Acetic Acid → 5-Methyl-1-(pyridin-4-yl)methyl-1H-benzimidazol-4-ylamine

Participants

Reaction Conditions

Reaction Steps

A 200-mL round-bottomed flask equipped with mechanical stirrer was charged with 5-Methyl-4-nitro-1-(pyridin-4-yl)methyl-1H-benzimidazole (881 mg, 3.46 mmol), iron powder (−325 mesh, 3.87 g, 6.92 mmol) and acetic acid (50 mL), and the resulting mixture stirred at 50° C. for 15 min. After this time the reaction was cooled to room temperature, diluted with 1:1 methylene chloride/methanol (1 L) and filtered through a pad of Celite 521. After washing the filter cake with 1:1 methylene chloride/methanol (2×50 mL), the filtrate was concentrated in vacuo. The resulting residue was dissolved in methylene chloride (50 mL) and vigorously stirred with 1M aqueous sodium hydroxide (50 mL). The resulting emulsion was filtered through a pad of Celite 521, the pad washed with methylene chloride (2×25 mL) and the organic layer of the filtrate separated and dried over sodium sulfate. Removal of the drying agent by filtration, followed by evaporation of the filtrate in vacuo gave a residue which was purified by flash chromatography. This purified material was dissolved in warm methylene chloride (15 mL) and the solution diluted with hexanes (35 mL). The resulting precipitate was filtered, washed with hexanes (3×100 mL) and dried under reduced pressure for 1.5 h to afford compound 2d as an off-white solid.

Provenance & Evidence