Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Refining method of high-purity cariprazine

A refining method and cariprazine technology, applied in the refining field of high-purity cariprazine, can solve problems such as by-product X being difficult to remove

Active Publication Date: 2020-06-23
NHWA PHARMA CORPORATION
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] In order to solve the problem that the by-product X in the prior art is difficult to remove, the present invention provides a method for refining cariprazine, so that impurities can be effectively removed before cariprazine is salified, and the product purity is improved

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Refining method of high-purity cariprazine
  • Refining method of high-purity cariprazine
  • Refining method of high-purity cariprazine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) Cariprazine crude product 10g is joined in the 250ml reaction bottle, add 50ml dichloromethane, 30ml ethanol, heat to reflux, make the solution clarification;

[0038] (2) Slowly add 75ml of ethyl acetate and stir for 20 minutes; slowly cool down to 30°C.

[0039] (3) Ice-water bath, cooled to 0-10°C, stirred for 3 hours;

[0040] (4) Filter, and wash the filter cake with 30ml ethyl acetate, and vacuum-dry to constant weight at 50°C to obtain 8.1g cariprazine crystals, yield 81%, purity (HPLC) 99.79, impurity X (63.78min) The content of 0.02%, such as figure 2 mentioned.

Embodiment 2

[0042] (1) Cariprazine crude product 10g is joined in 250ml reaction bottle, add 30ml dichloromethane, 70ml ethanol, heat to reflux, make solution clarification;

[0043] (2) Slowly add 75ml of ethyl acetate and stir for 20 minutes; slowly cool down to 30°C.

[0044] (3) Ice-water bath, cooled to 0-10°C, stirred for 5 hours;

[0045] (4) filter, and wash the filter cake with 15ml ethyl acetate, and vacuum-dry to constant weight at 50 ℃, obtain 8.4g cariprazine crystal, yield 84%, purity (HPLC) 99.68, impurity X (63.33min) The content of 0.04%, such as image 3 shown.

Embodiment 3

[0047] (1) Add 20 g of cariprazine crude product into a 500 ml reaction flask, add 40 ml of methylene chloride and 60 ml of ethanol, and heat to reflux to make the solution clear;

[0048] (2) Slowly add 100ml of ethyl acetate and stir for 20 minutes; slowly cool down to 30°C.

[0049] (3) Ice-water bath, cooled to 0-10°C, stirred for 3 hours;

[0050] (4) filter, and wash the filter cake with 30ml ethyl acetate, and vacuum-dry to constant weight at 50 ℃, obtain 17.1g cariprazine crystal, yield 85.5%, purity (HPLC) 99.88, the content of impurity X 0.02% ,Such as Figure 4 shown.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a refining method of high-purity cariprazine. The refining method comprises the following steps: adding dichloromethane and alcohol into a cariprazine crude product, heating and stirring until the crude product is dissolved, adding an ester solvent or a ketone solvent; cooling, crystallizing, filtering, collecting cariprazine crystals, washing cariprazine crystals by ethylacetate, and drying cariprazine crystals in vacuum to obtain high-purity cariprazine. According to the refining method, the yield of cariprazine is 80% or above, the purity (HPLC) reaches 99.5%, andthe impurity content is reduced to about 0.1%.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a method for refining high-purity cariprazine. Background technique [0002] Cariprazine hydrochloride, chemical name trans-1-{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}- 3,3-Dimethylurea hydrochloride, a D 2 and D 3 Receptor partial agonists, especially for D 3 Receptors have high selectivity for 5-HT 1A Also has partial agonism, co-developed by Gedeon Richter and Forest Laboratories. On September 17, 2015, the FDA approved it for the treatment of schizophrenia and bipolar disorder. [0003] The structure of cariprazine is shown below: [0004] [0005] The preparation method of cariprazine disclosed at home and abroad mainly contains 2 classes at present: [0006] (1) Patent CN1829703 reports 2,3-dichlorophenylpiperazine (VII) and trans-tert-butyl (4-(2-oxoethyl)cyclohexyl)ammonium formate (X) as key intermediates , intermediate IX was obtained...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/135
CPCC07D295/135C07B2200/13
Inventor 曹龙吉张威杨相平
Owner NHWA PHARMA CORPORATION
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com