Improved method for preparing valsartan

Abstract

The invention discloses an improved method for preparing valsartan. According to the invention, certain steps required for preparing the valsartan in certain patents in the past are improved. The improved method comprises the following steps of: adding (N-(1-valeryl)-N-[4-[2-(5-cyan)-phenyl]benzyl]-L-valine methyl ester valsartan, sodium azide, triethylamine hydrochloride and a solvent into a reactor, and directly performing diazotization reaction; adding a sodium hydroxide solvent for saponification reaction after the diazotization reaction; and purifying the obtained product to finally obtain the valsartan product with high purity. According to the method, the diazotization reaction time is short, the loss of energy is reduced, the reaction process is environment-friendly, the yield and the purity of the product are high, the industrial production cost is greatly reduced, and the industrial production is easily realized.

Description

technical field [0001] The invention relates to the field of fine chemicals, in particular to an improved method for preparing valsartan. Background technique [0002] Valsartan is an orally effective and specific angiotensin II (AT1) receptor antagonist that selectively acts on AT1 receptor subtypes, blocking the combination of Ang II and AT1 receptors to inhibit vasoconstriction and the release of aldosterone, resulting in a hypotensive effect. It was successfully developed by the Swiss Novartis company, first listed in Germany, approved by the US FDA in 1996, and listed in the US in 1997. [0003] In the preparation method of U.S. Patent No. 5,399,578A, in the step of diazotization, the catalyst it uses is tributyltin chloride, and the reaction time is more than 40 hours. Since the catalyst contains tin, the residual tin will be brought to the final products, and the content exceeds the requirements of ICH, and organotin is a highly toxic compound, which is very difficu...

AI Technical Summary

Problems solved by technology

[0003] In the preparation method of U.S. Patent No. 5,399,578A, in the step of diazotization, the catalyst it uses is tributyltin chloride, and the reaction time is more than 40 hours. Since the catalyst contains tin, the residual tin will be brought to the final products, and the content exceeds the requirements of ICH, and organotin is a highly toxic compound, which is very difficult to control;

[0004] In Chinese Patent Publication Nos. CN101270096A and CN101817795A, the diazotization has been optimized and improved respectively, not only canceling the use of organotin compounds as catalysts, but also using aromatic hydrocarbon solvents as reaction solvents in CN101817795A, indeed in their final products There is no organic tin residue, but it also causes a series of problems, such as low yield, long diazonium reaction time, high content of optical isomers, complicated crystallization process, and difficult operation, which makes the reaction The cost is high, the energy consumption is large, and it is in conflict with the energy conservation and emission reduction advocated by the state, so it is difficult to be suitable for large-scale industrial production