Ethyl Salicylate → HCID 57505638, compound

HRID 2391397Notes

Reaction equation

HRID 2391397 reaction equation
[C:1]([O:10][CH2:11][CH3:12])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].CC(C)([O-])C.[K+].I[C:20]1[CH:21]=[CH:22][C:23]2[N:24]([CH:26]=[C:27]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:28]=2)[N:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:32]1([C:30]([NH:29][C:27]2[N:28]=[C:23]3[CH:22]=[CH:21][C:20]([O:4][C:3]4[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=4[C:1]([O:10][CH2:11][CH3:12])=[O:9])=[N:25][N:24]3[CH:26]=2)=[O:31])[CH2:33][CH2:34]1

Participants

6

Reactant 4

HCID 8365Ethyl SalicylateHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505638HCID 57505638, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl salicylate (1010 mg, 6.1 mmol) in N,N-dimethylformamide (8 mL) was added potassium tert-butoxide (840 mg, 6.4 mmol) at 0° C., and the mixture was stirred at 0° C. for 5 min and at room temperature for 25 min. To the reaction mixture were added N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (1.0 g, 3.1 mmol) and potassium carbonate (420 mg, 3.1 mmol), and the mixture was stirred at 100° C. for 24 hr. The solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and water were added to the residue. The aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→90/10) to give ethyl 2-({2[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)benzoate (200 mg, 18%) as a white solid.

Workup

  1. stirringthe mixture was stirred at 100° C. for 24 hr
  2. customThe solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and water
  3. additionwere added to the residue
  4. extractionThe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3)
  5. washCombined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→90/10)

Sources & evidence

ORD record
ord-53d79b56365e408fa8df88d6191d0cb7
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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