2',3'-Dideoxy-3'-fluorouridine → HCID 67703950, compound

HRID 1376464Notes

Reaction equation

HRID 1376464 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][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+]>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[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]([NH:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:3]=1

Participants

5

Reactant 3

HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178508733HCID 178508733, compound

Product 1

HCID 67703950HCID 67703950, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-benzylamino-9H-purine (0.64 g, 2.7 mmoles) and 2',3'-dideoxy-3'-florouridine (0.50 g, 2.2 mmoles) were suspended in 50 ml 10 mM potassium phosphate buffer containing 0.04% potassium azide. After the pH was adjusted to 7.0, purified purine nucleoside phosphorylase (15,700 I.U.) and thymidine phosphorylase (4,000 I.U.) (Krenitsky, et al., Biochemistry, 20, 3615, 1981 and U.S. Pat. No. 4,381,344) were added to the reaction and the suspension was stirred at 45° C. After 24 hours, purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase immobilized onto 10 ml of DEAE-cellulose were added. After an additional two days, 150 ml of methanol was added to the reaction. The reaction was filtered through Celite and the filtrate was applied to an ionic exchange column (AG1-X2, 2.5×10 cm, OH-- form). After eluting the product with methano, fraction were combined and concentrated. The residue was then purified by flash chromatography on silica gel (5×20 cm column) with dichloromethane:methanol (95:5). Solvent was removed and lyophilization yielded 0.42 g of 2-amino-6-benzylamino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (54%): mp 90°-94° C.; [α]D20 -16.2 (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 282 (17.5); at pH13, 282 (17.7); 1H NMR (300 MHz, DMSO-d6) δ7.95 (s, 1H, H8), 7.93 (b, 1H, NH), 7.28 (m, 5H, C6H5), 6.23 (dd, 1H, H1', J=9.4 Hz, J=5.6 Hz), 5.87 (b, 2H, NH2), 5.54 (t, 1H, OH5', J=5.7 Hz), 5.40 (dd, 1H, H3', J=53.7 Hz, J=4.2 Hz), 4.68 (b, 2H, CH2), 4.19 (dt, 1H, H4', J=27.2 Hz, J=4.4 Hz), 3.60 (m, 2H, H5' and H5"), 2.90 and 2.58 (m, 2H, H2' and H2"); MS (ci) 359 (M+1), 339 (M-F), 241 (MH2 --C5H8FO2).

Workup

  1. custompurified purine nucleoside phosphorylase (15,700 I.U.) and thymidine phosphorylase (4,000 I.U.) (Krenitsky, et al., Biochemistry, 20, 3615, 1981 and U.S
  2. addition4,381,344) were added to the reaction
  3. additionwere added
  4. waitAfter an additional two days
  5. addition150 ml of methanol was added to the reaction
  6. filtrationThe reaction was filtered through Celite
  7. washAfter eluting the product with methano, fraction
  8. concentrationconcentrated
  9. customThe residue was then purified by flash chromatography on silica gel (5×20 cm column) with dichloromethane:methanol (95:5)
  10. customSolvent was removed

Sources & evidence

ORD record
ord-cf796e08469f4d9a9c7420915e08e28e
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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