6-methylindolo [1, 2-a] quinoxaline compound and synthesis method thereof

Abstract

According to the 6-methylindolo [1, 2-a] quinoxaline compound and the synthesis method thereof, amino indole arene is used as a raw material, under the mediation of cheap and easily available polymethylhydrosiloxane, an efficient catalytic system is used, carbon dioxide is firstly captured to generate estersil, then the estersil reacts with amino in the raw material to generate a formamide intermediate, and the 6-methylindolo [1, 2-a] quinoxaline compound is synthesized by the synthesis method of the 6-methylindolo [1, 2-a] quinoxaline compound. The intermediate is not immediately subjected to intramolecular cyclization, and then is subjected to formylation again to generate a dicarboxamide intermediate, and then is subjected to corresponding cyclization and subsequent reduction to obtain the methyl-substituted quinoxaline compound. The method is easy to operate, continuous conversion of two-molecule carbon dioxide is achieved through a one-pot method, a target compound is finally obtained in two different reduction state forms, and a new scheme is provided for research of carbon dioxide in the field of synthesis.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis and specifically relates to a 6-methylindole[1,2- a ]Quinoxaline compounds and their synthesis methods. Background Art

[0002] Based on the development needs of green chemistry, the chemical utilization of carbon dioxide has become a research hotspot in the field of organic synthesis in recent years. Through the unremitting efforts of chemists, a series of reactions involving carbon dioxide have been realized one after another, and a large number of carboxylic acids, amides, esters, alcohols, aldehydes, alkanes and aromatic compounds in the fields of medicine, materials, pesticides, etc. have been accurately obtained. [a)Aresta, M. Carbon Dioxide as Chemical Feedstock, Wiley, Weinheim, 2010. [b)He, LN Carbon Dioxide Chemistry, Science Press, Beijing, 2013. [c) Wang,S.; Xi, CJ Chem. Soc. Rev. 2019, 48, 382. Looking at the above progress, it is mainly focused on the utilization of single molecule carbon dioxide, and the transformation form is relatively simple. It is worth mentioning that Yu Dagang and other research groups recently used photochemical methods to realize a series of corresponding transformations involving di / trimolecular carbon dioxide, and synthesized a large number of carboxylic acid compounds, opening up a new direction for the research of carbon dioxide in the field of organic synthesis. [d) Ju, T.; Zhou, YQ; Gao, KG; Fu, Q.; Ye, JH; Sun, GQ; Liu, XF; Chen, L.; Liao, LL; Yu, DG Nat.Catal. 2021, 4, 304. [e) Gui, YY; Chen, XW; Mo, XY; Yue, JP;Yuan, R.; Liu, Y.; Liao, LL; Ye, JH; Yu, DGJ Am. Chem. Soc. 2024,146, 2919. Although the conversion of di / trimolecular CO2 has made important progress in the field of synthesis, it ultimately generates the target compound in a single reduced state. On the contrary, due to the thermodynamic stability and kinetic inertness caused by the structure of CO2 itself, there are still huge challenges in further realizing the diversified conversion of multi-molecular CO2 in this field, and related research is urgently needed. Summary of the invention

[0003] In view of the problems existing in the prior art, the present invention aims to provide a 6-methylindole [1,2- a ] Quinoxaline compounds and their synthesis method, using aminoindole aromatic hydrocarbons and carbon dioxide as reaction raw materials, heating the reaction in an organic solvent and then separating and purifying to obtain 6-methylindole [1,2- a ]Quinoxaline compounds have readily available raw materials, simple reaction operations, mild reaction conditions, low production costs, high atomic utilization rates, and can be achieved without pressurization.

[0004] The present invention is achieved through the following technical solutions: A 6-methylindole[1,2- a ] A method for synthesizing quinoxaline compounds, comprising the following steps: Polymethylhydrogensiloxane, copper acetate, 1,2-bis(diphenylphosphino)benzene, aminoindole aromatic compounds and copper trifluoromethanesulfonate were added to the organic solvent in sequence, and after heating and stirring under a carbon dioxide gas environment, the 6-methylindole[1,2- a ]Quinoxaline compounds.

