反应详情

温度

110 °C

5-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 148.1, 60 mg, 0.134 mmol), pyrimidin-5-ylboronic acid (50 mg, 0.403 mmol), Pd(Ph3P)4 (12.43 mg, 10.76 μmol) and finely ground K3PO4 (143 mg, 0.672 mmol) were added to a MW vial and treated with toluene (672 μL). The vial was sealed, evacuated/purged with argon then the RM was stirred 110° C. for 16 h, diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 56.0 mg, 0.081 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Diol, from 15% to 20% in 6 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=1.00 min, m/z=446.3 [M+H]+, m/z=444.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.09-3.20 (m, 4H) 3.50-3.60 (m, 4H) 7.38 (d, J=8.28 Hz, 2H) 7.86 (d, J=9.16 Hz, 2H) 8.23 (d, J=2.38 Hz, 1H) 8.84 (d, J=2.38 Hz, 1H) 9.13 (s, 2H) 9.22 (s, 1H) 10.37 (s, 1H).

1. customThe vial was sealed
2. customevacuated/purged with argon
3. additiondiluted with DME (2 mL)
4. filtrationthe supernatant was filtered
5. customthe solvent was evaporated off under reduced pressure
6. customto give a residue which
7. customwas purified by preparative SFC (Column Diol, from 15% to 20% in 6 min)