反应详情

温度

65 °C

To a solution of (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinonitrile (Example 1; 0.5 g, 1.3 mmol) in MeOH (50 ml), was added a 25% aqueous solution (2 ml) of KOH (400 mg) at 25° C., followed by the addition of 0.1 ml of 30% H2O2. The resulting dark red solution was heated to 65° C. for 1 h, cooled to 25° C., and concentrated. The resulting residue was dissolved in EtOAc (50 ml), washed with water (30 ml), dried, filtered and concentrated. The resulting solid was purified by column chromatography (DCM-MeOH=30:1) to give the title compound (0.30 g, 60%). 1H NMR (400 MHz, CDCl3) δ 9.06 (d, J=7.0 Hz, 1H), 7.90 (br s, 1H), 7.35-7.32 (m, 2H), 7.25 (d, J=7.2 Hz, 1H), 7.00-6.95 (m, 2H), 6.00 (br s, 1H), 5.66 (br s, 2H), 5.21-5.17 (m, 1H), 1.86-1.82 (m, 1H), 1.54 (d, J=6.8 Hz, 3H), 0.96-0.92 (m, 2H), 0.69-0.67 (m, 2H). MS: Calcd.: 398. Found: [M+H]+ 399.

1. temperaturecooled to 25° C.
2. concentrationconcentrated
3. dissolutionThe resulting residue was dissolved in EtOAc (50 ml)
4. washwashed with water (30 ml)
5. customdried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting solid was purified by column chromatography (DCM-MeOH=30:1)