[0005] Preferably, the 6-methylindole[1,2- a ]The reaction formula of quinoxaline compounds is:

[0006] Wherein, R is selected from hydrogen, alkyl, alkoxy, halogen, phenyl or heterocycle.

[0007] Preferably, the molar ratio of the polymethylhydrogensiloxane, copper acetate, 1,2-bis(diphenylphosphino)benzene, aminoindole aromatic compounds and copper trifluoromethanesulfonate is 10:0.02:0.04:1:1.

[0008] Preferably, the concentration of the aminoindole aromatic compound in the solvent is 0.1 mol / L.

[0009] Preferably, the solvent is 1,4-dioxane and ethylene glycol dimethyl ether.

[0010] Preferably, the catalyst is copper acetate and copper trifluoromethanesulfonate.

[0011] Preferably, the ligand is 1,2-bis(diphenylphosphino)benzene.

[0012] Preferably, the aminoindole aromatic compounds include 2-(1H-indol-1-yl)aniline, 2-(4-methyl-1H-indol-1-yl)aniline, 2-(4-(benzyloxy)-1H-indol-1-yl)aniline, 2-(4-methoxy-1H-indol-1-yl)aniline, 2-(4-fluoro-1H-indol-1-yl)aniline, 2-(5-methyl-1H-indol-1-yl)aniline, 2-(5-fluoro-1H-indol-1-yl)aniline, 2-(5 2-(5-(p-methylphenyl)-1H-indol-1-yl)aniline, 2-(5-(4-(trifluoromethyl)phenyl)-1H-indol-1-yl)aniline, 2-(5-(naphthalen-1-yl)-1H-indol-1-yl)aniline, 2-(5-(thiophen-2-yl)-1H-indol-1-yl)aniline, 2-(6-chloro-1H-indol-1-yl)aniline, 2-(6-fluoro-1H-indol-1-yl)aniline Preferably, the carbon source is carbon dioxide, the heating temperature is 65°C-120°C, and the stirring time is 0.5 h-24 h.

[0013] A 6-methylindole[1,2- a ] Quinoxaline compounds are prepared by the above-mentioned synthesis method, and the structural formula of the aminoindole aromatic compounds is:

[0014] Wherein, R is selected from hydrogen, alkyl, alkoxy, halogen, phenyl or heterocycle.

[0015] Compared with the prior art, the present invention has the following beneficial technical effects: The invention uses aminoindole aromatic hydrocarbons as raw materials, sequentially adds polymethylhydrogensiloxane as a reducing agent, copper acetate as a catalyst, 1,2-bis(diphenylphosphino)benzene as a ligand, aminoindole aromatic hydrocarbon compounds and copper trifluoromethanesulfonate into an organic solvent, and heats and stirs under a carbon dioxide gas environment to separate and purify the obtained 6-methylindole[1,2- a ] Quinoxaline compounds. Under the mediation of cheap and readily available polymethylhydrogensiloxane, an efficient catalytic system is used to first capture carbon dioxide to generate silicon esters, which then react with the amino group in the raw material to generate a formamide intermediate, which does not immediately undergo intramolecular cyclization, and then undergoes formylation again to generate a diformamide intermediate, followed by corresponding cyclization and subsequent reduction to obtain methyl-substituted quinoxaline compounds. The method is simple to operate, and a one-pot method is used to achieve continuous conversion of two molecules of carbon dioxide, and the target compound is finally obtained in two different reduced states, which provides a new solution for the study of carbon dioxide in the field of synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The product prepared in Example 1 1 H NMR spectrum; Figure 2 The product prepared in Example 1 13 C NMR spectrum; Figure 3 The product prepared in Example 2 1 H NMR spectra; Figure 4 The product prepared in Example 2 13 C NMR spectrum; Figure 5 The product prepared in Example 3 1 H NMR spectra; Figure 6 The product prepared in Example 3 13 C NMR spectrum; Figure 7 The product prepared in Example 4 1 H NMR spectra; Figure 8 The product prepared in Example 4 13 C NMR spectrum; Fig. 9 The product prepared in Example 5 1 H NMR spectra; Fig.10 The product prepared in Example 5 13 C NMR spectrum; Fig.11 The product prepared in Example 6 1 H NMR spectra; Fig.12 The product prepared in Example 6 13 C NMR spectrum; Fig.13 The product prepared in Example 7 1 H NMR spectra; Fig.14 The product prepared in Example 7 13 C NMR spectrum; Fig.15 The product prepared in Example 8 1 H NMR spectra; Fig.16 The product prepared in Example 8 13 C NMR spectrum; Fig.17 The product prepared in Example 9 1H NMR spectra; Fig.18 The product prepared in Example 9 13 C NMR spectrum; Fig.19 The product prepared in Example 10 1 H NMR spectra; Fig. 20 The product prepared in Example 10 13 C NMR spectrum; Fig.21 The product prepared in Example 11 1 H NMR spectra; Fig. 22 The product prepared in Example 11 13 C NMR spectrum; Fig.23 The product prepared in Example 12 1 H NMR spectra; Fig.24 The product prepared in Example 12 13 C NMR spectrum; Fig.25 The product prepared in Example 13 1 H NMR spectra; Fig.26 The product prepared in Example 13 13 C NMR spectrum; Fig. 27 The product prepared in Example 14 1 H NMR spectra; Fig.28 The product prepared in Example 14 13 C NMR spectrum. DETAILED DESCRIPTION

