Method for preparing 4-amino-2-quinolinone compound through cyclization of 1, 6-alkene nitrile under catalysis of visible light

Abstract

The invention discloses a method for preparing a 4-amino-2-quinolinone compound through visible light catalysis of cyclization of 1, 6-alkene nitrile, which comprises the following steps: mixing a copper-based photosensitizer, a 1, 6-alkene nitrile compound as shown in a formula I, amine and a solvent in an inert atmosphere, reacting for 12-48 hours at 15-35 DEG C under illumination, and post-treating the reaction liquid to obtain the 4-amino-2-quinolinone compound as shown in a formula II, the method is mild, efficient, green and suitable for large-scale production; # imgabs0 #

Description

Technical Field

[0001] This invention relates to a method for preparing 4-amino-2-quinolinone compounds by visible light-catalyzed cyclization of 1,6-enyl acrylonitrile. Background Technology

[0002] 2-Quinolinones are important heterocyclic scaffolds found in many natural products, bioactive molecules, and drugs, and are also important synthetic intermediates for constructing complex molecules. For example, 3-O-Methylviridicatin can be used in anti-inflammatory drugs and HIV inhibitors; laquinimod and tipfarnib have anticancer properties; and herbicide with a 2-quinolinone core structure is widely used in the pesticide field. Representative molecular structures of drugs and pesticides containing 2-quinolinone structures are shown below:

[0003]

[0004] Based on this, researchers have developed various strategies for synthesizing 2-quinolinone compounds over the past few decades. Solvent-free thermal condensation (see Tetrahedron Lett., 2020, 61, 151-778.) and acid-catalyzed intramolecular Friedel-Crafts cyclization (see Tetrahedron Lett., 2020, 61, 152-535.) have provided effective strategies for preparing 2-quinolinone compounds. In addition, gold catalysis (see J. Org. Chem., 2017, 82, 2558-2569) and high-iodine reagent catalysis (see Org. Lett., 2018, 20, 7929-7932) are also important methods for synthesizing 2-quinolinone compounds. Unfortunately, the above-mentioned methods for preparing 2-quinolinones all suffer from drawbacks to varying degrees, such as demanding reaction conditions, difficulty in obtaining catalysts, and cumbersome operation.

[0005] In 2021, Li Yamin's research group achieved the synthesis of 4-amino-2-quinolinone compounds via the cyclization of 1,6-enyl nitrile using peroxide (TBHP) catalysis (see Org Lett., 2021, 23, 6158-6163), which also became a new method for synthesizing 2-quinolinone compounds. Although this method overcomes some of the shortcomings of the methods mentioned above, it still has limitations such as harsh reaction conditions, insufficient safety of peroxide as a catalyst making it unsuitable for large-scale production, and large catalyst dosage that does not conform to the concept of green synthesis. Therefore, it is particularly urgent to find a mild, efficient, and green method for preparing 2-quinolinone compounds. Summary of the Invention

[0006] To address the limitations of current synthesis technologies, this invention provides a method for the preparation of 4-amino-2-quinolinone compounds by visible light-catalyzed cyclization of 1,6-enyl acrylonitrile. This method is mild, efficient, and environmentally friendly, and suitable for large-scale production.

[0007] The technical solution of the present invention is as follows:

[0008] A method for preparing 4-amino-2-quinolinone compounds by visible light photocatalytic cyclization of 1,6-enyl acrylonitrile, comprising:

[0009] Under an inert atmosphere, a copper-based photosensitizer, a 1,6-enriched nitrile compound of Formula I, an amine, and a solvent are mixed and reacted under light at 15–35°C (preferably 25°C) for 12–48 h (preferably 24 h). The reaction solution is then post-treated to obtain a 4-amino-2-quinolinone compound of Formula II.

