Studies On The Industry Synthesis Of Rivaroxaban And The Biological Activities Of Its Derivatives

This paper mainly introduces the thrombosis and kinds of antithrombotic drugs. it focuses on the anticoagulant drugs Rivaroxaban. Rivaroxaban is a new type of oral anticoagulant drug. It has highly effective and direct FXa inhibitor, direct oral, ease to use and needless of continuous monitoring.At first, using 2-Aminoethanol as the starting materials, in the presence of Na H, step cyclization reaction with 2-Chloroethyl Acetate, generate Morpholin-3-one. And then Ullmann reaction occurs with 4-Iodoaniline, under the action of Cu I, generate 4-(4-Aminophenyl)morpholin-3-one.Then, using Phthalimide and epichlorohydrin as raw material, under the action of K2CO3, for preparing the(S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione. And then it occurs the reaction with the key intermediate. Then through CDI cyclization and Methylamine to generate(S)-4-(4-(5-(aminomethyl)-2–oxooxazolidin-3-yl)phenyl) morpholin-3-one., which was condensed with 5-chlorothiophene-2-carbonyl chloride to afford the target compound.This route involves eight steps reaction, readily available raw materials, its reaction conditions is mild, high yield, product separation and purification is simple, less environmental pollution, so it is suitable for industrial production.On the basis of this route, we synthesizes 13 derivatives of rivaroxaban, and biological activity of these derivatives were tested, we concluded: These 13 derivatives have some anticoagulant factor Xa inhibition, but they are inferior to rivaroxaban.