反应详情

To a solution of N-(tert-butoxycarbonyl)ethylenediamine (431 mg) and 4-(2-methyl-1H-imidazol-1-yl)benzaldehyde (500 mg) in dichloromethane (10 ml) was added acetic acid (323 mg), and the mixture was stirred at room temperature for 1 hour. To the mixture was added, under ice-cooling, sodium triacetoxyborohydride (855 mg), and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated, and the residue was dissolved in ethyl acetate. The solution was extracted with water, and the aqueous layer was made alkaline with sodium hydroxide solution. The mixture was extracted with dichloromethane and dried with sodium sulfate, and sodium sulfate was filtered off. To the filtrate was added triethylamine (543 mg) and then was added at 0° C. chloroacetyl chloride (455 mg), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was washed with sodium bicarbonate solution and brine, dried and concentrated, and the residue was dissolved in DMF (15 ml). To the solution was added sodium hydride in oil (129 mg), and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated, and the residue was dissolved in ethyl acetate. The solution was washed with water and brine, dried and concentrated, and the residue was purified with column chromatography (ethyl acetate) to give 4-(tert-butoxycarbonyl)-1-[4-(2-methyl-1H-imidazol-1-yl)benzyl]-2-piperazinone. To the obtained 4-(tert-butoxycarbonyl)-1-[4-(2-methyl-1H-imidazol-1-yl)benzyl]-2-piperazinone was added trifluoroacetic acid (8 ml), and the mixture was stirred at room temperature for 1 hour and concentrated. The residue was dissolved in dichloromethane (20 ml). To the solution was added triethylamine (1.58 g) and then was added 6-chloronaphthanlene-2-sulfonyl chloride (700 mg), and the mixture was stirred at room temperature for 1 hour. The reaction solution was separated, and the organic layer was washed with brine, dried and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate) to give colorless crystals of the title compound (70 mg).

1. additionTo the mixture was added, under ice-
2. temperaturecooling
3. concentrationThe reaction solution was concentrated
4. dissolutionthe residue was dissolved in ethyl acetate
5. extractionThe solution was extracted with water
6. extractionThe mixture was extracted with dichloromethane
7. dry with materialdried with sodium sulfate, and sodium sulfate
8. filtrationwas filtered off
9. additionTo the filtrate was added triethylamine (543 mg)
10. additionwas added at 0° C. chloroacetyl chloride (455 mg)
11. stirringthe mixture was stirred at room temperature for 30 minutes
12. washThe reaction solution was washed with sodium bicarbonate solution and brine
13. customdried
14. concentrationconcentrated
15. dissolutionthe residue was dissolved in DMF (15 ml)
16. additionTo the solution was added sodium hydride in oil (129 mg)
17. stirringthe mixture was stirred at room temperature for 3 hours
18. concentrationThe reaction solution was concentrated
19. dissolutionthe residue was dissolved in ethyl acetate
20. washThe solution was washed with water and brine
21. customdried
22. concentrationconcentrated
23. customthe residue was purified with column chromatography (ethyl acetate)