Scale-Up Synthesis of a TRPV1 Antagonist Featuring a Facile Thiazolo[5,4-d]pyrimidine Formation

Abstract

An efficient and practical synthesis of a TRPV1 inhibitor bearing a thiazolo[5,4-d]pyrimidine core was developed. The initial synthesis was modified to facilitate acylation of 5-aminopyrimidine and subsequent thiazole formation. The synthesis features an efficient two-pot, five-step process for the construction of the thiazolo[5,4-d]pyrimidine ring. The new route is concise, chromatography-free, and amenable to large-scale preparation.

Cu-Catalyzed [3 + 3] Annulation for the Synthesis of Pyrimidines via β-C(sp3)–H Functionalization of Saturated Ketones

“…(Scheme 1). 11 However, the majority of these methods suffered from harsh reaction conditions (microwave irradiation, strong basic conditions), 7a,8 starting materials that require multistep synthesis, [6][7][8]10 expensive catalysts, 9 and less atom efficiency. 10 Therefore, a simple and effective method for the synthesis of pyrimidine from simple and readily available starting materials still remains highly desirable.…”