反应详情

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline (193 mg, 0.55 mmol) in DCM (5 mL) at 0° C. was added 3-chloroperbenzoic acid (70%, 218 mg, 0.89 mmol) and the mixture stirred for 40 min. The mixture was diluted with DCM and then aq sodium thiosulfate was added, followed by addition of saturated aq sodium bicarbonate solution. The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure. To the residue were added THF (3 mL) and 5-methyl-1H-pyrazol-3-amine (163 mg, 1.67 mmol) and the mixture was stirred at rt for 4 days. The mixture was concentrated under reduced pressure and purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (79 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.44 Hz, 3H) 2.19 (s, 3H) 3.05 (q, J=7.35 Hz, 2H) 6.03 (s, 1H) 7.55 (t, J=7.82 Hz, 1H) 7.74 (d, J=6.97 Hz, 1H) 7.95-8.06 (m, 2H) 8.51 (d, J=8.10 Hz, 1H) 8.67 (s, 1H) 10.58 (br s, 1H) 12.16 (br s, 1H); LC-MS (ESI) m/z 399 (M+H)+.

1. customThe organic layer was separated
2. dry with materialdried over sodium sulfate
3. concentrationconcentrated under reduced pressure
4. stirringthe mixture was stirred at rt for 4 days
5. concentrationThe mixture was concentrated under reduced pressure
6. custompurified by preparative HPLC (Varian diphenyl reverse phase column
7. washeluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O)