反应详情

(8R,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride (27.6 mg, 0.085 mmol, 1.0 equivalent, prepared as described in Example 55, Part B) was suspended in dichloromethane (1.0 mL) in a 4-mL scintillation vial. Triethylamine (43 mg, 0.425 mmol, 5.0 equivalents) was added followed by 4-(trifluoromethyl)benzene-1-sulfonyl chloride (27 mg, 0.11 mmol, 1.3 equivalents) as a solution in dichloromethane (0.1 mL). The reaction was stirred for 15 minutes. The mixture was loaded directly onto a 4 g silica gel column and with 0:100 to 50:50 ethyl acetate:heptanes (flow rate=18 mL/minute) over 20 minutes to give the title compound as a white solid (25 mg, 62%). 1H NMR (400 MHz, CDCl3) δ ppm 7.95 (d, J=1.4 Hz, 1H), 7.92 (d, J=1.4 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.82 (d, J=8.4 Hz, 2H), 5.53-5.25 (m, 1H), 4.17 (td, J=9.4, 3.0 Hz, 1H), 4.12-4.00 (m, 1H), 3.97 (d, J=13.4 Hz, 1H), 3.79 (d, J=3.5 Hz, 2H), 2.99-2.55 (m, 5H), 2.14-1.92 (m, 2H), 0.95 (ddt, J=12.1, 7.0, 2.0 Hz, 4H); MS (ESI+) m/z expected 497.1; found: 497.0 (M+H)+; [α]D24.1=0.19 (c=0.12, CH3OH).