Method for preparing 9-oxo-10(9H)-acridineacetic acid

Abstract

The invention discloses a method for preparing 9-oxo-10(9H)-acridineacetic acid, and belongs to the field of organic synthesis. The method comprises the following steps: (1) under the effects of a metal carbonate, a catalyst and a solvent, performing a condensation reaction on o-chlorobenzoic acid (a) and aniline (b) to prepare an intermediate c; (2) under the effects of toluene and p-toluenesulfonic acid, performing a cyclization reaction on the intermediate c by refluxing and dehydrating to prepare an intermediate d; (3) dissolving the intermediate d in dimethyl formamide , successively adding 60% NaH, KI and ethyl chloroacetate, reacting at room temperature to obtain a wet intermediate e; and (4) hydrolyzing the wet intermediate d with NaOH to obtain a crude product f, and refining the crude product f to obtain the 9-oxo-10(9H)-acridineacetic acid product. The method has the advantages of low cost consumption, small pollution during reaction, smooth and easy-controlling reaction and high product yield, and has better industrial application value.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing acridoneacetic acid. Background technique [0002] Acridone derivatives have become a research hotspot in the field of medicine in recent years due to their good antibacterial, anti-inflammatory, anti-malarial and anti-cancer activities. Electrostatic attraction binds to DNA, and some 9-aminoacridine derivatives have been clinically used as DNA intercalation reagents due to their good pharmacological and biological activities. As an important pharmaceutical intermediate, acridone acetic acid has received more and more attention. [0003] The traditional method for preparing acridone acetic acid has problems such as large solvent consumption, low yield, violent reaction and serious pollution. For example, when the condensation reaction synthesizes the intermediate N-phenylanthranilic acid, the base usually used in the literature is a metal hydr...

AI Technical Summary

Problems solved by technology

[0003] The traditional method for preparing acridone acetic acid has problems such as large solvent consumption, low yield, violent reaction and serious pollution.

For example, when the condensation reaction synthesizes the intermediate N-phenylanthranilic acid, the base usually used in the literature is a metal hydroxide (such as: NaOH), which easily leads to a strong alkalinity in the system and difficult control of the pH value. The commonly used The catalyst is copper powder, the catalyst is easily deactivated, cannot be reused, and the reaction temperature is high, the reaction process is more violent, which is not conducive to industrial scale-up production

For example: in the literature of the steps of cyclization reaction to synthesize acridone, concentrated sulfuric acid is generally used for dehydration, and the product yield is low, and at the same time, environmental pollution is caused because the concentrated sulfuric acid cannot be recycled.