Thymidine → HCID 67704911, Verbindung

HRID 1683181

Reaktionsgleichung

Reaktionsgleichung von HRID 1683181
[H-].[Na+].[NH2:3][C:4]1[N:12]=[C:11]2[C:7]([N:8]=[CH:9][NH:10]2)=[C:6]([O:13][CH2:14][CH2:15][CH3:16])[N:5]=1.[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20](N2C=C(C)C(=O)NC2=O)[CH2:19]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>CN(C)C=O.CS(C)=O.C(O)CC>[NH2:3][C:4]1[N:12]=[C:11]2[C:7]([N:8]=[CH:9][NH:10]2)=[C:6]([O:13][CH2:14][CH2:15][CH3:16])[N:5]=1.[NH2:3][C:4]1[N:12]=[C:11]2[C:7]([N:8]=[CH:9][N:10]2[C@@H:20]2[O:21][C@H:22]([CH2:23][OH:24])[C@@H:18]([F:17])[CH2:19]2)=[C:6]([O:13][CH2:14][CH2:15][CH3:16])[N:5]=1

Komponenten

11

Edukt 6

HCID 5789ThymidineHCID 24758Sodium hydrideHCID 330393'-FluorothymidineHCID 62657Potassium Phosphate, TribasicHCID 10290740Potassium azideHCID 178458949HCID 178458949, Verbindung

Produkt 2

HCID 67704911HCID 67704911, VerbindungAusbeute 113,7 %HCID 178458949HCID 178458949, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 10311-PropanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2-Amino-6-n-propoxy-9H-purine was prepared by displacement of the chlorine group on 2-amino-6-chloropurine (Aldrich Chemical Company) by propanol (Aldrich Chemical Company) in the presence of sodium hydride. 2-Amino-6-n-propoxy-9H-purine (0.50 g, 2.6 mmoles) was dissolved in dimethylformamide (5 ml, DMF) and dimethylsulphoxide (5 ml, DMSO). 3'-Deoxy-3'-fluorothymidine (0.76 g, 3.1 mmoles) and 30 ml 10 mM potassium phosphate buffer, pH 6.8, containing 0.04% potassium azide were added. Purified purine nucleoside phosphorylase (7,500 I.U.) and thymidine phosphorylase (3750 I.U.) adsorbed onto 5 ml DEAE-cellulose resin were added to the reaction mixture and the suspension stirred at 37° C. After 24 days, the reaction was filtered and the filtrate applied to a series of coupled columns. The initial column contained AG1-X2 (OH-form, 2.5×10 cm) while the second column contained Amberlite XAD-2 resin (2.5×20 cm). After sample application, the columns were washed with water (500 ml) and the product eluted with methanol. Product-containing fractions were then flash chromatographed down a silica gel column (4.8×20 cm) using dichloromethane:methanol (95:5) as eluant. Solvent was evaporated in vacuo and lyophilisation yielded 0.46 g of 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-propoxy-9H-purine (56%): mp 128° C.;

Aufarbeitung

  1. additionwere added
  2. additionwere added to the reaction mixture
  3. filtrationthe reaction was filtered
  4. washAfter sample application, the columns were washed with water (500 ml)
  5. washthe product eluted with methanol
  6. customflash chromatographed down a silica gel column (4.8×20 cm)
  7. customSolvent was evaporated in vacuo and lyophilisation

Quellen und Nachweise

ORD-Eintrag
ord-9de20ebafd664eb584c20dd3bdf8eb28
Quelldatensatz
uspto-grants-1997_06
Patentnummer
US05637574

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