Preparation method for vortioxetine

Abstract

The invention discloses a preparation method for vortioxetine. The preparation method comprises the following steps of (1) performing diazotization on a compound 4 to obtain a compound 5; (2) coupling the compound 5 and a compound 6 to obtain a compound 7; (3) deacetylating the compound 7 to obtain 1-(2-(2,4-dimethyl phenylthio)phenyl)piperazine (i.e. vortioxetine) shown in formula 8. According to the method, operation is simplified, the yield is increased, the cost is greatly reduced, and the method is more suitable for industrial expansion, and has remarkable creativity and practical application value.

Description

technical field [0001] The invention relates to a preparation method of vortioxetine (chemical name: 1-(2-(2,4-dimethylphenylthio)phenyl)piperazine, CAS Registry Number: 508233-74-7). Background technique [0002] On September 30, 2013, Vortioxetine, an emerging antidepressant jointly researched and developed by Lundbeck of Denmark and Takeda Pharmaceutical Company of Japan, was approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in adults. [0003] Major depressive disorder (MDD), commonly referred to as depression, is a mental illness characterized by mood changes and other symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy pleasurable activities. Episodes of depression usually occur throughout a person's life, although some people may experience them only once. [0004] Other signs and symptoms of MDD include loss of interest in daily activities, significant changes in weight or die...

AI Technical Summary

Problems solved by technology

[0012] 1. Use 2,4-dimethyliodobenzene and o-bromothiophenol as starting materials, both of which are very expensive, difficult to purchase, and too expensive for industrialization;

[0013] 2. Using bis(dibenzylideneacetone) palladium and binaphthyl diphenylphosphine as catalysts, the price is relatively expensive. Although the purchase is more convenient, the industrialization cost is still too high and cannot be recycled;

[0014] 3. The reaction is an anhydrous and anaerobic reaction with harsh conditions and is not suitable for industrial operation

[0019] 1. Use 2,4-dimethylthiophenol and o-bromoiodobenzene as starting materials, both of which are very expensive, difficult to purchase, and too expensive for industrialization;

[0020] 2. Using bis(dibenzylideneacetone) palladium or palladium acetate and binaphthyl diphenylphosphine as catalysts is more expensive. Although the purchase is more convenient, the industrialization cost is still too high and cannot be recycled;

[0021] 3. The reaction is an anhydrous and anaerobic reaction with harsh conditions and is not suitable for industrial operation

[0026] 1. Use 2,4-dimethylthiophenol and 4-(2-bromophenyl)-1-tert-butoxycarbonylpiperazine as starting materials, both of which are relatively expensive, difficult to purchase, and industrialized the cost is too high;

[0027] 2. Using palladium as a catalyst is relatively expensive. Although it is more convenient to purchase, the cost of industrialization is still too high and cannot be recycled;

[0028] 3. The reaction is an anhydrous and anaerobic reaction with harsh conditions and is not suitable for industrial operation;

[0034] 1. Using 2,4-dimethylthiophenol and o-bromoiodobenzene as starting materials, both of which are relatively expensive, difficult to purchase, and too expensive for industrialization;

[0035] 2. Using palladium as a catalyst is relatively expensive. Although it is more convenient to purchase, the cost of industrialization is still too high and cannot be recycled;

[0036] 3. The reaction is an anhydrous and anaerobic reaction with harsh conditions and is not suitable for industrial operation;

Images