SCHEME 1.

Synthesis of isothiocyanate (ITC)-containing AR antagonists 12a, 12b, and NAC conjugate 13. Reagents and conditions: (a) CuI, Pd(PPh₃)₂Cl₂, TEA, CH₃CN, r.t., 2 hr; (b) DIPEA, MOMBr, THF, r.t., 6 hr; (c) H₂, Pd/C, r.t., overnight. (d) NaOAc, EtOH, reflux, 10 days; (e) DMSO, 80°C, overnight; (f) HCl, MeOH, 3 hr; (g) TEA, MsCl, DCM, r.t., 30 min; (h) NaN₃, DMF, r.t., 6 hr; (i) 1. PPh₃, THF, reflux, overnight; 2.CS₂, THF, reflux, 5 hr; (j) NAC, NaHCO₃, acetonitrile, 45°C, overnight