Method for synthesizing azaindoline derivative

A technology of azaindoline and derivatives, which is applied in the field of synthesis of azaindoline derivatives, can solve problems such as poor functional group compatibility, harsh reaction conditions, and poor atom economy, and achieve convenient post-processing, simple catalysts, and synthetic The effect that key efficiency is high

Active Publication Date: 2019-11-22
WENZHOU UNIVERSITY
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Problems solved by technology

This type of reaction has disadvantages such as poor compatibility of functional groups and harsh reaction conditions, and has certain limitations.
literature( Org. Lett. 2015 , 17, 3806-3809) reported a method of using hypervalent iodine (III) to directly oxidize diamination to synthesize azaindole compounds. Although this method does not require harsh temperatures, it needs to pre-halogenate pyridine. The reaction process For halogen elimination, the steps are cumbersome, a large amount of additives are required, the atom economy is poor, and most of the reaction systems are only suitable for the construction of pyridocyclic compounds with a relatively single product skeleton, which has certain limitations.

Method used

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  • Method for synthesizing azaindoline derivative

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Experimental program
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Effect test

Embodiment 1

[0024] The preparation of 1,3-dimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, the structural formula is as follows:

[0025] Under nitrogen protection, the starting material N-allyl-N-methylpyridin-3-amine (0.5 mmol) and the catalyst Y[N(SiMe 3 ) 2 ] 3 (10 mol%), reacted at 100 ℃ for 24 h to prepare 1,3-dimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, and the isolated yield of the product was 90%.

[0026] 1 H NMR (CDCl 3 , 500 MHz, ppm): δ 7.75 (d, J = 5.0 Hz, 1H), 6.85 (dd, J = 5.1, 7.8 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H), 3.52 (t, J = 8.8 Hz, 1H), 3.26-3.22 (m, 1H), 2.82 (t, J = 8.5 Hz, 1H), 2.67 (s, 3H), 1.32 (d, J = 7.0 Hz,3H). 13 C NMR (CDCl 3 , 125 MHz, ppm): δ 156.9, 146.5, 137.8, 121.8, 112.0, 62.1,36.6, 35.6, 17.1.

Embodiment 2

[0028] The preparation of 1,3,5-trimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, the structural formula is as follows:

[0029] Under nitrogen protection, the starting material N-allyl-N,6-dimethylpyridin-3-amine (0.5 mmol) and the catalyst Y[N(SiMe 3 ) 2 ] 3 (10 mol%), reacted at 100 ℃ for 24 h to prepare 1,3,5-trimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, and the isolated yield of the product was 81% .

[0030] 1 H NMR (CDCl 3 , 500 MHz, ppm): δ 6.75 (d, J = 7.9 Hz, 1H), 6.54 (d, J =7.9 Hz, 1H), 3.47 (t, J = 8.6 Hz, 1H), 3.26-3.21 (m, 1H), 2.84 (t, J = 8.3Hz, 1H), 2.67 (s, 3H), 2.40 (s, 3H), 1.33 (d, J = 7.0 Hz, 3H). 13 C NMR (CDCl 3 ,125 MHz, ppm): δ 156.6, 146.4, 144.4, 120.8, 113.3, 62.6, 36.9, 36.4, 23.4,17.5.

Embodiment 3

[0032] The preparation of 5-chloro-1,3-dimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, the structural formula is as follows:

[0033] Under nitrogen protection, the starting materials N-allyl-6-chloro-N-methylpyridin-3-amine (0.5 mmol), dibenzylamine (10 mol%) and catalyst Y were added to toluene (3 mL).[ N(SiMe 3 ) 2 ] 3 (10 mol%), reacted at 100 ℃ for 24 h to prepare 5-chloro-1,3-dimethyl-2,3-dihydro-1H-pyrrole[3,2-b]pyridine, and the isolated yield was 86%.

[0034] 1 H NMR (CDCl 3 , 500 MHz, ppm): δ 6.91 (dd, J = 0.6, 8.2 Hz, 1H), 6.55(d, J = 8.2 Hz, 1H), 3.57 (t, J = 8.9 Hz, 1H), 3.29-3.23 (m, 1H), 2.91 (dd, J = 8.0, 8.7 Hz, 1H), 2.71 (s, 3H), 1.33 (d, J = 6.9 Hz, 3H). 13 C NMR (CDCl 3,125 MHz, ppm):δ 157.4, 145.7, 138.7, 121.7, 114.8, 62.3, 36.6, 35.8, 17.4.

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Abstract

The invention discloses a method for synthesizing azaindoline derivatives, and belongs to the technical field of organic synthesis. Pyridine carbon-hydrogen bond activation functionalization is catalyzed by rare earth, so that synthesis of azaindoline derivatives with diversified structures is achieved. Specifically, in a rare earth catalytic system, various alkenyl-substituted aminopyridine is used as a raw material to prepare the azaindoline derivative. The method disclosed by the invention is wide in raw material source or easy to prepare, simple and convenient to operate, controllable in selectivity, high in yield, mild in condition and wide in universality.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a synthesis method of azaindoline derivatives through the activation of pyridine carbon-hydrogen bonds and intramolecular cyclization reactions to realize structural diversification. Background technique [0002] Azaindolines are an important class of organic compounds, which are not only important components of natural products and medicines, but also have unique optical properties. Therefore, the development of diverse and efficient new methods for the synthesis of azaindolines has always been an important topic in organic synthetic chemistry. [0003] In the existing technology for the preparation of azaindolines, the skeleton of azaindole compounds has always been constructed by derivatization reactions of pre-existing pyridine skeletons. However, the classical Fischer indole synthesis and Friedel-Craft reaction are difficult to be derived from the synthesis of aza...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 邵银林谢乐萍叶鹏清陈久喜程天行沈柯婷邹锦萱徐北航孙佳妮
Owner WENZHOU UNIVERSITY
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