A strategy for the synthesis of 2-aryl-3-dimethylaminopyrazolo-[3,4-c]pyridines that utilizes [4+1] cycloaddition reactions of 5-arylazo-2,3,6-trisubstituted pyridines

In order to explore the viability and generality of a recently uncovered [4+1] cycloaddition based strategy for the preparation of pyrazolo[3,4-c]pyridine derivatives, members of a series of 5-arylazo-2,3,6-trisubstituted pyridines were prepared by reactions of 3-oxo-2-arylhydrazonopropanals with 3-oxo-3-phenylpropionitrile. The results show that 3-oxo-3-phenylpropionitrile reacts with hydrazone substrates, which do not contain electron-withdrawing substituents on the N-aryl ring of the arylhydrazone moieties, to efficiently produce 6-aryl-2-phenyl-5-aiylazonicotinonitriles. In contrast, 2-amino-6-aryl-5-arylazo-3-benzoylpyridines are generated in reactions of 3-oxo-2-arylhydrazonopropanals, which contain electron-withdrawing substituents on the N-aryl moiety. In the forecasted manner, the 6-aryl-2-phenyl-5-arylazonicotinonitriles undergo smooth reactions with dimethylformamide dimethylacetal (DMF-DMA) that led to formation of a new class of 2-aryl-3-dimethylaminopyrazolo[3,4-c]pyridines. The mechanism for this process involves a [4+1] cycloaddition reaction that takes place through initial nucleophilic addition of dimethylamino)methoxycarbene, generated from DMF-DMA, to the azadiene moiety of the arylazopyridines followed by cyclization of the formed zwitterionic intermediate. (C) 2013 Elsevier Ltd. All rights reserved.