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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)85-88
Number of pages4
JournalACS Combinatorial Science
Volume14
Issue number2
DOIs
StatePublished - Feb 13 2012

Fingerprint

Nitriles
Cycloaddition
Oxides
Amines
Screening
Throughput
Molecules
Meldrum's acid
ketene

Keywords

  • 2·3-component reaction
  • isoxazolino-β-ketoamide product
  • isoxazolino-β-ketoamides
  • one pot

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Expedient synthesis of a 72-membered isoxazolino-β-ketoamide library by a 2·3-component reaction. / Knapp, John M.; Zhu, Jie S.; Wood, Alex B.; Kurth, Mark J.

In: ACS Combinatorial Science, Vol. 14, No. 2, 13.02.2012, p. 85-88.

Research output: Contribution to journalArticle

Knapp, John M. ; Zhu, Jie S. ; Wood, Alex B. ; Kurth, Mark J. / Expedient synthesis of a 72-membered isoxazolino-β-ketoamide library by a 2·3-component reaction. In: ACS Combinatorial Science. 2012 ; Vol. 14, No. 2. pp. 85-88.
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