反应详情

温度

80 °C

686 mg of 4-(diphenylmethoxy)-1-piperidinepropanamine and 477 mg of ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylate were dissolved in 7 ml of N,N-dimethylformamide; 0.73 ml of N-ethyldiisopropylamine was added, followed by stirring in an oil bath (80° C.) for 18.5 hours. After cooling, ice water and sodium chloride were added, followed by extraction with ethyl acetate-tetrahydrofuran (1:1); the extract was washed with saturated saline, dried over magnesium sulfate and concentrated 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, dissolved in 5 ml of ethyl acetate; a solution of 95 mg of fumaric acid in 5 ml of ethanol was added, followed by concentration. Acetone-ethyl ether (1:2) was added to the residue to cause recrystallization; the crystal precipitate was collected by filtration and washed with ethyl ether to yield 211 mg of the title compound.

1. temperatureAfter cooling
2. extractionfollowed by extraction with ethyl acetate-tetrahydrofuran (1:1)
3. washthe extract was washed with saturated saline
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. washeluted with ethyl acetate:methanol:triethylamine (50:5:1)
7. customThe desired fraction was collected
8. dissolutiondissolved in 5 ml of ethyl acetate
9. additiona solution of 95 mg of fumaric acid in 5 ml of ethanol was added
10. concentrationfollowed by concentration
11. additionAcetone-ethyl ether (1:2) was added to the residue
12. customrecrystallization
13. filtrationthe crystal precipitate was collected by filtration
14. washwashed with ethyl ether