Synthesis of 5-aminothiazoles as building blocks for library synthesis

A convenient route to 4-phenyl-5-aminothiazoles is described, which offers control over substitution at the 2-position. 2-N-Acylglycinamides were dithionated and a subsequent TFAA-mediated cyclisation step was followed by removal of the 5-N-trifluoroacetyl group providing the free amines. Though applicable generally the method was found to be most effective when introducing aromatic substituents at the 2-position, whereupon moderate overall yields of the 5-amino compounds were obtained.

A series of 2-N-acylglycinamides was converted into differently 2-substituted-5-aminothiazoles by treatment with Lawesson's reagent followed by TFAA-mediated cyclisation and subsequent hydrolysis of the trifluoroacetamide.