反应详情

温度

60 °C

6.55 g of 4-(diphenylmethoxy)-1-piperidinepropanol was dissolved in 100 ml of tetrahydrofuran; 2.12 g of sodium tert-butoxide was added, followed by stirring at an external temperature of 60° C. for 40 minutes. After cooling, 4.86 g of 2-[6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-2-methylpropionitrile was added, followed by refluxing under heating for 5 hours. After cooling, 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; in 7.90 g of the residue was dissolved in 5 ml of pyridine; 5 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 extracted with ethyl acetate-methanol-triethylamine (50:5:1). The desired fraction was collected and concentrated under reduced pressure; the residue (6.26 g) was dissolved in ethanol; 1.52 ml of a 4 N solution of hydrogen chloride in ethyl acetate was added, followed by concentration under reduced pressure. The residue was crystallized from methanol-ethanol (1:5), washed with ethanol-ethyl acetate (1:5), and dried, to yield 5.19 g of the title compound.

1. temperatureAfter cooling
2. temperatureby refluxing
3. temperatureunder heating for 5 hours
4. temperatureAfter cooling
5. additionsaline was added
6. extractionthe reaction mixture was extracted with ethyl acetate
7. washwashed with saturated saline
8. dry with materialdried over magnesium sulfate
9. concentrationAfter concentration under reduced pressure
10. washeluted with ethyl acetate-methanol-triethylamine (50:5:1)
11. customThe desired fraction was collected
12. concentrationconcentrated under reduced pressure
13. dissolutionin 7.90 g of the residue was dissolved in 5 ml of pyridine
14. addition5 ml of acetic anhydride was added
15. stirringby stirring at room temperature for 15 hours
16. additionAfter saline was added
17. extractionthe reaction mixture was extracted with ethyl acetate
18. washwashed with saturated saline
19. dry with materialdried over magnesium sulfate
20. concentrationAfter concentration under reduced pressure
21. extractionextracted with ethyl acetate-methanol-triethylamine (50:5:1)
22. customThe desired fraction was collected
23. concentrationconcentrated under reduced pressure
24. dissolutionthe residue (6.26 g) was dissolved in ethanol
25. addition1.52 ml of a 4 N solution of hydrogen chloride in ethyl acetate was added
26. concentrationfollowed by concentration under reduced pressure
27. customThe residue was crystallized from methanol-ethanol (1:5)
28. washwashed with ethanol-ethyl acetate (1:5)
29. customdried