反应详情

温度

-40 °C

To a stirred solution of ethyl 4-(1H-pyrazol-3-ylamino)quinazoline-2-carboxylate (595 mg, 2.1 mmol) in THF (15 mL) at −40° C., was added dropwise a 2 M solution of 4-fluorophenylmagnesium bromide in THF (4.2 mL, 8.4 mmol). The mixture was stirred at −40° C. for 2 h and then stored at −30° C. for 18 h. The reaction was quenched by adding 0.5 N HCl at 0° C. and the mixture was extracted with EtOAc (2×20 mL). The solid precipitate from the combined organic layers was removed by filtration and the resulting filtrate was washed with brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with 0-5% MeOH/DCM to afford (4-(1H-pyrazol-3-ylamino)quinazolin-2-yl)bis(4-fluorophenyl)methanol as a solid (75 mg, 8%). 1H NMR (300 MHz, DMSO-d6) δ 12.50 (s, 1H), 10.66 (s, 1H), 8.67 (d, J=8.1, 1H), 7.81-7.87 (m, 2H), 7.60-7.62 (m, 2H), 7.42-7.47 (m, 4H), 7.07-7.13 (m, 4H), 6.66 (s, 1H), 6.26 (s, 1H); LC-MS (ESI) m/z 430 (M+H)+.

1. waitstored at −30° C. for 18 h
2. customThe reaction was quenched
3. additionby adding 0.5 N HCl at 0° C.
4. extractionthe mixture was extracted with EtOAc (2×20 mL)
5. customThe solid precipitate from the combined organic layers was removed by filtration
6. washthe resulting filtrate was washed with brine
7. dry with materialThe organic phase was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude product was purified by silica gel chromatography
11. washeluting with 0-5% MeOH/DCM