The Synthetic Study Of Montelukast

Montelukast is a selective, orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor. Montelukast sodium is a useful therapeutic agent for treating respiratory diseases such as asthma and allergic rhinitis. According to the global sales data of IMS and Thomson Reuters, Montelukast has a large market share, and there will be a growing sales trend year by year.This article studied a new process for preparing Montelukast Sodium, and its intermediate2-(2-3-(2-(7-chloro-2-quinolinyl)ethenyl) phenyl-3-hydroxypropyl-)phenyl-2-propanol. This process used2-(2-3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl-3-hydroxypropyl-)phenyl-2-propanol as the starting marterial, under the role of (-)-chlorodiisopinocampherylborane, selectively reduce reaction to produce Chiral compounds2, the yield of this step is95.2%. then under the condition of N, N-diisopropyl-ethylamine and Methanesulfonyl chloride, the hydroxy group of the chiral compound2were converted into leaving group and the compound32were obtained, then under the role of Cesium carbonate and PEG-400, the compound32reacted with1-(mercaptomythyl)cyclopropaneacetic acid, and then reaction with Isopropylamine to produce Montelukast Isopropylamine salt33,the yield of this step was80%.Then followed by conversion of this Isopropylamine salt to the corresponding sodium salt,the yield of this step was81%the total yield of this route was61.7%and the HPLC purity of the final product was99.5%, the structure of the final product and the intermediates was confirmed by1HNMR and13C NMR.The starting marterial of this route was cheap and easy to obtain, and the operation was easy, and could be effectively used in the industry.