Process Improvement On The Synthesis Of S-(1-ethylpyrrolidin-2-yl) Methanamine And Synthesis Of Dihydrochmemoindenopyrroles Derivatives

This paper consisted of two parts.The first part was focused on process improvement on the synthesis of?S?-?1-ethylpyrrolidin-2-yl?methanamine.The second one was focused on the synthesis of dihydrochromenoindeno coumarin fused pyrrole derivatives.The first part is divided into two chapters.In first chapter,we simply outlined pharmacological characteristics of antipsychotics sulpiride and imply that?S?-?1-ethylpyrrolidin-2-yl?methanamine is an important synthetic intermediates.Then we summarized synthetic methods of?S?-?1-ethylpyrrolidin-2-yl?methanamine with brief comments on the advantages and disadvantages of each route.The protocal we chose is arising from henry reaction to give 1-ethyl-2-nitromethylenepyrrolidine,which was then reduced with hydrogen in the presence of a catalyst.At last,chiral separation happened.The influence of temperature,reaction media,hydrogen pressure on the yield of?S?-?1-ethylpyrrolidin-2-yl?methanamine was investigated.The total yield increased from 8.1%of the literature to 14%.Compared with the reported methods,this new procedure has the advantages of safety,easy operation,low cost,and being environment-friendly.The influence of temperature,reaction media,hydrogen pressure on the yield of?S?-?1-ethylpyrrolidin-2-yl?methanamine was investigated.The second part is also divided into two chapters.In third chapter,there is a brief introduction of biological activity and synthesis of pyrrolocoumarin derivatives.In forth chapter,a novel synthesis of dihydrochromenoindeno[1,2-b]pyrrolocoumarin derivatives has been developed.We developed the protocol for the synthesis of a series of novel dihydrochromenoindeno[1,2-b]pyrroles in high to excellent yields from the reaction of substituted 4-aminocoumarin and ninhydrin in an equimolar ratio under microwave irradiation.18 novel pyrrolocoumarin derivatives were obtained.The structure of the product was characterized by ¹H-NMR,¹³C-NMR and HRMS-ESI.The structure of12-?4-fluorophenyl?-dihydroxy-6H-chromeno[4,3-b]indeno[1,2-d]pyrrole-6,11-dione was further confirmed by X-ray crystallographic analysis.The possible reaction mechanism was also proposed.No catalysts were required under our conditions.