Thymidine → HCID 67703970, compound

HRID 1376455Notes

Reaction equation

HRID 1376455 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1.[F:18][C@@H:19]1[C@@H:23]([CH2:24][OH:25])[O:22][C@@H:21](N2C=CC(=O)NC2=O)[CH2:20]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:21]2[O:22][C@H:23]([CH2:24][OH:25])[C@@H:19]([F:18])[CH2:20]2)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178508671HCID 178508671, compound

Product 1

HCID 67703970HCID 67703970, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-phenylamino-9H-purine (0.63 g, 2.7 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in 50 ml, 10 mM potassium phosphate buffer, 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 2 days, 100 ml MeOH 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:methanol (97:2:1). Fractions containing product were combined and flash chromatographed on a second silica gel column (2.5×20 cm) with hexane:acetone (6:4). Solvent was removed and lyophilization yielded 0.364 g of 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-phenylamino-9H-purine (49%): mp 193°-194° C.;

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:methanol (97:2:1)
  7. additionFractions containing product
  8. customflash chromatographed on a second silica gel column (2.5×20 cm) with hexane:acetone (6:4)
  9. customSolvent was removed

Sources & evidence

ORD record
ord-add2e756c7b04537af3a763b27a05eec
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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