An improved synthesis of telmisartan via the copper-catalyzed cyclization of o-haloarylamidines

Junchi Zhang; Rui Li; Fuqiang Zhu; Changliang Sun; Jingshan Shen

doi:10.1039/d0ra00886a

An improved synthesis of telmisartan via the copper-catalyzed cyclization of o-haloarylamidines

RSC Adv. 2020 Apr 3;10(23):13717-13721. doi: 10.1039/d0ra00886a. eCollection 2020 Apr 1.

Authors

Junchi Zhang^{1

2}, Rui Li^{1

2}, Fuqiang Zhu³, Changliang Sun³, Jingshan Shen^{1

2}

Affiliations

¹ CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS) 555 Zuchongzhi Road Shanghai 201203 People's Republic of China shenjingshan@simm.ac.cn.
² University of Chinese Academy of Sciences No. 19A Yuquan Road Beijing 100049 People's Republic of China.
³ Topharman Shanghai Co., Ltd Building 1, No. 388 Jialilue Road, Zhangjiang Hitech Park Shanghai 201203 People's Republic of China changliang.sun@topharman.cn.

Abstract

A concise synthetic route was designed for making telmisartan. The key bis-benzimidazole structure was constructed via the copper-catalyzed cyclization of o-haloarylamidines. By adopting this approach, telmisartan was obtained in a 7-step overall yield of 54% starting from commercially available 3-methyl-4-nitrobenzoic acid, and the use of HNO₃/H₂SO₄ for nitration and polyphosphoric acid (PPA) for cyclization in the reported literatures were avoided.