Pyrazolo quinoline-7-carboxylate

Condensation of 1- and /V(6)-alkyl and unsubstituted 6-aminoindazoles with diethyl ethoxy-methylenemalonate in Dowtherm A at elevated temperature gave the ethyl 6,9-dihydro-9-oxo-pyrazolo[3,4 /]quinoline-8-carboxylates (88) (Equation (49)) <83JHC1351>. The 6-ethyl-8-carboxylic acid derivative is a potent antibacterial agent. 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Intramolecular nitrilimine cycloadditions gave new pyrazolo[4,3-c]pyrrolizines 50 <04H(63)1423>. The syntheses of 5-substituted ethyl 3-oxo-2/7-pyrazolo[4,3-c]pyridlne-7-carboxylates 51 <04H(63)609> and 5//-pyrazolo[4,3-c]quinolines 52 <04H(63)1883> have been described. Ring-closure reactions of 3-arylhydrazonoalkyl-quinolin-2-ones gave rise to 1-aryl-pyrazolo[4,3-c]quinolin-2-ones <04JHC681>. 

Wang et al. [49] developed a highly regioselective Povarov reaction of an aromatic aldehyde, l//-indazol-5-amine, and methyl 3-oxobutanoate catalyzed by iodine. This novel reaction selectively gave 3/f-pyrazolo[4,3-y]quinolin-9-yl acetates 20, rather than 3//-pyrazolo[4,3-/jquinoline-8-carboxylate derivatives. Further, they [50] also extended the reaction using tetrahydropy ran-4-one instead of methyl-3 -oxobutanoate for the synthesis of 7-aiylpyrano[3,4-c]pyrazolo[3,4-/]quinoline derivatives 21 (Scheme 10.16). 

The synthesis of l-methyl-l,4-dihydro-9H-pyrazolo[4,3-(i]quinoline-9-one 72, inhibitor of protein kinase C, has been performed by means of cyclization of 4-[(4-fluorophenyl)amino]-l-methyl-lH-pyrazole-5-carboxylic acid (Scheme 33) [227]. The main trends in development of research studies in the field of [b]-annelated fluoroquinolones are dealt with use of these compounds for the synthesis of novel [ij]-annelated systems, a varying of substituents at C-7, and also with obtaining of new 2-substituted fluoroquinolones. 

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