Phosphorus oxychloride → HCID 57811364, compound

HRID 660467Notes

Reaction equation

HRID 660467 reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[N:10][N:11]=1.[OH:30][CH:31]1[O:37][C@H:36]([C@@H:38]([CH2:40][OH:41])[OH:39])[C@H:34](O)[C@H:32]1[OH:33]>N1C=CC=CC=1>[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([O:16][CH:34]2[CH:32]([OH:33])[CH:31]([OH:30])[O:37][CH:36]2[CH:38]([OH:39])[CH2:40][OH:41])=[O:15])=[N:10][N:11]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 11105941D-GlucofuranoseHCID 53465279Lesinurad

Product 1

HCID 57811364HCID 57811364, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
0 °C

Procedure

Phosphorus oxychloride (2.4 mmol) is added dropwise over 5 mins to a solution of 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid (810 mg, 2.0 mmol) in pyridine (20 mL) at 0° C. The mixture is stirred at 0° C. for a further 1 hour and then a solution of 1,2:5,6-Di-O-isopropilydene-□-D-glucofuranose (320 mg, 2.0 mmol) in pyridine (5 mL) is added dropwise over 5 mins. The mixture is stirred at 0° C. for a further 1 hour and 1 hour at 20° C. and then is quenched by addition of water (1 mL). Volatile solvents are removed in vacuo and DCM (200 mL) added. The organic phase is washed with water (1×50 mL), saturated sodium carbonate solution (1×50 mL) and brine (1×50 mL), dried over Na2SO4 and concentrated to dryness. Ethanol and water are added to produce a solid which is collected by filtration. Additional product is recovered by extraction of the filtrate with DCM. Combined product is concentrated, dried and purified by column chromatography (acetone/DCM eluent). The combined solids are dissolved in acetic acid (25 mL) and water (5 mL) mixture, heated at 60° C. for 3 hours. Volatile solvents are removed in vacuo. Ethanol and water are added to produce a solid which is collected by filtration.

Workup

  1. stirringThe mixture is stirred at 0° C. for a further 1 hour and 1 hour at 20° C.
  2. customis quenched by addition of water (1 mL)
  3. customVolatile solvents are removed in vacuo and DCM (200 mL)
  4. additionadded
  5. washThe organic phase is washed with water (1×50 mL), saturated sodium carbonate solution (1×50 mL) and brine (1×50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionEthanol and water are added
  9. customto produce a solid which
  10. filtrationis collected by filtration
  11. customAdditional product is recovered by extraction of the filtrate with DCM
  12. concentrationCombined product is concentrated
  13. customdried
  14. custompurified by column chromatography (acetone/DCM eluent)
  15. dissolutionThe combined solids are dissolved in acetic acid (25 mL)
  16. temperaturewater (5 mL) mixture, heated at 60° C. for 3 hours
  17. customVolatile solvents are removed in vacuo
  18. additionEthanol and water are added
  19. customto produce a solid which
  20. filtrationis collected by filtration

Sources & evidence

ORD record
ord-6134da952e384b7f80c62beab9105c41
Source dataset
uspto-grants-2011_12
Patent number
US08084483B2

Reaction notes

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