Hydrochloric Acid → HCID 90402674, compound

HRID 2200758Notes

Reaction equation

HRID 2200758 reaction equation
Br[C:2]1[N:10]([CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:9]2[C:8](=[O:16])[N:7]([CH2:17][CH2:18][CH2:19][O:20][Si](C(C)(C)C)(C)C)[C:6](=[O:28])[N:5]([CH3:29])[C:4]=2[N:3]=1.[F:30][C:31]1[CH:32]=[C:33]([OH:37])[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O>[F:30][C:31]1[CH:32]=[C:33]([CH:34]=[CH:35][CH:36]=1)[O:37][C:2]1[N:10]([CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15])[C:9]2[C:8](=[O:16])[N:7]([CH2:17][CH2:18][CH2:19][OH:20])[C:6](=[O:28])[N:5]([CH3:29])[C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 97433-FluorophenolHCID 11430Potassium CarbonateHCID 90402984HCID 90402984, compound2×

Product 1

HCID 90402674HCID 90402674, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

8-Bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl-7-isopentyl-3-methyl-1H-purine-2,6(3H,7H)-dione (0.50 g, 1.03 mmol, intermediate 82), 3-fluorophenol (0.098 mL, 1.08 mmol) and potassium carbonate (0.29 g, 2.06 mmol) were combined in DMF (8 mL) and heated at 90° C. for 15 h. The reaction was cooled to room temperature and acidified with 6N HCl to pH=1. The reaction was stirred for 1 h then diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were washed with 1N LiCl (2×100 mL), dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to yield a golden oil. The oil was purified using a 24 g silica gel flash column eluted with a gradient of 20% ethyl acetate/hexanes to 100% ethyl acetate to give 8-(3-fluorophenoxy)-1-(3-hydroxypropyl)-7-isopentyl-3-methyl-1H-purine-2,6(3H,7H)-dione (0.20 g, 48% yield) as a white solid. LCMS retention time=3.524 min and 96% purity, LCMS MH+=405.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. washThe combined extracts were washed with 1N LiCl (2×100 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customto yield a golden oil
  8. customThe oil was purified
  9. washeluted with a gradient of 20% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-0251ab0cd1cc42b89d0b24793332f7ec
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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