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A kind of alololol hydrochloride and preparation method thereof

A technology of arolol hydrochloride and ethyl acetate, applied in the field of medicine, can solve the problems of not being able to obtain pure arolol hydrochloride, low yield, large solvent system and the like

Inactive Publication Date: 2016-02-24
北京博爱旺康医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The researchers of the present invention have found through a large number of tests that the solubility of arololol hydrochloride in methanol, water, ethyl acetate, and acetone is not large. If these solvents are used for recrystallization, the solvent system is very large on the one hand and is not suitable for industrial scale-up. On the one hand, after the recrystallization step is repeated twice, not only the yield is low, but also the product purity is not high, and HPLC shows that there are two impurities exceeding the standard at t=13.8min and t=15.3min
Due to the poor stability of alololol in the solvent state, if arololol is first refined and then salted, it is also impossible to obtain arololol hydrochloride with good purity, and the yield is lower

Method used

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  • A kind of alololol hydrochloride and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1 Arololol hydrochloride syrup of the present invention

[0030] 1) Put 5-(2-mercapto-4-thiazolyl)-2-thiophenecarboxamide and acetonitrile in a three-necked flask, reflux for 0.5h under stirring, keep warm, add epichlorohydrin, and continue to reflux until HPLC monitors the reaction At the end, the reaction solution was lowered to room temperature, suction filtered, stirred, a large amount of solids precipitated, stirred overnight, continued to stir in an ice-water bath for 3 hours, collected solids by suction filtration, rinsed with acetonitrile, and air-dried at 40°C to obtain a solid product;

[0031] 2) Put the solid product, methanol, and tert-butylamine in a three-necked flask, and react under slight reflux for 10 hours. The reaction solution was concentrated to remove the solvent, and the residue was dissolved with methyl tert-butyl ether and methanol, and HCL gas was introduced to saturation, and the solid was precipitated and filtered. The solid was ...

Embodiment 2

[0034] Embodiment 2 Arololol hydrochloride enteric-coated tablet of the present invention

[0035] 1) Put 5-(2-mercapto-4-thiazolyl)-2-thiophenecarboxamide and acetone in a three-necked flask, reflux for 1 hour under stirring, keep warm, add epichlorohydrin, and continue to reflux until the end of the reaction monitored by HPLC , the reaction solution was lowered to room temperature, suction filtered, stirred, a large amount of solids were precipitated, stirred overnight, continued to stir in an ice-water bath for 5 hours, collected solids by suction filtration, rinsed with acetone, and air-dried at 60°C to obtain a solid product;

[0036] 2) Put the solid product, ethanol, and tert-butylamine in a three-necked flask, and react under slight reflux for 15 hours. The reaction solution was concentrated to remove the solvent, and the residue was dissolved in methyl tert-butyl ether and ethanol, and HCL gas was introduced to saturation, and the solid was precipitated and filtered. ...

Embodiment 3

[0039] Embodiment 3 Arololol hydrochloride injection of the present invention

[0040] 1) Put 5-(2-mercapto-4-thiazolyl)-2-thiophenecarboxamide and ethyl acetate in a three-necked flask, reflux for 0.8h under stirring, keep warm, add epichlorohydrin, and continue to reflux to HPLC Monitor the completion of the reaction, lower the reaction solution to room temperature, suction filter, stir, a large amount of solids precipitate, stir overnight, continue stirring in an ice-water bath for 3-5 hours, collect solids by suction filtration, rinse with ethyl acetate, and dry at 50 °C to obtain solid product;

[0041]2) Put the solid product, acetone, and tert-butylamine in a three-necked flask, and react under slight reflux for 12 hours. The reaction liquid is concentrated to remove the solvent, and the residue is dissolved in methyl tert-butyl ether and acetone, and HCL gas is introduced to saturation, and the solid is precipitated and filtered. The solid was collected and dried to o...

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Abstract

The invention belongs to the medical technical field, and specifically discloses a high-purity arotinolol hydrochloride and a preparation method thereof. Through lots of research trials, the technicians of the invention find out the fact that the arotinolol hydrochloride having the purity of more than 99.95% can be obtained through the steps of combining two steps of reactions ammonolysis and salification and directly forming a hydrochloride, and then carrying out stirring and washing with absolute ethyl alcohol twice.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to arololol hydrochloride and a preparation method thereof. Background technique [0002] Arololol hydrochloride, chemical name 5-[2-[(3-tert-butylamino-2-hydroxypropyl) mercapto]-4-thiazolyl]-2-thiophenecarboxamide hydrochloride, is a selective β1-adrenergic receptor inhibitors, with weak α1-adrenoceptor antagonistic effect, can inhibit α1-adrenergic receptor excitation while lowering blood pressure, reduce sympathetic tension, and reduce β-receptor blockade Adverse reactions, relieve diastolic blood pressure, and make the antihypertensive effect more ideal. Clinically, it is mainly used to treat mild to moderate essential hypertension, angina pectoris, tachyarrhythmia and essential tremor. [0003] Alololol hydrochloride was developed by Sumitomo Pharmaceutical Co., Ltd. of Japan, and it was listed in Japan for the first time in 1985. J.PharmaceuticalSciences, 67 (9...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D417/04
CPCC07D417/04
Inventor 黄华
Owner 北京博爱旺康医药科技有限公司
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