Succinic anhydride → HCID 53963029, compound

HRID 982162

Reaction equation

HRID 982162 reaction equation
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]([NH:16][C:15]1[CH:17]=[CH:18][N:11]([C@@H:4]2[O:5][C@H:6]([CH2:9][OH:10])[C@@H:7]([OH:8])[C:3]2([F:2])[F:19])[C:12](=[O:13])[N:14]=1)=[O:26])([OH:25])=[O:24]

Participants

4

Reactant 2

HCID 7922Succinic anhydrideHCID 60749Gemcitabine Hydrochloride

Product 1

HCID 53963029HCID 53963029, compoundYield 105.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Two hundred mg of 2'-deoxy-2',2'-difluorocytidine, hydrochloride, was dissolved in 2 ml of pyridine, and then 134 mg of succinic anhydride was added. The mixture was stirred at ambient temperature for 1.25 hours, and was then concentrated under vacuum. The residue was dissolved in dichloromethane/methanol, and the solution was absorbed on 1.5 g of silica gel, which was then slurried in dichloromethane and loaded on a 4 g silica gel column. The column was eluted with a gradient solvent, starting with dichloromethane and ending with methanol. The product-containing fractions were combined and freeze-dried overnight to obtain 255 mg of product mixture. It was dissolved in 3 ml of 0.01M ammonium acetate, and was chromatographed on a 22 ml mono-Q fast flow column (Pharmacia Inc.), eluting with the ammonium acetate gradient buffer which has previously been described. Evaporation of the product-containing fractions gave 81 mg of a mixture of the mono-acylated products named in the heading.

Workup

  1. concentrationwas then concentrated under vacuum
  2. dissolutionThe residue was dissolved in dichloromethane/methanol
  3. customthe solution was absorbed on 1.5 g of silica gel, which
  4. washThe column was eluted with a gradient solvent
  5. customfreeze-dried overnight

Sources & evidence

ORD record
ord-7d004f8fccf74db4998e6c80989ff5f4
Source dataset
uspto-grants-1991_02
Patent number
US04994558

Linked notes

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