Synthesis method of carboxyl-substituted quinoline-2, 4-diketone or ester-substituted phenanthridine compound

Abstract

The invention relates to a synthesis method of a carboxyl-substituted quinoline-2, 4-diketone or ester-substituted phenanthridine compound, and discloses a method for synthesizing a carboxyl-substituted quinoline-2, 4-diketone or ester-substituted phenanthridine compound by taking N-(2-cyanoaryl)-N-methacrylamide as a substrate, sodium formate as a C1 source and alkali as an additive under visible light conditions in the presence of a hydrogen atom transfer agent and a photocatalyst. And the carboxylation tandem cyclization reaction of the N-(2-cyano aryl)-N-methacrylamide is realized. According to the reaction, the carboxyl-substituted quinoline-2, 4-diketone compound or the ester-substituted phenanthridine compound is synthesized at excellent yield under the conditions of room temperature and visible light. The method has the advantages of mild reaction conditions, good substrate compatibility, simple operation, cheap and easily available raw materials, simple preparation, stable structure and the like.

Description

Technical Field

[0001] The present invention discloses a tandem cyclization reaction using N-(2-cyanoaryl)-N-alkylacrylamide as a substrate under environmentally friendly visible light conditions. This method provides a convenient pathway for the synthesis of carboxyl-substituted quinoline-2,4-diones. Using formate as a Cl source, potassium phosphate as a base, DABCO as a hydrogen atom transfer agent, and 4CzIPN as a photocatalyst, the tandem cyclization reaction is performed with a wide range of substrates. Advantages of the present invention include mild conditions, a green reaction without the need for transition metal catalysts, and simple operation; readily available and inexpensive raw materials, a broad range of sources, simple preparation, and a stable structure. Background Art

[0002] N-heterocyclic compounds are unique scaffolds in organic and medicinal chemistry. They are not only present in a variety of biologically active molecules, but also are important synthons that can be transformed into a series of valuable structures (a) T. Henkel, RMB Brunne, H. Müller, F. Reichel, Angew. Chem. Int. Ed. 1999, 38, 643-647; b) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 2, 284-287. Moreover, almost half of the top 200 marketed drugs contain nitrogen-containing heterocycles (NA McGrath, M. Brichacek, JT Njardarson, J. Chem. Educ. 2010, 87, 1348-1349). Therefore, the efficient synthesis of these molecules is one of the most important tasks of synthetic chemists, and people have made great efforts for this over the past century (a) AR Katritzky, C W Rees, Comprehensive Heterocyclic Chemistry, Academic Press: New York, 1984; b) C. Cabrele, O. Reiser, J. Org. Chem. 2016, 81, 10109-10125; c) GN Papadopoulos, MG Kokotou, N. Spiliopoulou, NF Nikitas, E. Voutyritsa, DIT Zaras, N. Kaplaneris, CG Kokotos, ChemSusChem. 2020, 13, 5934-5944; d) Q.-W. Gui, B.-B. Wang, S. Zhu, F.-L. Li, M.-X. Zhu, M. Yi, J.-L. Yu, Z.-L. Wu, W.-M. He, Green Chem. 2021, 23, 4430-4434; e) G. N. Papadopoulos, M. G. Kokotou, N. Spiliopoulou, N. F. Nikitas, E. Voutyritsa, D. I. Tzaras, N. Kaplaneris, C. G. Kokotos, Chem Sus Chem 2020, 13, 5934-5944.) In recent decades, free radical cascade reactions have become a versatile tool for preparing various functional molecules.This synthetic strategy will open up new avenues for the rapid accumulation of molecular complexity (a) S. Tang, Y.-L. Deng, J. Li, W.-X. Wang, Y.-C. Wang, Z.-Z. Li, L. Yuan, S.-L. Chen, R.-L. Sheng, Chem. Commun. 2016, 52, 4470-4473; b) J. Yu, H.-X. Sheng, S.-W. Wang, Z.-H. Xu, S. Tang, S.-L. Chen, Chem. Commun. 2019, 55, 4578-4581; c) G. Zhang, Y. Liu, J.-B. Zhao, Y. Li, Q. Zhang, Sci. China Chem.2019,62,1476-149;d)X.-X.Wu,Z.-G.Ma,T.-T.Feng,C.Zhu,Chem.Soc.Rev.2021,50 ,11577-11613; e)S.Tang,Y.-L.Deng,J.Li,W.-X.Wang,Y.-C.Wang,Z.-Z.Li,L.Yuan,S.-L .Chen,R.-L.Sheng,Chem.Commun.2016,52,4470-4473; f)Y.-L.Deng,S.Tang,G.-L.Ding, M.-W. Wang, J. Li, Z.-Z. Li, L. Yuan, R.-L. Sheng, Org. Biomol. Chem. 2016, 14, 9348-9353.). Since cyano group is a valuable and readily available functional group for preparing various functional groups, its application as a radical acceptor in cascade reactions has recently provided multiple opportunities for conveniently constructing various important carbocyclic and heterocyclic rings (a) E. Voutyritsa, I. Triandafillidi, CG Kokotos, ChemCatChem 2018, 10, 2466-2470; b) K. Sun, Q.-Y. Lv, Y.-W. Lin, B. Yu, W.-M. He, Org. Chem. Front. 2021, 8, 445-465; c) F. Zhao, S. Guo, Y. Zhang, T. Sun, B. Yang, Y. Ye, K. Sun, Org. Chem. Front. 2021, 8, 6895-6900.). The present invention uses cheap and readily available N-(2-cyanoaryl)-N-alkylacrylamide compounds as raw materials under visible light conditions to efficiently synthesize carboxyl-substituted quinoline-2,4-diones or ester-substituted phenanthridines. The reaction is simple to operate, environmentally friendly, and can be carried out at room temperature without the need for transition metals. Summary of the Invention

