Microwave‐assisted Solid‐phase Synthesis of N‐substituted‐2‐aminobenzo[d][1,3] Thiazine Derivatives from a BOMBA Resin

Abstract

An efficient solid‐phase methodology has been developed for the synthesis of N‐acyl and N‐sulfonyl substituted 2‐aminobenzo[d][1,3]thiazine derivatives. The key step in this methodology is the preparation of backbone amide linker‐bound 2‐aminobenzo[d][1,3]thiazine resin through cyclization reaction between isothiocyanates and BOMBA resin under microwave irradiation. This 2‐aminobenzo[d][1,3]thiazine core skeleton resin undergoes substitution reactions with various electrophiles, such as acid halides and sulfonyl halides, to generate N‐acyl and N‐sulfonyl substituted 2‐aminobenzo[d][1,3]thiazine resins, respectively. Finally, N‐acyl and N‐sulfonyl‐substituted 2‐aminobenzo[d][1,3]thiazine derivatives are prepared in good yields and purities by cleavage of the respective resins under trifluoroacetic acid (TFA) in dichloromethane (DCM).