ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Multigram-scale synthesis of GSK 2,256,294, an inhibitor of soluble epoxide hydrolase in clinical evaluation

Meibo Duan, Siyu Fu, Yu Han, Ye Tian, Jia Jiang, Yongpeng Xing, Yunlei Hou, and Yanfang Zhao

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China

E-mail: duanmeibostu@sina.com

Received: 27 October 2021  Accepted: 19 November 2021

Abstract:

This paper described the development of an improved, practical and efficient protocol method for the multigram-scale synthesis of GSK 2,256,294, an orally bioavailable potent and selective inhibitor of sEH. The key to this optimization was the design and development of a novel synthetic strategy, which involved the preparation of 4-(aminomethyl)-3-(trifluoromethyl)benzonitrile (3) and 4-chloro-N,6-dimethyl-1,3,5-triazin-2-amine (6). The developed process provided an overall yield of 26.8%, which enabled us to rapidly synthesize large quantities of GSK 2,256,294 in 99% purity.

Graphical abstract

Keywords: Multigram-scale synthesis; sEH inhibitor; Gabriel reaction; ‘one-pot’ procedure

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-021-01993-1

Chemical Papers 76 (5) 2883–2891 (2022)