反应详情

—Step 6: To a solution of 101f (257 mg, 0.387 mmol) in THF/i-PrOH/H2O (5.0/3.0/2.0 mL) was added LiOH (46 mg, 1.95 mmol) at room temperature. The reaction was stirred for 1 h. The mixture was diluted with water (15 mL) and extracted with DCM (15 mL×3). The combined organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 101 (95 mg, 39% two steps) as a white solid. MS-ESI: [M+H]+ 624.2. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.0 Hz, 1H), 9.70 (s, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.50-7.48 (m, 1H), 7.29-7.27 (m, 1H), 6.85 (s, 1H), 6.46-6.44 (m, 2H), 6.27-6.23 (m, 2H), 6.05-6.00 (m, 1H), 5.61-5.59 (m, 1H), 4.98-4.96 (m, 1H), 4.72-4.70 (m, 1H), 4.55-4.53 (m, 1H), 4.39-4.29 (m, 3H), 4.19-4.16 (m, 2H), 3.96-3.94 (m, 1H), 375-3.73 (m, 4H, overlap), 3.64-3.60 (m, 1H), 2.61-2.59 (m, 2H), 2.53-2.51 (m, 2H), 1.30 (s, 6H).

1. extractionextracted with DCM (15 mL×3)
2. washThe combined organic layer was washed with brine (10 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue solid was purified by reverse-phase prep-HPLC