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

HRID 37073

반응식

HRID 37073 반응식
[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+].[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

참가 물질

6

반응물 4

HCID 5789Thymidine2회HCID 65275O-(6)-MethylguanineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide3회

생성물 1

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

시약·촉매·용매 1

HCID 62657Potassium Phosphate, Tribasic용매3회

반응 조건

온도
37 °C

실험 절차

2-Amino-6-methoxypurine (0.8 g, 4.8 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 (0.4 g, 1.6 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 20 ml of 10 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (2,400 I.U.) and purine nucleoside phosphorylase (3,900 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 6, the reaction was diluted to 100 ml with 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. On day 10, the reaction was diluted to 200 ml with 5 mm potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. On day 16, 2,640 I.U. of thymidine phosphorylase and 4,360 I.U. of purine nucleoside phosphorylase were added. On day 24, the reaction was filtered and the filtrate was evaporated. The residue was suspended in methanol. The suspension was filtered and the filtrate evaporated. The residue was dissolved in water and applied to a 2.5×7 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). After the solvent was removed under vacuum, the residue was dissolved in water and lyophilized to obtain title compound which analyzed as a 0.5 hydrate.

후처리

  1. addition4,381,344) were added
  2. waitOn day 6
  3. waitOn day 10
  4. waitOn day 16, 2,640 I.U
  5. waitOn day 24
  6. filtrationthe reaction was filtered
  7. customthe filtrate was evaporated
  8. filtrationThe suspension was filtered
  9. customthe filtrate evaporated
  10. dissolutionThe residue was dissolved in water
  11. washAfter washing the column with water
  12. washthe product was eluted with methanol/water (9/1)
  13. customAfter the solvent was removed under vacuum
  14. dissolutionthe residue was dissolved in water

출처 및 근거

ORD 기록
ord-0de01bdf3c3c4f4ebdb71e4b467ed52e
출처 데이터셋
uspto-grants-1995_05
특허 번호
US05420115

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