反应详情

温度

-40 °C

To a suspension of ethyl 4-(1H-pyrazol-3-ylamino)quinazoline-2-carboxylate (0.110 g, 0.39 mmol) in THF (5 mL) under argon at −40° C. was added (2-methoxyphenyl)magnesium bromide (0.5 M solution in THF; 2.32 mL, 1.16 mmol). The mixture was stirred at −40° C. for 3 h and quenched with 0.5 N HCl (10 mL). The organic layer was separated. The aqueous layer was washed with 10% MeOH/CH2Cl2 (50 mL×2). The combined organic layers were washed with brine (25 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on preparative HPLC (Phenomenex phenylhexyl reverse phase column, eluted with gradient of solvent B=0.05% HOAc/CH3CN and solvent A=0.05% HOAc/H2O) to afford (4-(1H-pyrazol-3-ylamino)quinazolin-2-yl)(2-methoxyphenyl)methanone as a yellow solid (0.023 g, 17%). 1H NMR (300 MHz, DMSO-d6) δ 3.50 (s, 3H), 6.58 (s, 1H), 7.15 (m, 2H), 7.70-7.50 (m, 4H), 7.88 (m, 2H), 8.75 (d, 1H), 10.68 (s, 1H), 12.42 (s, 1H); LC-MS (ESI) m/z 346 (M+H)+.

1. customquenched with 0.5 N HCl (10 mL)
2. customThe organic layer was separated
3. washThe aqueous layer was washed with 10% MeOH/CH2Cl2 (50 mL×2)
4. washThe combined organic layers were washed with brine (25 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified on preparative HPLC (Phenomenex phenylhexyl reverse phase column
9. washeluted with gradient of solvent B=0.05% HOAc/CH3CN and solvent A=0.05% HOAc/H2O)