Preparation method for rivaroxaban intermediate and rivaroxaban

Abstract

The invention discloses a rivaroxaban intermediate, a structural formula of the rivaroxaban intermediate is represented by the following formula (III). The invention further discloses a preparation method for rivaroxaban. The method is characterized by: carrying out a cyclization reaction for 4-(4-isocyanatophenyl)-3-morpholinone and (R)-epichlorohydrin under a catalytic action of magnesium halide to generate (S)-4- morpholinonephenyloxazolidinone, followed by carrying out functional group conversion to obtain 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidine-3-yl] phenyl}-morpholine-3-ketone, then reacting with 5-chlorothiophene-2-formyl chloride to prepare the rivaroxaban. The preparation method provided by the present invention has advantages of mild reaction conditions, simple operation, high reaction yield and the like. In addition, the use of toxic and harmful reagents is avoided during the synthesis process, such that environmental pollution is reduced, and the method is applicable for the industrial production.

Description

technical field The invention belongs to the technical field of medicine synthesis, in particular to a preparation method of an anticoagulant drug rivaroxaban intermediate and rivaroxaban. Background technique Thrombosis is the formation of local blood clots. Among them, arterial thrombosis can lead to myocardial infarction, stroke, acute coronary syndrome and peripheral arterial disease, etc.; venous thrombosis can cause pulmonary embolism. Arteriovenous thrombosis is the leading cause of cardiovascular disease morbidity and death, and it is also one of the leading causes of death in cancer patients. Venous thromboembolism (VTE) is a type of disease caused by blood coagulation in veins to form thrombus, which can cause deep vein thrombosis and its serious complication—pulmonary embolism, which can quickly endanger the life of the patient. Due to the hidden symptoms of these diseases, especially deep vein thrombosis, 80% of patients without clinical manifestations are miss...

AI Technical Summary

Problems solved by technology

Although the above-mentioned technical schemes have their own advantages, there are dangerous reaction reagents such as butyllithium or tert-butyllithium, highly toxic reagent phosgene, or expensive raw materials, and the reaction route is long, the environment is seriously polluted, and the cost is relatively high. High, low yield, not conducive to the defects of industrial production