Process Optimization And Pilot Production Of Hepatitis C NS3 Inhibitor AR00312025

Hepatitis C is a common hazard for human health,which currently has 0.43%of the incidence in our country and results in significant infectious disease.At present,there are no broadly effective therapies for the viral disease,limited with antiviral treatment or the combined usage of interferon ingeneral.So it is difficult to achieve the ideal therapeutic targets,meanwhile,greater undesired side effects occured.It is urgent that a drug with good efficacy and lower toxicity and side effects would be invented,which has a broad market prospect.Currently a variety of the theoretical researches,corresponding drug design for the treatment way and related inhibitors have been reported.The use of NS3 inhibitors in the treatment of hepatitis C is a kind of effective treatment method.The purpose of this paper is focused on the synthetic method,conditionsoptimization and parameters selection for a NS3 inhibitor AR00312025 in order to complete the production in compliance with the GMP requirements.Nine steps of operation were involved in the whole process:two steps for deblocking of BOCs,three steps for condensation reactions between carboxylic acids and amines;another ester condensation;key construction of the macrocyclic ring;general hydrolysis and acidification and salt formation to meet the requirements of drug production.Methods reported in the literatures have been reviewed in order to carry out production effectively.Appropriate adjustments were investigated to meet the actual production including the optimization of the reaction parameters,reaction conditions and operational control.These would produce the perfect product with sufficient purity in each step,which can be directly used for the next step and meet the production requirement.In conclusion,the overall yield reached more than 35%and the purity of the product was over 97%after the completion of the whole nine unit operations.