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

5-substituted pyridazine-4-amine derivative, preparation method and application

A technology of amine derivatives and pyridazine, which is applied in the field of compound synthesis and application, can solve the problems of pyridazine derivative synthesis and less research on anti-tumor activity, and achieve excellent inhibitory activity, simple preparation method, and high safety.

Pending Publication Date: 2022-02-15
SHAANXI INST OF INT TRADE & COMMERCE
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the substituted pyridazine compounds that have been reported to be synthesized are mainly pyridazinones and 3,6-substituted pyridazine derivatives. According to literature research, pyridazinone and 3,6-substituted pyridazine Derivatives are mainly used in the field of pesticides as insecticides, fungicides, herbicides, plant growth regulators, etc., and are still in the research stage in the field of anti-tumor drugs
However, there are relatively few reports on the synthesis and antitumor activity of 4,5-substituted pyridazine derivatives.

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
  • 5-substituted pyridazine-4-amine derivative, preparation method and application
  • 5-substituted pyridazine-4-amine derivative, preparation method and application
  • 5-substituted pyridazine-4-amine derivative, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0047] Concrete preparation method comprises the following steps:

[0048] 1) Under nitrogen protection, 5-bromopyridazin-4-amine N, N-dimethylformamide DMF and water to obtain a mixed solution A;

[0049] 2) Add compound A, inorganic base and palladium catalyst to the mixed solution in step 1), and stir at 80° C. to 120° C. for 1 to 5 hours; obtain mixed solution B;

[0050] 3) Dilute the mixed solution B with water, extract with ethyl acetate, take the organic phase, wash, dry, and concentrate under reduced pressure to obtain the crude product;

[0051] 4) The obtained crude product is separated and purified by column chromatography to obtain the target product.

[0052] Further, in the step 1), the mass volume ratio of 5-bromopyridazin-4-amine to N,N-dimethylformamide is 1000-3000mg:20-50mL; the N,N-dimethylformamide The volume ratio of methyl formamide and water is 1-4:1-10.

[0053] Further, in the step 2), the molar mass ratio of compound A to 5-bromopyridazin-4-ami...

Embodiment 1

[0056] Example 1 Synthesis of 5-(1-propen-2-yl)pyridine pyridazin-4-amine, whose structural formula is shown in (Ia),

[0057]

[0058] The compound of present embodiment structural formula as shown in (Ia), its preparation method is:

[0059] 1) Dissolve 5-bromopyridazin-4-amine (3) (1.7g, 10.0mmol) in a mixed solution of N,N-dimethylformamide (30mL) and water (5mL) under nitrogen protection , to obtain the mixture A;

[0060] 2) Then add isopropenylboronic acid pinacol ester (2.4g, 14.0mmol), sodium carbonate (2.1g, 20.0mmol) and Pd(dppf)Cl to the mixture A 2 (366mg, 0.50mmol), the mixture was stirred at 100°C for 2 hours; a mixture B was obtained;

[0061] 3) Then the mixed liquid B was diluted with water (60 mL), extracted with ethyl acetate (3×100 mL), the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a crude product;

[0062] 4) The crude product was separated and purified ...

Embodiment 2

[0065] Example 2 Synthesis of 5-(cyclopent-1-en-1-yl)pyridazin-4-amine, whose structural formula is shown in (Ib),

[0066]

[0067] In the present embodiment, the preparation method of the compound shown in structural formula as (Ib), comprises:

[0068] 1) Dissolve 5-bromopyridazin-4-amine (3) (1.7g, 10.0mmol) in a mixed solution of N,N-dimethylformamide (30mL) and water (5mL) under nitrogen protection , to obtain the mixture A;

[0069] 2) Then add 1-cyclopenteneboronic acid pinacol ester (2.7g, 14.0mmol), sodium carbonate (2.1g, 20.0mmol) and Pd(dppf)Cl in the mixed solution A 2 (366mg, 0.50mmol), the mixture was stirred at 100°C for 2 hours to obtain a mixed solution B;

[0070] 3) Then add water (60mL) to the mixture B to dilute, extract with ethyl acetate (3×100mL), wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and then concentrate under reduced pressure to obtain a crude product;

[0071] 4) The crude product was separated and pu...

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 belongs to the technical field of compound synthesis and application, and particularly relates to application of a 5-substituted pyridazine-4-amine derivative in preparation of antitumor drugs, the structural formula of the 5-substituted pyridazine-4-amine derivative is shown as a formula (I), in the formula (I), R is alkenyl or aryl; the alkenyl is allyl or cyclopentenyl; aryl is phenyl, substituted phenyl, substituted pyridyl, naphthyl, indolyl or quinolyl. The 5-substituted pyridazine-4-amine derivative provided by the invention has excellent inhibitory activity on tumor cells, can be widely applied as a medicine for resisting tumor diseases, and is low in toxicity, simple in preparation method and mild in condition; a new thought is provided for development and application of pyridazine antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of compound synthesis and application, and specifically relates to a 5-substituted pyridazin-4-amine derivative, a preparation method and application. Background technique [0002] Malignant tumors are currently one of the major diseases that seriously affect human health and threaten human life. There are more than 100 types of known cancers, and any part of the body may be invaded by cancer. Therefore, conquering cancer is listed as the top priority of research , the research topic of developing drugs that can effectively treat tumors, have less toxic side effects, and lower drug resistance has become an important problem that scientists need to solve urgently. [0003] Pyridazines are a class of heterocyclic compounds with a wide range of biological activities, and have a wide range of applications in the field of pharmaceutical research. Since the first case of naturally occurring pyridazine derivative ...

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): A61K31/50A61K31/501A61P35/00C07D237/20C07D401/04C07D403/04
CPCA61K31/50A61K31/501A61P35/00C07D237/20C07D401/04C07D403/04
Inventor 刘斌徐小娜唐文强朱周静仝红娟王艳娇
Owner SHAANXI INST OF INT TRADE & COMMERCE
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