推进贱金属催化：镍催化硼化/钯催化铃木伸缩工艺的开发与实施

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-02-10 DOI:10.1021/acs.oprd.4c00498

Matthew V. Joannou, Matthew J. Goldfogel, Eric M. Simmons, Steven R. Wisniewski

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引用次数: 0

摘要

本文报道了利用廉价的NiCl2·6H2O预催化剂进行硼化反应的镍催化硼化/钯催化铃木伸缩工艺的开发和实施。硼化反应的发展是通过初步的机制调查来了解脱卤副产物的起源。borylation流被压缩成Suzuki偶联，在afimetoran （toll样受体7/8 （TLR 7/8）的拮抗剂）的五环核心形成双杂芳基键。铃木反应的优化和伸缩过程的公斤级示范展示了利用镍催化开发可扩展的临床api路线的可行性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Advancing Base Metal Catalysis: Development and Execution of a Ni-catalyzed Borylation/Pd-catalyzed Suzuki Telescoped Process

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Advancing Base Metal Catalysis: Development and Execution of a Ni-catalyzed Borylation/Pd-catalyzed Suzuki Telescoped Process

The development and execution of a nickel-catalyzed borylation/palladium-catalyzed Suzuki telescoped process utilizing the inexpensive NiCl₂·6H₂O precatalyst for the borylation step are reported. The development of the borylation reaction was guided by a preliminary mechanistic investigation to understand the origin of the dehalogenated side product. The borylation stream was telescoped into a Suzuki coupling to form a bis-heteroaryl bond in the pentacyclic core of afimetoran, an antagonist of toll-like receptors 7/8 (TLR 7/8). The optimization of the Suzuki reaction and kilogram-scale demonstration of the telescoped process showcase the viability of utilizing nickel catalysis in the development of scalable routes to clinical APIs.

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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.