Synthesis of 2-Amino-5-Carboxamide Thiazole Derivatives via Dehydrative Cyclization of Thiourea Intermediate Resin on Solid Phase

Abstract

In this study, we synthesized 2-amino-5-carboxamide thiazole derivatives on solid phase. The synthesis of the library starts with the reductive amination of the 4-formyl-3-methoxy phenoxy resin to prevent isomer formation. The dehydrative cyclization of thiourea intermediate resin, which is the key step in the synthetic process, was successfully synthesized using alpha-bromoketone in the presence of the DMF so as to afford 2-amino-5-carboxylate thiazole resin. The resulting resin is coupled with various amines. Finally, the 2-amino-5-carboxamide thiazole resin was cleaved from the polymer support using a TFA and DCM cocktail. The physicochemical properties of the proposed 2-amino-5-carboxamide thiazole derivatives were calculated and showed potential to be an reasonable oral bioavailability drug properties as determined by Lipinski's Rule.