Oxidzing Aldehyde With Sodium Chlorite And Hydrogen Peroxide Under Neutral Conditions And Synthesis Of Pazopanib Trimerrimer Impurities

Part ?:3,4-Dimethoxy-6-nitrobenzoic acid is an important intermediate for the synthesis of oxazolidines,and its general synthesis method mostly oxidizes aldehydes to acids.At present,Potassium permanganate is used industrially,and this method produces a large amount of manganese slag,and the by-product treatment cost is high.This study is intended to find a new,green,economical and efficient method for the oxidation of benzaldehyde to benzoic acid compounds.Oxygen peroxide is initially used for oxidation,but the reaction is severe,and a large amount of gas is generated to cause an explosion hazard,and the process is difficult to control.In this experiment,the method of oxidizing aldehyde to acid under neutral conditions was screened by H₂O₂ and NaClO₂.The effects of temperature,feed amount and solvent on the reaction were investigated.The optimal experimental conditions were obtained and the scope of application was extended.The system has a high conversion rate for both electron-deficient and electron-rich compounds.In addition,this study also scaled up the oxidation system to 100g,the yield was still above 93%,the purity exceeded 99.5%.Part ?:Pazopanib is a new oral angiogenesis inhibitor that is mainly used to treat Renal Cell Carcinoma?RCC?and is highly selective for vascular endothelial growth factor receptor?VEGFR?by inhibiting neovascularization.It makes the tumor cells die of ischemia.There could produce more than five kinds of impurities in the production,and the structure of the dimers and trimers of the related substances has been determined,due to the difficulty in synthesis and the production of trimer impurities.The content of trimer impurities is extremely small,which brings great difficulties to quality control.The research group has completed the synthesis of dimer impurities.In this paper,a synthetic study of trimer impurities will be conducted.2-Bromotoluene and2-methylbenzonitrile will be used as raw materials for the Grignard coupling.The body product is synthesized by the steps of nitration,hydrogenation,bromine substitution,Suzuki coupling,reduction,amino coupling,sulfonylation and the like to synthesize pazopanib trimer impurities.The most difficulty in this route is the synthesis of the intermediate[bis-?5-chloro-2-methyl-phenyl?-?4-nitro-phenyl?]-methane,which has been explored in practical experiments.This intermediate has been obtained so far,and subsequent studies are underway.