Synthesis of novel hexahydroquinolines and 6‐amino‐2‐oxopyridine‐3,5‐dicarbonitriles incorporating sulfamethoxazole via [3 + 3] annulation

Abstract

Cyclic enaminone and cyanoacetamide derivative with incorporated sulfamethoxazole moiety were prepared. Their reactions with arylidenemalononitrile derivatives in ethanol or pyridine/piperidine at reflux yielded the corresponding hexahydroquinoline and 6‐amino‐2‐oxopyridine‐3,5‐dicarbonitrile derivatives incorporating sulfamethoxazole. The mechanism and structural elucidation of products were discussed.

Synthesis and synthetic applications of cyanoacetamides

“…Thus, these compounds are versatile intermediates for the synthesis of wide variety of various nitrogen-containing heterocycles. [2][3][4][5][6][7][8] The present review of literature is expected to provide a comprehensive survey of the synthetic utility of cyanoacetamides as precursors for a variety of monocyclic five-membered, six-membered and fused heterocycles and to supplement the information available in two earlier reviews that have appeared in 1999 by Litvinov 9 and in 2008 by Fadda et al 1 . A brief survey of the methods for the synthesis of cyanoacetamides that have recently appeared is also included.…”

“…addition of activated methylene in the cyanoacetamides 3aw-fv to several arylidenmalononitrile 175 in ethanol42 or pyridine4 containing piperidine at reflux yielded pyrido[1,2-a]thieno[3,2-e]pyrimidine derivatives 358a-v via the intermediacy of 354-357 (Scheme 165, Table58). compound 3s in 1,4-dioxane containing triethylamine affected cyclization into the tetrahydrobenzo[4,5]thieno[2,3-b]pyridine derivative 361 (Scheme 167) 25. reaction of methyl o-(azidomethyl)benzoates 367a-c with 2-cyanoacetamides to produce triazolo[1,5b][2,4]benzodiazepines 368a-j was achieved by the action of either MeONa, t-BuOK, EtONa, or KOH (Scheme 170, Table61) 153.…”