[0010] in,

[0011] The molar ratio of the 1,6-enonitrile compound, amine, and copper-based photosensitizer shown in Formula I is 1:1.5-2.5:0.025-0.1, preferably 1:2:0.05;

[0012] The amine is selected from N,N-diisopropylethylamine and triethylamine, preferably N,N-diisopropylethylamine;

[0013] The solvent is selected from toluene, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, methanol, tetrahydrofuran, and ethanol, with acetonitrile being preferred;

[0014] The volume molar ratio of the solvent to the 1,6-acrylonitrile compound shown in Formula I is 15 to 25:1, ml / mmol, preferably 20:1, ml / mmol;

[0015] The following light sources can be used for illumination: 15W blue LED, 15W green LED, 15W white LED, with 15W blue LED being preferred.

[0016] The copper-based photosensitizer is selected from at least one of PS1 to PS6, with PS1 being preferred;

[0017] The structural formulas of copper-based photosensitizers PS1 to PS6 are as follows:

[0018]

[0019] During the reaction, petroleum ether:ethyl acetate (volume ratio 1:1) was used as the developing solvent for TLC monitoring. After the reaction was completed, the specific post-processing method was as follows: the reaction solution was concentrated under vacuum to 10-25% of the original volume, and then loaded onto a silica column (preferably 300 mm high and 30 mm in diameter). The product was purified using petroleum ether:ethyl acetate (volume ratio 1:1) as the elution reagent at a elution rate of 2 ml / min. The target product eluent was obtained by TLC detection. The eluents were combined and the solvent was removed by vacuum distillation to obtain the 4-amino-2-quinolinone compound represented by Formula II.

[0020] The reaction formula is as follows:

[0021]

[0022] In formula I or formula II,

[0023] R1 is H, methyl, methoxy, fluorine, chlorine, bromine, trifluoromethyl or thiophene, preferably H, methyl, methoxy, fluorine, chlorine, bromine or trifluoromethyl;

[0024] Specifically, 1,6-enonitrile compounds include one of the following:

[0025]

[0026] The 1,6-acrylonitrile compounds used in this invention can be prepared according to methods disclosed in existing literature.

[0027] The technical principles of this invention include:

[0028] Photocatalytic synthesis is one of the research directions of our group. For photoreactions, a certain potential is required, and the catalyst needs to match the potential of this reaction for the reaction to occur. In this invention, the structure of the copper-based photosensitizer has a certain influence on the reaction. By changing the group on the N ligand of the photosensitizer, the potential of the photosensitizer can be changed, making it more suitable for the reaction.

[0029] In the reaction for the preparation of 4-amino-2-quinolinone compounds by cyclization of 1,6-acrylonitrile, this invention uses N,N-diisopropylethylamine and the easily synthesized PS1 photosensitizer, which increases the yield of the reaction and greatly improves the convenience of the reaction.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] 1) The 1,6-acrylonitrile raw material used in this invention can be obtained by combining inexpensive and varied fragments through simple chemical reactions. Therefore, the raw material is simple and readily available, and the functional groups are varied.

[0032] 2) This invention yields 4-amino-2-quinolinone compounds via photo-oxidation-reduction reaction. The reaction conditions are mild, the substrate is universal, and the reaction is highly efficient.

[0033] 3) This invention uses inexpensive copper complexes as photosensitizers to replace peroxides as catalysts for the synthesis of 4-amino-2-quinolinone compounds, resulting in high reaction safety and good economy. Attached Figure Description

[0034] Figure 1 The reaction mechanism involved in the photocatalytic reaction of this invention. Detailed Implementation

[0035] The present invention is further described below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0036] The raw material 1,6-acrylonitrile of this invention can be prepared according to literature, and the typical steps are as follows:

[0037]

[0038] An o-aminobenzonitrile compound S1 (5 mmol, 1.0 equiv.) and sodium bicarbonate (6 mmol, 1.2 equiv.) were added to a three-necked flask equipped with a magnetic flask. The argon gas was purged three times. Then, 2-butanone (15 ml) was added to the apparatus, followed by the slow addition of acryloyl chloride (5.5 mmol, 1.1 equiv.). The reaction was carried out at 100 °C for 24 h. After the reaction was completed, saturated sodium bicarbonate solution (30 ml) was added to quench the reaction. The mixture was then extracted with dichloromethane (3 × 30 ml). The organic phases were combined and the solvent was removed by rotary evaporation. The product S2 was obtained by column chromatography.

