反应详情

To a degassed solution of the title compound from Example 3 Step A (24.0 mg, 0.038 mmol) in EtOAc (2 mL) was added platinum(IV) oxide (8.0 mg). The reaction mixture was fitted with a hydrogen balloon attached to a 3-way adapter. The reaction flask was then evacuated and back-filled with hydrogen. After this process was repeated three times, the reaction mixture was placed under a hydrogen atmosphere and was stirred vigorously. After 45 min, the reaction mixture was filtered through Celite, rinsing with EtOAc. The mixture was concentrated in vacuo and used without further purification: LCMS m/z 640.6 [M+H]+. To a solution of the hydrogenation product in 1,4-dioxane (2 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 30 min, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (50 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 612.5 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.12 (d, J=8.0 Hz, 1H), 8.11 (s, 1H), 8.08 (t, J=8.0 Hz, 1H), 7.74 (dd, J=8.0, 1.5 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.09 (t, J=8.5 Hz, 1H), 5.20 (s, 2H), 2.97-2.94 (m, 2H), 2.91-2.88 (m, 2H).

1. customattached to a 3-way adapter
2. customThe reaction flask was then evacuated
3. additionback-filled with hydrogen
4. filtrationthe reaction mixture was filtered through Celite
5. washrinsing with EtOAc
6. concentrationThe mixture was concentrated in vacuo
7. customused without further purification
8. stirringthe resulting mixture was stirred at 50° C
9. waitAfter 30 min
10. filtrationfilter
11. customPurification by reverse phase HPLC (50 to 100% acetonitrile in water