Uridine → 9-beta-D-arabinofuranosyl-6-ethyl(methyl)amino-9H-purine

HRID 21503

Reaction equation

HRID 21503 reaction equation
[CH2:1]([C:3]1[N:11]=[C:10]([NH:12][CH3:13])[N:9]=[C:8]2[C:4]=1[NH:5][CH:6]=[N:7]2)[CH3:2].C1C(=O)NC(=O)N([C@@H:22]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@@H:23]2[OH:30])C=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=CC(=O)NC2=O)O[C@H](CO)[C@@H](O)[C@H]1O>C(#N)C.C(O)CC>[CH2:1]([C:3]1[N:11]=[C:10]([NH:12][CH3:13])[N:9]=[C:8]2[C:4]=1[NH:5][CH:6]=[N:7]2)[CH3:2].[C@@H:22]1([N:7]2[CH:6]=[N:5][C:4]3[C:8]2=[N:9][C:10]([NH:12][CH3:13])=[N:11][C:3]=3[CH2:1][CH3:2])[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@@H:23]1[OH:30]

Participants

9

Reactant 5

HCID 6029UridineHCID 18323Uracil ArabinosideHCID 62657Potassium Phosphate, TribasicHCID 10290740Potassium azideHCID 194347436-Ethyl(methyl)aminopurine

Product 2

HCID 194347436-Ethyl(methyl)aminopurineHCID 677833739-beta-D-arabinofuranosyl-6-ethyl(methyl)amino-9H-purineYield 157%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
37 °C

Procedure

6-Ethyl(methyl)aminopurine was prepared by nucleophilic displacement of the chlorine group on 6-chloropurine (Sigma Chemicals, St. Louis, Mo.) by ethylo(methyt)amine in acetonitrile. 6-Ethyl(methyl)aminopurine (2.8 mmoles, 0.5 g) and uracil arabinoside (5.6 mmoles, 1.38 g) were suspended in 575 ml of a 10 mM potassium phosphate, 0.04% potassium azide solution, pH of 7.4, containing 10% n-propanol (v/v). Purified uridine phosphorylase (6000 I.U.) and purine nucleoside phosphorylase (8400 I.U.) (Krenitsky, T. A. et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) were added and the solution stirred at 37° C. Nineteen days later the reaction was filtered and the filtrate chromatographed on a 2.5×13 cm column containing Dowex-1-hydroxide resin. The resin was eluted with 90% methanol/water (v/v). Fractions containing the product were combined and the solvent removed under vacuum. The residue was dissolved in 30% n-propanol/water (v/v) and chromatographed on BioRad P-2 column (7.5×90 cm). Product containing fraction were combined and after lyophilization yielded 0.680 g of 9-β-D-arabinofuranosyl-6-ethyl(methyl)amino-9H-purine. NMR and mass spectrometry were consistent with the structure. Anal. Calcd. for C13H19N5O4 : Calcd: C,50.48; H,6.19; N,22.64. Found: C,50.36; H,6.25; N,22.52.

Workup

  1. addition4,381,344) were added
  2. filtrationNineteen days later the reaction was filtered
  3. customthe filtrate chromatographed on a 2.5×13 cm column
  4. additioncontaining Dowex-1-hydroxide resin
  5. washThe resin was eluted with 90% methanol/water (v/v)
  6. additionFractions containing the product
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in 30% n-propanol/water (v/v)
  9. customchromatographed on BioRad P-2 column (7.5×90 cm)
  10. additionProduct containing fraction

Sources & evidence

ORD record
ord-be38f18f1a8e47958be83d10fe34bb13
Source dataset
uspto-grants-1995_06
Patent number
US05424295

Linked notes

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