Thymidine → HCID 9860968, compound

HRID 1376449Notes

Reaction equation

HRID 1376449 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]([CH3:13])[CH3:12])[N:3]=1.[F:14][C@@H:15]1[C@@H:19]([CH2:20][OH:21])[O:18][C@@H:17](N2C=CC(=O)NC2=O)[CH2:16]1.[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+].CO>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:17]2[O:18][C@H:19]([CH2:20][OH:21])[C@@H:15]([F:14])[CH2:16]2)=[C:4]([N:11]([CH3:13])[CH3:12])[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178483098HCID 178483098, compound

Product 1

HCID 9860968HCID 9860968, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-dimethylamino-9H-purine (0.46 g, 2.6 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in potassium phosphate buffer (50 ml, 10 mM), pH 7.0, containing potassium azide 0.04%. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) (Krenitsky et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 19 days, MeOH (170 ml) was added to the reaction. The reaction was applied to a column containing AG1-X2 (OH- form, 2.5×10 cm) and eluted with MeOH. Fractions containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (88:12). Solvent was removed and lyophilization yielded 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(dimethylamino)-9H-purine 0.17 g (26%): mp 96°-100° C.; TLC Rf 0.79 (silica gel, MeCN: 15N NH4OH:H2O/85:5:10);

Workup

  1. additionwas added to the reaction
  2. additioncontaining AG1-X2 (OH- form, 2.5×10 cm)
  3. washeluted with MeOH
  4. additionFractions containing product
  5. concentrationconcentrated
  6. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (88:12)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-1d28815844a24e739e27d043dc7015bc
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

Loading…