Thymidine → HCID 15693485, compound

HRID 1376457Notes

Reaction equation

HRID 1376457 reaction equation
[CH3:1][N:2]([CH3:12])[C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][NH:7]2.[F:13][C@@H:14]1[C@@H:18]([CH2:19][OH:20])[O:17][C@@H:16](N2C=CC(=O)NC2=O)[CH2:15]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:13][C@@H:14]1[C@@H:18]([CH2:19][OH:20])[O:17][C@@H:16]([N:7]2[CH:6]=[N:5][C:4]3[C:8]2=[N:9][CH:10]=[N:11][C:3]=3[N:2]([CH3:12])[CH3:1])[CH2:15]1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178483060HCID 178483060, compound

Product 1

HCID 15693485HCID 15693485, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

6-Dimethylamino-9H-purine (0.42 g, 2.6 mmoles), (Aldrich Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 moles) 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 6 days, 172 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 (92:8). Solvent was removed and lyophilization yielded 0.341 g of 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-dimethylamino-9H-purine (55%): mp 105°-107° C.; [α]D20 -23.3 (c=0.52, DMF); UV λmax (ε×10-3) at pH 7, 275 (25.1); at pH 13, 274 (18.4); 1H NMR (300 MHz, DMSO-d6) δ8.35 and 8.20 (2s, 2H, H2 and H8), 6.40 (dd, 1H, H1', J=9.3 Hz, J=5.6 Hz), 5.46 (t, 1H, OH5', J=5.7 Hz), 5.43 (dd, 1H, H3', J=53.8 Hz, J=4.5 Hz), 4.22 (dt, 1H, H4', J=27.1 Hz, J=4.4 Hz), 3.58-3.61 (m, 2H, H5' and H"), 3.43 (b, 6H, CH3NCH3), and 2.82-3.10 and 2.55-2.70 (m, 2H, 2' and H2"); MS (ci) 282 (M+1), 262 (M-F), 164 (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 (92:8)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-3ec4a95d82c44d75848eb2de39a3b4d8
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

Loading…