反应详情

温度

80 °C

A mixture of the Intermediate 45 (2.0 g, 3.77 mmol), 3-amino-4-fluoro phenylboronic acid (0.92 g, 5.94 mmol), Na2CO3 (0.88 g, 8.3 mmol) and catalytic amount of Pd(PPh3)4 in a mixture of toluene/EtOH/water (4:2:1) (28 mL) was stirred at 80° C. for 1 h. The mixture was cooled, and the solvents were removed. Water (5 mL) was added and the mixture was extracted with dichloromethane (3×5 mL). The combined organic fractions were washed with brine (5 mL), dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 40M, eluting with EtOAc/isohexane to give the title compound as a yellow gum. 1H NMR (CDCl3, 500 MHz) δ 8.42 (s, 1H), 7.91 (s, 1H), 7.77 (s, 2H), 7.10 (dd, J=11, 8 Hz, 1H), 6.77 (dd, J=8.5, 2.5 Hz, 1H), 6.64 (m, 1H), 5.72 (d, J=8.5 Hz, 1H), 4.98 (d, J=17.5 Hz, 1H), 4.40 (m, 1H), 4.10 (d, J=17.5 Hz, 1H), 2.64 (s, 3H), 0.74 (d, J=6.5 Hz, 3H). LCMS=561.5 (M+H)+.

1. temperatureThe mixture was cooled
2. customthe solvents were removed
3. additionWater (5 mL) was added
4. extractionthe mixture was extracted with dichloromethane (3×5 mL)
5. washThe combined organic fractions were washed with brine (5 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customthe solvent was evaporated under reduced pressure
9. customThe residue was purified by column chromatography on silica gel Biotage 40M
10. washeluting with EtOAc/isohexane