Hydrochloric Acid → 6-Butyl-2-chloroimidazo[1,2-b]pyridazine

HRID 1160751Notes

Reaction equation

HRID 1160751 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[Cl-].C([Zn+])CCC.[Cl:12][C:13]1[N:14]=[C:15]2[CH:20]=[CH:19][C:18](Cl)=[N:17][N:16]2[CH:22]=1.Cl>O1CCCC1.[Cl-].[Zn+2].[Cl-].Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([C:18]1[CH:19]=[CH:20][C:15]2[N:16]([CH:22]=[C:13]([Cl:12])[N:14]=2)[N:17]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 144223582,6-Dichloroimidazo[1,2-b]pyridazineHCID 178418339ButyllithiumHCID 178448261HCID 178448261, compound2×

Product 1

HCID 230280946-Butyl-2-chloroimidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418745HCID 178418745, compoundCatalystHCID 8028TetrahydrofuranSolvent4×

Procedure

Zinc chloride (2.04 g, 15.0 mmol) was dried at 180° C. for 2 hours under vacuum and then cooled to room temperature, and anhydrous tetrahydrofuran (20.0 mL) was added thereto. n-Butyl lithium (1.6 M, 9.0 mL, 14.4 mmol) was added dropwise thereto over about 30 minutes under ice-cooling and stirred for 30 minutes under ice-cooling, to prepare a solution of n-butylzinc chloride in tetrahydrofuran. Separately, a suspension of 2,6-dichloroimidazo[1,2-b]pyridazine (1.88 g, 10.0 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.16 g, 0.30 mmol) in anhydrous tetrahydrofuran (20.0 mL) was prepared under a nitrogen atmosphere, and the previously prepared solution of n-butylzinc chloride in tetrahydrofuran while being maintained at 3 to 6° C. was added dropwise thereto over 30 minutes. The mixture was stirred for 15 minutes under ice-cooling and for 3 hours at room temperature, then poured into a saturated saline solution and adjusted to pH 2 with dilute hydrochloric acid. The reaction solution was extracted twice with ethyl acetate, and the extracts were combined, dehydrated over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4), to give the title compound as pale yellow crystals. The yield was 2.03 g (96.8%).

Workup

  1. temperatureover about 30 minutes under ice-cooling
  2. temperaturecooling
  3. customwas prepared under a nitrogen atmosphere
  4. additionwas added dropwise
  5. waitover 30 minutes
  6. stirringThe mixture was stirred for 15 minutes under ice-
  7. temperaturecooling and for 3 hours at room temperature
  8. additionpoured into a saturated saline solution
  9. extractionThe reaction solution was extracted twice with ethyl acetate
  10. concentrationconcentrated under reduced pressure
  11. customThe residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-1bc8330e9c73414283e1d2852b78f0ac
Source dataset
uspto-grants-2010_10
Patent number
US07816526B2

Reaction notes

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