反应详情

温度

0 °C

To a solution of 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methyl-4-(methylthio)quinazoline (152 mg, 0.454 mmol) in DCM (3 mL) at 0° C. was added 70% meta-chloroperoxybenzoic acid (168 mg, 0.681 mmol), and the mixture was stirred for 40 min at 0° C. DCM (15 mL) was added and the mixture was washed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL), dried over Na2SO4, and concentrated under reduced pressure. To the residue (154 mg) was added 5-methyl-1H-pyrazol-3-amine (132 mg, 1.36 mmol) in THF (4 mL), and the mixture was stirred at rt overnight and then concentrated under reduced pressure. The residue was purified by reverse phase HPLC (Varian Diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/5% ACN/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methyl-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (62.3 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ 12.08-12.20 (m, 1H), 10.53-10.66 (m, 1H), 8.66 (s, 1H), 8.57 (d, J=8.7 Hz, 1H), 7.93-8.03 (m, 2H), 7.66 (s, 1H), 7.48 (d, J=7.5 Hz, 1H), 5.99 (s, 1H), 2.51 (s, 4H), 2.18 (s, 3H). LCMS (ESI) m/z 386 (M+H)+.

1. washthe mixture was washed with saturated aq NaHCO3 (20 mL) and saturated aq sodium thiosulfate (20 mL)
2. dry with materialdried over Na2SO4
3. concentrationconcentrated under reduced pressure
4. stirringthe mixture was stirred at rt overnight
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by reverse phase HPLC (Varian Diphenyl reverse phase column
7. washeluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/5% ACN/H2O)