Trifluoromethyl containing quinazoline derivative and preparation method and application thereof

Abstract

The present invention discloses a trifluoromethyl containing quinazoline derivative and a preparation method and application thereof. The preparation method comprises the following steps of: under the condition that copper and ligand exist, an N-cyano substituted aryl carboxamides compound reacting with a togni reagent in a solvent, and after completion of the reaction, obtaining the trifluoromethyl containing quinazoline derivative after treatment. The reaction substrate is readily available, the operation is convenient, the obtained quinazolinone derivative is of rich diversity, the required reaction condition is mild, and the reaction time is short. The all-in-one-pot reaction is realized, and not only a structural mother kernel of quinazoline is obtained, but also trifluoromethyl is introduced into the mother kernel structure. And the quinazolinone compound contains the spiropyran compound can be synthesized, which cannot be achieved by the prior art. The obtained product has good activity in inhibiting enzyme acetylcholinesterase and butyrylcholinesterase.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of a trifluoromethyl-containing quinazolinone derivative, and the inhibitory activity of the compound on acetylcholinesterase and butyrylcholinesterase is tested. Background technique [0002] Quinazolinones are a class of substances with biological activity or medicinal value. Many natural products contain the structural nucleus of quinazolinones, and are favored by the majority of medical workers, showing good biological activity. The following are the structural representatives of quinazolinones with biological activity: [0003] [0004] Due to the strong electron-withdrawing properties, lipophilicity and stable C-F bond of trifluoromethyl, the introduction of it into organic compounds can significantly change the acidity, dipole moment, polarity and chemical and metabolic stability of the compound, so Compounds containing trifluoromethy...

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Problems solved by technology

[0004] Due to the strong electron-withdrawing properties, lipophilicity and stable C-F bond of trifluoromethyl, the introduction of it into organic compounds can significantly change the acidity, dipole moment, polarity and chemical and metabolic stability of the compound, so Compounds containing trifluoromethyl groups have been widely used in the fields of medicine and pesticides, and the development of methods for introducing trifluoromethyl groups into organic molecules has become a hot topic in current research. For decades, chemists have developed various types of vectors The reaction of organic molecules introducing trifluoromethyl groups, but these reactions have the disadvantages of harsh reaction conditions, rare raw materials and poor selectivity. In recent years, driven by the research of organometallics, significant research progress has been made in trifluoromethylation reactions. At the same time, the classical reaction via the trifluoromethyl radical was thoroughly explored

[0005] The methods commonly used in the past for the synthesis of quinazolinone compounds mainly use raw materials such as anthranilic acid and o-bromoaniline, but they have disadvantages such as low yield, poor adaptability to substrates, and harsh conditions for the reaction.

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