Dibenzo[c,e]azepine derivative and preparation method thereof

Abstract

The invention discloses a dibenzo[c,e]azepine derivative and a preparation method thereof. The derivative is prepared by using [1,1'-biphenyl]-2,2'-dinitrile and an aryl boronic acid as reactants; thereagents are easy to prepare, have relatively wide sources, relatively low cost, and relatively low toxicity, and is not easy to affect human health. The reaction is performed in a solvent, and the solvent is any one of toluene, xylene, methanol, tetrahydrofuran, N,N-dimethylformamide, and N,N-dimethylacetamide. When the reaction is carried out, a palladium catalyst and an acid promoter are added, wherein the palladium catalyst is any one of palladium trifluoroacetate, tetrakis(triphenylphosphine) palladium, diacetylacetone palladium, bis(dibenzylideneacetone) palladium, and tris(dibenzylideneacetone) dipalladium. A reaction temperature is 100-120 DEG C, a reaction time is 20-30 h, and reaction conditions are mild, easy to reach, and safe. The method can directly synthesize a target product without separating intermediate products, and the yield can be up to 95%.

Description

technical field [0001] The invention relates to the field of organic synthesis, and more specifically relates to a diphenyl[c,e]azepine derivative and a preparation method thereof. Background technique [0002] Diphenyl[c,e]azepine derivatives are an important class of nitrogen-containing seven-membered heterocyclic compounds. Compared with five- and six-membered nitrogen-containing heterocycles, although seven-membered nitrogen-containing heterocycles are naturally The distribution is relatively small, but its remarkable pharmaceutical activity and unique reactivity make it an important research content in the fields of organic synthesis and drug development, and the relevant research results also have important theoretical significance and application value. [0003] In the prior art, diarylo[c,e]azepine and its derivatives are mainly prepared by the following methods: [0004] [0005] 1. Boc (di-tert-butyl dicarbonate)-protected aminoketone compound A obtains dibenzo...

AI Technical Summary

Problems solved by technology

[0005] 1. Boc (di-tert-butyl dicarbonate)-protected aminoketone compound A obtains dibenzo[c,e]azepine derivatives through intramolecular cyclization (Angew.Chem, Int.Ed.2017,56 , 15589-15593 and Chem.Sci.2019, 10, 2473-2477); 2. The imidoyl chloride compound B connected with the aryl group undergoes intramolecular cyclization to obtain dibenzo[c,e]azepine derivatives ( J.Chem.Soc., PerkinTrans.1 1993,2961-2967); 3. Substrate C and CNBr were cyclized under the action of ethanol ammonia to obtain dibenzo[c,e]azepine derivatives (J.Org .Chem.1982,47,3658-3660); 4. Substrate D undergoes tandem reduction / intramolecular cyclization in a sodium-containing 1-pentanol boiling solution to obtain dibenzo[c,e]azepine derivatives However, there are certain defects in the above-mentioned preparation methods, such as the preparation of raw materials A and B in methods 1 and 2 is very difficult, expensive, and difficult to obtain; CNBr in method 3 is a highly toxic and volatile substance , it is easy to cause a greater impact on the life safety of the experimenters; method 4 needs to be carried out in a boiling solution of 1-pentanol, the reaction conditions are harsh, and the experiment has a greater risk; The practicability and applicability are greatly limited, and it cannot be promoted on a large scale

Images