Efficient solid-phase synthesis of 2, 4-disubstituted 5-carbamoyl-thiazole derivatives using a traceless support. Issue 21 (27th May 2015)

• Record Type: Journal Article
• Authors: Kim, Daehun; Baek, Dong Jae; Lee, Doohyun; Liu, Kwang-Hyeon; Bae, Jong-Sup; Gong, Young-Dae; Min, Kyung Hoon; Lee, Taeho
• Is Part Of: Tetrahedron. Volume 71:Issue 21(2015)
• Page Start: 3367
• Page End: 3377
• Publication Date: 2015-05-27
• Subjects: 5-Carbamoyl-thiazole -- Solid-phase synthesis -- Combinatorial chemistry -- Traceless support -- Heterocycles; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.03.104
• Languages: English
• ISSNs: 0040-4020

Abstract

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. Graphical abstract: