4-hydroxy-2-quinolones. 153*. Synthesis of hetarylamides of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Abstract

Keywords: 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid, amidation, intramolecular cyclization.We have previously proposed the preparation of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamides and this has been introduced satisfactorily into the synthesis of N-alkyl-[2], arylalkyl- [3], and aryl-[4] substituted derivatives. There are differences in some details of carrying out the experiment but a common feature is shared, i.e. all are based on the initial separation of the corresponding quinoline-3-carboxylic acid. In most cases such a course was justified even though the method of activating the carbonyl carbon atom of the carboxyl group in the starting quinoline-3-carboxylic acid has to be modified each time based on the properties of the starting amine.One of the reported methods can evidently also be used for synthesis of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid hetarylamides 1. It should immediately be noted, however, that when 2-oxo-1,2-dihydroquinoline-3-carboxylic acid chlorides react with azahetarylamines they frequently form stable N-acylhetarylamine salts rather than the amides [5]. For this reason we have not studied the "acid chloride" variant in this work. The use here of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid imidazolide (2) as the acylating agent appears more promising and, in fact, shows fully satisfactory results (method A, Table 1). None the less it has been noted before [4] that the imidazolide 2 is unusually unreactive and thus needs the use of high boiling solvents and in some cases has led to serious complications. Hence, for example, with acylation of the thermally unstable 2-amino-5-isobutyl-1,3,4-thiadiazole under these conditions the corresponding hetarylamide 1n could be obtained, but due to the low reaction rate it proved to be so strongly charged with gray-brown colored degradation products of the free amine that purification of the final product proved impossible even

4-hydroxy-2-quinolones. 191.* synthesis, tautomerism and biological activity of benzimidazol-2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids

“…In contrast to protons H-5 and H-6 in the some fragment, which give rise to a well-resolved sextet with coupling constant of about 3.0 Hz typical for benzimidazoles, an almost unresolved broad multiplet with intensity corresponding to 2H is found for protons H-4 and H-7. We have already found such behavior in a study of the 1 H NMR spectrum of a compound with similar structure, namely, the benzimidazol-2-ylamide of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid [23]. This behavior is attributed specifically to the carbamide bridge connecting the two heterocyclic fragments.…”

Synthesis and Regularities of the Structure–Activity Relationship in a Series of N-Pyridyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides

“…However, sometimes imidazolides of aromatic and heterocyclic carboxylic acids exhibit amazing resistance to the action of nucleophiles. In particular, one of these compounds is imidazolide of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (1), which reacts with anilines and aminopyridines only with prolonged boiling in DMF [29,30]. Its inertness to water was also noted although usually N-acylimidazoles are hydrolyzed very easily even under the action of air moisture.…”