Pyrazolo quinolin-7-ones

Quiroga J, Mejia D, Insuasty B et al (2001) Regioselective synthesis of 4, 7, 8, 9-tetrahydro-2H-pyrazolo[3, 4-b]-quinolin-5(6H)-ones. Mechanism and structural analysis. Tetrahedron 57(32) 6947-6953... 

Jarro Q, Braulio I, Angelina H et al (1998) Synthesis of 4-aryl-4, 7, 8, 9-tetrahydro-6H-pyrazolo[3, 4-b]quinolin-5-ones. J Heterocycl Chem 35(3) 575-578... 

Tu and co workers [114] reported a series of new pyrazolo[4,3-/ quinolin-7-ones 68 synthesized by a MCR of an aromatic aldehyde with Meldrum s acid and l//-indazol-5-amine in ethylene glycol without any catalyst under microwave irradiation. Among various polar solvents tested, ethylene glycol gave the highest yields. Various (hetero)aromatic aldehydes could be used (Scheme 52). 

Organ and co-workers [120] described a unique approach to MCRs using a microwave-assisted, continuous flow process for the synthesis of new series of tetrahydro-pyrazolo[3,4-6]quinolin-5(6//)-ones 79. An aldehyde, dimedone, and 5-amino-3-methyl-l//-pyrazole were reacted, yielding the desired compound 79 in moderate to excellent yields. It was proved that the electronic properties of the substituted benzaldehydes have an important impact on the conversions as with electron-donating groups rather low yields were obtained (Scheme 60). 

A microwave-assisted three-component coupling reaction of 5-amino-3-phenyl-pyrazole, a cychc 1,3-dicarbonyl compound and an aromatic aldehyde has been described by Chebanov and co-workers [121]. Depending on the apphed reaction conditions a series of 4-aryl-3-phenyl-l,4,6,7,8,9-hexahydro-l// pyrazolo[3,4-h] quinolin-5-ones 80, 9-p-tolyl-6,6-dimethyl-2-phenyl 5,6,7,9-tetrahydro-pyrazolo [5,l-h]quinazolin-8-ones 81, or 4-aryl-5a-hydroxy-4,5,5a,6,7,8-hexahydropyra-zolo[4,3-c]quinolizin-9-ones 82 can be formed (Scheme 61). 

Peng J, Hao W, Wang X et al (2009) Microwave-assisted synthesis of pyrazolo[4, 3-f quinolin-7-one derivatives via multi-component reactions. Chin J Chem 27 1707-1710... 

Mali JR, Pratap UR et al (2010) Water-mediated one-pot synthetic route for pyrazolo[3, 4-b]quinolines. Tetrahedron Lett 51 3980-3982... 

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). 

Wang W Li YL, Wang XS (2012) Highly efficient synthesis of 7-aryl-pyrano[3,4-c] pyrazolo[4,3-f]quinoline derivatives catalyzed by iodine. ARKIVOC vi 214-221 Lin XF, Cui SL, Wang YG (2006) Molecular iodine catalyzed one-pot synthesis of substituted quinolines from imines and aldehydes. Tetrahedron Lett 47 3127-3130 Jin G, Zhao J, Han J, Zhu S, Zhang J (2010) Iodine-promoted imino-Diels-Alder reaction of fluorinated imine with enol ether synthesis of 2-perfluorophenyl tetrahydroquinoline derivatives. Tetrahedron 66 913-917... 

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. 

Not only [jj]-annelated fluoroquinolones, but also polycyclic fluoroquinolones, in which an additional ring is annelated to [c]- or [/ ]-sides proved to possess antineoplastic action. Research studies on antineoplastic activity of 5-cyclopropyl-6,8-difluoro-7-(2,6-dimethyl-4-pyridinyl)-5H-pyrazolo[4,3-c] quinolin-3(2H)-ones 106 have shown that derivatives containing the cyclohexyl group in position 2 are the most effective inhibitors of topoisomerase II of HeLa cells (mammalian cancer), while the dimethylaminocyclohexyl compound has shown the best data on cytotoxicity towards P388 (leukemia) cells (Table 9) [312]. 

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