Pyridazine → ethyl 4-[6-chloro-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]-4H-pyridazine-1-carboxylate

HRID 515560Notes

Reaction equation

HRID 515560 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[Cl:7][C:8]1[C:9]([CH3:25])=[C:10]([CH3:24])[C:11]2[N:12]([CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[N:16]=2)[N:13]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1>ClCCl>[Cl:7][C:8]1[C:9]([CH3:25])=[C:10]([CH3:24])[C:11]2[N:12]([C:14]([CH:30]3[CH:29]=[CH:28][N:27]([C:2]([O:4][CH2:5][CH3:6])=[O:3])[N:26]=[CH:31]3)=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[N:16]=2)[N:13]=1

Participants

5

Reactant 3

HCID 9259PyridazineHCID 10928Ethyl chloroformateHCID 593677146-Chloro-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazine

Product 1

HCID 59367713ethyl 4-[6-chloro-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazin-3-yl]-4H-pyridazine-1-carboxylateYield 82.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

7.8 ml (82 mmol) of ethyl chloroformate are added, dropwise, to a suspension of 9.00 g (32.6 mmol) of 6-chloro-2-(4-fluorophenyl)-7,8-dimethylimidazo[1,2-b]pyridazine and 11.9 ml (163 mmol) of pyridazine in 160 ml of dichloromethane at 10° C. The medium is stirred at 10° C. for a further hour and then left to stir for 3 hours. It is then poured into ice-cold water and the product is extracted with ethyl acetate. After several washes with water, the organic phase is dried over sodium sulfate and the solvent is concentrated under reduced pressure. The black residue is then solubilized in dichloromethane and stirred in the presence of animal charcoal, to give a dark-brown solid after filtration through a Büchner funnel and evaporation of the solvent under reduced pressure. The product is chromatographed on a neutral alumina column, elution being carried out with a mixture of dichloromethane and petroleum ether (80/20), to give 11.5 g of a beige powder after crystallization from diethyl ether and drying.

Workup

  1. waitleft
  2. stirringto stir for 3 hours
  3. additionIt is then poured into ice-cold water
  4. extractionthe product is extracted with ethyl acetate
  5. dry with materialAfter several washes with water, the organic phase is dried over sodium sulfate
  6. concentrationthe solvent is concentrated under reduced pressure
  7. stirringstirred in the presence of animal charcoal
  8. customto give a dark-brown solid
  9. filtrationafter filtration
  10. customthrough a Büchner funnel and evaporation of the solvent under reduced pressure
  11. customThe product is chromatographed on a neutral alumina column, elution
  12. additionbeing carried out with a mixture of dichloromethane and petroleum ether (80/20)

Sources & evidence

ORD record
ord-29e3cac4a3354877adb724e8be22d47e
Source dataset
uspto-grants-2015_08
Patent number
US09108971B2

Reaction notes

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