Direct Synthesis of a PDE4 Inhibitor by Using Pd–Cu-Catalyzed C–H/C–Br Coupling of Benzoxazole with a Heteroaryl Bromide

Abstract

A short and practical synthetic route of a PDE4 inhibitor (1) was established by using Pd–Cu-catalyzed C–H/C–Br coupling of benzoxazole with a heteroaryl bromide. The combination of Pd(OAc)2-Cu(OTf)2-PPh3 was found to be effective for this key step. Furthermore, telescoping methods were adopted to improve the yield and manufacturing time, and a two-step synthesis of 1 was accomplished in 71% overall yield.