Benzofuran [2, 3-c] pyridine compound and synthetic method thereof

Abstract

The invention relates to a benzofuran [2, 3-c] pyridine compound and a synthetic method thereof. The benzofuran [2, 3-c] pyridine compound has a general formula shown in the specification, wherein R1 is phenyl, 3-bromo-phenyl, 4-bromo-phenyl, 4-chloro-phenyl, 4-methoxy-phenyl, 3-methyl-phenyl or 4-methyl-phenyl; R2 is hydrogen or 5-chlorine, 5-bromine, 5-tert-butyl, 3,5-ditert-butyl, 4-methoxy, 5-methoxy, 5-methyl, 3,5-dimethyl and 4,5-dimethyl; R3 is methyl or phenyl, 4-bromo-phenyl, 3-bromo-phenyl, 2-chloro-phenyl, 4-chloro-phenyl, 4-methoxy-phenyl and 4-methyl-phenyl. According to the synthetic method disclosed by the invention, alpha-bromoacetophenone or a derivative thereof as well as 4-(2-hydroxyphenyl)-3-butylene-2-ketone or a derivative thereof are used as reactants, and a one-pot method is adopted to synthesize the benzofuran [2, 3-c] pyridine compound. The synthetic method is simple and convenient in step, mild in condition and high in yield.

Description

technical field [0001] The invention belongs to the technical field of synthesis of organic intermediates, in particular to benzofuro[2,3-c]pyridine compounds and a synthesis method thereof. Background technique [0002] Benzofuro[2,3-c]pyridine organic heterocyclic compounds are widely used in organic synthesis, medicine and other fields, and are important pharmaceutical intermediates. In addition, many molecules with physiological activity also contain such structural units. For example, D.G. Wishka et al. synthesized a benzofuro[2,3-c]pyridine compound (I), which is a central nervous system active drug (WO02 / 100857A1); L.A.Gharat et al. synthesized benzofuro[2,3-c]pyridine compound (II), which is an inhibitor of phosphodiesterase-10 (WO2011 / 132051A2). The above-mentioned method for synthesizing benzofuro[2,3-c]pyridine compounds has complicated steps and harsh reaction conditions, for example, it needs to be carried out under anhydrous and oxygen-free reaction conditio...

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Problems solved by technology

The above-mentioned method for synthesizing benzofuro[2,3-c]pyridine compounds has complex steps and harsh reaction conditions, for example, it needs to be carried out under anhydrous and oxygen-free reaction conditions, etc.

Wen et al. used 3-chloropyridine to react with tributyltin chloride at -78°C, and the resulting product reacted with o-iodophenol under the condition of palladium chloride to generate intermediate 2-(3-chloropyridine-4 -yl) phenol, the intermediate is cyclized under the catalysis of tert-butyl sodium to obtain benzofuro[2,3-c]pyridine, and the total yield of the reaction is about 27% (Wen Song Yue and Jie Jack Li, A Concise Synthesis of All Four Possible Benzo[4,5]furopyridines via Palladium-Mediated Reactions.Org.Lett.,Vol.4,No.13,2002), the reaction is not only demanding on temperature, complicated process, but also adopts Transition metal catalysts, resulting in expensive

In short, the reaction conditions of the currently known synthetic routes are relatively harsh, which greatly limits the industrial application of this type of compound.

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