Two-Directional Approach for the Rapid Synthesis of 2,4-Bis-Aminoaryl Pyridine Derivatives

We have developed two different approaches in parallel to rapidly access 2,4-bis aminoaryl pyridine compounds from a common starting material. The C-4/C-2 approach uses palladium-mediated coupling reactions to sequentially functionalize C-4 and then C-2. An alternative C-2/C-4 route uses a regioselective SNAr reaction to first substitute at C-2 then subsequently at C-4 by a palladium-mediated reaction. Both approaches have been used successfully to provide a range of 2,4-bis-aminoaryl pyridine compounds.