Development of a Scalable Synthetic Route to BMS-986251, Part 2: Synthesis of the Tricyclic Core and the API

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2021-06-15 DOI:10.1021/acs.oprd.1c00125

Srinivas Kalidindi, Aravind S. Gangu, Sankar Kuppusamy, Shunmugaraj Sathasivam, Vijaykumar Shekarappa, Saravanan Murugan, Sivasankar Bondigela, Moorthy Kandasamy, Kishore Ghanta, Arun Vinodini, Abhishek Shrikant, Ravikumar Ramachandran, William P. Gallagher, Nathaniel Kopp, Francisco González-Bobes*, Martin D. Eastgate, Rajappa Vaidyanathan*

引用次数: 4

Abstract

BMS-986251, a potent and efficacious RORγt inverse agonist, was synthesized starting from 6-iodotetralone using 13 chemical transformations with only eight isolated intermediates. The synthesis involved a four-step telescoped diastereoselective aza-Michael reaction-annulation sequence followed by installation of the heptafluoro-iso-propyl side chain and final amidation to furnish the desired API.

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BMS-986251可扩展合成路线的开发，第二部分:三环核心和API的合成

BMS-986251是以6-碘四酮为起始原料，经过13次化学转化，仅分离到8个中间体，合成了一种高效的rorγ γt逆转录激动剂。该合成包括四步伸缩非对映选择性叠氮-迈克尔反应-环化序列，然后安装七氟-异丙基侧链，最后进行酰胺化以获得所需的原料药。

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.