Catalytic Deuterium Incorporation within Metabolically Stable β‑Amino C–H Bonds of Drug Molecules

An efficient deuteration process of β-amino C–H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B­(C6F5)3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/ba...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2019-09, Vol.141 (37), p.14570-14575
Main Authors: Chang, Yejin, Yesilcimen, Ahmet, Cao, Min, Zhang, Yuyang, Zhang, Bochao, Chan, Jessica Z, Wasa, Masayuki
Format: Article
Language:English
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Summary:An efficient deuteration process of β-amino C–H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B­(C6F5)3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d 6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of β-deuterated bioactive amines with up to 99% deuterium incorporation.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b08662