5-Fluorouracil → 1-(Pyridine-3-carbonyloxymethyl)-5-fluorouracil

HRID 359897Notes

Reaction equation

HRID 359897 reaction equation
[CH:1]1[NH:8][C:6](=[O:7])[NH:5][C:3](=[O:4])[C:2]=1[F:9].C(N(CC)CC)C.[C:17]([O:25][CH2:26]Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1>CC(N(C)C)=O>[N:20]1[CH:21]=[CH:22][CH:23]=[C:18]([C:17]([O:25][CH2:26][N:8]2[CH:1]=[C:2]([F:9])[C:3](=[O:4])[NH:5][C:6]2=[O:7])=[O:24])[CH:19]=1

Participants

5

Reactant 3

HCID 33855-FluorouracilHCID 8471TriethylamineHCID 14608830Chloromethyl nicotinate

Product 1

HCID 131323931-(Pyridine-3-carbonyloxymethyl)-5-fluorouracil

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

5-FU (1.31 g, 0.01 mol) was dissolved in 5 mL of dimethylacetamide and treated with triethylamine (2.78 mL, 0.02 mol). Chloromethyl nicotinate (2.95 g, 0.012 mol) in 5 mL of dimethylacetamide was added in one portion, and the mixture was stirred for 24 hours, filtered, washed with ethyl acetate and evaporated. The residue was chromatographed on a column of silica gel, using as eluent first benzene, then 3:1 benzene/chloroform, then 1:1 benzene/chloroform, then 3:1 chloroform/benzene, then chloroform and finally 99:1 chloroform/methanol. Unreacted nicotinate was eluted initially, followed by the 1,3-bis-isomer and finally the 1-isomer. The 1-isomer (1.3 g, 50%) melted at 190°-192° C. and had the formula ##STR159## as confirmed by NMR analysis.

Workup

  1. filtrationfiltered
  2. washwashed with ethyl acetate
  3. customevaporated
  4. customThe residue was chromatographed on a column of silica gel
  5. washwas eluted initially

Sources & evidence

ORD record
ord-ec2d8cc723814259ad794f4adde99f27
Source dataset
uspto-grants-1991_03
Patent number
US05002935

Reaction notes

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