反应详情

A solution of (S)-(1-methylpyrrolidin-2-yl)methanol (109 mg, 0.94 mmol) in THF (5 mL) was treated with 1 M solution of potassium t-butoxide (0.95 mL, 0.944 mmol) and stirred for 15 min. A solution of Example 9B (190 mg, 0.47 mmol) was added to the reaction mixture and stirred for 6 hours. The reaction mixture was quenched with saturated NH4Cl solution, concentrated in vacuo, partitioned between EtOAc and brine, dried (MgSO4), filtered, and concentrated. The residue was purified using an Analogix® Intelliflash280™ (SiO2, 0-15% methanol in dichloromethane) to afford the title compound (175 mg, 75% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (t, J=7.3 Hz, 3H), 1.17-1.42 (m, 11H), 1.49-1.83 (m, 5H), 1.82-2.03 (m, 1H), 2.17 (q, J=8.7 Hz, 1H), 2.32 (s, 3H), 2.54-2.67 (m, 1H), 2.83-3.01 (m, 1H), 3.92-4.10 (m, 2H), 4.14 (t, J=7.3 Hz, 2H), 7.28 (d, J=8.8 Hz, 1H), 7.32 (s, 1H), 7.72 (dd, J=9.0, 2.2 Hz, 1H), 7.95 (d, J=2.0 Hz, 1H). MS (DCI/NH3) m/z 498 (M+H)+. Anal. calcd for C25H34F3N3O2S: C, 60.34; H, 6.99; N, 8.44. Found: C, 60.27; H, 7.09; N, 8.40.

1. stirringstirred for 6 hours
2. customThe reaction mixture was quenched with saturated NH4Cl solution
3. concentrationconcentrated in vacuo
4. custompartitioned between EtOAc and brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified