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

Preparation and separation method of raloxifene dimer

A dimer, liquid phase preparation technology, applied in the field of medicine, can solve the problems of high price of SIN-1, limited production, difficult to separate and obtain pure raloxifene dimer, etc., and achieves low cost and environmental friendliness. , the effect of high purity

Active Publication Date: 2019-12-03
CHONGQING SHENGHUAXI PHARMA CO LTD +1
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there are literature reports on the synthesis method of raloxifene dimer: literature Sci. Pharm. 2012; 80:605-617 degrades raloxifene dimer with hydrochloric acid at room temperature, but the dimer in the reaction solution of this method The proportion of body impurities is less than 1%, it is difficult to separate and obtain the pure product of raloxifene dimer; document Chem. Res. Toxicol. 2003, 16, 1264-1276 uses raloxifene and 5-amino-3-(4- Morpholinyl)-1,2,3-oxadiazole hydrochloride (SIN-1) reacts to prepare raloxifene dimer. Since the preparation of SIN-1 requires the use of highly toxic potassium cyanide as a raw material, it is environmentally friendly The production of SIN-1 is limited on the Internet, so the price of SIN-1 is more expensive, and it is difficult to buy SIN-1 of gram pole on the market

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 and separation method of raloxifene dimer
  • Preparation and separation method of raloxifene dimer
  • Preparation and separation method of raloxifene dimer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Preparation of crude product of raloxifene dimer

[0030] Synthetic route such as figure 1 shown.

[0031] Step 1. Add 5g of raloxifene, 150mL of methanol, 5mL of ethylenediamine, and 15mL of 30% hydrogen peroxide into the reaction bottle, stir in an ice bath, and cool to 0~5°C;

[0032] Step 2, add a total of 3.25g of ferric chloride, and control the temperature not to exceed 50°C;

[0033] Step 3, after adding ferric chloride, reflux and stir for 1 hour;

[0034] Step 4. Concentrate the reaction solution under reduced pressure at 20~25°C, add 25mL of methanol and 25mL of acetone, stir well and then filter with suction;

[0035] Step 5. Add the filtered solid to 6M hydrochloric acid, stir evenly, filter with suction, wash the filter cake once with 25 mL of water, and dry at 50°C under normal pressure to obtain 4.8 g of crude raloxifene dimer, as figure 2 As shown, the HPLC purity of raloxifene dimer in the crude product was 51.3% (25.6min).

[0036] The...

Embodiment 2

[0044] Example 2 Preparation of refined product of raloxifene dimer

[0045] Step 6. Purifying the crude raloxifene dimer above by preparative liquid chromatography, and collecting the preparation solution containing raloxifene dimer;

[0046] Step 7. Concentrate the collected preparation solution to dryness under reduced pressure at 20°C, add water, stir evenly, filter with suction, wash the filter cake once with water, and dry 1.9g of refined raloxifene dimer at 50°C under normal pressure ,Such as image 3 As shown, the HPLC purity of the refined product is 96.9%.

[0047] Preparative chromatographic purification conditions are:

[0048] Chromatographic column: C18 50×500mm 10µm;

[0049] Flow rate: 35mL / min;

[0050] Column temperature: 25°C;

[0051] Wavelength: 280nm;

[0052] Gradient elution conditions are shown in the table below:

[0053]

[0054] Wherein A is acetonitrile, and the mobile phase B is 0.02M potassium dihydrogen phosphate, and the pH is adjuste...

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
wavelengthaaaaaaaaaa
wavelengthaaaaaaaaaa
wavelengthaaaaaaaaaa
Login to View More

Abstract

The invention discloses a preparation and separation method of raloxifene dimer. The preparation and separation method comprises the steps that raloxifene hydrochloride is taken as a raw material andpolymerized under the effects of hydrogen peroxide, alkyl diamine and ferric trichloride to generate a crude raloxifene dimer product; and the crude raloxifene dimer product is purified through preparative chromatography to obtain a refined raloxifene dimer product. The defects of large separation difficulty, high cost and using of a toxic reagent in the prior art are avoided; and the preparationand separation method of the raloxifene dimer has the advantages that operation is easy, environment friendliness is achieved, the cost is low, and the prepared dimer is high in purity, and a good foundation is laid for quality research and control of raloxifene.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a method for preparing and separating medicine raloxifene dimers. Background technique [0002] Raloxifene (compound I), chemical name is [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothienyl-3-yl][4-[2-(1-piperidinyl) )ethoxy]phenyl]methanone is a selective estrogen receptor modulator first developed by Lilly Company in the United States. It was approved by the FDA in December 1997 and listed in the United States in January 1998. It is used for prevention and treatment Postmenopausal osteoporosis in women. The chemical structural formula of Raloxifene is as follows: [0003] . [0004] Raloxifene dimer (compound II), an impurity that may be produced during the preparation and storage of raloxifene, has the following structural formula: [0005] . [0006] At present, there are literature reports on the synthesis method of raloxifene dimer: literature Sci. Pharm. 2012; 80:605-...

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): C07D333/56
CPCC07D333/56
Inventor 王庆曾应淑
Owner CHONGQING SHENGHUAXI PHARMA CO LTD
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