化学
工具箱
管道(软件)
可扩展性
背景(考古学)
药物发现
水准点(测量)
过程(计算)
纳米技术
组合化学
计算机科学
数据库
操作系统
古生物学
生物
生物化学
材料科学
程序设计语言
地理
大地测量学
作者
Gregory L. Beutner,Eric M. Simmons,Sloan Ayers,Christopher Y Bemis,Matthew J. Goldfogel,Candice L. Joe,Jonathan Marshall,Steven R. Wisniewski
标识
DOI:10.1021/acs.joc.1c01073
摘要
As sp2–sp3 disconnections gain acceptance in the medicinal chemist’s toolbox, an increasing number of potential drug candidates containing this motif are moving into the pharmaceutical development pipeline. This raises a new set of questions and challenges around the novel, direct methodologies available for forging these bonds. These questions gain further importance in the context of process chemistry, where the focus is the development of scalable processes that enable the large-scale delivery of clinical supplies. In this paper, we describe our efforts to apply a wide variety of standard, photo-, and electrochemical sp2–sp3 cross-coupling methods to a pharmaceutically relevant intermediate and optimize each through a combination of high throughput and mechanistically guided experimentation. With data regarding the performance, benefits, and limitations of these novel methods, we evaluate them against a more traditional two-step palladium-catalyzed process. This work reveals trends and similarities between these sp2–sp3 bond-forming methods and suggests a path forward for further refinements.
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