Methyl iodide → Istradefylline

HRID 375292Notes

Reaction equation

HRID 375292 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])/[CH:6]=[CH:7]/[C:8]1[NH:16][C:15]2[C:14](=[O:17])[N:13]([CH2:18][CH3:19])[C:12](=[O:20])[N:11]([CH2:21][CH3:22])[C:10]=2[N:9]=1.[C:28](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])/[CH:6]=[CH:7]/[C:8]1[N:16]([CH3:28])[C:15]2[C:14](=[O:17])[N:13]([CH2:18][CH3:19])[C:12](=[O:20])[N:11]([CH2:21][CH3:22])[C:10]=2[N:9]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 64457888-[(1E)-2-(3,4-Dimethoxyphenyl)ethenyl]-1,3-diethyl-3,9-dihydro-1H-purine-2,6-dione

Product 1

HCID 5311037IstradefyllineYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 64 (1.20 g, 3.24 mmol) obtained in Example 7 was dissolved in 25 ml of dimethylformamide. To the solution were added 1.12 g (8.10 mmol) of potassium carbonate and subsequently 0.40 ml (6.49 mmol) of methyl iodide, and the resultant mixture was stirred at 50° C. for 30 minutes. After cooling, insoluble matters were filtered off, and 100 ml of water was added to the filtrate. The mixture was extracted three times with 50 ml of chloroform. The extract was washed twice with water and once with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, followed by evaporation under reduced pressure. The obtained crude crystals were purified by silica gel column chromatography (eluent: 40% ethyl acetate/hexane), followed by recrystallization from isopropanol to give 840 mg (yield 68%) of Compound 65 as pale yellow needles.

Workup

  1. temperatureAfter cooling
  2. filtrationinsoluble matters were filtered off
  3. addition100 ml of water was added to the filtrate
  4. extractionThe mixture was extracted three times with 50 ml of chloroform
  5. washThe extract was washed twice with water and once with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customfollowed by evaporation under reduced pressure
  8. customThe obtained crude crystals
  9. customwere purified by silica gel column chromatography (eluent: 40% ethyl acetate/hexane)
  10. customfollowed by recrystallization from isopropanol

Sources & evidence

ORD record
ord-56be62b458524879a119ab168fbb21a5
Source dataset
uspto-grants-1996_01
Patent number
US05484920

Reaction notes

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