Solid-phase syntheses of heterocycles containing the 2-aminothiophenol moiety

Efficient and general procedures have been developed for the solid-phase pr eparation of substituted benzothiazoles (1), 3,4-dihydro-1,4-benzothiazines (2), 3,4-dihydro-1,4-benzothiazine-1,1-dioxides (3), 3,4-dihydro-3-oxo-1,4 -benzothiazines (4), and 3,4-dihydro-3-oxo-1,4-benzothiazine-1,1-dioxides ( 5). ALL five classes of compounds were prepared from a common intermediate, resin-bound 2-amino-4-carboxythiophenol, in a minimal number of steps. Thi s intermediate was generated by (i) coupling 4-fluoro-3-nitrobenzoic acid o nto Wang resin, or onto an amino acid bound to the resin, (ii) substitution of the aryl fluoride with a protected thiol, (iii) reduction of the nitro group, and (iv) removal of sulfur protection. Reaction with the appropriate substrates and reagents to effect cyclization gave the substituted core st ructures, which were modified further to introduce additional point(s) of d iversity. Following cleavages from the solid support, the compounds were ob tained in high initial purities and good isolated yields after purification .