Synthetic Development and Scale-Up of the Aminoindazole Fragment of Lenacapavir

IF 3.3 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2026-09-30 DOI:10.1021/acs.oprd.6c00302

Lennie Lin,Anna M. Wagner,Jason Davy,Chloe Y. Wong,Wen-Tau T. Chang,B. Michael O’Keefe,Alexander F. G. Goldberg,Huy Van Huynh,Hongwei Sun,Wei Wang,Scott A. Wolckenhauer

引用次数: 0

Abstract

Abstract We describe herein the development and scale-up of the aminoindazole fragment of lenacapavir, a drug recently approved for long-acting treatment of HIV (Sunlenca) and pre-exposure prophylaxis (as Yeztugo and Yeytuo). This five-step route to fragment 1 was developed from the initial “fit-for-purpose” large-scale synthesis to a commercially viable process. Key improvements include an alternative condition to hydroxylamine-O-sulfonic acid-mediated nitrile formation and a significant overhaul of the key Miyaura borylation process. The culmination of all development efforts improved the final product quality and process safety, resulting in a more efficient and higher-yielding process.

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Lenacapavir胺茚唑片段的合成、开发及规模化生产

摘要：本文描述了lenacapavir的氨基吲哚唑片段的开发和扩大规模，lenacapavir是一种最近被批准用于长效HIV治疗（Sunlenca）和暴露前预防（Yeztugo和Yeytuo）的药物。这五步路线片段1从最初的“适合用途”的大规模合成发展到商业上可行的过程。关键的改进包括替代羟胺-邻磺酸介导的腈生成条件和关键的Miyaura硼化工艺的重大改革。所有开发努力的最终结果提高了最终产品的质量和过程安全性，从而产生了更有效和更高产量的过程。

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.