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

HRID 2391361

Reaction equation

HRID 2391361 reaction equation
[CH3:1][C:2]1([CH3:10])[C:4]([CH3:6])([CH3:5])[CH:3]1[C:7]([OH:9])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[NH2:23][C:24]1[N:25]=[C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:34]=[CH:35][C:36]([F:49])=[C:37]([NH:39][C:40]([C:42]4[N:46]([CH3:47])[N:45]=[C:44]([CH3:48])[CH:43]=4)=[O:41])[CH:38]=3)=[N:28][N:27]2[CH:50]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C(=O)C>[F:49][C:36]1[CH:35]=[CH:34][C:33]([O:32][C:29]2[CH:30]=[CH:31][C:26]3[N:27]([CH:50]=[C:24]([NH:23][C:7]([CH:3]4[C:4]([CH3:5])([CH3:6])[C:2]4([CH3:1])[CH3:10])=[O:9])[N:25]=3)[N:28]=2)=[CH:38][C:37]=1[NH:39][C:40]([C:42]1[N:46]([CH3:47])[N:45]=[C:44]([CH3:48])[CH:43]=1)=[O:41]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 1521152,2,3,3-Tetramethylcyclopropanecarboxylic acidHCID 516892Sodium BicarbonateHCID 57505567N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride

Product 1

HCID 57505600N-{2-fluoro-5-[(2-{[(2,2,3,3-tetramethylcyclopropyl)carbonyl]amino}imidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 19%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2,2,3,3-tetramethylcyclopropanecarboxylic acid (102 mg, 0.72 mmol) in tetrahydrofuran (4.0 mL) were added N,N-dimethylformamide (20 μL, 0.26 mmol) and oxalyl chloride (63 mL, 0.72 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a solution of N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide.hydrochloride (200 mg, 0.48 mmol) in N,N-dimethylacetamide (4.0 mL), and the mixture was stirred at room temperature for 3 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, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1) and precipitated from hexane/ethyl acetate to give the title compound (46 mg, 19%) as a white powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 3 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/hexane=3/1)
  8. customprecipitated from hexane/ethyl acetate

Sources & evidence

ORD record
ord-49c8ac0a391b47a4b16a3e5da7cb7dcd
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Linked notes

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