Dissociation method and application of titanium complex drug

A drug and complexing technology, applied in the direction of organic chemistry, etc., can solve the problems of inability to provide products with good quality, increase the difficulty of product purification, and low yield of target substances.

A drug and complexing technology, applied in the direction of organic chemistry, etc., can solve the problems of inability to provide products with good quality, increase the difficulty of product purification, and low yield of target substances.

CN110845384AActive Publication Date: 2020-02-28广东省科学院珠海产业技术研究院有限公司
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  • Dissociation method and application of titanium complex drug
  • Dissociation method and application of titanium complex drug
  • Dissociation method and application of titanium complex drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] (1) Add 50 g of titanium tetrachloride to the solution of 60 g of A, and react for 1 hour;

[0041] (2) Pour the reaction solution into 300ml of 1% isopropanol solution and stir for 0.5 hours;

[0042] (3) Add 200g 40% citric acid solution, pH<4, stir for 0.5 hours;

[0043] (4) Layering and concentration of the organic layer to obtain (3S, 4S)-4-acetyl-3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl) nitrogen heterocycle Butan-2-one 40g, yield 66.7%, purity 99.5%.

Embodiment 2

[0045] (1) Add 50 g of titanium tetrachloride to the solution of 60 g of A, and react for 1 hour;

[0046] (2) Pour the reaction solution into 300ml of 1% isopropanol solution and stir for 0.5 hours;

[0047] (3) Add 250g 40% citric acid solution, pH<4, stir for 0.5 hours;

[0048] (4) Layering and concentration of the organic layer to obtain (3S, 4S)-4-acetyl-3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl) nitrogen heterocycle Butan-2-one 42g, yield 70%, purity 99.7%.

Embodiment 3

[0050] (1) Add 50 g of titanium tetrachloride to the solution of 60 g of A, and react for 1 hour;

[0051] (2) Pour the reaction solution into 300ml 0.5% isopropanol solution and stir for 0.5 hour;

[0052] (3) Add 250g 40% citric acid solution, pH<4, stir for 0.5 hours;

[0053] (4) Layering and concentration of the organic layer to obtain (3S, 4S)-4-acetyl-3-((R)-1-hydroxyethyl)-1-(4-methoxyphenyl) nitrogen heterocycle Butan-2-one 45g, yield 75%, purity 99.7%.

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Abstract

The invention discloses a dissociation method and application of a titanium complex drug. According to the dissociation method, the stronger coordination property of citric acid and metal ions is utilized, the citric acid competes with drug molecules for coordination of titanium ions, the drug molecules complexed in the titanium complexation drug are released, and then separation operation is performed to collect the released drug molecules. According to the dissociation method disclosed by the invention, the purity of the drug compound can be obviously improved, because the citric acid can becompletely complexed with the titanium ions, a titanium complex formed by the drug molecules and the titanium ions is disintegrated, and then the dissociated drug compound is directly concentrated and collected through separation operation, so that the drug compound is obtained. The method is simple and efficient, the obtained drug compound has fewer impurities and higher purity, and the qualityof the drug is obviously improved.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a dissociation method of a titanium complex drug and its application. Background technique [0002] Any substance that affects the purity of a drug is collectively referred to as an impurity. Impurity research is an important part of drug development. It includes selecting appropriate analytical methods, accurately distinguishing and measuring the content of impurities, and comprehensively determining the reasonable limits of impurities based on the results of pharmaceutical, toxicological and clinical research. This research runs through the entire process of drug development. The adverse reactions of drugs in clinical use are not only related to the pharmacological activity of the drug itself, but also sometimes have a lot to do with the impurities in the drug. For example, high-molecular impurities such as polymers in antibiotics such as penicillin are the main ...

Claims

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Application Information

Patent Timeline
28 Feb 2020
Publication
CN110845384A
IPC
C07D205/08
CPC
C07D205/08
Inventors
莫德欢; 张所德