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

Reaktionsgleichung

Reaktionsgleichung von HRID 2391361
[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]

Komponenten

8

Edukt 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

Produkt 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-carboxamideAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-49c8ac0a391b47a4b16a3e5da7cb7dcd
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08273741B2

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