反应详情

1.0 g of 4-(diphenylmethyl)-1-piperazinepropanol was dissolved in 10 ml of N,N-dimethylformamide; 142 mg of a 60% dispersion of sodium hydride in mineral oil was added, followed by stirring at room temperature under reduced pressure for 40 minutes. To the reaction mixture, 973 mg of ethyl 2-(3,6-dichloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate was added, followed by stirring at 0° C. for 2 hours. Ice water was added, followed by extraction with ethyl acetate; the extract was washed with saturated saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with hexane:ethyl acetate:triethylamine (50:50:1). The desired fraction was collected and concentrated under reduced pressure; the crystal precipitated was dissolved in 5 ml of ethyl acetate; 1.01 ml of a 4 N hydrogen chloride solution in ethyl acetate acid was added, followed by concentration again. The residue was recrystallized from methanol, collected by filtration, washed with ethyl acetate and dried to yield 424 mg of the title compound.

1. stirringby stirring at 0° C. for 2 hours
2. extractionfollowed by extraction with ethyl acetate
3. washthe extract was washed with saturated saline
4. dry with materialdried with magnesium sulfate
5. concentrationThe dry product was concentrated under reduced pressure
6. washeluted with hexane:ethyl acetate:triethylamine (50:50:1)
7. customThe desired fraction was collected
8. concentrationconcentrated under reduced pressure
9. customthe crystal precipitated
10. dissolutionwas dissolved in 5 ml of ethyl acetate
11. addition1.01 ml of a 4 N hydrogen chloride solution in ethyl acetate acid was added
12. concentrationfollowed by concentration again
13. customThe residue was recrystallized from methanol
14. filtrationcollected by filtration
15. washwashed with ethyl acetate
16. customdried