Method for preparing sartan drug main ring 5-(4'-formyl biphenyl-2-group)-1H-tetrazole treating hypertension

A formyl biphenyl and high blood pressure technology, applied in the chemical pharmaceutical field, can solve problems affecting product purity and yield, unfavorable production and labor protection, flammable and explosive, etc., to achieve suppression of side reactions, reduction of emissions, and discharge of three wastes little effect

Active Publication Date: 2008-06-18
NANTONG SHIMEIKANG PHARMA CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, because the cyclization of benzyl alcohol has poor stability at high temperature, it is easy to produce impurities, which affects the purity and yield of the product
In addition, trialkyltin chloride is used as a catalyst in the cyclization process. Since this kind of substance is extremely dangerous, it is flammable, explosive and toxic when it meets water and oxygen, so it is not conducive to production and labor protection.

Method used

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  • Method for preparing sartan drug main ring 5-(4'-formyl biphenyl-2-group)-1H-tetrazole treating hypertension
  • Method for preparing sartan drug main ring 5-(4'-formyl biphenyl-2-group)-1H-tetrazole treating hypertension
  • Method for preparing sartan drug main ring 5-(4'-formyl biphenyl-2-group)-1H-tetrazole treating hypertension

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Bromination Reaction: Preparation of Sartan Bromide IV

[0030] In the flask, add 19.3g (0.10mol) of sartan biphenyl III and 200ml of chloroform, under stirring, heat up to 40°C, turn on the high-pressure sodium lamp, and slowly add about 16.0g (0.10mol) of bromine (sartan biphenyl The molar ratio of III and bromine=1:1), control the rate of addition, the reaction produces a large amount of hydrogen bromide gas, which is absorbed with liquid caustic soda, and the bromine is added dropwise in about 1.5 hours. After 4.5 hours of reaction, the chloroform was distilled off, and 100 ml of absolute ethanol was added for recrystallization; after drying, 24.0 g of a white solid product was obtained, the HPLC analysis content was 98%, and the yield was 88.2%;

[0031] Esterification reaction: Preparation of sartan benzyl ester V

[0032] In the flask, add 27.1g (0.10mol) sartan bromide IV, 10.7g (0.13mol) sodium acetate (the molar ratio of sartan bromide IV to sodium acetate=1:...

Embodiment 2

[0040] Bromination Reaction: Preparation of Sartan Bromide IV

[0041] In the flask, add 19.3g (0.10mol) of sartanbiphenyl III and 200ml of chloroform, under stirring, heat up to 61°C for reflux reaction, turn on the high-pressure sodium lamp, and slowly add about 19.2g (0.12mol) of bromine (sartanbiphenyl) dropwise. The molar ratio of benzene III to bromine=1:1.2), control the rate of addition, so that the liquid under the reflux condensation has no obvious yellow, the reaction produces a large amount of hydrogen bromide gas, which is absorbed with liquid caustic soda, and the bromine is added dropwise in about 2 hours. After the addition, continue to keep warm and light for 3 hours, and the reaction is completed for a total of 5 hours; then evaporate the chloroform, add 100ml of absolute ethanol for recrystallization; after drying, 24.4g of a white solid product is obtained, the HPLC analysis content is 99%, and the yield is 90%;

[0042] Esterification reaction: Preparation...

Embodiment 3

[0051] Bromination Reaction: Preparation of Sartan Bromide IV

[0052] In the flask, add 19.3g (0.10mol) of sartan biphenyl III and 200ml of dichloroethane, under stirring, raise the temperature to 70°C for reaction, turn on the high-pressure sodium lamp and slowly add about 16.0g (0.10mol) of bromine (sartan The molar ratio of tanbiphenyl III to bromine=1:1), control the rate of addition, the reaction produces a large amount of hydrogen bromide gas, which is absorbed with liquid caustic soda, and the bromine is added dropwise in about 1.5 hours. Hours, a total of 4.5h to complete the reaction, dichloroethane was distilled off, and 100ml of absolute ethanol was added for recrystallization; after drying, 24.2g of a white solid product was obtained, the HPLC analysis content was 98%, and the yield was about 89%;

[0053] Esterification reaction: Preparation of sartan benzyl ester V

[0054] In the flask, add 27.1g (0.10mol) sartan bromide IV, 10.7g (0.20mol) sodium acetate (the...

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Abstract

The invention belongs to drug synthesis, particularly relates to the main ring of Sartan drug for the treatment of the hypertension i.e. 5-(4'-formyl biphenyl-2-base)-1H-tetrazole. The preparation method comprises the following procedures, bromination, esterification, cyclization, hydrolysis and oxidation. Utilizing the triethylamine hydrochloride to serve as the catalyst, the method of the invention inhibits the side reaction, promotes the purity and the yield of the product, avoids the residue of the poisonous matter in the drug intermediate, reduces the waste discharge, realizes the clean production and protects the environment.

Description

technical field [0001] The invention relates to a preparation method of 5-(4'-formylbiphenyl-2-yl)-1H-tetrazolium, which is the main ring of sartan drugs for treating hypertension, and belongs to the field of chemical pharmacy. Background technique [0002] The main ring used in the synthesis of sartan antihypertensive drugs is mainly N-triphenylmethyl-5-(4'-bromomethylbiphenyl-2-yl)-1H-tetrazolium (I). Due to the difficulty in preparation and purification of this intermediate, its price has remained high. In order to further reduce the cost of drug production and improve the quality of drugs, the new intermediate 5-(4'-formylbiphenyl-2-yl )-1H-tetrazolium (II) was successfully developed. [0003] [0004] 5-(4'-Formylbiphenyl-2-yl)-1H-tetrazolium (II) is a new type of pharmaceutical intermediate, which can be used to produce multiple sartan antihypertensive drugs, such as valsartan , losartan, irbesartan, olmesartan, and candesartan. Compared with the traditional sart...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D257/04
Inventor 王俊华
Owner NANTONG SHIMEIKANG PHARMA CHEM
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