反应详情

温度

110 °C

5,6-dichloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 43.2, 500 mg, 1.424 mmol), trimethylboroxime (179 mg, 1.424 mmol), Pd(PPh3)4, (165 mg, 0.142 mmol), K2CO3 (295 mg, 2.136 mmol) and dioxane (4069 μL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 110° C. for 72 h. The RM was filtered through a pad of Celite®, which was washed with EtOAc. The combined filtrates were evaporated to dryness under reduced pressure and the residue was purified by flash chromatography (Silica gel column, 24 g, cyclohexane/EtOAc-EtOH (9:1)+0.1% NH4OH, gradient from 5% to 25% EtOAc-EtOH (9:1)+0.1% NH4OH) and recrystallized from cyclohexane/EtOAc to afford the title compound as a light yellow solid. UPLC-MS (Condition 1) tR=2.76 min, m/z=331.0 [M+H]+, m/z=329.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.64 (s, 3H) 7.39 (d, J=9.05 Hz, 2H) 7.87 (d, J=9.05 Hz, 2H) 8.38 (d, J=1.71 Hz, 1H) 8.94 (d, J=1.96 Hz, 1H) 10.60 (s, 1H).

1. customwas sealed
2. customevacuated/purged with argon
3. filtrationThe RM was filtered through a pad of Celite®, which
4. washwas washed with EtOAc
5. customThe combined filtrates were evaporated to dryness under reduced pressure
6. customthe residue was purified by flash chromatography (Silica gel column, 24 g, cyclohexane/EtOAc-EtOH (9:1)+0.1% NH4OH, gradient from 5% to 25% EtOAc-EtOH (9:1)+0.1% NH4OH)
7. customrecrystallized from cyclohexane/EtOAc