[0017] The present invention is further described in detail below in conjunction with specific embodiments, which are intended to explain the present invention rather than to limit it.

[0018] Example 1 6-Methylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(1H-indol-1-yl)aniline and 0.2 mmol of copper trifluoromethanesulfonate Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 33.0 mg of a yellow solid with a yield of 71%. The product structure is as follows:

[0019] like Figure 1 and Figure 2 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.45 (t, J = 9.6Hz, 2H), 7.97 (d, J = 8.6 Hz, 2H), 7.63 – 7.51 (m, 2H), 7.49 – 7.39 (m, 2H), 7.18 (s, 1H), 2.83 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.3, 135.5, 133.0,130.2, 129.7, 129.4, 129.0, 127.9, 124.3, 124.1, 122.7, 122.6, 114.6, 114.6,100.3, 22.2. Example 2 6,8-Dimethylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(4-methyl-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 25.6 mg of a yellow solid with a yield of 52%. The product structure is as follows:

[0020] like Figure 3 and Figure 4 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.3Hz, 1H), 8.16 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 6.4 Hz, 1H), 7.51 (t, J = 7.1 Hz,1H), 7.39 (t, J = 7.7 Hz, 2H), 7.19 (d, J = 7.1 Hz, 1H), 7.05 (s, 1H), 2.77 (s, 3H), 2.68 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.1, 135.7, 132.6, 131.9,130.1, 129.3, 129.1, 128.9, 127.6, 124.2, 123.8, 122.4, 114.5, 112.0, 98.3,22.2,19.0. Example 3 8-(Benzyloxy)-6-methylindolo[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(4-(benzyloxy)-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 42.0 mg of a light yellow solid with a yield of 62%. The product structure is as follows:

[0021] like Figure 5 and Figure 6 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.4Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 7.7 Hz,3H), 7.48 – 7.38 (m, 5H), 7.33 (s, 1H), 6.85 (d, J = 7.8 Hz, 1H), 5.30 (s, 2H), 2.79 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.4, 153.4, 136.9, 136.0, 134.1,130.2, 129.3, 128.7, 128.6, 128.0, 127.5, 127.4, 125.1, 124.1, 120.8, 114.6,107.7, 102.7, 97.7, 70.1, 22.3. Example 4 8-Methoxy-6-methylindole[1,2- a ] Preparation of quinoxaline; 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formate silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(4-methoxy-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 25.2 mg of a light yellow solid with a yield of 48%. The product structure is as follows:

[0022] like Figure 7 and Figure 8 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 7.7Hz, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 7.8 Hz,1H), 7.47 – 7.38 (m, 2H), 7.28 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 4.04 (s, 3H), 2.79 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.3, 154.3, 135.8, 134.0, 130.2,129.2, 128.6, 127.6, 125.3, 124.1, 120.5, 114.7, 107.4, 101.3, 97.6, 55.5,22.1. Example 5 8-Fluoro-6-methylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(4-fluoro-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 36.0 mg of a yellow solid with a yield of 72%. The product structure is as follows:

