Dimethylformamide → 3-{[[(2-Cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-5-trifluoromethyl-benzonitrile

関与物質

反応手順

To a solution of [2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine (28 mg, 0.073 mmol) in DMF (2 mL) at 0° C. under nitrogen was added sodium hydride (4.4 mg, 0.11 mmol, 60% dispersion in mineral oil). The reaction was stirred for 30 minutes, allowing it to warm to room temperature. The reaction mixture was then treated with 3-(bromomethyl)-5-(trifluoromethyl)benzonitrile (19.3 mg, 0.073 mmol) at room temperature and stirred for overnight. Solvent was removed in vacuo. The residue was diluted with ethyl acetate and washed with satd. sodium bicarbonate solution, water and brine, dried over anhydrous magnesium sulphate and concentrated in vacuo. The product was purified on Biotage column (12+S), eluting with 2% ethyl acetate in heptane (1CV), 2-20% (10CV), 20% (2CV) to yield the title compound (21 mg, 49%) as a colorless oil, 1H NMR (400 MHz, CDCl3) δ ppm 1.07 (m, 4H) 1.2 (m, 3H) 1.65(m, 3H) 1.73 (m, 1H) 3.18 (s, 3H) 4.06 (s, 3H) 4.2 (m, 1H) 4.67-5.04 (m, 2H) 5.4 (m, 1H) 7.39 (s, 1H) 7.50 (m, 3H) 7.5 (m, 2H). MS (ES+) Calc: 566.2, Found: 567.5 (M+1). According to the procedures described in Examples 42-45 and using the appropriate amine, Examples 46-50 were prepared.

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