A series of novel N-aryl-debenzeyldonepezil derivatives (1–26) were designed and synthesized as cholinesterase inhibitors by the modification of anti-Alzheimer’s disease drug donepezil, using Palladium catalyzed Buchwald-Hartwig cross-coupling reaction as a key chemical synthesis strategy. This evidence concerns the gene BCHE and early-onset autosomal dominant Alzheimer disease.