Method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile

Abstract

The present invention discloses a method for preparing a 4-amino-2-quinolinone compound by cyclizing 1,6-alkenenitrile under visible light catalysis. The method comprises: mixing a copper-based photosensitizer, a 1,6-alkenenitrile compound represented by Formula I, an amine, and a solvent under an inert atmosphere; reacting the mixture under light at 15 to 35° C. for 12 to 48 hours; and then post-treating the reaction solution to obtain a 4-amino-2-quinolinone compound represented by Formula II. The method is mild, efficient, green, and suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to a method for preparing 4-amino-2-quinolinone compounds by cyclizing 1,6-alkenenitrile catalyzed by visible light. Background Art

[0002] 2-Quinolinone is an important heterocyclic scaffold found in many natural products, bioactive molecules, and pharmaceuticals. It is also a crucial synthetic intermediate for building complex molecules. For example, 3-O-Methylviridicatin is used as an anti-inflammatory drug and HIV inhibitor, while Laquinimod and Tipfarnib exhibit anti-cancer properties. Herbicides, which have 2-quinolinone as their core structure, are also widely used in the pesticide field. The molecular structures of representative drugs and pesticides containing 2-quinolinone structures are as follows:

[0003]

[0004] Based on this, over the past few decades, researchers have developed different strategies for synthesizing 2-quinolinone compounds, among which solvent-free heating condensation (see Tetrahedron Lett., 2020, 61, 151778.) and acid-catalyzed intramolecular Friedel-Crafts cyclization (see Tetrahedron Lett., 2020, 61, 152535.) provide effective strategies for the preparation of 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-quinolinone all have more or less disadvantages such as harsh reaction conditions, difficulty in obtaining catalysts, and cumbersome operations.

[0005] In 2021, Li Yamin's research group achieved the synthesis of 4-amino-2-quinolinone compounds by the cyclization of 1,6-enenitrile catalyzed by peroxide (TBHP) (see Org Lett., 2021, 23, 6158-6163), which also became a new method for synthesizing 2-quinolinone compounds. Although this method solves some of the shortcomings of the above methods, there are still limitations such as severe reaction conditions, insufficient safety of peroxide as a catalyst and unsuitable for mass 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] In view of the limitations of current synthesis technology, the present invention provides a method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile. The method is mild, efficient, green and suitable for large-scale production.

[0007] The technical solutions of the present invention are as follows:

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

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

[0010] in,

[0011] The molar ratio of the 1,6-alkenenitrile compound represented by formula I, the amine, and the copper-based photosensitizer is 1:1.5-2.5:0.025-0.1, preferably 1:2:0.05;

[0012] The amine is selected from one of 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, preferably acetonitrile;

[0014] The volume molar ratio of the solvent to the 1,6-alkenenitrile compound represented by 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, preferably 15W blue LED;

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

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

[0018]

[0019] During the reaction, TLC monitoring was performed using a developing solvent of petroleum ether:ethyl acetate in a volume ratio of 1:1. After the reaction was completed, the specific post-treatment method was as follows: the reaction solution was concentrated in vacuo to 10-25% of the original volume, and then loaded onto a silica column (preferably with a column height of 300 mm and a diameter of 30 mm) and purified using a petroleum ether:ethyl acetate in a volume ratio of 1:1 at an elution rate of 2 ml / min. The target product eluate was obtained by TLC detection, and the eluates were combined and the solvent was removed by distillation under reduced pressure to obtain a 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 thienyl, preferably H, methyl, methoxy, fluorine, chlorine, bromine or trifluoromethyl;

[0024] Specifically, the 1,6-alkenenitrile compound is one of the following:

[0025]

[0026] The raw material 1,6-alkene nitrile compound used in the present invention can be prepared according to the method disclosed in existing literature.

[0027] The technical principles of the present invention include:

[0028] Photocatalytic synthesis is one of our group's research areas. Light reactions require a certain potential, and the catalyst must match this potential for the reaction to occur. The structure of the copper-based photosensitizer in this invention has a certain influence on the reaction. By modifying the groups on the photosensitizer's N ligand, the photosensitizer's potential can be altered, making it more suitable for the reaction.

[0029] The present invention uses N,N-diisopropylethylamine and a simple and easy-to-synthesize PS1 photosensitizer in the reaction of preparing 4-amino-2-quinolinone compounds through cyclization of 1,6-alkenenitrile, thereby increasing the yield of the reaction and greatly improving the convenience of the reaction.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] 1) The 1,6-alkenenitrile raw material used in the present invention can be obtained by combining cheap and variable fragments through simple chemical reactions. Therefore, the raw material is simple and easy to obtain, and the functional groups are variable.

[0032] 2) The present invention obtains 4-amino-2-quinolinone compounds through photooxidation-reduction reaction, with mild reaction conditions, good substrate universality, and high reaction efficiency.

