Potassium Carbonate → N-[6-[(5-Bromo-3-pyridinyl)oxy]imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1668144Notes

Reaction equation

HRID 1668144 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.[Br:17][C:18]1[CH:19]=[C:20]([OH:24])[CH:21]=[N:22][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[Br:17][C:18]1[CH:19]=[C:20]([O:24][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]=[N:22][CH:23]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 5995293-Bromo-5-hydroxypyridineHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505687N-[6-[(5-Bromo-3-pyridinyl)oxy]imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 85.5%

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 (1.7 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) were added 5-bromopyridine-3-ol (1.7 g, 10 mmol) and potassium carbonate (1.7 g, 13 mmol), and the mixture was stirred at 140° C. for 8 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 silica gel column chromatography (ethyl acetate/hexane=50/50→100/0), and precipitated from ethyl acetate/diisopropyl ether to give the title compound (1.6 g, 85%) as a 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 silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  8. customprecipitated from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-6760b451a69c4c4d9d98a55ead059e83
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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