[0039] Product S2 (3 mmol, 1.0 equiv.) and potassium carbonate (6 mmol, 2 equiv.) were added to a three-necked flask equipped with a magnetic inlet. The argon atmosphere was purged three times. Then, acetone (15 ml) and iodomethane (4.5 mmol, 1.5 equiv.) were added to the apparatus, and the reaction was carried out at 40 °C for 16 h. After the reaction was completed, the product was extracted with dichloromethane (3 × 30 ml). The organic phases were combined, the solvent was removed by rotary evaporation, and the product S3 was obtained by column chromatography.

[0040] The photosensitizer PS1 used in the following examples is synthesized as follows:

[0041] Synthesis of photosensitizer PS1:

[0042]

[0043] In a 50 mL three-necked flask, Cu(MeCN)4PF6 (1 mmol, 1.0 equiv.) and 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (1 mmol, 1.0 equiv.) were added. The mixture was purged with argon three times, and then 30 mL of dry dichloromethane was added. The mixture was stirred at 35 °C for 4 hours. Then, a solution of 2,9-dimethyl-4,7-diphenylphenanthroline (1 mmol, 1.0 equiv.) in dichloromethane (10 mL) was slowly added at room temperature. After the addition was complete, the mixture was stirred at 35 °C for another 3 hours. After the reaction was complete, the mixture was cooled to room temperature, and 150 mL of n-hexane was added to precipitate the crude product. The product was filtered and the filter cake was washed with 3 × 30 mL of n-hexane. The resulting filter cake was the photosensitizer PS1, with a yield of 1 mmol and a yield of 100%.

[0044] Examples of synthesis of 4-amino-2-quinolinone compounds:

[0045] Example 1

[0046]

[0047] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyanophenyl)acrylamide (0.2 mmol, 37.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 22.2 mg, or 60%.

[0048] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.58-7.48(m,2H),7.34(dd,J=8.6,1.1Hz,1H),7.21(ddd,J=8.2,7.2,1.1Hz,1H),4.47(s,2H),3.71(s,3H),2.15(s,3H). 13 C NMR (101MHz, CDCl3) δ163.00,145.82,138.69,129.77,121.20,121.09,114.73,114.55,103.39,29.53,10.45.

[0049] Example 2

[0050]

[0051] Photosensitizer 4CzIPN (0.01 mmol, 17 mg, 5 mol%) and N-methyl-N-(2-cyanophenyl)acrylamide (0.2 mmol, 37.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, TLC analysis showed no product, indicating a yield of 0%.

[0052] Example 3

[0053]

[0054] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyanophenyl)acrylamide (0.2 mmol, 37.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 48 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 22.6 mg, representing a yield of 61%.

[0055] Example 4

[0056]

[0057] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyanophenyl)acrylamide (0.2 mmol, 37.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then tetrahydrofuran (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 48 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 12.9 mg, or 35%.

[0058] Example 5

[0059]

[0060] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyanophenyl)acrylamide (0.2 mmol, 37.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and triethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 4.44 mg, representing a yield of 13%.

[0061] Example 6

[0062]

[0063] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-fluorophenyl)acrylamide (0.2 mmol, 40.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-6-fluoro-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 24.7 mg, or 60%.

[0064] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.47-7.11(m,3H),4.39(s,2H),3.73(s,3H),2.18(s,3H). 13 C NMR (101MHz, CDCl3) δ162.72,158.80,156.41,144.94,135.27,117.47,117. 24,116.16,116.08,115.72,115.64,107.05,106.81,104.88,29.85,10.64.

[0065] Example 7

[0066]

[0067] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-chlorophenyl)acrylamide (0.2 mmol, 44.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-6-chloro-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 25.7 mg, representing a yield of 58%.

[0068] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.55(d,J=2.3Hz,1H),7.46(dd,J=9.0,2.3Hz,1H),7.27(d,J=9.0Hz,1H),4.51(s,2H),3.69(s,3H),2.16(s,3H). 13 C NMR (101MHz, CDCl3) δ162.73,144.89,137.21,129.65,126.81,120.94,115.96,115.94,104.53,29.73,10.60.

