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

HRID 1376440Notes

Reaction equation

HRID 1376440 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([S:11][CH3:12])[N:3]=1.[F:13][C@@H:14]1[C@@H:18]([CH2:19][OH:20])[O:17][C@@H:16](N2C=CC(=O)NC2=O)[CH2:15]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:16]2[O:17][C@H:18]([CH2:19][OH:20])[C@@H:14]([F:13])[CH2:15]2)=[C:4]([S:11][CH3:12])[N:3]=1

Participants

7

Reactant 4

HCID 5789Thymidine3×HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178503507HCID 178503507, compound

Product 1

HCID 867511902-amino-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-methylmercapto-9H-purineYield 47.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-methylmercapto-9H-purine (0.49 g 2.7 mmoles, Aldrich 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 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (7850 I.U.) and thymidine phosphorylase (2000 I.U.) (Krenitsky et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) were added to the reaction mixture and the suspension stirred at 45° C. After 17 days, additional purine nucleoside phosphorylase (7850 I.U.) and thymidine phosphorylase (2000 I.U.) were added. After another 104 days, additional purine nucleoside phosphorylase (15,700 I.U.) and thymidine phosphorylase (52,500 I.U.) were added. Four days later the reaction was poured into methanol 600 ml and denatured protein was removed by filtration through Celite. The filtrate was applied to an AG1-X2 column (2.5×10 cm, OH- form) and the product was eluted with methanol. Solvent was removed in vacuo and the residue flash chromatographed on silica gel (2.5×20 cm) using dichloromethane:methanol (95:5). Solvent was removed and lyophilization yielded 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-methylmercapto-9H-purine (0.31 g).

Workup

  1. addition4,381,344) were added to the reaction mixture
  2. waitAfter another 104 days
  3. customwas removed by filtration through Celite
  4. washthe product was eluted with methanol
  5. customSolvent was removed in vacuo
  6. customthe residue flash chromatographed on silica gel (2.5×20 cm)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-70abffd797354ed78b23f3e9421f8c52
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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