4-Aminophenol → N-[6-(4-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1667937Notes

Reaction equation

HRID 1667937 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]([CH3:13])([O-])C.[K+].I[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([CH:22]=[C:23](C3(C(N)=O)CC3)[N:24]=2)[N:21]=1.C(=O)([O-])[O-].[K+].[K+].C[N:38](C)[CH:39]=[O:40]>[Cl-].[Na+].O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:16]2[CH:17]=[CH:18][C:19]3[N:20]([CH:22]=[C:23]([NH:38][C:39]([CH:13]4[CH2:10][CH2:9]4)=[O:40])[N:24]=3)[N:21]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 4034-AminophenolHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 86630641HCID 86630641, compound

Product 1

HCID 57505463N-[6-(4-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 4-aminophenol (0.33 g, 3.05 mmol) in N,N-dimethylformamide (10 mL) was added potassium tert-butoxide (0.36 g, 3.17 mmol), and the mixture was stirred at room temperature for 2 hr. N (6-Iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (0.80 g, 2.44 mmol) and potassium carbonate (0.17 g, 1.22 mmol) were added to the reaction mixture, and the mixture was stirred using a microwave synthesizer with heating at 150° C. for 30 min. After cooling the reaction mixture, saturated brine was added to the mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2→ethyl acetate) to give the title compound (376 mg, 50%) as a dark brown powder.

Workup

  1. stirringthe mixture was stirred
  2. temperaturewith heating at 150° C. for 30 min
  3. additionwas added to the mixture
  4. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  5. washwashed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2→ethyl acetate)

Sources & evidence

ORD record
ord-8fc67d3b491c4e82ac70ba7801d2bcc9
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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