Scheme 3. Synthesis of Benzothiophene-2-carboxamides and Benzothiophene-2-methylamines (Series III and IV).

Reagents and conditions: (i) R²-amine, EDC·HCl, HOBt, DIPEA, DMF, rt, 3–12 h, 16–98%; (ii) 25% NH₄OH, HBTU, Et₃N, DMF, rt, 30 min, 36%; (iii) R²-amine, Na(OAc)₃BH, acetic acid, THF, rt, 12 h, 15–39%; (iv) LiAlH₄, TMSCl, THF or CH₂Cl₂, 0 °C to rt, 2–6 h, 8–66%; (v) K₂CO₃, ethyl thioglycolate, DMF, rt to 60 °C, 22 h, 93–97%; (vi) NaOH, EtOH/H₂O (1:1), reflux, 1.5 h, 91%–quant.