Preparation method of antidepressant drug Vortioxetine

A vortioxetine and antidepressant technology, applied in the field of medicine and chemical industry, can solve problems such as long steps, and achieve the effect of simple operation

Active Publication Date: 2015-01-21
NANTONG FINC PHARMA CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Although the method is simple to operate and has certain advantages in cost, the steps are long and the yield is only 48.7%.

Method used

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  • Preparation method of antidepressant drug Vortioxetine
  • Preparation method of antidepressant drug Vortioxetine
  • Preparation method of antidepressant drug Vortioxetine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0037] 13.8 g (0.1 mol) of compound 2,4-dimethylthiophenol of formula (4), 28.3 g (0.1 mol) of 2-bromoiodobenzene, 10.3 g (0.12 mol) of piperazine, 16.8 g (0.3 mol) potassium hydroxide and 1.9 g (0.01 mol) cuprous iodide, 33.4 g (0.12 mol) tetrabutylammonium chloride, add 300 mL of water, stir and heat up to 85-90 ° C, react for 11 hours, After the reaction is complete, extract three times with dichloromethane, 300ml each time, combine the organic layers, wash the organic layer with saturated brine and pure water, collect the organic layer, dry, evaporate the dichloromethane, add 150 mL of acetone to the residue for recrystallization , 26.6 g of white solid was obtained, the yield was 89.3%, and the purity was 97.2%.

Embodiment 3

[0039] 13.8 g (0.1 mol) of compound 2,4-dimethylthiophenol of formula (4), 28.3 g (0.1 mol) of 2-bromoiodobenzene, 10.3 g (0.12 mol) of piperazine, Add 12.0 g (0.3 mol) sodium hydroxide and 1.9 g (0.01 mol) cuprous iodide, 48.3 g (0.15 mol) tetrabutylammonium bromide, add 300 mL of water, stir and raise the temperature to 85-90 ° C, react for 11 hours, After the reaction is complete, extract three times with dichloromethane, 300ml each time, combine the organic layers, wash the organic layer with saturated brine and pure water, collect the organic layer, dry, evaporate the dichloromethane, add 150 mL of acetone to the residue for recrystallization , 26.8 g of white solid was obtained, the yield was 89.3%, and the purity was 96.5%.

Embodiment 4

[0041]13.8 g (0.1 mol) of compound 2,4-dimethylthiophenol of formula (4), 28.3 g (0.1 mol) of 2-bromoiodobenzene, 10.3 g (0.12 mol) of piperazine, 12.0 g (0.3 mol) sodium hydroxide and 1.9 g (0.01 mol) cuprous iodide, 29.1 g (0.11 mol) 18-crown-6, add 300 mL of water, stir and heat up to 85-90 ° C, react for 10 h, After the reaction is complete, extract three times with dichloromethane, 300ml each time, combine the organic layers, wash the organic layer with saturated brine and pure water, collect the organic layer, dry, evaporate the dichloromethane, add 150 mL of acetone to the residue for recrystallization , 22.4 g of white solid was obtained, the yield was 75.2%, and the purity was 96.8%.

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Abstract

The invention relates to a preparation method of an antidepressant drug Vortioxetine, which belongs to the technical field of pharmaceutical chemicals. According to the method, by taking water as a solvent, a compound 2,4-dimethylbenzenethiol shown in a formula (4), a compound 2-bromoiodobenzene shown in a formula (3) and a compound piperazine shown in a formula (2) react with copper iodide, a phase transfer reagent and alkali in an aqueous solution so as to obtain a compound shown in a formula (1). The method disclosed by the invention is easily-obtained in raw materials and simple in process; and one-pot reaction operation can be performed, and water is taken as a solvent, so that the method is green and environmental-friendly, and facilitates the industrialized production of the bulk drug.

Description

technical field [0001] The invention relates to a preparation method of vortioxetine, which belongs to the technical field of medicine and chemical industry. Background technique [0002] Vortioxetine is a new type of antidepressant drug developed by Lundbeck of Denmark and Takeda Pharmaceutical of Japan. In September 2013, the drug was approved by the US Food and Drug Administration (FDA). ] piperazine, its structural formula is: [0003] [0004] The drug is thought to work through a combination of 2 mechanisms of action: modulation of receptor activity and inhibition of reuptake. In vitro studies have shown that vortioxetine is a 5-HT3 and 5-HT7 receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and a 5-hydroxytryptamine transporter (SERT) inhibitor. Non-clinical studies in vivo have shown that vortioxetine can enhance the levels of neurotransmitters in specific areas of the brain-serotonin, norepinephrine, dopamine, acetylcholine, an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/096
CPCC07D295/096
Inventor 刘学键
Owner NANTONG FINC PHARMA CHEM
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