A Three-Step Synthesis of Acotiamide for the Treatment of Patients with Functional Dyspepsia

A three-step synthesis of acotiamide is described. The agent is marketed in Japan for treatment of patients with functional dyspepsia. We designed a one-pot method to prepare the key intermediate 5a from 2 via an acyl chloride and amide and then reacted with 6 to obtain 1 under solvent-free conditio...

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Bibliographic Details
Published in:Organic process research & development 2015-12, Vol.19 (12), p.2006-2011
Main Authors: Fu, Kai, Yang, Liu, Wang, Qiu-Fen, Zhan, Fu-Xu, Wang, Bin, Yang, Qian, Ma, Zhi-Jia, Zheng, Geng-Xiu
Format: Article
Language:English
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Summary:A three-step synthesis of acotiamide is described. The agent is marketed in Japan for treatment of patients with functional dyspepsia. We designed a one-pot method to prepare the key intermediate 5a from 2 via an acyl chloride and amide and then reacted with 6 to obtain 1 under solvent-free condition. With the use of DCC, the unavoidable impurity 5b was also successfully converted into the desired 1. After isolation of 1, we carried forward to the next step of HCl salt formation, which was proved to be a very effective procedure for the removal of practically all major impurities. The process is cost-effective, simple to operate, and easy to scale-up.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.5b00256