Patent ID: 6229017
Filing Date: 2001-05-08
Classification: C07D

Abstract:
A process for preparing quinolone- and naphthyridonecarboxylic acids and esters thereof of the formula (I). ##STR9##whereinR.sup.1 comprises a component selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 -alkyl groups;R.sup.2 comprises a halogen group;R.sup.3 comprises a halogen group;R.sup.4 comprises a component selected from the group consisting of hydrogen, halogen and nitro groups;Y comprises a component selected from the group consisting of C.sub.1 -C.sub.6 alkyl, 2-fluoroethyl, cyclopropyl, fluorocyclopropyl, isopropyl, 4-fluorophenyl and 2,4-difluorophenyl groups; andA comprises a component selected from the group consisting of nitrogen, C--R.sup.6 groups, wherein R.sup.5 is selected from the group consisting of hydrogen, methyl, methoxy, halogen, nitro and cyano;the process comprising the steps of:a) acylating, in the presence of a base,(a) a benzoyl chloride or a nicotinoyl chloride of the formula (II) ##STR10##wherein R.sup.2, R.sup.3, R.sup.4 and A are each as defined under formula (I) and R.sup.6 comprises halogen;with (b) an aminoacrylic ester of the formula (III) ##STR11##wherein R.sup.1' comprises a component selected from the group consisting of C.sub.1 -C.sub.4 -alkyl groups; andZ.sup.1 and Z.sup.2 independently of one another each comprise a component selected from the group consisting of C.sub.1 -C.sub.4 -alkyl groups, C.sub.1 -C.sub.4 -alkyl groups together with a linking nitrogen atom forming a 5- to 6-membered saturated or unsaturated rings, said 5- to 6-membered saturated or unsaturated rings containing up to two further hetero groups selected from the group consisting of O and S atoms and a SO.sub.2 group;to produce a (het)-aroylacrylic ester of the formula (IV) ##STR12##wherein R.sup.1' comprises a component selected from the group consisting of C.sub.1 -C.sub.4 -alkyl groups and R.sup.2, R.sup.3, R.sup.4 and A each are as defined in formula (I), R.sup.6 is as defined under formula (II), and Z.sup.1 and Z.sup.2 are each as defined in formula (III);b) subjecting the (het)-aroylacrylic ester of the formula (IV) to an amine exchange with an amine of the formula (V)H.sub.2 N--Y (V),wherein Y is as defined in formula (I), to produce a (het)-aroylacrylic ester of the formula (VI) ##STR13##whereinR.sup.1' comprises a component selected from the group consisting of C.sub.1 -C.sub.4, alkyl groups andR.sup.2, R.sup.3, R.sup.4, Y and A are each as defined under formula (I) andR.sup.6 is as defined under formula (II),c) cyclizing the (het)-aroylacrylic ester of the formula (VI) in the presence of the base without utilizing a polar solvent selected from the group consisting of dimethylformamide, dimethyl sulfoxide, tetramethylene sulfone, and N-methylpyrrolldone, to produce a quinolone or naphthyridone ester of the formula (I) wherein R.sup.1 comprises a component selected from the group consisting of C.sub.1 -C.sub.4 alkyl groups;wherein the intermediates of the formulae (IV) and (VI) are not isolated and steps a) to c) are carried out in the same non-polar to slightly polar solvent.