A phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound and preparation method thereof

Abstract

The invention provides a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound and a preparation method thereof, and relates to the technical field of preparation methods of pyrrolo[1,2-a]quinoxaline compounds. The phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound is prepared by ring-opening cyclization reaction of cycloalkylsilyl peroxide under catalyst, oxidant and suitable temperature conditions with 2-(1-pyrrolyl)aniline and cycloalkylsilyl peroxide as substrates. On the one hand, the substrate used in the invention is cheap and easy to obtain, and the yield is high. On the other hand, the preparation method of the invention is simple, green and environmentally friendly, and easy to realize industrial production. On the other hand, the preparation method of the invention enriches the types of pyrrolo[1,2-a]quinoxaline compounds, and provides more choices for finding such compounds with pharmacological activity.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation methods of pyrrolo[1,2-a]quinoxaline compounds, and specifically relates to a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound and a preparation method thereof. Background Art

[0002] Pyrrolo[1,2-a]quinoxaline compounds are a class of nitrogen-containing heterocyclic compounds widely found in many natural alkaloids and bioactive molecules. In pharmaceutical chemistry, such compounds are considered to be active skeletons for drug design. Compounds containing pyrrolo[1,2-a]quinoxaline core structural units often have excellent biological activities, such as anti-malarial, anti-kala-azar, anti-HIV-1, anti-cancer, etc. Therefore, such compounds have a wide range of applications in biology, medicine and other fields. In view of the important research and application value of such compounds, more and more researchers are committed to developing simple and efficient synthetic methods to construct novel pyrrolo[1,2-a]quinoxaline derivatives, in order to enrich the types of such compounds and explore valuable drug molecules.

[0003] In recent years, the research on the synthesis methods of pyrrolo[1,2-a]quinoxaline derivatives has received extensive attention, and many substituted pyrrolo[1,2-a]quinoxaline derivatives have been reported. However, the types of this class of compounds still cannot meet the needs of drug development, and their synthesis methods still need to be further studied. According to the relevant literature, phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compounds have not been reported. As a new pyrrolo[1,2-a]quinoxaline derivative, this compound not only enriches the types of this compound, but also provides new ideas for the research on the synthesis methods of this class of compounds.

[0004] At present, there are many reports on the synthesis methods of pyrrolo[1,2-a]quinoxaline compounds, which are listed as follows:

[0005] As early as 1965, Cheeseman and Tuck used o-phenylenediamine and 2,5-diethoxytetrahydrofuran to synthesize pyrrolo[1,2-a]quinoxaline. Under heating conditions, o-phenylenediamine and 2,5-diethoxytetrahydrofuran can be coupled and cyclized to obtain 2-(1-pyrrolyl)aniline, and then 2-(1-pyrrolyl)aniline can be refluxed under formic acid to generate the target product pyrrolo[1,2-a]quinoxaline. The chemical reaction formula is as follows.

[0006]

[0007] In 2015, Ma Chen's research group at Shandong University used 2-(1-pyrrolyl)aniline and acetophenone as raw materials, I2 as catalyst, and DMSO as oxidant. 3 and sp 2 Cross-dehydrogenation coupling generates pyrrolo[1,2-a]quinoxaline compounds, and the chemical reaction formula is as follows.

[0008]

[0009] In 2016, Ma Chen's research group synthesized a pyrrolo[1,2-a]quinoxaline compound again. The reaction used 2-(1-pyrrolyl)aniline and dibenzoylmethane as substrates, p-toluenesulfonic acid as a catalyst, and constructed a phenyl-substituted pyrrolo[1,2-a]quinoxaline compound through the cleavage of the carbon-carbon bond and the formation of the imine bond. The chemical reaction formula is as follows.

[0010]

[0011] In 2017, Ma Chen's research group once again reported a synthetic strategy for pyrrolo[1,2-a]quinoxaline compounds. The reaction uses 2-(1-pyrrolyl)aniline and dimethyl sulfoxide as raw materials. Under the action of acetic acid, dimethyl sulfoxide produces methyl radicals at high temperature, and forms imine intermediates through free radical addition, and finally forms pyrrolo[1,2-a]quinoxaline compounds through electrophilic substitution. The chemical reaction formula is as follows.

