Synthesis of 5-Functionalized 1-(Hetero)Aryl-1,2-Thiazine 1-Oxides Through the CSIC Reaction Strategy

Herein, we report an efficient strategy for the synthesis of C5-functionalized 1-(hetero)aryl-1,2-thiazine 1-oxides (in other words C5-functionalized six-membered endocyclic sulfoximines) based on the CSIC reaction. The starting compounds are readily available 2,2-disubstituted 3-bromopropanenitriles and imino(methyl)(hetero/aryl)-λ6-sulfanones. The reaction can be performed in a one-pot fashion. The method worked well and provided previously unreported spirocyclic and S-heteroaryl substituted 1,2-thiazine 1-oxides. These compounds were designed as multi-target small molecules and a preliminary in silico study indicated their good binding affinity to CLK4 and MAO B – the receptors associated with cancer and neurodegenerative diseases.