title: An Atom-Economical Method To Prepare Enantiopure Benzodiazepines with N-Carboxyanhydrides.
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.
authors.affiliation: Department of Process Research and Development, Merck & Co., Inc. , Rahway, New Jersey 07065, United States.
authors.forename: Patrick S
authors.identifier: 0000-0002-6102-815X
authors.initials: PS
authors.lastname: Fier
authors.affiliation: Department of Process Research and Development, Merck & Co., Inc. , Rahway, New Jersey 07065, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Whittaker
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001569:Benzodiazepines / Q000138:chemical synthesis*; D002245:Carbon Dioxide / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D000812:Anhydrides; D000814:Aniline Compounds; D014867:Water; D001569:Benzodiazepines; D002245:Carbon Dioxide