8-Hydroxyquinoline → 4-hydroxymethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole

HRID 499774Notes

Reaction equation

HRID 499774 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])=[CH:4][C:3]=1[F:15].[OH:16][CH2:17][C:18]1[N:19]=[CH:20][NH:21][CH:22]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[OH:16][CH2:17][C:18]1[N:19]=[C:20]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]3=[O:14])=[CH:4][C:3]=2[F:15])[NH:21][CH:22]=1

Participants

6

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 593866611-iodo-2-fluoro-4-(2-oxopyridin-1(2H)-yl)benzeneHCID 178519868HCID 178519868, compound

Product 1

HCID 1785160734-hydroxymethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Alternatively as shown in Scheme 4, 1-iodo-2-fluoro-4-(2-oxopyridin-1(2H)-yl)benzene 3-2 prepared as above, is treated with 4-hydroxymethylimidazole II-1 in the presence of 8-hydroxyquinoline, and K2CO3 in DMSO. The resulting mixture is degassed before being charged with CuI to give 4-hydroxymethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole 4-1. The compound 4-1 is treated with thionyl chloride to give 4-chloromethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole which is then treated with NaN3 to result in 4-azidomethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole 4-2. The azide 4-2 is reduced with Ph3P to give 4-aminomethyl-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)imidazole 4-3. The compound 4-3 is then treated with 5-chlorothiophene-2-carboxylic acid 1-5 to give the title compound 21.

Workup

  1. customprepared as above,
  2. customThe resulting mixture is degassed
  3. additionbefore being charged with CuI

Sources & evidence

ORD record
ord-593c7409ac754478b7f91f6b137e3987
Source dataset
uspto-grants-2010_08
Patent number
US07767697B2

Reaction notes

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