反应详情

温度

80 °C

A mixture of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 56.1, 5.7 g, 12.75 mmol), pyrimidine-5-boronic acid (2.5 g, 19.77 mmol), PdCl2(dppf)-(CH2Cl2) (0.625 g, 0.765 mmol), Na2CO3 (19.13 mL, 38.3 mmol) and DME (100 mL) was stirred at 80° C. for 2.5 h under argon atmosphere. The RM was filtered through Hyflo®, diluted with EtOAc (100 mL), washed with a sat. aq. solution of NaHCO3 and with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc) to give the title compound product as a pink crystalline solid. UPLC-MS (Condition 2) tR=1.01 min, 393.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.42 (d, J=8.99 Hz, 2H) 7.88 (d, J=9.38 Hz, 2H) 8.56 (d, J=2.35 Hz, 1H) 9.03 (d, J=2.35 Hz, 1H) 9.10 (s, 2H) 9.32 (s, 1H) 10.69 (s, 1H).

1. filtrationThe RM was filtered through Hyflo®
2. additiondiluted with EtOAc (100 mL)
3. washwashed with a sat. aq. solution of NaHCO3 and with brine
4. dry with materialdried over Na2SO4
5. customthe solvent was evaporated off under reduced pressure
6. customto give the crude product which
7. customwas purified by flash chromatography (Biotage Silica gel column, 120 g, Eluent: n-hexane/EtOAc from 20% to 60% EtOAc)