Betrixaban intermediate preparation method

Abstract

The invention discloses a method for preparing the key intermediate compound B of Betrixaban, wherein a compound A represented by the following formula is reduced by using hydrazine hydrate as a reducing agent under the catalysis of ferric chloride. Compared to the existing preparation method, the preparation method of the invention has advantages of controllable reaction, mild reaction condition,simple post-treatment, high yield, no generation of dechlorination impurity and substantially reduced production cost, and is suitable for industrial production, wherein the yield is more than 90%, and the purity is more than 98%.

Description

technical field [0001] The invention relates to the technical field of a reduction synthesis method of an intermediate of Betrixaban. Background technique [0002] Betrixaban is a highly selective coagulation factor Xa inhibitor developed by Portola Pharmaceuticals, Inc for acute venous thromboembolism (VTE) in high-risk patients with acute medical illness prevention and treatment. Compound B is an important intermediate for the synthesis of Betrixaban, which is obtained from compound A through reduction. [0003] Through literature search, the method for reducing A to B has been reported both at home and abroad at present, wherein Milenium Company mentions in its preparation method patent (WO2007056517 / CN102336702), with platinum carbon (5% through vulcanization), at 30psi React under hydrogen pressure for 16h to obtain the target compound B. [0004] The synthesis method is as follows: [0005] [0006] However, there are Pt / C expensive in this method, the reaction ...

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Problems solved by technology

[0016] However, this route uses hydrogen pressurized reduction, the conditions are harsh, and dechlorination impurities are produced during the reaction process.

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