Solid-phase parallel synthesis of substituted dihydroimidazolyl dihydrobenzimidazol-2-ones

The solid-phase synthesis of substituted (4,5-dihydro-1H-imidazole-2-yl)-1,3-dihydro-2H-benzimidazol-2-ones is described. Following the amide reduction of a resin-bound (MBHA resin) amino acid, the primary amine was selectively acylated with 4-fluoro-3-nitrobenzoic acid. Treatment with POCl3, displacement of the fluoro group, and reduction of the nitro group generated an o-dianiline. Cyclization with 1,1-carbonyldiimidazole resulted in a benzimidazolone analogue, which was subsequently N-alkylated with an alkyl halide. The compounds were cleaved from the solid-support using anhydrous HF and characterized by LC–MS and 1H and 13C NMR spectroscopy.