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A method for synthesizing [a]-cyclized indole derivatives

A technology of indole derivatives and synthetic methods, which is applied in the field of synthesizing [a]-cyclized indole derivatives, can solve problems such as low yields, and achieve the effects of green and simple methods, avoiding preactivation, and high atom economy

Inactive Publication Date: 2020-05-19
NANJING UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these traditional methods for synthesizing [a]-cyclized indole compounds usually require pre-activation of indole substrates, and after a multi-step synthetic route, often only low yields can be obtained

Method used

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  • A method for synthesizing [a]-cyclized indole derivatives
  • A method for synthesizing [a]-cyclized indole derivatives
  • A method for synthesizing [a]-cyclized indole derivatives

Examples

Experimental program
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Effect test

experiment example 1

[0026] Synthesis of 2,3-Dihydro-1H-pyrrole[1,2-a]indole

[0027] Accurately weigh the 1H-indole reactant (0.2mmol, 23.4mg), transfer to the reaction vessel, add 1,3-dibromopropane (0.5mmol, 50μL), PdCl 2 (MeCN) 2 (10%mmol, 5.2mg), norbornene (1.0mmol, 94.2mg), cesium carbonate (0.8mmol, 260.7mg), add dropwise 1mLDMA and 9μL water in a thick-walled pressure-resistant tube, tighten the reaction tube stopper The reaction system was sealed, heated to 80°C, and reacted for 12 hours under the condition of stirring in an oil bath. After the reaction, the reaction solution was cooled to room temperature, filtered through short silica gel to remove insoluble impurities, extracted three times with ethyl acetate and water, and extracted once with brine, and the organic phase was removed from the solvent to obtain a crude product, which was separated by column chromatography (Eluent: ethyl acetate / petroleum ether=1:50), a pure and dry product was obtained with a yield of 60%. 1 H NMR (...

experiment example 2

[0029] Synthesis of 2,3-Dihydro-1H-pyrrole[1,2-a]indole

[0030] Accurately weigh the 1H-indole reactant (0.2mmol, 23.4mg), transfer to the reaction vessel, add 1-bromo-3-chloropropane (0.5mmol,), PdCl 2 (MeCN) 2 (10%mmol, 4.48mg), norbornene (0.2mmol, 55mg), cesium carbonate (0.8mmol, 10.8mg), add dropwise 1mLDMA and 9μL water in a thick-walled pressure-resistant tube, tighten the reaction tube plug to make the reaction The system was sealed, heated to 80°C, and reacted for 12 hours under the condition of stirring in an oil bath. After the reaction, the reaction solution was cooled to room temperature, filtered through short silica gel to remove insoluble impurities, extracted three times with ethyl acetate and water, and extracted once with brine, and the organic phase was removed from the solvent to obtain a crude product, which was separated by column chromatography (Eluent: ethyl acetate / petroleum ether=1:50), a pure and dry product was obtained with a yield of 34%. 1 ...

experiment example 3

[0032] Synthesis of 2,3-Dihydro-1H-pyrrole[1,2-a]indole

[0033] Accurately weigh the 1H-indole reactant (0.2mmol, 23.4mg), transfer to the reaction vessel, add 1,3-dibromopropane (0.5mmol, 50μL), PdCl 2 (MeCN) 2 (10%mmol, 5.2mg), norbornene (1.0mmol, 94.2mg), cesium carbonate (0.8mmol, 260.7mg), add dropwise 1mL of DMF and 9μL of water in a thick-walled pressure-resistant tube, tighten the reaction tube stopper to The reaction system was sealed, heated to 80°C, and reacted for 12 hours under the condition of stirring in an oil bath. After the reaction, the reaction solution was cooled to room temperature, filtered through short silica gel to remove insoluble impurities, extracted three times with ethyl acetate and water, and extracted once with brine, and the organic phase was removed from the solvent to obtain a crude product, which was separated by column chromatography (Eluent: ethyl acetate / petroleum ether=1:50), a pure and dry product was obtained with a yield of 49%.1...

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Abstract

The invention discloses a method for synthesizing an [a]-cycloindole compound. Under the action of a palladium catalyst, norbornene as a transient-directed medium and a dihaloalkane as an alkylating agent are boiled in one pot under the action of an alkali so that substituted indole C2-site alkylation and N-H ring closing domino reactions are realized to produce the [a]-cycloindole compound. The method is carried out under mild conditions, directly utilizes commercial substituted indole as a substrate, is free of a pre-functionalization process and reaction processes, has high atomic economy and modifies the simple indole small molecule structure. The [a]-cycloindole derivative can be further used for research on medicine or total synthesis and has a high potential value and a broad application prospect in the field of pharmaceutical chemistry.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis chemistry, and in particular relates to a method for synthesizing [a]-cyclized indole derivatives. Background technique [0002] Many biologically active natural and unnatural compounds contain indole skeletons. For example, indole alkaloids account for a quarter of the numerous alkaloid compounds. As an important class of organic compounds, indole compounds are widely used in the fields of medicine, pesticide, food, feed additive and dye industry. The core structure of [a]-cyclized indole exists in many biologically active indole derivatives such as mitomycin and vincamine, which are widely used in materials chemistry, medicinal chemistry, dyes and other fields. At present, there are only a few reports on the synthesis of [a]-cyclized indole, such as the one-pot method of intramolecular alkyl transfer reaction using indole organoboron reagents, as shown in A in the following scheme (I...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04C07D471/04
CPCC07D471/04C07D487/04
Inventor 姜超高亚东李建华
Owner NANJING UNIV OF SCI & TECH
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