A kind of preparation method of vortioxetine hydrobromide α crystal form

A technology of vortioxetine hydrobromide and hydrobromide, which is applied in the field of pharmaceutical preparation and can solve the problems of low purity of vortioxetine hydrobromide α crystal form, high desolvation temperature, and large particle size. , to achieve the effect of good crystallinity, low drying temperature and high crystal purity

Active Publication Date: 2022-05-13
微研优仿医药科技(江苏)有限公司
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Problems solved by technology

[0008] Aiming at the problems in the prior art that the desolvation temperature is high and the time is long, the obtained vortioxetine hydrobromide α crystal form has low purity and large particle size, etc., the present invention provides a simpler vortioxetine Preparation method of Tine hydrobromide α crystal form

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  • A kind of preparation method of vortioxetine hydrobromide α crystal form
  • A kind of preparation method of vortioxetine hydrobromide α crystal form
  • A kind of preparation method of vortioxetine hydrobromide α crystal form

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[0038] The first aspect of the present invention provides a kind of preparation method of vortioxetine hydrobromide α crystal form, it comprises the steps:

[0039] (1) heating and dissolving the crude product of vortioxetine hydrobromide in organic solvent A to obtain solution A;

[0040] (2) filtering the solution A, cooling the filtrate to crystallize, and filtering the precipitated solid A;

[0041] (3) Solvent B is used to beat the solid A, and filter and dry to obtain the vortioxetine hydrobromide α crystal form.

[0042] In the present invention, first the crude product of vortioxetine hydrobromide is dissolved in an organic solvent (such as organic solvent A) to prepare a solution with a certain concentration, wherein the crude product of vortioxetine hydrobromide can be in any form Vortioxetine hydrobromide, e.g. amorphous, non-alpha crystalline, polymorphic or mixtures thereof. Those skilled in the art can also prepare various forms of vortioxetine hydrobromide cru...

Embodiment 1

[0070] Example 1 Summary of the invention: provide a kind of preparation method of vortioxetine hydrobromide α crystal form, it comprises the steps:

[0071] (1) Add 50 ml of 90% V / V isopropanol aqueous solution to 10.00 g of vortioxetine hydrobromide crude product, heat to reflux to dissolve, and obtain solution A;

[0072] (2) Filtrate the above solution A while it is hot, and cool the filtrate naturally to room temperature (25° C.) and stir for 1 hour to crystallize, and filter, rinse the filter cake with methyl tert-butyl ether, and drain to obtain solid A;

[0073] (3) Using 150ml of methyl tert-butyl ether to reflux and beat the solid A for 1.5 hours, the system was cooled to room temperature, filtered, rinsed, drained, and vacuum-dried at room temperature for 20 hours to obtain the vortioxetine hydrogen Bromate α crystal form 8.56g. The XRPD and DSC spectra of this sample can be found in figure 1 and figure 2 .

Embodiment 2

[0074] Example 2 Summary of the invention: provide a kind of preparation method of vortioxetine hydrobromide α crystal form, it comprises the steps:

[0075] (1) Add 60 ml of 90% V / V isopropanol aqueous solution to 10.00 g of vortioxetine hydrobromide crude product, heat to reflux to dissolve, and obtain solution A;

[0076] (2) Filter the above solution A while it is hot, transfer the filtrate into a crystallization bottle and stir, and cool the filtrate naturally to room temperature (22°C) and stir for 1 hour to crystallize, filter, and rinse the filter cake with methyl tert-butyl ether , dry to obtain solid A;

[0077] (3) Use 120ml of methyl tert-butyl ether to reflux and beat the solid A for 2 hours, cool the system to room temperature, filter, rinse, drain, and vacuum dry at room temperature for 14 hours to obtain the vortioxetine hydrogen Bromate α crystal form 8.23g. The XRPD and DSC spectra of this sample can be found in image 3 and Figure 4 .

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Abstract

The invention relates to the technical field of medicine preparation, in particular to a preparation method of vortioxetine hydrobromide alpha crystal form. It comprises the following steps: (1) heating and dissolving crude vortioxetine hydrobromide in organic solvent A to obtain solution A; (2) filtering the solution A, cooling the filtrate to crystallize, and filtering the precipitated solid A; (3) Using solvent B to beat the solid A, filter and dry to obtain the α crystal form of vortioxetine hydrobromide. The method provided in the present invention prepares the alpha crystal form of vortioxetine hydrobromide with low desolvation temperature, low drying temperature and simple operation, and the obtained crystal form has higher purity, better crystallinity, good stability and uniform particles. The method of the invention has good reproducibility, high yield, low production cost and is suitable for industrialized production.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of vortioxetine hydrobromide alpha crystal form. Background technique [0002] Depression is a mental disorder with high prevalence, high recurrence rate, and high suicide rate. It is prone to physical dysfunction and cognitive impairment, causing great harm to individuals and families. According to the World Health Organization report, depression is expected to become the second most burdensome disease after heart disease by 2020. [0003] Vortioxetine hydrobromide is developed by Danish Lundbeck company, and its chemical name is 1-[2-(2,4-dimethylphenylsulfanyl) phenyl] piperazine hydrobromide, and its structural formula is shown in formula 1 , the compound has been approved by the FDA in the United States for the treatment of severe depression. Its trade name is Brintellix, and its oral tablets contain vortioxetine hydrobromide as the active ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/096
CPCC07D295/096C07B2200/13
Inventor 姚新大赵国新徐震亚秦秋明
Owner 微研优仿医药科技(江苏)有限公司
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