Water → 6-(2-methoxy-ethoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide

HRID 2098233Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2098233
[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[F:8][C:9]([F:39])([F:38])[C:10]1[CH:11]=[C:12]([C:16]2[CH:37]=[CH:36][C:19]3[NH:20][C:21]([NH:23][C:24]([C:26]4[N:27]=[C:28]5[CH:33]=[CH:32][C:31](Cl)=[N:30][N:29]5[CH:35]=4)=[O:25])=[N:22][C:18]=3[CH:17]=2)[CH:13]=[CH:14][CH:15]=1.O>CN(C=O)C>[F:8][C:9]([F:39])([F:38])[C:10]1[CH:11]=[C:12]([C:16]2[CH:37]=[CH:36][C:19]3[NH:20][C:21]([NH:23][C:24]([C:26]4[N:27]=[C:28]5[CH:33]=[CH:32][C:31]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[N:30][N:29]5[CH:35]=4)=[O:25])=[N:22][C:18]=3[CH:17]=2)[CH:13]=[CH:14][CH:15]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 178522475HCID 178522475, Verbindung

Produkt 1

HCID 1784961026-(2-methoxy-ethoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-methoxy-ethanol (0.013 mL) in dry DMF (0.25 mL), sodium hydride (8 mg, 60% dispersion in mineral oil) was added, and the mixture was stirred at room temperature for 20 minutes under nitrogen. 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide (30 mg) was added to the reaction mixture, and the mixture was warmed to 70° C. The reaction was monitored by LCMS for 1 hour until substantially complete. After cooling the reaction mixture, 10 mL of water was added and the reaction mixture was stirred for 10 minutes. The reaction was then filtered through a fine fritted funnel and the crude product was washed with water. After air drying, the product was purified by column chromatography (pre-packed silica column) using a gradient of 0 to 6% 2M ammonia-methanol in DCM. 20 mg of 6-(2-methoxy-ethoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide was obtained. LCMS (m/z): 497.8. 1H NMR (400 MHz, DMSO-d6) δ 8.83 (1H, s) 8.14 (1H, d) 7.93-8.03 (2H, m) 7.83 (1H, s) 7.67-7.74 (2H, m) 7.57-7.63 (1H, m) 7.51 (1H, dd) 7.10 (1H, d) 4.42-4.49 (2H, m) 3.70-3.76 (2H, m) 3.32-3.34 (3H, m).

Aufarbeitung

  1. temperaturethe mixture was warmed to 70° C
  2. waitThe reaction was monitored by LCMS for 1 hour
  3. additionwas added
  4. stirringthe reaction mixture was stirred for 10 minutes
  5. filtrationThe reaction was then filtered through a fine fritted funnel
  6. washthe crude product was washed with water
  7. customAfter air drying
  8. customthe product was purified by column chromatography (pre-packed silica column)

Quellen und Nachweise

ORD-Eintrag
ord-e627fef6bae247d390bcaf55c39d5a61
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08450354B2

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