Thymidine → 9-(2-Deoxy-2-fluoro-beta-D-ribofuranosyl)-6-iodo-9H-purine

HRID 37085Notes

Reaction equation

HRID 37085 reaction equation
[I:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.[F:11][C@@H:12]1[C@H:16]([OH:17])[C@@H:15]([CH2:18][OH:19])[O:14][C@H:13]1N1C=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>[F:11][C@@H:12]1[C@H:16]([OH:17])[C@@H:15]([CH2:18][OH:19])[O:14][C@H:13]1[N:6]1[CH:5]=[N:4][C:3]2[C:7]1=[N:8][CH:9]=[N:10][C:2]=2[I:1]

Participants

7

Reactant 4

HCID 5789Thymidine3×HCID 1508512'Fluoro-2'-deoxyuridineHCID 54630676-Iodo-9H-purineHCID 10290740Potassium azide2×

Product 1

HCID 152935769-(2-Deoxy-2-fluoro-beta-D-ribofuranosyl)-6-iodo-9H-purine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 62657Potassium Phosphate, TribasicSolvent2×

Conditions

Temperature
37 °C

Procedure

6-Iodopurine (Sigma Chemical Company; 0.7 g, 2.7 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.4 g, 1.7 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 20 ml of 10 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (2,640 I.U.) and purine nucleoside phosphorylase (4,360 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) were added and the suspension stirred at 37° C. On day 21, the reaction was diluted to 50 ml with 5 mm potassium phosphate buffer, pH 7, which contained 0.04% (w/v) potassium azide and 4000 I.U. of thymidine phosphorylase and 6,500 I.U. of purine nucleoside phosphorylase were added. On day 43, the reaction was diluted to 250 ml with water and 2,000 I.U. thymidine phosphorylase and 3,250 I.U. purine nucleoside phosphorylase were added. On day 57, the reaction was filtered. The filtrate was evaporated. The residue was suspended in warm methanol and filtered. The filtrate was evaporated. The residue was dissolved in water/n-propanol (7/3) and applied to a 7.5×90 cm column of Biogel P-2 (Bio-Rad) with water/n-propanol (7/3) as the solvent. Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in hot methanol and water added until a precipitate formed. The methanol was removed under vacuum. After standing overnight the suspension was filtered. The filter cake contained the bulk of the product. The filtrate was evaporated and the above procedure repeated to precipitate the remaining product. The filter cakes were combined and suspended in water. Lyophilization yielded the title compound.

Workup

  1. addition4,381,344) were added
  2. waitOn day 21
  3. waitOn day 43
  4. waitOn day 57
  5. filtrationthe reaction was filtered
  6. customThe filtrate was evaporated
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. dissolutionThe residue was dissolved in water/n-propanol (7/3)
  10. additionProduct containing fractions
  11. customthe solvent removed under vacuum
  12. dissolutionThe residue was dissolved in hot methanol
  13. additionwater added until a precipitate
  14. customformed
  15. customThe methanol was removed under vacuum
  16. filtrationthe suspension was filtered
  17. customThe filtrate was evaporated
  18. customto precipitate the remaining product

Sources & evidence

ORD record
ord-3602e642de3744dbb5b5b92c53747bf0
Source dataset
uspto-grants-1995_05
Patent number
US05420115

Reaction notes

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