盐酸维拉佐酮的合成工艺改进研究

目的对盐酸维拉佐酮的合成工艺进行改进。方法以4-(4-乙酰基哌嗪-1-基)苯酚为起始原料,经Duff反应、取代、环化、脱保护、酰胺化得到关键中间体5-(1-哌嗪基)-苯并呋喃-2-甲酰胺,再与3-(4-氯丁酰基)-1H-吲哚-5-甲氰缩合、成盐得到盐酸维拉佐酮。结果合成了目标化合物盐酸维拉佐酮,并利用~1H-NMR、MS确证了结构,质量分数为99.8%,该路线的总收率为22.5%。结论该合成工艺原料廉价易得、操作简单,适于工业化生产。

Improvement of synthetic process of vilazodone hydrochloride

Objective To improve the process for synthesis of vilazodone hydrochloride.Methods The key intermediate 5-(1- piperazinyl)benzofuran-2-carboxamide was prepared from 4-(4-acetylpiperazine-1-yl)phenol by Duff reaction, substitution, cyclization, deprotection, and amidation. Vilazodone hydrochloride was synthesized from 5-(1-piperazinyl)benzofuran-2-carboxamide and 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile by substitution and salification.Results The target compound vilazodone hydrochloride was synthesized and characterized by1H-NMR and MS. The purity was 99.8%, and the total yield of this synthetic route was 22.5%. Conclusion The synthetic process with facile material and simple operation simplified method is applicable to industrial production.