Unlock instant, AI-driven research and patent intelligence for your innovation.
Refining method for apixaban
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A purification method and apixaban technology, applied in the purification field of apixaban, can solve the problems of complicated operation, poor solubility, waste of energy and the like, and achieve the effects of low dissolution temperature, simple operation and high yield
Active Publication Date: 2017-03-22
LEPU PHARMACEUTICAL CO LTD
View PDF4 Cites 4 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0007] In this route, apixaban acid often exists in crude apixaban as an impurity, and it is difficult to completely remove it due to its structural similarity with apixaban
The solubility of apixaban in a single solvent is not good, and the general refining operation requires the method of heating, dissolving and crystallizing. Even if repeated refining is performed, it is easy to cause the residue of apixaban acid to exceed the standard, which is not only cumbersome to operate, but also wastes energy. , not conducive to industrial production
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0020] A method for refining Apixaban, the specific steps are as follows:
[0021] Add 14kg of dichloromethane to the 50L reaction kettle, start stirring, add 1.4kg of crude apixaban, then add 14kg of methanol, stir for 30 minutes until completely dissolved, filter out insolubles if necessary; put 2.5kg of 3wt% sodiumhydroxide Add the solution into the reaction kettle, stir for 1 hour, and let stand to separate the liquid; transfer the organic layer into a 50L reaction kettle, start stirring, slowly add 28kg of n-hexane, mix well, leave it under natural conditions for 4 hours to precipitate solids, and filter; The solid was air-dried at 60° C. for 8 hours to obtain 1.3 kg of fine apixaban product. HPLC: 99.92%, Apixabanic acid 0%, H 1 NMR (d6-DMSO δ: 7.71(br, 1H), 7.51(m, 2H), 7.43(br, 1H), 7.35(m, 2H), 7.28(m, 2H), 7.00(m, 2H), 4.06 (m,2H), 3.79(s,3H), 3.58(m,2H), 3.20(m,2H), 2.39(m,2H), 1.83(m,4H).
Embodiment 2
[0023] A method for refining Apixaban, the specific steps are as follows:
[0024] At 25°C, add 25kg of dichloromethane into the 50L reaction kettle, start stirring, add 1.8kg of crude apixaban, then add 15kg of methanol, stir for 30 minutes until completely dissolved, filter out insolubles if necessary; put 6.2kg Add 3wt% sodiumhydroxide solution into the reaction kettle, stir for 1 hour, let stand to separate the liquid; transfer the organic layer into a 50L reaction kettle, start stirring, slowly add 28kg cyclohexane, mix well, and place it under natural conditions for 4 hours The solid was precipitated and filtered; the solid was air-dried at 60° C. for 8 hours to obtain 1.6 kg of fine apixaban product. HPLC: 99.91%, Apixabanic acid: 0%.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
PUM
Login to View More
Abstract
A refining method for apixaban comprises the following steps: 1) dissolving an apixaban crude product in a mixed solvent of dichloromethane and methanol, to obtain an apixaban solution; 2) adding a sodiumhydroxide solution, stirring and washing the apixaban solution of the step 1), and then separating to obtain an organic layer; and 3) adding n-hexane to the organic layer of the step 2) under stirring, mixing evenly, placing to separate out a solid under natural conditions, filtering, and drying to obtain refined apixaban. The refined apixaban obtained by the refining method is from white to off-white in color, and has the advantages of high quality and high yield; the method has low required dissolution temperature, has simple operation, and is suitable for industrialized production.
Description
technical field [0001] The invention belongs to the field of pharmacy and chemical industry, and in particular relates to a method for refining apixaban. Background technique [0002] Apixaban, chemical name: 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5, 6,7-tetrahydro-1H-pyrazol[3,4-c]-pyridine-3-carboxamide, CAS: 503612-47-3, structure: [0003] [0004] Apixaban is an anticoagulantdrug jointly declared by Pfizer and Bristol-Myers Squibb. It has an important clinical effect on the prevention of venous thromboembolism in patients after hip or knee replacement. It may also be used to prevent stroke risk in patients with atrial fibrillation. Apixaban was launched in the European Union and the United States in 2011 and 2012, respectively. [0005] At present, the preparation methods of apixaban and similar methods reported in the literature include: WO2007001385A2, WO03026652A1, WO0039131A1, and their routes are summarized as follows: [0006] [...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to View More 
Login to View More 
