The antipsychotic drug olanzapine which does not inhibit PDE4 can be converted into the inhibitor of PDE4B via linking its N-10 position with an appropriately N-substituted 1,2,3-triazole moiety through a methylene linker. All these compounds were conveniently prepared by a CuAAC method under ultrasound irradiation at room temperature and evaluated for their PDE4 inhibitory potential in vitro. Three of them were identified as selective inhibitors of PDE4B (IC₅₀ ∼ 5–6 μM) over PDE4D. Overall, the present research reports one of the few examples of an ultrasound assisted CuAAC method used in medicinal chemistry.