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Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
An Atom-Economical Method To Prepare Enantiopure Benzodiazepines with N-Carboxyanhydrides
Patrick S Fier1, Aaron M Whittaker1
1Department of Process Research and Development, Merck & Co., Inc. , Rahway, New Jersey 07065, United States.
Abstract:
The development of a rapid, one-pot synthesis of diazepinones with simple reagents is described. N-Carboxyanhydrides (NCAs) are employed as amino acid building blocks that react with o-ketoanilines sequentially as electrophiles and nucleophiles to form diazepinones with water and carbon dioxide as byproducts. Notably, these reactions enable the coupling of stereodefined amino acid derived NCAs without racemization. This method is demonstrated by an improved synthesis of a key intermediate toward a bromodomain and extra-terminal (BET) bromodomain inihibitor.
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