Trifluoroacetic acid → URAT1 inhibitor 8

HRID 2178114Notes

Reaction equation

HRID 2178114 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[CH:6][C:7]=1[CH2:8][OH:9].[C:11]([C:13]1[CH:14]=[C:15]([S:20]([N:23](CC2C=CC(OC)=CC=2OC)[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=2)(=[O:22])=[O:21])[CH:16]=[CH:17][C:18]=1F)#[N:12].C(=O)([O-])[O-].[K+].[K+].C(O)(C(F)(F)F)=O>CS(C)=O.C(Cl)Cl.CO.CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[CH2:8][OH:9])[O:10][C:18]1[CH:17]=[CH:16][C:15]([S:20]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=2)(=[O:21])=[O:22])=[CH:14][C:13]=1[C:11]#[N:12]

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 212878153-Chloro-4-(hydroxymethyl)phenolHCID 1176533623-cyano-N-(2,4-di methoxybenzyl)-4-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide

Product 1

HCID 86271138URAT1 inhibitor 8Yield 26.2%

Reagents, catalysts & solvents 5

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3-chloro-4-(hydroxymethyl)phenol (120 mg, 0.54 mmol) and 3-cyano-N-(2,4-di methoxybenzyl)-4-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide (Preparation 18, 100 mg, 0.22 mmol) in DMSO (1.5 mL) was added potassium carbonate (78 mg, 0.56 mmol) and the reaction stirred at room temperature for 72 hours. Water (10 mL) and EtOAc (15 mL) were added and the layers separated. The aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried over magnesium sulphate and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with 3:2 EtOAc:heptanes. The residue (76 mg, 0.13 mmol) was dissolved in DCM (2 mL) and treated with TFA (2 mL). The reaction was stirred at room temperature for 18 hours. MeOH (1 mL) was added and the reaction concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with 10-30% EtOAc in DCM to afford the title compound (25 mg, 44%) as a colourless solid (25 mg, 44%).

Workup

  1. customthe layers separated
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography
  7. washeluting with 3:2 EtOAc
  8. stirringThe reaction was stirred at room temperature for 18 hours
  9. concentrationthe reaction concentrated in vacuo
  10. customThe crude product was purified by silica gel column chromatography
  11. washeluting with 10-30% EtOAc in DCM

Sources & evidence

ORD record
ord-54adccfd4a814341b5ef42bbcb43ad51
Source dataset
uspto-grants-2015_06
Patent number
US09067922B2

Reaction notes

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