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

HRID 1194486

Reaktionsgleichung

Reaktionsgleichung von HRID 1194486
Cl.[F:2][C:3]1([F:19])[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]1=[O:13].[C:20]1(=[O:26])[O:25][C:23](=[O:24])[CH2:22][CH2:21]1>N1C=CC=CC=1>[C:23]([CH2:22][CH2:21][C:20]([O:10][CH2:9][C@H:6]1[O:5][C@@H:4]([N:11]2[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]2=[O:13])[C:3]([F:2])([F:19])[C@@H:7]1[OH:8])=[O:26])([OH:25])=[O:24]

Komponenten

4

Edukt 2

HCID 7922Succinic anhydrideHCID 60749Gemcitabine Hydrochloride

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Versuchsvorschrift

A 600 mg portion of dry 2'-deoxy-2',2'-difluorocytidine, hydrochloride, was added to 6 ml of dry pyridine, and 804 mg of succinic anhydride was added. The reaction mixture was stirred at ambient temperature for 1.5 hours. The mixture was then concentrated to an oil under vacuum, and the oil was stored overnight in the freezer. It was then allowed to stand at ambient temperature for 4 hours, and was chromatographed over a 500 ml Q-Sepharose column (Pharmacia Inc.). The oil was dissolved in 6 ml of 0.1M ammonium acetate buffer, and was passed over the column, eluting with a gradient buffer which changed from 0.1M to 1.0M ammonium acetate, at pH 8.0 at all times. Analytical chromatography of the mixture on a small mono-Q column, showed the bisacylated and tris-acylated products were present, as well as mono-acylated product and a small amount of starting material. The product-containing fractions, amounting to about 200 ml, were placed in a 37° C. bath, for 68 hours. At the end of that time, the tris-acylated product has been decomposed and both mono- and bisacylated products were still present.

Aufarbeitung

  1. additionwas added
  2. concentrationThe mixture was then concentrated to an oil under vacuum
  3. waitthe oil was stored overnight in the freezer
  4. waitto stand at ambient temperature for 4 hours
  5. customwas chromatographed over a 500 ml Q-Sepharose column (Pharmacia Inc.)
  6. dissolutionThe oil was dissolved in 6 ml of 0.1M ammonium acetate buffer
  7. washeluting with a gradient buffer which
  8. customwere placed in a 37° C.
  9. waitfor 68 hours

Quellen und Nachweise

ORD-Eintrag
ord-22176d7625274ef5befbbdd8635ffddd
Quelldatensatz
uspto-grants-1989_03
Patentnummer
US04814438

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