化学
氧化还原
胺化
卤化
卤化物
组合化学
芳基
药物发现
流动化学
催化作用
有机化学
生物化学
烷基
作者
Morgan J. Cordell,Matt R. Adams,Jean‐François Vincent‐Rocan,John G. Riley
标识
DOI:10.1002/ejoc.202101143
摘要
Abstract By using photo‐redox catalysis in flow the newly marketed drug entrectinib (referred to by the brand name Rozlytrek) was synthesized in 6 linear steps from readily available building blocks under mild conditions. Evaluation of multiple intermediates for their use in the critical C−N amination step in flow led to the finding that more electron deficient aryl‐halides achieve higher conversion to the desired product. Data supports that more electron rich aryl‐halides undergo a significant amount of hydro‐dehalogenation compared to the productive C−N bond formation. Through evaluating various entry points into the synthesis of entrectinib, shorter routes were identified albeit in low yields. The modularity of this route will allow chemists to rapidly synthesize a diverse library of compounds through this route. Via different synthetic intermediates, a scale‐up route was discovered for the synthesis of entrectinib using photo‐redox in flow in less steps than previously reported, highlighting the utility of flow chemistry in the pharmaceutical industry.
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