Sodium Thiosulfate → HCID 178507660, compound

HRID 1187292Notes

Reaction equation

HRID 1187292 reaction equation
COC(=O)[NH:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([CH:12]([OH:23])[C:13]2[C:21]3[C:20]([OH:22])=[N:19][CH:18]=[N:17][C:16]=3[NH:15][CH:14]=2)[C:6]=1[F:24].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1.C(OCC)(=O)C>[NH2:4][C:5]1[C:6]([F:24])=[C:7]([C:12]([C:13]2[C:21]3[C:20]([OH:22])=[N:19][CH:18]=[N:17][C:16]=3[NH:15][CH:14]=2)=[O:23])[C:8]([F:11])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 178501975HCID 178501975, compound

Product 1

HCID 178507660HCID 178507660, compoundYield 50.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a reaction vessel, {2,4-difluoro-3-[hydroxy-(4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-phenyl}-carbamic acid methyl ester (38, 690 mg, 1.97 mmol) is dissolved in 200 mL of tetrahydrofuran and Dess-Martin periodinane (877.3 mg, 2.068 mmol) is added. The resulting mixture is stirred at room temperature for 3 hours, then 20 mL of saturated aqueous sodium bicarbonate, 5 mL of saturated aqueous sodium thiosulfate, and 100 mL of ethyl acetate are added for extraction. The organic layer is isolated and the aqueous layer extracted with 50 mL of ethyl acetate. The organic fractions are combined and washed with water, then brine, dried with magnesium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is suspended in acetonitrile, sonicated for 1 hour, then filtered to collect the solid material, which is then washed with acetonitrile. The resulting material is suspended in 15 mL of dioxane, and combined with 15 mL of 10N aqueous sodium hydroxide, and heated to reflux for 5 hours. The reaction mixture is adjusted to approximately pH 6 with 6N hydrochloric acid and extracted with ethyl acetate. The organic layer is concentrated under vacuum and the resulting material purified by silica gel chromatography eluting with methanol and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (39, 287 mg). MS (ESI) [M−H+]−=289.1.

Workup

  1. customThe organic layer is isolated
  2. extractionthe aqueous layer extracted with 50 mL of ethyl acetate
  3. washwashed with water
  4. dry with materialbrine, dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated under vacuum
  7. customsonicated for 1 hour
  8. filtrationfiltered
  9. customto collect the solid material, which
  10. washis then washed with acetonitrile
  11. temperatureheated
  12. temperatureto reflux for 5 hours
  13. extractionextracted with ethyl acetate
  14. concentrationThe organic layer is concentrated under vacuum
  15. customthe resulting material purified by silica gel chromatography
  16. washeluting with methanol and dichloromethane
  17. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-65589920cd7e4723a338834dc6d14deb
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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