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

HRID 37090

반응식

HRID 37090 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+].[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

참가 물질

7

반응물 5

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

생성물 1

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

시약·촉매·용매 1

HCID 62657Potassium Phosphate, Tribasic용매

반응 조건

온도
37 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fdcf9504610c4ef1ad9d8a836d174eef
출처 데이터셋
uspto-grants-1995_05
특허 번호
US05420115

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