Ethyl 2-chloroacetoacetate → Ethyl 6-chloro-2-methylimidazo[1,2-b]pyridazine-3-carboxylate

HRID 2282210Notes

Reaction equation

HRID 2282210 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.Cl[CH:10]([C:16](=O)[CH3:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:16]([CH3:17])[N:8]=2)[N:7]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 216436-Amino-3-chloropyridazine

Product 1

HCID 14091884Ethyl 6-chloro-2-methylimidazo[1,2-b]pyridazine-3-carboxylateYield 32.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 6-chloropyridazin-3-amine (5.3 g, 41 mmol), ethyl 2-chloro-3-oxobutanoate (6.7 g, 41 mmol) and ethanol (50 mL) was heated under reflux for 2 days. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate solution and ethyl acetate were added to the obtained residue, and the insoluble material was filtered off. The filtrate was extracted with ethyl acetate, and the collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added to the obtained residue, and the insoluble material was filtered off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) and washed with ethyl acetate/diisopropyl ether to give the title compound (3.2 g, 32%) as a colorless solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 days
  3. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium bicarbonate solution and ethyl acetate
  4. additionwere added to the obtained residue
  5. filtrationthe insoluble material was filtered off
  6. extractionThe filtrate was extracted with ethyl acetate
  7. washthe collected organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. additionEthyl acetate and diisopropyl ether were added to the obtained residue
  12. filtrationthe insoluble material was filtered off
  13. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  14. washwashed with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-5631d7238b14423890bb45fc0873a081
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

Loading…