[0003] The present invention aims to provide a method for preparing carboxyl-substituted quinoline-2,4-diones or ester-substituted phenanthridines by a carboxylation tandem cyclization reaction using readily available raw materials, simple operation, mild reaction conditions, and environmentally friendly methods using inexpensive and readily available 4CzIPN as a photocatalyst, potassium phosphate as a base, DABCO as a hydrogen atom transfer agent (HAT), and dimethyl sulfoxide as a solvent. To achieve the above objectives, the present invention provides the following technical solutions:

[0004] Under visible light conditions, N-(2-cyanoaryl)-N-alkylacrylamides undergo a tandem cyclization reaction at room temperature (Equation 1). Following the reaction, the products are isolated and characterized using conventional purification methods to yield the corresponding carboxyl-substituted quinoline-2,4-diones or ester-substituted phenanthridines.

[0005] The structures of carboxyl-substituted quinoline-2,4-dione compounds or ester-substituted phenanthridine compounds are as follows:

[0006]

[0007] Substituent R 1 is one or more of H, an alkyl group having 1 to 4 carbon atoms, an alkoxy group, a phenyl group, an ester group, and a thiomethyl group; the substituent R 2 is one or both of an alkyl group or a benzyl group having 1 to 4 carbon atoms; the substituent R 3 It is one or both of an alkyl group or a cycloalkyl group having 1 to 2 carbon atoms.

[0008] Wherein, the reaction process is shown in the following reaction formula:

[0009]

[0010] As shown in the above reaction formula, the present invention uses blue light as a light source and N-(2-cyanoaryl)-N-alkyl acrylamide (I) as a substrate to achieve visible light-induced tandem cyclization reaction at room temperature to generate carboxyl-substituted quinoline-2,4-diones (II) or ester-substituted phenanthridines (III).

[0011] In the present invention, the reaction is carried out under irradiation of white light (6500K), purple light (400-405nm), blue light (460-465nm), green light (525-530nm) or red light (700-705nm), with 18W blue light (460-465nm) being optimal, and the reaction light source is 460-465nm blue light.

[0012] In the present invention, in the reaction, the solvent is one or more of dichloromethane, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide, preferably dimethyl sulfoxide, and 0.5-3 mL of solvent is added for every 0.1 mmol of N-(2-cyanoaryl)-N-methylacrylamide, and the optimal amount of solvent is 2 mL.

[0013] In the present invention, the reaction is carried out in the presence of a base, which is any one or two of sodium carbonate, potassium carbonate, cesium carbonate, potassium tert-butoxide, potassium phosphate, and 1,8-diazacyclo[5,4,0]undecene-7 (DBU), preferably potassium phosphate; the molar concentration of the base in the solvent is 0.05-0.15M, preferably 0.1-0.15M, and most preferably 0.1M.

[0014] In the present invention, the reaction is carried out in the presence of a photocatalyst, and the photocatalyst is any one or more of fac-Ir(ppy)3 (Shanghai Bide Pharmaceutical Technology Co., Ltd.), 4CzIPN, 4CzIPN-CH3, 4CzIPN-tBu, DCA, and Ru(bpy)Cl2·6H2O. The preferred photocatalyst is 4CzIPN. The molar concentration of the photocatalyst in the solvent is preferably 0.0005-0.0020M, and the optimal concentration is 0.0015M.

