Study On The Synthesis Of Vinyl-ACCA, An Important Intermediate Of Simeprevir

27 September 2013, Janssen Pharmaceutical K.K. announced today that the Japanese Ministry of Health Labour and Welfare(MHLW) has approved simeprevir for the treatment of genotype-1 chronic hepatitis C virus(HCV).As part of a combination therapy with pegylated interferon and ribavirin in clinical trials, simeprevir has demonstrated strong efficacy, 89 percent of patients with previously untreated genotype-1 HCV achieving a sustained virological response(SVR).The primary endpoint in all clinical studies for simeprevir was an SVR 12 weeks after the last dose of treatment. In studies that included patients who had relapsed after stopping previous HCV treatment, results showed an SVR-12 of 96 percent.(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid(vinyl-ACCA) is a key building block of simeprevir, which inhibitors of the hepatitis C virus NS3 protease.This paper plans to design a simple route is more advantages than the existing production process and carries on the optimization for large scale production at first,unfortunately, this plan cannot be expected due to the chemical problems. At last we used the Boehringer Ingelheim Company’s patent route as base. To verify and analysis,the reaction is more convenient through to change the protection group(with diphenyl ketone substitution benzaldehyde) at the same effect, use cheaper raw materials;make the post processing is greatly simplified after optimization of the key steps; to reduce the time of processing; at the same time improve enzyme utilization in the step of enzymatic hydrolysis by enzyme applied to reduce environmental pollution; Due to these all above improve the total yield increase 8% and the total production cost was reduced to 30%~40% compare to the literature. After all, this change is very significative for process.