The Synthesis And Quality Standard Research Of Roflumilast

Objective: This paper is mainly on the synthesis and quality research of roflumilastraw materials and of which could lead the foundation of its preclinical data.Methods: Roflumilast was prepared from4-diflurormethoxy-3-hydroxybenzaldehydevia alkylation, oxidation and amidation, and the synthesized compound wascharacterized by HPLC, IR, MS and NMR. The industrial parameters weredetermined by pilot scale experiments and the potential impurities were synthesizedafter analyzing. The quality standard of roflumilast, its related substances and residualsolvents were studied by HPLC or GC method.Results: The IR, HPLC, MS and NMR data of the synthetic compound was consistentwith those reported and indicated that the substance is roflumilast. Completed threebatches of pilot scale and the purity is greater than99.7%. Synthesized17roflumilastrelated substances, of which8are new compounds. The methodology results showedthat those methods had a perfect specificity and a good linear relationship.Conclution: The established methods, including routings and detection methods, aresimple and reliable. In addition, the relevant experiments in preclinical data ofroflumilast raw material were completed.