反应详情

To 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (150 mg, 0.41 mmol) in DCM (5 mL) cooled to 0° C. was added 3-chloroperbenzoic acid (70%, 42 mg, 0.17 mmol) and the mixture stirred for 15 min. The mixture was diluted with DCM and then a sodium thiosulfate solution, followed by a saturated sodium bicarbonate solution was added. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. To the obtained residue was added THF (4 mL) and 5-methyl-1H-pyrazol-3-amine (185 mg, 1.9 mmol) and the mixture stirred at rt for 30 min. The crude mixture was concentrated under reduced pressure and then purified by preparative HPLC (Varian C-18 reverse phase column, eluted with gradient of solvent B=0.05% formic acid/ACN and solvent A=5% ACN/0.05% formic acid/H2O) to afford 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol (50 mg, 37%). LC-MS (ESI) m/z 332 (M+H)+.

1. additionwas added
2. dry with materialThe organic layer was dried over sodium sulfate
3. concentrationconcentrated under reduced pressure
4. stirringthe mixture stirred at rt for 30 min
5. concentrationThe crude mixture was concentrated under reduced pressure
6. custompurified by preparative HPLC (Varian C-18 reverse phase column
7. washeluted with gradient of solvent B=0.05% formic acid/ACN and solvent A=5% ACN/0.05% formic acid/H2O)