[0012]

[0013] The research groups of Valérie Thiéry and Jiang Gaoxi used 1-(2-nitrophenyl)pyrrole and 2-(1-pyrrolyl)aniline as substrates and alcohol compounds to react, and synthesized pyrrolo[1,2-a]quinoxaline compounds through oxidative cyclization reactions. The reaction conditions used by Valérie Thiéry's research group were iron powder and hydrochloric acid reflux reaction, reducing the nitro group to an amino group and then reacting with benzyl alcohol. The research group of Jiang Gaoxi directly used 2-(1-pyrrolyl)aniline as a raw material and oxygen as an oxidant to react in the absence of a catalyst to obtain the final product. The chemical reaction formula is as follows.

[0014]

[0015] Yan Rulong's research group has also conducted a series of studies on the synthesis of pyrrolo[1,2-a]quinoxaline compounds. In 2017, the research group developed a strategy to construct alkyl alcohol-substituted pyrrolo[1,2-a]quinoxaline compounds through a tetrahydrofuran ring-opening cyclization reaction using 2-(1-pyrrolyl)aniline and tetrahydrofuran as reaction substrates. The reaction uses ferric chloride as a catalyst and 70% tert-butyl hydroperoxide as an oxidant. The carbon radical formed by tetrahydrofuran is used to react with 2-(1-pyrrolyl)aniline for free radical addition to promote the ring-opening cyclization reaction of tetrahydrofuran. Tetrahydrofuran acts as both a reaction substrate and a reaction solvent in this reaction. The chemical reaction formula is as follows.

[0016]

[0017] In 2018, Yan Rulong's research group used 2-(1-pyrrolyl)aniline and cyclobutanone oxime as reaction substrates to synthesize a series of alkylnitrile-substituted pyrrolo[1,2-a]quinoxaline compounds. The reaction used oxygen as an oxidant and copper pivalate as a catalyst. Through the ring-opening reaction of cyclobutanone oxime, a butyronitrile radical was formed. Subsequently, the butyronitrile radical and 2-(1-pyrrolyl)aniline underwent a free radical addition cyclization reaction to obtain the target product. The research group successfully captured the butyronitrile radical intermediate using a free radical scavenger and inferred a reasonable reaction mechanism. The chemical reaction formula is as follows.

[0018]

[0019] In 2021, Jiang Nan's research group used 2-(1-pyrrolyl)aniline and vinylene carbonate as reaction substrates to construct a methyl-substituted pyrrolo[1,2-a]quinoxaline compound through intermolecular cyclization reaction. In this reaction, vinylene carbonate forms vinyl alcohol by losing a part of carbon dioxide; then vinyl alcohol reacts with 2-(1-pyrrolyl)aniline to form imine by removing a molecule of water, and finally obtains the target product through carbon-carbon bond coupling cyclization. The reaction uses metal rhodium as a catalyst, does not require oxidants and additives, and the reaction conditions are simple. The chemical reaction formula is as follows.

[0020]

[0021] Timothy F. Jamison's research group used 2-pyrroloisocyanatobenzene and phenyliodine (III) dicarboxylate as reaction substrates under visible light-induced conditions, and constructed a series of cyclohexyl-substituted pyrrolo[1,2-a]quinoxaline compounds through the cyclization reaction between the two. The reaction used metal iridium as a photocatalyst and a household 26W fluorescent lamp as a light source. The cyclohexyl free radical was added to the isonitrile group to form an imine intermediate, and finally the target product was obtained through an intramolecular coupling cyclization reaction. The chemical reaction formula is as follows.

[0022]

[0023] In view of the important pharmacological properties and application value of pyrrolo[1,2-a]quinoxaline compounds in drug synthesis, it is of great significance to synthesize the compounds in a low-cost and high-efficiency manner using simple and readily available substrates under mild reaction conditions. At present, a variety of 4-substituted pyrrolo[1,2-a]quinoxaline compounds have been reported, and the substituents mainly involve alkyl alcohols, alkyl nitriles, aryls, alkyls, etc. However, 4-phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compounds have not yet been reported, so it is necessary to explore the preparation method of 4-phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compounds. Summary of the invention

[0024] In view of this, the present invention provides a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound.

[0025] Also provided is a method for preparing a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound.

[0026] The technical solution adopted by the present invention to solve its technical problem is:

[0027] A phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound having the general formula:

[0028]

[0029] Where: R 1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine or bromine;

[0030] R 2 is selected from hydrogen, methyl, fluorine or chlorine.

