A new palladacyclic N-heterocyclic carbene precatalyst was designed by the combination of 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene (AnIPr) with an achiral 2-naphthyl-4,4-dimethyloxazoline palladacyclic fragment. Applying this precatalyst enabled a general protocol for Pd-catalyzed C-N cross-coupling reactions of challenging five- or six-membered ring heteroaryl chlorides and various heterocyclic amines. The desired aminated products, including commercial pharmaceuticals or key intermediates such as piribedil, cyprodinil, V600EBRAF inhibitor, tripelennamine, 517-β-hydroxysteroid dehydrogenase inhibitor, brexpiprazole, and sonidegib, were achieved in good to excellent yields (>61 examples, ≤99% yields).