Potassium Carbonate → N-{6-[(2-methyl-1H-indol-6-yl)oxy]imidazo[1,2-b]pyridazin-2-yl}cyclopropanecarboxamide

HRID 1663883Notes

Reaction equation

HRID 1663883 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][C:18]1[NH:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[C:22]([OH:27])[CH:21]=2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:17][C:18]1[NH:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[C:22]([O:27][C:2]1[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]=1)[CH:21]=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 148785962-Methyl-1H-indol-6-olHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505618N-{6-[(2-methyl-1H-indol-6-yl)oxy]imidazo[1,2-b]pyridazin-2-yl}cyclopropanecarboxamideYield 36.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (360 mg, 1.1 mmol), 2-methyl-1H-indole-6-ol (320 mg, 2.2 mmol), potassium carbonate (450 mg, 3.3 mmol) and N,N-dimethylformamide (4 mL) was stirred at 120° C. for 24 hr. The solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and water were added to the residue, and 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 (ethyl acetate/hexane=20/80→90/10) to give the title compound (140 mg, 36%) 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 (ethyl acetate/hexane=20/80→90/10)

Sources & evidence

ORD record
ord-97569a7d582e4dc58ec4d120ec024fd5
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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