Preparation method of sitafloxacin

A technology of sitafloxacin and compounds, applied in the field of preparation of sitafloxacin, can solve the problems of low product yield, cumbersome post-processing, high cost, etc., and achieve low impurity content, high product yield and purity, and total product Effect of Yield Improvement

Active Publication Date: 2016-02-03
SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The synthetic route of the prior art has the disadvantages of relatively long steps, cumbersome post-treatment, low product yield, and high cost. It is of great significance to find an economical and simple synthetic route

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 method of sitafloxacin
  • Preparation method of sitafloxacin
  • Preparation method of sitafloxacin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Preparation of compound Ⅲ

[0034]

[0035] Under nitrogen protection, 2,3,4-trichloro-5-fluorobenzoic acid (II) (20.9g, 80mmol), (1.5g, 8mmol) cuprous iodide, (2.9g, 16mmol) 1,10-phenanthroline, 100ml N,N-dimethylformamide, (21.2g, 100mmol) anhydrous potassium phosphate, drop (39.6g, 160mmol) (1R, 2S)-(-)-cis -1-Amino-2-fluorocyclopropane p-toluenesulfonate N,N-dimethylformamide solution, reaction temperature 20-25°C, stirring reaction, maintaining reaction for 10 hours, after the reaction, adjust PH=4.5, Cooled to 0°C, filtered to obtain 21.0 g of solids, yield 93%, although the 3-position chlorine atom and 4-position chlorine atom may participate in the 2-position coupling competition reaction from theoretical analysis, the content of compound III was 99.1% through instrumental detection and analysis, The impurity A content was 0.5%, and the impurity B was not detected.

Embodiment 2

[0037] Preparation of compound Ⅲ

[0038] Under nitrogen protection, 2,3,4-trichloro-5-fluorobenzoic acid (II) (20.9g, 80mmol), (0.8g, 8mmol) cuprous chloride, (2.9g, 16mmol) 1,10-phenanthroline, 100ml N,N-dimethylformamide, (32.6g, 100mmol) anhydrous cesium carbonate, drop (29.7g, 120mmol) (1R, 2S)-(-)-cis -1-Amino-2-fluorocyclopropane p-toluenesulfonate N,N-dimethylformamide solution, reaction temperature 20-25°C, stirring reaction, maintaining reaction for 10 hours, after the reaction, adjust PH=4.5, After cooling to 0°C, 20.5 g of solid compound III was obtained by filtration with a yield of 91%. According to instrumental analysis, the content of compound III was 99.2%, the content of impurity A was 0.3%, and the content of impurity B was not detected.

Embodiment 3

[0040] Preparation of compound Ⅳ

[0041]Add (17.4g, 60mmol) compound III and 150mL dichloromethane into a 250mL four-neck flask equipped with a stirrer, thermometer and circulating condensing device, turn on the stirrer and circulating condensing device, raise the temperature to 50°C, and stir until compound III is completely Dissolved to obtain compound III solution; 20g commercially available bis(trichloromethyl)carbonate was dissolved in 40mL of dichloromethane to obtain bis(trichloromethyl)carbonate solution; the bis(trichloromethyl)carbonate ) carbonate solution was slowly added dropwise to the compound III solution for 1.5 hours, and then the temperature was raised to 60° C. for 2 hours to obtain the compound IV solution. After cooling down to room temperature, the compound IV solution was suction-filtered, dried and weighed to 18.0 g, the yield was 98%, and the HPLC purity was 99.9%.

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 preparation method of sitafloxacin. A synthetic method of the invention utilizes 2,3,4-trichlorine-5-fluorobenzoic acid as a starting material, a key intermediate V is generated through coupling and two-step condensation, and then the intermediate V is subjected to condensation and deprotection reaction, so that the sitafloxacin is prepared. The staring material of the sitafloxacin is easy to obtain, and aftertreatment is easy, and the product yield is increased, so that an economic and simple and convenient synthetic route is provided, and the sitafloxacin is suitable for large-scale production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, in particular to a preparation method of sitafloxacin. Background technique [0002] Sitafloxacin is a powerful broad-spectrum quinolone antibacterial drug newly developed by Daiichi Pharmaceutical Sankyo Co., Ltd. after levofloxacin. It has dual inhibitory effects on pneumococcal DNA gyrase and topoisoenzyme. It is used for Treatment of severe refractory bacterial infections, recurrent infections, and certain drug-resistant bacterial infections. [0003] Because sitafloxacin contains a cis-fluorocyclopropylamine group in its structure, it has good pharmacokinetic characteristics and can reduce adverse reactions. Its antibacterial activity in vitro is significantly stronger than most similar drugs. The antibacterial activity against Gram-negative bacteria, Gram-positive cocci and anaerobic bacteria is 4-32 times that of levofloxacin, and it also has a good bactericidal effect on many comm...

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): C07D401/04
CPCC07D401/04
Inventor 左翠永崔校园其他发明人请求不公开姓名
Owner SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
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