Unlock instant, AI-driven research and patent intelligence for your innovation.
Preparation method of key intermediate of edoxaban
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
An equation and reaction system technology, applied in the direction of organic chemistry, etc., can solve the problems of low reaction yield, poor stability of hydrochloride, affecting reaction progress, etc., to improve the reaction yield, improve the reaction yield and purity, and reduce the dosage. Effect
Pending Publication Date: 2022-01-25
JIANGSU VCARE PHARMATECH
View PDF2 Cites 1 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
[0006] In the existing process for preparing this compound, both raw materialcompound A and compound B participate in the reaction in the form of a salt, but the hydrochloride of compound B has poor stability, and a large amount of alkali needs to be used in the reaction system to neutralize and participate in the reaction. A large amount of solvent needs to be used, and a large amount of salt exists in the reaction system, which affects the progress of the reaction, resulting in a generally low reaction yield
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
[0039]
[0040] DMF (120g) was placed in a 500mL reaction flask, followed by adding compound A (22.5g, 0.079mol, 1.00eq.), compound B (18.9g, 0.083mol, 1.05eq.) and sodium acetate (6.5g, 0.079mol , 1.00eq.), heated to 95 ° C for 8h. Add 240 g of water, keep it at 85°C for 1 hour, solids precipitate out, filter with suction, rinse the filter cake with water, and dry to obtain 32.5 g of compound I as an off-white solid, with a yield of 88.1% and a purity of 98.2%.
Embodiment 2
[0042]
[0043] DMF (120g) was placed in a 500mL reaction flask, followed by adding compound A (22.5g, 0.079mol, 1.00eq.), compound B (18.9g, 0.083mol, 1.05eq.) and sodium acetate (9.7g, 0.118mol , 1.50eq.), heated to 90 ° C for 7h. Add 240g of water, keep it at 85°C for 1 hour, solids precipitate out, filter with suction, rinse the filter cake with water, and dry to obtain 34.3g of compound I as an off-white solid, with a yield of 93.0% and a purity of 98.9%.
Embodiment 3
[0045]
[0046] DMF (120g) was placed in a 500mL reaction flask, followed by adding compound A (22.5g, 0.079mol, 1.00eq.), compound B (18.9g, 0.083mol, 1.05eq.) and sodium acetate (19.4g, 0.236mol , 3.00eq.), heated to 85 ° C for 6h. Add 240g of water, continue to keep warm at 85°C for 1h, solids precipitate out, filter with suction, rinse the filter cake with water, and dry to obtain 34.1g of compound I as off-white solid, yield: 92.5%, purity: 98.6%.
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
The invention relates to a preparation method of a key intermediate of edoxaban which is a blood coagulation factor X (FXa) blocker drug, in particular to a preparation method of a compound I that is tert-butyl [(1R,2S,5S)-2-[[2-[(5-chloropyridin-2-yl) amino]-2-oxoacetyl] amino]-5-(dimethylaminocarbonyl) cyclohexyl] carbamate. According to the method, the compound I is prepared from a compound A and a compound B in a free state in a reaction system with N,N-dimethylformamide as a solvent in the presence of sodium acetate. The raw materials adopted by the method are safe and stable, the reaction yield is high, and the method is suitable for industrial mass production.
Description
technical field [0001] The present invention relates to a kind of preparation method of the key intermediate of coagulation factor X (FXa) blocker drugedoxaban, be specifically related to a kind of compound I: [(1R, 2S, 5S)-2-[[2-[ A preparation method of (5-chloropyridin-2-yl)amino]-2-oxoacetyl]amino]-5-(dimethylaminocarbonyl)cyclohexyl]carbamate tert-butyl belongs to the technical field of medicinal chemistry. Background technique [0002] Chinese patent CN103214414B discloses a preparation method of compound I. In acetonitrile, in the presence of triethylamine (4.6 equivalents), the oxalate of compound A reacts with the hydrochloride of compound B at 60°C. However, this method is unsatisfactory on an industrial level, and the experimental yield of the compound I product is only 62%, and a large amount of base triethylamine is also needed in the reaction, and the volume ratio of triethylamine: acetonitrile is 1: 3.3 , the application of a large amount of triethylamine ma...
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