[0023] like Fig. 9 and Fig.10 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.9Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.53 (t, J = 7.9 Hz,1H), 7.47 – 7.36 (m, 2H), 7.13 (s, 1H), 7.06 (t, J = 8.7 Hz, 1H), 2.76 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 157.0 (d, J = 250.1 Hz), 155.2, 135.9, 134.8 (d, J =9.9 Hz), 129.8, 129.6, 127.9, 124.6 (d, J = 7.8 Hz), 124.5, 118.9 (d, J = 23.2Hz), 114.6, 110.6 (d, J = 3.9 Hz), 106.9 (d, J = 18.1 Hz), 95.7, 22.3. Example 6 6,9-dimethylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube in which the formic acid silyl ester solution is generated is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-methyl-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 15.8 mg of a yellow solid with a yield of 32%. The product structure is as follows:

[0024] like Fig.11 and Fig.12 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.4Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.69 (s, 1H), 7.56(t, J = 7.0 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 2.80 (s, 3H), 2.56 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.1, 135.4,132.2, 131.4, 130.2, 129.7, 129.4, 129.3, 127.8, 126.3, 123.8, 122.0, 114.5,114.2, 99.8, 22.1, 21.5. Example 7 Preparation of 9-fluoro-6-methylindolo[1,2-a]quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-fluoro-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 42.1 mg of a yellow solid with a yield of 84%. The product structure is as follows:

[0025] like Fig.13 and Fig.14 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.36 – 8.25(m, 2H), 7.94 (d, J = 8.0 Hz, 1H), 7.60 – 7.49 (m, 2H), 7.41 (t, J = 7.6 Hz, 1H), 7.30 – 7.19 (m, 1H), 7.03 (s, 1H), 2.76 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ158.7 (d, J = 240.8 Hz), 154.7, 135.5, 130.9, 129.8, 129.7, 129.5, 128.0,124.2, 115.6 (d, J = 9.5 Hz), 114.1, 113.1, 112.9, 106.7 (d, J = 23.0 Hz), 99.7(d, J = 5.4 Hz), 22.2. Example 8 9-methoxy-6-methylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube in which the formic acid silyl ester solution is generated is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-methoxy-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 21.5 mg of a yellow solid with a yield of 41%. The product structure is as follows:

[0026] like Fig.15 and Fig.16 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.23 ​​(d, J = 8.3Hz, 1H), 8.16 (d, J = 9.3 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.51 – 7.44 (m, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 2.5 Hz, 1H), 7.09 (d, J = 9.3 Hz, 1H), 6.92(s, 1H), 3.89 (s, 3H), 2.72 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.4, 154.5,135.5, 130.0, 129.8, 129.3, 128.0, 127.5, 123.6, 115.3, 115.2, 114.0, 102.1,99.3, 55.4, 22.2. Example 9 6-methyl-9-(p-tolyl)indole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube in sequence, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube in which the formic acid silyl ester solution is generated is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-(p-tolyl)-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 25.8 mg of a yellow solid with a yield of 40%. The product structure is as follows:

[0027] like Fig.17 and Fig.18 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.7Hz, 2H), 8.13 (s, 1H), 7.97 (d, J = 7.9 Hz, 1H), 7.78 (d, J = 8.9 Hz, 1H), 7.63(d, J = 8.0 Hz, 2H), 7.59 (d, J = 8.1 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.31 (d, J =7.8 Hz, 2H), 7.20 (s, 1H), 2.83 (s, 3H), 2.44 (s, 3H). 13 C NMR (100 MHz, CDCl3)δ 155.2, 138.4, 136.9, 135.9, 135.8, 132.2, 130.3, 130.2, 129.6, 129.5,127.8, 127.3, 124.1, 123.9, 120.3, 114.8, 114.6, 100.2, 22.4, 21.1. Example 10 6-methyl-9-(4-(trifluoromethyl)phenyl)indolo[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction was completed, the reaction tube in which the formic acid silyl ester solution was generated was removed from the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-(4-(trifluoromethyl)phenyl)-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 62.5 mg of a yellow solid with a yield of 83%. The product structure is as follows:

