反应详情

[step 1] 6-Methoxycarbonyl-4-methyl-2-propylbenzimidazole (EP502314; 500 mg, 2.29 mmol) was suspended in ethanol (15 mL), 4 mol/L aqueous sodium hydroxide solution (3.1 mL) was added, and the mixture was stirred under reflux for 7 hr. The mixture was concentrated under reduced pressure, and water (20 mL) was added. Under ice-cooling, the mixture was adjusted to pH 1 with 2 mol/L hydrochloric acid, and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in dichloromethane, aminoacetaldehyde dimethylacetal (0.50 mL, 4.58 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (527 mg, 2.75 mmol) and 1-hydroxybenzotriazole (421 mg, 2.75 mmol) were added, and the mixture was stirred at room temperature for 6 hr. To the mixture were added saturated aqueous sodium hydrogen carbonate solution (100 mL) and chloroform (100 mL), and the organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 6-(2,2-dimethoxyethylcarbamoyl)-4-methyl-2-propylbenzimidazole.

1. temperatureunder reflux for 7 hr
2. concentrationThe mixture was concentrated under reduced pressure, and water (20 mL)
3. additionwas added
4. temperatureUnder ice-cooling
5. extractionextracted with chloroform
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in dichloromethane
10. stirringthe mixture was stirred at room temperature for 6 hr
11. washthe organic layer was washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure