Separation and identification of an impurity from the istradefylline intermediate

Abstract

Istradefylline is a selective adenosine antagonist for the A2a receptor, and it is used to treat the Parkinson's disease and improve dyskinesia in the early stage of the Parkinson's disease. An impurity in the istradefylline intermediate A1 (6-amino-1,3-diethyl-2,4-(1H,3H)-pyrimidinedione) was identified by high performance liquid chromatography (HPLC); it was separated by preparative HPLC and further characterized by UV, IR, MS, NMR, 2D NMR and single-crystal XRD analyses. The impurity was identified as (E)-N-ethyl-2-cyano-3-ethylamino-2-butenamide, which originated from the synthetic process of the intermediate A1. The structure of this impurity might affect the efficiency and safety of istradefylline; therefore, the research and control of this impurity are necessary for ensuring the quality of istradefylline.