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

HRID 2391470Notes

Reaction equation

HRID 2391470 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[C:19]([Cl:26])=[C:20]([OH:25])[C:21]([CH3:24])=[CH:22][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[NH2:17][C:18]1[C:19]([Cl:26])=[C:20]([C:21]([CH3:24])=[CH:22][CH:23]=1)[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

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1576415-Amino-6-Chloro-o-CresolHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505706N-[6-(3-amino-2-chloro-6-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 64.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (2.0 g, 6.1 mmol) in N,N-dimethylformamide (20 mL) were added 3-amino-2-chloro-6-methylphenol (1.9 g, 12 mmol) and potassium carbonate (2.1 g, 15 mmol), and the mixture was stirred at 140° C. for 12 hr. After cooling the mixture to room temperature, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=50/50→80/20) and precipitated from methanol/diisopropyl ether to give the title compound (1.4 g, 64%) as a pale-yellow powder.

Workup

  1. temperatureAfter cooling the mixture to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=50/50→80/20)
  8. customprecipitated from methanol/diisopropyl ether

Sources & evidence

ORD record
ord-006dad8c4bb149f5a71c02c6cde7c13e
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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