反应详情

Using a similar procedure to that described in Example 1, step 5, 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol (0.2312 g, 0.954 mmol) was reacted with methanesulphonyl chloride (0.151 mL, 1.91 mmol) and triethylamine (0.266 mL, 1.91 mmol) in tetrahydrofuran (30 mL), followed by cis-3-fluoro-4-[2-(trifluoromethyl)benzylamino]piperidine (0.3950 g, 1.43 mmol) and potassium carbonate (0.2642 g, 1.91 mmol) in 2-propanol (30 mL). Purification by flash chromatography (alumina, CH2Cl2 --MeOH--NH3 (aq); 98:2:0.2; then silica gel, CH2Cl2 --MeOH--NH3 (aq); 94:6:0.6) gave 0.2096 g (44%) of the title compound, free base. The oxalate salt was prepared in MeOH--Et2O; mp 116°-120° C. Found: C, 52.70; H, 5.09; N, 12.22. Cl26 H28F4N6. 2C2H2O4 requires: C, 52.94; H, 4.74; N, 12.35%. δH (360 MHz, d6 -DMSO) 1.81 (1H, m), 1.92-2.03 (3H, m), 2.69-3.12 (7H, m), 3.30 (1H, m), 3.60 (1H, m), 3.99 (2H, s), 5.04 (1H, d, J=46.4 Hz), 7.31-7.33 (2H, m), 7.48-7.51 (2H, m), 7.66-7.71 (2H, m), 7.79 (1H, s), 7.84 (1H, d, J=7.4 Hz), 9.01 (2H, s), 11.17 (1H, s). m/e (ES+) 501 (M+H)+.

1. customPurification by flash chromatography (alumina, CH2Cl2