Method for synthesizing 7-bromo-6-chloro-4-quinazolinone

Abstract

The invention discloses a method for synthesizing 7-bromo-6-chloro-4-quinazolinone. The method comprises the following steps of: (1) dripping liquid bromine into suspension of m-chlorotoluene, n-butyl bromide and anhydrous ferric trichloride, washing with water and a saturated sodium bicarbonate solution, distilling, and recrystallizing; (2) mixing water, pyridine, tertiary butanol and the like, dissolving a product in the step (1) and potassium permanganate in a mixed solution, heating and refluxing, continuously adding potassium permanganate, filtering, washing with boiling water, regulating the pH value, cooling and filtering; (3) dissolving a product in the step (2) in a mixed solution of stronger ammonia water and ethyl acetate at room temperature under the protection of nitrogen, dripping into suspension of cuprous oxide and stronger ammonia water, adding ethylene diamine tetraacetic acid (EDTA), regulating the pH value, evaporating the ethyl acetate, cooling, and performing suction filtration; and (4) mixing a product in the step (3) and formamide, dissolving in dimethyl formamide (DMF), heating and refluxing, cooling, precipitating, filtering, washing with absolute ethanol, and recrystallizing by using ethylene glycol monomethyl ether. The method has the advantages of cheap raw materials, simplified steps and practicable process, avoids 6-bromoisatin, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediate synthesis. Background technique [0002] 7-Bromo-6-chloro-4(3H)-quinolone is an important intermediate for the synthesis of Stenorol, an effective drug against poultry coccidiosis, which is commonly used in the market and related compounds. The main component of Sudan is hemosanone hydrobromide. It was first extracted from Changshan, a traditional Chinese medicine, by Cyanamid Company of the United States, and then the company completed the research on the artificial synthesis of Changshanone. The medicine is mainly used for preventing and treating coccidiosis of domestic animals and poultry. The advantages of the phloxanthone are small dosage, good clinical effect and no drug resistance or little drug resistance. According to the latest research, this type of compound can also inhibit the excessive production of collagen and the production of cell activity. At the same time,...

AI Technical Summary

Problems solved by technology

[0004] 1. EmanuelM et al. used 6-bromoisatin as a raw material to obtain 7-bromo-6-chloro-4(3H)-quinolone through a three-step reaction, but the raw material 6-bromoisatin has not yet been industrialized in China, so the raw material was prepared The steps are cumbersome, currently only imported or small-scale production in the laboratory, so the price is higher

[0005] 2. Mao Zhongxing, Mao Guanxing, Jin Junting, and Huang Wenbin disclosed a synthetic method. The second step in the synthesis uses a single solvent water, and the raw materials are not soluble in water, so the reaction yield is low, or even not. carry out; the fourth step reaction yield is also lower, only 67%

[0006] 3. Zhang Yue, Niu Yuhuan, Dong Bofang, Wang Yinhua, Di Xiaotao, Du Huiru, 2006, 23 (8): 822-824. Disclosed a synthetic method, the steps of the synthetic method are cumbersome, and there are side reactions in the second step reaction occurs, the product needs to be separated, and the reaction yield is only 26.5%

[0007] 4. Jin Liqiong, Liang Jianping, Wang Xuehong, Hua Lanying, 2009, 26 (11): 1137-1140. A synthetic method is disclosed in which the synthetic route is complicated and the reaction time is long; the fourth step reaction will produce 6-bromoindigo A mixture of red and 4-bromoisatin, the product needs to be separated and purified

High cost, not suitable for industrial production