5-Amino-2-methylphenol → N-[6-(5-amino-2-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1667905Notes

Reaction equation

HRID 1667905 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH3:11])=[C:8]([OH:10])[CH:9]=1.I[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([NH:22][C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])[N:21]=2)[N:18]=1>CN(C)C=O>[NH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH3:11])=[C:8]([CH:9]=1)[O:10][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([NH:22][C:23]([CH:25]3[CH2:26][CH2:27]3)=[O:24])[N:21]=2)[N:18]=1

Participants

5

Reactant 3

HCID 178185-Amino-2-methylphenolHCID 24758Sodium hydrideHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Product 1

HCID 57505483N-[6-(5-amino-2-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 31.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (56 mg, 1.40 mmol) in N,N-dimethylformamide (2.0 mL) was added a solution of 5-amino-2-methylphenol (173 mg, 1.40 mmol) in N,N-dimethylformamide (1.0 mL), and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added a solution of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (306 mg, 0.933 mmol) in N,N-dimethylformamide (1.5 mL), and the mixture was stirred at 110° C. for 24 hr. The solvent was evaporated under reduced pressure, and ethyl acetate and water were added to the residue. The aqueous layer was extracted three times with ethyl acetate. 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→90/10) to give the title compound (94 mg, 31%) as a brown powder.

Workup

  1. stirringthe mixture was stirred at 110° C. for 24 hr
  2. customThe solvent was evaporated under reduced pressure, and ethyl acetate and water
  3. additionwere added to the residue
  4. extractionThe aqueous layer was extracted three times with ethyl acetate
  5. washCombined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=17/83→90/10)

Sources & evidence

ORD record
ord-40ccf7b0ece242b5a6d6cb76fbc5fe0c
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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