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

Simple preparation method for posaconazole and piperazine intermediate thereof

A kind of technology of posaconazole and intermediate, which is applied in the field of preparation of 1--4-piperazine, and can solve problems such as being unfavorable for industrialized production and the like

Inactive Publication Date: 2010-09-08
BEIJING D VENTUREPHARM TECH DEV
View PDF9 Cites 35 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The method finally obtains the product after 21 steps of reaction. It is mentioned in the patent that the intermediates are separated and purified by column chromatography in multiple steps, which is not conducive to industrial 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
  • Simple preparation method for posaconazole and piperazine intermediate thereof
  • Simple preparation method for posaconazole and piperazine intermediate thereof
  • Simple preparation method for posaconazole and piperazine intermediate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Synthesis of 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine

[0029]

[0030] Add 300 grams of N,N-bis(2-chloroethyl)-4-nitroaniline and 120 grams of p-methoxyaniline into a 3-liter three-necked flask. 1.5 liters of N,N-dimethylformamide was added with stirring, and 20 grams of sodium hydroxide were added in portions. Heated to 100°C for 24 hours. Stop the reaction, stir to cool down, add water to dilute, and then extract three times with 2 liters of chloroform. The organic phase was dried by adding anhydrous potassium carbonate, filtered with suction, and concentrated to remove chloroform. The residue was recrystallized by adding 1,4-dioxane to obtain 202.4 g of the target compound 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine, with a yield of 87%. mp.195.4°C.

Embodiment 2

[0031] Example 2 Synthesis of 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine

[0032] Add 52.5 g of N,N-bis(2-chloroethyl)-4-nitroaniline and 18.4 g of p-methoxyaniline into a 500 ml three-necked flask. 200 ml of toluene was added with stirring, and 2 g of sodium hydroxide were added in portions. Heat to reflux for 24 hours. Stop the reaction, stir and lower the temperature to 50-60°C, add water to dilute, and separate the liquids. The organic phase was washed twice with water, dried by adding anhydrous potassium carbonate,

[0033] Suction filtration, concentration to remove toluene. The residue was recrystallized by adding 1,4-dioxane to obtain 35.2 g of the target compound 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine, with a yield of 88.5%. mp.194.6°C.

Embodiment 3

[0034] Example 3 Synthesis of 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine

[0035] Add 52.5 g of N,N-bis(2-chloroethyl)-4-nitroaniline and 18.4 g of p-methoxyaniline into a 500 ml three-necked flask. 200 ml of N,N-dimethylformamide was added with stirring, and 2 g of sodium hydroxide was added in portions. Heated to 100°C for 24 hours. Stop the reaction, stir and lower the temperature to 50-60°C, add water to dilute, and then extract three times with 450 ml of chloroform. The organic phase was dried by adding anhydrous potassium carbonate, filtered with suction, and concentrated to remove chloroform. The residue was recrystallized by adding 1,4-dioxane to obtain 34.4 g of the target compound 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine, with a yield of 87%. mp.195.1°C.

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 discloses a method for preparing 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine intermediate. The piperazine intermediate has a structural formula II. The compound is a main intermediate of a novel medicament posaconazole for treating invasive fungal infection.

Description

technical field [0001] The invention relates to a preparation method of 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine. The compound can be further used to prepare posaconazole, a novel drug for treating invasive fungal infections. Background technique [0002] Posaconazole (chemical name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-tri Azol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3 -base]-1,2,4-triazol-3-one, posacaonazole), has the following structure (see formula I): [0003] [0004] Formula Ⅰ [0005] Posaconazole has a broad antibacterial spectrum, good safety and tolerability, and provides a new treatment option for the prevention and treatment of deep fungal infections. The drug is a broad-spectrum triazole antifungal drug approved by the US FDA on September 15, 2006, and is used for refractory diseases or fungal infections caused by other drug resistance. [0006] The publicly reported method for prepa...

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): C07D295/135C07D405/14A61P31/10
Inventor 夏季红谌伦华陈安平张志强郭夏刘海丽
Owner BEIJING D VENTUREPHARM TECH DEV
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