Benzaldehyde → 5-Methoxy-3-(2-phenyl-1H-imidazol-1-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one

HRID 2089966Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2089966
[NH2:1][C:2]1[C:7](=[O:8])[C:6]([O:9][CH3:10])=[CH:5][N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:3]=1.[CH:21]([CH:23]=O)=O.[CH:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[NH4+:33].[Cl-].OP(O)(O)=O>CO.O.C([O-])(O)=O.[Na+]>[CH3:10][O:9][C:6]1[C:7](=[O:8])[C:2]([N:1]2[CH:23]=[CH:21][N:33]=[C:25]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:3][N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:20])[F:19])[CH:12]=2)[CH:5]=1

Komponenten

9

Edukt 5

HCID 240BenzaldehydeHCID 1004Phosphoric AcidHCID 7860GlyoxalHCID 25517Ammonium ChlorideHCID 59436209HCID 59436209, Verbindung

Produkt 1

HCID 580722075-Methoxy-3-(2-phenyl-1H-imidazol-1-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-oneAusbeute 29,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A solution of 3-amino-5-methoxy-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (300 mg, 1.05 mmol) and glyoxal (40% solution, 0.240 mL, 2.10 mmol) in MeOH (3 mL) was stirred at room temperature for 24 h. To the solution were added benzaldehyde (0.428 mL, 4.21 mmol) and NH4Cl (225 mg, 4.21 mmol). The mixture was heated to reflux for 2 h. To the mixture was added H3PO4 (0.142 mL). The mixture was heated to reflux for 20 h. The mixture was diluted with water and saturated NaHCO3 aqueous solution, extracted with AcOEt, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC and recrystallized with AcOEt/hexane to yield the title compound (126 mg, 29% yield) as a white solid: mp 167-170° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.94 (3H, s), 7.19 (1H, d, J=1.5 Hz), 7.31-7.49 (5H, m), 7.61 (1H, d, J=1.5 Hz), 7.68-7.91 (4H, m), 8.80 (1H, s). Anal. Calcd for C21H15F3N4O2.0.7H2O: C, 59.35; H, 3.89; N, 13.18. Found: C, 59.28; H, 3.69; N, 13.12.

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 20 h
  5. extractionextracted with AcOEt
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC
  10. customrecrystallized with AcOEt/hexane

Quellen und Nachweise

ORD-Eintrag
ord-5b76fd7f0fcc4f4e83a580b313095ff0
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435995B2

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