Synthesis of novel series of 3,5-disubstituted imidazo[1,2-d] [1,2,4]thiadiazoles involving SNAr and Suzuki-Miyaura cross-coupling reactions

The first access to 3,5-disubstituted imidazo[1,2-d][1,2,4]thiadiazole derivatives is reported. The series were generated from 2-mercaptoimidazole, which afforded the key intermediate bearing two functional positions. The SNAr reactivity toward tosyl release at the C-3 position was investigated and a regioselective electrophilic iodination in C-5 position was performed to allow a novel C-C bond using Suzuki-Miyaura reaction. Palladium-catalyzed cross-coupling conditions were optimized. A representative library of various boronic acids was employed to establish the scope and limitations of the method. To complete this methodological study, the influence of the nature of the C-3 imidazo[1,2-d][1,2,4]thiadiazole substitutions on the arylation in C-5 was investigated.

Automated summary

The first access to 3,5-disubstituted imidazo[1,2-d][1,2,4]thiadiazole derivatives is reported. The method involves the synthesis of a key intermediate from 2-mercaptoimidazole and the regioselective electrophilic iodination in the C-5 position using the Suzuki-Miyaura reaction. Palladium-catalyzed cross-coupling reactions with various boronic acids were optimized to establish the scope and limitations of the method.