Thymidine → HCID 67703984, compound

HRID 1376448Notes

Reaction equation

HRID 1376448 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2NCCC)=[C:4](C)[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:36]1([N:44]2C=C(C)C(=O)N[C:45]2=O)O[C@H](CO)[C@@H:38](O)[CH2:37]1>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:19]2[O:20][C@H:21]([CH2:22][OH:23])[C@@H:17]([F:16])[CH2:18]2)=[C:4]([N:44]([CH3:45])[CH2:36][CH2:37][CH3:38])[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 67703958HCID 67703958, compound

Product 1

HCID 67703984HCID 67703984, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-methylpropylamino-9H-purine (0.54 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 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 8 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 (92:8). Solvent was removed and lyophilization yielded 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(methylpropylamino)-9H-purine (0.40 g, 56%): mp 80°-84° 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 (92:8)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-b569375954314fbe952f85c95f03c001
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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