Efficient synthesis of tetramethylsulfonylguanidines between a free sulfonamide group and HBTU

The reaction of a sulfonamide moiety with HBTU (O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate) during amide coupling, leading to the formation of tetramethylsulfonylguanidines, is described. Optimised conditions showed that HBTU was as a convenient agent for the synthesis of tetramethylsulfonylguanidines, in basic conditions. A panel of diverse sulfonamides was used to demonstrate the scope of this procedure.