Sildenafil Intermediate 1 - Methyl - 3 - N-propyl -4 - Nitro-pyrazole-5 - Carboxamide,

Sildenafil is the first oral therapeutic agent for erectile dysfunction, SildenafiI is a selective inhibitor of cGMP-specific phosphodiesterase (PDE-5).Nowadays,sildenafil is protected by State Intellectual Property Office, so it is very expensive.At the same time,it is reported that the population of male erectile dysfunction is very high,then it is very necessary to study and product this drug.By the end of the patent in 2014,we would have made a deference in economy and society.In this paper,1-methyl-3-propyl-4-nitro-5-formamide was synthesized from 2-pentanone and diethyl oxalate via claisen condensation,hydrazinolytic cyclization,methylation, hydrolysis, nitration. 3-propylpyrazole-5-carboxylic ethyl ester was prepared by the "one-pot" method.As the reactions of methylation and hydrolysis were completed in one reactor,the intermidiate needn't be isolated and purified by silicon colum chromatography,but was hydrolyzed directly.In the course of the preparation for 1-methyl-3-propyl-4-nitro- pyrazole-5-formamide,the post-processing methods is improved by steaming to remove most dichloro sulfoxide, have a small amount of the Second Thionyl chloride to ensure the flow of residue, and then slowly infusion residue low temperature(0-20℃)concentrated ammonia solution,salt out,the product rapiddly crystallizate out. The method improved is simple,saving acetone, methylene chloride, and other reagent consumption, getting products of good quality and high yield.During the experiment,we paid attention to the following reaction conditions which affect the reaction yield,such as choice of solvent, reaction time, reaction temperature,the speed of agitator and etc.,by means of orthogonal design method and corresponding method,the optimum reactant compostion and reaction conditions were obtained.The synthesized products were confirmed by m.p,IR,1H-NMR and else analysis to be consistent with the target products.Moreoverthe novel process mentioned above provide a better way to obtain 1-methyl-3-propyl-4-nitro-5-formamide and was simple,mild,and more suitable for industrial production.