反应 #160949

反应方程式

(R)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethyl)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide

ethylene

TBAF

THF

→

title compound

(R)-6-(3-Hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethyl)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

反应条件

后处理

1. 1
   workup.ADDITIONwas added
2. 2
   其他The solvent was evaporated off under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in EtOAc (40 mL)
4. 4
   洗涤washed 3 times with sat. aq. NaHCO3 and brine
5. 5
   干燥dried over Na2SO4
6. 6
   其他the solvent was evaporated off under reduced pressure
7. 7
   其他to give a residue which
8. 8
   其他was purified by preparative SFC (Column Diol, isocratic 27% in 9 min)

实验过程

A mixture of (R)-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethyl)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide (Stage 16.1, 68 mg, 0.114 mmol) and ethylene damien (38.4 μL, 0.569 mmol) in a MW vial and sealed under an argon atmosphere 1 M TBAF in THF (1.707 mL, 1.707 mmol) was added and the RM was stirred at 80° C. for 20 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in EtOAc (40 mL), washed 3 times with sat. aq. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Diol, isocratic 27% in 9 min) to afford the title compound as an off-white solid. UPLC-MS (Condition 3) tR=0.98 min, m/z=468.2 [M+H]+, m/z=466.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.78 (m, 1H) 1.83 (dd, J=8.80, 4.40 Hz, 1H) 2.96 (d, J=11.74 Hz, 1H) 3.19-3.29 (m, 2H) 3.40-3.50 (m, 1H) 4.20 (br. s, 1H) 4.83 (br. s, 1H) 6.39 (d, J=1.96 Hz, 1H) 7.65 (d, J=8.80 Hz, 2H) 7.77 (br. s, 1H) 8.02 (d, J=9.05 Hz, 2H) 8.05 (d, J=2.45 Hz, 1H) 8.76 (d, J=2.20 Hz, 1H) 10.33 (s, 1H) 12.91 (br. s, 1H).

来源