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).