CN105646470A - Refining method for rivaroxaban - Google Patents
Refining method for rivaroxaban Download PDFInfo
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- CN105646470A CN105646470A CN201410670860.6A CN201410670860A CN105646470A CN 105646470 A CN105646470 A CN 105646470A CN 201410670860 A CN201410670860 A CN 201410670860A CN 105646470 A CN105646470 A CN 105646470A
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- acetic acid
- glacial acetic
- razaxaban
- purification
- weight part
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Abstract
The invention discloses a refining method for rivaroxaban. The refining method has the advantages of simple operation, mild reaction conditions, cheap and easily obtained used reagents, high yield and high final product purity, and is harmless to a human body and environment.
Description
Technical field
The present invention relates to the process for purification of a kind of razaxaban, belong to chemicals technical field of purification.
Background technology
Razaxaban, English name Rivaroxaban, No. CAS: 366789-02-8. Razaxaban sheet releases listing in July, 2011 in the U.S. by Bayer pharmaceuticals, be a kind of highly selective can be directly oral Xa factor inhibitor, the inherence of blood coagulation cascade and external path is interrupted by anticoagulant factor Xa, thus the generation of Trombin inhibiting and thrombosis. Razaxaban is Trombin inhibiting (activation factor II) not, does not also prove that it has impact for thrombocyte.
Razaxaban is mainly used in select a time hip joint or replacement knee in arthroplasty adult patients, to prevent venous thromboembolism (VTE). Venous thromboembolism comprises venous thrombosis (DVT) and pulmonary infarction (PE), is one of main cause of death of the mankind. Deep venous thrombosis is complication common after orthopaedics major operation, and its main harm can make suffering limb swelling, affects activity, can disable time serious; The more important thing is that the pulmonary infarction of 90% comes from DVT embolus and comes off, can be fatal time serious. For full hip-joint displacement, after displacement, very easily there is DVT. Along with total hip arthroplasty at home universal, after displacement, DVT problem is day by day outstanding.
In the prior art, such as Chinese patent 00818966.8, utilizing Flash silica gel chromatography post that profit is cut down his class's crude product and carry out purifying, complicated operation, production cost height, the purity of products obtained therefrom is not high yet.
Summary of the invention
It is an object of the invention to provide the process for purification of a kind of razaxaban, simplify production operation, reduce production cost, it is to increase product yield and product purity.
The process for purification of razaxaban provided by the invention is specially:
Being dropped in reactor by razaxaban crude product, add Glacial acetic acid, be heated to 100��120 DEG C, molten clear rear insulated and stirred, filters, and filtrate is cooled to 15��20 DEG C, crystallize out, filters, uses Glacial acetic acid drip washing, take out filter, dry.
The razaxaban process for purification of the present invention is further:
Razaxaban crude product 1.8 weight part is put in reactor, adds Glacial acetic acid 18��22 weight part, be heated to 110 DEG C, molten clear rear insulated and stirred, heat filtering, filtrate is cooled to 15��20 DEG C, brilliant in the analysis of this temperature, filters, with 2��4 pbw of glacial acetic acid drip washing, take out filter, dry.
In one particular embodiment of the present invention, razaxaban crude product 1.8 weight part is put in reactor, adds Glacial acetic acid 20 weight part, be heated to 110 DEG C, molten clear rear insulated and stirred, heat filtering, filtrate is cooled to 15��20 DEG C, crystallize out, filter, with 3 pbw of glacial acetic acid drip washing, take out filter, dry.
The razaxaban process for purification of the present invention is simple to operate, and reaction conditions is gentle, and agents useful for same is cheap and easy to get, to human body and environmentally friendly, and receipts rate height, finished product purity height.
In the prior art, in the method that in Chinese patent 00818966.8 specification sheets, embodiment 44 is recorded, employing be the method for silica gel chromatography, this kind of method receipts rate is low, and purity is low, complicated operation, and batch output is little, is not suitable for industrialized production.
The present invention adopts the method for recrystallization, and the present inventor finds in an experiment, is different from general organic solvent, and Glacial acetic acid is especially suitable for use as the recrystallization solvent of razaxaban. With the recrystallization solvent of Glacial acetic acid as razaxaban, crystallization effect is good, and brilliant type is single, stable, receipts rate height, product purity height.
Embodiment
The invention will be further described by the following examples, but this is not limitation of the present invention, those skilled in the art are according to the basic thought of the present invention, it is possible to make various amendment or improvement, as long as but do not depart from the basic thought of the present invention, all within the scope of the present invention.
