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

HRID 1663719

Reaction equation

HRID 1663719 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-30c0b424956d40fca0135b0618641151
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Linked notes

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