Unlock instant, AI-driven research and patent intelligence for your innovation.
Synthesis method of donepezil hydrochloride
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 technology of donepezil hydrochloride and its synthesis method, which is applied in the field of drug synthesis, can solve the problems of less than 20% total route yield, complex hydride preparation process, and many operation steps, so as to solve the problem of selectivity, reduce the generation of by-products, The effect of high safety factor
Active Publication Date: 2019-04-19
SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD +2
View PDF8 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
[0004] The total yield of this route is less than 20%
[0012] The disadvantage is that the product donepezil reacted with benzyl bromide in the last step of the process will further react with benzyl bromide to produce impurities, which need to be refined to remove, and the yield is only 70-75%.
[0013] In EP0711756A1, 5,6-dimethoxy-2-[(4-pyridyl)methylene]-1-indanone is first reacted with benzyl bromide to obtain donepezil by catalytic hydrogenation. Take off to generate more impurities, and the product needs to be refined many times to be qualified, resulting in a low yield
[0014] CN101723878A directly uses hydride 5,6-dimethoxy-2-(4-piperidinylmethyl)-1-indanone as raw material to condense with substituted benzyl sulfonate to obtain donepezil, with a higher yield and a purity of 97 % or so, but the preparation process of hydride is still complicated
[0017] The disadvantage of this process is that there are many operating steps, resulting in low 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
[0037] Embodiment 1: the synthesis of compound III
[0038] In a three-necked flask equipped with a condenser tube and a stirrer, add 60 mL of acetone, 9.6 g of 5,6-dimethoxy-1-indanone, 5.55 g (0.05 mol) of anhydrouscalciumchloride, and 4-pyridinecarbaldehyde 5.89g, potassiumiodide 0.96g, stirred at 40-50°C for 4h, HPLC monitored that the reaction was basically complete, cooled to room temperature, filtered, concentrated the filtrate, added 100mL of ethyl acetate to crystallize, filtered, and dried in vacuo to obtain 12.96g of compound III , the yield was 92.2%, and the purity by HPLC was 99.7%.
Embodiment 2
[0039] Embodiment 2: the synthesis of compound III
[0040] In a three-necked flask equipped with a condenser tube and a stirrer, add 60 mL of acetone, 9.6 g of 5,6-dimethoxy-1-indanone, 11.97 g (0.075 mol) of anhydrouscoppersulfate, and 5.89 g of 4-pyridinecarbaldehyde g, potassiumiodide 0.96g, stirred at 40-50°C for 4h, HPLC monitored that the reaction was basically complete, cooled to room temperature, filtered, concentrated the filtrate, added 100mL of 2-butanone to crystallize, filtered, and dried in vacuo to obtain 12.89g of compound III , yield 91.7%, HPLC detection purity 99.6%.
Embodiment 3
[0041] Embodiment 3: the synthesis of compound III
[0042] In a three-necked flask equipped with a condenser tube and a stirrer, add acetone 60mL, 5,6-dimethoxy-1-indanone 9.6g, potassiumcarbonate 8.98g (0.065mol), 4-pyridinecarbaldehyde 5.89g, Potassiumiodide 0.96g, stirred at 40-50°C for 4h, HPLC monitored that the reaction was basically complete, cooled to room temperature, filtered, concentrated the filtrate, added 100mL of chloroform to crystallize, filtered, and dried in vacuo to obtain 12.93g of compound III with a yield of 92.0% , HPLC detection purity 99.8%.
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 belongs to the technical field of medicine, and discloses a synthesis method of donepezilhydrochloride. 5,6-dimethoxyl-1-indanone and 4-pyridyl aldehyde are taken as the primary raw materials, a mixed catalyst is adopted to produce an intermediate (I), a hydrogen source is used to replace hydrogen gas to carry out catalytic transfer hydrogenation reactions, and the reaction productreacts with benzyl chloride to obtain donepezilhydrochloride. The adopted catalyst can be completely removed through filtering, the post treatment is simple, the reaction conditions are mild, moreover, the selectivity problem of hydrogen reduction in the prior art is solved, the yield and purity are high, and the synthesis method is suitable for industrial production.
Description
technical field [0001] The invention belongs to the field of drug synthesis, in particular to a method for synthesizing donepezilhydrochloride. Background technique [0002] Donepezil hydrochloride is a highly selective, long-acting and reversible acetylcholinesterase inhibitor developed by Japan Eisai Co., Ltd. for the treatment of mild to moderate Alzheimer's disease. The synthetic route involved in Eisai Pharmaceuticals is: [0003] [0004] The total yield of this route is less than 20%. [0005] The method of synthesizing donepezil hydrochloride mainly contains following several at present [0006] Method 1: German Bayer company discloses the following reaction formula in patent EP0711756A1: [0007] [0008] There is a selectivity problem in the hydrogenation of the last step of the above-mentioned process method, which leads to an increase in impurities (the crude product contains 5%), low and unstable yield, difficult recovery of the catalyst and other shor...
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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/32
CPCC07D211/32
Inventor 李明杰李俊广李成
Owner SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
Login to View More 
Login to View More