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Method for preparing valsartan

A technology of valsartan and compound, which is applied in the field of drug synthesis to achieve the effect of maintaining optical purity and avoiding the problem of product racemization

Inactive Publication Date: 2015-01-21
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there is "racemization of the product due to too strong alkalinity" in the current conventional synthesis method, so it is necessary to provide a new synthesis method to solve the above technical problems

Method used

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  • Method for preparing valsartan
  • Method for preparing valsartan
  • Method for preparing valsartan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] 1. Preparation of Valsartan

[0044] Add 20mL of methanol, 5.56g of N-(trityl)-5-(4'-bromomethylbiphenyl-2-yl)tetrazolium and 0.81g of sodium methoxide into a 100mL flask at room temperature, and react for 180 minutes at room temperature . After TLC showed that the reaction was complete, the reaction solution was filtered, and 25 mL of dichloromethane was added to the reaction solution, washed with saturated sodium bicarbonate until there were no bubbles, washed with water, separated, the organic phase was dried with anhydrous sodium sulfate, suction filtered, and reduced pressure Remove dichloromethane to obtain the product of the first step.

[0045] Dissolve the product from the previous step in dichloromethane, add 2.27 g of D.D.Q. and stir for 180 minutes at room temperature. After the reaction is complete, the reaction solution is filtered and spin-dried under reduced pressure to obtain the second-step product.

[0046] Under anhydrous conditions, put the produ...

Embodiment 2

[0053] 1. Preparation of Valsartan

[0054] Add 20mL of methanol, 5.56g of N-(trityl)-5-(4'-bromomethylbiphenyl-2-yl)tetrazolium and 1.2g of sodium methoxide into a 100mL flask at room temperature, and react for 180 minutes at room temperature . After TLC showed that the reaction was complete, the reaction solution was filtered, and 25 mL of dichloromethane was added to the reaction solution, washed with saturated sodium bicarbonate until there were no bubbles, washed with water, separated, the organic phase was dried with anhydrous sodium sulfate, suction filtered, and reduced pressure Remove dichloromethane to obtain the product of the first step.

[0055] Dissolve the product from the previous step in dichloromethane, add 2.27 g of D.D.Q. and stir for 180 minutes at room temperature. After the reaction is complete, the reaction solution is filtered and spin-dried under reduced pressure to obtain the second-step product.

[0056] Under anhydrous conditions, put the produc...

Embodiment 3

[0063] 1. Preparation of Valsartan

[0064] Add 20mL of methanol, 5.56g of N-(trityl)-5-(4'-bromomethylbiphenyl-2-yl)tetrazolium and 0.81g of sodium methoxide into a 100mL flask at room temperature, and react for 180 minutes at room temperature . After TLC showed that the reaction was complete, the reaction solution was filtered, and 25 mL of dichloromethane was added to the reaction solution, washed with saturated sodium bicarbonate until there were no bubbles, washed with water, separated, the organic phase was dried with anhydrous sodium sulfate, suction filtered, and reduced pressure Remove dichloromethane to obtain the product of the first step.

[0065] Dissolve the product from the previous step in dichloromethane, add 3.27 g of D.D.Q. and stir for 120 minutes at room temperature. After the reaction is complete, the reaction solution is filtered and spin-dried under reduced pressure to obtain the second-step product.

[0066] Under anhydrous conditions, put the produ...

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Abstract

The invention provides a method for preparing valsartan. The method comprises the following steps: firstly, reacting N-(triphenylmethyl)-5-(4'-formyl-biphenyl-2-yl) tetrazolium with sodium methoxide, secondly, adding dichlorodicyanobenzoquinone (DDQ) and oxidizing, thirdly, reacting with L-valine methyl ester, fourthly, alkylating with valeryl chloride, fifthly, removing triphenylmethyl group and sixthly removing ester group and acidifying to obtain the target product valsartan. According to the method, a novel method for preparing valsartan is provided by virtue of the Williamson ether synthesis step and DDQ oxidation step, since potassium dihydrogen phosphate is adopted as a buffering reagent in the triphenylmethyl group removal process and a 1.3mol / L sodium hydroxide solution is used in the hydrolysis process, the problem of racemization of the product generated caused by too strong alkaline is avoided and the method is of important significance in maintaining the optical purity of the valsartan product.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for preparing valsartan. Background technique [0002] Valsartan (chemical name: N-(1-pentanoyl)-N-[4-2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine) can be used for Various types of high blood pressure, and have a good protective effect on the heart, brain and kidney. Hypertensive patients such as myocardial infarction, heart failure, proteinuria, and diabetes can be used routinely, and can be used in combination with diuretics (such as hydrochlorothiazide). The structural formula of valsartan is as follows: [0003] [0004] The literature on valsartan is quite abundant, especially concentrated on the synthetic route, as Ivica uses 2'-tetrazolyl-4-formyl biphenyl (tetrazolyl is protected) as raw material, and L-valine The secondary amine intermediate is prepared by condensation of methyl ester, followed by n-valerylation, and finally the trityl protecting group of tetr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D257/04
CPCC07D257/04
Inventor 虞心红袁永翔卢琳王庆庆潘程王天池封丛鹏
Owner EAST CHINA UNIV OF SCI & TECH
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