A kind of preparation method of diphenyl[c,e]azepine derivative

Abstract

The invention discloses a diphenyl[c,e]azepine derivative and a preparation method thereof, by reacting [1,1'-biphenyl]-2,2'-dinitrile and arylboronic acid The reactant is prepared by the reaction of the reactant; the reactant is easy to prepare, has wide sources, low cost, low toxicity, and is not easy to affect human health. The reaction is carried out in a solvent, and the solvent is any one of toluene, xylene, methanol, tetrahydrofuran, N,N-dimethylformamide and N,N-dimethylacetamide; Added palladium catalyst and acid accelerator; palladium catalyst is palladium trifluoroacetate, palladium tetraphenylphosphine, bisacetylacetonate palladium, bis(dibenzylideneacetone) palladium and tris(dibenzylideneacetone) dipalladium Any one; the reaction temperature is 100-120°C, the reaction time is 20-30 hours, the reaction conditions are mild, easy to achieve, and safe. The invention can directly synthesize the target product without separating intermediate products, and the highest yield can reach 95%.

Description

technical field [0001] The invention relates to the field of organic synthesis, and more specifically relates to a preparation method of diphenyl[c,e]azepine derivatives. 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[c,e]azepi...

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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

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