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

Method for synthesizing quinolone main cycle compound

A technology of a cyclic compound and a synthesis method is applied in the field of key intermediates of antibacterial quinolones, and can solve the problems of low purity, incomplete reaction, difficulty in handling dimethylamine and the like

Active Publication Date: 2012-05-23
ZHEJIANG BENLI TECH CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The main disadvantages of this process are: 1) there is a reaction equilibrium relationship in the amine exchange reaction, and the reaction is not complete; 2) it is extremely difficult to handle the dimethylamine produced during the amine exchange, and the conventional method is to use hydrochloric acid to convert dimethylamine into Dimethylamine hydrochloride aqueous solution is separated, but the dimethylamine in this solution can hardly be degraded by the bacteria in the biochemical pool; , has no further use value, so it will eventually become an amine nitrogen pollutant that cannot be degraded and has a great impact on the environment

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 synthesizing quinolone main cycle compound
  • Method for synthesizing quinolone main cycle compound
  • Method for synthesizing quinolone main cycle compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Preparation of ethyl formyl acetate sodium salt: In a reaction kettle equipped with a stirrer, add 22g of ethyl acetate, 38g of ethyl formate, 200mL of toluene and 17g of sodium ethoxide in sequence, and slowly raise the temperature to 70°C under stirring, while the pressure Rising to 8 atm, the reaction was completed after 6 hours, and a mixed solution containing ethyl formylacetate sodium salt was prepared, which was cooled to 0°C for later use, wherein the amount of ethyl formylacetate sodium salt was 0.23 mol.

[0068] Add 15.4g of dimethylamine complex and 150mL of toluene into the reaction flask, cool in an ice-salt bath to 0-5°C, then add dropwise the above mixed solution containing ethyl formyl acetate sodium salt, stir the reaction for 40 minutes, stop, After the reaction solution was washed with water, the organic layer was distilled, and 30.0 g of a fraction at 118-121°C (7.5 mmHg) was taken, namely N,N-ethyl dimethylaminoacrylate, with a yield of 91.2%.

[0...

Embodiment 2

[0073] Preparation of ethyl formyl acetate sodium salt: In a reaction kettle equipped with a stirrer, add 22g of ethyl acetate, 38g of ethyl formate, 200mL of toluene and 17g of sodium ethoxide in sequence, and slowly raise the temperature to 70°C under stirring, while the pressure Rising to 8 atm, the reaction was completed after 6 hours, and a mixed solution containing ethyl formylacetate sodium salt was prepared, which was cooled to 0°C for later use, wherein the amount of ethyl formylacetate sodium salt was 0.23 mol.

[0074] Add 15.4g of dimethylamine complex and 150mL of toluene into the reaction flask, cool in an ice-salt bath to 0-5°C, then add dropwise the above mixed solution containing ethyl formyl acetate sodium salt, stir the reaction for 40 minutes, stop, After the reaction solution was washed with water, the organic layer was distilled, and 30.0 g of a fraction at 118-121°C (7.5 mmHg) was taken, namely N,N-ethyl dimethylaminoacrylate, with a yield of 91.2%.

[0...

Embodiment 3

[0079] One of the raw materials, 2,4,5-trifluoro-3-methoxybenzoyl chloride, was changed to 45.5g 2,4-dichloro-5-fluorobenzoyl chloride, and other conditions were the same as in Example 1 to obtain 52.6g The main ring compound of ciprofloxacin, i.e. 1-cyclopropyl-6-fluoro-7-chloro-1,4-dihydro-4-oxoquinolinyl-3-carboxylic acid ethyl ester, the yield is 85.0 %.

[0080] 1 MR(CDCl 3 )δ: 1.2 ~ 1.6 (4H, m, CH 2 ), 1.43 (3H, m, -OCH 2 CH 3 ), 3.53 (1H, m), 4.46 (2H, m, -OCH 2 CH 3 ), 8.07 (1H, d, ArH), 8.15 (1H, d, ArH), 8.54 (1H, s, CH=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 synthesizing a quinolone main cycle compound shown in a formula (I), which comprises the following steps of: (1) performing amino exchange reaction on alpha-substituted aroyl-beta-dimethylaminoethyl acrylate shown in a formula (II) and amines shown in the formula (A) in an organic solvent, introducing CO2 to perform reaction with a byproduct dimethylamine, andafter the reaction is finished, distilling reaction liquid to recycle a dimethylamine complex compound shown in the formula (B) to obtain residual mother liquid; and (2) performing ring-closure reaction on the residual mother liquid and an acid-binding agent 1, and after the reaction is finished, separating reaction products to prepare the carbstyril main-ring compound shown in the formula (I). In the method, a raw material reutilizing method is adopted to recycle and apply mechanically the reaction byproduct dimethylamine with relatively greater influence on the environment, so the reaction can be cyclically performed; and as the gas CO2 is introduced in the amino exchange reaction to make the byproduct dimethylamine form the dimethylamine complex compound which has a relatively lower boiling point and is easy to separate, the reaction is performed in a positive direction and the yield is further improved.

Description

(1) Technical field [0001] The invention relates to a key intermediate of a class of antibacterial drug quinolones, namely a synthesis method of quinolone main ring compounds. (2) Background technology [0002] Quinolones are a class of chemically synthesized antibacterial drugs that have developed rapidly since their inception. Due to their advantages such as broad antibacterial spectrum, strong antibacterial activity, convenient administration, small adverse reactions, and no cross-resistance with other antibiotics, they have become clinical combination drugs. The first choice, the dosage has surpassed the cephalosporin antibiotics, and has become the largest antibacterial drug. [0003] Quinolones have become a hot spot for people to research and develop. Many literatures have reported the synthesis of quinolone main ring compounds, but the synthesis methods reported have long steps, low yields, and large amounts of three wastes. Inadequacies. At present, the synthesis ...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/56C07D498/06C07D513/06
Inventor 章鹏飞顾海宁李小玲
Owner ZHEJIANG BENLI TECH CO LTD
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com