Sodium hydride → HCID 178467752, compound

HRID 1194659Notes

Reaction equation

HRID 1194659 reaction equation
[CH2:1]([NH:8][C:9]1[NH:18][C:17]2[C:16](=[O:19])[N:14]([CH3:15])[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:24]([O:26][CH2:27][CH2:28][CH:29]([C:33](O)=[O:34])[C:30](O)=[O:31])[CH3:25]>CN(C)C=O>[CH2:1]([N:8]1[C:9]2=[N:10][C:11]3[N:12]([CH3:21])[C:13](=[O:20])[N:14]([CH3:15])[C:16](=[O:19])[C:17]=3[N:18]2[C:33]([OH:34])=[C:29]([CH2:28][CH2:27][O:26][CH2:24][CH3:25])[C:30]1=[O:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1003823,9-Dihydro-1,3-dimethyl-8-((phenylmethyl)amino)-1H-purine-2,6-dioneHCID 17872155beta-Ethoxyethylmalonic acid

Product 1

HCID 178467752HCID 178467752, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of 7.43 g of 8-benzylaminotheophylline in 104 ml of dry N,N-dimethyl-formamide add portionwise over 10 minutes 1.19 g of a 60% dispersion of sodium hydride. Heat the mixture to 50° C. under a nitrogen atmosphere for 30 minutes. Add 13.30 g of the diethyl ester of β-ethoxyethylmalonic acid. Heat the mixture to 150° C. under a nitrogen atmosphere for approximately 37 hours. Allow the system to cool to room temperature and remove the solvent in vacuo. Add a mixture of water:chloroform (1:2.5) to the resulting semisolid. Acidify the aqueous portion with 3M HCl. Extract the product from the aqueous portion with chloroform. Wash the chloroform extracts with brine, dry over anhydrous sodium sulfate, filter and remove the solvent in vacuo to give the crude product. Triturate the crude product with ether. Purify the crude product by column chromatography on silica gel and triturate the major fraction with hexane to give the title compound, mp 156.5°-157.5° C.

Workup

  1. temperatureHeat the mixture to 150° C. under a nitrogen atmosphere for approximately 37 hours
  2. temperatureto cool to room temperature
  3. customremove the solvent in vacuo
  4. additionAdd
  5. additiona mixture of water:chloroform (1:2.5) to the resulting semisolid
  6. extractionExtract the product from the aqueous portion with chloroform
  7. washWash the chloroform
  8. dry with materialdry over anhydrous sodium sulfate
  9. filtrationfilter
  10. customremove the solvent in vacuo
  11. customto give the crude product
  12. customTriturate the crude product with ether
  13. customPurify the crude product by column chromatography on silica gel
  14. customtriturate the major fraction with hexane

Sources & evidence

ORD record
ord-8dc92f6df62c41b88a5e1289fc339d0b
Source dataset
uspto-grants-1989_03
Patent number
US04816458

Reaction notes

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