选择性雌激素受体降解剂GDC-9545 (girestrant)结晶驱动非对构选择性Pictet-Spengler缩合的高效制造工艺

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2021-11-09 DOI:10.1021/acs.oprd.1c00263

Jie Xu*, Cheol K. Chung, Andrew McClory, Kyle A. Mack, Michael E. Dalziel, Alec Fettes, Kyle Clagg, Ngiap-Kie Lim, Georg Wuitschik, Christian Jenny, Laure Finet, Michael Kammerer, Haiming Zhang, Rémy Angelaud, Francis Gosselin

{"title":"选择性雌激素受体降解剂GDC-9545 (girestrant)结晶驱动非对构选择性Pictet-Spengler缩合的高效制造工艺","authors":"Jie Xu*, Cheol K. Chung, Andrew McClory, Kyle A. Mack, Michael E. Dalziel, Alec Fettes, Kyle Clagg, Ngiap-Kie Lim, Georg Wuitschik, Christian Jenny, Laure Finet, Michael Kammerer, Haiming Zhang, Rémy Angelaud, Francis Gosselin","doi":"10.1021/acs.oprd.1c00263","DOIUrl":null,"url":null,"abstract":"GDC-9545 is a selective estrogen receptor degrader that is being developed as a treatment for ER+/HER2– breast cancer. A robust, convergent manufacturing process for GDC-9545 was developed. The process features a Wenker aziridine synthesis to produce the key starting material tryptamine 11, a highly efficient C–N coupling between aminoazetidine 9 and 2,6-difluoro-4-bromobenzaldehyde diethyl acetal (33) to construct key intermediate 10, and a crystallization-driven diastereoselective Pictet–Spengler reaction to furnish the active pharmaceutical ingredient GDC-9545·tartrate.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"26 3","pages":"568–582"},"PeriodicalIF":3.1000,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Efficient Manufacturing Process for the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) via a Crystallization-Driven Diastereoselective Pictet–Spengler Condensation\",\"authors\":\"Jie Xu*, Cheol K. Chung, Andrew McClory, Kyle A. Mack, Michael E. Dalziel, Alec Fettes, Kyle Clagg, Ngiap-Kie Lim, Georg Wuitschik, Christian Jenny, Laure Finet, Michael Kammerer, Haiming Zhang, Rémy Angelaud, Francis Gosselin\",\"doi\":\"10.1021/acs.oprd.1c00263\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"GDC-9545 is a selective estrogen receptor degrader that is being developed as a treatment for ER+/HER2– breast cancer. A robust, convergent manufacturing process for GDC-9545 was developed. The process features a Wenker aziridine synthesis to produce the key starting material tryptamine 11, a highly efficient C–N coupling between aminoazetidine 9 and 2,6-difluoro-4-bromobenzaldehyde diethyl acetal (33) to construct key intermediate 10, and a crystallization-driven diastereoselective Pictet–Spengler reaction to furnish the active pharmaceutical ingredient GDC-9545·tartrate.\",\"PeriodicalId\":55,\"journal\":{\"name\":\"Organic Process Research & Development\",\"volume\":\"26 3\",\"pages\":\"568–582\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2021-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Process Research & Development\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.oprd.1c00263\",\"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://pubs.acs.org/doi/10.1021/acs.oprd.1c00263","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: 4

摘要

GDC-9545是一种选择性雌激素受体降解剂，正在开发用于治疗ER+/HER2 -乳腺癌。开发了GDC-9545的稳健、融合制造工艺。该工艺以Wenker叠氮吡啶合成为主要原料色胺11，氨基叠氮吡啶9与2,6-二氟-4-溴苯甲醛二乙基缩醛(33)之间的高效C-N偶联为主要中间体10，结晶驱动的非对映选择性Pictet-Spengler反应为主要活性药物成分ggc -9545·酒石酸盐。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Efficient Manufacturing Process for the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) via a Crystallization-Driven Diastereoselective Pictet–Spengler Condensation

查看原文本刊更多论文

Efficient Manufacturing Process for the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) via a Crystallization-Driven Diastereoselective Pictet–Spengler Condensation

GDC-9545 is a selective estrogen receptor degrader that is being developed as a treatment for ER+/HER2– breast cancer. A robust, convergent manufacturing process for GDC-9545 was developed. The process features a Wenker aziridine synthesis to produce the key starting material tryptamine 11, a highly efficient C–N coupling between aminoazetidine 9 and 2,6-difluoro-4-bromobenzaldehyde diethyl acetal (33) to construct key intermediate 10, and a crystallization-driven diastereoselective Pictet–Spengler reaction to furnish the active pharmaceutical ingredient GDC-9545·tartrate.

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.