Synthesis Of 2-Aminonicotinonitriles And 4,5-dihydro-1H-pyrazole Derivatives

Heterocyclic compounds have always been the focus in the field of pharmaceutical research with various active entities and therapeutic drugs, thus two commonly seen heterocycles,2-Aminonicotinonitrile and 4,5-dihydropyrazole were discussed in this dissertation. Recent findings reveal that 2-Aminonicotinonitrile-based A2A receptor antagonists and 4,5-dihydropyrazole derived Chkl inhibitors have their own specific advantages in the treatment of PD and tumor, thus arousing much attention among R&D institutions and pharmaceutical corporations. In order to achieve new synthetic methods and leading compounds, we conducted researches on them in this dissertation.The pharmacological and synthetic research cases of 2-Aminonicotinonitriles and 4, 5-dihydropyrazole in recent years were concluded, and both of them exhibited widespread bioactivities, while the existed synthetic methods were all single with limited kinds of products.To obtain a simple and efficient synthetic method, we conceived and designed a multicomponent strategy toward 2-Aminonicotinonitrile with copper as catalyst and oxime ester, aromatic aldehyde and malononitrile as strating materials, and a synthetic route toward 4,5-dihydropyrazole with a similar copper catalyst, oxime ester and N-sulfonylimine as starting materials, thus resulting in a divergent synthesis by copper-catalyzed cyclization of oxime ester; optimization and screening experiments were carried out among some basic materials and optimal conditions for these two reactions were achieved, then 26 2-Aminonicotinonitriles and 15 were synthesized through the strategies (scalable and 97% yields for basic materials), and related reaction mechanism was proposed. That suggests our success in obtaining a simple, efficient and extensively applicable synthetic method.