Practical and Efficient Approach to Scalable Synthesis of Rucaparib

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-11-15 DOI:10.1021/acs.oprd.4c00366

Jinjae Park, Cheol-Hong Cheon

引用次数: 0

Abstract

A scalable synthesis of rucaparib was developed from methyl 5-fluoro-2-methyl-3-nitrobenzoate and 4-cyanobenzaldehyde. Methyl 5-fluoro-2-methyl-3-nitrobenzoate was converted into a 2-aminocinnamonitrile derivative, which was subjected to the imino-Stetter reaction with 4-cyanobenzaldehyde to yield trisubstituted indole-3-acetonitrile. The reduction of both nitriles, followed by azepinone scaffold construction and selective monomethylation, completed the synthesis of rucaparib. This synthetic route features the use of inexpensive starting materials, scalability, and ease of purification through recrystallization.

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Rucaparib 可扩展合成的实用高效方法

以 5-氟-2-甲基-3-硝基苯甲酸甲酯和 4-氰基苯甲醛为原料，开发了一种可扩展的芦卡帕利合成方法。5-氟-2-甲基-3-硝基苯甲酸甲酯被转化为 2-氨基肉桂腈衍生物，该衍生物与 4-氰基苯甲醛发生亚氨基-斯泰特反应，生成三取代吲哚-3-乙腈。将这两种腈还原，然后构建氮杂环庚酮支架并进行选择性单甲基化，就完成了 rucaparib 的合成。这条合成路线的特点是使用廉价的起始材料、可扩展性和易于通过重结晶纯化。

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.