Efficient solid-phase synthesis of 2,4-disubstituted 5-carbamoyl-thiazole derivatives using a traceless support

Abstract

An efficient protocol for the solid-phase synthesis of 2,4-disubstituted 5-carbamoyl-thiazole derivatives has been developed. After the reaction scopes were investigated in solution-phase, the polymer-supported synthesis route was progressed using a sulfide linker in a traceless manner. The solid-phase synthetic protocol started with the Thorpe-Ziegler type cyclization of 2-chloroacetamide and polymer-bound cyanocarboimidodithioate, which is derived from Merrifield resin. The resulting 5-carbamoyl-thiazole was introduced to one substitution by N-acylation. After the oxidation of sulfides to sulfones for subsequent cleavage, nucleophilic desulfonative substitution with amines and thiols gave the target 2,4-disubstituted 5-carbamoyl-thiazole derivatives in good purities and overall yields.