反应详情

A solution of tert-butyl (3-oxopropyl)carbamate (4.2 g) and 4-benzylpiperazin-1-amine (4.6 g) in methanol (60 mL) was heated under reflux for 3 hours, and the solvent was distilled off under reduced pressure. After the residue was dissolved in methanol (60 mL), acetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added thereto, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, made alkaline with 1N sodium hydroxide and potassium carbonate, and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was dissolved in ethyl acetate (10 mL). and then a 4N hydrochloric acid-ethyl acetate solution (100 ml) was slowly added at 0° C., followed by stirring at room temperature for 5 hours. The precipitate was collected by filtration, dried, and then suspended in acetonitrile (200 mL). DBU (14.6 g) and CDI (7.8 g) were added thereto, and the mixture was heated under reflux for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with an aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate), and recrystallized from diethyl ether to obtain the title compound (3.1 g, 46%) as white crystals.

1. temperatureunder reflux for 3 hours
2. distillationthe solvent was distilled off under reduced pressure
3. dissolutionAfter the residue was dissolved in methanol (60 mL)
4. additionacetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. extractionextracted with dichloromethane
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customThe residue obtained
10. stirringby stirring at room temperature for 5 hours
11. filtrationThe precipitate was collected by filtration
12. customdried
13. additionDBU (14.6 g) and CDI (7.8 g) were added
14. temperaturethe mixture was heated
15. temperatureunder reflux for 15 hours
16. concentrationThe reaction mixture was concentrated under reduced pressure
17. additionthe residue was diluted with an aqueous sodium bicarbonate solution
18. extractionextracted with dichloromethane
19. dry with materialThe extract was dried over anhydrous sodium sulfate
20. distillationthe solvent was distilled off under reduced pressure
21. customThe residue was purified by basic silica gel column chromatography (ethyl acetate)
22. customrecrystallized from diethyl ether