Ultrasound Assisted One-pot and Sequential Synthesis of 3-methylene-isoindolin-1-ones and their in vitro Evaluation

Background: 3-Methyleneisoindolin-1-one derivatives containing a pyridin-2-ylmethyl substituent on their ring nitrogen were designed as potential bioactive agents. A one-pot synthesis of these compounds was achieved via sequential C-C coupling, followed by C-Si bond cleavage and subsequent tandem C-C/C-N bond forming reaction under ultrasound irradiation. Method: The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH, and finally coupling with 2-iodo-N-(pyridin-2-ylmethyl)benzamide. The in vitro evaluation of these compounds was performed to identify some initial hit molecules one of which showed dose dependent inhibition of PDE4B.