Method for preparing novel Pranoprofen key intermediates

The technology of a compound, azanthone, is applied in the field of preparation of new important intermediates of pranoprofen, which can solve the problems of phosphorus oxychloride post-processing difficulties, environmental pollution, and difficulty in industrial production, etc.

Inactive Publication Date: 2008-04-16
BEIJING D VENTUREPHARM TECH DEV
View PDF0 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In this method, 2-chloronicotinic acid is first reacted with phenol to generate an intermediate formula (II) compound, and (II) compound is reacted to obtain a compound shown in formula (I) in the presence of a cyclizing agent. Phosphorus oxychloride is used as a cyclizing agent, and in In the actual operation process, the yield of this step reaction is extremely low, and sometimes it is even difficult to reproduce
At the same time, the use of a large amount of phosphorus oxychloride not only causes post-processing difficulties, but also produces a large amount of environmental pollution, which is difficult to realize in 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
  • Method for preparing novel Pranoprofen key intermediates
  • Method for preparing novel Pranoprofen key intermediates
  • Method for preparing novel Pranoprofen key intermediates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment 1: Preparation of 2-phenoxynicotinic acid

[0025] Into a 10L three-necked flask, sequentially add 4064ml of anhydrous methanol, 1096g of sodium methoxide, 3088g of phenol and 1600.0g of 2-chloronicotinic acid, and heat to reflux. The solvent was recovered until the temperature of the reaction liquid reached 175-180°C, and the stirring was continued for 2 hours. After cooling, add 6.4L of water and adjust the pH value to 4-5 with concentrated hydrochloric acid. Then adjust the pH to weak alkaline with 10% sodium bicarbonate solution, and extract with ethyl acetate. The aqueous phase was separated, and the pH value was adjusted to 1-2 with concentrated hydrochloric acid, and a large amount of white solid was precipitated. After suction filtration, the filter cake was dried at 60° C. for 24 hours to obtain 2084 g of white solid with a yield of 95.36%. Melting point: 177.0-179.0°C.

Embodiment 2

[0026] Embodiment 2: Preparation of 9-oxa-1-azanthone

[0027] Add 4086ml of polyphosphoric acid and 1224g of 2-phenoxynicotinic acid into a 10L three-necked flask, raise the temperature to 135-140°C and stir for 10 hours. After cooling, 12L of water was added dropwise in an ice bath, and then 3.0L of 33.3% NaOH solution was added dropwise, a large amount of off-white solid precipitated, and was suction filtered. The filter cake was washed with 10% NaOH solution until alkaline. Then wash with water until neutral, and filter with suction. The filter cake was dried at 60°C for 24 hours to obtain 1029 g of white solid. The yield was 91.2%. Melting point: 182-183°C.

Embodiment 3

[0028] Embodiment 3: Preparation of 9-oxa-1-azanthone

[0029] Add 4500ml of polyphosphoric acid and 1224g of 2-phenoxynicotinic acid into a 10L three-necked flask, heat up to 135-140°C and stir for 8 hours. After cooling, 12L of water was added dropwise in an ice bath, and then 3.2L of 33.3% NaOH solution was added dropwise, a large amount of off-white solid precipitated, and was suction filtered. The filter cake was washed with 10% NaOH solution until alkaline. Then wash with water until neutral, and filter with suction. The filter cake was dried at 60°C for 24 hours to obtain 1020 g of white solid. The yield is 90%. Melting point: 182-183°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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to view more

Abstract

The present invention discloses a preparation method to produce a compound with formula (I) 9-oxa-1-aza athrone, in which a compound with formula (II) reacts with a cyclization reagent under high temperature to obtain the compound with the formula (I), which is an important medium substance in preparation process of Pranoprofen.

Description

technical field [0001] The present invention relates to the preparation method of formula (I) compound 9-oxa-1-azanthone, which is an important intermediate for preparing anti-inflammatory and analgesic drug pranoprofen. Background technique [0002] Pranoprofen is mainly used for anti-inflammatory and analgesic treatment of chronic rheumatoid arthritis, joint deformity, low back pain, neck, shoulder and wrist syndrome and periodontitis, as well as analgesic and antipyretic for acute upper respiratory tract inflammation, after trauma, after minor surgery And anti-inflammatory analgesic after tooth extraction, has very valuable pharmacological properties. [0003] [0004] Pranoprofen [0005] The compound shown in formula (I) is an important intermediate for preparing pranoprofen. "Organic Medicine Synthesis Method", written by Chen Fen'er, in 1998, the conventional synthesis method of this compound was reported in China Medical Science and Technology Press, as shown in...

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): C07D491/052C07D213/00C07D309/00
Inventor 杨利民卢文
Owner BEIJING D VENTUREPHARM TECH DEV
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