Study On The Synthesis And Quality Standard Of Crisaborole

Atopic dermatitis is a very common skin disease in the clinic.The global prevalence is extremely high.It is usually sick in childhood.Both men and women can get sick.According to incomplete statistics,in developed countries,there are about 35% of children and 15% of adults suffer from AD.Refer to the relevant synthetic route,screen and optimize the synthetic route of Crisaborole,and design a new synthetic route and carry out process optimization,related substance inspection and quality standard research for this route.Provide a reference for fully synthetic industrial production and quality control.(1)Synthesis of Crisaborole: We use two routes to fully synthesize Crisaborole,route 5 is the optimization of the original route,and route 6takes 4-bromo-3-meth-ylphenol as the starting route.The advantage of the two roads is that the raw materials are cheap and easy to obtain.Optimized in two steps of boriding reaction and ring-closing reaction,palladium catalyst is used instead of boric acid ester to avoid the use of catalyst n-butyl lithium and low temperature experimental conditions of-78 ?,which is beneficial to labor protection in industrial production and simplify experiment process.(2)Compared with route six,route five has more synthetic steps and longer experiment time;route four uses 4-bromo-3-methylphenol,which is cheaper than 2-bromo-5-hydroxybenzaldehyde,which can be greatly reduced.Synthesis cost.In the sixth route,the reaction step is reduced,but when the bromination is carried out by using BPO as a catalyst,a side reaction occurs,the purity of the product is low,and the product needs to be recrystallized and purified,and the BPO is incompletely removed in the product,which increases the difficu Lty of post-treatment.(3)Quality standard of Crisaborole :The quality control of Crisaborole has not been established in China.The main content including the melting point of chrome bromide is 119.5~120.The high-performance liquid chromatography method is used to investigate and determine the content of Crisaborole.The resu Lts show that the impurity content of the laboratory-made samples(the total impurity content does not exceed 1.0%)meets the requirements,and the impurities produced by the acid,alkali and oxidation destruction experiments can also be completely separated from the main peak.The content of the three batches of samples was between 98% and 102%.