Potassium Carbonate → N-[6-(3-amino-4-chlorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1667906Notes

Reaction equation

HRID 1667906 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.[NH2:17][C:18]1[CH:19]=[C:20]([OH:25])[CH:21]=[CH:22][C:23]=1[Cl:24].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:17][C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][C:23]=1[Cl:24])[O:25][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

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 50700783-Amino-4-chlorophenolHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505452N-[6-(3-amino-4-chlorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (800 mg, 2.44 mmol), 3-amino-4-chlorophenol (422 mg, 2.93 mmol), potassium carbonate (843 mg, 6.10 mmol) and N,N-dimethylformamide (6.0 mL) was stirred using a microwave synthesizer at 180° C. for 30 min. 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=17/83→75/25) to give the title compound (610 mg, 73%) as a brown powder.

Workup

  1. customat 180° C.
  2. customfor 30 min
  3. customThe solvent was evaporated under reduced pressure, ethyl acetate, tetrahydrofuran and water
  4. additionwere added to the residue
  5. extractionthe aqueous layer was extracted three times with ethyl acetate/tetrahydrofuran
  6. washCombined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltrated
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=17/83→75/25)

Sources & evidence

ORD record
ord-7b5d2857daa246bf8089e54f9e16e683
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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