Thymidine → HCID 178521290, compound

HRID 1376472Notes

Reaction equation

HRID 1376472 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4](NCCO)[N:3]=1.F[C@@H]1[C@@H](CO)[O:19][C@@H:18](N2C=CC(=O)NC2=O)[CH2:17]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>[OH:19][CH2:18][CH2:17][NH:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178508751HCID 178508751, compound

Product 1

HCID 178521290HCID 178521290, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-((2-hydroxyethyl)amino)-9H-purine (0.55 g, 2.6 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) 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 and the suspension was stirred at 45° C. After 18 days, 150 ml MeOH was added to the reaction mixture. The resulting mixture 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:acetone (96:2:2). Solvent was removed and lyophilization yielded 0.14 g of 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-((2-hydroxyethyl)amino-9H-purine (19%): mp 144° C.; [α]D20 -29.4° C. (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 282 (12.0); at pH 13, 281 (13.213.9); 1H NMR (300 MHz, DMSO-d6) δ7.93 (s, 1H, H8), 7.14 (b, 1H, NH), 6.21 (dd, 1H, H1', J=9.4 Hz, J=5.6 Hz), 5.85 (bs, 2H, NH2), 5.30-5.35 (m, 2H, OH5' and H3'), 4.74 (b, 1H, OH), 4.18 (dt, 1H, H4', J=27.1 Hz, J=4.4 Hz), 3.42-3.62 (b, 6H, H, H5',H5", NCH2CH2O), 2.76-3.01 and 2.49-2.63 (m, 2H, H2' and H2"); MS (ci) 313 (M+1), 293 (M-F), 195 (MH2 --C5H8FO2).

Workup

  1. additionwas added
  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:acetone (96:2:2)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-91943ab22a4d4391ac9eecca0aacbc26
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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