反应详情

温度

100 °C

A stirred mixture of (R)-5-cyano-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 70.2, 1 g, 2.55 mmol), NaHSO3 (0.953 g, 15.3 mmol) and ethylenediamine (7.66 g, 1.27 mmol) was treated dropwise with 40% aq. ammonium silfide (4.34 mL, 25.5 mmol) and heated at 100° C. for 18 h. The cooled mixture was treated with EtOAc, washed with sat. aq. NaHCO3 and brine, was dried over anhydrous Na2SO4 and the solvent was evaporated off under reduced pressure. The crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/(5% aq. NH3 in MeOH) from 0 to 40% (5% aq. NH3 in MeOH)) to afford the product as a pale-yellow solid. HPLC (Condition 4) tR=3.89 min, UPLC-MS (Condition 8) tR=0.72 min, m/z=436.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.67-1.98 (m, 3H) 3.40-3.75 (m, 8H) 4.30 (br. s, 1H) 4.91 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.78-7.91 (m, 2H) 8.06 (d, J=2.35 Hz, 1H) 8.71 (d, J=2.35 Hz, 1H) 10.17 (s, 1H).

1. washwashed with sat. aq. NaHCO3 and brine
2. dry with materialwas dried over anhydrous Na2SO4
3. customthe solvent was evaporated off under reduced pressure
4. customThe crude product was purified by flash chromatography (RediSep® Silica gel column, DCM/(5% aq. NH3 in MeOH) from 0 to 40% (5% aq. NH3 in MeOH))