Thymidine → HCID 15293575, compound

HRID 37078Notes

Reaction equation

HRID 37078 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH:11][CH3:12])[N:3]=1.[F:13][C@@H:14]1[C@H:18]([OH:19])[C@@H:17]([CH2:20][OH:21])[O:16][C@H:15]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+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:15]2[O:16][C@H:17]([CH2:20][OH:21])[C@@H:18]([OH:19])[C@H:14]2[F:13])=[C:4]([NH:11][CH3:12])[N:3]=1

Participants

6

Reactant 4

HCID 5789Thymidine2×HCID 1457471H-Purine-2,6-diamine, N6-methyl-2×HCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide2×

Product 1

HCID 15293575HCID 15293575, compound

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent2×

Conditions

Temperature
37 °C

Procedure

2-Amino-6-methylaminopurine (J. A. Montgomery and L. B. Holum, J.A.C.S. 80:404, 1958; 0.51 g; 3.1 mmoles) 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 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. 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 suspension 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 0.49 g of 2-amino-6-methylaminopurine and 4,000 I.U. thymidine phosphorylase and 14,000 I.U. purine nucleoside phosphorylase were added. On day 14, the reaction was evaporated. The residue was suspended in methanol/water and the suspension filtered. The filtrate was evaporated. The residue was dissolved in 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). After the solvent was removed under vacuum, the residue was dissolved in water and filtered through a 0.22 μm-pore membrane filter. Lyophilization of the filtrate yielded title compound that anlyzed as a 0.5 hydrate.

Workup

  1. addition4,381,344) were added
  2. waitOn day 6
  3. waitOn day 14
  4. customthe reaction was evaporated
  5. filtrationthe suspension filtered
  6. customThe filtrate was evaporated
  7. dissolutionThe residue was dissolved in water
  8. washAfter washing the column with water
  9. washthe product was eluted with methanol/water (1/1)
  10. customAfter the solvent was removed under vacuum
  11. dissolutionthe residue was dissolved in water
  12. filtrationfiltered through a 0.22 μm-pore membrane
  13. filtrationfilter

Sources & evidence

ORD record
ord-054203484a0f464c943cf3202a7f1286
Source dataset
uspto-grants-1995_05
Patent number
US05420115

Reaction notes

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