文献类型：期刊文献

英文题名：Unconventional Synthetic Process of Fasudil Hydrochloride: Costly Homopiperazine Was Avoided

作者：Zhao, Jianhong[1];Wang, Dingding[1];Yang, Wu-Lin[1];Niu, Jinming[1];Wu, Weiting[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Minist Educ, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200237, Peoples R China

年份：2022

卷号：26

期号：1

起止页码：91

外文期刊名：ORGANIC PROCESS RESEARCH & DEVELOPMENT

收录：;EI(收录号：20214911271993);WOS:【SCI-EXPANDED(收录号:WOS:000764122600007)，CCR-EXPANDED(收录号:WOS:000764122600007)】；

基金：This research was supported by the East China University of Science and Technology. We appreciate the anonymous reviewers' valuable suggestions for improvements to this paper.

语种：英文

外文关键词：fasudil hydrochloride; homopiperazine; one-pot process; practical synthesis

摘要：An efficient, robust, and cost-effective synthetic process of fasudil hydrochloride 1 was developed. Starting from readily available ethylenediamine and 5-isoquinoline sulfonyl chloride, the target product 1 was prepared through a six-step reaction, including sulfonamidation, protection, nucleophilic substitution, deprotection, cyclization, and salification. The process afforded 1 in 67.1% overall yield (based on 5-isoquinoline sulfonyl chloride) with 99.94% purity. Compared to the earlier published methodologies, the use of homopiperazine or its derivatives as intermediates was avoided. The salient features of this environmentally friendly synthetic route include easily available starting materials and operational simplicity, which could be suitable for large-scale industrial production.