Method for refining edoxaban

An edoxaban, refined technology, applied in the refined field of edoxaban, can solve the problems of complex operation process, low product purity, high impurity content, etc., and achieve high purity, reduce impurity content, and simple operation

Inactive Publication Date: 2018-03-06
TIANJIN HANKANG PHARMA BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The preparation method of edoxaban is disclosed in the prior art, such as US7365205B2, CN1894238A, etc. However, the above-mentioned method still has problems such as very complicated operation process, low product purity, high impurity content, etc., so there is an urgent need for a good refined method Let's refine Edoxaban

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] (1) Put 5.0 g of crude edoxaban into a one-mouth bottle, add 80 ml of pure ethanol aqueous solution (ethanol: pure water = 1:3), and stir to dissolve at 45°C;

[0016] (2) Then add 600ml of diethyl ether and acetone mixture (diethyl ether: acetone = 1: 2.5), and stir and crystallize at 20°C for 2 hours;

[0017] (3) The edoxaban crystals precipitated were collected by filtration, washed with 100ml of the above ether and acetone mixed solution and dried in an oven at 30°C to obtain 4.5g edoxaban crystals with a yield of 90% and a purity (HPLC )99.2%.

Embodiment 2

[0019] (1) Put 5.0 g of crude edoxaban into a one-mouth bottle, add 100 ml of pure ethanol aqueous solution (ethanol: pure water = 1:4), and stir to dissolve at 40°C;

[0020] (2) Then add 550ml of diethyl ether and acetone mixed solution (diethyl ether: acetone = 1:1), and stir and crystallize at 25°C for 4 hours;

[0021] (3) The edoxaban crystals precipitated were collected by filtration, washed with 100ml of the above ether and acetone mixed solution and dried in an oven at 30°C to obtain 4.6g edoxaban crystals with a yield of 92% and a purity (HPLC )99.4%.

Embodiment 3

[0023] (1) Put 5.0 g of crude edoxaban into a one-mouth bottle, add 120 ml of pure ethanol aqueous solution (ethanol: pure water = 1:3), and stir to dissolve at 35° C.;

[0024] (2) Then add 500ml of isopropyl ether and acetone mixture (isopropyl ether: acetone = 1:3), and stir and crystallize at 30°C for 5 hours;

[0025] (3) The precipitated Edoxaban crystals were collected by filtration, washed with 100ml of the above-mentioned isopropyl ether and acetone mixture and dried in an oven at 30°C to obtain 4.55g of Edoxaban crystals, with a yield of 91%, a purity of (HPLC) 99.2%.

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PUM

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Abstract

The invention belongs to the field of medicinal chemistry, and relates to a refined method for edoxaban. The crude edoxaban is first stirred and dissolved in an ethanol pure aqueous solution, then a mixed solution of ethers and ketones is added, and the mixture is stirred and crystallized; Washing, vacuum drying to obtain pure edoxaban crystals, the yield is over 90%, the purity (HPLC) reaches 99.4%, and the impurities are reduced to about 0.1%.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a refined method for edoxaban. Background technique [0002] Edoxaban, chemical name: N-(5-chloropyridin-2-yl)-N'-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[( 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)oxalamide, tosylate was used in the formulation. It is a small-molecule oral anticoagulant developed by Daiichi Sankyo Co., Ltd., and is a coagulation factor X (FXa) inhibitor. During the blood coagulation process, activated coagulation factor X (FXa) activates prothrombin (FII) into thrombin (FIIa), which promotes the formation of fibrin and thus forms thrombus. Therefore, FXa has become the main target for the development of a new generation of anticoagulant drugs. point. [0003] The preparation method of edoxaban is disclosed in the prior art, such as US7365205B2, CN1894238A, etc. However, the above-mentioned method still ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D513/04
CPCC07D513/04
Inventor 严洁王志凤
Owner TIANJIN HANKANG PHARMA BIOTECH
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