Solid-Phase Synthesis and Spectral Properties of 2-Alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones:A Combinatorial Approach for 2-Alkylthioimidazocoumarins

摘要

The solid-phase synthesis of 2-alkylthio-6H-pyrano[2,3-F]benzimidazole-6-ones (2-alkylthioimidazocoumarins) is described.7-Fluoro-4-methyl-6-nitro-2-oxo-2H-l-benzopyran-3-carboxylic acid was coupled to Rink amide resin via its carboxyl group.The resin-bound scaffold then underwent aromatic nucleophilic substitution with primary amines,followed by reduction of the nitro group with tin (II) chloride.Subsequent cyclization of the o-dianilino intermediates with thiocarbonyldiimidazole (TCD) afforded resin-bound l,3-dihydro-2-thioxo-6H-pyrano[2,3-f]benzimidazole-6-ones,which were then S-alkylated with alkyl halides in the presence of N,N-diisopropylethylamine (DIEA).The desired products were obtained in good yield with high purity after trifluoroacetic acid cleavage.The unique spectral properties of 2-alkylthioimidazocoumarins indicate that they may be useful in photodynamic therapy.