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

HRID 1376442Notes

Reaction equation

HRID 1376442 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]([CH2:14][CH3:15])[CH2:12][CH3:13])[N:3]=1.[F:16][C@@H:17]1[C@@H:21]([CH2:22][OH:23])[O:20][C@@H:19](N2C=CC(=O)NC2=O)[CH2:18]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+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:19]2[O:20][C@H:21]([CH2:22][OH:23])[C@@H:17]([F:16])[CH2:18]2)=[C:4]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[N:3]=1

Participants

6

Reactant 4

HCID 5789Thymidine2×HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178463887HCID 178463887, compound

Product 1

HCID 677039762-amino-6-diethylamino-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purine

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-diethylamino-9H-purine (0.47 g 2.3 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.41 g, 1.8 mmoles) were suspended in potassium phosphate buffer (10 mM) 50 ml), pH 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (5350 units) and thymidine phosphorylase (2000 unit (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 14 days, additional purine nucleoside phosphorylase (15,700 units) and thymidine phosphorylase (4000 units) were added to the reaction mixture. After a total reaction time of 123 days, denatured protein was removed by filtration and the filtrate was applied to a column of AG1-X2 (2.5×10 cm, OH- form). After the column was washed with methanol, fractions containing product were pooled, evaporated and chromatographed on silica gel (2.5×20 cm) using dichloromethane:methanol (97:3). Solvent was removed and lyophilization yielded 2-amino-6-diethylamino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine.

Workup

  1. addition4,381,344) were added to the reaction mixture
  2. customAfter a total reaction time of 123 days
  3. customwas removed by filtration
  4. washAfter the column was washed with methanol, fractions
  5. additioncontaining product
  6. customevaporated
  7. customchromatographed on silica gel (2.5×20 cm)
  8. customSolvent was removed

Sources & evidence

ORD record
ord-f52f3f2a072a493ea12d7555e6fa8a71
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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