[0015] In the present invention, the reaction is carried out in the presence of a hydrogen atom transfer agent (HAT), which is any one or more of p-MePhSH, triethylenediamine (DABCO), quinine, p-BuPhSH, nBuSH, and iPr3SiSH. The preferred hydrogen atom transfer agent (HAT) is DABCO. The molar concentration of the hydrogen atom transfer agent (HAT) in the solvent is preferably 0.0005-0.005 M, and most preferably 0.0025 M.

[0016] In the present invention, the formate is any one or more of sodium formate, potassium formate, and cesium formate, and the preferred formate is sodium formate. The molar concentration of sodium formate in the solvent is preferably 0.5-10M, and the most preferred is 2.5M.

[0017] In the present invention, the reaction time is 12-36 hours, preferably 24 hours, the reaction temperature under visible light is 25-80°C, and the optimal reaction temperature under visible light is 25-35°C.

[0018] The building-up reaction of the present invention comprises the following steps:

[0019] Synthesis of N-(2-cyanophenyl)-N-methylacrylamide:

[0020]

[0021] According to a previous preparation report (Org. Chem. Front., 2024, 11, 4436-4441), a 100 mL round-bottom flask equipped with a magnetic stir bar was charged with 2-aminobenzonitrile (1.18 g, 10 mmol, 1.0 equiv.), anhydrous triethylamine (1.52 g, 15 mmol, 1.5 equiv.), and DCM (40 mL), then cooled to 0°C in an ice-water bath. Methacryloyl chloride (1.14 g, 11 mmol, 1.1 equiv.) was slowly added to the solution at 0°C, followed by stirring at room temperature for 12 hours. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography on silica gel (1:20 to 1:5 EtOAc:PE) to afford N-(2-cyanophenyl)methacrylamide (1.67 g, 9 mmol, 90%) as a white solid.

[0022] To a solution of N-(2-cyanophenyl)methacrylamide (1.67 g, 9 mmol) in THF (30.0 mL) at 0°C was added a magnetic stir bar and 60% NaH (540 mg, 13.5 mmol, 1.5 equiv.) and stirred for 30 minutes. Methyl iodide (1.92 g, 13.5 mmol) was then added and the reaction was warmed to room temperature. After stirring for 8 hours, the reaction was quenched with water and the aqueous layer was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (1:10 to 1:3 EtOAc:PE) to afford 1aN-(2-cyanophenyl)-N-methylacrylamide (1.40 g, 7 mmol, 78%) as a yellow solid. Most substrate preparations followed the reaction pathway of 1a.

[0023]

[0024] According to a previous preparation report (Org. Chem. Front., 2023, 10, 3995), 2-bromo-6-fluorobenzonitrile A (20.0 mmol, 1.0 equiv.), MeNH2·HCl (30.0 mmol, 1.5 equiv.), and NaOH (30.0 mmol, 1.5 equiv.) were added to a 100 mL pressure bottle equipped with a magnetic stir bar. The mixture was stirred in CH3CN (40 mL) at 80°C under air for 12 h. After completion of the reaction, the mixture was cooled to room temperature, extracted with ethyl acetate (100 × 3 mL), and washed with saturated brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to obtain intermediate B.

[0025] To a 100 mL pressure bottle equipped with a magnetic stir bar, substituted phenylboronic acid (15 mmol, 1.5 equiv.), PdCl2(PPh3)2 (0.3 mmol, 0.02 equiv.), and Cs2CO3 (42.0 mmol, 2.8 equiv.) were added, along with MeCN (150 mL) and H2O (7.5 mL), respectively. The reaction mixture was stirred at 80°C under a nitrogen atmosphere for 12 h. After completion, the mixture was cooled to room temperature and extracted with ethyl acetate (100 x 3 mL). The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford crude product C, which was not further purified.

[0026] Compound C (10 mmol) and triethylamine (20 mmol, 2.0 equiv.) obtained above were dissolved in DCM (24 mL) and the corresponding methacryloyl chloride (1.5 equiv.) was added dropwise at 0°C. The reaction mixture was stirred at 0°C overnight. After completion of the reaction, the resulting solution was extracted with DCM (30 × 3 mL). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by column chromatography on silica gel using petroleum ether / ethyl acetate (20:1 to 10:1) as the eluent afforded the desired substrate 1. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The following are the hydrogen and carbon nuclear magnetic spectra of the nuclear magnetic resonance instrument of Example 1.

