Methane → Lesinurad

HRID 38745Notes

Reaction equation

HRID 38745 reaction equation
[OH-:1].[Na+].[Br:3][C:4]1[N:5]([C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:28]([CH:35]3[CH2:37][CH2:36]3)=[CH:27][CH:26]=2)[C:6]([S:9][CH2:10][C:11](NC2C=CC(S(=O)(=O)N)=CC=2Cl)=[O:12])=[N:7][N:8]=1.C>C(O)C>[Br:3][C:4]1[N:5]([C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:28]([CH:35]3[CH2:37][CH2:36]3)=[CH:27][CH:26]=2)[C:6]([S:9][CH2:10][C:11]([OH:1])=[O:12])=[N:7][N:8]=1

Participants

5

Reactant 3

HCID 297MethaneHCID 14798Sodium HydroxideHCID 115199512-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)-N-(2-chloro-4-sulfamoylphenyl)acetamide

Product 1

HCID 53465279Lesinurad

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium hydroxide solution (2M aqueous, 33.7 mL, 67 mmol, 2 eq) was added to a suspension of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)-N-(2-chloro-4-sulfamoylphenyl)acetamide (prepared by previously published procedures, see US 2009/0197825; 20 g, 34 mmol) in ethanol (200 mL) and the mixture heated at reflux for 4 hours. Charcoal (10 g) was added, the mixture stirred at room temperature for 12 hours and the charcoal removed by filtration. The charcoal was washed several times with ethanol and the filtrate then concentrated. Water (200 mL) was added and then concentrated to approx. one third volume to remove all ethanol. Water (200 mL) and ethyl acetate (250 mL) were added, the mixture stirred vigorously for 15 min and the organic layer removed. The aqueous layer was cooled to 0° C. and acidified by treatment with HCl (1N) resulting in the formation of a cloudy oily precipitate. The mixture was extracted with ethyl acetate (3×) and the combined organic extracts dried over sodium sulfate and concentrated to give 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid as an off white solid (11.2 g, 82%).

Workup

  1. customprepared by previously published procedures
  2. temperatureat reflux for 4 hours
  3. customthe charcoal removed by filtration
  4. washThe charcoal was washed several times with ethanol
  5. concentrationthe filtrate then concentrated
  6. additionWater (200 mL) was added
  7. concentrationconcentrated
  8. customto remove all ethanol
  9. additionWater (200 mL) and ethyl acetate (250 mL) were added
  10. stirringthe mixture stirred vigorously for 15 min
  11. customthe organic layer removed
  12. temperatureThe aqueous layer was cooled to 0° C.
  13. customresulting in the formation of a cloudy oily precipitate
  14. extractionThe mixture was extracted with ethyl acetate (3×)
  15. dry with materialthe combined organic extracts dried over sodium sulfate
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-3bf07a84810d4d41aa162f2a8e296ede
Source dataset
uspto-grants-2013_09
Patent number
US08524754B2

Reaction notes

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