Unlock instant, AI-driven research and patent intelligence for your innovation.
Method for preparing high optical purity pitavastatin calcium raw material drug
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 pitavastatin calcium and raw materials, which is applied in the field of preparation of cholesterol-lowering drugs, can solve problems such as low yield and difficult separation and purification, and achieve low-cost effects
Active Publication Date: 2009-07-01
CHINA RESOURCES DOUBLE CRANE PHARMA COMPANY
View PDF3 Cites 6 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
Solve the technical problems of the existing preparation of pitavastatin calciumraw material drug separation and purification difficulty, 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.
[0036] Put 27g of compound II and 62.5g (1.25eq) of phosphorusylide 1 into a 1L single-port reaction flask, add 680ml of anhydrousacetonitrile, stir, heat to 70-80°C for 24 hours, and TLC monitors that the reaction is basically complete. The solvent was distilled off, and the residue was 45.7 g of a slurry separated by column. Yield 90%.
[0041] 2: Preparation of (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline]-5-carbonyl-(3R)-hydroxy-6-heptenoic ac...
Embodiment 2
[0082] 1: (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline]-5-carbonyl-(3R)-3-(tert-butyldimethylsiloxane ) Preparation of ethyl 6-heptenoate
[0083] Reaction formula:
[0084]
[0085] Steps
[0086] Put 18g of compound II and 66.01 (2.0eq) of phosphorusylide 1 into a 1L single-port reaction flask, add 700ml of anhydrous THF, stir, heat to 60-70°C for 48 hours, and TLC monitors that the reaction is basically complete. The solvent was distilled off, and the residue was 27.4 g of slurry separated by column, but the yield decreased to 81%.
[0087] [α] D 25 : -8.10 (c, 1.1; MeOH).
Embodiment 3
[0089] 1: (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline]-5-carbonyl-(3R)-3-(tert-butyldimethylsiloxane ) Preparation of ethyl 6-heptenoate
[0090] Reaction formula:
[0091]
[0092] Steps
[0093]Put 18g of compound II and 59.4 (1.8eq) of phosphorusylide 1 into a 1L single-port reaction flask, add 600ml of anhydroustoluene and stir, heat to 100°C for 12 hours, and TLC monitors that the reaction is basically complete. The solvent was distilled off, and the residue was 28.4 g of slurry separated by column, the yield was 85%.
[0094] [α] D 25 : -8.10 (c, 1.1; MeOH)
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 method for preparing a raw materialdrug of pitavastatincalcium with high optical purity, which mainly solves the technical problems of high difficulty in separation and purification of the raw materialdrug of pitavastatincalcium and low yield. The method comprises the following steps: 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarbaldehyde II and (3R)-3-alkylsilyloxy-5-carbonyl-6-triphenyl (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline]-5-carbonyl-(3R)- 3-Alkylsilyloxy-6-heptenoate IV, IV is deprotected with a deprotecting agent to obtain (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3- Quinoline]-5-carbonyl-(3R)-hydroxyl-6-heptenoic acid ester V, which was mixed with NaBH in a mixed solvent of an alcohol and an ether compound 4 or KBH 4 And selective reduction under the action of the ligand, the reaction temperature is -100 ° C to 0 ° C, to obtain (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinoline] -(3R,5S)-dihydroxy-6-heptenoic acid ester VI, which is hydrolyzed into calcium salt with alkali to obtain pitavastatin calcium. It is mainly used in the preparation of HMG-CoA reductase inhibitors, a drug for lowering blood lipids.
Description
Technical field: [0001] The present invention relates to a kind of preparation method of cholesterol-lowering medicine, is the new preparation method of cholesterol-lowering medicine (HMG-CoA reductase inhibitor) pitavastatin calciumcrude drug (I): [0002] technical background: [0003] Pitavastatin calcium (I) is Japanese Patent Application No. 1-279866, EP304063, disclosed in U.S. Patent No. 5,011,930 as a hypolipidemic drug (HMG-CoA reductase inhibitor), and pitavastatin calcium is produced by Japan Nissan Chemical Industry Co., Ltd. It was developed and jointly applied by Nissan Chemical Industry Co., Ltd., Kowa Co., Ltd. and Sankyo Co., Ltd., and was approved for marketing in Japan in July 2003 for the treatment of hypercholesterolemia. The product name is , film-coated tablets with formulation specifications of 1 mg and 2 mg. [0004] Since the first statin drug lovastatin was launched in 1987, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors...
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 
