Thymidine → HCID 67703987, compound

HRID 1376465Notes

Reaction equation

HRID 1376465 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][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[N:3]=1.[F:18][C@@H:19]1[C@@H:23]([CH2:24][OH:25])[O:22][C@@H:21](N2C=CC(=O)NC2=O)[CH2:20]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:21]2[O:22][C@H:23]([CH2:24][OH:25])[C@@H:19]([F:18])[CH2:20]2)=[C:4]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178444749HCID 178444749, compound

Product 1

HCID 67703987HCID 67703987, compoundYield 61.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-hexylamino-9H-purine (0.63 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 to the reaction and the suspension was stirred at 45° C. After 9 days, 150 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:methanol/97:2:1. Solvent was removed and lyophilization yielded 0.48 g of 2-amino-9(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-hexylamino-9H-purine (61%): mp 50°-51° C.; TLC Rf 0.86 (silica gel, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -13.2° (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 281 (15.4); at pH 13, 281 (15.4); 1H NMR (400 MHz, DMSO-d6) δ7.89 (s, 1H, H8), 7.30 (b, 1H, NH), 6.19 (dd, 1H, H1', J=9.7 Hz, J=5.6 Hz), 5.77 (b, 2H, NH2), 5.56 (m, 1H, OH5'), 5.38 (dd, 1H, H3', J=53.7 Hz, J=4.2 Hz), 4.17 (dm, 1H, H4', J=27.5 Hz, 3.57 (t, 2H, H5' and H5", J=5.0 Hz, 3.35 (b, 2H, NCH2CH2 (CH2)3CH3), 2.78-2.97 and 2.47-2.60 (m, 2H, H2, and H2") 1.52 (m, 2H, NCH2CH2 (CH2)3CH3), 1.27 (b, 6H, NCH2CH2 (CH2)3CH3), and 0.84 (t, 3H, NCH2CH2 (CH2)3CH3, J=6.8 Hz); MS (ci) 353 (M+1), 333 (M-F), 235 (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
  7. customSolvent was removed

Sources & evidence

ORD record
ord-9080a2461f804a54a578171814902991
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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