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

HRID 37075

Reaktionsgleichung

Reaktionsgleichung von HRID 37075
[CH:1]1([NH:4][C:5]2[N:13]=[CH:12][N:11]=[C:10]3[C:6]=2[N:7]=[CH:8][NH:9]3)[CH2:3][CH2:2]1.[F:14][C@@H:15]1[C@H:19]([OH:20])[C@@H:18]([CH2:21][OH:22])[O:17][C@H:16]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.C1(NC2N=C3C(NC=N3)=CN=2)CC1.[NH4+].[OH-]>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[CH:1]1([NH:4][C:5]2[N:13]=[CH:12][N:11]=[C:10]3[C:6]=2[N:7]=[CH:8][N:9]3[C@@H:16]2[O:17][C@H:18]([CH2:21][OH:22])[C@@H:19]([OH:20])[C@H:15]2[F:14])[CH2:3][CH2:2]1

Komponenten

10

Edukt 8

HCID 5789Thymidine3×HCID 14797Potassium Hydroxide2×HCID 14923Ammonium HydroxideHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azideHCID 113098196-(Cyclopropylamino)-9H-purineHCID 67535543(Cyclopropylamino) purineHCID 178420900HCID 178420900, Verbindung

Produkt 1

HCID 100409666-(Cyclopropylamino)-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-9H-purine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

6-(Cyclopropylamino)-9H-purine (0.2 g, 1.1 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 suspended in 20 ml of 5 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 (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. 4,381,344) were added and the suspension stirred at 37° C. On day 5, 0.2 g of 6-(cyclopropylamino)purine and 2,000 I.U. of thymidine phosphorylase and 5,540 I.U. of purine nucleoside phosphorylase were added. On day 9, 0.2 g of 6 (cyclopropylamino) purine was added and the pH of the reaction was adjusted to 7.0 with KOH. Thymidine phosphorylase (2,000 I.U.) and purine nucleoside phosphorylase (5,540 I.U.) were added. On day 20, the pH of the reaction was adjusted to 9.4 with NH4OH and the reaction was applied to a 2.5×8.5 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing with water, the product was eluted with water/methanol (7/3). 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 0.4 hydrate.

Aufarbeitung

  1. addition4,381,344) were added
  2. waitOn day 20
  3. washAfter washing with water
  4. washthe product was eluted with water/methanol (7/3)
  5. customthe solvent removed under vacuum
  6. dissolutionThe residue was dissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-1774b0714a6f42688356dd52b53265b5
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05420115

Verknüpfte Notizen

Wird geladen…