Synthesis method of cariprazine key intermediate 1-(2,3-dichlorophenyl)piperazine hydrochloride

Abstract

The invention discloses a synthesis method of a cariprazine key intermediate 1-(2,3-dichlorophenyl)piperazine hydrochloride, and belongs to the field of medicine synthesis. The method comprises the following steps: (1) taking a compound 1 and a compound a as raw materials, and conducting reacting to obtain a compound 2; (2) carrying out nitro reduction reaction by taking the compound 2 and a reducing agent as raw materials to obtain a compound 3; and (3) taking the compound 3 as a raw material, and carrying out diazotization reaction and deprotection reaction to obtain the 1-(2,3-dichlorophenyl)piperazine hydrochloride. The raw materials used in the synthesis method are low in toxicity, low in cost and easy to obtain, no noble metal catalyst or phosphorus ligand is used, the equipment requirement is simple, the product yield is high, the purity is high, and the synthesis method is suitable for large-scale industrial production and has a good application prospect.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for synthesizing 1-(2,3-dichlorophenyl)piperazine hydrochloride, a key intermediate of cariprazine. Background technique [0002] With the increasing pressure of life and work in modern society, the incidence of schizophrenia in various countries in the world is showing a trend of rapid growth. Schizophrenia is a chronic and disabling disorder in which symptoms can be grouped into three broad categories: positive symptoms (hallucinations, delusions, disturbances in thought, and movement), negative symptoms (such as lack of motivation and social avoidance), and cognitive symptoms (executive capacity problems, attention, and working memory). The disease can cause patients to be unable to work and live normally, and the recurrence rate and disability rate are high, which has caused a heavy burden on patients, their families and society. At present, the second-generation anti...

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Problems solved by technology

Although the method is short in steps, there is a big problem: the key raw material bis(2-chloroethyl)ammonia hydrochloride belongs to a class of compounds that are very easy to cause allergies, and a small amount of dust of this compound will make the skin Itching, redness, and inflammation; if a large amount comes into contact with the skin or is inhaled into the lungs, it can cause extensive redness and swelling throughout the body, and even ulceration

However, the yield of this method is not high, and it needs to use expensive palladium catalyst and phosphine ligand. The high cost makes this process only suitable for laboratory-scale synthesis, and there is no cost advantage for mass production

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