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

HRID 37090

反応式

HRID 37090 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([O: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+].[OH-].[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+]>[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]([O:11][CH3:12])[N:3]=1

参加物

7

反応物 5

HCID 5789ThymidineHCID 14797Potassium HydroxideHCID 65275O-(6)-MethylguanineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide

生成物 1

HCID 98827462-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-methoxy-9H-purine収率 84.5%

試薬・触媒・溶媒 1

HCID 62657Potassium Phosphate, Tribasic溶媒

反応条件

温度
37 °C

実験手順

2-Amino-6-methoxypurine (2.0 g, 12 mmoles) which may be prepared according to R. W. Balsiger and J. A. Montgomery (J. Org. Chem. 20:1573, 1960) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.88 g; 3.6 mmoles) which may be prepared according to J. F. Codington et al., (J. Org. Chem. 29:558, 1964) were suspended in 250 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. The pH of the suspension was adjusted to 7.0 with KOH. Thymidine phosphorylase (41,700 I.U.) and purine nucleoside phosphorylase (83.300 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) which had been absorbed onto 10.5 g of DEAE-cellulose (25 ml) were added and the suspension shaken at 37° C. After 24 hours 1.0 g of 2-amino-6-methoxypurine and 250 ml of the above buffer were added and the temperature increased to 50° C. After another 24 hours the reaction was filtered. The filter cake was washed with water and the filtrates combined and the solvent removed under vacuum. The residue was dissolved in warm water and the pH adjusted to pH 9.4 with NH4OH. The solution was applied to a 2.5×15 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing the column with water, the product was eluted with methanol/water (9/1). Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in warm water/methanol and filtered through a 0.22 μm-pore nylon membrane filter. Lyophilization of the filtrate yielded 0.91 g of title compound that analyzed as a 0.5 hydrate.

後処理

  1. custom4,381,344) which had been absorbed onto 10.5 g of DEAE-cellulose (25 ml)
  2. additionwere added
  3. additionAfter 24 hours 1.0 g of 2-amino-6-methoxypurine and 250 ml of the above buffer were added
  4. temperaturethe temperature increased to 50° C
  5. filtrationAfter another 24 hours the reaction was filtered
  6. washThe filter cake was washed with water
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in warm water
  9. washAfter washing the column with water
  10. washthe product was eluted with methanol/water (9/1)
  11. additionProduct containing fractions
  12. customthe solvent removed under vacuum
  13. dissolutionThe residue was dissolved in warm water/methanol
  14. filtrationfiltered through a 0.22 μm-pore nylon membrane
  15. filtrationfilter

出典と根拠

ORDレコード
ord-fdcf9504610c4ef1ad9d8a836d174eef
出典データセット
uspto-grants-1995_05
特許番号
US05420115

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