A Dication-Mediated Rapid 4-Amination of Methoxy Pyridine

Abstract

Abstract 4-Aminopyridines are key structures in pharmaceuticals. SNAr reactions typically require electron-deficient starting materials, and it remains difficult to overcome this limitation without the use of transition metals. Herein, we report the urea-based organic dication as a highly effective reagent for the activation of 4-methoxypyridine with respect to amination reactions. This method broadly tolerates functional groups, including electron-withdrawing and -donating substituents and even free nucleophiles. This method allows chromatographic procedures to be bypassed during workups, ultimately leading to a more sustainable profile.