Scheme 2. Synthesis of Piperidine “C-linked” Analogs.
Reagents and conditions: (a) Cs2CO3, Pd((t-butyl)3P)2, toluene: EtOH: H2O (9:3:1), 120 °C, overnight, 30-35% (b) 10% Pd/C, 60 psi, CH3OH, 16 h, 80%, (c) 4M HCl in dioxane 89-98%, (d) DIEA,3,4-dichloroisocyanate, DMF, 10-45% (e) DIEA, EDCI, HOBT, 3,4-dichlorophenylacetic acid, DMF, 30-85%