反应详情

To N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)acetamide (90 mg, 0.24 mmol) in DCM (5 mL) at 0° C. was added 3-chloroperbenzoic acid (70%, 77 mg, 0.3 mmol) and the mixture stirred for 40 min. The mixture was diluted with DCM and then aq sodium thiosulfate and saturated aq sodium bicarbonate were added. 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 (107 mg, 1.1 mmol) and the mixture was stirred at rt for 1 h. The mixture was concentrated under reduced pressure and purified by preparative HPLC (Varian diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O) to afford N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-8-yl)acetamide (37 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.17 (s, 3H) 2.24 (s, 3H) 5.93 (s, 1H) 7.59 (t, J=8.10 Hz, 1H) 7.92-8.12 (m, 2H) 8.34 (d, J=8.29 Hz, 1H) 8.57-8.75 (m, 2H) 9.52 (s, 1H) 10.76 (br s, 1H) 12.20 (br s, 1H); LC-MS (ESI) m/z 428 (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 1 h
5. concentrationThe mixture was concentrated under reduced pressure
6. custompurified by preparative HPLC (Varian diphenyl reverse phase column
7. washeluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O)