Separation and identification of an impurity from the istradefylline intermediate

Abstract

Istradefylline is a selective adenosine antagonist for the A_2a 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.