[0031] A method for preparing a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound comprises the following steps:

[0032] S1: adding a compound having the general formula 1, a compound having the general formula 2, a catalyst, and a solvent into a reaction container to obtain a reactant;

[0033] S2: oxidizing the reactant with an oxidant at a predetermined temperature for a predetermined time to obtain a mixture;

[0034] S3: extracting the mixture with an organic solvent and separating and purifying it by silica gel column chromatography to obtain a compound having the general formula 3;

[0035] The compound of general formula 1 is:

[0036] The compound of general formula 2 is:

[0037] The compound of general formula 3 is:

[0038] Preferably, in step S1, the catalyst is one of cuprous iodide, cupric bromide, copper acetate, copper pivalate, and copper trifluoromethanesulfonate.

[0039] Preferably, in step S1, the solvent is one of N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide and nitromethane.

[0040] Preferably, in the step S1, the molar ratio of the compound having the general formula 1 to the compound having the general formula 2 is 1:1.5-2.

[0041] Preferably, the molar ratio of the compound having the general formula 1 to the catalyst is 1:0.05-0.1.

[0042] Preferably, in the step S2, the oxidant is one of oxygen, potassium persulfate, sodium persulfate, potassium peroxymonosulfonate, tert-butyl hydroperoxide, and tert-butyl peroxide.

[0043] Preferably, in the step S2, the predetermined temperature is 70°C-100°C, and the predetermined time is 8h-12h.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] The invention uses 2-(1-pyrrolyl)aniline and cycloalkylsilyl peroxide as substrates, and prepares a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound through a ring-opening cyclization reaction of cycloalkylsilyl peroxide under catalyst, oxidant and suitable temperature conditions. On the one hand, the substrate used in the invention is cheap and easy to obtain, and the yield is high. On the other hand, the preparation method of the invention is simple, green and environmentally friendly, and easy to realize industrial production. On the other hand, the preparation method of the invention enriches the types of pyrrolo[1,2-a]quinoxaline compounds, and provides more choices for finding such compounds with pharmacological activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 is the product 3aa obtained in Example 1 of the present invention 1 H NMR.

[0047] Figure 2 is the product 3aa obtained in Example 1 of the present invention 1 C NMR.

[0048] Figure 3 is the product 3ba obtained in Example 2 of the present invention 1 H NMR.

[0049] Figure 4 is the product 3ba obtained in Example 2 of the present invention 1 C NMR.

[0050] Figure 5 is the product 3ca obtained in Example 3 of the present invention 1 H NMR.

[0051] Figure 6 is the product 3ca obtained in Example 3 of the present invention 1 C NMR.

[0052] Figure 7 is the product 3da obtained in Example 4 of the present invention 1 H NMR.

[0053] Figure 8 is the product 3da obtained in Example 4 of the present invention 1 C NMR.

[0054] Fig. 9 is the product 3ea obtained in Example 5 of the present invention 1 H NMR.

[0055] Fig.10 is the product 3ea obtained in Example 5 of the present invention 1 C NMR.

[0056] Fig.11 is the product 3ab obtained in Example 6 of the present invention 1 H NMR.

[0057] Fig.12 is the product 3ab obtained in Example 6 of the present invention 1 C NMR.

[0058] Fig.13 is the product 3ac obtained in Example 7 of the present invention 1 H NMR.

[0059] Fig.14is the product 3ac obtained in Example 7 of the present invention 1 C NMR.

[0060] Fig.15 is the product 3ad obtained in Example 8 of the present invention 1 H NMR.

[0061] Fig.16 is the product 3ad obtained in Example 8 of the present invention 1 C NMR. DETAILED DESCRIPTION

[0062] The technical solutions and technical effects of the embodiments of the present invention are further described in detail below in conjunction with the accompanying drawings of the present invention.

[0063] A phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound having the general formula:

[0064]

[0065] Where: R 1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine or bromine;

[0066] R 2 is selected from hydrogen, methyl, fluorine or chlorine.

[0067] Compared with the prior art, the present invention has the following beneficial effects:

[0068] The invention uses 2-(1-pyrrolyl)aniline and cycloalkylsilyl peroxide as substrates, and prepares a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound through a ring-opening cyclization reaction of cycloalkylsilyl peroxide under catalyst, oxidant and suitable temperature conditions. On the one hand, the substrate used in the invention is cheap and easy to obtain, and the yield is high. On the other hand, the preparation method of the invention is simple, green and environmentally friendly, and easy to realize industrial production. On the other hand, the preparation method of the invention enriches the types of pyrrolo[1,2-a]quinoxaline compounds, and provides more choices for finding such compounds with pharmacological activity.

