Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation

A pitavastatin calcium, asymmetric technology, applied in the field of cholesterol-lowering drugs in the field of medicinal chemistry technology, can solve problems such as the source of chiral side chains, and achieve the effect of solving expensive

Active Publication Date: 2009-03-18
JIANGSU WANBANG BIOPHARMLS +1
View PDF2 Cites 28 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to address the deficiencies in the prior art, to provide a method for preparing pitavastatin calcium bulk drug by asymmetric hydrogenation, which mainly solves the problem of the chiral side chain source of pitavastatin calcium bulk drug in the existing preparation

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
  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation
  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation
  • Method for preparing pitavastatin calcium raw material medicine using asymmetric hydrogenation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0030] The embodiments of the present invention are described in detail below: the present embodiment is implemented under the premise of the technical solution of the present invention, and detailed implementation and specific operation process are provided, but the protection scope of the present invention is not limited to the following implementation example.

[0031] 1. Preparation of (S)-4-benzyloxy-3-hydroxybutyric acid ethyl ester and chiral catalyst (using Sunphos

[0032] For example, others can be prepared in a similar way). Reaction formula:

[0033]

[0034] Steps

[0035] Schlenk reaction tube, pumped and baked three times, added [RuCl 2 (p-Cymene)] 2 (21.6mg, 35.3μmol, 1eq), Sunphos (56.1mg, 77.0μmol, 2.2eq), replace nitrogen three times, add EtOH / CH 2 Cl 2 (9mL / 3mL), heated to 40°C for 3.5h, and dried to obtain an orange powdery solid catalyst.

[0036]

[0037] In a 150mL small beaker, add I (50.0g, 211.6mmol, 1eq), EtOH (80mL), chiral catalyst (S...

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

No PUM Login to View More

Abstract

The invention relates to a method for preparing a pitavastatin calcium raw material by asymmetric hydrogenation in the technical field of medicinal chemistry. The method comprises the following steps: performing catalytic hydrogenation on 4-benzyloxy-ethyl-acetoacetate I by using a chiral catalyst to prepare (S)-4-benzyloxy-3-hydroxy-ethyl-butyrate, and then obtaining the pitavastatin calcium through a series of reactions such as Claisen condensation, reduction, hydroxyl protection, removal of benzyl, oxidation and the like. In the invention, the highly-efficient chirality added value is realized by the use of catalytic amount of the chiral catalyst (wherein the ratio of substrate to the catalyst can reach 3, 000 to 1), and by performing the asymmetric hydrogenation and the reduction on non-chiral ketones to generate chiral alcohols compounds directly (wherein the enantioselectivity can be up to 94.3 percent).

Description

technical field [0001] The invention relates to a method for lowering cholesterol drugs in the technical field of medicinal chemistry, in particular to a method for preparing pitavastatin calcium crude drug by asymmetric hydrogenation. Background technique [0002] Pitavastatin calcium is Japanese Patent Application Publication No. 1-279866, EP304063, disclosed in U.S. Patent No. 5011930 as a blood lipid-lowering drug (HMG-CoA reductase inhibitor), and pitavastatin calcium is developed by Japan Nissan Chemical Industry Co., Ltd. And by Nissan Chemical Industry Co., Ltd., Xinghe Co., Ltd. and Sankyo Co., Ltd., it was approved to be listed in Japan in July 2003 for the treatment of hypercholesterolemia. The trade name "LIVALO R ", the formulation specifications are 1mg and 2mg film-coated tablets. [0003] Pitavastatin calcium inhibits the synthesis of cholesterol in the liver by inhibiting the rate-limiting enzyme of cholesterol synthesis, HMG-CoA reductase. Pitavastatin ca...

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
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/14C07B53/00A61P3/06
Inventor 张兆国范为正孟庆华
Owner JIANGSU WANBANG BIOPHARMLS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com