Synthesis And Application Of Isoindolinone And Isoindoline Compounds

Isoindolinones and isoindolins are very pharmaceutical building block in natural products and synthetic drugs.However,the process of extracting or separating such alkaloids from natural products is relatively complicated,and the traditional methods have the disadvantages of harsh reaction conditions,low yield and complex postprocessing.Therefore,the search for efficient,economical and simple synthetic methods has become the focus of research on isoindolinones and isoindolines.In this thesis,isoindolinones and isoindolines were synthesized without solvents and catalysts.And two compounds with important pharmacological activities,Lenalidomide and DWP205190,were further synthesized.The synthesis of isoindolinones was studied in this thesis.The reaction time and temperature were optimized in solvent-and catalyst-free conditions by using methyl 2-(bromomethyl)benzoate and aniline as the reaction model.Then 24 different substituted isoindolinone compounds were synthesized from different substituted methyl 2-(holomethyl)benzoate and substituted amines with nearly 99% yield and purity,which has a high atomic economy and practicality.The synthesis of isoindolines was studied in this thesis.The reaction time and temperature were optimized in solvent-and catalyst-free conditions by using odichlorobenzyl and aniline as the reaction model.Then 15 different substituted isoindoline compounds were synthesized from different substituted amines and odichlorobenzyl.All of which have achieved good yields and the method is highly practical and simple to operate.Based on the above work,Lenalidomide intermediate was synthesized in solventand catalyst-free conditions,and the reaction time,temperature and dissociation base(triethanolamine)were optimized.Then Lenalidomide was synthesized by Fe powder reduction.Moreover,DWP205190 was synthesized for the first time by using 3-(cyclopentyloxy)-4-methoxyaniline and methyl 2-(bromomethyl)benzoate in solventand catalyst-free conditions with a good yield and purity.