2'Fluoro-2'-deoxyuridine → 5,6-Dichloro-1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)benzimidazole

HRID 356990

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HRID 356990 반응식
[F:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1N1C=CC(=O)NC1=O.[Cl:18][C:19]1[C:27]([Cl:28])=[CH:26][C:22]2[N:23]=[CH:24][NH:25][C:21]=2[CH:20]=1>C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O>[Cl:28][C:27]1[C:19]([Cl:18])=[CH:20][C:21]2[N:25]([C@@H:3]3[O:4][C@H:5]([CH2:8][OH:9])[C@@H:6]([OH:7])[C@H:2]3[F:1])[CH:24]=[N:23][C:22]=2[CH:26]=1

참가 물질

4

반응물 2

HCID 1508512'Fluoro-2'-deoxyuridineHCID 3317755,6-Dichloro-1H-benzimidazole2회

생성물 1

HCID 106635385,6-Dichloro-1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)benzimidazole수율 67%

시약·촉매·용매 1

HCID 31348Citrate용매

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온도
80 °C

실험 절차

2'-Deoxy-2'-fluorouridine, compound 13 (0.99 g, 4 mmol), which can be prepared by the method of Codington et al. (Codington et al., 1968), was dissolved in 800 mL of 50 mM pH 6.0 citrate buffer. 5,6-dichlorobenzimidazole, compound 14 (0.30g, 1.6 mmoles), which can be prepared by the method of Townsend et al. (Townsend et al., 1970), was added and the reaction was placed in a 50° C. water bath. N-deoxyribo-furanosyl transferase (60,000 units; see Cook et al., 1990) was added and the reaction mixture was gently shaken overnight. 5,6-dichlorobenzimidazole, compound 14 (0.30 g, 1.6 mmoles) was added and the reaction continued for 2 days. The enzyme was precipitated by heating to 80° C. followed by cooling to room temperature. Celite® (50-60 g) was added and the reaction mixture filtered. The product was extracted with ethyl acetate (3×). The ethyl acetate was removed in vacuo and the residue purified by chromatography on 75 g of basic alumina eluted with chloroform/methanol (95:5, v/v) followed by (9:1, v/v), then (2:1, v/v), and finally (1:1, v/v). The product containing fractions were combined and the solvents removed in vacuo to give 0.54 g (67%) of compound 15.

후처리

  1. additionwas added
  2. customwas placed in a 50° C.
  3. additionN-deoxyribo-furanosyl transferase (60,000 units; see Cook et al., 1990) was added
  4. waitthe reaction continued for 2 days
  5. customThe enzyme was precipitated
  6. temperatureby cooling to room temperature
  7. additionCelite® (50-60 g) was added
  8. filtrationthe reaction mixture filtered
  9. extractionThe product was extracted with ethyl acetate (3×)
  10. customThe ethyl acetate was removed in vacuo
  11. customthe residue purified by chromatography on 75 g of basic alumina
  12. washeluted with chloroform/methanol (95:5
  13. additionThe product containing fractions
  14. customthe solvents removed in vacuo

출처 및 근거

ORD 기록
ord-a8db238572a74333acdcc02875b00c34
출처 데이터셋
uspto-grants-1998_11
특허 번호
US05840743

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