Method for preparing high-purity ethanesulfonic acid nintedanib

A technology of nintedanib ethanesulfonate and nintedanib ethanesulfonate, applied in the direction of organic chemistry, etc., can solve the problems that the purity results of nintedanib ethanesulfonate have not been disclosed, and no reports have been seen.

Inactive Publication Date: 2015-10-28
NANJING CHIA TAI TIANQING PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these methods disclose the preparation process of nintedanib ethanesulfonate, the purity results of nintedanib ethanesulfonate obtained under the preparation process are not disclosed.
[0007] To obtain high purity, especially to obtain nintedanib ethanesulfonate within the reporting limits (single maximum impurity shall not be greater than 0.1%) in the impurity reporting limit in the raw material drug of ICH (International Conference on Harmonization of Technical Requirements for Registration of Drugs for Human Use), Further refining treatment is still required, and such a refining treatment method has not been reported

Method used

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  • Method for preparing high-purity ethanesulfonic acid nintedanib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] The refining effects of different solvents (commonly used recrystallization solvents) in the same refining process were investigated.

[0024] Dissolve the crude product of nintedanib ethanesulfonate (refer to Chinese patent CN101883755 (patent authorization announcement number) for the preparation method) in different solvents, stir and heat up to reflux until all nintedanib ethanesulfonate in the system is dissolved . After the solid is dissolved, the temperature is lowered under stirring. After the temperature is lowered to 29°C to 31°C, the finished solid of nintedanib ethanesulfonate is obtained by direct filtration.

[0025] Please refer to the table below for the inspection items and results:

[0026]

[0027] Conclusion: Under the same refining operation process, the refining effect of methanol is the best, and the effect of removing the largest single impurity is the strongest. Other solvents have basically no impurity removal effect, and the maximum single...

Embodiment 2

[0029] Investigate the effect of different methanol usage on the refining effect under the same refining operation process.

[0030] Dissolve the crude product of nintedanib ethanesulfonate (refer to Chinese patent CN101883755 (patent authorization announcement number) for the preparation method) in different proportions of methanol, stir and heat up to reflux until all nintedanib ethanesulfonate in the system dissolve clear. After the solid is dissolved, the temperature is lowered under stirring. After the temperature is lowered to 25°C to 35°C, the finished solid of nintedanib ethanesulfonate is obtained by direct filtration.

[0031] Please refer to the table below for the inspection items and results:

[0032]

[0033] Conclusion: Under the same refining operation process, when the ratio of crude product:methanol is lower than 1:2.5, there is basically no impurity removal effect; the effect of removing the largest single impurity is obvious when the ratio of crude prod...

Embodiment 3

[0035] Investigate the effect of different filtration temperatures after cooling down on the refining effect under the same refining operation process.

[0036] Dissolve the crude product of nintedanib ethanesulfonate (refer to Chinese patent CN101883755 (patent authorization announcement number) for the preparation method) in methanol of the same proportion, stir and heat up to reflux until all nintedanib ethanesulfonate in the system dissolve clear. After the solid was dissolved, the temperature was lowered under stirring, and after cooling to different temperatures, the finished solid of nintedanib ethanesulfonate was obtained by direct filtration, and the solid was filtered to remove the solvent and then sampled for testing.

[0037] Please refer to the table below for the inspection items and results:

[0038]

[0039] Conclusion: Under the same refining process, different filtration temperatures have a great influence on the refining effect. When the filtration temp...

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Abstract

The invention discloses a refining method for preparing ethanesulfonic acid nintedanib. Through a refining mode of combining recrystallization and backflow washing, the impurity content in a finished product is reduced remarkably, so that the medication safety of medicine is guaranteed, and the refining method is simple in process and suitable for industrialized batch production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a method for preparing high-purity nintedanib ethanesulfonate. Background technique [0002] Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown cause, characterized by interstitial fibrosis with honeycombing changes in both lungs. About 15% of idiopathic pulmonary fibrosis (IPF) cases are acute, and they are often found to have progressive dyspnea when they seek treatment for upper respiratory tract infection, and die of respiratory and circulatory failure within more than 6 months. The vast majority of IPF is chronic (there may be intermediate subacute), but the average survival time of chronic is only 3.2 years. The chronic type does not seem to have evolved from the acute type, and the exact relationship is not yet known. [0003] Lung cancer is one of the most common malignant tumors in the world, and it has become the first cause of death from malign...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/34
CPCC07D209/34
Inventor 郭璇柴雨柱徐丹朱春霞田舟山单佳琪吴春霞杨岚
Owner NANJING CHIA TAI TIANQING PHARMA
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