Development of Adagrasib’s Commercial Manufacturing Route

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2023-02-17 DOI:10.1021/acs.oprd.2c00386

David R. Snead*, Yonghong Gan*, Thomas Scattolin, Dinesh J. Paymode, Michal Achmatowicz, Duane E. Rudisill, Ephraim S. Vidal, Tawfik Gharbaoui, Phil Roberts, Jianbo Yang, Zhangbing Shi, Wei Liu, Joshua Bolger, Zhen Qiao and Cheng-yi Chen*,

引用次数: 6

Abstract

A commercial route to adagrasib (1) was developed to support clinical and commercial needs. Yield was improved to 32% over six chemical steps. A doubly regioselective S_NAr reduced consumption of a chiral intermediate, reaction optimization led to parts per million palladium catalysis, and a new method to deprotect Cbz-groups were developed to mitigate risk associated with benzyl iodide.

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Adagrasib商业化生产路线的发展

adagasib(1)的商业路线被开发以支持临床和商业需求。六个化学步骤的收率提高到32%。双区域选择性SNAr降低了手性中间体的消耗，反应优化导致了百万分之一的钯催化，并且开发了一种新的去保护cbz基团的方法来降低与碘化苄相关的风险。

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.