Synthesis And Process Optimization Of Nilotinib

Chronic myelogenous leukemia (CML) is a malignant disease of hematopoietic tissue. Nevertheless CML transform an incurable disease to a chronic disease on account of the presence of the tyrosine kinase inhibitor (TKI). TKI is a kind of small molecular compound that can inhibit tyrosine kinase.Imatinib is a small molecules drug that opens up a new era of targeted CML therapy, but it is easy to appear the drug-resistant mutants in the process of treatment. Nilotinib is a new type of ATP competitive inhibitors with high affinity activity, and the amino pyrimidine is the basic drug groups. Nilotinib is a new medicine that reformed from imatinib's chemical structure which has already listed.The project's research content is mainly divided into two parts.Firstly,it is to determine the nilotinib's synthesis route by mains of researching relevant document, and then begin the corresponding work to get the intermediate compounds and characterize them. Eventually I complete the whole reaction route and obtaine the characterization of the nilotinib. The second part is to optimize the reaction for the low yield unit reactions in the process. To try the other synthetic routes or design a new synthetic route on the basis of the original which optimization effect is not ideal. All my work is to strive to receive the production process that low cost, environmentally friendly, easy operation and suitable for the operation of the industrial.I get through the entire synthesis route to get the nilotinib that is the target. At the same time, optimizing the reaction conditions of the units, especially the key units reactions, in addition to try new reaction routes. Finally I successfully achieve the synthesis process improvements for the key intermediate compound 6. In the new synthetic route raw materials are cheap and accessible,reaction conditions are mild, the reaction yield is higher, and the post-processing are simplify, so it is more suitable for industrial production. Although I have not obtained remarkable achievement for other reactions, the process are improved on the basis of the original.