Scheme 1. Synthesis of cinnoline analogues.

Reagents and conditions:

(a) HNO₃, SnCl₄, CH₂Cl₂, −70°C; (b) Fe, NH₄HCO₃, toluene, water, reflux; (c) NaNO₂, acetic acid, 70%H₂SO₄, Et₃N; (d) POCl₃, PCl₅; (e) 2-fluoropyridine-5-boronic acid, Pd(PPh₃)₄, Cs₂CO₃, diglyme; (f) i. 4-(pyridin-3-yl)piperidin-4-ol or 4-methylpiperidin-4-ol, K₂CO₃, DMSO, reflux; or ii. K₂CO₃, DMSO, reflux, then H₂, 10% Pd/C, methanol, 75 psi.