[0069] Example 8

[0070]

[0071] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-bromophenyl)acrylamide (0.2 mmol, 53.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-6-bromo-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 21.4 mg, or 40%.

[0072] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.67(d,J=2.2Hz,1H),7.56(dd,J=9.0,2.2Hz,1H),7.18(d,J=9.0Hz,1H),4.51(s,2H),3.66(s,3H),2.13(s,3H). 13 C NMR (101MHz, CDCl3) δ162.69,144.84,137.56,132.40,123.95,116.40,116.22,114.12,104.45,29.70,10.60.

[0073] Example 9

[0074]

[0075] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-methylphenyl)acrylamide (0.2 mmol, 40.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3,6-trimethylquinoline-2(1H)-one. The substance was a white solid, with a yield of 22.2 mg, representing a yield of 55%.

[0076] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.37-7.29(m,2H),7.25-7.18(m,1H),4.47(s,2H),3.68(s,3H),2.42(s,3H),2.13(s,3H). 13 C NMR (101MHz, CDCl3) δ162.87,145.74,136.65,130.89,130.60,121.06,114.58,114.44,103.26,29.49,20.85,10.46.

[0077] Example 10

[0078]

[0079] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-methoxyphenyl)acrylamide (0.2 mmol, 43.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-6-methoxy-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 21.4 mg, representing a yield of 49%.

[0080] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.24(s,1H),7.11(dd,J=9.2,2.7Hz,1H),6.96(d,J=2.8Hz,1H),4.36(s,2H),3.84(s,3H),3.66(s,3H),2.12(s,3H). 13 C NMR (101MHz, CDCl3) δ162.60,154.29,145.23,133.35,117.39,115.85,115.49,104.56,104.35,55.84,29.68,10.63.

[0081] Example 11

[0082]

[0083] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-trifluoromethylphenyl)acrylamide (0.2 mmol, 50.8 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-6-trifluoromethyl-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 32.2 mg, or 63%.

[0084] Characterization data: 1H NMR (400MHz, CDCl3) δ7.80(s,J=2.0Hz,1H),7.73(dd,J=8.8,2.0Hz,1H),7.42(d,J=8.8Hz,1H),4.53(s,2H),3.72(s,3H),2.16(s,3H). 13 C NMR (101MHz, CDCl3) δ162.95,145.36,140.73,126.22,123.46,123.13,118.77,114.95,114.53,104.75,29.84,10.55.

[0085] Example 12

[0086]

[0087] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-3-fluorophenyl)acrylamide (0.2 mmol, 40.8 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-5-fluoro-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 24.3 mg, representing a yield of 59%.

[0088] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.45-7.35(m,J=8.3,6.2Hz,1H),7.10(d,J=8.6Hz,1H),6.94-6.77(m,1H),5.07(s,2H),3.66(s,3H),2.09(s,3H). 13 C NMR (101MHz, CDCl3) δ162.39,158.72,145.49,140.53,129.56,110.62,107.94,104.47,102.30,30.23,9.95.

[0089] Example 13

[0090]

[0091] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-3-chlorophenyl)acrylamide (0.2 mmol, 44.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-5-chloro-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 22.2 mg, representing a yield of 51%.

[0092] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.35(t,J=8.1Hz,1H),7.29-7.26(m,J=2.2Hz,1H),7.18(d,J=7.8,1.3Hz,1H),5.58(s,2H),3.69(s,3H),2.12(s,3H). 13 C NMR (101MHz, CDCl3) δ161.96,146.79,141.20,129.86,129.02,124.79,114.12,112.21,103.61,30.58,10.66.

[0093] Example 14

[0094]

[0095] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-3-chlorophenyl)acrylamide (0.2 mmol, 40.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-5-chloro-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 20.6 mg, representing a yield of 51%.

[0096] Characterization data: 1H NMR (400MHz, CDCl3) δ7.42(d,J=8.2Hz,1H),7.13(s,1H),7.02(d,J=8.2,1.5Hz,1H),4.44(s,2H),3.68(s,3H),2.48(s,3H),2.12(s,3H). 13 C NMR (101MHz, CDCl3) δ163.16,145.88,140.21,138.78,122.53,120.95,114.82,112.48,102.53,29.51,21.97,10.38.

