Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing poly-substituted quinoline compound

A multi-substitution and compound technology, which is applied in the field of preparation of multi-substituted quinoline compounds, can solve problems such as lack of flexibility in substitution forms

Active Publication Date: 2011-10-12
合肥华纳生物医药科技有限公司
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the substrate form of this method is fixed, the synthesized products have limitations and the substitution form lacks flexibility; at the same time, this method is powerless for the synthesis of quinoline compounds with substituents on both rings

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 poly-substituted quinoline compound
  • Method for preparing poly-substituted quinoline compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The preparation of embodiment 1 6-quinoline acetic acid (R 4 for methylene carboxyl)

[0023] 4.8 mol of acrolein, 1.37 mol of p-aminophenylacetic acid, and 0.68 mol of ferrous sulfate heptahydrate were successively put into the reactor, stirred evenly, and 4.5 mol of concentrated sulfuric acid was slowly added dropwise. After the dropwise addition, heat to reflux, and after the reflux reaction for about 20 hours, the reaction system is cooled to room temperature. Add 1.15 L of 32% sodium hydroxide solution to the reaction system, adjust the pH of the system to 13, filter after stirring fully, collect the filtrate, and adjust the pH of the filtrate to 4.0 with glacial acetic acid. The precipitated solid was filtered and recrystallized with 150ml of methanol to obtain 179.6g of 6-quinolineacetic acid with a yield of 70%; colorless crystals with a melting point of 220°C-222°C. H NMR spectrum ( 1 H NMR, 200MHz, DMSO) δ8.87(dd, J=4.17, 1.64Hz, 1H), 8.33(d, J=7.58Hz, 1H),...

Embodiment 2

[0024] The preparation of embodiment 2 6-quinoline ethyl acetate (R 4 6-methylenecarbonyloxyethyl)

[0025] Put 0.96mol 6-quinolineacetic acid and 26mol absolute ethanol into the reaction kettle successively, then add 20ml concentrated sulfuric acid, heat and reflux for about 6 hours, cool to room temperature, concentrate to remove ethanol, and dissolve with 68ml 15% sodium carbonate solution After the concentrate was stirred evenly, it was extracted 4 times with 500 ml of ethyl acetate, and the extracts were combined and concentrated to obtain 134.3 g of ethyl 6-quinoline acetate with a yield of 65%. Proton nuclear magnetic resonance (1H NMR, 200MHz, DMSO) δ8.87 (dd, J=4.17, 1.64Hz, 1H), 8.33 (d, J=7.58Hz, 1H), 7.98 (d, J=8.59Hz, 1H ), 7.86(d, J=1.77Hz, 1H), 7.68(dd, J=8.59, 2.02Hz, 1H), 7.51(dd, J=8.34, 4.04Hz, 1H), 4.15(q, J=7.2Hz , 2H), 3.80(s, 2H) 1.30(t, J=7.2Hz, 3H).

Embodiment 3

[0026] The preparation of embodiment 3 6-quinoline isopropionic acid ethyl esters (R 4 6-(2-methyl)-ethoxycarbonylmethylene)

[0027]At -78°C, under the protection of argon, add dropwise 0.17mol tetrahydrofuran solution of ethyl 6-quinoline acetate to 0.221mol tetrahydrofuran solution of lithium diisopropylamide, stir for 1 hour, then add dropwise 0.179mol iodine Methane tetrahydrofuran solution, after that, react at -78°C for 3 hours, then raise the temperature naturally, stir and react for 12 hours, after the reaction is completed, quench the reaction with 20ml of 30% ammonium chloride solution for 0.5h, remove the tetrahydrofuran by rotary evaporation, add 500ml of dichloro Diluted with methane and concentrated to obtain 216.6 g of yellow liquid ethyl 6-quinoline isopropionate with a yield of 55%. H NMR spectrum ( 1 H NMR, 200MHz, DMSO) δ8.87(dd, J=4.17, 1.64Hz, 1H), 8.33(d, J=7.58Hz, 1H), 7.98(d, J=8.59Hz, 1H), 7.86(d , J=1.77Hz, 1H), 7.68 (dd, J=8.59, 2.02Hz, 1H), 7.51...

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
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for preparing a poly-substituted quinoline compound shown in constitutional formula (I). The method comprises the steps of: mixing aniline compound shown in constitutional formula (II) with 2-alkenyl aldehyde or 2-alkenyl ketone; adding green vitriol as a catalyst; carrying out heating circumfluence reaction in sulphuric acid for 2 to 20 hours; cooling a reactionsystem till the temperature of the reaction system reaches room temperature and then carrying out post treatment to obtain the poly-substituted quinoline compound shown in the constitutional formula (I). The method can be applied to various substrates and materials are cheap and highly available; and poly-substituted quinoline compound banks with diverse structures can be synthesized by optimizingand regulating substrates involved in the reaction, and the compounds can be widely applied to the fields such as pharmacochemistry, biomedicine and materials science and the like.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method of multi-substituted quinoline compounds. Background technique [0002] Quinoline compounds are important heterocyclic compounds that are widely distributed in nature, and many natural products contain quinoline rings in their structures. Quinolines are also important intermediates for various synthetic drugs. It has been found that quinoline compounds have biological activities such as anti-malarial, anti-inflammatory, bactericidal, anti-viral, anti-cancer, anti-filtering pathogens, anti-asthma and antiemetic. Medicinal chemists have also been interested in applying quinoline compounds to new target enzymes, hoping to apply them to various protease inhibitors such as HIV reverse transcriptase inhibitors. Many new functional materials such as new dyes and new luminescent materials developed in recent years contain quinoline rings in their struc...

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): C07D215/02C07D215/12C07D215/48C07D215/20C07D215/18
Inventor 许峰刘迎春高源
Owner 合肥华纳生物医药科技有限公司