Method for preparing 2,3-dichloroquinoxaline derivatives in one pot

Abstract

The invention belongs to the field of drug synthesis, and specifically relates to a new method for preparing 2,3-dichloroquinoxaline derivatives in one pot. Friendly silica gel or methanesulfonic acid is used as the catalyst, and the intermediate separation and purification steps are omitted, the operation is simple, the cost is low, the reaction conditions are mild, and it is environmentally friendly, and it is easy to industrialize large-scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a novel method for preparing 2,3-dichloroquinoxaline derivatives in one pot. Background technique [0002] 2,3-Dichloroquinoxaline derivatives, whose structure is shown in formula I, are an important class of pharmaceutical and fine chemical intermediates, which can undergo nucleophilic aromatic substitution reactions under mild conditions without the need for metal catalysts. A series of drugs or compounds with anti-tumor, anti-inflammatory, anti-psychotic and other pharmacological effects can be synthesized by introducing substituents at the 2-position and / or 3-position of quinoxaline. Therefore, they have received extensive attention in the field of biomedicine. [0003] [0004] At present, there are two main methods for preparing 2,3-dichloroquinoxaline derivatives. One is to use substituted o-phenylenediamine and oxalic acid as raw materials, and first react in ...

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Problems solved by technology

[0004] At present, there are two main methods for preparing 2,3-dichloroquinoxaline derivatives. One is to use substituted o-phenylenediamine and oxalic acid as raw materials, and first react in aqueous hydrochloric acid to obtain 2,3-dihydroxyquinoxaline Derivatives, after separation and purification, react with chlorinated reagents such as phosphorus pentachloride or phosphorus oxychloride. This method needs to be carried out in two steps. The 2,3-dihydroxyquinoxaline derivatives obtained by the reaction must be separated before they can be The chlorination reaction is cumbersome to operate, and the cost of manpower and reagents is high. A large amount of hydrochloric acid reagents used at the same time have problems such as reaction vessel corrosion and environmental pollution; another method is to replace o-phenylenediamine and diethyl oxalate as raw materials , using diethyl oxalate or ethanol as a solvent to react to obtain 2,3-dihydroxyquinoxaline derivatives, and then react with chlorinated reagents such as phosphorus pentachloride or phosphorus oxychloride after separation and purification. This method also requires separation Two steps, wherein, if diethyl oxalate is used as solvent, the amount of diethyl oxalate must be greatly excessive to make the reaction proceed, which not only causes a lot of waste of reagents, increases production costs, but also makes post-processing inconvenient and seriously pollutes the environment , if ethanol is used as a solvent, the obtained 2,3-dihydroxyquinoxaline derivatives must also be separated to carry out subsequent chlorination reactions, all of which have defects such as cumbersome operations and high labor costs

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