An investigation of the synthesis of vilazodone

作者：Fan Hu, Weike Su · 发表于：Journal of Chemical Research · 年份：2019 · DOI：10.1177/1747519819893293 · 被引用次数：4 · 研究领域：Synthesis and pharmacology of benzodiazepine derivatives、Multicomponent Synthesis of Heterocycles、Chemical synthesis and alkaloids

A novel synthetic route toward vilazodone is described by using 4-cyanoaniline and 5-bromo-2-hydroxybenzaldehyde as starting materials, with an overall yield of 24% and 99% purity. First, the intermediate (3-(4-chlorobutyl)-1 H-indole-5-carbonitrile) is synthesized via diazotization of 4-cyanoaniline, followed by Fischer indole cyclization with 6-chlorohexanal. Subsequently, another intermediate, 5-(piperazin-1-yl)benzofuran-2-carboxamide, is generated via aromatic nucleophilic substitution of 5-bromobenzofuran-2-carboxamide with piperazine. Finally, vilazodone is obtained via nucleophilic substitution of the above two key intermediates by treatment with Et 3 N/K 2 CO 3 . In comparison to the original process, this route avoids the use of expensive and toxic reagents and resolves issues such as safety, environmental concerns, and high costs.