反应详情

1.04 g of 4-(diphenylmethoxy)-1-piperidinepropanol was dissolved in 14 ml of N,N-dimethylformamide; 141 mg of sodium hydride (60% in oil) was added, followed by stirring at room temperature under reduced pressure for 50 minutes. Under ice cooling, 1.00 g of N-(6-chloro[1,2,4]triazolo[4,3-b]pyridazine-3-carbonyl)-2,2-dimethylglycine ethyl ester was added, followed by stirring at ice temperature for 1 hour, then at room temperature for 2 hours. After saline was added, the reaction mixture was extracted with ethyl acetate-tetrahydrofuran (1:1) and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol-triethylamine (50:5:1). The desired fraction was collected and concentrated under reduced pressure; 1.62 g of the residue was dissolved in 2 ml of pyridine; 1 ml of acetic anhydride was added, followed by stirring at room temperature for 15 hours. After saline was added, the reaction mixture was extracted with ethyl acetate, washed with saturated saline, and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol-triethylamine (50:5:1). The desired fraction was collected and concentrated under reduced pressure; 1.32 g of the residue was dissolved in ethanol; a solution of 511 mg of fumaric acid in ethanol was added, followed by concentration under reduced pressure. The residue was powdered from diethyl ether and dried to yield 1.53 g of the title compound.

1. stirringby stirring at ice temperature for 1 hour
2. waitat room temperature for 2 hours
3. additionAfter saline was added
4. extractionthe reaction mixture was extracted with ethyl acetate-tetrahydrofuran (1:1)
5. dry with materialdried over magnesium sulfate
6. concentrationAfter concentration under reduced pressure
7. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
8. customThe desired fraction was collected
9. concentrationconcentrated under reduced pressure
10. dissolution1.62 g of the residue was dissolved in 2 ml of pyridine
11. addition1 ml of acetic anhydride was added
12. stirringby stirring at room temperature for 15 hours
13. additionAfter saline was added
14. extractionthe reaction mixture was extracted with ethyl acetate
15. washwashed with saturated saline
16. dry with materialdried over magnesium sulfate
17. concentrationAfter concentration under reduced pressure
18. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
19. customThe desired fraction was collected
20. concentrationconcentrated under reduced pressure
21. dissolution1.32 g of the residue was dissolved in ethanol
22. additiona solution of 511 mg of fumaric acid in ethanol was added
23. concentrationfollowed by concentration under reduced pressure
24. customdried