Embodiment 1:
Razaxaban crude product 1.8kg is put in 20L glass reaction still, adds Glacial acetic acid 20kg, be heated to 110 DEG C, molten clear rear insulated and stirred 10min, heat filtering, filtrate is cooled to 15��20 DEG C, brilliant in the analysis of this temperature, filter, with 3kg Glacial acetic acid drip washing, take out filter, forced air drying, obtain white solid, it is razaxaban highly finished product, receipts rate 65%, it may also be useful to the high-efficient liquid phase chromatogram condition detection of embodiment 1 in Chinese patent 201310556108.4, purity 99.7%.
Comparative example:
According to the method that embodiment 44 in Chinese patent 00818966.8 specification sheets is recorded, by razaxaban crude product 1.8kg Flash silica gel chromatography column purification, with methylene chloride-methanol mixture wash-out, collect elutriant, drying under reduced pressure, obtains off-white color solid, is razaxaban. Receipts rate 43%, it may also be useful to the high-efficient liquid phase chromatogram condition detection of embodiment 1 in Chinese patent 201310556108.4, purity 82%.
Claims (3)
1. a process for purification for razaxaban, drops into razaxaban crude product in reactor, adds Glacial acetic acid, be heated to 100��120 DEG C, and molten clear rear insulated and stirred, filters, and filtrate is cooled to 15��20 DEG C, crystallize out, filters, uses Glacial acetic acid drip washing, take out filter, dry.
2. process for purification as claimed in claim 1, it is characterised in that, razaxaban crude product 1.8 weight part is put in reactor, add Glacial acetic acid 18��22 weight part, it is heated to 110 DEG C, molten clear rear insulated and stirred, heat filtering, filtrate is cooled to 15��20 DEG C, brilliant in the analysis of this temperature, filter, with 2��4 pbw of glacial acetic acid drip washing, take out filter, dry.
3. process for purification as claimed in claim 1, it is characterised in that, razaxaban crude product 1.8 weight part is put in reactor, add Glacial acetic acid 20 weight part, it is heated to 110 DEG C, molten clear rear insulated and stirred, heat filtering, filtrate is cooled to 15��20 DEG C, crystallize out, filters, with 3 pbw of glacial acetic acid drip washing, take out filter, dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410670860.6A CN105646470A (en) | 2014-11-21 | 2014-11-21 | Refining method for rivaroxaban |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410670860.6A CN105646470A (en) | 2014-11-21 | 2014-11-21 | Refining method for rivaroxaban |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105646470A true CN105646470A (en) | 2016-06-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410670860.6A Pending CN105646470A (en) | 2014-11-21 | 2014-11-21 | Refining method for rivaroxaban |
Country Status (1)
| Country | Link |
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| CN (1) | CN105646470A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110003193A (en) * | 2019-04-02 | 2019-07-12 | 北京四环制药有限公司 | It is a kind of to prepare the razaxaban and preparation method thereof for being easy to crush |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102786516A (en) * | 2012-08-21 | 2012-11-21 | 湖南师范大学 | Method for synthesizing rivaroxaban |
| CN104016975A (en) * | 2014-06-27 | 2014-09-03 | 深圳翰宇药业股份有限公司 | Preparation method of rivaroxaban |
| CN104031036A (en) * | 2014-05-16 | 2014-09-10 | 南通常佑药业科技有限公司 | Method for preparing rivaroxaban |
-
2014
- 2014-11-21 CN CN201410670860.6A patent/CN105646470A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102786516A (en) * | 2012-08-21 | 2012-11-21 | 湖南师范大学 | Method for synthesizing rivaroxaban |
| CN104031036A (en) * | 2014-05-16 | 2014-09-10 | 南通常佑药业科技有限公司 | Method for preparing rivaroxaban |
| CN104016975A (en) * | 2014-06-27 | 2014-09-03 | 深圳翰宇药业股份有限公司 | Preparation method of rivaroxaban |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110003193A (en) * | 2019-04-02 | 2019-07-12 | 北京四环制药有限公司 | It is a kind of to prepare the razaxaban and preparation method thereof for being easy to crush |
| CN110003193B (en) * | 2019-04-02 | 2023-12-05 | 北京四环制药有限公司 | Rivaroxaban easy to crush and preparation method thereof |
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Application publication date: 20160608 |
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| WD01 | Invention patent application deemed withdrawn after publication |