Tetrahydrofuran → 2-Chloro-6-propylimidazo[1,2-b]pyridazine

2,6-Dichloroimidazo[1,2-b]pyridazine (1.6 g, 8.5 mmol), [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (catalytic amount) and dehydrated tetrahydrofuran (20 ml) were introduced into a 100-ml three-necked flask under a nitrogen stream and stirred under ice-cooling, and a solution of propylmagnesium chloride in tetrahydrofuran (2 M, 6.4 ml, 12.8 mmol) was added dropwise thereto at 10° C. or less. After dropping, the mixture was stirred for 1 hour at the same temperature, for 1 hour at room temperature and for 2 hours at 50 to 60° C. After the reaction was completed, the reaction solution was left and cooled, and water (50 ml) was added thereto, and the mixture was stirred and extracted with ethyl acetate (20 ml×2). The organic layers were combined, washed with water, dried over magnesium sulfate and concentrated, and the residues were purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give the title compound as orange crystals (containing a small amount of impurities). The yield was 0.8 g (48.2%).

1. temperaturecooling
2. customat 10° C. or less
3. stirringthe mixture was stirred for 1 hour at the same temperature, for 1 hour at room temperature and for 2 hours at 50 to 60° C
4. waitthe reaction solution was left
5. temperaturecooled
6. stirringthe mixture was stirred
7. extractionextracted with ethyl acetate (20 ml×2)
8. washwashed with water
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customthe residues were purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

ORD record

ord-f9d1283fd1194fa4a09c933add71bce1

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816526B2