Method for preparing 2-(2-nitrophenyl) pyrrole and 2,5-bis(2-nitrophenyl) pyrrole compounds

Abstract

The invention discloses a method for preparing 2-(2-nitrophenyl) pyrrole and 2,5-bis(2-nitrophenyl) pyrrole compounds. In the method, a compound shown in a general formula V and a compound shown in a general formula VI undergo reaction similar to nucleophilic aromatic substitution reaction under the alkali condition to obtain a compound shown in a general formula VII in a mode of high efficiency and high regioselectivity. The reaction has high regioselectivity; even if an N-H pyrrole compound or a pyrrole compound with an N-H substituent group is used as a substrate, the aromatic substitutionreaction can still be performed at 2-position and 5-position of the pyrrole compound to obtain a C-arylation product in a mode of high regioselectivity; and no N-arylation product is generated. Thus,the characteristic ensures that the reaction can be used in the pyrrole compound which contains activated hydrogen, thereby expanding the application scope of the method.

Description

technical field [0001] The invention relates to a method for preparing 2-(2-nitrophenyl)pyrroles and 2,5-bis(2-nitrophenyl)pyrroles. Background technique [0002] Many 2-arylpyrrole and 2,5-diarylpyrrole compounds have important biological activities and are widely used as lead compounds in drug discovery and development. For example: the compound of formula I can be used as a selective ligand for α-adrenergic receptors (references: Pittala, V.; Romeo, G. et al. Bioorg. Med. Chem. Lett. 2006, 16, 150-153 ); the compound of formula II is a kind of β-secretase inhibitor, and is used as a lead compound in the drug development for the treatment of Alzheimer's disease (references: Cole, D.C.; Manas, E.S.et al.J.Med.Chem .2006,49,6158-6161); formula III compound is the lead compound of EP1 receptor antagonist (references: (a) Hall, A.; Atkinson, S.; Brown, S.H.et al.Bioorg.Med.Chem . Lett. 2006, 16, 3657-3662; (b) Hall, A.; Brown, S.H. et al. Bioorg. Med. Chem. Lett. 2007, 17, 7...

AI Technical Summary

Problems solved by technology

But this method needs pyrrole compound to be prepared into magnesium salt or zinc salt in advance, or needs to use higher reaction temperature and expensive metal catalyst, but can only obtain medium yield, so be subject to certain restriction when using [references: (a) Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211-241; (b) Proch, S.; Kempe, R. Angew. 3135-3138; (c) Stuart, D.R.; Fagnou, K.Science.2007, 316, 1172-1175; (d) Hull, K.L.; Sanford, M.S.J.Am.Chem.Soc.2007, 129, 11904-11905]

Directly introducing aryl substituents on heterocyclic rings through nucleophilic aryl substitution reactions is also a convenient method for the synthesis of aryl-substituted heterocyclic compounds, but this method has not yet been used to introduce aryl substituents at the 2-position of pyrrole compounds. [Partial references: (a) Bunnett, J.F.; Zahler, R.E.Chem.Rev.1951, 49, 273-412; (b) Shi, Y.J.; Humphrey, G.et al.Adv.Synth.Catal. 2006, 348, 309-312; (c) Ueno, M.; Yonemoto, M. et al. Chem. Commun. 2007, 2264-2266]; and if a pyrrole compound without an N-protecting group is used as a reactant , the reaction takes place on the N-atom, not on the C-atom on the pyrrole ring

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