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

Preparation method of pitavastatin calcium

A technology of pitavastatin calcium and cyclopropyl, which is applied in the field of preparation of cholesterol-lowering drugs, can solve problems such as unfavorable industrial production, unfriendly environment, complicated operation, etc., and achieve the effects of reducing the difficulty of the reaction, being environmentally friendly, and high yield

Active Publication Date: 2014-01-15
XUZHOU WANBANG JINQIAO PHARMA +1
View PDF8 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The present invention aims at the problems of long steps, complicated operation and unfriendly environment caused by the use of highly corrosive reagents in the existing pitavastatin calcium synthesis technology, which seriously corrodes equipment and is unfavorable for industrialized 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
  • Preparation method of pitavastatin calcium
  • Preparation method of pitavastatin calcium
  • Preparation method of pitavastatin calcium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Preparation of Compound II

[0048] Reaction formula:

[0049]

Embodiment 1-1

[0051] Steps:

[0052] Add 29.1g of compound I, 17.2g of methyldichlorosilane, 8g of ferric chloride, 40.2g of halogenation reagent phosphorus tribromide, and 60ml of acetonitrile into a 100ml three-necked flask, stir and reflux at 75~85°C under nitrogen protection, until TLC Detect that the reaction is complete, add dilute hydrochloric acid to the reaction system to terminate the reaction, let stand for stratification, separate the organic layer, and wash with sodium bicarbonate and saturated brine, separate the washing liquid from the organic layer, add anhydrous magnesium sulfate to the organic layer, After drying, filtering, and concentrating the filtrate under reduced pressure, 30.5 g of compound was obtained, which was confirmed to be compound II by comparison with the melting point data of standard compound II. The melting point of compound II was 138-140°C, and the yield of compound II was 86%.

Embodiment 1-2

[0054] Add 29.1g of compound I, 17.2g of methyldichlorosilane, 8g of ferric chloride, 40.2g of phosphorus tribromide, and 60ml of acetonitrile into a 100ml three-necked flask, stir at 65~75°C under nitrogen protection, and TLC detects that the reaction is complete. Add dilute hydrochloric acid to the reaction system to terminate the reaction, let stand to separate the layers, separate the organic layer, and wash with sodium bicarbonate and saturated brine, separate the washing liquid from the organic layer, add anhydrous magnesium sulfate to the organic layer, dry, filter, The filtrate was concentrated under reduced pressure to obtain 28.4 g of compound, which was confirmed to be compound II by comparison with the melting point data of standard compound II. The melting point of compound II was 138-140 °C, and the yield of compound II was 80%.

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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a preparation method of a cholesterol reduction drug, particularly relates to a preparation method of pitavastatin calcium as a crude drug of the cholesterol reduction drug, and aims at the problems that the pitavastatin calcium synthetic technology in the prior art is long in steps and complicated in operation, and uses strongly corrosive reagents which is environmentally unfriendly, causes serious corrosion to equipment, and may not facilitate industrial production. The invention provides the new preparation method of the pitavastatin calcium, the new preparation method is as follows: 3-bromomethyl-2-cyclopropyl-4-(4-fluorophenyl)quinoline is prepared from 2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehyde by a one step reaction, and then reacts with an organophosphorus reagent to obtain pitavastatin calcium intermediate phosphorus ylide, on the basis of improving of the yield to 80%, the reaction steps are reduced, and the reaction difficulty is reduced, and hydroxylamine hydrochloride is selected as a deprotection reagent, so that the new preparation method is mild in reaction conditions, environmentally friendly, high in yield, and beneficial to industrial production.

Description

[0001] Technical field [0002] The present invention involves a preparation method for cholesterol drugs, especially the preparation methods involved in Parer's bulldin calcium of cholesterol drugs. [0003] Background technique [0004] NISSAN Chemical Industry, KOWA and SANKYO (now Daichi Sankyo) jointly developed and listed to sell Pingchang. [0005] Bulls Heatin Calcium is another potential superbattin, low-dose (0.1mg, 0.3mg, 1mg / kg) drop-down LDL-C curative effect is similar to Ten Dose, andPatients are more effective.Compared with Sippedine, Luocetine, and Atvatin, although they can reduce the TC dose -dependence, this product is the best effect. [0006] Pingchang calcium is regarded as a "Super Jettin" product because of its tiny dosage but excellent efficacy.100 million US dollars, so Pingchang Calcium is also called the "heavy bomb" in the third generation of his third generation, and its development prospects are very broad.Therefore, the domestic and foreign pharma...

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
IPC IPC(8): C07D215/14C07F9/60
CPCC07D215/14C07F9/60
Inventor 王鹏李孝成陆沛传陆海波
Owner XUZHOU WANBANG JINQIAO PHARMA
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