[0033] 3) The present invention uses a cheap copper complex as a photosensitizer to replace peroxide as a catalyst for synthesizing 4-amino-2-quinolinone compounds, which has high reaction safety and good economic efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 : The reaction mechanism involved in the photocatalytic reaction of the present invention. DETAILED DESCRIPTION

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

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

[0037]

[0038] To a three-necked flask equipped with a magnetic rod, o-aminobenzonitrile compound S1 (5 mmol, 1.0 equiv.) and sodium bicarbonate (6 mmol, 1.2 equiv.) were added, and the argon gas was replaced three times. Then, 2-butanone (15 ml) was added to the apparatus, and acryloyl chloride (5.5 mmol, 1.1 equiv.) was slowly added dropwise. 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, and then the mixture was 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] To a three-necked flask equipped with a magnetic rod, product S2 (3 mmol, 1.0 equiv.) and potassium carbonate (6 mmol, 2 equiv.) were added. The argon atmosphere was purged three times, and then acetone (15 ml) and iodomethane (4.5 mmol, 1.5 equiv.) were added. The reaction was allowed to proceed at 40°C for 16 h. After completion of the reaction, the mixture was extracted with dichloromethane (3 x 30 ml). The organic phases were combined and the solvent was removed by rotary evaporation. Column chromatography afforded product S3.

[0040] The synthesis method of the photosensitizer PS1 used in the following examples is as follows:

[0041] Synthesis of photosensitizer PS1:

[0042]

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

[0044] Synthesis Example of 4-amino-2-quinolinone compounds:

[0045] Example 1

[0046]

[0047] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The product was obtained as a white solid in a yield of 22.2 mg (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] To a dry Schlenk reaction tube, add the 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.). The atmosphere 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 from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, TLC analysis revealed no product, resulting in a 0% yield.

[0052] Example 3

[0053]

[0054] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 48 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The product was obtained as a white solid in a yield of 22.6 mg (61%).

[0055] Example 4

[0056]

[0057] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and tetrahydrofuran (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 48 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The product was obtained as a white solid in a yield of 12.9 mg (35%).

[0058] Example 5

[0059]

[0060] To a dry Schlenk reaction tube, add 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.). The atmosphere was purged with argon three times, followed by the addition of acetonitrile (4 ml) and triethylamine (0.4 mmol, 2.0 equiv.). The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The product was obtained as a white solid in a yield of 4.44 mg (13%).

[0061] Example 6

[0062]

[0063] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6-fluoro-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 24.7 mg, a 60% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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.). The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6-chloro-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 25.7 mg, a 58% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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). The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6-bromo-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 21.4 mg, a 40% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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.). The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3,6-trimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 22.2 mg, a 55% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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). The atmosphere 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 from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6-methoxy-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 21.4 mg, a 49% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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). The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6-trifluoromethyl-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent PE / EA = 1:1) to obtain the corresponding product. The yield was 32.2 mg, a 63% yield, as a white solid.

[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] To a dry Schlenk reaction tube, add 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). The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-5-fluoro-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 24.3 mg, a 59% yield, as a white solid.

[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] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-5-chloro-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 22.2 mg, a 51% yield, as a white solid.

[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] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-5-chloro-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (eluent: PE / EA = 1:1) to obtain the corresponding product. The yield was 20.6 mg, a 51% yield, as a white solid.

[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] To a dry Schlenk reaction tube, 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. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-6,7-dimethoxy-1,3-dimethylquinolin-2(1H)-one was purified by column chromatography (PE:EA = 1:1). The product was obtained as a white solid in a yield of 21.3 mg (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] To a dry Schlenk reaction tube, photosensitizer PS1 (0.01 mmol, 10 mg, 5 mol%) and N-methyl-N-(2-cyano-4-(thien-2-yl)phenyl)acrylamide (0.2 mmol, 52.0 mg, 1.0 equiv.) were added. The atmosphere was purged with argon three times, and acetonitrile (4 ml) and N,N-diisopropylethylamine (0.4 mmol, 2.0 equiv.) were added. The reaction tube was placed 3 cm from a 15 W blue LED light source and allowed to react at 25°C for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation, and the corresponding 4-amino-1,3-dimethyl-6-(thien-2-yl)quinolin-2(1H)-one was purified by column chromatography (eluent PE / EA = 1:1) to obtain the corresponding product. The product was obtained as a white solid in a yield of 20.0 mg (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 visible light catalytic cyclization of 1,6-alkenenitrile, characterized in that: The method comprises: Under an inert atmosphere, a copper-based photosensitizer, a 1,6-alkenenitrile compound of Formula I, an amine, and a solvent are mixed and reacted under light at 15-35°C for 12-48 hours. The reaction solution is then post-treated to obtain a 4-amino-2-quinolinone compound of Formula II. in, The amine is N,N-diisopropylethylamine; The solvent was acetonitrile; The lighting uses 15W blue LED; The copper-based photosensitizer is PS1, and its structural formula 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 according to claim 1, characterized in that: The molar ratio of the 1,6-alkenenitrile compound represented by 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 according to claim 1, characterized in that: The volume molar ratio of the solvent to the 1,6-alkenenitrile compound represented by formula I is 15-25:1, ml / mmol.

4. The method for preparing 4-amino-2-quinolinone compounds by visible light catalytic cyclization of 1,6-alkenenitrile according to 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. The target product eluate is obtained by TLC detection, the eluates are combined, and the solvent is removed by distillation under reduced pressure to obtain a 4-amino-2-quinolinone compound represented by Formula II.

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