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A kind of preparation method of N-acyl substituted indole derivative

A technology of indole derivatives and acyl substitution, which is applied in the field of novel preparation of indole derivatives, can solve the problem of low yield and the like, and achieves the effects of simple operation, environmental friendliness and easy availability of raw materials

Active Publication Date: 2021-06-25
长兴宜生药物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction is relatively simple, but the yield is not high

Method used

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  • A kind of preparation method of N-acyl substituted indole derivative
  • A kind of preparation method of N-acyl substituted indole derivative
  • A kind of preparation method of N-acyl substituted indole derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1-benzoyl-5-methoxy-1 H -Synthesis of methyl indole-2-carboxylate (I-a)

[0032] (1) Add the raw material 2-benzamido-3-(2-bromo-5-methoxyphenyl)methyl acrylate (1.95g, 5mmol) into a 50mL single-necked bottle, and the catalyst is CuI (0.01g, 0.05 mmol), the base is sodium methoxide (1.08g, 20mmol), at 150 o Reaction in DMF under the condition of C, TLC followed the reaction, after the reaction was completed, it was cooled, separated by column chromatography, distilled under reduced pressure, and dried to obtain 1.35g of solid product, the yield was 87%, and the product melting point was 114.1~114.7 o c.

[0033] (2) Add the raw material 2-benzamido-3-(2-chloro-5-methoxyphenyl)methyl acrylate (1.73g, 5mmol) into a 50mL single-necked bottle, and the catalyst is palladium acetate (0.02g, 0.10mmol), the base is sodium ethylate (0.68g, 10mmol), at 90 o Under the condition of C, react in toluene, follow the reaction by TLC, after the reaction, after cooling, separate by c...

Embodiment 2

[0035] 1-benzoyl-5-methoxy-1 H - Synthesis of isopropyl indole-2-carboxylate (I-b)

[0036] (1) Add the raw material 2-benzamido-3-(2-bromo-5-methoxyphenyl)isopropyl acrylate (2.09g, 5mmol) into a 50mL single-necked bottle, and the catalyst is CuCl (0.10g, 1mmol), the base is sodium carbonate (2.12g, 20mmol), at 170 o The reaction was carried out in dimethyl sulfoxide under the condition of C, and the reaction was tracked by TLC. After the reaction was completed, it was cooled, separated by column chromatography, distilled under reduced pressure, and dried to obtain 1.23 g of the product, with a yield of 73% and a melting point of 109.1~110.2 o c.

[0037] (2) Add the raw material 2-benzamido-3-(2-chloro-5-methoxyphenyl)isopropyl acrylate (1.87g, 5mmol) into a 50mL single-necked bottle, and the catalyst is tris(dibenzylidene Dipalladium (0.92g, 1mmol), the base is potassium carbonate (1.59g, 15mmol), at 110 o Reaction in DMF under C conditions, TLC tracking reaction, after...

Embodiment 3

[0039] 1-benzoyl-5,6-dimethoxy-1 H -Synthesis of methyl indole-2-carboxylate (I-c)

[0040] (1) Add the raw material 2-benzamido-3-(2-bromo-4,5-dimethoxyphenyl)methyl acrylate (2.10g, 5mmol) into a 50mL single-necked bottle, and the catalyst is CuBr (0.07 g, 0.5mmol), the base is potassium bicarbonate (0.25g, 2.5mmol), at 110o Reaction in toluene under C conditions, TLC tracking reaction, after the reaction, after cooling, column chromatography separation, vacuum distillation, drying, to get the product 1.49g, yield 88%, product melting point 115.4 ~ 116.4 o c.

[0041] (2) Add the raw material 2-benzamido-3-(2-chloro-4,5-dimethoxyphenyl)methyl acrylate (1.88g, 5mmol) into a 50mL single-necked bottle, and the catalyst is four (three Phenylphosphine) palladium (0.58g, 0.5mmol), the base is sodium bicarbonate (0.25g, 3.0mmol), at 40 o Reaction in dioxane under the condition of C, TLC followed the reaction, after the reaction was completed, cooled, separated by column chromato...

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Abstract

The invention discloses a compound as shown in formula (I) N ‑Acyl-substituted indole derivatives preparation method, the method uses the compound shown in formula (II) as a raw material, under the action of a base and a catalyst at 40~170 o Carry out cyclization reaction in C organic solvent, trace by thin layer chromatography until the raw material reaction is complete, the reaction solution is separated and purified to obtain the compound shown in formula (I) N -Acyl-substituted indole derivatives; the ratio of the base to the feed material of the compound represented by formula (II) is 0.2 to 4.0:1.0, and the ratio of the catalyst to the feed material of the compound represented by formula (II) The amount ratio is 0.01-0.2:1.0; the preparation method of the present invention has short reaction steps, simple operation, simple and easy-to-obtain raw materials, can be carried out under heating conditions, and the yield is high, which is beneficial to industrial production; the reaction is environmentally friendly and avoids In addition to a strong acid system, only a catalytic amount of common copper salt catalyst or palladium salt catalyst can be used, and the yield is as high as 88%.

Description

technical field [0001] The present invention relates to a N - Novel process for the preparation of acyl-substituted indole derivatives. Background technique [0002] Indole compounds widely exist in medicinal plants and are heterocyclic natural products with the largest variety and widest distribution. It has been found that most indole compounds have important biological activities and have been widely used in medicine and pesticides. Therefore, the synthesis and activity screening of new indole compounds has become a research hotspot in current drug discovery. However, the classic synthetic methods such as Larock indole synthesis and Ficher indole synthesis have problems such as regioselectivity in the reaction process, or the use of environmentally unfriendly reagents, which are not suitable for industrial production. In recent years, on the basis of the rapid development of the Ullman reaction, copper-catalyzed arylation reactions have made some progress. [0003] Ind...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/42
CPCC07D209/42
Inventor 李坚军陈永健孙坚裴金凤苏为科
Owner 长兴宜生药物科技有限公司