Fused quinoline heterocycles X. First synthesis of new four heterocyclic ring systems 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinoline derivatives

ABSTRACT

A novel, simple, and efficient synthetic methodology for the synthesis of hitherto unreported tetracyclic 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinolines, in one step, has been developed by coupling of various active methylene compounds with diazotized heterocyclic amines. Reacting 2,4-dichloroquinoline-3-carbonitrile (1) with cyanoacetic acid hydrazide (2) in the presence of triethylamine in refluxing MeOH gave the unexpected 3-amino-4-chloro-1H-pyrazolo[4,3-c]quinoline (4), instead of the desired tetracyclic ring system 3 (Scheme 1). Refluxing 4 with excess of cyclic secondary amines 5a–c in boiling dimethylformamide yielded the corresponding 4-amino-pyrazolo[4,3-c]quinolines 6a–c. Diazotization of compounds 4 and 6a–c with sodium nitrite and concentrated HCl at −5 °C gave the corresponding diazonium salts 17a–d, which were then subjected to couple with different active methylene nitriles, namely, 2-cyanothioacetamide (12), ethyl cyanoacetate (13), malononitrile (14), 2-cyanoacetamide (15), and 2-cyano-N-phenylacetamide (16), in aqueous ethanol containing sodium acetate as a buffer solution. The coupling reaction of diazonium salts 17 with 12, 13, and 14 leading to the novel perianellated tetracyclic ring system 10-amino-6,9-disubstituted-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinolines 19, 23, and 27, respectively, in one step, is described for the first time. On the other hand, coupling reaction of diazonium salt 17a with both 15 and 16 yielded the previously unknown tetracyclic 10-amino-6-chloro-[1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinoline-9-carboxamides 28a and 28b, respectively (Scheme 6). No chromatographic techniques have been used for the purification of the products. The structures of all the newly synthesized compounds were unambiguously confirmed by spectroscopic and analytical techniques.

GRAPHICAL ABSTRACT

KEYWORDS:

• Azo-coupling reaction
• diazotization
• fused [1,2,4]triazino[4′,3′:1,5]pyrazolo[4,3-c]quinolines
• pyrazolo[4,3-c]quinoline-3-carbonitriles
• synthesis