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 degrees C by sulfated polyborate under solvent-free conditions has been developed for enamines and enaminones synthesis. Selected Bronsted 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.

Automated summary

A method for synthesizing enamines and enaminones through the activation of methyl ketones or active methylenes and N, N-dimethylformamide dimethyl acetal at 110 degrees C by sulfated polyborate under solvent-free conditions has been developed. The use of selected Bronsted acid, optimized reaction conditions, and easy separation method allows for high yields of 82-97%, making this process cost-effective and eco-friendly. This method has been successfully applied to the synthesis of intermediates for Imatinib and Nilotinib, as well as Ocinaplon with high yields.