Scheme 4.

Reagents and conditions: (a) NH₄OH, EDC, HOBt, DMF, RT, 72 h; (b) Lawesson's reagent, THF, RT, 17 h; (c) 1-chloro-3-phenyl acetone, EtOH, 85 °C, 3 h; (d) 1-chloro-3-phenyl acetone, 130 °C, 2 h; (e) BOC-ON, triethylamine, THF, RT, 3–16 h; (f) TFA, RT, 0.5 h or HCl in EtOAc (∼4M), RT, 20 min; (g) 47, 1-butanol, DIPEA, 150 °C, 10 min in microwave or 47, 2-propanol, DIPEA, 70 °C, 15 h; (h) 6 N HCl, methanol, 60 °C, 1 h or HCl in EtOAc (∼4 M), 1:1 EtOAc/MeOH, RT, 15 min; (i) trifluoroacetic anhydride, pyridine, THF, 0 °C to RT, 2 h; (j) HONH₂ HCl, ethanol, Na₂CO₃, 85 °C, 72 h; (k) [4-(methyl)phenyl]acetic acid, HBTU, DIPEA, HOBt, DMF, RT, 1.5 h; (l) NaOAc, ethanol, water, 85 °C, 5 h; (m) 1-amino-3-phenylpropan-2-ol, EDC, HOBt, DCM, RT, 1.5 h; (n) Dess–Martin periodinane, DCM, RT, 15 min; (o) Burgess reagent, THF, 120 °C, 10 min in microwave; (p) phenylacetohydrazide or 2-(4-methylphenyl)acetohydrazide, HBTU, DCM, RT, 14 h; (q) Lawesson's reagent, toluene, 150 °C, 10 min in microwave.