Pyrazolo pyridine-6-carboxylates

The ring closure of 7V-(5-unsubstituted pyrazol-4-yl)aminomethylenema-lonates (898) in boiling Dowtherm A for 15 min gave l//-pyrazolo[4,3-b]pyridine-6-carboxylates (899) in 56-88% yields [76JCS(P1)507 77JAP(K)77086], but N-( 1,5-dimethylpyrazol-4-yl)aminomethylenemalo-nate (900) afforded 2//-pyrazolo[4,3-/j]pyridine-6-carboxylate (901) in 65% yield under similar conditions [76JCS(P1)507]. 

The ring closure of (V-(l-substituted 3-pyrazolyl)aminomethylenemalo-nates (1104, R = Me, Et, R1 = H) by heating in diphenyl ether at 220°C for 30 min afforded 2-substituted pyrazolo[3,4-b]pyridine-5-carboxylates (1105) in 67-71% yields (76GEP2617157 77GEP2646670, 77USP-4038281, 77USP4038283). 

The ring closure of ylides (1391) by heating in boiling xylene for 1.5 hr afforded pyrazolo[l,5-a]pyridine-3-carboxylates (1393) in 14-25% yields [73JCS(P1)2580]. The pyrazolo[l,5-a]pyridines (1393) were probably formed from the intermediate dihydropyrazolo[l,5-a]pyridines (1392) by the formal elimination of ethyl formate. 

In the pyrazolo [ 1,5-a]pyridine series, the reaction of hydrazine with the 2,3-dimethoxycarbonyl derivative afforded the corresponding 2-hydrazide, whereas saponification and decarboxylation gave the 3-carboxylic acid.169 Further, several 2-substituted 3-carboxamides, -hydrazides, and -carboxylic acids were obtained,169,239 using standard methods. Decarboxylation was also reported.169 A number of transformations of py razolo [3,4-h]pyridine... 

Chebanov et al. [202] noted that condensation of the unsaturated acids 236 with 5-aminopyrazoles 220-222 never yielded isomers with opposite location of the aryl and carboxyl groups on the pyridine or pyrimidine rings, respectively. In the case of the multicomponent reaction of aminopyrazoles 220-222 with pyruvic acid 239 and aromatic aldehydes a different direction was observed. Refluxing of the starting materials in acetic acid led exclusively to pyrazolo[3,4-Z ]pyridine-4-carboxylic acids 249-251 instead of the anticipated carboxylic acids 243-248 (Scheme 3.69). The three-component procedures led only to the formation of heteroaromatized compounds even under a nitrogen atmosphere [202]. 

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. 

Transformation of alkyl (5-oxo-l-phenyl-4,5-dihydro-l/-/-pyrazol-3-yl)acetates into 5-heteroaryl-3-oxo-2-phenyl-3,5-dihydro-2H-pyrazolo[4,3-c]pyridine-7-carboxylates (03H197)... 

Treatment of 19 with hydrazine and monosubstituted hydrazines in ethanol at room temperature or under reflux gave 5-amino- 21 (R=H) and 5-aminosubstituted pyrazolo[4,3-c]pyridine-7-carboxylates 21 (R H), while with hydroxylamine hydrochloride the corresponding 5-hydroxy derivative 22 was formed in 82% peld. Nitrosation of 21 (R=H) with... 

Compound 30a (R =R =Me) was transformed with 4-methylaniline into 2H-pyrazolo[4,3-c]pyridine-7-carboxylate 20, identical with that prepared previously (Scheme 12, see also Scheme 8). 

Pyrazolo[l,5-a]pyridines from 1-ammopyridinium salts and carboxylic acid dilorides... 

A mixture of diethyl (l-ethyl-5-pyrazolyl)aminomethylenemalonate and excess POCI3 refluxed 10 hrs. -> ethyl 4-diloro-l-ethyl-lH-pyrazolo[3,4-b]pyridine-5-carboxylate. Y 79%. F. e. by a 2-step process s. H. Hohn, T. Denzel, and W. Janssen, J. Heterocyclic Chem. 9, 235 (1972). 

Hydrazides of 4-arylethynyl-5-carboxylic acid undergo a regioselective base-catalysed 6-endo-dig cyclization with the formation of pyrazolo[3,4-c]pyridine-7-ones (Scheme 32)45... 

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