Scheme 3.

Synthesis of C2 substituted quinoline analogs 18–23. Reagents and conditions: a) Tf₂O, Et₃N, CH₂Q₂; b) o-ClC₆H₄B(OH)₂, Pd(PPh₃)₄, Et₃N, dioxane, 100 ^oC, 60%, 2 steps; c) XPhos-Pd-G₂, 4-pyridyl boronic acid, Na₂CO₃, dioxane/H₂O, 60 ^oC, 66%; d) LiAlH₄, THF, 52%; e) MeMgBr, THF, −20 ^oC, 35%; f) R₁R₂NH, MeOH, 10–70%; g) NaOH, THF/H2O, 70%; h) R₁R₂NH, EDCI, HOBt, iPr₂EtN, DMF, 11–45%