Patent · US Expired

Solid phase and combinatorial synthesis of substituted 2-methylene-2, 3-dihydrothiazoles and of arrays of substituted 2-methylene-2, 3-dihydrothiazoles

US5847150A · kind A · utility

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Key dates

Filing dateApr 16, 1997
Grant dateDec 8, 1998
Priority date
Expiry dateApr 16, 2017

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC07D277/14
  • WIPO fieldOrganic fine chemistry
  • WIPO sectorChemistry

Abstract

A solid phase method for the synthesis of a plurality of differently substituted 2-methylenethiazoles with a wide variety of side-chain substituents as compounds of potential therapeutic interest. The 2-methylenethiazoles are prepared by acylation of a substrate-bound primary or secondary amine with cyanoacetic acid and reaction of the resulting cyanoacetamide with an isothiocyanate in the presence of a base. Alkylation with an appropriate alkyl halide under acidic conditions yields differently substituted, support-bound 2-methylene-2,3-dihydrothiazoles. These may be screened on the substrate or cleaved from the substrate and then screened in solution. The efficient synthesis of a wide variety of 2-methylenethiazoles using automated synthesis technology of the present method makes these compounds attractive candidates for the generation and rapid screening of diverse thiazole-based libraries. The method disclosed here provides an easy and fast access to highly diverse heterocyclic compounds of therapeutic interest, amenable to automatization.

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