反应详情

A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (8.06 g, 0.025 mole), chloroacetaldehyde dimethyl acetal (6.23 g; 0.05 mole), potassium carbonate (6.91 g, 0.05 mole) and sodium bromide (2.57 g, 0.025-mole) in 100 ml of dry DMF was stirred at reflux for 8 hours. After four hours at reflux an additional amount of the alkylating agent (6.23 g, 0.05 mole) was added. The mixture was filtered and the DMF was removed under vacuum. The oily residue was redissolved in methylene chloride and washed sequentially with water, aqueous 1.0N NaOH, water and saturated NaCl solution. The solvent was evaporated and the product was further purified by chromatography using a gradient elution of methanol-methylene chloride containing 0.25% of ammonia. The appropriate fractions were combined and evaporated to give a yellow residue. Recrystallization from ethyl acetate-petroleum ether yielded the title compound as a white solid; wt. 5.5 g (59.8%), mp 64°-67°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.32 (s, 1H); 4.83 (t, 2H); 4.42 (bs, 2H); 4.08 (d, 2H); 3.55 (m, 2H); 3.50 (m, 2H); 2.41 (m, 6H); 1.1 (t, 6H).

1. temperatureat reflux for 8 hours
2. temperatureAfter four hours at reflux an additional amount of the alkylating agent (6.23 g, 0.05 mole)
3. additionwas added
4. filtrationThe mixture was filtered
5. customthe DMF was removed under vacuum
6. dissolutionThe oily residue was redissolved in methylene chloride
7. washwashed sequentially with water, aqueous 1.0N NaOH, water and saturated NaCl solution
8. customThe solvent was evaporated
9. customthe product was further purified by chromatography
10. washa gradient elution of methanol-methylene chloride containing 0.25% of ammonia
11. customevaporated
12. customto give a yellow residue
13. customRecrystallization from ethyl acetate-petroleum ether