Synthesis method of 4-3 (H) quinazolinone and derivative thereof

Abstract

The invention provides a synthesis method of 4-(3H) quinazolinone and a derivative thereof (formula III), which is characterized in that imidazole hydrochloride is used as a catalyst, and 2, 3-disubstituted quinazolinone and the derivative thereof are synthesized from anthranilic acid and a derivative thereof and a DMF (Dimethyl Formamide) derivative by a one-pot method in the absence of other catalysts or additives. The synthesis method disclosed by the invention has good functional group tolerance, and 4-(3H) quinazolinone and derivatives thereof can be synthesized for research in medicines or other fields. According to the synthetic method, dichloromethane, corrosive concentrated hydrochloric acid and a metal catalyst are not used, harsh reaction conditions, gas protection and an autoclave are not needed, the reaction time is short, and the synthetic method has certain value in industrial production.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a synthesis method of 4-(3H) quinazolinone and derivatives thereof. Background technique [0002] 4-(3H)quinazolinone is a class of important nitrogen-containing heterocyclic compounds with a benzopyrimidinone skeleton, which exists in many natural bases such as ethosine, cameline, and citrine. Quinazolinone compounds have a wide range of application potentials because their quinazolinone skeletons are easily modified by multiple functional genes, especially in the field of medicine. Substances containing quinazolinone structures have been found to have a variety of biopharmacological activities. Including antibacterial, antiviral, antitumor, antihypertensive, antiallergic, anti-inflammatory and analgesic, enzyme inhibition, etc. For example, the recently approved new drug Idelalisib, as a 4-(3H) quinazolinone-based P13K inhibitor, is used to treat some hematolog...

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Problems solved by technology

The traditional 4-(3H) quinazolinone synthesis mainly includes: use phosphinimine and isocyanate, substituted phenol (or other nucleophile) to synthesize 4-(3H) quinazolinone core by Aza-Wittig reaction, the The method has mild conditions and high yield, but isocyanate is highly toxic; 4-(3H)quinazolinone is synthesized by using 4H-3,1-benzoxazin-4-one as an intermediate, and the method is simple to separate and purify. However, there are many reaction steps; 4(3H)-quinazolinone is synthesized in one pot with anthranilic acid and formamide. This method has few steps, but the temperature is too high, the reactants are easily carbonized and blackened, and the product is difficult to separate and purify, resulting in the production of The efficiency is reduced; there are also bibliographic reports on the synthesis of 4(3H)-quinazolinones with organic metals as catalysts. This type of method has simple raw materials, but there are disadvantages such as catalysts that are harmful to the environment and are expensive; the newly reported solid-phase method is used to synthesize quinazolinones. The mother nucleus of oxazolinone, this method can be used for the synthesis of large combinatorial library, and product purity is high, but reaction steps is many, and total yield is low, therefore, develops a kind of new simple synthesis method environmentally friendly and low toxicity to construct quinone The mother nucleus of oxazolinone is of great significance

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