Refining preparation process of high-purity aprepitant

A preparation process and aprepitant technology, which is applied in the field of refining and preparation technology of high-purity aprepitant, can solve the problems of insignificant effect and inability to meet API impurity residues and other problems

Active Publication Date: 2018-02-16
GUANGXI ENANTIOTECH PHARM CO LTD
View PDF4 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The impurity removal method reported in the literature includes recrystallization of ethyl acetate, methanol / ethyl acetate, and acetone to remove impurities. By repeating the above purification process, it is found that the residual amount of intermediate a reaches 0.9%, and the residual amount of intermediate b reaches 1%. The effect of multiple purifications is still not obvious, and the API impurity residue below 0.1% cannot be satisfied

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 preparation process of high-purity aprepitant
  • Refining preparation process of high-purity aprepitant
  • Refining preparation process of high-purity aprepitant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Synthesis of Aprepitant Crude Product

[0031] Add 30.0 g of raw material intermediate a, 10.3 g of raw material intermediate b, and 100 ml of acetonitrile into the three-necked flask, react at 35 ° C for 1.5 h, and obtain 33 g of crude aprepitant by suction filtration, with a purity (HPLC) of 97.1%;

[0032] (2) Crude refined

[0033] Add the crude product (30g) into 600ml of methyl isobutyl ketone, heat to 50-60°C to dissolve the solid, cool to 0-10°C to crystallize for 1 hour, filter with suction, and dry under reduced pressure at 50°C to obtain the refined product of white crystals 27.5g, 91.6% yield, 99.8% purity (HPLC), maximum 0.04% impurity.

Embodiment 2

[0035] Add the crude product (18g) prepared in Example 1 into 600ml of methyl isobutyl ketone, heat to 50-60°C to dissolve the solid, cool to 0-10°C for crystallization for 1 hour, suction filter, and dry under reduced pressure at 50°C 16 g of refined white crystals were obtained, with a yield of 88%, a purity (HPLC) of 99.9%, and a maximum purity of 0.05%.

Embodiment 3

[0037] Add the crude product (18 g) prepared in Example 1 into 600 ml of 2-butanone, heat to 50-60°C to dissolve the solid, cool to 0-10°C to crystallize for 1 hour, filter with suction, and dry under reduced pressure at 50°C to obtain white The crystallized refined product was 15.7g, the yield was 87.2%, the purity (HPLC) was 99.8%, and the maximum purity was 0.06%.

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 discloses a refining preparation process of high-purity aprepitant. The refining preparation process comprises the following steps: (1) reacting by virtue of intermediates a and b as theraw materials in a solvent A for 1-1.5 hours, so as to obtain an aprepitant crude product; and (2) adding the aprepitant crude product into a solvent B, heating for dissolving, and refining the mixture, so as to obtain an aprepitant pure product. According to the refining preparation process, methyl isobutyl ketone is used as a purifying solvent for purification, so that a relatively good technical effect is achieved, and the contents of main impurity raw material intermediates a and b and process impurities in the aprepitant crude product can be remarkably decreased; and an HPLC detection result shows that the purity of aprepitant reaches above 99.8%, and the impurity limits are all less than 0.1%.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry and relates to a process for refining and preparing high-purity aprepitant. Background technique [0002] Aprepitant is a selective high-affinity antagonist of the human substance P neurokinin 1 (NK1) receptor. Low affinity for serotonin receptor 3 (5-HT3), dopamine receptor, and glucocorticoid receptor targets of other existing drugs for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV) or no affinity. Aprepitant inhibits cisplatin-induced emesis in the acute and delayed phases, and enhances the antiemetic activity of the 5-HT3 receptor antagonist ondansetron and the glucocorticoid dexamethasone on cisplatin-induced emesis. The structural formula of aprepitant is as follows: [0003] [0004] The synthesis method of the main API is [0005] [0006] The impurity removal method reported in the literature includes recrystallization of e...

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): C07D413/06
CPCC07D413/06
Inventor 李彦雄徐亮毛波
Owner GUANGXI ENANTIOTECH PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap