Synthesis of Maleimide Derivatives and Benzo[1,4]oxetane Derivatives: a Modification Method of Amine-Containing Pharmaceuticals

Maleimide-modified drug molecules can improve the stability and selective release of drugs. This study developed an easy-to-operate, mild, and safe synthetic drug-molecule modification strategy. This strategy employs the easily substituted characteristics of the substrate aminomaleimide and various amine-containing molecules under catalyst-free conditions. This method is suitable for various types of primary amines and secondary amines. When reacting with <i>N</i>-methylbenzylamine, benzo[1,4]oxazepane derivatives can be obtained by temperature adjustment. At the same time, the method has good tolerance for substrate functional groups, and 7 maleimide-modified drug molecular fragments were obtained in high yield (80-85%). This article has confirmed that the drug molecules modified by this method still have active reaction sites and can be further modified.