反应详情

To tert-Butyl 3-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4-ylamino)-5-methyl-1H-pyrazole-1-carboxylate (100 mg, 0.20 mmol) was added 20% TFA/DCM, and the mixture was stirred at rt for 2.5 h. The mixture was concentrated and the residue was purified by preparative reverse-phase HPLC (TFA as a modifier). The fractions containing the desired product were neutralized with saturated aq NaHCO3 and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxy-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine as an off-white solid (33 mg, 41%). 1H NMR (250 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.54 (s, 1H), 8.67 (d, J=2.0 Hz, 1H), 8.59 (d, J=8.16 Hz, 1H), 7.97-8.06 (m, 2H), 7.22-7.28 (m, 2H), 5.97 (s, 1H), 3.93 (s, 3H), 2.17 (s, 3H). LCMS (ESI) m/z 401 (M+H)+.

1. concentrationThe mixture was concentrated
2. customthe residue was purified by preparative reverse-phase HPLC (TFA as a modifier)
3. additionThe fractions containing the desired product
4. extractionextracted with EtOAc (100 mL)
5. customThe organic layer was separated
6. washwashed with brine (2×10 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure