Thymidine → HCID 10426568, compound

HRID 37080Notes

Reaction equation

HRID 37080 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([O:11][CH2:12][CH2:13][CH3:14])[N:3]=1.[F:15][C@@H:16]1[C@H:20]([OH:21])[C@@H:19]([CH2:22][OH:23])[O:18][C@H:17]1N1C=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[OH-].[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+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:17]2[O:18][C@H:19]([CH2:22][OH:23])[C@@H:20]([OH:21])[C@H:16]2[F:15])=[C:4]([O:11][CH2:12][CH2:13][CH3:14])[N:3]=1

Participants

7

Reactant 5

HCID 5789Thymidine2×HCID 14797Potassium HydroxideHCID 95802Purine, 2-amino-6-propoxy-HCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide2×

Product 1

HCID 10426568HCID 10426568, compound

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent2×

Conditions

Temperature
37 °C

Procedure

2-Amino-6-propoxypurine (0.3 g, 1.6 mmoles) which may be prepared according to R. W. Balsiger and J. A. Montgomery (J. Org. Chem. 25:1573, 1960) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.52 g, 2.1 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 50 ml of 2 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. The pH of the suspension was adjusted to 7.0 with KOH. Thymidine phosphorylase (4,000 I.U.) and purine nucleoside phosphorylase (14,000 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) were added and the reaction stirred at 37° C. On day 6, the reaction was diluted to 250 ml with 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide, and 4,000 I.U. of thymidine phosphorylase and 14,000 I.U. of purine nucleoside phosphorylase were added. On day 14, the solvent was removed under vacuum. The residue was suspended in methanol/water and the suspension was filtered. The filtrate was evaporated. The residue was dissolved in hot water and applied to a 2.5×13 cm column of anion exchange resin (Bio-Rad AG1X2 hydroxide form). After washing the column with water, the product was eluted with methanol/water (1/1). Product-containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and lyophilized to obtain title compound that analyzed as 0.9 hydrate.

Workup

  1. addition4,381,344) were added
  2. waitOn day 6
  3. waitOn day 14
  4. customthe solvent was removed under vacuum
  5. filtrationthe suspension was filtered
  6. customThe filtrate was evaporated
  7. dissolutionThe residue was dissolved in hot water
  8. washAfter washing the column with water
  9. washthe product was eluted with methanol/water (1/1)
  10. customthe solvent removed under vacuum
  11. dissolutionThe residue was dissolved in water

Sources & evidence

ORD record
ord-603a69c4f1624a80ac55a3e14e32391d
Source dataset
uspto-grants-1995_05
Patent number
US05420115

Reaction notes

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