Method for synthesizing anastrozole

Abstract

The invention discloses a novel method for synthesizing anastrozole, and belongs to the technical field of medicinal chemistry. The method comprises the following steps: 3,5-dibromo toluene used as a starting material reacts to produce 3,5-dibromo methyl toluene under the effect of a brominating agent NBS (N-bromosuccinimide), and reacts to produce an intermediate 3,5-bis[(2,2-dimethyl) cyano methyl]- bromo methyl benzene through a cyanidation reaction, a methylation reaction and a bromination reaction; and then the intermediate reacts with 1,2,4-triple nitrogen oxazole sodium to produce the anastrozole. The novel method is characterized in that the second step of cyano substitution reaction is improved. The method has the advantages that the process is simple, the efficiency is greatly improved, the yield is improved to 83 percent to 88.20 percent, the cost is reduced, the solvent use amount is reduced, the environment is further protected, and little side reaction is caused; and as the cost is reduced, the method is very beneficial to and suitable for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of anastrozole. Background technique [0002] Anastrozole is a highly efficient and highly selective non-steroidal aromatase inhibitor and a representative drug of the third generation of aromatase inhibitors. , less adverse reactions, good tolerance, worthy of clinical application. [0003] [0004] Chemical Name: [0005] a,a,a'a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-diethylcyanobenzene. [0006] 2,2'-[5-(1H-1,2,4-Tripyrrol-1-yl-methyl)-1,3-phenylene]bis(2-methylpropionitrile) [0007] Chemical Structure: [0008] Molecular formula: C17H19N5 Molecular weight: 293.37 [0009] As an important pharmaceutical intermediate, the synthetic method of anastrozole, at present, the technical route generally adopted in industrialized large-scale production is as follows: [0010] [0011] In the process of synthesizing int...

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Problems solved by technology

[0013] It has the following disadvantages: 1. Due to the residual HBr in the intermediate 1, hydrogen cyanide gas will be produced in the reaction process, especially in the vacuum distillation process, which is very dangerous

2. The excess of potassium cyanide in the reaction is 1.5 times. When extracting with chloroform, due to the large proportion of chloroform, it is necessary to frequently transfer materials, and these materials contain high-concentration potassium cyanide solution, so the risk is greatly increased

3. The steps in the process are cumbersome. After concentration, extraction, re-concentration, crystallization and other steps, the labor intensity is high and the efficiency is low. In addition, the large amount of solvent is used, which increases the cost and the pressure on environmental protection

4. The yield of this process is low and the cost is high, which is very unfavorable for industrial production

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