反应详情

Chloroacetyl chloride (33 μl, 0.42 mmol) was added drop wise to a solution of 5-[(1R)-1-methyl-2-(methylamino)ethoxy]-N-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}quinazolin-4-amine (172 mg, 0.40 mmol, obtained as described in Example 103, preparation of starting materials)) and DIPEA (139 μl, 0.8 mmol) in DCM (2 ml). The mixture was stirred at room temperature for 1 hour. THF (5 ml) was added to the solution and dimethylamine was bubbled in the reaction mixture. After 30 minutes, the solvents were evaporated under vacuum. The mixture was diluted with DCM, washed with water and brine, and dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 2 to 4% 7N ammonia-methanol in DCM) to give the title compound (85 mg, 41%) as a pale solid; NMR spectrum (CDCl3) 1.53 (d, 3H), 2.28 (s, 6H), 2.30 (s, 3H), 2.53 (s, 3H), 3.15-3.05 (m, 5H), 3.54 (dd, 1H), 3.95 (dd, 1H), 5.10 (m, 1H), 6.91 (d, 1H), 7.12 (m, 3H), 7.46 (d, 1H), 7.55 (d, 1H), 7.64 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass spectrum: MH+ 515.

1. customwas bubbled in the reaction mixture
2. waitAfter 30 minutes
3. customthe solvents were evaporated under vacuum
4. additionThe mixture was diluted with DCM
5. washwashed with water and brine
6. dry with materialdried over MgSO4
7. customAfter evaporation of the solvents
8. customthe residue was purified by chromatography on silica gel (eluant: 2 to 4% 7N ammonia-methanol in DCM)