Scheme 1. Synthesis of Piperazine and Diazepine “N-linked” Analogs.
Reagents and conditions: (a) DIEA, EtOH, 100 °C, 2h, 80-88%; (b) DIEA, NMP, 120 °C, 8h, 80-88%; (c) 4M HCl in dioxane, 2h, 89-98%; (d) EDCI/HOBt or HBTU, DIEA, 3,4-Cl2Ph(CH2)nCO2H, DMF, 30-85%; (e) DIEA, 3,4-dichlorobenzylsulfonyl chloride, DMF, 15%; (f) DIEA, 3,4-dichloroisocyanate, DMF, 10-45%; (g) NaH, THF, CH3I, 0 °C to rt, 22%.