反应详情

Acetic anhydride (66 μl, 0.70 mmol) was added drop wise to a solution of 5-{[(2R)-2-(methylamino)propyl]oxy}-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (250 mg, 0.58 mmol, obtained as described in Example 115, preparation of starting materials) and potassium carbonate (161 mg, 1.16 mmol) in acetone (10 ml). The mixture was stirred at room temperature for 2 hours. After evaporation of the solvents, the residue was diluted in DCM. The solution washed with aqueous sodium bicarbonate and dried over magnesium sulfate. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 2 to 5% 7N ammonia-methanol in DCM) to give the title compound (230 mg, 84%); NMR Spectrum: (CDCl3) 1.28 (d, 3H), 1.94 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.90 (s, 3H), 4.30-4.10 (m, 2H), 5.38 (m, 1H), 6.92 (m, 2H), 7.08 (d, 1H), 7.14 (dd, 1H), 7.48 (d, 2H), 7.53 (s, 1H), 7.64 (t, 1H), 8.27 (d, 1H), 8.60 (s, 1H), 9.51 (s, 1H); Mass spectrum: MH+ 472.

1. customAfter evaporation of the solvents
2. additionthe residue was diluted in DCM
3. washThe solution washed with aqueous sodium bicarbonate
4. dry with materialdried over magnesium sulfate
5. customAfter evaporation of the solvents
6. customthe residue was purified by chromatography on silica gel (eluant: 2 to 5% 7N ammonia-methanol in DCM)