[0069] A method for preparing a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound comprises the following steps:

[0070] S1: adding a compound having the general formula 1, a compound having the general formula 2, a catalyst, and a solvent into a reaction container to obtain a reactant;

[0071] S2: oxidizing the reactant with an oxidant at a predetermined temperature for a predetermined time to obtain a mixture;

[0072] S3: extracting the mixture with an organic solvent and separating and purifying it by silica gel column chromatography to obtain a compound of formula 3;

[0073] The compound of general formula 1 is:

[0074] The compound of general formula 2 is:

[0075] The compound of general formula 3 is:

[0076] Furthermore, in step S1, the catalyst is one of cuprous iodide, cupric bromide, copper acetate, copper pivalate, and copper trifluoromethanesulfonate.

[0077] Furthermore, in the step S1, the solvent is one of N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and nitromethane.

[0078] Furthermore, in the step S1, the molar ratio of the compound having the general formula 1 to the compound having the general formula 2 is 1:1.5-2.

[0079] Furthermore, the molar ratio of the compound having the general formula 1 to the catalyst is 1:0.05-0.1.

[0080] Furthermore, in the step S2, the oxidant is one of oxygen, potassium persulfate, sodium persulfate, potassium peroxymonosulfonate, tert-butyl hydroperoxide, and tert-butyl peroxide.

[0081] Furthermore, in the step S2, the predetermined temperature is 70°C-100°C, and the predetermined time is 8h-12h.

[0082] For ease of understanding, the present invention is further illustrated by the following examples:

[0083] Embodiment 1:

[0084] Compound 1a (1.0 mmol, 158 mg), compound 2a (1.5 mmol, 375 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Afterwards, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3aa with a yield of 87%. The reaction equation is as follows:

[0085]

[0086] Please see Figure 1 and Figure 2 The above product 3aa was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0087] 1 H NMR (400MHz, CDCl3, ppm):7.96-7.95(m,2H),7.92-7.86(m,2H),7.83-7.80(m,1H),7.56-7.51(m,1 H),7.49-7.39(m,4H),7.01-6.99(m,1H),6.85-6.83(m,1H),3.18-3.11(m,4H),2.43-2.33(m,2H); 13 C NMR (100MHz, CDCl3, ppm): δ=200.13,156.67,137.16,136.06,133.08,129.62,128.68,128.23 ,127.47,127.13,126.11,125.19,114.34,113.78,113.73,106.62,38.15,34.97,22.75; HRMS calcd for C 21 H 19 N2O[M+H] + 315.1492; found:315.1494.

[0088] Embodiment 2:

[0089] Compound 1b (1.0 mmol, 172 mg), compound 2a (1.5 mmol, 375 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Afterwards, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ba with a yield of 83%. The reaction equation is as follows:

[0090]

[0091] Please see Figure 3 and Figure 4 The above product 3ba was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0092] 1H NMR (400MHz, CDCl3, ppm): 7.98-7.96 (m, 2H), 7.87-7.86 (m, 1H), 7.79 (d, J = 8.4Hz, 1H), 7.63 (s, 1H), 7.56-7.52 (m, 1H), 7.4 6-7.42(m,2H),7.25-7.22(m,1H),6.98-6.96(m,1H),6.84-6.82(m,1H),3.17-3.10(m,4H),2.54(s,3H),2.41-2.34(m,2H); 13 C NMR (100MHz, CDCl3, ppm): δ=200.17,155.60,137.52,137.16,134.02,133.06,129.30,128.67,12 8.24,127.21,126.46,126.17,114.03,113.86,113.60,106.29,38.18,34.93,22.78,21.88; HRMS calcd for C 22 H 21 N2O[M+H] + 329.1649; found:329.1650.

