Preparation method of 3-substituted indolemethylamine derivative

Abstract

The invention discloses a preparation method of a 3-substituted indolemethylamine derivative. An indole derivative reacts with imine under the catalysis of titanocene dichloride and a ligand as catalysts to obtain the 3-substituted indolemethylamine derivative, wherein the ligand is phenol, catechol or phloroglucinol. The method has the advantages of simple operation, efficient and mild reaction, cheap and nontoxic catalysts, and good chemical selectivity, allows a single product to be obtained, and can be widely used to prepare the 3-substituted indolemethylamine derivative.

Description

technical field

[0001] The invention relates to a preparation method of 3-substituted indole methylamine derivatives. Background technique

[0002] At present, the research on indole chemistry is one of the most active fields in heterocyclic chemistry, especially the 3-substituted indole methylamine derivatives, which have good physiological activities, and their indole nucleus The synthesis of physiologically active natural products or derived compounds as raw materials for activity screening has always been the core of indole chemistry research, and it is also an important class of heterocyclic compounds in organic synthesis. 3-substituted indole methylamine derivatives show great potential in medicine, can synthesize antipyretic analgesics, stimulants, antihypertensive drugs, vasodilators, etc., while known 3-substituted indole methylamines Alkaloids have medicinal uses such as anticancer, antibacterial, antiviral, and treatment of high blood pressure. In terms of pesti...

Examples

Embodiment 1

[0013] Taking the preparation of the following formula compound N-[1-methylindolyl-3-(2-chlorophenyl)methine]-4-methylbenzenesulfonamide as an example, the raw materials used and the preparation method thereof are as follows:

[0014]

[0015] 0.2930g (1.0mmol) N-(2-chloro-phenylmethine)-4-methyl-benzenesulfonimide, 250μL (2.0mmol) N-methylindole, 0.0075g (0.03mmol) Add titanocene dichloride and 0.0056g (0.06mmol) phenol into 1mL acetonitrile, react at room temperature for 6 hours, TLC detects that the reaction is complete, stop the reaction, remove the solvent, and mix the mixture with ethyl acetate and n-hexane at a volume ratio of 3:1. Liquid is mobile phase column chromatography separation product, obtains white solid N-[1-methylindolyl-3-(2-chlorophenyl) methine]-4-methylbenzenesulfonamide, and its productive rate is 91%.

[0016] The resulting product was characterized by a Bruker Avance superconducting Fourier digital NMR spectrometer, and the characterization data ...

Embodiment 2

[0020] In Example 1, phenol was replaced with equimolar catechol, reacted at room temperature for 6 hours, other steps were the same as in Example 1, and white solid N-[1-methylindolyl-3-(2 -Chlorophenyl)methine]-4-methylbenzenesulfonamide, the yield was 78%.

Embodiment 3

[0022] In Example 1, phenol was replaced with equimolar phloroglucinol, reacted at room temperature for 6 hours, other steps were the same as in Example 1, and white solid N-[1-methylindolyl-3-(2 -Chlorophenyl)methine]-4-methylbenzenesulfonamide, the yield was 70%.

technical field

[0001] The invention relates to a preparation method of 3-substituted indole methylamine derivatives. Background technique

[0002] At present, the research on indole chemistry is one of the most active fields in heterocyclic chemistry, especially the 3-substituted indole methylamine derivatives, which have good physiological activities, and their indole nucleus The synthesis of physiologically active natural products or derived compounds as raw materials for activity screening has always been the core of indole chemistry research, and it is also an important class of heterocyclic compounds in organic synthesis. 3-substituted indole methylamine derivatives show great potential in medicine, can synthesize antipyretic analgesics, stimulants, antihypertensive drugs, vasodilators, etc., while known 3-substituted indole methylamines Alkaloids have medicinal uses such as anticancer, antibacterial, antiviral, and treatment of high blood pressure. In terms of pesti...

Examples

Embodiment 1

[0013] Taking the preparation of the following formula compound N-[1-methylindolyl-3-(2-chlorophenyl)methine]-4-methylbenzenesulfonamide as an example, the raw materials used and the preparation method thereof are as follows:

[0014]

[0015] 0.2930g (1.0mmol) N-(2-chloro-phenylmethine)-4-methyl-benzenesulfonimide, 250μL (2.0mmol) N-methylindole, 0.0075g (0.03mmol) Add titanocene dichloride and 0.0056g (0.06mmol) phenol into 1mL acetonitrile, react at room temperature for 6 hours, TLC detects that the reaction is complete, stop the reaction, remove the solvent, and mix the mixture with ethyl acetate and n-hexane at a volume ratio of 3:1. Liquid is mobile phase column chromatography separation product, obtains white solid N-[1-methylindolyl-3-(2-chlorophenyl) methine]-4-methylbenzenesulfonamide, and its productive rate is 91%.

[0016] The resulting product was characterized by a Bruker Avance superconducting Fourier digital NMR spectrometer, and the characterization data ...

Embodiment 2

[0020] In Example 1, phenol was replaced with equimolar catechol, reacted at room temperature for 6 hours, other steps were the same as in Example 1, and white solid N-[1-methylindolyl-3-(2 -Chlorophenyl)methine]-4-methylbenzenesulfonamide, the yield was 78%.

Embodiment 3

[0022] In Example 1, phenol was replaced with equimolar phloroglucinol, reacted at room temperature for 6 hours, other steps were the same as in Example 1, and white solid N-[1-methylindolyl-3-(2 -Chlorophenyl)methine]-4-methylbenzenesulfonamide, the yield was 70%.

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