Sulfated Polyborate Catalyzed Improved Synthesis of Enamines and Enaminones Based Intermediates of Imatinib, Nilotinib and Ocinaplon

An activation of methyl ketones or active methylenes and N, N‐dimethylformamide dimethyl acetal at 110 °C by sulfated polyborate under solvent‐free conditions has been developed for enamines and enaminones synthesis. Selected Brønsted acid, optimized reaction conditions, and easy separation method lead to 82–97 % yield, making this process cost‐effective and eco‐friendly. We chose boric acid for scale‐up activity in the interest of readers and industries. The optimized reaction condition was applied to demonstrate a 10 gram scale for the intermediate of Imatinib and Nilotinib with an 80 % from 3‐acetylpyridine. This method is extendable to produce Ocinaplon intermediate with 80.6 % yield using 4‐acetyl pyridine as starting material. A cost‐effective and eco‐friendly activation of methyl ketones or active methylenes and N, N‐dimethylformamide dimethyl acetal at 110 °C by sulfated polyborate under solvent‐free conditions has been developed for enamines and enaminones synthesis. The improved protocol was applied to 10 gram scale synthesis of intermediates of Imatinib and Nilotinib with 80 % yield and Ocinaplon with 80.6 % yield.