Novel method of producing dronedarone key intermediate

A compound and basic technology, which is applied in the field of preparation of 4-[3-propoxy]-benzoic acid alkyl esters, can solve problems such as no effective solution, and achieves prevention of by-product generation, high yield, and high efficiency. Strong control effect

Inactive Publication Date: 2008-04-02
BEIJING VENTUREPHARM BIOTECH
View PDF2 Cites 24 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the published reports about the preparation method of dron

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
  • Novel method of producing dronedarone key intermediate
  • Novel method of producing dronedarone key intermediate
  • Novel method of producing dronedarone key intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Under nitrogen protection, 172 g of 1-chloro-3-bromopropane was added to 300 ml of butanone, and 158 g of anhydrous potassium carbonate was added. The temperature was raised to reflux, and a mixed solution of 200 milliliters of butanone and 152 grams of methyl p-hydroxybenzoate was added dropwise. After the dropwise addition was completed, the reaction was refluxed for 5 hours. Cool to room temperature, filter with suction, and wash the filter cake with a small amount of butanone. The filtrates were combined, and the solvent was evaporated under reduced pressure to obtain methyl 4-(3-chloropropoxy)benzoate as 205 g of off-white solid, with a yield of 90%. HPLC purity 98.5%.

Embodiment 2

[0036] Under nitrogen protection, 172 g of 1-chloro-3-bromopropane was added to 300 ml of butanone, and 158 g of anhydrous potassium carbonate was added. The temperature was raised to reflux, and a mixed solution of 200 milliliters of butanone and 152 grams of methyl p-hydroxybenzoate was added dropwise. After the dropwise addition was completed, the mixture was cooled to room temperature and stirred for 24 hours. Suction filtration, the filter cake was washed with a small amount of butanone. The filtrates were combined, and the solvent was distilled off under reduced pressure to obtain methyl 4-(3-chloropropoxy)benzoate as 180 g of off-white solid, with a yield of 79%. HPLC purity 98.0%.

Embodiment 3

[0038] Under nitrogen protection, 172 g of 1-chloro-3-bromopropane was added to 250 ml of toluene, and 50 g of sodium hydroxide was added. The temperature was raised to reflux, and a mixed solution of 150 milliliters of toluene and 152 grams of methyl p-hydroxybenzoate was added dropwise. After the dropwise addition was completed, the reaction was refluxed for 4 hours. Cool to room temperature, filter with suction, and wash the filter cake with a small amount of toluene. The filtrates were combined, and the toluene was evaporated under reduced pressure to obtain methyl 4-(3-chloropropoxy)benzoate as 172 g of off-white solid, with a yield of 75.5%. HPLC purity 97.8%.

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

No PUM Login to view more

Abstract

The present invention relates to a preparation method of 4-[3-(2-butyl-amino) propoxy]- benzoic alkyl ester (a compound of formula (1)). The p-hydroxide benzene methyl formate and 1, 3 methylparaben react to prepare compound III under alkaline conditions. Then the products and putrescine dock to synthesize compound I under alkaline conditions. The compound is a key intermediate for preparing drugs of treating arrhythmic diseases, hydrochloride Juenaidalong. Wherein, R represents C1-C4 alkyl; X, X1 and X2 are halogen atoms, such as Cl, Br and I; but X1 and X2 are different from each other.

Description

technical field [0001] The invention relates to a preparation method of 4-[3-(dibutylamino)propoxy]-benzoic acid alkyl ester, and the compound can be used for preparing dronedarone, a drug for treating arrhythmia. Background technique [0002] Dronedarone, a benzofuran derivative, is a newly developed drug for treating arrhythmia. The structure and characteristics are similar to the cardiovascular drug amiodarone, but the drug does not contain iodine and is less lipophilic. Therefore, the curative effect of amiodarone is maintained, and there is no extracardiac adverse reaction of amiodarone. It is expected to appear safer and better tolerated by patients as an alternative to amiodarone for the treatment of arrhythmias. With the continuous acceleration of social modernization, people are under increasing social pressure, and the number of cardiovascular disease patients in our country is also increasing. Cardiovascular disease is listed as one of the top ten causes of dea...

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): C07C213/02C07C217/54
Inventor 杨利民
Owner BEIJING VENTUREPHARM BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap