Triethylamine → 1-(8-{2-[1-(isoxazol-3-ylcarbonyl)-4-phenylpiperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

関与物質

反応手順

To a pre-cooled (0° C.) solution of 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride (25.3 mg, 0.05 mmol) in dichloromethane (3 mL) was added isoxazole-5-carbonyl chloride (7.2 mg, 0.055 mmol) and triethylamine (15 μL, 0.11 mmol). The resulting mixture was stirred overnight at ambient temperature and was then diluted with ethyl acetate (20 mL). After being washed with saturated sodium bicarbonate solution, the organic phase was dried over anhydrous sodium sulfate and evaporated. The crude product was purified by flash chromatography on silical gel, eluting with a gradient of 0-10% methanol in ethyl acetate to afford 1-(8-{2-[1-(isoxazol-3-ylcarbonyl)-4-phenylpiperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole as amorphous solid (18.4 mg, 68%). 1H NMR (300 MHz, CDCl3) δ 8.32 (d, J=1.8 Hz), 7.67 (dd, J=2.6, 7.0 Hz, 1H), 7.43-7.38 (m, 2H), 7.34-7.24 (m, 4H), 7.21-7.13 (m, 2H), 6.74 (d, J=1.8 Hz), 4.64 (br, 1H), 4.23-4.18 (m, 1H), 3.93-3.89 (m, 1H), 3.45-3.27 (m, 4H), 2.58 (s, 3H), 2.44-2.31 (m, 4H), 1.96-1.86 (m, 10H), 1.67-1.60 (m, 2H). HRMS m/z (M+H)+ calcd: 524.3026, obsd: 524.3024.

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