Potassium Carbonate → N-[6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]amino}-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1668069Notes

Reaction equation

HRID 1668069 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.[CH3:17][N:18]1[C:22]([CH2:23][NH:24][C:25]2[CH:26]=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=2[CH3:31])=[CH:21][C:20]([CH3:33])=[N:19]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:17][N:18]1[C:22]([CH2:23][NH:24][C:25]2[CH:26]=[C:27]([CH:28]=[CH:29][C:30]=2[CH3:31])[O:32][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]4[CH2:16][CH2:15]4)=[O:13])[N:10]=3)[N:7]=2)=[CH:21][C:20]([CH3:33])=[N:19]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamideHCID 575054353-{[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]amino}-4-methylphenol

Product 1

HCID 57505617N-[6-(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]amino}-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 72.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (210 mg, 0.64 mmol), 3-{[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]amino}-4-methylphenol (220 mg, 0.96 mmol), potassium carbonate (220 mg, 1.6 mmol) and N,N-dimethylformamide (1.5 mL) was stirred under microwave irradiation at 150° C. for 40 min. 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 (×4). 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 (methanol/ethyl acetate=0/100→5/95) to give the title compound (200 mg, 72%) as a brown solid.

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 with ethyl acetate/tetrahydrofuran (×4)
  4. washCombined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→5/95)

Sources & evidence

ORD record
ord-4daaa814400e4556a72915ff3ad338f1
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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