反应详情

温度

80 °C

1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester (9.45 g, 34.0 mmol), Na2CO3 (39.2 mL, 78 mmol) and PdCl2(dppf) (0.956 g, 1.307 mmol) were added to 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 25.2, 12 g, 26.1 mmol) in DME (160 mL). The mixture was evacuated/purged 3 times with argon, and stirred at 80° C. for 22 h. The RM was diluted with EtOAc (350 mL), washed with water (4×150 mL) and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 850 g, EtOAc/n-hexane (1:2)) and crystallized from iPr2O/EtOAc to give the title product as a white solid. HPLC (Condition 5) tR=7.52 min, UPLC-MS (Condition 3) tR=1.22 min, m/z=483/485 [M+H]+.

1. customThe mixture was evacuated/purged 3 times with argon
2. additionThe RM was diluted with EtOAc (350 mL)
3. washwashed with water (4×150 mL)
4. extractionextracted with EtOAc
5. dry with materialThe combined extracts were dried over Na2SO4
6. customthe solvent was evaporated off under reduced pressure
7. customto give the crude product which
8. customwas purified by flash chromatography (Silica gel column, 850 g, EtOAc/n-hexane (1:2))
9. customcrystallized from iPr2O/EtOAc