Synthesis Of Sivelestat

Systemic Inflammatory Response Syndrome ( SIRS ) is originated systemic inflammatory response include infection, burn, wounds, operation, pancreatitis and ischemia-reperfusion etc. many factors . the new clinical concept had become a research focus in recent. Sivelestat sodium hydrate is a kind of drug which was exploited by Ono, it treat with a kind of disease which named'systemic inflammatory response syndrome', for short'SIRS'. The drug was approved on April 11, 2002 in Japan and it was launched for ALI of treatment . in dysfunction of SIRS, the ALI is very intractable. Except for treating with ALI , sivelestat may be for a kind of new nerve protectant. It can utendus adjunctive therapy of cerebral ischemia, cerebral hemorrhage, cerebral trauma etc. That's the reason what the paper carry through the research.sivelestat sodium hydrate in the paper is synthesed by Glycine benzyl ester p-toluenesulfonate salt , 2-Nitrobenzoyl chloride, 4-Hydroxybenzenesulfonic acid and pivoloyl chloride as initiat materials. at first, Glycine benzyl ester p-toluenesulfonate salt and 2-Nitrobenzoyl chloride condensation reaction result to the intermediate A , then the intermediate A is reduct result to the intermediate B by Fe; meanwhile, condensation reaction of pivoloyl chloride and 4-Hydroxybenzenesulfonic acid result to the intermediate C, compound C acylation react with Thionyl chloride result to compoud D, then B and D result to the end product by a series condensation, hydrogenation and salificat with sodium hydroxide. In order to improve reaction rate and reduce material cost, we do a series of experiments, research each step reaction mechanism and optimalize technology.the article innovation include some ways. 1. we improve technology of the intermediate C , the yield raise from 44.5% on the paper to 67.8%. 2. in the nitration reduction, Acetic acid replace to hydrochloric acid which is benefit for decrease by-product. 3. In the preparation of the intermediate E, we improve the post-processing, it relieve burden of the post-processing and it is benefit for environmental protection. 4. In the preparation of end product, we evaporate to dryness after the reaction, the yield raise from 80.8% to 98.8%, HPLC is achieved to 99.3%. 5. All reaction are mild without extra temprature and pressure in the paper route. they have no three waste burden also. So it fits for industrialization manufacture. The product was authenticated by melting point, elemental analysis, IR spectrum, UV spectrum, MS spectrum, 1HNMR spectrum, 13CNMR spectrum etc.