Thymidine → HCID 67703975, compound

HRID 1376468Notes

Reaction equation

HRID 1376468 reaction equation
[CH2:1]([NH:4][C:5]1[N:13]=[C:12]([NH2:14])[N:11]=[C:10]2[C:6]=1[N:7]=[CH:8][NH:9]2)[CH:2]=[CH2:3].[F:15][C@@H:16]1[C@@H:20]([CH2:21][OH:22])[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>[CH2:1]([NH:4][C:5]1[N:13]=[C:12]([NH2:14])[N:11]=[C:10]2[C:6]=1[N:7]=[CH:8][N:9]2[C@@H:18]1[O:19][C@H:20]([CH2:21][OH:22])[C@@H:16]([F:15])[CH2:17]1)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178456874HCID 178456874, compound

Product 1

HCID 67703975HCID 67703975, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

6-(Allylamino)-2-amino-9H-purine (0.51 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 0.40% 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 7 days, 100 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 were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone:methanol (96:2:2). Solvent was removed and lyophilization yielded 0.314 g of 6-(allylamino)-2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (46%): mp 128°-129° C.; TLC Rf 0.70 (silica gel, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -15.2 (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 281 (14.7); at pH 13, 281 (14.0); 1H NMR (300 MHz, DMSO-d6) δ7.91 (s, 1H, H8), 7.44-7.48 (b, 1H, NH), 6.20 (dd, 1H, H1', J=9.3 Hz, J=5.6 Hz), 5.82-5.95 (M, 3H), 5.51 (t, 1H, OH5', J=5.8 Hz), 5.38 (dd, 1H, H3', J=53.7 Hz, J=4.3 Hz), 5.03-5.14 (m, 2H), 4.25 (dt, 1H, H4', J=27.4 Hz, J=4.5 Hz), 4.0-5.05 (b, 2H, NCH2), 3.57 (t, 2H, H5', and H5", J=5.0 Hz), and 2.75-3.00 and 2.45-2.62 (m, 2H, H2' and H2" ; MS (ci) 309 (M+1), 289 (M-F), 191 (MH2 --C5H8FO2).

Workup

  1. additionwas added
  2. additioncontaining AG1-X2 (OH-- form, 2.5×10 cm)
  3. washeluted with MeOH
  4. additionFractions containing
  5. concentrationconcentrated
  6. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone:methanol (96:2:2)
  7. customSolvent was removed

Sources & evidence

ORD record
ord-78b98f534540484ea4ea923e5da7d592
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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