Potassium Carbonate → Methyl 3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)benzoate

HRID 1663717Notes

Reaction equation

HRID 1663717 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[OH:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=1)[C:21]([O:23][CH3:24])=[O:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:14]1([C:12]([NH:11][C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([O:17][C:18]4[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=4)[C:21]([O:23][CH3:24])=[O:22])=[N:7][N:6]3[CH:8]=2)=[O:13])[CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 88068Methyl 3-HydroxybenzoateHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505482Methyl 3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)benzoateYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (518 mg, 1.58 mmol), methyl 3-hydroxybenzoate (360 mg, 2.37 mmol), potassium carbonate (654 mg, 4.73 mmol) and N,N-dimethylformamide (4.0 mL) was stirred at 110° C. for 2 days. The solvent was evaporated under reduced pressure, ethyl acetate, tetrahydrofuran and water were added to the residue, and the aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran. Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→85/15) to give methyl 3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)benzoate (225 mg, 41%) as a white powder.

Workup

  1. customThe solvent was evaporated under reduced pressure, ethyl acetate, tetrahydrofuran and water
  2. additionwere added to the residue
  3. extractionthe aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran
  4. washCombined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→85/15)

Sources & evidence

ORD record
ord-ca8e2cead7484d2881f7e1ec57d0168a
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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