The Optimization To Synthesis Of Isoprinosine And Its Application

P-nitrotoluene was reduced to p-methyl aniline by reduced iron powder in acidic conditions.A small amount of ammonium chloride was added to promote the reduction reaction carried out.the inorganic phase and the organic phase was separated by using benzene and sodium carbonate solution extracting after cooling.Nature of p-methylaniline is dissolved in inorganic acid and p-nitrotoluene is not dissolved inorganic acid was used in extraction separation.then p-methylaniline was obtained as a white solid.Orthogonal experiment was carried out to explore the optimal reaction conditionsP-methylaniline obtained in the previous step was acetylated with acetic anhydride in an anhydrous environment.Reaction was carried out at a temperature of 70 ? for 1h,The unreacted acetic anhydride was removed by cool water,and unreacted p-toluidine is removing by hot water.The white solid is obtained is p-methyl acetanilide.Orthogonal experiment was carried out to explore the optimal reaction conditions P-methylacetanilide,potassium permanganate(potassium permanganate is added portionwise),magnesium sulfate heptahydrate were put in a 100 mL three-necked flask,30 mL of water was added,heated with stirring,and the reaction lasted 8 to 11 h,the reaction solution was centrifuged after cooling,the supernatant was added hydrochloric acid to pH=2~3,White crystals was separated form the supernatant.the crystals was washed with ethanol,purified by recrystallization,dried and weighed to obtain the compound:p-acetylamino benzoic acid.Orthogonal experiment was carried out to explore the optimal reaction conditions.Acetamido-benzoic acid dissolved in ethanol(ethanol was overdosed to ensure that the acetylamino benzoic acid was completely dissolved),l-dimethylamino-2-propanol was added dropwise.Reaction was carried out at a temperature of 40~50 ? for 2h,or at room temperature for 3~5h.After the reaction was stopped,suction filtration was carried out.The filtrate was concentrated by heating off half of the solution,then excess of ethyl acetate was sdded to precipitate crystals.The precipitate crystals washed with ethylacetate and dried to give a white crystalline powder.Orthogonal experiment was.carried out to explore the optimal reaction conditionsDimethylamino isopropanol acetamido benzoate was dissolved in ethanol,inosine and water were added,reaction system was stirred for distillation under reduced pressure.ethyl acetate was azeotropically dehydrated to anhydrous distilled off,separated,washed,and dried to give a white powder: isoprinosine.Isoprinosine was prepared as tablets and capsules,in accordance with the disintegration performance of the Chinese Pharmacopoeia 2005 edition and the Chinese Pharmacopoeia 2010 version of the test preparation,dissolution,light resistance,high temperature resistance,high humidity resistance,to detect the physical and chemical properties are in line with the Pharmacopoeia requirements.