[0097] Example 15

[0098]

[0099] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4,5-dimethoxyphenyl)acrylamide (0.2 mmol, 49.2 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (PE:EA = 1:1) to obtain the corresponding 4-amino-6,7-dimethoxy-1,3-dimethylquinoline-2(1H)-one. This substance was a white solid, with a yield of 21.3 mg, or 43%.

[0100] Characterization data: 1 H NMR (400MHz, DMSO-d6) δ7.48(s,1H),6.86(s,1H),6.09(s,2H),3.90(s,3H),3.84(s,3H),3.57(s,3H),1.96(s,3H). 13 C NMR (101MHz, DMSO-d6) δ162.61,151.39,148.05,144.53,134.46,107.68,105.82,98.56,98.19,56.80,56.27,29.87,11.44.

[0101] Example 16

[0102]

[0103] Photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-(thiophen-2-yl)phenyl)acrylamide (0.2 mmol, 52.0 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then acetonitrile (4 mL) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm away from a 15 W blue LED light source and reacted at 25 °C for 24 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the product was purified by column chromatography (eluting PE / EA = 1:1) to obtain the corresponding 4-amino-1,3-dimethyl-6-(thiophen-2-yl)quinoline-2(1H)-one. The substance was a white solid, with a yield of 20.0 mg, representing a yield of 39%.

[0104] Characterization data: 1 H NMR (400MHz, CDCl3) δ7.76(dd,J=8.8,2.0Hz,1H),7.71(d,J=2.0Hz,1H),7.35(d,J=8.8Hz,1H),7.32(dd, J=3.6,1.2Hz,1H),7.31-7.28(m,1H),7.10(dd,J=5.1,3.6Hz,1H),4.49(s,2H),3.72(s,3H),2.16(s,3H). 13 C NMR (101MHz, CDCl3) δ162.82,145.87,143.42,137.96,128.20,127.84,127.78,124.70,123.14,118.48,115.09,115.04,103.73,29.67,10.60.

Claims

1. A method for preparing 4-amino-2-quinolinone compounds by cyclization of 1,6-alkenenitrile under visible light catalysis, characterized in that: The method comprises: Under an inert atmosphere, a copper-based photosensitizer, a 1,6-alkenenitrile compound shown in formula I, an amine and a solvent are mixed, and reacted at 15 to 35° C. for 12 to 48 hours under light, and then the reaction solution is post-treated to obtain a 4-amino-2-quinolinone compound shown in formula II; in, The amine is selected from one of N,N-diisopropylethylamine and triethylamine; The solvent is selected from one of toluene, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, methanol, tetrahydrofuran, and ethanol; The copper-based photosensitizer is selected from at least one of PS1 to PS6; the structural formula of the copper-based photosensitizer PS1 to PS6 is as follows: The reaction formula is as follows: In Formula I or Formula II, R1 is H, methyl, methoxy, fluorine, chlorine, bromine, trifluoromethyl or thienyl.

2. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The molar ratio of the 1,6-alkenenitrile compound shown in formula I, the amine, and the copper-based photosensitizer is 1:1.5-2.5:0.025-0.

1.

3. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The amine is N,N-diisopropylethylamine.

4. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The solvent was acetonitrile.

5. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The volume molar ratio of the solvent to the 1,6-alkene nitrile compound shown in formula I is 15-25:1, ml / mmol.

6. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The lighting uses the following light sources: 15W blue LED, 15W green LED, 15W white LED.

7. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The copper-based photosensitizer was PS1.

8. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile as claimed in claim 1, characterized in that: The post-treatment method is as follows: the reaction solution is vacuum concentrated to 10-25% of the original volume, then loaded onto a silica column, and purified using petroleum ether:ethyl acetate in a volume ratio of 1:1 as an elution reagent at an elution rate of 2 ml / min, and the target product eluate is obtained by TLC detection, the eluate is combined, and the solvent is removed by reduced pressure distillation to obtain a 4-amino-2-quinolinone compound shown in formula II.

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