[0093] Embodiment 3:

[0094] Compound 1c (1.0 mmol, 188 mg), compound 2a (1.5 mmol, 375 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ca with a yield of 78%. The reaction equation is as follows:

[0095]

[0096] Please see Figure 5 and Figure 6 The above product 3ca was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0097] 1H NMR (600MHz, CDCl3, ppm):7.98-7.96(m,2H),7.83(d,J=9.0Hz,1H),7.80-7.79(m,1H),7.55-7.53(m,1H),7.45-7.43(m,2H),7.24(d,J=2 .4Hz,1H),7.03-7.01(m,1H),6.96-6.95(m,1H),6.85-6.84(m,1H),3.94(s,3H),3.16-3.14(m,2H),3.12-3.10(m,2H),2.39-2.34(m,2H); 13 C NMR (150MHz, CDCl3, ppm): δ=200.19,158.89,153.96,137.24,133.04,130.79,130.51,128.67,1 28.25,128.17,126.13,113.88,113.78,112.68,106.12,97.80,55.93,38.21,34.83,22.79; HRMS calcd for C 22 H 21 N2O2[M+H] + 345.1598; found:345.1599.

[0098] Embodiment 4:

[0099] Compound 1d (1.0 mmol, 176 mg), compound 2a (1.5 mmol, 375 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3da with a yield of 82%. The reaction equation is as follows:

[0100]

[0101] Please see Figure 7 and Figure 8 The above product 3da was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0102] 1H NMR (400MHz, CDCl3, ppm):7.98-7.95(m,2H),7.84-7.83(m,1H),7.77-7.73(m,1H),7.57-7.52(m,2H),7.46- 7.42(m,2H),7.21-7.16(m,1H),7.01-7.00(m,1H),6.84-6.82(m,1H),3.17-3.10(m,4H),2.41-2.33(m,2H); 13 CNMR (100MHz, CDCl3, ppm): δ = 200.00, 159.87 (d, J = 241.9Hz, 1C), 157.89, 137.22 (d, J = 11.4Hz, 1C), 137.07, 133.10, 128.66, 128.1 7,125.84,124.08,114.93(d,J=11.5Hz,1C),114.71(d,J=24.7Hz,1C),114.78,114.53,113.82,106.97,38.04,34.85,22.56; HRMS calcd for C 21 H 18 FN2O[M+H] + 333.1398; found:333.1397.

[0103] Example 5

[0104] Compound 1e (1.0 mmol, 192 mg), compound 2a (1.5 mmol, 375 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ea with a yield of 89%. The reaction equation is as follows:

[0105]

[0106] Please see Fig. 9 and Fig.10 The above product 3ea was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0107] 1H NMR (600MHz, CDCl3, ppm): 7.98-7.95 (m, 2H), 7.87-7.86 (m, 1H), 7.75-7.73 (d, J = 9.0Hz, 1H), 7.57-7.54 (m, 2H), 7.46-7.44 (m, 2H), 7 .42-7.41(m,1H),7.21-7.16(m,1H),7.02-7.01(m,1H),6.86-6.85(m,1H),3.17-3.15(m,2H),3.13-3.11(m,2H),2.39-2.35(m,2H); 13 C NMR (150MHz, CDCl3, ppm):200.03,157.89,137.15,137.03,133.12,130.26,129.08,128.70, 128.21,127.09,126.10,126.01,114.90,114.65,114.11,107.16,38.05,34.83,22.48.; HRMS calcd for C 21 H 18 ClN2O[M+H] + 349.1102; found:349.1106.

[0108] Example 6

[0109] Compound 1a (1.0 mmol, 158 mg), compound 2b (1.5 mmol, 396 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ab with a yield of 85%. The reaction equation is as follows:

[0110]

[0111] Please see Fig.11 and Fig.12 The above product 3ab was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0112] 1H NMR(400MHz, CDCl3,ppm):8.02-7.98(m,2H),7.92-7.89(m,2H),7.85-7.82(m,1H),7.51-7.40(m,2 H),7.13-7.08(m,2H),7.00-6.99(m,1H),6.86-6.85(m,1H),3.16-3.11(m,4H),2.42-2.34(m,2H); 13 C NMR (100MHz, CDCl3, ppm): δ = 198.54, 165.813 (d, J = 252.8Hz, 1C), 156.54, 136.03, 133.58, 130.90 (d, J = 9.1Hz, 1C), 129.6 0,127.46,127.18,126.10,125.22,115.73(d,J=21.6Hz,1C),114.38,113.80,113.75,106.57,38.03,34.84,22.67; HRMS calcd for C 21 H 18 FN2O[M+H] + 333.1398; found:333.1398.

