The Research Of The Preparation Process Of Asthma Drug, Pranlukast

The thesis focused on the research and development of synthesis Pranlukast preparation process.Our synthetic route is started from the two important intermediates 4-phenyl-1-bromobutane and 3-amino-hydroxyacetophenone hydrochloride salt prepared by our group classmates. After etherification, hydrolysis, amidation, condensation of ketone and ester, cyclization, amine solution, amide dehydration cyanide, the cyanide reacted with sodium azide to the target product, pranludast.There are many synthetic methods reported by literatures. There are following characteristics compared with other preparation process reported by papers. The materials are easy to get and cheap. The amount of reactions is reduced. The operations are classical and simple. High yields are obtained in many reactions. So, the byproducts are reduced, harmful substances are avoided emission, the costs are reduced. The total yield is 42.3%. And the process is optimized. Especially, the condensation and cyclization are combined to a one-pot reaction, which reduced the amount of solvent and reaction time. The yield of one-pot reaction reached to 93%. The HPLC purity reached to 99%. In the preparation process of 8-[-4(4-butoxy-pheny)-benzoyl]amine-4-oxo-4H-1-benzopyran-2-cyanide, the cyanuric chloride is used as dehydrating agent, the price is cheaper than that of phosphorus compounds. And the reagent is friendly to environment. The HPLC purity is more than 98%. So, the material is very suitable for industrial production.