Method for synthesizing 2-amino five-membered heterocyclic derivative

Abstract

The invention discloses a method for synthesizing a 2-amino five-membered heterocyclic derivative. In the method, a route which is opposite to the conventional amination reaction is adopted, nitrogen polar reversed amine is taken as an amination reagent, a cheap cupric salt is taken as a catalyst, triphenylphosphine is taken as a ligand, lithium tert-butoxide is taken as an alkali, toluene is taken as a solvent, and the amination reagent undergoes a C-N coupling reaction with five-membered heterocyclic molecules, so that a five-membered heterocyclic two-position amination reaction is realized. The method has the characteristics of mild conditions, quick reaction, low cost, large-scale preparation, and the like. Due to the adoption of the method, the defects of harsh reaction conditions (high reaction temperature and long term), large quantity of side reactions, low yield, and the like existing in the conventional Ullmann reaction are avoided to a large extent, and the limitation on the use of a high-cost noble metal palladium catalyst is avoided.

Description

technical field [0001] The invention relates to a method for synthesizing 2-amino five-membered heterocyclic derivatives. Background technique [0002] The five-membered heterocyclic structure widely exists in nature, and its 2-position derivatization (especially 2-position amination) products are compounds or intermediates with important uses in the fields of medicine, biology and materials. For example, nucleic acids, vitamins, antibiotics, hormones, pigments and alkaloids related to physiological activities all contain five-membered heterocyclic structures; pramoxine used to treat Parkinson's disease, meloxicam used for anti-inflammation and the third generation The antibiotic cefdinir is a derivative of the 2-position amination of the five-membered heterocycle; the polymer containing the derivative of thiophene can be applied in the field of photoelectric materials. [0003] The early synthesis of 2-amino five-membered heterocyclic compounds mainly relied on complex rea...

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Problems solved by technology

[0003] The early synthesis of 2-amino five-membered heterocyclic compounds mainly relied on complex reaction precursors with functional groups to obtain them through cycloaddition reactions, but this method has limitations such as difficult availability of raw materials, many side reactions, and low yields; in recent years, it has developed The method of utilizing transition metal catalyzed C-N coupling reaction to synthesize such compounds, such as Buchwald-Hartwig reaction [J.P.Wolfe, S.Wagaw, J.F.Marcoux, S.L.Buchwald, Acc.Chem.Res.1998, 31, 805; J.F.Hartwig, Acc.Chem.Res.2008, 41, 1534], Ullman and Goldberg reaction [S.V.Ley, A.W.Thomas, Angew.Chem.Int.Ed.2003, 42, 5400], etc. can effectively realize the corresponding amination reaction, These methods require pre-formation of the 2-halogenated five-membered heterocyclic substrate (which is a relatively difficult preparation reaction), and the reaction temperature is high during coupling; some recent transition metal-catalyzed C-H activated oxidative coupling reaction methods avoid [D.Monguchi, T.Fujiwara, H.Furukawa, A.Mori, Org.Lett.2009, 11, 1607; Q.Wang, S.L.Schreiber, Org.Lett .2009, 11, 5178; S.H.Cho, J.Y.Kim, S.Y.Lee, S.Chang, Angew.Chem.Int.Ed.2009, 48, 9127], but this method needs to use a large excess of amine, and the waste of amine is serious; In addition, the use of non-catalytic methods [M.Kienle, C.Dunst, P.Knochel, Org.Lett.2009, 11, 5158] can also achieve five-membered hybrid 2-amination, the disadvantage is that it needs to use active zinc that is inconvenient to operate Reagent

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