Preparation method of multi-substituted tetrahydroquinoxaline derivative

A technology of tetrahydroquinoxaline and compound is applied in the field of preparation of polysubstituted tetrahydroquinoxaline derivatives, and can solve the problems of unfavorable industrial production, flammability and explosion of hydrogen and high danger

Inactive Publication Date: 2019-08-09
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route requires the use of chiral ruthenium complexes and hydrogen. Ruthenium is a noble metal with high toxicity and high price; while hydrogen is flammable, explosive, and dangerous, which is not conducive to industrial production.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1 Preparation of compound 3a: Weigh out o-aminophenylimine 2a (0.10 mmol) and rhodium acetate (0.001 mmol), and add 2.0 mL of redistilled dichloromethane to each reaction tube. Increase the temperature and keep the reaction temperature at 40℃. Dissolve methyl aryldiazoacetate 1a (0.15mmol) in 2mL of distilled dichloromethane and inject it into the reaction system through a peristaltic pump for 1 hour. The reaction was continued at ℃ for 3h, and the reaction was over. The solvent was removed by rotary evaporation at 40 ℃, and then column chromatography (eluent: petroleum ether: ethyl acetate = 1:10 ~ 1:5) was used to separate the tetrahydroquinoxaline compounds 3a, the yield is 75%, and the dr is 95:5, see Table 1.

[0025] .

[0026] Characterization of the product tetrahydroquinoxaline compound 3a: 1 HNMR(300MHz, CDCl 3 ) δ 8.60(s,1H), 7.57-7.54(m,2H),7.34-7.31(m,3H),6.92-6.57(m,8H),5.30(s,1H),5,19( s, 1H), 4.07 (s, 1H ), 3.63 (s, 3H ); 13 C NMR (75MHz, CDCl 3 )...

Embodiment 2-12

[0027] Examples 2-12 Preparation of compounds (3b to 3l).

[0028] Examples 2-12 are the same as in Example 1. See Table 1 for the change of substituents, compound number, d.r. value, yield, etc. in the reaction.

[0029] Table 1.

[0030] Example1 / R4

2 / R 1 / R 2 / R 3

productd.r. Yield(%) 11a / C 6 H 4

2a / H / H / H3a 95:575 21a / C 6 H 4

2b / H / H / CH 3

3b 95:563 31a / C 6 H 4

2c / H / H / NO 2

3c 95:585 41a / C 6 H 4

2d / H / H / COC 6 H 5

3d 95:583 51a / C 6 H 4

2e / H / OCH 3 / H

3e 95:577 61a / C 6 H 4

2f / NO 2 / H / H

3f 95:595 71a / C 6 H 4

2g / Br / H / H3g 95:581 81a / C 6 H 4

2h / Cl / H / H 3h 95:580 91b / 4-MeOC 6 H 4

2a / H / H / H3i 95:567 101c / 4-BrC 6 H 4

2a / H / H / H3j 95:563 111d / 3-BrC 6 H 4

2a / H / H / H3k 95:570 121e / 3-ClC 6 H 4

2a / H / H / H3l 95:575

[0031] The product tetrahydroquinoxaline compounds 3b to 3l are characterized as follows:.

[0032] Characterization of product 3b: 1 H NMR (300 MHz, CDCl 3 ) δ 8.79 (s, 1H ), 7.56-7.53 (m,2H...

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PUM

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Abstract

The invention discloses a preparation method of a tetrahydroquinoxaline compound shown in the formula (V). Aryl methyl diazoacetate and o-aminophenyl imine compounds are subjected to a [5+1] cyclization reaction under the catalysis of rhodium acetate to generate the tetrahydroquinoxaline compound. The preparation method has the advantages that the raw materials are cheap and easy to obtain, the preparation route is short, the operation is simple and convenient, the reaction conditions are mild, the time is short, and the energy consumption is low; the reaction conversion rate and the atom utilization rate are high, few by-products are generated, the diastereoselectivity is high, and the product is easy to separate and purify; a novel tetrahydroquinoxaline derivative is convenient to prepare, and a diverse compound framework is provided. The formula (V) is shown in the description.

Description

Technical field [0001] The invention belongs to the technical field of organic synthetic chemistry and relates to a preparation method of a multi-substituted tetrahydroquinoxaline derivative. Background technique [0002] Tetrahydroquinoxaline derivatives, as a very important framework structure, are commonly found in biologically active compounds and natural products. For example, Hunanamycin A (I) is a natural product extracted from Bacillus from the ocean. This substance is related to the degradation products of riboflavin and has a significant inhibitory effect on the bacterial pathogen Salmonella enterica (Org. Lett., 2013, 15, 390-393). N-substituted-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid derivatives (II) show very superior antiproliferative activity, and can also inhibit tubulin polymerization. Block the cell cycle in G2 / M phase and induce apoptosis (Eur. J. Med. Chem., 2018, 143, 8-20). Tetrahydroquinoxaline compounds (III) are used as M2 acetylcholine ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/44
CPCC07D241/44
Inventor 管晓渝刘章琴胡文浩
Owner SOUTHWEST UNIV
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