反应详情

温度

60 °C

Methyl 1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole-7-carboxylate (0.44 g) and tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (0.3 g) were dissolved in acetonitrile (5.0 ml) and water (5.0 ml), potassium carbonate (2.4 g) was added, and the mixture was stirred at 60° C. overnight. The reaction mixture was cooled to room temperature, and the mixture was extracted with ethyl acetate. The extract was washed successively with 10% aqueous citric acid solution, aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (0:10→10:0) was concentrated under reduced pressure, and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was dissolved in 4N hydrochloric acid-ethyl acetate solution, and the mixture was stirred for 30 min. The reaction mixture was concentrated, purified by HPLC, and the object fraction was concentrated, diluted with aqueous calcium carbonate solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and converted to hydrochloride with 4N hydrochloric acid-ethyl acetate solution to give the object product (9.3 mg).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionthe mixture was extracted with ethyl acetate
3. washThe extract was washed successively with 10% aqueous citric acid solution, aqueous sodium bicarbonate and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was evaporated under reduced pressure
6. washa fraction eluted with ethyl acetate-hexane (0:10→10:0)
7. concentrationwas concentrated under reduced pressure
8. washa fraction eluted with ethyl acetate
9. concentrationwas concentrated under reduced pressure
10. dissolutionThe residue was dissolved in 4N hydrochloric acid-ethyl acetate solution
11. stirringthe mixture was stirred for 30 min
12. concentrationThe reaction mixture was concentrated
13. custompurified by HPLC
14. concentrationthe object fraction was concentrated
15. additiondiluted with aqueous calcium carbonate solution
16. extractionthe mixture was extracted with ethyl acetate
17. washThe extract was washed with saturated brine
18. dry with materialdried over anhydrous magnesium sulfate
19. customThe solvent was evaporated under reduced pressure