Research On The Synthesis Of Retigabine And Azilsartan’s Impurities

Epilepsy is a chronic disorder characterized by recurrent seizures.At present, thereare about0.5-1%(50million) of the people with epilepsy in the world.Moreover, thediscrimination upon the adult with epilepsy will exist for a long time and it’s hard toremove. Epilepsy is harmful to the humanbeing.Retigabine(Ezogabine) is a new anticonvulsant drug.The drug was developed byValeant Pharmaceuticals and GlaxoSmithKline, It was approved by the EuropeanMedicines Agency under the trade name Trobalt on March28,2011, and by the UnitedStates Food and Drug Administration (FDA), under the trade name Potiga, on June10,2010, add-on treatment of partial seizures in adults. The target compound was synthesizedfrom3-fluoroaniline by acetylation and nitrification to give N-(5-fluoro-2-nitrophenyl)acetamide(3), which was subjected to condensation with (4-fluorophenyl)methanamine toafford N-(5-((4-fluorobenzyl)amino)-2-nitrophenyl)acetamide(4), followed by deacetyl-ation, reduction, acylation. The structure of retigabine was confirmed by1H-NMR and MS,and the overall yield was39.6%.Impurities is very important during the pharmaceutical research and development.Azilsartan was developed by Takeda Pharmaceutical Company Limited, it is an orallyactive angiotensin II blocker. In the analysis of synthetic process and reaction mechanism,we speculate there are8Impurities produced in the process, namely Azilsartan ImpuritiesA,B,C,D,H,I,J,K. These8impurities were synthesized and the structure of them wereconfirmed. the synthesis of the8impurities is important to the improvement of syntheticprocess and the confirmation of adverse reaction caused by the impurities.