反应详情

To a solution of 1.38 g of 3-(N,N-dimethylaminomethyl-ene)aminosulfonyl -2,2-diethyl-1-propanol in 30 ml of tetrahydrofuran, 0.23 g of 60% oily sodium hydride was added, followed by stirring at room temperature for 1 hour. To the reaction mixture, 0.74 g of 6-chloro-7-methylimidazo [1,2-b]pyridazine was added, followed by refluxing under heating conditions for 1 hour. After cooling, the reaction mixture was neutralizedwith 1 N hydrochloric acid and extracted with ethyl acetate-tetrahydrofuran(1:1). After the extract was washed with water and dried over MgSO4, the solvent was distilled off under reduced pressure. To the residue was added 14 ml of 6 N hydrochloric acid, followed by stirring at 110° C. for 30 minutes. After cooling, the mixture was concentrated under reduced pressure, and the residue adjusted to a pH of 7 by addition of aqueous solution of sodium hydrogen carbonate and then extracted with ethyl acetate. After saline washing, the extract was dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue subjected to column chromatography using 100 g of silica gel, eluted with chloroform-methanol (5:1), and crystallized from a mixed solvent of methanol and ethyl acetate, to yield 1.19 g of the title compound.

1. temperatureby refluxing under heating conditions for 1 hour
2. temperatureAfter cooling
3. extractionextracted with ethyl acetate-tetrahydrofuran(1:1)
4. washAfter the extract was washed with water
5. dry with materialdried over MgSO4
6. distillationthe solvent was distilled off under reduced pressure
7. additionTo the residue was added 14 ml of 6 N hydrochloric acid
8. stirringby stirring at 110° C. for 30 minutes
9. temperatureAfter cooling
10. concentrationthe mixture was concentrated under reduced pressure
11. additionthe residue adjusted to a pH of 7 by addition of aqueous solution of sodium hydrogen carbonate
12. extractionextracted with ethyl acetate
13. washAfter saline washing
14. dry with materialthe extract was dried over magnesium sulfate
15. distillationThe solvent was distilled off under reduced pressure
16. washeluted with chloroform-methanol (5:1)
17. customcrystallized from a mixed solvent of methanol and ethyl acetate