[0028] Figure 2 The following are the hydrogen and carbon nuclear magnetic resonance spectra of Example 7.

[0029] Figure 3 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 8.

[0030] Figure 4 The following are the hydrogen and carbon nuclear magnetic resonance spectra of Example 9.

[0031] Figure 5 The following are the hydrogen and carbon nuclear magnetic resonance spectra of Example 10.

[0032] Figure 6 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 11.

[0033] Figure 7 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 12.

[0034] Figure 8 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 13.

[0035] Figure 9 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 14.

[0036] Figure 10 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 17.

[0037] Figure 11 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 18.

[0038] Figure 12 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 20.

[0039] Figure 13 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 25.

[0040] Figure 14 These are the hydrogen and carbon nuclear magnetic resonance spectra of Example 26.

[0041] Figure 15 This is the NMR spectrum of the NMR instrument 3a in the application example. DETAILED DESCRIPTION

[0042] The present invention is further described in detail with reference to the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention, and are protected by the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products. The purity of the product is identified by measuring nuclear magnetic resonance.

[0043] Example 1:

[0044]

[0045] Such as the synthesis of N-methacryloylbenzamide:

[0046] According to the previous preparation literature report (Org. Chem. Front., 2024, 11, 4436-4441), compound (R in Example 1) was prepared in a 100 mL round-bottom flask. 1 The substituents are H, R 2To the mixture was added 2-aminobenzonitrile (1.18 g, 10 mmol, 1.0 equiv.), anhydrous triethylamine (1.52 g, 15 mmol, 1.5 equiv.), and DCM (40 mL), followed by cooling to 0°C in an ice-water bath. Methacryloyl chloride (1.14 g, 11 mmol, 1.1 equiv.) was slowly added to the solution at 0°C, followed by stirring at room temperature for 12 hours. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography on silica gel (1:20 to 1:5 EtOAc:PE) to afford N-(2-cyanophenyl)methacrylamide (1.67 g, 9 mmol, 90%) as a white solid.

[0047] To a solution of N-(2-cyanophenyl)methacrylamide (1.67 g, 9 mmol) in THF (30.0 mL) at 0°C was added a magnetic stir bar and 60% NaH (540 mg, 13.5 mmol, 1.5 equiv) and stirred for 30 minutes. Methyl iodide (1.92 g, 13.5 mmol) was then added and the reaction was warmed to room temperature. After stirring for 8 hours, the reaction was quenched with water and the aqueous layer was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (1:10 to 1:3 EtOAc:PE) to afford 1aN-(2-cyanophenyl)-N-methylacrylamide (1.40 g, 7 mmol, 78%) as a yellow solid.

[0048] A mixture of 1a (20.0 mg, 0.1 mmol), NaCOOH (34.0 mg, 0.5 mmol), 4CzIPN (1.6 mg, 2 mol%), K3PO4 (42.4 mg, 2.0 equiv.), DABCO (5.6 mg, 0.05 mmol), and DMSO (2 mL) was added to a 10 mL oven-dried quartz tube and irradiated with an 18 W blue LED at room temperature under air (1 atm). After 24 h of reaction, the reaction mixture was acidified with 15 mL of 2M aqueous HCl and extracted with ethyl acetate (EA) at least six times (5 mL x 6). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography (5% AcOH with petroleum ether / ethyl acetate as eluent, 1 / 4 to 1 / 2) to afford the desired product 2a as a colorless solid. The target product 2a is a known compound with a melting point of 155-156°C. Nuclear magnetic resonance spectroscopy further confirmed the target product. The product parameters are (1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2a): known compound. 4Colorless solid (22.23mg, 90%). 1 H NMR (600MHz, CDCl3) δ8.00 (dd, J = 7.9, 1.6Hz, 1H), 7.65-7.59 (m, 1H), 7.20-7.13 (m, 2H), 3.46 (s, 3H), 3.32-3.20 (m, 2H), 1.34 (s, 3H). 13 C NMR (151MHz, CDCl3) δ196.18,176.91,173.44,143.22,136.18,128.52,123.21,119.61,115.06,54.12,39.47,30.08,25.27.

[0049] Example 2

[0050] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in the absence of light. The reaction was stopped and the same post-treatment as above was performed, but the target product 2a was not obtained. This indicates that the reaction cannot proceed in the absence of light.

[0051] Example 3

[0052] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out in the absence of potassium phosphate. The reaction was stopped and the same post-treatment as above was performed, but the target product 2a was not obtained. This suggests that potassium phosphate has a certain effect on the reaction.

