N -Monoacylation of Sulfonimidamides

Abstract

N-Monoacylated sulfonimidamides, the aza analogue of N-acylsulfonamides which are a common motif in drug discovery, were exclusively synthesized by using a 1:1-premixed mixture of an acyl chloride and pyridazine as the acylating agent, while diacylation exclusively occurred when N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) was used as the coupling agent. The monoacylation is fast, easy to operate, and applicable to both aromatic and aliphatic acyl chlorides to give the corresponding products in moderate or high overall yields. A two-step N,N′-diacylated product exemplifies that the sulfonimidamide moiety provides one more handle than its sulfonamide isostere. This stepwise functionalization approach can be used to fine-tune the desired properties of compounds in medicinal chemistry.