Purification method of ticagrelor

A technology of ticagrelor and purification method, applied in the preparation of ticagrelor, in the field of pharmaceutical industry, can solve problems such as no research and reports, and achieve the effects of easy control operation, high product purity, and low purification cost

Inactive Publication Date: 2016-07-27
XUZHOU WANBANG JINQIAO PHARMA +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, based on this preparation method, supporting the formation of a suitable refining and purification process is of great significance for industrial production, but unfortunately, there is no relevant research and research on this part in the prior art at home and abroad. to report

Method used

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  • Purification method of ticagrelor
  • Purification method of ticagrelor

Examples

Experimental program
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Effect test

Embodiment 1

[0024] The homemade 100g crude ticagrelor (HPLC purity 95.5%, isomer 1.3%) and 500g ethyl acetate were heated to 50oC and stirred to dissolve. Heat filtration, collect filtrate, add 1000g normal hexane in filtrate. After the addition, lower the temperature and stir to crystallize until a large amount of white solid is precipitated, and keep stirring at 10oC to 15oC for 1 hour. After filtering, the filter cake was rinsed with a mixed solution of 150 g of ethyl acetate and 300 g of n-hexane. After vacuum drying at 40oC for 8 hours, 87g of off-white solid was obtained. The HPLC purity was 99.89%, isomer 0.003%, the largest single impurity amount was 0.005%, and the total impurity amount was 0.011%.

Embodiment 2

[0026] 100g of self-made crude ticagrelor (HPLC purity 95.5%, isomer 1.3%) and 600g of acetone were heated to 35oC and stirred to dissolve. Heat filtration, collect filtrate, add 1800g isooctane in filtrate. After the addition, cool down and stir to crystallize until a large amount of white solids are precipitated, then keep stirring at 5oC to 10oC for 2 hours. After filtering, the filter cake was rinsed with 200g of acetone and 600g of isooctane mixture. Vacuum drying at 45oC for 10 hours yielded 83 g of off-white solid with HPLC purity of 99.80%, isomer 0.006%, maximum single impurity amount 0.008%, and total impurity amount 0.020%.

Embodiment 3

[0028] 100g of self-made crude ticagrelor (HPLC purity 95.5%, isomer 1.3%) and 700g of n-butanol were heated to 55oC and stirred to dissolve. Heat filtration, collect filtrate, add 2800g n-hexane in filtrate. After the addition, cool down and stir to crystallize until a large amount of white solids are precipitated, and keep stirring at 15oC to 20oC for 2 hours. After filtering, the filter cake was rinsed with a mixture of 230g n-butanol and 920g n-hexane. After vacuum drying at 50oC for 12 hours, 83 g of off-white solid was obtained, with HPLC purity of 99.76%, isomer 0.008%, maximum single impurity amount 0.009%, and total impurity amount 0.024%.

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Abstract

Belonging to the technical field of pharmaceutical industry, the invention relates to the preparation field of ticagrelor, in particular to a purification method of ticagrelor. Directed at the purification blank of ticagrelor at present, especially the blank of purification technology for the product obtained by a preparation method involved in the invention, the invention discloses a purification method of ticagrelor. The method consists of the steps of: dissolving a ticagrelor crude product in a first solvent, performing hot filtration to remove solid therein, and adding a second solvent into the filtrate while it is hot, conducting cooling till a lot of solid precipitate, carrying out low temperature heat preservation until no solid precipitate, and carrying out filtration and drying, thus obtaining a ticagrelor pure product. The purification method disclosed by the invention can decrease the total impurity content of the product from 4.5% to less than 0.2%, the purified ticagrelor has purity of more than 99.75%, and the biggest individual impurity is below 0.1%.

Description

technical field [0001] The invention relates to the field of preparation of ticagrelor, in particular to a purification method of ticagrelor, and belongs to the technical field of pharmaceutical industry. Background technique [0002] Ticagrelor (also known as ticagrelor) belongs to cyclopentyl triazolopyrimidine compounds, the chemical name is (1 S ,2 S ,3 R ,5 S )-3-[7-[(1 R ,2 S )-2-(3,4-difluorophenyl)cyclopropylamino]-5-(thiopropyl)-3 H -[1,2,3]triazol[4,5- d ]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol, molecular formula: C 23 h 28 f 2 N 6 o 4 S, CAS number: 274693-27-5, the structural formula is as follows: [0003] [0004] Ticagrelor is a new type of selective small molecule anticoagulant drug developed by AstraZeneca. The drug can reversibly act on the purine 2 receptor (purinoceptor2, P2) subtype P2Y12 on vascular smooth muscle cells (VSMC), and has obvious inhibitory effect on platelet aggregation caused by ADP, and the effect is ra...

Claims

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Application Information

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IPC IPC(8): C07D487/04
Inventor 乔德水鹿婷陈胜高雪芹
Owner XUZHOU WANBANG JINQIAO PHARMA
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