Triethylamine → N-[6-(4-fluoro-3-{[(methoxyamino)carbonyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1668012Notes

Reaction equation

HRID 1668012 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[Cl-].[CH3:14][O:15][NH3+:16].C(N(CC)CC)C.[NH2:24][C:25]1[CH:26]=[C:27]([CH:44]=[CH:45][C:46]=1[F:47])[O:28][C:29]1[CH:30]=[CH:31][C:32]2[N:33]([CH:35]=[C:36]([NH:38][C:39]([CH:41]3[CH2:43][CH2:42]3)=[O:40])[N:37]=2)[N:34]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[F:47][C:46]1[CH:45]=[CH:44][C:27]([O:28][C:29]2[CH:30]=[CH:31][C:32]3[N:33]([CH:35]=[C:36]([NH:38][C:39]([CH:41]4[CH2:43][CH2:42]4)=[O:40])[N:37]=3)[N:34]=2)=[CH:26][C:25]=1[NH:24][C:1]([NH:16][O:15][CH3:14])=[O:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11639O-methylhydroxylammonium chlorideHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 57505446N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505561N-[6-(4-fluoro-3-{[(methoxyamino)carbonyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideYield 27.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1,1′-carbonyldiimidazole (297 mg, 1.833 mmol), O-methylhydroxyammonium chloride (153 mg, 1.833 mmol) and triethylamine (0.25 mL, 1.833 mmol) in N,N-dimethylformamide (4.0 mL) was stirred at room temperature for 30 min. A solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.611 mmol) in N,N-dimethylformamide (2.0 mL) was further added to the mixture, and the mixture was stirred at room temperature for 2 days. Under ice-cooling, aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was recrystallized from tetrahydrofuran/ethanol to give the title compound (67 mg, 27%) as colorless crystals.

Workup

  1. temperatureUnder ice-cooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was recrystallized from tetrahydrofuran/ethanol

Sources & evidence

ORD record
ord-62ed0c72d5a547ac9deeb980d1ef48ef
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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