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

HRID 2089966Notes

Reaction equation

HRID 2089966 reaction equation
[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

Participants

9

Reactant 5

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

Product 1

HCID 580722075-Methoxy-3-(2-phenyl-1H-imidazol-1-yl)-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-oneYield 29.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5b76fd7f0fcc4f4e83a580b313095ff0
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

Loading…