反应详情

6-Chloro-2-methylimidazo[1,2-b]pyridazine (5.00 g, 29.8 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.08 g, 0.15 mmol) were suspended in dry ether (40 ml)-dry THF (20 ml) and then stirred under ice-cooling, during which a solution of ethylmagnesium bromide in ether (3 M, 15 ml, 45 mmol) was added dropwise thereto over 5 minutes (internal temperature 10° C. or less). The temperature of the reaction solution was increased to room temperature, and the mixture was stirred at the same temperature for 2 hours and under reflux with heating for 3 hours. The reaction solution, while being stirred, was left and cooled to room temperature, and water (30 ml) was added little by little. Further, the reaction mixture was stirred at room temperature and adjusted to about pH 5 to 6 with conc. hydrochloric acid. The organic layer and the aqueous layer were separated from each other, and the aqueous layer was extracted with ethyl acetate (70 ml×2). The organic layers were combined and washed with water (250 ml×3). The organic layer was dried over magnesium sulfate and concentrated, and the residues were purified by silica gel column chromatography (chloroform:ethyl acetate=2:1→1:1), and the resulting crude oil was further purified by silica gel column chromatography (ethyl acetate), and the title compound was obtained as pale red oil. The yield was 1.32 g (27.4%).

1. additionwas added dropwise
2. stirringthe mixture was stirred at the same temperature for 2 hours
3. temperatureunder reflux
4. temperaturewith heating for 3 hours
5. stirringThe reaction solution, while being stirred
6. waitwas left
7. temperaturecooled to room temperature
8. stirringFurther, the reaction mixture was stirred at room temperature
9. customThe organic layer and the aqueous layer were separated from each other, and the aqueous layer
10. extractionwas extracted with ethyl acetate (70 ml×2)
11. washwashed with water (250 ml×3)
12. dry with materialThe organic layer was dried over magnesium sulfate
13. concentrationconcentrated
14. customthe residues were purified by silica gel column chromatography (chloroform:ethyl acetate=2:1→1:1)
15. customthe resulting crude oil was further purified by silica gel column chromatography (ethyl acetate)