[0028] like Fig.19 and Fig. 20 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.47 – 8.37(m, 2H), 8.11 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.77 –7.69 (m, 3H), 7.58 (t, J = 7.8 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.17 (s, 1H), 2.81 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.1, 144.7, 135.5, 134.3, 132.7,130.4, 129.9, 129.7, 129.5, 129.2 (q, J = 32.4 Hz), 128.0, 127.6, 125.8 (q, J =4.1 Hz), 124.5, 124.4 (q, J= 270.2 Hz), 123.8, 121.0, 115.0, 114.5, 100.6,22.1. Embodiment 11 6-methyl-9-(naphthalen-1-yl)indole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-(naphthalene-1-yl)-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 32.3 mg of yellow oil with a yield of 45%. The product structure is as follows:

[0029] like Fig.21 and Fig. 22 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.54 (dd, J =8.6, 4.0 Hz, 2H), 8.07 (s, 1H), 8.02 (d, J = 8.1 Hz, 1H), 8.00 – 7.93 (m, 2H), 7.92 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.1 Hz, 1H), 7.64 – 7.49 (m, 4H), 7.49 –7.42 (m, 2H), 7.24 (s, 1H), 2.86 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.2,140.2, 135.3, 133.8, 132.3, 131.9, 130.2, 130.1, 129.4, 129.2, 128.3, 128.0,127.7, 127.4, 127.0, 126.1, 126.0, 125.8, 125.4, 124.2, 123.6, 114.6, 114.2,100.6, 22.2. Example 12 6-methyl-9-(thien-2-yl)indole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction was completed, the reaction tube in which the formic acid silyl ester solution was generated was removed from the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(5-(thiophene-2-yl)-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 38.4 mg of an orange solid with a yield of 61%. The product structure is as follows:

[0030] like Fig.23 and Fig.24 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 9.2Hz, 2H), 8.07 (s, 1H), 7.94 (d, J = 6.6 Hz, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.57 –7.51 (m, 1H), 7.43 – 7.36 (m, 2H), 7.31 (d, J= 4.4 Hz, 1H), 7.15 – 7.11 (m,1H), 7.06 (s, 1H), 2.77 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 155.0, 144.6,135.4, 132.1, 130.2, 129.9, 129.4, 129.3, 129.0, 128.1, 127.9, 124.6, 124.2,123.0, 122.9, 119.2, 114.8, 114.5, 100.4, 22.1. Embodiment 13 10-Chloro-6-methylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 65 °C for 30 minutes to obtain a light yellow solution. After the reaction is completed, the reaction tube that produces the formic acid silyl ester solution is taken out of the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(6-chloro-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in a 120 °C oil bath for 24 hours. After the reaction is completed, it is cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 34.7 mg of a yellow solid with a yield of 65%. The product structure is as follows:

[0031] like Fig.25 and Fig.26 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H),8.23 (d, J = 8.2 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.79 (d, J = 8.7 Hz, 1H), 7.55(t, J = 7.8 Hz, 1H), 7.45 – 7.34 (m, 2H), 7.03 (s, 1H), 2.75 (s, 3H).13 C NMR(100 MHz, CDCl3) δ 155.0, 135.8, 132.7, 130.2, 129.8, 129.7, 127.9, 127.3,124.4, 123.4, 123.3, 114.3, 114.2, 99.8, 22.2. Embodiment 14 10-Fluoro-6-methylindole[1,2- a Preparation of quinoxaline 0.004 mmol of copper acetate, 0.008 mmol of 1,2-bis(diphenylphosphino)benzene and 0.124 g of polymethylhydrogensiloxane were added to a 20 mL Shrek tube, and then 1.0 mL of dry 1,4-dioxane was added, and then carbon dioxide was pumped in three times using a double-row tube and an oil pump. Stir at 70 °C for 50 minutes to obtain a light yellow solution. After the reaction was completed, the reaction tube in which the formic acid silyl ester solution was generated was removed from the oil bath. Subsequently, 1.0 mL of ethylene glycol dimethyl ether, 0.2 mmol of 2-(6-fluoro-1H-indol-1-yl)aniline and 0.2 mmol of Cu(OTf)2 were added in sequence under a carbon dioxide atmosphere. The Shrek tube was sealed and stirred in an oil bath at 115 °C for 23 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed with water three times. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 40.0 mg of a yellow solid with a yield of 80%. The product structure is as follows:

