Preparation method of irbesartan

Abstract

The invention discloses a preparation method of irbesartan, which comprises the following steps of: 1) using irbesartan imidazole hydrochloride and 2-cyano-4'-bromomethylbiphenyl as raw materials, conducting alkylation reaction in a water-aprotic solvent non-homogeneous system under the effect of inorganic base and phase transfer catalyst to prepare irbesartan hydrocarbon; and 2) taking the irbesartan hydrocarbon prepared in the step 1 and azimino compounds and conducting cyclization reaction in polar solvent under the effect of cyclization catalyst to prepare irbesartan. The preparation method of irbesartan provided by the invention has the advantages of simplicity and convenience in operation, easiness in obtaining raw materials, easiness in realization of reaction conditions, high yield, low cost, environmental friendly and the like, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of irbesartan. Background technique [0002] Hypertension is one of the most common cardiovascular diseases in the world today. Epidemiological studies show that there are currently 600 million hypertensive patients in the world, and the prevalence of hypertension is about 10%. Over the past few decades, the prevalence of hypertension in my country has been increasing rapidly. The "Investigation Report on the Nutrition and Health of Chinese Residents" released at the press conference of the State Council Information Office on October 12, 2004 pointed out that the prevalence of hypertension in Chinese adults The prevalence rate is 18.8%, and the number of patients is 160 million; according to the figures published in the "2007 China Hypertension Disease Diagnosis and Treatment Standards and Development Strategies Forum" held in 2007: there are 200 million hypertensive patients in my country, and new ones are ...

AI Technical Summary

Problems solved by technology

[0007] (1) Sodium hydride is a dangerous reagent. It can explode when it meets water or humid air and releases hydrogen gas. It is dangerous to use and store;

[0008] (2) The reaction solvent is DMF, which is miscible with water and has a high boiling point. After the reaction is completed, because DMF is miscible with water, it is difficult to handle, it is easy to pollute the environment, and it cannot be recycled, resulting in high cost;

[0009] (3) Alkyl tin chloride and sodium azide or alkyl tin azide are used in the cyclization reaction. These substances are highly corrosive and pose a threat to equipment and operators. In addition, tin is easy to remain in the product, causing heavy metal Exceeding the standard, and the price is expensive, which increases the cost of the product

[0012] Disadvantages of this method: compound 4 and compound 6 are not commonly used chemical reagents, they need multi-step reactions to obtain, difficult to purchase and prepare, high cost of raw materials, not conducive to large-scale industrial production

[0015] This method uses TTBB as the starting raw material, which can avoid the use of alkyl azides, but the price of TTBB is several times that of brominated biphenyls. Using this route to produce irbesartan, the cost of raw materials is too high, so industrialized large-scale production is limited

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