An efficient, practical approach to the synthesis of 2,4-disubstituted thiazoles and oxazoles: Application to the synthesis of GW475151

A new method for the synthesis of 2,4-disubstituted oxazoles and thiazoles and 2,4,5-trisubstituted oxazoles from readily available starting materials is described. The methodology has been applied on multigram scale and invo lves transfer of oxidation state through a molecular framework. In particul ar the oxazole-containing amino acid fragment of the 5,5-transfused lactam GW475151, 1, has been prepared in excellent yield and purity.