Synthesizing and refining methods of rivaroxaban

Abstract

The invention relates to the field of pharmaceutical chemistry, and provides synthesizing and refining methods of rivaroxaban. The synthesis method comprises a step 1) of performing condensation reaction on 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one(LF-II) and 5-chlorothiophene-2-carboxylic acid (SMI) under an alkaline system to prepare crude rivaroxaban; the refining method further comprises a step 2) of stirring and crystallizing the crude rivaroxaban and an alcohol solution at room temperature to obtain high-purity refined rivaroxaban which meets requirements of desired crystal form. The synthesizing and refining methods are simple in operation of preparation processes, high in yield, low in pollution, and suitable for large-scale industrial production.

Description

technical field

[0001] The invention belongs to the field of drug synthesis, in particular to a method for synthesizing and refining rivaroxaban. Background technique

[0002] Rivaroxaban (I), English name: Rivaroxaban. Its chemical name is: 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidine -5-yl}methyl)-2-thiophenecarboxamide, its molecular formula is: C 19 h 18 ClN 3 o 5 S.

[0003]

[0004] Rivaroxaban is a high-efficiency selective factor Xa inhibitor jointly developed by Bayer and Johnson & Johnson. It was approved for marketing in Canada and the European Union in 2008 under the trade name Xarelto. It was officially launched in China in June 2009, and was approved by the US FDA in July 2011. Rivaroxaban is the first oral direct factor Xa inhibitor in the world. It can directly inhibit factor Xa in free or bound state with high selectivity and produce anticoagulant effect. It has high bioavailability and wide spectrum of treatment diseas...

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