反应详情

温度

135 °C

2-Chloro-5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Method 2; 1.6 g, 5.0 mmol) and (R)-2-amino-2-(4-fluorophenyl)ethanol (2.0 g, 11.0 mmol) were added to a solution of n-BuOH (8 ml) and DIEA (0.8 g, 6.0 mmol) in a sealed tube. The reaction was heated to 135° C. for 72 hrs, cooled to 25° C., and concentrated. The resulting residue was purified by column chromatography (DCM-MeOH=50:1) to give the title compound (0.7 g, 31%). 1H NMR (400 MHz, CD3OD) δ 7.49 (d, J=9.5 Hz, 1H), 7.41-7.38 (m, 2H), 7.07-7.02 (m, 2H), 5.40 (s, 1H), 5.10-5.01 (m, 1H), 4.62-4.55 (m, 1H), 3.91-3.79 (m, 2H), 1.33-1.31 (m, 6H). MS: Calcd.: 414. Found: [M+H]+ 415.

1. temperaturecooled to 25° C.
2. concentrationconcentrated
3. customThe resulting residue was purified by column chromatography (DCM-MeOH=50:1)