Adagrasib (MRTX849) 核心起始材料的工艺开发与制造

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-01-26 DOI:10.1021/acs.oprd.3c00485

Thomas Scattolin*, Dinesh Jagannath Paymode, David Robinson Snead, Zhichao Lu, Stanley Yu, Maxime Robert-Monpate, Maria Noelia Chao, Thomas Michael Haas, Hanhui Wang, Xuewei Liang and Cheng-yi Chen,

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引用次数: 0

摘要

β-酮酯 1 是用于阿达拉西布第二代合成的关键起始原料之一。本报告介绍了一种新的、精简的、操作简单的、更环保的三步伸缩方案，该方案已在 100 公斤的批量中得到验证，总产率达到 70%。报告还讨论了最初路线的缺点和质量问题。此外，还介绍了克服这些挑战并最终形成新合成路线的工艺开发工作。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Process Development and Manufacture of the Core Starting Material of Adagrasib (MRTX849)

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Process Development and Manufacture of the Core Starting Material of Adagrasib (MRTX849)

β-Ketoester 1 is one of the critical starting materials used in the second-generation synthesis of adagrasib. Disclosed within is a new, streamlined, operationally simple, and more environmentally friendly three-step telescoped protocol which was demonstrated on a >100 kg batch with an overall yield of 70%. Identification of the shortcomings and the quality issues of the initial route are discussed. The process development work overcoming these challenges and leading to the new route of synthesis is described.

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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.