反应详情

5-Bromo-6-(pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 15.1, 60 mg, 0.139 mmol) and (1H-pyrazol-3-yl)boronic acid (62.4 mg, 0.558 mmol), Pd(PPh3)2Cl2 (11.75 mg, 0.017 mmol), Na2CO3 (73.9 mg, 0.697 mmol), DME (592 μL), water (169 μL) and EtOH (85 μL) were added to a MW vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation at 130° C. for 30 min. Additional 1-H-Pyrazole-3-boronic acid, (31.2 mg, 0.279 mmol) was added to the RM and was subjected to further MW irradiation at 130° C. for 30 min. The RM was diluted with THF (2 mL), treated with Si-Thiol (1.44 mmol/g, 58.1 mg, 0.084 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 2-EP, from 10% to 15% in 6 min) to yield the title compound as a white solid. UPLC-MS (Condition 3) tR=1.02 min, m/z=418.4 [M+H]+, m/z=462.2 [M+formic acid-H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.90 (m, 4H) 3.19 (t, J=6.21 Hz, 4H) 6.40 (d, J=1.88 Hz, 1H) 7.35 (d, J=8.66 Hz, 2H) 7.75 (br. s, 1H) 7.87 (d, J=9.03 Hz, 2H) 8.04 (d, J=2.26 Hz, 1H) 8.75 (d, J=2.38 Hz, 1H) 10.22 (br. s, 1H) 12.70-13.19 (m, 1H).

1. customwas sealed
2. customevacuated/purged with argon
3. customsubjected to MW irradiation at 130° C. for 30 min
4. customwas subjected to further MW irradiation at 130° C. for 30 min
5. filtrationthe supernatant was filtered
6. customthe solvent was evaporated off under reduced pressure
7. customto give a residue which
8. customwas purified by preparative SFC (Column 2-EP, from 10% to 15% in 6 min)