来那卡巴韦复合吡唑片段的合成开发与规模化应用

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-07-31 DOI:10.1021/acs.oprd.4c00235

Nathaniel Kadunce, Olivier St-Jean, Amy Cagulada, Wen-Tau T. Chang, Alexander F. G. Goldberg, Zilin Huang, Jihun Kang, Jinsik Kim, Kyoungchan Kwon, Olga Lapina, Lennie Lin, Trevor J. Rainey, Lyubov Roever, Nisha P. Shah, Scott A. Wolckenhauer

{"title":"来那卡巴韦复合吡唑片段的合成开发与规模化应用","authors":"Nathaniel Kadunce, Olivier St-Jean, Amy Cagulada, Wen-Tau T. Chang, Alexander F. G. Goldberg, Zilin Huang, Jihun Kang, Jinsik Kim, Kyoungchan Kwon, Olga Lapina, Lennie Lin, Trevor J. Rainey, Lyubov Roever, Nisha P. Shah, Scott A. Wolckenhauer","doi":"10.1021/acs.oprd.4c00235","DOIUrl":null,"url":null,"abstract":"We describe herein the process development and scale-up of a complex cyclopropyl pyrazole fragment of lenacapavir, a drug recently approved for long-acting treatment of HIV (Sunlenca). A ten-step asymmetric synthesis was developed utilizing simple starting materials capable of supporting the commercial supply chain of lenacapavir. Key aspects of this development effort were the oxidation strategy to elaborate the core and optimization of the fluorination reaction to afford the final product.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthetic Development and Scale-Up of a Complex Pyrazole Fragment of Lenacapavir\",\"authors\":\"Nathaniel Kadunce, Olivier St-Jean, Amy Cagulada, Wen-Tau T. Chang, Alexander F. G. Goldberg, Zilin Huang, Jihun Kang, Jinsik Kim, Kyoungchan Kwon, Olga Lapina, Lennie Lin, Trevor J. Rainey, Lyubov Roever, Nisha P. Shah, Scott A. Wolckenhauer\",\"doi\":\"10.1021/acs.oprd.4c00235\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"We describe herein the process development and scale-up of a complex cyclopropyl pyrazole fragment of lenacapavir, a drug recently approved for long-acting treatment of HIV (Sunlenca). A ten-step asymmetric synthesis was developed utilizing simple starting materials capable of supporting the commercial supply chain of lenacapavir. Key aspects of this development effort were the oxidation strategy to elaborate the core and optimization of the fluorination reaction to afford the final product.\",\"PeriodicalId\":55,\"journal\":{\"name\":\"Organic Process Research & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Process Research & Development\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.oprd.4c00235\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.oprd.4c00235","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}

引用次数: 0

摘要

我们在本文中介绍了来那卡韦复杂环丙基吡唑片段的工艺开发和规模化生产，来那卡韦是最近获批的一种用于长效治疗艾滋病病毒（Sunlenca）的药物。利用能够支持来那卡韦商业供应链的简单起始原料，开发出了十步不对称合成法。这项研发工作的关键环节是制定核心的氧化策略和优化氟化反应以获得最终产品。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthetic Development and Scale-Up of a Complex Pyrazole Fragment of Lenacapavir

查看原文本刊更多论文

Synthetic Development and Scale-Up of a Complex Pyrazole Fragment of Lenacapavir

We describe herein the process development and scale-up of a complex cyclopropyl pyrazole fragment of lenacapavir, a drug recently approved for long-acting treatment of HIV (Sunlenca). A ten-step asymmetric synthesis was developed utilizing simple starting materials capable of supporting the commercial supply chain of lenacapavir. Key aspects of this development effort were the oxidation strategy to elaborate the core and optimization of the fluorination reaction to afford the final product.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.