Studies On The Synthesis Of Tadalafil

The research background,classification,action mechanisms,clinical application and market prospect of the erectile dysfunction targeted drugs were briefly introduced in this paper.Mainly describes the phosphodiesterase 5(PDE5)inhibitor’s drug tadalafil,and its synthetic route selection and the research of synthetic process were described in detail.As the first long-acting PDE5 inhibitor approved by FDA,it had a broad market prospect in the field of ED treatment and had practical significance for the synthesis of its generic drug.Based on the comparison and analysis of the synthetic route described in the references and considerations of industrialized production,we designed a synthetic route suitable for industrialization,Using D-methyl tryptophan hydrochloride and piperonal as starting materials,through three steps of P-S condensation,acetylation,cyclization,we got the final targeted product,the yield was 79.62%,the purity of the product was 99.99% by HPLC.The reaction conditions of each steps in the synthetic process were examined in detail,the structures of most of intermediates and the final product were corroborated by 1H-NMR、MS.The paper had entered the kilogram pilot batch in the foundation of the lab batch,and further verified the stability of the process.This route had the advantages of high yield,simple operation,easy to obtain raw materials,and so on.and it laid a certain foundation for industrialized production.At present,the company had completed the verification batch and prepared for the BE clinical trial.