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

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.