Thymidine → HCID 86751193, compound

HRID 1376454Notes

Reaction equation

[CH2:1]([N:3]1[CH:11]=[N:10][C:9]2[C:4]1=[N:5][C:6]([NH:12][CH3:13])=[N:7][CH:8]=2)[CH3:2].[F:14][C@@H:15]1[C@@H:19]([CH2:20][OH:21])[O:18][C@@H](N2C=CC(=O)NC2=O)C1.[N-]=[N+]=[N-].[K+].[C@@H:34]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)[CH2:35]1>P([O-])([O-])([O-])=O.[K+].[K+].[K+].CO>[F:14][C@@H:15]1[C@@H:19]([CH2:20][OH:21])[O:18][C@@H:1]([N:3]2[CH:11]=[N:10][C:9]3[C:4]2=[N:5][C:6]([NH:12][CH3:13])=[N:7][C:8]=3[CH2:34][CH3:35])[CH2:2]1

Participants

Conditions

Temperature: 45 °C

Procedure

6 Ethylmethylamino-9H-purine (0.46 g, 2.6 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 moles) 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 6 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 (9:1). Solvent was removed and lyophilization yielded 0.323 g of 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-ethylmethylamino-9H-purine (50%): mp 99°-100° C.; TLC Rf 0.75 (silica gel, MeCN:15N NH4OH:H2O/85:5:10);

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 (9:1)
customSolvent was removed

Sources & evidence

ORD record: ord-4e3c31de414049b9b557090eb5bca3d4
Source dataset: uspto-grants-1997_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05663154

Reaction notes

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