Scheme 1.

Synthesis of second generation, C4-derivatized analogs

Reagents and conditions: (a) coupling conditions, 21-92%; (b) 4-tert-butylbenzoyl chloride, CH₃CN, 150°C, MW, 1 h, 25-95%; (c) LiOH, THF:H₂O (1.5:1), rt, 18 h, 15-93%; (d) CuCN, DMF, 120 °C, 6 h, 78%; (e) TMSN₃, CuI, DMF, MeOH, 18 h, 90 °C, 36%; (f) TMS-diazomethane, CH₂Cl₂:MeOH (1:1), rt, 2 h, 56-74%; (g) Cu powder, pyrrole or pyrazole, or imidazole, Cs₂CO₃, 150 °C, CH₃CN, 27-58%; (h) Raney Ni, NaBH₄, 0°C to rt, 17 h, 91%; (i) paraformaldehyde, NaCNBH₃, rt, 18 h, 53%.