Non-concerted nucleophilic [4+1] cycloaddition of (dimethylamino)methoxycarbene to arylazonicotinates in the synthesis of pyrazolo[3,4-c]pyridines and pyrazolo[4′,3′:4,5]pyrido[2,3-d]pyrimidines

Abstract

A novel reaction between 2-amino-5-arylazonicotinonitriles 3c–g and dimethylformamide dimethylacetal (DMF-DMA), leading to the formation of a new class of pyrazolo[3,4-c]-pyridine derivatives 8, has been developed. The process is believed to take place via a non-concerted [4+1] cycloaddition pathway involving nucleophilic addition of (dimethylamino)-methoxycarbene, generated from DMF-DMA, to the arylazonicotinates 3c–g. The pyridine derivatives 8 were observed to react with ammonia in refluxing acetic acid to yield novel pyrazolo[4′,3′:4,5]pyrido[2,3-d]pyrimidine derivatives 9. Other members of the pyrido[2,3-d]pyrimidine family 13 were synthesized by reactions between 2-amino-5-arylazonicotinate ethyl esters 3a,b and DMF-DMA, which produce amidine derivatives 10a,b that undergo cyclization to generate the corresponding pyrido[2,3-d]pyrimidines13a,b when treated with ammonia in refluxing acetic acid. Finally, the results of this effort revealed that pyrido[2,3-d]pyrimidines 13a,b also react with DMF-DMA to produce pentaazacyclopenta [a]naphthalene derivatives 14. The structures of all new substances prepared in this investigation were determined by using X-ray crystallographic analysis and spectroscopic methods.