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

HRID 1160758Notes

Reaction equation

HRID 1160758 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7](Cl)=[N:6][N:5]2[CH:11]=1.O1C[CH2:15][CH2:14][CH2:13]1.C([Mg]Br)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>[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH2:13][CH2:14][CH3:15])=[N:6][N:5]2[CH:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 144223582,6-Dichloroimidazo[1,2-b]pyridazineHCID 178455851HCID 178455851, compound

Product 1

HCID 230280952-Chloro-6-propylimidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 962WaterSolvent

Procedure

2,6-Dichloroimidazo[1,2-b]pyridazine (10.0 g, 53.2 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.43 g, 0.80 mmol) were added to tetrahydrofuran (80.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 31.9 ml, 63.8 mmol) was added dropwise over 60 minutes to the mixture under ice-cooling. The mixture was stirred for 10 minutes under ice-cooling, and the reaction mixture was warmed to room temperature and stirred for 2 hours at room temperature. Cold water (700 ml) was added to the reaction mixture which was then acidified with conc. hydrochloric acid, and the precipitated solids were collected by filtration, and the insoluble solids were washed with dilute hydrochloric acid and then with water. On one hand, the filtrate was extracted with ethyl acetate, and the extracts were combined and washed with dilute hydrochloric acid, a saturated saline solution, an aqueous saturated sodium bicarbonate solution and a saturated saline solution in this order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtrated and concentrated. The concentrated residues and the solids collected by filtration were purified by silica gel column chromatography (ethyl acetate:hexane=3:7), to give the title compound as white crystals. The yield was 9.21 g (88.5%).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred for 2 hours at room temperature
  4. filtrationthe precipitated solids were collected by filtration
  5. washthe insoluble solids were washed with dilute hydrochloric acid
  6. extractionOn one hand, the filtrate was extracted with ethyl acetate
  7. washwashed with dilute hydrochloric acid
  8. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltrated
  10. concentrationconcentrated
  11. filtrationThe concentrated residues and the solids collected by filtration
  12. customwere purified by silica gel column chromatography (ethyl acetate:hexane=3:7)

Sources & evidence

ORD record
ord-b9665b757f9e4b43838a4ddcd351c348
Source dataset
uspto-grants-2010_10
Patent number
US07816526B2

Reaction notes

Loading…