Thymidine → HCID 67704911, compound

HRID 1683181

Reaction equation

HRID 1683181 reaction equation
[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

Participants

11

Reactant 6

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

Product 2

HCID 67704911HCID 67704911, compoundYield 113.7%HCID 178458949HCID 178458949, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 10311-PropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
37 °C

Procedure

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.;

Workup

  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

Sources & evidence

ORD record
ord-9de20ebafd664eb584c20dd3bdf8eb28
Source dataset
uspto-grants-1997_06
Patent number
US05637574

Linked notes

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