Succinic anhydride → 5'-O-(3-Carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine

HRID 982160

Reaktionsgleichung

Reaktionsgleichung von HRID 982160
[F:1][C:2]1([F:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]1=[O:12].[C:19]1(=[O:25])[O:24][C:22](=[O:23])[CH2:21][CH2:20]1>C(O)C>[C:22]([CH2:21][CH2:20][C:19]([O:9][CH2:8][C@H:5]1[O:4][C@@H:3]([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[C:2]([F:1])([F:18])[C@@H:6]1[OH:7])=[O:25])([OH:24])=[O:23]

Komponenten

4

Edukt 2

HCID 7922Succinic anhydrideHCID 60750Gemcitabine

Produkt 1

HCID 98204035'-O-(3-Carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

Dry 2'-deoxy-2',2'-difluorocytidine (311 mg) was added to dry ethanol and brought to reflux. Succinic anhydride (2.5 g) was added in portions over a half hour period and the mixture was refluxed an additional 1/2 hour. The mixture was concentrated in vacuo and the resulting crude product was placed on a silica gel column and eluted with a step gradient of 5%, 20%, and 50% methanol in methylene chloride. The desired product was isolated in the 50% methanol in methylene chloride wash and contained 148 mg of material. This product was combined with product from a similar experiment providing a total of 253 mg of material. This material was taken up in 8 ml of 0.01M ammonium acetate solution. The pH was adjusted with ammonium hydroxide to 8.6 and the solution placed on a freshly packed mono-Q anion exchange column (Pharmacia Inc., 800 Centennial Avenue, Piscataway, N.J. 08854). Desired fractions were combined, frozen, and lyophilized. The residue was dissolved in distilled water, frozen, and lyophilized several more times, then dissolved in a small amount of methanol and benzene, frozen, and lyophilized providing 60 mg of the desired title product. The proton NMR spectra was consistent with the structure of the desired product:

Aufarbeitung

  1. temperatureto reflux
  2. temperaturethe mixture was refluxed an additional 1/2 hour
  3. concentrationThe mixture was concentrated in vacuo
  4. washeluted with a step gradient of 5%, 20%, and 50% methanol in methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-6d3600d283e14f7dbc71ff60431e799a
Quelldatensatz
uspto-grants-1991_02
Patentnummer
US04994558

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