C-H功能化在开发简明聚合途径中的应用磷脂酰肌醇-3激酶抑制剂Nemiralisib

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2021-02-09 DOI:10.1021/acs.oprd.0c00486

Robert N. Bream, Hugh Clark, Dean Edney, Antal Harsanyi, John Hayler, Alan Ironmonger*, Nadine Mc Cleary, Natalie Phillips, Catherine Priestley, Alastair Roberts, Philip Rushworth, Peter Szeto, Michael R. Webb, Katherine Wheelhouse*

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引用次数: 4

摘要

本文介绍了一种改进的和可扩展的方法来制造nemiralisib，一种磷脂酰肌醇-3-激酶抑制剂。结合三个连续的催化反应，包括钯催化的C-H功能化和铱催化的硼化，显著简化和缩短了合成序列。修订后的路线已成功地在一个多公斤规模的试验工厂实施，交付了100公斤的产品。

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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Application of C–H Functionalization in the Development of a Concise and Convergent Route to the Phosphatidylinositol-3-kinase Delta Inhibitor Nemiralisib

This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C–H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.

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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.