Acetonitrile → 6-chloro-2-(2-morpholin-4-yl-ethyl)-2H-pyridazin-3-one

HRID 28400

Reaktionsgleichung

Reaktionsgleichung von HRID 28400
[Cl:1][C:2]1[N:7]=[N:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl.Cl[CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:7]=1

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 178516069HCID 178516069, Verbindung2×

Produkt 1

HCID 693065856-chloro-2-(2-morpholin-4-yl-ethyl)-2H-pyridazin-3-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

6-Chloro-pyridazin-3-ol (5.34 g, 40.8 mmol), 4-(2-chloro-ethyl)-morpholine hydrochloride (7.61 g, 40.8 mmol) and potassium carbonate (11.3 g, 81.7 mmol) were added to 20 mL of acetonitrile, 10 mL of N,N-dimethylformamide and 0.5 mL of water. The reaction mixture was heated using an oil bath at 116° C. After 4 hours, LC/MS showed the disappearance of 6-chloro-pyridazin-3-ol and the formation of the alkylated product. After cooling to room temperature, 100 mL of water was added to the mixture. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4, concentrated, and subjected to flash column chromatography (ethyl acetate/hexane/triethyl amine; 1:6:0.05) on silica gel to give 6-chloro-2-(2-morpholin-4-yl-ethyl)-2H-pyridazin-3-one after removal of solvents in vacuo. To the residue was added 20 mL of 4 M aqueous HCl and 20 mL of methanol were added (pH ˜2). The mixture was concentrated to get a solid residue, which could be further purified through re-crystallisation in hot ethanol. Finally, 4.2 g (37%) of the product as a mono hydrochloride salt was obtained as colourless solid material.

Aufarbeitung

  1. temperatureThe reaction mixture was heated
  2. customat 116° C
  3. extractionThe aqueous phase was extracted twice with ethyl acetate
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9d8d8eea0bd341f387a93dc97fd224bc
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419979B2

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