Synthesis of a 6-CF₃-Substituted 2-Amino-dihydro-1,3-thiazine β-Secretase Inhibitor by <i>N</i>,<i>N</i>-Diethylaminosulfur Trifluoride-Mediated Chemoselective Cyclization

Abstract

The synthesis of a 6-CF₃-substituted 2-amino-dihydro-1,3-thiazine via N, N-diethylaminosulfur trifluoride (DAST)-mediated cyclization of N-hydroxypropyl thiourea 6 is described. This reaction gave 6-CF₃-1,3-thiazine 7 with high chemical yield and chemoselectivity, suppressing the common byproduct of oxazine 8. This new protocol enabled access to 6-CF₃-substituted 1,3-thiazine β-secretase inhibitor 2.