反应详情

温度

130 °C

A mixture of (1S,2S)-2-fluoro-N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide (230 mg, 0.648 mmol), (3-bromo-5-fluoro-4-methyl-2-pyridyl)methanol (143 mg, 0.648 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (46 mg, 0.065 mmol) and saturated aqueous sodium carbonate solution (0.3 mL) in acetonitrile (3 mL) was heated under microwave irradiation (Biotage) at 130° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (30 mL) and washed with water (15 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 min). Desired fractions were combined and evaporated in vacuo to afford the title compound as an off-white solid (26 mg, 11%). 1H NMR (400 MHz, DMSO) δ 10.98 (s, 1H), 9.16 (s, 1H), 8.54 (s, 2H), 7.99 (m, 2H), 7.59 (d, J=8.4 Hz, 1H), 5.08-4.81 (m, 2H), 4.24 (s, 2H), 2.34-2.22 (m, 1H), 2.00 (s, 3H), 1.70 (m, 1H), 1.20 (m, 1H). LCMS (Method E): RT=6.66 min, M+H+=370.0.

1. washwashed with water (15 mL)
2. customThe organic layer was separated
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto provide a residue that
7. customwas purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 min)
8. customevaporated in vacuo