Hydrochloric Acid → 6-Ethyl-2-methylimidazo[1,2-b]pyridazine

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 a solution of ethylmagnesium bromide in ether (3 M, 15 ml, 45 mmol) was added dropwise thereto with stirring under ice-cooling 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 was left to cool to room temperature under stirring, and water (30 ml) was added little by little. Further, the pH of reaction mixture was adjusted to about 5 to 6 with concentrated hydrochloric acid under stirring at room temperature. 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. temperaturecooling over 5 minutes (internal temperature 10° C. or less)
2. stirringthe mixture was stirred at the same temperature for 2 hours
3. temperatureunder reflux
4. temperaturewith heating for 3 hours
5. waitThe reaction solution was left
6. temperatureto cool to room temperature
7. stirringunder stirring
8. customFurther, the pH of reaction mixture
9. stirringunder stirring at room temperature
10. customThe organic layer and the aqueous layer were separated from each other, and the aqueous layer
11. extractionwas extracted with ethyl acetate (70 ml×2)
12. washwashed with water (250 ml×3)
13. dry with materialThe organic layer was dried over magnesium sulfate
14. concentrationconcentrated
15. customthe residues were purified by silica gel column chromatography (chloroform:ethyl acetate=2:1→1:1)
16. customthe resulting crude oil was further purified by silica gel column chromatography (ethyl acetate)

ORD record

ord-9efc729ee1a84731ae7fb1ee203212ae

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07307165B2