Isolation, synthesis and identification of degraded impurities in Letermovir

Letermovir is a cytomegalovirus inhibitor for cytomegalovirus infection a hematopoietic-cell transplantation. In the degradation test of Letermovir, five new impurities were detected at levels of ND ∼ 2.21 % (by oxide, thermal or photolytic). These impurities were synthesized directly, characterized and identified by HRMS NMR spectra and X-ray crystallography. Then co-injected with commercial products to confirm their retention times in HPLC . The possible formation pathways and synthetic methods of these impurities were discussed in details. Furthermore, the toxicological properties of impurities were evaluated by ACD/Percepta 14.52.0 (Build 3525) software.