反应详情

温度

50 °C

1-(2-Chlorobenzyl)-2-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzimidazole-5-carbonitrile (280.6 mg) was dissolved in N,N-dimethylformamide (50 ml), and to the solution was added sodium hydride (41.5 mg). The reaction mixture was stirred under ice-cooling for 10 minutes. 2-Chlorotriethylamine hydrochloride (178.5 mg) and triethylamine (0.167 ml) were added, and the mixture was stirred at 70° C. for 18 hours. After allowing to cool, to the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was dissolved in 2-methyl-2-propanol (30 ml) and heated at 50° C. To the solution was added powdered potassium hydroxide (1.119 g), and the mixture was stirred for 1 hour. After allowing to cool, to the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was purified by HPLC using condition 1 to give the title compound (280.9 mg, 60%).

1. temperaturecooling for 10 minutes
2. stirringthe mixture was stirred at 70° C. for 18 hours
3. temperatureto cool, to the reaction mixture
4. extractionthe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. dissolutionThe resultant residue was dissolved in 2-methyl-2-propanol (30 ml)
9. additionTo the solution was added powdered potassium hydroxide (1.119 g)
10. stirringthe mixture was stirred for 1 hour
11. temperatureto cool, to the reaction mixture
12. additionwas added saturated aqueous sodium bicarbonate solution
13. extractionthe mixture was extracted with ethyl acetate
14. washThe organic layer was washed with saturated brine
15. dry with materialdried over anhydrous sodium sulfate
16. concentrationconcentrated in vacuo
17. customThe resultant residue was purified by HPLC