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

Synthesis method of moxifloxacin hydrochloride impurity

A technology of moxifloxacin hydrochloride and its synthesis method, which is applied in the field of medicinal chemistry, can solve problems such as the synthesis method not mentioned, and achieve the effect of simple and easy operation and high purity

Inactive Publication Date: 2013-12-25
GUILIN PHARMA
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although above-mentioned two documents all disclose the impurity shown in above-mentioned formula (I), do not mention its synthetic method

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
  • Synthesis method of moxifloxacin hydrochloride impurity
  • Synthesis method of moxifloxacin hydrochloride impurity
  • Synthesis method of moxifloxacin hydrochloride impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] a) In the reaction flask, add 10 g of moxifloxacin hydrochloride (purchased from Suzhou Langke Technology Co., Ltd.), 100 ml of 90% (w / w) formic acid and 80 ml of 35% (w / w) formaldehyde solution, and stir at 95°C Reflux the reaction until complete (about 4h), cool to room temperature, and concentrate the reaction solution to dryness under reduced pressure, add 50ml of water to wash with water, then concentrate to dryness under reduced pressure; add 50ml of water to the obtained residue, heat and stir to dissolve, add an appropriate amount of activated carbon (0.5 g), stirred for 30 min, filtered, the filtrate was adjusted to pH = 7 with 5% (w / w) sodium hydroxide solution, crystals were precipitated, filtered, washed with water, and dried at 60°C to obtain 9 g of the intermediate;

[0032] b) Take 9g of the intermediate and place it in a beaker, add 50ml of ethanol, heat to dissolve, adjust its pH=2 with 10% (v / v) hydrochloric acid, then add an appropriate amount of activ...

Embodiment 2

[0041]1. Preparation of moxifloxacin hydrochloride

[0042] 1a) 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid-O 3 , O 4 -Synthesis of boron diacetate

[0043] The synthetic route is as follows:

[0044]

[0045] In a 500ml reaction bottle, add 140g of acetic anhydride, 0.4g of zinc chloride, and 25g of boric acid in sequence, stir evenly, and slowly heat up to 35-40°C. After the reaction, the temperature rises to 110±2°C, reacts for 1.5h, and then cools down to 60~70°C, add 80g 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid ethyl ester, then heat up to React at 85-95°C for 3 hours, TLC shows a product spot, cool down to 40°C, slowly add the reaction solution into 700 g of ice water, stir for 60 minutes, filter, rinse the filter cake with ice water, and dry at 40°C , to obtain 100g of light yellow solid, melting point: 110~116℃;

[0046] 1b) 1-cyclopropyl-7-[(S,S)-2,8-diazo-bicyclo[4.3.0]nonan-8-yl]-...

Embodiment 3

[0062] Embodiment 3 (synthetic impurity with moxifloxacin)

[0063] a) In the reaction flask, add 10 g of moxifloxacin (purchased from Suzhou Langke Technology Co., Ltd.), 70 ml of 85% (w / w) formic acid and 34 ml of 40% (w / w) formaldehyde solution, and stir and reflux at 90 ° C. to complete (about 4.5h), cooled to room temperature, the reaction solution was concentrated to dryness under reduced pressure, added 50ml of water to wash, and then concentrated to dryness under reduced pressure; the resulting residue was added to 50ml of water, heated and stirred to dissolve, and an appropriate amount of activated carbon (0.4g ), stirred for 20 min, filtered, and the filtrate was adjusted to pH=7 with 10% (w / w) sodium hydroxide solution, crystals were precipitated, filtered, washed with water, and dried at 70°C to obtain 8 g of the intermediate;

[0064] b) Put the intermediate obtained in step a) into a beaker, add 50ml of methanol, heat to dissolve, adjust its pH=4 with 5% (v / v) hy...

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 synthesis method of moxifloxacin hydrochloride impurity shown in a formula (I). The synthesis method comprises the following steps of: (a) weighting moxifloxacin or moxifloxacin hydrochloride, methanoic acid and formaldehyde in a molar ratio of 1: (45-145): (20-77), putting in a reflux device, carrying out heating reflux till completely reacting, concentrating reaction liquid to be dry, washing with water, drying, dissolving obtained residues with water, then carrying out decoloring treatment, adjusting the pH value of obtained filtrate to neutral, cooling, crystalizing, separating out crystals, and drying, thus obtaining a midbody; and (b) dissolving the midbody by using an organic solvent, adjusting the pH value of an obtained solution to 1-4 by using hydrochloric acid, then carrying out decoloring treatment, adding water to obtained filtrate, cooling, crystalizing, separating out crystals, and drying, thus obtaining the compound shown in the formula (I). The synthesis method is simple and easy to operate; and the obtained product has high purity (above 99.5%) and can be directly used as an impurity comparison substance.

Description

technical field [0001] The invention relates to a method for synthesizing impurities of moxifloxacin hydrochloride, which belongs to the field of medicinal chemistry. Background technique [0002] Moxifloxacin Hydrochloride (Moxifloxacin Hydrochloride, 1-cyclopropyl-7-(S,S-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-8-methoxy Base-1,4-dihydro-4-oxo-3-quinoline carboxylic acid hydrochloride) is the fourth generation of fluoroquinolone antibacterial drugs. It has a broad-spectrum antibacterial effect, has been established as an antibacterial drug for animals and animals, and can effectively treat infections caused by various bacteria. Its structural formula is as follows: [0003] [0004] Since the A and B positions on the moxifloxacin quinoline ring are relatively active (as shown in the following formula), substitution reactions are prone to occur in acidic and alkaline media, and the following five impurities A, B, C, D, and E may be produced: [0005] [0006] Imp...

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): C07D471/04
Inventor 郑清四林梅芳
Owner GUILIN 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