Work

Expedient Synthesis of a 72-Membered Isoxazolino-β-ketoamide Library by a 2·3-Component Reaction

Year: 2011

Type: article

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.

Source: ACS Combinatorial Science

DOI: 10.1021/co200199h

Authors: John M. Knapp, Jie S. Zhu, Alex B. Wood, Mark J. Kurth

Institution: University of California, Davis

Language: English

Topic: Multicomponent Synthesis of Heterocycles

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Award: Complex Heterocycles and Hybrid Strategies for Pilot Scale Libraries