12 was prepared from 11 and chloroacetaldehyde in water using a buffer to control pH. Compound 12 was converted in two steps to 14 , the etheno bridged analog of the coccidiostat 1. Several methods were used to prepare 8-phenylimidazo1,2-c]pyrimidine ( 16 ). In terms of yield the best method was the reaction of the aminopyrimidine 15 with chloroacetaldehyde in acetone and in the presence of calcium carbonate as an acid scavenger. Reaction of the 4-chloro-pyrimidine 19 with aminoacetaldehyde diethyl acetal gave 16 directly in modest yield.