Method for synthesizing valsartan

A synthesis method and a technology for valsartan, applied in the field of preparation of antihypertensive drugs, can solve the problems of troublesome purification process, reduced yield, low yield and the like, and achieve the improvement of total yield, reduction of consumption of raw materials, and reduction of pollution. Effect

Inactive Publication Date: 2012-04-18
HEFEI UNIV OF TECH
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Problems solved by technology

However, in the process of synthesizing N-(2'-cyanobiphenyl-4-methylene)-N-n-valeryl valine methyl ester, high-boiling toluene is used as a solvent, which requires a higher temperature In the process of synthesizing valsartan methyl ester, diisopropylethylamine is used, which will lead to the generation of by-products; at the same time, tributyltin azide is used as azide Nitriding reagent, the yield is low, the yield of azidation reaction is about 70%, and the total yield of this method is 47%

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  • Method for synthesizing valsartan
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Embodiment Construction

[0029] 1. Preparation of intermediate I N-(2'-cyanobiphenyl-4-methylene)-L-valine methyl ester hydrochloride

[0030] 1.1 Weigh 15g K 2 CO 3 Put it into a 250mL three-neck flask, add 100mL dichloroethane as a solvent, then weigh 13.2g (0.1mol) of L-valine methyl ester hydrochloride and 27.2g (0.1mol) of 4′-bromomethyl-2 - Add cyanobiphenyl to the three-necked flask, and add 1.7g (0.01mol) CuCl 2 and 2.0g (0.01mol) FeCl 2 As a catalyst, control the reaction temperature at 30-35°C, stir and react for 24 hours, after the reaction is complete, add 40 mL of deionized water and stir for 5 minutes, separate the mixed reaction liquid, keep the organic phase, and extract the water phase with 20 mL of dichloroethane, Combine the organic phases, wash with 30mL deionized water, remove the solvent by rotary evaporation, add 60mL dichloroethane, stir until the above product is completely dissolved, cool the temperature to 0-5°C, add 5mL concentrated hydrochloric acid, stir for 1h, and so...

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Abstract

The invention discloses a method for synthesizing valsartan. The method comprises the following steps of: performing coupling reaction of 4'-brooethyl-2-cyanobiphenyl and L-valine methyl ester or L-valine methyl ester hydrochloride to obtain an intermediate I, namely N-(2'-cyanobiphenyl-4-methylene)-L-valine methyl ester or hydrochloride thereof, performing acylation reaction of the intermediate I and valeroyl chloride to obtain an intermediate II, namely N-(2'-cyanobiphenyl-4-methylene)-N-n-valery-L-valine methyl ester, finally putting the intermediate II into a system of zinc chloride and sodium azide and performing azido reaction to obtain an intermediate III, namely valsartan methyl ester, and hydrolyzing the intermediate III under alkaline conditions to obtain a target product. In the method, the yield of the valsartan methyl ester which is taken as an example is over 75 percent; and compared with other prior arts with the total yield of 40 percent, the method has the advantages that raw materials consumed for each ton of product are greatly reduced.

Description

1. Technical field [0001] The invention relates to a preparation method of antihypertensive drugs, in particular to a synthesis method of valsartan. 2. Background technology [0002] Hypertension has become a major killer that endangers human health. Once the disease occurs, it will be used for life. Therefore, drugs for the treatment of hypertension have huge market potential and development prospects. Antihypertensive drugs represented by losartan, valsartan and irbesartan are AngII receptor inhibitors, which are currently one of the most widely used antihypertensive drugs. Valsartan is the second sartan drug used in clinical practice, with positive curative effect, good safety and high tolerance. Among the main antihypertensive drugs, valsartan is also the fastest growing product with broad market prospects and great development value. [0003] The chemical name of valsartan is N-(1-oxopentyl)-N-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine, CSA No.: 137862-53-4, its...

Claims

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Application Information

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IPC IPC(8): C07D257/04
Inventor 冯乙巳章丰丰徐中秋耿烨谢传奇
Owner HEFEI UNIV OF TECH
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