反应详情

温度

140 °C

5-Bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide (Stage 22.2, 206 mg, 0.5 mmol) and (R)-pyrrolidin-3-ol (52.3 mg, 0.6 mmol) were dissolved in iPrOH (1 mL). DIPEA (192 μL, 1.1 mmol) was added and the RM mixture was stirred at 140° C. for 1 h in a sealed vial. After cooling at RT, the RM was dissolved in EtOAc, washed with 0.5 M HCl and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 20% to 100% EtOAc). The resulting product was triturated under n-heptane, filtered and dried to afford the title compound as a white crystalline powder. HPLC (Condition 4) tR=5.68 min, UPLC-MS (Condition 3) tR=1.15 min, m/z=462.1 [M+H]+.

1. temperatureAfter cooling at RT
2. washwashed with 0.5 M HCl and brine
3. dry with materialdried over Na2SO4
4. customthe solvent was evaporated off under reduced pressure
5. customto give a crude product which
6. customwas purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 20% to 100% EtOAc)
7. customThe resulting product was triturated under n-heptane
8. filtrationfiltered
9. customdried