title: Expedient synthesis of a 72-membered isoxazolino-β-ketoamide library by a 2·3-component reaction.
abstract: An efficient 2·3-component reaction (2·3CR; a 2-component reaction followed, in one pot, by a3-component reaction) is presented for the synthesis of isoxazolino-β-ketoamides. This 2·3CR proceeds by (i) a Meldrum's acid-generated acyl ketene, which is trapped by an amine to form a β-ketoamide intermediate in a 2CR followed, in one pot, by (ii) a Mannich reaction followed by elimination of dimethyl amine·HCl to generate an α,β-unsaturated β-ketoamide dipolarophile that reacts in a nitrile oxide 1,3-dipolar cycloaddition reaction. This one-pot 2·3CR process delivers the targeted isoxazolino-β-ketoamide product. A total of 72 compounds are presented, all of which have been submitted to the NIH Molecular Libraries Small Molecule Repository for high-throughput biological screening.
authors.forename: John M
authors.initials: JM
authors.lastname: Knapp
authors.forename: Jie S
authors.initials: JS
authors.lastname: Zhu
authors.forename: Alex B
authors.initials: AB
authors.lastname: Wood
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kurth
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000577:Amides; D007555:Isoxazoles; D054852:Small Molecule Libraries; C520957:beta-ketoamide