Thymidine → HCID 67703972, compound

HRID 1376474Notes

Reaction equation

HRID 1376474 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][CH3:12])[N:3]=1.[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>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:16]2[O:17][C@H:18]([CH2:19][OH:20])[C@@H:14]([F:13])[CH2:15]2)=[C:4]([NH:11][CH3:12])[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178482427HCID 178482427, compound

Product 1

HCID 67703972HCID 67703972, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-methylamino-9H-purine (0.43 g, 2.6 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in 40 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 2 days, 100 m, 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 (96:4). Solvent was removed and lyophilization yielded 0.35 g of 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-methylamino-9H-purine (56%): mp 111° C.; TLC RfO. (silica gel, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -30.0 (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 280 (13.2); at pH 13, 280 (13.2); 1H NMR (300 MHz, DMSO-d6) δ7.91 (s, 1H, H8), 7.30 (b, 1H, NH), 6.22 (dd, 1H, H1', J=9.4 Hz, J=5.5 Hz), 5.85 (bs, 2H, NH2), 5.55 (t, 1H, OH5', J=5.3 Hz), 5.40 (dd, 1H, H3', J=53.7 Hz, J=4.0 Hz), 4.19 (dm, 1H, H4', J=27.5 Hz), 3.59 (t, 2H, H5' and H5", J=4.6 Hz), 2.82-2.96 and 2.50-2.61 (m, 5H, NCH3, H2' and 2"); MS (ci) 283 (M+1), 263 (M-F), 165 (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 (96:4)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-596e860481744c4f9dc4a6fde83f3dff
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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