2-Fluoroadenine → 9-(2,3-Dideoxy-3-fluoro-beta-D-ribofuranosyl)-2-fluoroadenine

HRID 465301Notes

Reaction equation

HRID 465301 reaction equation
C([O:4][CH2:5][C@H:6]1[O:10][C@@H:9](N2C=C(C)C(=O)NC2=O)[CH2:8][C@@H:7]1[F:20])(=O)C.[F:21][C:22]1[N:30]=[C:29]2[C:25]([NH:26][CH:27]=[N:28]2)=[C:24]([NH2:31])[N:23]=1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(#N)C>[F:20][C@@H:7]1[C@@H:6]([CH2:5][OH:4])[O:10][C@@H:9]([N:28]2[CH:27]=[N:26][C:25]3[C:29]2=[N:30][C:22]([F:21])=[N:23][C:24]=3[NH2:31])[CH2:8]1

Participants

5

Reactant 3

HCID 127902-FluoroadenineHCID 453016Thymidine, 3'-deoxy-3'-fluoro-, 5'-acetateHCID 11708267Bistrimethylsilylacetamid

Product 1

HCID 156140629-(2,3-Dideoxy-3-fluoro-beta-D-ribofuranosyl)-2-fluoroadenine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2.88 g (10 mMoles) 1-(5-O-acetyl-2,3-dideoxy-3-fluoro-β-D-ribofuranosyl) thymine, 4.6 g (30 mMoles) 2-fluoroadenine, 7.4 ml bistrimethylsilyl acetamide, and 250 ml acetonitrile was heated on reflux for 25 minutes. Subsequently, 6.5 ml (33 mMoles) trifluoromethanesulfonic acid trimethyl ester was added and the reaction mixture heated on reflux for further 8 hours. After removal of the solvent under vacuum the residue was suspended in 100 ml chloroform and neutralized with NaHCO3 solution. The organic phase was dried over sodium sulfate filtered and the chloroform removed under vacuum. The residue was separated by column chromatography on silica gel, eluting with chloroform (1 l of 5% n-hexane; 15 l of 2.5% n-hexane; 1 l of 1% n-hexane). The obtained mixture was deacetylated in a conventional manner by means of ammonia/methanol and was subjected to column chromatographic separation. Chloroform (1% methanol) was used as eluent. 0.51 g was isolated of the β anomer, the title compound. Further compound remained in the mixture with the α anomer.

Workup

  1. temperaturewas heated
  2. temperatureon reflux for 25 minutes
  3. temperaturethe reaction mixture heated
  4. temperatureon reflux for further 8 hours
  5. customAfter removal of the solvent under vacuum the residue
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe chloroform removed under vacuum
  9. customThe residue was separated by column chromatography on silica gel
  10. washeluting with chloroform (1 l of 5% n-hexane; 15 l of 2.5% n-hexane; 1 l of 1% n-hexane)
  11. customwas subjected to column chromatographic separation
  12. custom0.51 g was isolated of the β anomer

Sources & evidence

ORD record
ord-d19dbe97603c42f0acd85979dc1c32cd
Source dataset
uspto-grants-1992_10
Patent number
US05153180

Reaction notes

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