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Expedient synthesis of a 72-membered isoxazolino-?-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-?-ketoamides. This 2·3CR proceeds by (i) a Meldrum's acid-generated acyl ketene, which is trapped by an amine to form a ?-ketoamide intermediate in a 2CR followed, in one pot, by (ii) a Mannich reaction followed by elimination of dimethyl amine·HCl to generate an ?,?-unsaturated ?-ketoamide dipolarophile that reacts in a nitrile oxide 1,3-dipolar cycloaddition reaction. This one-pot 2·3CR process delivers the targeted isoxazolino-?-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.

SUBMITTER: Knapp JM

PROVIDER: S-EPMC3278521 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Expedient synthesis of a 72-membered isoxazolino-β-ketoamide library by a 2·3-component reaction.

Knapp John M JM Zhu Jie S JS Wood Alex B AB Kurth Mark J MJ

ACS combinatorial science 20120103 2

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, ...[more]

PMID: 22181856

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