Chemical synthesis method of 3, 6-dichloro-2-aminopyridine

Abstract

The invention discloses a chemical synthesis method of 3, 6-dichloro-2-aminopyridine. The target product 3, 6-dichloro-2-aminopyridine is obtained after simple post-processing through one-step reaction by using ammonization reagent and by using 2, 3, 6-trichloropyridine as a starting raw material, the yield is high and the product quality is high. Compared with the existing disclosed technique, the chemical synthesis method of 3, 6-dichloro-2-aminopyridine has the advantages that the reaction steps are fewer, the raw materials are easy to obtain, the energy consumption is low, the production cost is low, the technological intrinsic safety is high and the industrial production is easier to realized.

Description

technical field [0001] The invention relates to a synthesis method of halogenated aminopyridine, in particular to a synthesis method of 3,6-dichloro-2-aminopyridine. Background technique [0002] Halogenated aminopyridines are important fine chemical intermediates and are widely used in the fields of medicine and pesticides. 3,6-dichloro-2-aminopyridine is an important intermediate in the synthesis of S1P1 receptor agonists in medicine. Due to its relatively difficult synthesis, there are few reports on the synthesis of 3,6-dichloro-2-aminopyridine at home and abroad. Only the patent WO2009154775A1 discloses its synthesis method: the first step is to use 6-chloro-2-aminopyridine as a raw material , react with pivaloyl chloride under the condition of toluene as solvent and triethylamine as acid-binding agent to generate N-(6-chloro-2-pyridyl)-pivalamide. In the second step, N-(6-chloro-2-pyridyl)-pivalamide is used as raw material, tetrahydrofuran is used as solvent...

AI Technical Summary

Problems solved by technology

The key step of this synthetic route is the second step. In this step reaction, a large amount of expensive n-butyllithium (the combination of n-butyllithium and N-(6-chloro-2-pyridyl)-pivalamide will be used. The molar ratio is 2.5), which makes the manufacturing cost high; at the same time, the use of n-butyl lithium makes the process anhydrous and oxygen-free operating conditions harsh, and the engineering is difficult

In the second step reaction, the reaction temperature is minus 78°C, which makes the reaction energy consumption high

In summary, the prior art has problems that need to be solved, such as long reaction steps, expensive reagents, high energy consumption, harsh process operating conditions, and difficulty in realizing large-scale production.

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