Thymidine → 2-amino-6-cyclobutoxy-9-(2,3-dideoxy-3-fluoro-beta-D-erythropentofuranosyl)-9H-purine

HRID 1683182Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([O:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)[N:3]=1.[F:16][C@@H:17]1[C@@H:21]([CH2:22][OH:23])[O:20][C@@H:19](N2C=CC(=O)NC2=O)[CH2:18]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:19]2[O:20][C@H:21]([CH2:22][OH:23])[C@@H:17]([F:16])[CH2:18]2)=[C:4]([O:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)[N:3]=1

Participants

Conditions

Temperature: 45 °C

Procedure

2-Amino-6-cyclobutoxy-9H-purine (0.50 g, 2.4 mmoles) and 2'3'-dideoxy-3'-fluorouridine (0.67 g, 2.9 mmoles) were suspended in potassium phosphate buffer (50 ml, 10 mM), pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 8 days, MeOH (150 ml) 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 (92:8) as eluant. Solvent was removed and lyophilization yielded 0.57 g of 2-amino-6-cyclobutoxy-9-(2,3-dideoxy-3-fluoro-β-D-erythropentofuranosyl)-9H-purine (70%): mp 139°-140° C.;

Workup

additionwas added to the reaction
additioncontaining AG1-X2 (OH- form, 2.5×10 cm)
washeluted with MeOH
additionFractions containing product
concentrationconcentrated
customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8) as eluant
customSolvent was removed

Sources & evidence

ORD record: ord-f6981e87c6774d6b93e7fd44e53760bb
Source dataset: uspto-grants-1997_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05637574

Reaction notes

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