Process Development to Synthesize SGD-11275 Utilizing a Pd-Catalyzed Acetamide Arylation and Gallium-Mediated Friedel–Crafts Acylation

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-11-26 DOI:10.1021/acs.oprd.4c00375

Tristan M. McGinnis, Noah Porter, Apparao Bokka, Kun-Liang Wu, Brooke Gill, Jared Abbruzzese, Aaron M. Whittaker, Srinath Thirumalai rajan

引用次数: 0

Abstract

An improved synthesis of SGD-11275 was developed to address inefficiencies in cost, time, and safety associated with the previous supply route. The new route features a Buchwald-Hartwig amination with acetamide optimized by high-throughput experimentation as well as a GaCl₃-mediated Friedel–Crafts acylation. Subsequent amide hydrolysis was demonstrated from the isolated Friedel–Crafts product and as a through-process with equal effectiveness. The new route reduced the commercial synthesis by three steps and increased the overall yield by 18.6%.

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利用钯催化乙酰胺芳基化和镓介导的 Friedel-Crafts 丙烯酰化合成 SGD-11275 的工艺开发

我们开发了一种改进的 SGD-11275 合成方法，以解决以前的供应路线在成本、时间和安全性方面的低效问题。新路线的特点是通过高通量实验优化了与乙酰胺的布赫瓦尔德-哈特维格胺化反应，以及由氯化镓介导的弗里德尔-卡夫斯酰化反应。从分离出的 Friedel-Crafts 产物中进行的后续酰胺水解，以及作为直通过程进行的酰胺水解，都具有相同的效果。新路线将商业合成减少了三个步骤，并将总产率提高了 18.6%。

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.