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
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  • Abstract
  • Description
  • Claims
  • Application Information

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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

Method used

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

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Experimental program
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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 ...

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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

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 吴晓东刘郝敏
Owner NANJING JIEYUN PHARMA TECH CO LTD
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