Thymidine → 2-Amino-6-(cyclopropylamino)-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-9H-purine

HRID 37071

Reaction equation

HRID 37071 reaction equation
Cl.[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][NH:9]2)=[C:5]([NH:12][CH:13]2[CH2:15][CH2:14]2)[N:4]=1.[F:16][C@@H:17]1[C@H:21]([OH:22])[C@@H:20]([CH2:23][OH:24])[O:19][C@H:18]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+]>[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@@H:18]2[O:19][C@H:20]([CH2:23][OH:24])[C@@H:21]([OH:22])[C@H:17]2[F:16])=[C:5]([NH:12][CH:13]2[CH2:15][CH2:14]2)[N:4]=1

Participants

6

Reactant 4

HCID 5789Thymidine2×HCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azideHCID 178479154HCID 178479154, compound

Product 1

HCID 99963492-Amino-6-(cyclopropylamino)-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-9H-purine

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Procedure

2-Amino-6-(cyclopropylamino)-9H-purine hydrochloride (0.3 g, 1.3 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.4 g, 1.6 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were dissolved in 20 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (2,000 I.U.) and purine nucleoside phosphorylase (5,540 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,444) were added and the reaction incubated at 37° C. On day 5, 2,000 I.U. thymidine phosphorylase and 5,540 I.U. purine nucleoside phosphorylase were added. On day 21, the reaction was applied to a 2.5×8 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing the column with water, the product was eluted with water/methanol (7/3). The 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 a 0.6 hydrate.

Workup

  1. addition4,381,444) were added
  2. customincubated at 37° C
  3. waitOn day 5, 2,000 I.U
  4. waitOn day 21
  5. washAfter washing the column with water
  6. washthe product was eluted with water/methanol (7/3)
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in water

Sources & evidence

ORD record
ord-fd110cd2291a49a1b7bf52e2acbd8400
Source dataset
uspto-grants-1995_05
Patent number
US05420115

Linked notes

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