[0113] Example 7

[0114] Compound 1a (1.0 mmol, 158 mg), compound 2c (1.5 mmol, 402 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ac with a yield of 87%. The reaction equation is as follows:

[0115]

[0116] Please see Fig.13 and Fig.14 The above product 3ac was subjected to NMR and high-resolution mass spectrometry analysis, and the data are as follows:

[0117] 1H NMR (400MHz, CDCl3, ppm):7.91-7.87(m,2H),7.80-7.78(m,1H),7.74-7.71(m,1H),7.67-7.63(m,1H),7.47- 7.36(m,3H),7.24-7.19(m,1H),6.98-6.96(m,1H),6.84-6.82(m,1H),3.14-3.10(m,4H),2.41-2.34(m,2H); 13 CNMR (100MHz, CDCl3, ppm): δ = 198.80, 162.93 (d, J = 246.2Hz, 1C), 156.37, 1 39.13(d,J=5.0Hz,1C),135.92,130.26(d,J=7.6Hz,1C),129.52,127.37,1 27.12,125.99,125.17,123.91,120.01(d,J=21.3Hz,1C),114.92(d,J=22. 2Hz,1C),114.36,113.73,113.69,106.51,38.23,34.66,22.48; HRMScalcd for C 21 H 18 FN2O[M+H] + 333.1398; found:333.1399.

[0118] Example 8

[0119] Compound 1a (1.0 mmol, 158 mg), compound 2d (1.5 mmol, 426 mg), copper pivalate (0.1 mmol, 16.5 mg), and N-methylpyrrolidone (6 mL) were added to a Schlenk reaction tube equipped with a magnet. An oxygen balloon was installed and the reaction was ventilated three times. The reaction was carried out at 80°C for 10 hours. The reaction progress was monitored by thin layer chromatography until the reaction was complete. Then, organic solvent extraction and silica gel column chromatography were used for separation and purification to obtain compound 3ad with a yield of 74%. The reaction equation is as follows:

[0120]

[0121] Please see Fig.15 and Fig.16 The above product 3ad was analyzed by NMR and high-resolution mass spectrometry, and the data are as follows:

[0122] 1H NMR (400MHz, CDCl3, ppm):7.92-7.88(m,4H),7.85-7.82(m,1H),7.51-7.40(m,4 H),6.99-6.98(m,1H),6.86-6.85(m,1H),3.15-3.10(m,4H),2.41-2.34(m,2H); 13 C NMR (100MHz, CDCl3, ppm): δ=198.93,156.49,139.51,136.00,135.42,129.68,129.59,128.98 ,127.45,127.21,126.08,125.25,114.41,113.81,113.76,106.58,38.08,34.79,22.60; HRMS calcd for C 21 H 18 ClN2O[M+H] + 349.1102; found:349.1106.

[0123] The substrates, products and yields of Examples 1 to 8 above are shown in Table 1:

[0124]

[0125]

[0126] It can be seen from the above examples 1 to 8 that the preparation method of the phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound prepared by ring-opening cyclization reaction using 2-(1-pyrrolyl)aniline and cycloalkylsilyl peroxide as substrates is simple and has a high yield.

[0127] What is disclosed above is only a preferred embodiment of the present invention, which certainly cannot be used to limit the scope of rights of the present invention. A person skilled in the art can understand that all or part of the processes of the above embodiments and equivalent changes made according to the claims of the present invention still fall within the scope of the invention.

Claims

1. A method for preparing a phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound, characterized in that: The following steps are involved: S1: adding a compound having the general formula 1, a compound having the general formula 2, a catalyst, and a solvent into a reaction container to obtain a reactant, wherein the catalyst is copper pivalate, and the solvent is one of N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and nitromethane; S2: oxidizing the reactant with an oxidant, reacting at a predetermined temperature for a predetermined time to obtain a mixture; the oxidant is oxygen, the predetermined temperature is 70°C-100°C, and the predetermined time is 8h-12h; S3: extracting the mixture with an organic solvent and separating and purifying it by silica gel column chromatography to obtain a compound having the general formula 3; The compound of general formula 1 is: The compound of general formula 2 is: The compound of general formula 3 is: Where: R 1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine or bromine; R 2 is selected from hydrogen, methyl, fluorine or chlorine.

2. A phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound according to claim 1, characterized in that: In the step S1, the molar ratio of the compound having the general formula 1 to the compound having the general formula 2 is 1:1.5-2.

3. A phenylbutanone-substituted pyrrolo[1,2-a]quinoxaline compound according to claim 1, characterized in that: In the step S1, the molar ratio of the compound of formula 1 to the catalyst is 1:0.05-0.1.

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