Preparation of 2-chlorin-4-amido-6,7-dimethoxy quinazoline

Abstract

The invention discloses a preparation method of 2-chloro-4-amido-6,7-dimethoxy quinazoline. The preparation method comprises the following steps: 3,4-dimethoxy benzaldehyde is taken as an initial raw material, then the following reactions are sequentially carried out: oxidizing reaction between the 3,4-dimethoxy benzaldehyde and oxydol, nitration reaction between the 3,4-dimethoxy benzaldehyde and nitric acid, reduction reaction of the 3,4-dimethoxy benzaldehyde and hydrogen ion obtained by iron powder and hydrochloric acid, reaction between the 3,4-dimethoxy benzaldehyde and sodium cyanate, chlorination reaction between the 3,4-dimethoxy benzaldehyde and phosphorus oxychloride, ammoniation reaction between the 3,4-dimethoxy benzaldehyde and ammonia liquor, etc., then the 2-chloro-4-amido-6,7-dimethoxy quinazoline is obtained. The synthetic method takes the commercialized 3,4-dimethoxy benzaldehyde as the initial raw material, and potassium permanganate is not used in the oxidizing reaction process, organic solvents (glacial acetic acid, DMF) are not used in the refining process, the noxious solvent N, N-amino dimethylbenzene or the organic solvent N, N-dimethyl formamide with high boiling point is not used in the chlorination process, so the use amounts of the organic solvents and the phosphorus oxychloride are reduced, thus reducing the production cost, simplifying the production process, protecting the health of operators, reducing 'three wastes' pollution, protecting the environment and greatly improving the reaction yield and the production efficiency.

Description

technical field

[0001] The invention belongs to the synthesis of oxazin drug intermediates, in particular, it relates to a preparation method for the chemical synthesis of 2-chloro-4-amino-6,7-dimethoxyquinazoline. Background technique

[0002] At present, 2-chloro-4-amino-6,7-dimethoxyquinazoline has good biological activity and pharmaceutical activity, and is an important class of pharmaceutical and fine chemical intermediates, which can be used in the synthesis of oxazin drugs . 2-Chloro-4-amino-6,7-dimethoxyquinazoline is synthetic prazosin hydrochloride (treatment of high blood pressure), terazosin hydrochloride (treatment of high blood pressure), doxazosin mesylate ( It is an important intermediate of oxazosin APIs such as treating benign prostatic hyperplasia), brazosin hydrochloride (treating mild to moderate essential hypertension), and alfuzosin (treating benign prostatic hyperplasia).

[0003] 1) Using vanillin as the starting material, the target compound (I) w...

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