Sodium hydride → (S)-(3,5-bis-trifluoromethyl-benzyl)-[2-(cyclopentyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-(2-methyl-2H-tetrazol-5-yl)-amine

Participants

Reaction Steps

To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (25.7 mg, 0.078 mmol) in DMF (0.1 mL) at room temperature was added sodium hydride (6 mg, 0.2 mmol). The mixture was stirred at room temperature for 1 hour. 2-(Bromomethyl)-1-(cyclopentyl(methoxy)methyl)-4-(trifluoromethyl)benzene (Enantiomer 1 from STEP D, 23.1 mg, 0.066 mmol) in DMF (0.2 mL) was added. The mixture was stirred at room temperature for 2 days. Solvent was removed in vacuo. The residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-25% ethyl acetate in heptane) to afford the title compound (7.5 mg, 19%). 1H NMR (400 MHz, CDCl3) δ ppm 1.04-1.16 (m, 1H) 1.22-1.33 (m, 1H) 1.38-1.50 (m, 3H) 1.51-1.63 (m, 2H) 1.65-1.76 (m, 1H) 2.02-2.14 (m, 1H) 3.07 (s, 3H) 4.19 (d, J=7.88 Hz, 1H) 4.20-4.23 (m, 3H) 4.72 (d, J=2.49 Hz, 2H) 4.76 (d, J=16.18 Hz, 1H) 4.90 (d, J=16.18 Hz, 1H) 7.35 (s, 1H) 7.51-7.58 (m, 2H) 7.66 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 595.2, Found: 596.5 (M+1) To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (27.2 mg, 0.084 mmol) in DMF (0.1 mL) at room temperature was added sodium hydride (6 mg, 0.2 mmol). The mixture was stirred at room temperature for 1 hour. 2-(Bromomethyl)-1-(cyclopentyl(methoxy)methyl)-4-(trifluoromethyl)benzene (Enantiomer 2 from STEP D, 24.5 mg, 0.070 mmol) in DMF (0.2 mL) was added. The mixture was stirred at room temperature overnight. Solvent was removed in vacuo. The residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in heptane) to afford the title compound (18.6 mg, 45%). The residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-30% ethyl acetate in hexanes) to afford a colorless oil (18.6 mg, 45%). 1H NMR (400 MHz, CDCl3) δ ppm 1.04-1.15 (m, 1H) 1.23-1.33 (m, 1H) 1.38-1.63 (m, 5H) 1.66-1.75 (m, 1H) 2.03-2.11 (m, 1H) 3.07 (s, 3H) 4.19 (d, J=7.88 Hz 1H) 4.21 (s, 3H) 4.72 (d, J=2.90 Hz, 2H) 4.76 (d, J=16.18 Hz, 1H) 4.90 (d, J=16.18 Hz, 1H) 7.35 (s, 1H) 7.51-7.58 (m, 2H) 7.66 (s, 2H) 7.77 (s, 1H). MS (ES+) Calc: 595.2, Found: 596.5 (M+1).

Provenance & Evidence