Solid phase and combinatorial synthesis of substituted thiophene

Details Solid phase and combinatorial synthesis of substituted thiophene Solid phase and combinatorial synthesis of substituted thiophene

1997-04-16

2000-10-24

Celsa, Bennett

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549 29, 549 68, 549 70, 514430, 514438, C07D33102, C07D33302, C07D33336, A01N 4302

Patent

active

061369845

ABSTRACT:
A solid phase method for the synthesis of a plurality of differently substituted thiophenes with a wide variety of side-chain substituents as compounds of potential therapeutic interest is disclosed. The thiophenes 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, followed by Thorpe-Ziegier-cyclization yields differently substituted, support-bound 3-aminothiophenes. These may be screened on the substrate or cleaved from the substrate and then screened in solution. Alternatively, the resin-bound 3-amino thiophenes or the synthetic intermediates can be subjected to further synthetic transformations (N-acylation, reduction) on the support, which permits the preparation of further therapeutically interesting compounds. The efficient synthesis of a wide variety of thiophenes using automated synthesis technology of the present method makes these compounds attractive candidates for the generation and rapid screening of diverse thiophene-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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