Acetic Acid → N-(4-dipropylaminobutyl)-4-{[(1H-imidazol-2-ylmethyl)-(2R)-pyrrolidin-2-ylmethylamino]-methyl}-benzamide

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Reaction Steps

The compound (53.8 mg) obtained in Example 1-4 was dissolved in methanol (0.8 ml). Then, the solution was added with trimethyl orthoformate (50 μl), acetic acid (50 μl), N-Boc-D-prolinal (manufactured by Aldrich Corporation) (25.7 mg) and stirred at room temperature for 10 minutes. Subsequently, sodium cyanoborohydride (24.4 mg) was added, followed by stirring overnight at room temperature. The solvent was distilled off under reduced pressure and the residue was then dissolved in chloroform, followed by washing with 1 mol/l sodium hydroxide and saturated saline solution and drying with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure and the residue was then purified through silica gel column chromatography (chloroform/methanol). Then, the purified product was dissolved in methanol (500 μl) and added with a 4 mol/l hydrogen chloride/dioxane solution (500 μl), followed by stirring at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was then purified through silica gel column chromatography (chloroform/methanol), thereby obtaining hydrochloride (33.9 mg) of the subject compound as a white solid.

Provenance & Evidence