Unconventional Synthetic Process of Fasudil Hydrochloride: Costly Homopiperazine Was Avoided

Abstract

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.

Complexes of N, N- and N, N, N- Sulfonamide Ligands as Therapeutic and Diagnostic Agents

“…The base abstracts the proton released during the nucleophilic attack on the amine by the sulfonyl chloride. Due to the moisture-sensitive nature of sulfonyl chlorides, solid sodium bicarbonate can be used as a base (Zhao et al, 2021). Using a solvent such as pyridine can serve dual purposes as the solvent and as the base that abstracts the proton.…”