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

Preparation method of 1-difluoroalkyl isoquinoline

A technology of difluoroalkylisoquinoline and difluoroacetic acid, which is applied in the field of preparation of 1-difluoroalkylisoquinoline, and achieves the effects of mild reaction conditions, strong operability, high reaction conversion rate and yield

Active Publication Date: 2017-03-29
SICHUAN UNIVERSITY OF SCIENCE AND ENGINEERING
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But a method for systematically synthesizing a large amount of 1-difluoroalkyl substituted isoquinoline compounds has not been reported, so it is necessary to develop a method for preparing 1-difluoroalkyl substituted isoquinoline compounds, which has a very wide range in various fields. application prospects

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 1-difluoroalkyl isoquinoline
  • Preparation method of 1-difluoroalkyl isoquinoline
  • Preparation method of 1-difluoroalkyl isoquinoline

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Preparation of compound 1-(2-ethoxy-1,1-difluoro-2-oxoethyl)-4-phenylisoquinoline-3-carboxylic acid ethyl ester:

[0025]

[0026] Add palladium chloride (53mg, 0.3mmol, 10mol%), 1,2-bis(diphenylphosphino)ethane (239mg, 0.6mmol, 20mol%) to a reaction tube protected by dry oxygen-free nitrogen. Potassium carbonate (828mg, 6mmol, 2.0equiv.), followed by methyl 2-isocyano-3,3-diphenylacrylate (2.5g, 9mmol, 3.0equiv.), ethyl bromodifluoroacetate (610mg, 3mmol , 1.0 equiv.) and anhydrous N-methylpyrrolidone (10 mL) were added. The reaction flask was placed in an oil bath at 80°C for full stirring for 12 hours. After confirming the end of the reaction by thin layer chromatography, cool the reaction flask to room temperature, add an appropriate amount of aqueous solution to quench the reaction, add ethyl acetate to extract the aqueous phase, combine the organic phases, wash the organic phases with saturated aqueous NaCl, and dry with anhydrous sodium sulfate The solvent was rec...

Embodiment 2

[0029] Preparation of compound 1-(2-ethoxy-1,1-difluoro-2-oxoethyl)-4-methylisoquinoline-3-carboxylic acid ethyl ester:

[0030]

[0031] Add palladium chloride (53mg, 0.3mmol, 10mol%), 1,2-bis(diphenylphosphino)ethane (239mg, 0.6mmol, 20mol%) to a reaction tube protected by dry oxygen-free nitrogen. Potassium carbonate (828mg, 6mmol, 2.0equiv.), followed by ethyl (Z)-2-isocyano-3-p-tolylbut-2-enoate (1.95g, 9mmol, 3.0equiv.), bromodifluoro Ethyl acetate (610 mg, 3 mmol, 1.0 equiv.) and anhydrous N-methylpyrrolidone (10 mL) were added. The reaction flask was placed in an oil bath at 80°C for full stirring for 12 hours. After confirming the end of the reaction by thin layer chromatography, cool the reaction flask to room temperature, add an appropriate amount of aqueous solution to quench the reaction, add ethyl acetate to extract the aqueous phase, combine the organic phases, wash the organic phases with saturated aqueous NaCl, and dry with anhydrous sodium sulfate The solvent ...

Embodiment 3

[0034] Preparation of compound ethyl 1-(2-(diethylamino)-1,1-difluoro-2-oxoethyl)-4-phenylisoquinoline-3-carboxylic acid ethyl ester:

[0035]

[0036] Add palladium chloride (53mg, 0.3mmol, 10mol%), 1,2-bis(diphenylphosphino)ethane (239mg, 0.6mmol, 20mol%) to a reaction tube protected by dry oxygen-free nitrogen. Potassium carbonate (828mg, 6mmol, 2.0equiv.), followed by methyl 2-isocyano-3,3-diphenylacrylate (2.5g, 9mmol, 3.0equiv.), 2-bromo-N,N-diethyl Benzyl-2,2-difluoroacetamide (687 mg, 3 mmol, 1.0 equiv.) and anhydrous N-methylpyrrolidone (10 mL) were added. The reaction flask was placed in an oil bath at 80°C for full stirring for 12 hours. After confirming the end of the reaction by thin layer chromatography, cool the reaction flask to room temperature, add an appropriate amount of aqueous solution to quench the reaction, add ethyl acetate to extract the aqueous phase, combine the organic phases, wash the organic phases with saturated aqueous NaCl, and dry with anhydrou...

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 relates to the field of organic synthesis, in particular to a preparation method of 1-difluoroalkyl isoquinoline. The method comprises the following steps: taking alkenyl isocyanide and a difluoroacetic acid derivative as raw materials, taking palladium chloride as a catalyst, taking organic phosphine as a ligand and taking inorganic salt as alkali in a polar solvent under protection of inert gas; fully stirring at a certain temperature; after reaction reaches an end point, separating and purifying to obtain the 1-difluoroalkyl isoquinoline. The method not only is gentle in reaction condition, high in operability, low in cost, high in safety and environment-friendly, but also is high in reaction conversion percent, high in yield and short in technological process; the reaction scale is easy to expand; and therefore, the preparation method of the 1-difluoroalkyl isoquinoline has the advantage of suitability for industrial production.

Description

Technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 1-difluoroalkyl isoquinoline. Background technique [0002] Isoquinoline structural units are widely used as dominant structures in natural products, chiral ligands, physiologically active compounds and organic materials. Therefore, the synthesis of isoquinoline has become a hot spot for organic chemists and medicinal chemists. [0003] At the same time, in the field of medicinal chemistry, the introduction of fluorine atoms or fluorine-containing groups into organic molecules is an important direction for the development of new anti-cancer drugs, anti-tumor drugs, anti-viral agents, anti-inflammatory drugs, and central nervous system drugs. It is particularly important that several 1-fluorine-containing substituted isoquinolines have been shown to have good physiological activities. Therefore, it is of great significance to develop a synthetic method of 1-cont...

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 Applications(China)
IPC IPC(8): C07D217/26
CPCC07D217/26
Inventor 刘应乐蒋维东徐斌杨义蒋燕刘晓强谢应
Owner SICHUAN UNIVERSITY OF SCIENCE AND ENGINEERING
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