反应详情

To a solution of methyl 4-[(3,4-dimethylphenyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (2.03 g, 6.03 mmol) in DMF (40 mL) at 0° C. was added sodium hydride (0.362 g, 9.05 mmol) followed by methyl iodide (5.66 mL, 91 mmol). The mixture was stirred at room temperature for 18 hours. 1M HCl/water was added and the mixture was extracted with EtOAc. The organic phase was washed with brine, dried over sodium sulfate and evaporated in vacuo. The crude product was purified on silica using EtOAc/hexanes 30-50% to provide the title compound as an off-white solid (2 g, 95%): 1H NMR (400 MHz, CDCl3) δ ppm 8.56-8.37 (m, 1 H), 8.03 (s, 1 H), 7.62-7.47 (m, 2 H), 6.93 (d, J=8.4 Hz, 1 H), 6.48 (d, J=2.3 Hz, 1 H), 6.40 (dd, J=2.5, 8.2 Hz, 1 H), 3.77 (s, 3 H), 3.57 (s, 3 H), 3.24 (s, 3 H), 3.04-2.95 (m, 2 H), 2.89 (s, 2 H), 2.17 (d, J=8.8 Hz, 6 H);); ES-LCMS: 351.3 (M+1).

1. extractionthe mixture was extracted with EtOAc
2. washThe organic phase was washed with brine
3. dry with materialdried over sodium sulfate
4. customevaporated in vacuo
5. customThe crude product was purified on silica