Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2021-04-22 DOI:10.1021/acs.oprd.1c00069

Hongshan Jin, Chengjun Wu, Shuhao Zhou, Yunting Xin, Tiemin Sun*, Chun Guo*

引用次数: 2

Abstract

Vilazodone combines the effects of a selective serotonin reuptake inhibitor with the 5-HT_1A receptor partial agonist activity. Here, we report the development of a viable and scalable process for manufacturing vilazodone that features a convergent synthetic approach, with low cost and high purity. The key indole synthesis was improved to first make up the hydrazone intermediate and then modify a pendant hydroxy group to realize a much increased overall yield. This process was successfully used to prepare >2 kg of vilazodone hydrochloride with a total yield of 56.2% and purity of 99.93%.

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新型双作用5 -羟色胺能抗抑郁药维拉唑酮的实用和可扩展制造工艺

维拉唑酮结合了选择性5-羟色胺再摄取抑制剂与5-HT1A受体部分激动剂活性的作用。在这里，我们报告了一种可行的、可扩展的生产维拉唑酮的工艺，该工艺具有低成本、高纯度的聚合合成方法。对关键吲哚的合成方法进行了改进，首先合成腙中间体，然后修饰一个悬垂的羟基，从而大大提高了总收率。该工艺成功制备了2 kg的盐酸维拉唑酮，总收率为56.2%，纯度为99.93%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.