Practical and Efficient Approach to Scalable Synthesis of Rucaparib

被引：0

作者：

Park, Jinjae ^{[1
]}

Cheon, Cheol-Hong ^{[1
]}

机构：

[1] Korea Univ, Dept Chem, Seoul 02841, South Korea

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2024年 / 28卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

rucaparib; PARP inhibitor; imino-Stetterreaction; chemoselective reduction; indole; IMINO-STETTER REACTION; REDUCTION; POLYMERS; CYANIDE;

D O I：

10.1021/acs.oprd.4c00366

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页码：4392 / 4399

页数：8

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