吡啶 C-H 键的 N-氟代苯磺酰亚胺的方便的后期氟化。
A Convenient Late-Stage Fluorination of Pyridylic C-H Bonds with N-Fluorobenzenesulfonimide.
机构信息
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
Medicinal Chemistry, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
出版信息
Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13244-13248. doi: 10.1002/anie.201606323.
Pyridine features prominently in pharmaceuticals and drug leads, and methods to selectively manipulate pyridine basicity or metabolic stability are highly sought after. A robust, metal-free direct fluorination of unactivated pyridylic C-H bonds was developed. This convenient reaction shows high functional-group tolerance and offers complimentary selectivity to existing C-H fluorination strategies. Importantly, this late-stage pyridylic C-H fluorination provides opportunities to rationally modulate the basicity, lipophilicity, and metabolic stability of alkylpyridine drugs.
吡啶在药物和药物先导物中具有重要作用，因此人们迫切需要开发选择性调节吡啶碱性或代谢稳定性的方法。本研究开发了一种稳健的、无需金属的未活化吡啶 C-H 键直接氟化方法。该反应具有高官能团容忍度，并为现有 C-H 氟化策略提供了补充选择性。重要的是，这种晚期吡啶 C-H 氟化为合理调节烷基吡啶药物的碱性、亲脂性和代谢稳定性提供了机会。
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