Studies On The Synthesis Of The Intermediate Of Sildenafil Citrate 1-methyl-3-proryl-4-nitropyrazole-5-carboxylic Acid

Sildenafil is the first oral therapeutic agent for erectile dysfunction.Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase(PDE5).Nowadays,siIdenafil 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-nitropyrazole-5-carboxylic acid 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.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 molar ratio of reactant, pH, 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,1~HNMR and else analysis to be consistent with the target products. Moreover,the novel process mentioned above provide a better way to obtain 1- methyl - 3- propyl- 4- nitropyrazole- 5 -carboxylic acid and was simple, mild,and more suitable for industrial production.