ChEBI: A cephalosporin compound having [(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl and [(3,5-dichloro-4-oxopyridin-1(4H)-yl)acetamido side-groups.
A solution of 1 eq. of the tert-butyl ester of 7-aminocephalosporanic acid and
1 eq. of dicyclohexylcarbodiimide in 100 ml of methylene chloride/DMF (1:1)
is cooled to 0°C. The mixture is combined with 1 eq. of 3,5-dichloro-4-
pyridone-1-acetic acid; after 5 min the ice bath is removed and the mixture
agitated for another 30 min at 25°C. The thus-formed urea is filtered off and
the filtrate filtered over silica gel (eluent: ethyl acetate/1% methanol). The
solvent is concentrated by evaporation, and the thus-obtained tert-butyl ester
of 7-(3,5-dichloro-1,4-dihydro-4-oxo-1-pyridylacetamido)cephalosporanic acid
is crystallized from ether.
1 eq. of the tert-butyl ester is dissolved in 30 ml of trifluoroacetic acid. After
30 minutes, the solution is evaporated and the thus-produced 7-(3,5-dichloro-
1,4-dihydro-4-oxo-1-pyridylacetamido)cephalosporanic acid crystallized from
ether.
1 eq. of the obtained 7-(3,5-dichloro-1,4-dihydro-4-oxo-1-pyridylacetamido)
cephalosporanic acid is dissolved in 60 ml of saturated aqueous sodium
bicarbonate solution at a pH of below 7 and combined with 1 eq. of 5-methyl-
1,3,4-thiadiazole-2-thiol in 20 ml of acetone. The reaction solution is agitated
for 2 hours at 80°C and at a pH of 6.3 under a nitrogen atmosphere. The
acetone is thereupon removed, the solution is washed with ether and acidified
to pH 2. The thus-obtained 3-(1-methyltetrazolyl-5-mercaptomethyl)-7-(3,5-
dichloro-1,4-dihydro-4-oxo-1-pyridylacetamido)-3-cephem-4-carboxylic acid is
filtered off and dried. IR spectrum confirmed the structure of cefazedone.
In practice it is usually used as sodium salt.