[0032] like Fig. 27 and Fig.28 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 8.61 – 8.55(m,1H), 7.98(d, J =7.9 Hz,1H),7.72(d, J =7.4 Hz,1H),7.60–7.54 (m,1H),7.44(t, J =7.6 Hz, 1H), 7.41–7.34 (m, 1H), 7.26– 7.21 (m, 2H), 2.85 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 154.9, 149.6 (d, J = 248.0 Hz), 135.4, 132.9 (d, J= 4.1 Hz), 130.9,129.2, 128.8, 128.1, 124.7, 123.5 (d, J = 7.8 Hz), 120.8 (d, J = 10.3 Hz), 118.4(d, J = 3.7 Hz), 117.7 (d, J = 30.6 Hz), 110.4 (d, J = 24.1 Hz), 101.8, 22.1。

Claims

1. A 6-methylindole[1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The following steps are involved: Polymethylhydrogensiloxane as a reducing agent, copper acetate as a catalyst, 1,2-bis(diphenylphosphino)benzene as a ligand, aminoindole aromatic compounds and copper trifluoromethanesulfonate were added to an organic solvent in sequence, and after heating and stirring under a carbon dioxide gas environment, 6-methylindole[1,2- a ]Quinoxaline compounds.

2. A 6-methylindole [1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The 6-methylindole[1,2- a ]The reaction formula of quinoxaline compounds is: Wherein, R is selected from hydrogen, alkyl, alkoxy, halogen, phenyl or heterocycle.

3. A 6-methylindole [1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The molar ratio of the polymethylhydrogensiloxane, copper acetate, 1,2-bis(diphenylphosphino)benzene, aminoindole aromatic compounds and copper trifluoromethanesulfonate is 10:0.02:0.04:1:

1.

4. A 6-methylindole [1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The concentration of the aminoindole aromatic hydrocarbon compound in the organic solvent is 0.1 mol / L.

5. A 6-methylindole [1,2- a ] A method for synthesizing quinoxaline compounds, wherein the organic solvent is 1,4-dioxane and ethylene glycol dimethyl ether.

6. A 6-methylindole [1,2- a ] The synthesis method of quinoxaline compounds, the specific process of separation and purification is: After the reaction, the reactant was cooled to room temperature, diluted with ethyl acetate, and then washed with water several times. The reactant was then concentrated in vacuo and purified by silica gel chromatography to obtain 6-methylindole[1,2- a ]Quinoxaline compounds.

7. A 6-methylindole [1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The aminoindole aromatic compounds include 2-(1H-indol-1-yl)aniline, 2-(4-methyl-1H-indol-1-yl)aniline, 2-(4-(benzyloxy)-1H-indol-1-yl)aniline, 2-(4-methoxy-1H-indol-1-yl)aniline, 2-(4-fluoro-1H-indol-1-yl)aniline, 2-(5-methyl-1H-indol-1-yl)aniline, 2-(5-fluoro-1H-indol-1-yl)aniline, 2-(5-methoxy-1H-indol-1-yl)aniline, 1H-indol-1-yl)aniline, 2-(5-(p-tolyl)-1H-indol-1-yl)aniline, 2-(5-(4-(trifluoromethyl)phenyl)-1H-indol-1-yl)aniline, 2-(5-(naphthalen-1-yl)-1H-indol-1-yl)aniline, 2-(5-(thiophen-2-yl)-1H-indol-1-yl)aniline, 2-(6-chloro-1H-indol-1-yl)aniline, 2-(6-fluoro-1H-indol-1-yl)aniline.

8. A 6-methylindole[1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The heating temperature is 65°C-120°C.

9. A 6-methylindole[1,2- a ] A method for synthesizing quinoxaline compounds, characterized in that: The stirring time is 0.5 h-24 h.

10. A 6-methylindole[1,2- a ] Quinoxaline compounds, characterized in that The 6-methylindole[1,2- a The structural formula of quinoxaline compounds is: Wherein, R is selected from hydrogen, alkyl, alkoxy, halogen, phenyl or heterocycle.

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