Hydrochloric Acid → Ethyl 6-n-propylimidazo[1,2-b]pyridazin-2-ylcarboxylate

HRID 1160762Notes

Reaction equation

HRID 1160762 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[N:7]=1.O1C[CH2:19][CH2:18][CH2:17]1.[Br-].C([Zn+])CC.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.O>[CH2:17]([C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[N:7]=1)[CH2:18][CH3:19]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 2779714ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylateHCID 178455869HCID 178455869, compound

Product 1

HCID 23028126Ethyl 6-n-propylimidazo[1,2-b]pyridazin-2-ylcarboxylate

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 962WaterSolvent

Procedure

Ethyl 6-chloroimidazo[1,2-b]pyridazin-2-ylcarboxylate (1.00 g, 4.43 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.24 g, 0.44 mmol) were added to tetrahydrofuran (8.0 ml) under a nitrogen stream, and a solution of n-propylzinc bromide in tetrahydrofuran (0.5 M, 13.3 ml, 6.65 mmol) was added dropwise thereto with stirring under ice-cooling. The mixture was stirred for 20 minutes under ice-cooling and for 0.5 hour at room temperature, and cold water (50.0 ml) was added to the reaction mixture which was then acidified with dilute hydrochloric acid. The reaction solution was extracted with ethyl acetate, and the extracts were combined and washed with dilute hydrochloric acid and a saturated saline solution. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The concentrated residue was purified by silica gel column chromatography (acetone:hexane=1:3) to give the title compound as white crystals. The yield was 0.77 g (74.8%).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred for 20 minutes under ice-
  3. extractionThe reaction solution was extracted with ethyl acetate
  4. washwashed with dilute hydrochloric acid
  5. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrated residue was purified by silica gel column chromatography (acetone:hexane=1:3)

Sources & evidence

ORD record
ord-f9adea78aa284774b0818f5d8e5eab53
Source dataset
uspto-grants-2010_10
Patent number
US07816526B2

Reaction notes

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