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

Preparation method of 5-bromine-7-azaindole

A technology of azaindole and bromopyridine, which is applied in the field of compound preparation, can solve the problems of cumbersome post-processing, heavy metal residues, and danger, and achieve the effects of shortening reaction time, easy control of conditions, and simple operation

Inactive Publication Date: 2018-11-06
NANJING JIEYUN PHARMA TECH CO LTD
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method requires hydrogenation under high-pressure environment, which is dangerous; bromine is required to participate in the reaction, resulting in a large amount of waste liquid, which pollutes the environment. The dehydrogenation step requires the use of heavy metals, which pollutes the environment and causes heavy metal residues. The operation is complicated and the post-treatment is cumbersome.

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 5-bromine-7-azaindole
  • Preparation method of 5-bromine-7-azaindole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] In a single-necked bottle, dissolve 1.0g of 2-amino-3-methyl-5-bromopyridine in 6.3g of triethyl orthoformate, then add 0.02g of p-toluenesulfonic acid, build a distillation device, and heat up to 85°C for reaction . The reaction was carried out for 1 hour, and TLC detected that the reaction of the raw materials was complete. Ethanol and triethyl orthoformate were distilled off under reduced pressure to obtain 1.29 g of ethyl N-(3-methyl-5-bromopyridin-2-yl)formimidate of formula (II), with a yield of 99%. Then, the obtained ethyl N-(3-methyl-5-bromopyridin-2-yl)formimidate was dissolved in 1.7 g of N-methylaniline, a distillation device was built, and the temperature was raised to 110° C. for reaction. The reaction was carried out for 2 hours, and TLC detected that the reaction of the raw materials was complete. Ethanol and triethyl orthoformate were distilled off under reduced pressure, and beating with methanol: water = 2:1 to obtain formula (Ⅲ) N-(3-methyl-5-bromo...

Embodiment 2

[0042] Under nitrogen protection, 0.19 g of sodium amide was added to 2 mL of N-methylaniline, and the temperature was raised to reflux for 30 minutes. Then 1.0g of N-(3-methyl-5-bromopyridin-2-yl)-N'-methyl-N'-phenylformamidine was dissolved in 2mL of N-methylaniline, and slowly dropped into the reaction system After 2 hours, TLC detected that the raw material had reacted completely. N-methylaniline was distilled off under reduced pressure. Water was added to quench the reaction, extracted with ethyl acetate, the organic phase was separated, dried over anhydrous sodium sulfate, and evaporated to dryness to obtain 0.39 g of 5-bromo-7azaindole of formula (IV), with a yield of 60%.

[0043] 1 H NMR (500MHz, CDCl 3) δ 10.90 (s, 1H), 8.34 (s, 1H), 8.05 (s, 1H), 7.37 (d, J=4.0Hz, 1H), 6.62 (d, J=3.0Hz, 1H).

[0044] Under nitrogen protection, 0.47 g of sodium tert-butoxide was added to 2 mL of N-methylaniline, and the temperature was raised to reflux for 30 minutes. Then 1.0g ...

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 5-bromine-7-azaindole. The method includes the steps that a, 2-amino-3-methyl-5-bromopyridine and triethyl orthoformate are utilized for obtaining N-(3-methyl-5-bromopyridine-2-radical) ethyl imidoformate; b, N-(3-methyl-5-bromopyridine-2-radical) ethyl ethyl imidoformate and N-methylaniline react to obtain N-(3-methyl-5-bromopyridine-2-radical)-N'-methyl-N'-benzamidine; c, N-(3-methyl-5-bromopyridine-2-radical)-N'-methyl-N'-benzamidine is subjected to a ring closing reaction under the effect of alkali, so that 5-bromine-7-azaindole is obtained.By synthesizing the imino acid ester compound, the one-step nucleophilic reaction is performed, then ring closing is performed, and finally 5-bromine-7-azaindole is obtained; synthesizing can be completed through three steps. The preparation method is easy to operate and suitable for industrialized production.

Description

technical field [0001] The invention relates to the technical field of compound preparation, in particular to a preparation method of 5-bromo-7azaindole. Background technique [0002] 7-Azaindole series compounds are an important class of heterocyclic intermediates with good biological and medicinal value, and are the core structure of many drugs, such as antineoplastic drugs, melatoninergic receptor ligands, dopamine D4 receptors, 5-HT receptors, p38 kinase inhibitors, thrombin inhibitors, etc., and thus are widely used in medical research. [0003] At present, there are relatively few methods for synthesizing 5-bromo-7azaindole at home and abroad, mainly by the following methods. The first method is to use 2-aminopyridine as raw material, through bromination, coupling and ring closure. The route of this method is complicated to operate, needs to use a large amount of bromine, the reaction is difficult to control, and the productive rate is low. The second method is to u...

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): C07D471/04
CPCC07D471/04
Inventor 吴晓东刘郝敏
Owner NANJING JIEYUN PHARMA TECH CO LTD
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