Acetic Acid → 4-[5-(4-fluorophenyl)-1-methyl-3-oxido-2-phenyl-1H-imidazol-4-yl]pyridin-2(1H)-one

HRID 23525Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[C:9]([C:12]2[CH:17]=[CH:16][N:15]=C(F)C=2)=[N:10][OH:11])=[CH:4][CH:3]=1.[CH:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH3:28][NH2:29].[C:30]([OH:33])(=O)[CH3:31]>C(Cl)Cl.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:29]([CH3:28])[C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N+:10]([O-:11])[C:9]=2[C:12]2[CH:17]=[CH:16][NH:15][C:30](=[O:33])[CH:31]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethane-1,2-dione 2-oxime (Example 1, Step B) (400 mg, 1.52 mmol) in acetic acid (7.6 mL) was added benzaldehyde (170 μL, 1.68 mmol) followed by methylamine (144 μL, 40 wt. % in H2O, 1.68 mmol), and the mixture was heated for 41 hours at 100° C. It was cooled and acetic acid was removed in vacuo. The residue was taken up in H2O and was concentrated in vacuo two times. This was repeated with toluene to obtain crude residue. The crude residue was dissolved in a mixture of CH2Cl2/MeOH, filtered off solid (unreacted, hydrolyzed imidazole), and the solvent was removed in vacuo. The crude product was pre-absorbed on silica gel and purified by flash chromatography eluting with 5% MeOH/CH2Cl2 followed by 10% 2M NH3 in MeOH/CH2Cl2 to obtain 270 mg of the title compound.

Workup

temperatureIt was cooled
customacetic acid was removed in vacuo
concentrationwas concentrated in vacuo two times
customto obtain crude residue
filtrationfiltered off solid (unreacted, hydrolyzed imidazole)
customthe solvent was removed in vacuo
customThe crude product was pre-absorbed on silica gel
custompurified by flash chromatography
washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-1e70f435aee645cbb542fdc2092f5543
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06852727B2

Reaction notes

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