Dimethylformamide → 3-ethyl-N-{2-fluoro-5-[(2-{[(2-methylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1-methyl-1H-pyrazole-5-carboxamide

HRID 2391371Notes

Reaction equation

HRID 2391371 reaction equation
[CH2:1]([C:3]1[CH:7]=[C:6]([C:8]([OH:10])=O)[N:5]([CH3:11])[N:4]=1)[CH3:2].CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[CH:25]=[C:26]([CH:44]=[CH:45][C:46]=1[F:47])[O:27][C:28]1[CH:29]=[CH:30][C:31]2[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]3[CH2:42][CH:41]3[CH3:43])=[O:39])[N:36]=2)[N:33]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C(=O)C>[CH2:1]([C:3]1[CH:7]=[C:6]([C:8]([NH:23][C:24]2[CH:25]=[C:26]([O:27][C:28]3[CH:29]=[CH:30][C:31]4[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]5[CH2:42][CH:41]5[CH3:43])=[O:39])[N:36]=4)[N:33]=3)[CH:44]=[CH:45][C:46]=2[F:47])=[O:10])[N:5]([CH3:11])[N:4]=1)[CH3:2]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 8205653-ethyl-1-methyl-1H-pyrazole-5-carboxylic acidHCID 57505466N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]-2-methylcyclopropanecarboxamide

Product 1

HCID 575056103-ethyl-N-{2-fluoro-5-[(2-{[(2-methylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1-methyl-1H-pyrazole-5-carboxamideYield 57.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid (158 mg, 1.03 mmol) in tetrahydrofuran (3.8 mL) were added N,N-dimethylformamide (20 μL, 0.26 mmol) and oxalyl chloride (90 μL, 1.03 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]-2-methylcyclopropanecarboxamide (250 mg, 0.73 mmol) in N,N-dimethylacetamide (5.0 mL), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate alone) and recrystallized from hexane/ethyl acetate to give the title compound (201 mg, 57%) as a white powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  3. washwashed with 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 alone) and
  8. customrecrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-387a9e8c755d4011a16a224791e8755e
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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