Synthesis And Optimization Of Quinazoline Derivatives In Key Intermediates Of Anti-Lung Cancer Drugs

Tinib is a new type of targeted anti-cancer drug.The drugs approved for listing in our country include Gefitinib,Erlotinib and Imatinib.The good market performance of these drugs makes its synthetic research and development a hot research point.It is very important to develop a synthetic route of quinazoline derivatives suitable for large-scale production because of its widespread presence in tinib drugs.Taking the key intermediates of synthetic gefitinib as an example,this paper designs a process for synthesizing the intermediates.Most of the literature reports are based on isovanillin,and the positioning of aldehyde group and methoxy make the nitrification of the raw material to form a by-product and is not easy to separate,which makes the quinazolinone yield low and the market price is expensive.In order to avoid this problem,the process of this paper is to change the order of nitro and carboxyl bonded benzene ring with cheap and easy-to-get veratrole,target Products 6-Acetoxy group-7-methoxy-quinazoline-4-one were obtained by nitrification,demethylation,reduction,condensation,open-loop oxidation,acylation and acylation.The route is compared with the reported process in the literature:the starting material is cheap and easy to get;the nitrate reduction avoids the use of heavy metal palladium,and the catalyst iron chloride and activated carbon can be used repeatedly;demethylation avoids the use of esulfonic acid and L-methionine;the use of formamidine acetate in the quinazolinone is higher than that in the literature.At the same time,the post-processing of the process is simple,the product loss is small,suitable for scale production.