Synthesis of [carbonyl-14C]sparfloxacin

A new antimicrobial quinolone, sparfloxacin (5-amino-1-cyclopropyl-7- (cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline -3- carboxylic acid, AT-4140; CAS 110871-86-8), was labeled by 14C for studies of disposition and metabolism. Ethyl pentafluoro[carbonyl-14C]benzoylacetate (I) was reacted with ethyl orthoformate, cyclopropylamine and then potassium tert-butoxide to give a quinolone intermediate (IV). A benzylamino derivative (V) obtained by condensation of IV and benzylamine was subject to catalytic hydrogenolysis and hydrolyzed to give the carboxyl derivative (VII), which was condensed with cis-2,6-dimethylpiperazine to form [carbonyl-14C]sparfloxacin. The average yield of 3 preparations was 41.5% and specific activities were 310.8-366.3 MBq (8.4-9.9 mCi)/mmol. Both chemical and radiochemical purities were greater than 99%.