反应详情

To a cooled (−78° C.) solution of the title compound of Example 1 Step B (161 mg, 0.58 mmol) in THF (3 mL) was added KHMDS (2.30 mL, 0.5 M in toluene, 1.15 mmol). After 30 min, a solution of the title compound of Example 2 Step A (357.0 mg, 1.16 mmol) in THF (3 mL) was added, and the resultant mixture was allowed to warm slowly to room temperature over 15 h. The mixture was then quenched by addition of sat. aq. NaHCO3, and the aqueous phase was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was taken forward without further purification. A small portion was removed and purified by reverse phase HPLC (85 to 100% CH3CN in H2O, both with 0.1% v/v TFA) for characterization: LCMS C, tr=3.12 min, m/z 506.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J=1.5 Hz, 1H), 7.79 (dd, J=8.0, 2.0 Hz, 1H), 7.63 (d, J=1.5 Hz, 1H), 7.33-7.25 (m, 3H), 7.11 (s, 1H), 4.02 (s, 3H), 3.89 (s, 3H), 3.83 (dddd, J=9.0, 9.0, 6.0, 6.0 Hz, 1H), 3.21 (dd, J=13.5, 9.0 Hz, 1H), 3.06 (dd, J=13.5, 6.0 Hz, 1H), 1.91-1.83 (m, 2H), 1.63-1.56 (m, 1H), 1.39-1.26 (m, 5H), 0.86 (t, J=6.5 Hz, 3H).

1. customThe mixture was then quenched by addition of sat. aq. NaHCO3
2. extractionthe aqueous phase was extracted with EtOAc
3. dry with materialThe organic phase was dried over anhydrous Na2SO4
4. concentrationconcentrated in vacuo
5. customThe crude product was taken forward without further purification
6. customA small portion was removed
7. custompurified by reverse phase HPLC (85 to 100% CH3CN in H2O
8. customLCMS C, tr=3.12 min, m/z 506.2 [M+H]+