Thymidine → 9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine

HRID 1376446Notes

Reaction equation

HRID 1376446 reaction equation
[CH2:1]([NH:7][C:8]1[N:16]=[CH:15][N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][NH:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20](N2C=CC(=O)NC2=O)[CH2:19]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>[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20]([N:12]2[CH:11]=[N:10][C:9]3[C:13]2=[N:14][CH:15]=[N:16][C:8]=3[NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:19]1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178444747HCID 178444747, compound

Product 1

HCID 677039649-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purineYield 29.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

6-Hexylamino-9H-purine (0.67 g, 2.6 mmoles, Sigma Chemical Company) 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 0.04% potassium azide. 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 4 days, MeOH (175 ml) was added to the reaction. The reaction was applied to a column containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8). Fractions containing product were pooled, concentrated, and then flash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1). Solvent was removed and lyophilization yielded 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine (29%) (0.22 g): mp 83° C.;

Workup

  1. additionwas added to the reaction
  2. additioncontaining product
  3. concentrationconcentrated
  4. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8)
  5. additionFractions containing product
  6. concentrationconcentrated
  7. customflash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1)
  8. customSolvent was removed

Sources & evidence

ORD record
ord-2c82d9ad36f847518d4b287323530f1c
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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