Sodium Carbonate → N-(2-fluoro-5-{[2-(glycoloylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 2391333

Reaktionsgleichung

Reaktionsgleichung von HRID 2391333
[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]4[CH:17]=[CH:18][C:19]([F:32])=[C:20]([NH:22][C:23]([C:25]5[N:29]([CH3:30])[N:28]=[C:27]([CH3:31])[CH:26]=5)=[O:24])[CH:21]=4)=[N:11][N:10]3[CH:33]=2)=[O:5])CC1.CO.Cl.C(OCC(O)=O)(=[O:39])C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.C(=O)([O-])[O-].[Na+].[Na+]>O.CO.CN(C)C=O>[F:32][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:12]2[CH:13]=[CH:14][C:9]3[N:10]([CH:33]=[C:7]([NH:6][C:4](=[O:5])[CH2:1][OH:39])[N:8]=3)[N:11]=2)=[CH:21][C:20]=1[NH:22][C:23]([C:25]1[N:29]([CH3:30])[N:28]=[C:27]([CH3:31])[CH:26]=1)=[O:24]

Komponenten

11

Edukt 7

HCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 83766Acetoxyacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21893726Hydrochloride methanolHCID 24767979N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide

Produkt 1

HCID 57505573N-(2-fluoro-5-{[2-(glycoloylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamideAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (507 mg, 1.13 mmol) was added 10% hydrogen chloride methanol solution (30 mL), and the mixture was stirred at 50° C. for 23 hr. The solvent was evaporated under reduced pressure. To the residue were added acetoxyacetic acid (242 mg, 2.05 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (336 mg, 1.75 mmol), 1-hydroxybenzotriazole (167 mg, 1.24 mmol), N-ethyldiisopropylamine (0.60 mL, 3.51 mmol) and N,N-dimethylformamide (10 mL), and the mixture was stirred at room temperature for 62 hr. Methanol (10 mL), water (10 mL) and saturated aqueous sodium carbonate solution (2 mL) were added to the mixture, and the mixture was stirred at room temperature for 2 hr and concentrated under reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by NH silica gel column chromatography (ethyl acetate/hexane=0/100→100/0-methanol/ethyl acetate=2/98) and crystallized from ethanol to give the title compound (94 mg, 19%) as a white powder.

Aufarbeitung

  1. customThe solvent was evaporated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 62 hr
  3. stirringthe mixture was stirred at room temperature for 2 hr
  4. concentrationconcentrated under reduced pressure
  5. additionA saturated aqueous sodium hydrogencarbonate solution was added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was separated
  11. custompurified by NH silica gel column chromatography (ethyl acetate/hexane=0/100→100/0-methanol/ethyl acetate=2/98)
  12. customcrystallized from ethanol

Quellen und Nachweise

ORD-Eintrag
ord-6ffa53c65dd64f0fb6d3bc5183e75fd5
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08273741B2

Verknüpfte Notizen

Wird geladen…