Synthesis Process Of Palbociclib

Palbociclib is a novel oral selective inhibitor of Cyclin-dependent 4/6 (CDK4/6). It was developed by the Pfizer. In February 3rd 2015, Palbociclib was approved by the accelerated approval process of the US FDA. In clinical practice it indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.The synthetic routes of Palbociclib reported in; the literatures was analyzed and compared, we designed a new synthetic route of Palbociclib which ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate as raw material and synthesized Palbociclib through nine chemical reactions. The main reactions were optimized and simplified the operation to improve the yield. It provided a new way for the synthesis of Palbociclib.A detailed study on the original process is carried out. We chose 5-Bromo-2,4-dichloropyrimidine as raw material and synthesized Palbociclib through six chemical reactions. The following points are the main contents of the research:the man reactions were optimized to improved the yield; improved the way of post treatment, simplified the operation, suitable for industrial production. The polymorphic forms of Palbociclib was studied to ensure the crystal form of API meet the requirement of preparation. The synthetic routes of all impurities of were designed, and synthetic impurities provided relevant information for drug application and a reliable basis for the analysis of API.