Synthesis of Designed Protease Inhibitors Ia
a Reagents and conditions: (a) acid A1, EDCI, HOBt, H2O–CH2Cl2 (1: 1), 0 °C, 24 h; (b) acid A2, SOCl2, THF, 0 °C to rt, 6 h; coupling: imidazole, EtOAc, acid chloride, 0 °C to rt, overnight; (c) acid A3, EDCI, HOBt, DIPEA, DMF–CH2Cl2 (1:1), 0 °C to rt, 24 h; (d) acid A4, SOCl2, EtOAc, DMF, rt to 50 °C, 6 h; coupling: NaHCO3, EtOAc, H2O, acid chloride, rt, 1 h; (e) Pd/C, HCO2NH4, MeOH, 50 °C, overnight; (f) (COCl)2, rt, overnight; (g) Et3N, THF, 0 °C to rt, 8 h.