Trimethyl orthoformate → 2-{[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl}-6-(3-dipropylaminopropyl)-naphtalene

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Reaction Steps

The compound (280 mg) obtained in Example 121-11 was dissolved in anhydrous methanol (5.0 ml) and added with trimethyl orthoformate (0.154 ml) and 2-imidazole carboxaldehyde (90.1 mg), followed by stirring at room temperature for 2 hours under a nitrogen atmosphere. Subsequently, the solution was added with sodium borohydride (53.3 mg) in an ice bath and stirred at room temperature for 30 minutes. After completion of the reaction, a saturated aqueous ammonium chloride solution was added to the solution, and the whole was stirred. The solution was subjected to extraction with chloroform. The extract was washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution. Then, the organic layer was dried with anhydrous sodium sulfate. The residue obtained was dissolved in anhydrous methanol (10 ml) and added with sodium cyanoborohydride (93.6 mg), acetic acid (3.00 ml), and 1-methyl-2-imidazole carboxaldehyde (120 mg), followed by stirring at room temperature for 2 days under a nitrogen atmosphere. After completion of the reaction, the solvent was distilled off and the residue was then dissolved in chloroform. The solution was added with a saturated aqueous sodium bicarbonate solution and stirred. The solution was subjected to extraction with chloroform and the extract was then washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution. The organic layer was dried with anhydrous sodium sulfate and then the solvent was distilled off. Subsequently, the residue was purified through silica gel column chromatography (chloroform/ethyl acetate) and treated with hydrochloric acid, thereby obtaining hydrochloride (318 mg) of the subject compound as a white solid.

Provenance & Evidence