反应详情

温度

140 °C

To a solution of 2-amino-3-chloro-benzamide (0.85 g, 5.00 mmol) and 3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde (1.23 g, 5.00 mmol) in N,N-dimethylacetamide (20 mL) were added sodium hydrogen sulfite (58.5 wt %, 1.37 g, 7.50 mmol) and p-toluenesulfonic acid monohydrate (3.80 g, 20.0 mmol). The reaction mixture was stirred at 140° C. for 16 hours under nitrogen, then cooled to room temperature. Solvent was evaporated under reduced pressure. Water (100 mL) was added, and the mixture was neutralized, to pH approximately 8 with 2 N aqueous NaOH solution. The separated solid was filtered, washed with water (50 mL), and dried under vacuum. Crude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and then 5% 7.0 M ammonia in methanol and CH2Cl2 as eluent) to give the title compound as a brown solid. Yield: 0.49 g (25%). MP 216-217° C. 1H NMR (400 MHz, DMSO-d6): δ 8.07 (d, J=7.81 Hz, 1H), 8.01-7.87 (m, 3H), 7.43 (t, J=7.81 Hz, 1H), 3.89 (t, J=5.85 Hz, 2H), 2.81 (t, J=5.85 Hz, 2H), 2.53 (br s, 4H), 2.30 (s, 6H), 1.75-1.60 (m, 4H). MS (ES+) m/z 398.11 (100%), 400.13 (40%).

1. temperaturecooled to room temperature
2. customSolvent was evaporated under reduced pressure
3. additionWater (100 mL) was added
4. filtrationThe separated solid was filtered
5. washwashed with water (50 mL)
6. customdried under vacuum
7. customCrude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2