反应详情

2,6-Dichloroimidazo[1,2-b]pyridazine (10.0 g, 53.2 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride (0.43 g, 0.80 mmol) were added to tetrahydrofuran (80.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 31.9 ml, 63.8 mmol) was added dropwise thereto under ice-cooling over 60 minutes. The reaction mixture was stirred for 10 minutes under ice-cooling, warmed to room temperature, and stirred for 2 hours at room temperature. To the reaction mixture was added cold water (700 ml), and acidified with concentrated hydrochloric acid. Then the deposited solid was collected by filtration, and insoluble solid was washed with dilute hydrochloric acid, then with water. At the same time, the filtrate was extracted with ethyl acetate, the extracts were combined, and washed with dilute hydrochloric acid, saturated brine, saturated sodium hydrogen carbonate solution, and saturated brine, in that order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The concentrated residue and the solid collected by filtration were purified by silica gel column chromatography (ethyl acetate:hexane=3:7) to give the title compound as white crystals. The yield was 9.21 g (88.5%).

1. temperatureunder ice-cooling over 60 minutes
2. temperaturecooling
3. stirringstirred for 2 hours at room temperature
4. filtrationThen the deposited solid was collected by filtration, and insoluble solid
5. washwas washed with dilute hydrochloric acid
6. extractionAt the same time, the filtrate was extracted with ethyl acetate
7. washwashed with dilute hydrochloric acid, saturated brine, saturated sodium hydrogen carbonate solution, and saturated brine, in that order
8. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. filtrationThe concentrated residue and the solid collected by filtration
12. customwere purified by silica gel column chromatography (ethyl acetate:hexane=3:7)