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

HRID 969726

Reaction equation

HRID 969726 reaction equation
[Br-].[CH2:2]([Zn+])[CH2:3][CH3:4].O1CCCC1.[Cl:11][C:12]1[N:13]=[C:14]2[CH:19]=[CH:18][C:17](Cl)=[N:16][N:15]2[CH:21]=1.Cl>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:11][C:12]1[N:13]=[C:14]2[CH:19]=[CH:18][C:17]([CH2:2][CH2:3][CH3:4])=[N:16][N:15]2[CH:21]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 144223582,6-Dichloroimidazo[1,2-b]pyridazineHCID 178455869HCID 178455869, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Under a nitrogen stream, a solution of n-propylzinc bromide in tetrahydrofuran (0.5 M, 7.98 ml, 3.99 mmol) was diluted with toluene (5.0 ml), and 2,6-dichloroimidazo[1,2-b]pyridazine (0.50 g, 2.66 mmol) and bis(triphenylphosphine)palladium(II) dichloride (0.19 g, 0.27 mmol) were added thereto, and the reaction mixture was stirred for 2 hours at 80° C. After cooling, to the reaction mixture was added cold water (50 ml), acidified with dilute hydrochloric acid, extracted with ethyl acetate, and the extracts were washed with dilute hydrochloric acid, a saturated saline, an aqueous saturated sodium bicarbonate solution and a saturated saline in this order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtrated and concentrated. The concentrated residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7) to give the title compound as white crystals. The yield was 0.31 g (59.6%).

Workup

  1. additionwere added
  2. temperatureAfter cooling, to the reaction mixture
  3. extractionextracted with ethyl acetate
  4. washthe extracts were washed with dilute hydrochloric acid
  5. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated
  8. customThe concentrated residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7)

Sources & evidence

ORD record
ord-f38b27477ba748549e40efb5c42ed7b5
Source dataset
uspto-grants-2007_12
Patent number
US07307165B2

Linked notes

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