Valsartan refining method

A refining method and technology of valsartan, applied in the field of medicinal chemistry, can solve the problems of unsuitability for industrial production, unsatisfactory method and high price of butanone, and achieve the effects of easy control of process conditions, improved particle size and low solvent cost.

Active Publication Date: 2013-12-11
SHANDONG XINHUA PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The applicant also tried to adopt the refining method in the patent CN101768128, but the experimental results showed that the method was not ideal: the crude product of valsartan with a D-isomer content of 5.9% was refined once, and the D-isomer content was only reduced to 4.2%, and the yield is low
In addition, the price of methyl ethyl ketone is also relatively high, which is not suitable for industrial production.

Method used

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  • Valsartan refining method

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Experimental program
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Effect test

Embodiment 1

[0024] Dissolve 35g of valsartan (the content of D-isomer is 5.9%) in a mixed solvent of 35ml of ethanol and 120ml of ethyl acetate, and then heat to 45±2°C to completely dissolve the solid. Then slowly lower to room temperature, a large amount of white solid will be precipitated during the cooling process. Suction filtration after 4 hours gave 28.2 g of valsartan with a yield of 80.6% and a D-isomer content of 0.02%.

Embodiment 2

[0026] Dissolve 35g of valsartan (4.5% D-isomer content) in a mixed solvent of 16ml of methanol and 100ml of ethyl formate, and then heat to 40±2°C to completely dissolve the solid. Then slowly lower to room temperature, a large amount of white solid will be precipitated during the cooling process. Suction filtration after 4 hours gave 30.2 g of valsartan with a yield of 86.3% and a content of D-isomer of 0.01%.

Embodiment 3

[0028] Dissolve 35g of valsartan (the D-isomer content is 6.1%) in a mixed solvent of 25ml of isopropanol and 100ml of methyl acetate, and then heat to 65±2°C to completely dissolve the solid. Then slowly lower to room temperature, a large amount of white solid will be precipitated during the cooling process. Suction filtration after 4 hours gave 29.9 g of valsartan with a yield of 85.4% and a D-isomer content of 0.07%.

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Abstract

The invention discloses a valsartan refining method, belonging to the technical field of medical chemistry. The method comprises the following steps: dissolving a valsartan crude product with isomer content of 1.0-10.0% in an alcohol solvent-ester solvent system; heating to 30-70 DEG C so as to completely dissolve the valsartan crude product; and slowly cooling, separating out crystals and filtering to obtain a valsartan refined product. The alcohol solvent is one of methanol, ethanol and isopropyl alcohol or the mixture of two or three of methanol, ethanol or isopropyl alcohol in any proportion; and the ester solvent is one of ethyl formate, ethyl acetate and methyl acetate or the mixture of two or three of ethyl formate, ethyl acetate and methyl acetate in any proportion. The mass ratio of the alcohol solvent to the ester solvent to the valsartan crude product is (0.05-1.0):(1.0-10.0):1. By adopting the method disclosed by the invention, the isomer content in the valsartan crude product is reduced to be hardly detected from 1.0-10.0%, and the quality of the finished product of valsartan is improved; the particle size of the finished product of valsartan is improved, thereby facilitating the product charge, centrifugation and drying; and the method is simple to operate, low in cost and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a method for refining valsartan. Background technique [0002] Valsartan is the second angiotensin Ⅱ receptor antagonist to be marketed and has become the first-line drug for the treatment of hypertension. In addition to treating hypertension, it can also be used to treat heart failure. Valsartan has become the fastest-growing hypertension drug due to its stable blood pressure reduction, strong curative effect, good safety, low side effects, once-a-day administration and good patient compliance. In the past two years, valsartan has become the leading variety in the global antihypertensive drug market. [0003] Valsartan is a chiral drug. During the preparation process, its chiral center is easily racemized to generate the D-isomer (impurity A in the EP Pharmacopoeia), which reduces the optical purity of valsartan. According to the structural characterist...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D257/04
Inventor 商艳梅宋广慧张滨郭照奎于小萍
Owner SHANDONG XINHUA PHARMA CO LTD
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