Thymidine → HCID 86751194, compound

HRID 1376463Notes

Reaction equation

HRID 1376463 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][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1.[F:19][C@@H:20]1[C@@H:24]([CH2:25][OH:26])[O:23][C@@H:22](N2C=CC(=O)NC2=O)[CH2:21]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:22]2[O:23][C@H:24]([CH2:25][OH:26])[C@@H:20]([F:19])[CH2:21]2)=[C:4]([S:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178509036HCID 178509036, compound

Product 1

HCID 86751194HCID 86751194, compoundYield 21.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-benzylmercapto-9H-purine (0.70 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 6.8, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 2 days, 200 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:methanol (95:5). Fractions containing products were pooled, concentrated, and further chromatographed on silica gel (2.5×20 cm) with ethyl acetate:hexane (1:1). Solvent was removed and lyophilization yielded 0.175 g of 2-amino-6-benzylmercapto-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (21%): mp 150°-151° C.; [α]D20 -20.8 (c=0.50 DMF); UV λmax (ε×10-3) at pH 7, 247 (14.0) and 312 (14.0); at pH 13, 247 (13.6) and 312 (13.8); 1H NMR (300 MHz, DMSO-d6) δ8.18 (s, 1H, 8), 7.47 and 7.27 (2m, 5H, C6H5), 6.83 (b, 2H, NH2), 6.26 (dd, 1H, H1', J=9.2 Hz, J=5.8 Hz), 5.42 (dd, 1H, H3', J=53.7 Hz, J=4.3 Hz), 5.17 (t, 1H, OH5', J=5.6 Hz), 4.55 (s, 2H, SCH2), 4.18 (dt, 1H, H4', J=26.7 Hz, J=4.9 Hz), 3.57 (t, 2H, H5' and H5", J=5.2 Hz), 2.91 and 2.62 (2m, 2H, H2', and H2"); MS (ci) 376 (M+1), 356 (M-F), 258 (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:methanol (95:5)
  7. additionFractions containing products
  8. concentrationconcentrated
  9. customfurther chromatographed on silica gel (2.5×20 cm) with ethyl acetate:hexane (1:1)
  10. customSolvent was removed

Sources & evidence

ORD record
ord-206487e6bbe94cd98efd07e3b1c6ae9a
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

Loading…