Synthesis of [1,3,4]Thiadiazolo[3′,2′:1,2]imidazo[4,5‑c]quinolines including Pictet–Spengler Reaction and Exploration of Their C‑2 Reactivity through SNAr

• Published in: Journal of organic chemistry 2017-12, Vol.82 (24), p.13700-13707
• Main Authors: Place, Matthieu, Copin, Chloé, Apotrosoaei, Maria, Constantin, Sandra, Vasincu, Ioana Mirela, Profire, Lenuta, Buron, Frédéric, Routier, Sylvain
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b02565

This work reports the design of [1,3,4]­thiadiazolo­[3′,2′:1,2]­imidazo­[4,5-c]­quinolines using a Pictet–Spengler reaction. The scope of the reaction was achieved from 6-(2-aminophenyl)­imidazo­[2,1-b]­[1,3,4]­thiadiazole derivatives and available aldehydes. A wide range of aldehydes were employed to examine the scope of the cyclization. In parallel, a mechanism investigation was realized and showed a hydride transfer which led to a dismutation of the intermediate species. To complete this methodological study, a “sequential” oxidation/SNAr procedure was performed to achieve C-2 nucleophilic substitution using several amine types.