Thymidine → 2-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-methylthio-9H-purine

HRID 37084Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([S:11][CH3:12])[N:3]=1.[F:13][C@@H:14]1[C@H:18]([OH:19])[C@@H:17]([CH2:20][OH:21])[O:16][C@H:15]1N1C=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1.[OH-].[K+]>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:15]2[O:16][C@H:17]([CH2:20][OH:21])[C@@H:18]([OH:19])[C@H:14]2[F:13])=[C:4]([S:11][CH3:12])[N:3]=1

Participants

Conditions

Temperature: 37 °C

Procedure

2-Amino-6-methylthiopurine (Sigma Chemical Company; 0.6 g, 3.3 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.3 g, 1.2 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 200 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (4,000 I.U.) and purine nucleoside phosphorylase (6,500 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) were added and the suspension stirred at 37° C. On day 14, the reaction was diluted to 400 ml with 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide and 8,000 I.U. thymidine phosphorylase and 6,500 I.U. purine nucleoside phosphorylase were added. On day 25, the pH of the reaction was adjusted to 6.9 with KOH. On day 39, the reaction was filtered. The filtrate was applied to a 2.5×13 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form) and the product was eluted with methanol/water (3/7). After the solvent was removed under vacuum, the residue was suspended in water and lyophilized to obtain title compound that analyzed as a 0.5 hydrate.

Workup

addition4,381,344) were added
waitOn day 14
waitOn day 25
waitOn day 39
filtrationthe reaction was filtered
washthe product was eluted with methanol/water (3/7)
customAfter the solvent was removed under vacuum

Sources & evidence

ORD record: ord-fc8ccdfdef164b638543f66f15d709e1
Source dataset: uspto-grants-1995_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05420115

Reaction notes

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