Synthesis method of nitrogenous medicine intermediate indole derivative

A synthesis method and a technology of nitrogen ligands, which are applied in the synthesis of heterocyclic fused compounds and the synthesis of nitrogen-containing drug intermediates indole derivatives, can solve the problems of cumbersome reactions, expensive catalysts, and low product yields. Achieve the effects of expanding scope, good application prospects and research value

Inactive Publication Date: 2017-06-20
THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] As mentioned above, although multiple methods for synthesizing indole compounds have been disclosed in the prior art, there are still some defects in these methods, such as low product yield, too expensive catalyst or too large amount of catalyst, too cumbersome reaction, and the substrate is still Need to expand etc.

Method used

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  • Synthesis method of nitrogenous medicine intermediate indole derivative
  • Synthesis method of nitrogenous medicine intermediate indole derivative
  • Synthesis method of nitrogenous medicine intermediate indole derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046]

[0047] At room temperature, add 100 mmol of the above formula (I) compound, 150 mmol of the above formula (II) compound, 5 mmol of catalyst palladium acetylacetonate (Pd(acac) 2 ), 15mmol of nitrogen-containing ligand L1 and 600mmol of acid accelerator methanesulfonic acid, then purged with nitrogen to keep the reaction atmosphere in an inert environment; stirring and heating up to 70°C, and stirring and reacting at this temperature for 30 hours;

[0048] After the reaction was over, the mixture was poured into ethyl acetate, followed by saturated NaHCO 3 Wash with aqueous solution and brine, separate the aqueous layer, extract the aqueous layer with ethyl acetate, combine the organic layers (that is, combine the washed organic layer and the organic layer obtained by extraction), and wash with anhydrous Na 2 SO 4 After drying, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether / ethyl ac...

Embodiment 2

[0051]

[0052] At room temperature, add 100 mmol of the above formula (I) compound, 200 mmol of the above formula (II) compound, 10 mmol of catalyst palladium acetylacetonate (Pd(acac) 2 ), 20mmol of nitrogen-containing ligand L1 and 800mmol of acid accelerator methanesulfonic acid, then purged with nitrogen to keep the reaction atmosphere in an inert environment; stirring and heating up to 80°C, and stirring and reacting at this temperature for 25 hours;

[0053] After the reaction was over, the mixture was poured into ethyl acetate, followed by saturated NaHCO 3 Wash with aqueous solution and brine, separate the aqueous layer, extract the aqueous layer with ethyl acetate, combine the organic layers (that is, combine the washed organic layer and the organic layer obtained by extraction), and wash with anhydrous Na 2 SO 4 After drying, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether / ethyl a...

Embodiment 3

[0056]

[0057] At room temperature, add 100 mmol of the above formula (I) compound, 250 mmol of the above formula (II) compound, 15 mmol of catalyst palladium acetylacetonate (Pd(acac) 2 ), 25mmol nitrogen-containing ligand L1 and 1000mmol acid accelerator methanesulfonic acid, then purging with nitrogen to keep the reaction atmosphere inert environment; stirring to heat up to 90°C, and stirring and reacting at this temperature for 20 hours;

[0058] After the reaction was over, the mixture was poured into ethyl acetate, followed by saturated NaHCO 3 Wash with aqueous solution and brine, separate the aqueous layer, extract the aqueous layer with ethyl acetate, combine the organic layers (that is, combine the washed organic layer and the organic layer obtained by extraction), and wash with anhydrous Na 2 SO 4 After drying, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether / ethyl acetate, the vo...

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Abstract

The invention relates to a synthesis method of an indole derivative shown by a nitrogenous medicine intermediate (III). The method comprises the following steps of in a solvent and in the insert gas atmosphere, under the existence of catalysts, nitrogenous ligands and acid promoters, a compound shown by a formula (I) and a compound shown by a formula (II) take a reaction; after the reaction is completed, post treatment is performed, so that a compound shown by the formula (III) is obtained. The formulas (I), (II) and (III) are shown as the accompanying drawing, wherein the R1 is selected from H or halogen; the R2 is selected from H, C1-C6 alkyls, C1-C6 alkoxy or halogen; or R2 and the substituted phenyl jointly form naphthyl. The method has the advantages that through the comprehensive selection and cooperation of the proper substrates, catalysts, nitrogenous ligands, acid promoters, solvents and the like, the range of the substrates is expanded; the aryl-substituted indol compound can be obtained at a good yield, so that the good application prospects and study values are realized in the field of organic chemical synthesis. The fire-new method is provided for the synthesis of the compounds of the kind.

Description

technical field [0001] The invention relates to a method for synthesizing a heterocyclic condensed compound, in particular to a method for synthesizing an indole derivative, a nitrogen-containing drug intermediate, and belongs to the technical field of organic chemical synthesis. Background technique [0002] In the field of organic chemical synthesis technology and medicinal chemistry, indole compounds, as a nitrogen-containing fused ring compound, often exist as important parent building blocks, intermediates and / or active units in the field of medicinal chemical intermediate synthesis technology , which also plays an important role and status in functional materials. [0003] For example, in the following drugs, the indole ring is its parent structure: [0004] [0005] It is precisely because of the important uses and application prospects of indole compounds that people have conducted a lot of research on their synthesis methods, mainly C-C coupling reactions, or co...

Claims

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Application Information

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IPC IPC(8): C07D209/08C07D209/10
CPCC07D209/08C07D209/10
Inventor 叶乐平卢贺敏湛美正马伟慧张丽鑫
Owner THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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