Thymidine → HCID 67703941, compound

HRID 1376466Notes

Reaction equation

HRID 1376466 reaction equation
[CH2:1]([S:4][C:5]1[N:13]=[CH:12][N:11]=[C:10]2[C:6]=1[N:7]=[CH:8][NH:9]2)[CH2:2][CH3:3].[F:14][C@@H:15]1[C@@H:19]([CH2:20][OH:21])[O:18][C@@H:17](N2C=CC(=O)NC2=O)[CH2:16]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:14][C@@H:15]1[C@@H:19]([CH2:20][OH:21])[O:18][C@@H:17]([N:9]2[CH:8]=[N:7][C:6]3[C:10]2=[N:11][CH:12]=[N:13][C:5]=3[S:4][CH2:1][CH2:2][CH3:3])[CH2:16]1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178460801HCID 178460801, compound

Product 1

HCID 67703941HCID 67703941, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

6-Propylthio-9H-purine (0.50 g, 2.6 mmoles) (Alfred Bader Division of Aldrich Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in 500 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 4 days, 175 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 (9:1). The product was then further chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (98:2). Solvent was removed and lyophilization yielded 0.27 g of 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-propylthio-9H-purine (39%): mp 85°-86° C.; TLC Rf 0.87 (silica gel, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -20.2° (c=0.5, DMF): UV λmax (ε×103-) at pH 7, 293 (20.0); at pH 13, 292 (20.4); 1H NMR (300 MHz, DMSO-d6) δ8.74 and 8.68 (2s, 2H, H2 and H8), 6.48 (dd, 1H, H1', J=9.0 Hz, J=5.8 Hz), 5.46 (dd, 1H, H3', J=53.4 Hz, J=4.2 Hz), 5.21 (t, 1H, OH5', J=5.6 Hz), 4.26 (dt, 1H, H4', J=26.2 Hz, J=4.8 Hz), 3.59-3.62 (m, 2H, H5' and H5"), 3.25 (b, 2H, SCH2CH2CH3), 2.95-3.20 and 2.62-2.80 (2m, 2H, H2' and H2"), 1.69-1.76 (m, 2H, SCH2CH2CH3) and 1.00 (t, 3H, SCH2CH2CH3, J=7.4 Hz); MS (ci) 313 (M+1), 293 (M-F), 195 (MH2 --C5H8FO2).

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 (9:1)
  7. customThe product was then further chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (98:2)
  8. customSolvent was removed

Sources & evidence

ORD record
ord-6ccbee84f67242dbbb1debbae1cd474b
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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