[0053] Example 4

[0054] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was performed without the photocatalyst 4CzIPN. The reaction was terminated and the same post-treatment as above was performed, but the target product 2a was not obtained. This indicates that a photocatalyst is a necessary condition.

[0055] Example 5

[0056] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was performed without the hydrogen atom transfer agent triethylenediamine (DABCO). The reaction was terminated and the same post-treatment as above was performed, but the target product 2a was not obtained. This indicates that a hydrogen atom transfer agent is essential.

[0057] Example 6

[0058] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out under heating at 80°C and without light irradiation. The reaction was terminated and the same post-treatment as above was performed, but the target product 2a was not obtained. This indicates that temperature has no effect on the reaction.

[0059] Example 7

[0060]

[0061] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2 The reaction system differed in that 1b (21.4 mg, 0.1 mmol) was added instead of the substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to yield 2b, a white solid. Nuclear magnetic resonance (NMR) analysis confirmed the target product, yielding 2-(1-ethyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2b): New compound. Colorless solid (19.58 mg, 75%). 1 H NMR(600MHz, CDCl3)δ8.01(dd,J=7.7,1.3Hz,1H),7.64-7.59(m,1H),7.16(dd,J=15.5,7 .9Hz,2H),4.29-3.86(m,2H),3.26(q,J=17.7Hz,2H),1.32(s,3H),1.21(t,J=7.1Hz,3H). 13 C NMR (151MHz, CDCl3) δ196.37,177.14,173.08,142.10,136.17,128.85,122.98,119.89,114.94,53.89,39.60,37.42,25.00,12.19.

[0062] Example 8

[0063]

[0064] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2The starting material 1c was obtained from nPr. 1c is a known compound (Org. Chem. Front., 2024, 11, 4436-4441) with a yield of 75%. The reaction system differs in that 1c (22.8 mg, 0.1 mmol) was added instead of the substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to obtain a white solid 2c. The target product 2c was an unknown compound and was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were: 2-(3-methyl-2,4-dioxo-1-propyl-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2c): New compound. Colorless solid (25.58 mg, 93%). 1 H NMR(600MHz, CDCl3) δ8.01(dd,J=7.9,1.7Hz,1H),7.61(ddd,J=8.7,7.4,1.7Hz,1H),7.15(dd,J=7.9,6 .3Hz,2H),4.06-3.89(m,2H),3.37-3.16(m,2H),1.72-1.57(m,2H),1.33(s,3H),0.95(t,J=7.4Hz,3H). 13 C NMR (151MHz, CDCl3) δ196.34,176.89,173.36,142.39,136.09,128.82,122.97,119.86,115.16,54.03,43.88,39.45,25.17,20.30,11.17.

[0065] Example 9

[0066]

[0067] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2The reaction system differed in that 1d (24.2 mg, 0.1 mmol) was added instead of the substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to yield 2d, a white solid. The target product 2d was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were 2-(1-butyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2d), a new compound. A colorless solid (26.89 mg, 93%). 1 H NMR (600MHz, CDCl3) δ8.00 (dd, J=8.0, 1.7Hz, 1H), 7.69-7.52 (m, 1H), 7.19 -7.06(m,2H),4.08-3.93(m,2H),3.37-3.16(m,2H),1.66-1.57(m,2H),1.42-1.34(m,2H),1.32(s,3H),0.93(t,J=7.4Hz,3H). 13 C NMR (151MHz, CDCl3) δ196.32,177.14,173.27,142.37,136.08,128.79,122. 94,119.86,115.13,53.99,42.22,39.47,29.04,25.15,20.08,13.89,13.87.

[0068] Example 10

[0069]

[0070] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2The starting material 1e was obtained from Bn. 1e is a known compound (Org. Chem. Front., 2024, 11, 4436-4441) with a yield of 79%. The reaction system differs in that 1e (27.6 mg, 0.1 mmol) is added instead of the substrate (1a). The reaction is terminated under blue light (465 nm) for 24 hours and then post-processed to obtain a white solid 2e. The target product 2e is an unknown compound and was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters are: 2-(1-benzyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2e): New compound. Colorless solid (29.08 mg, 90%). 1 H NMR (600MHz, CDCl3) δ8.03 (dd, J=7.7, 1.6Hz, 1H), 7.47 (ddd, J=8.7, 7.3, 1.7Hz, 1H), 7.25-7.15 (m, 5H), 7.15-7. 10(m,1H),7.04(d,J=8.4Hz,1H),5.48(d,J=14.3Hz,1H),5.14(d,J=15.3Hz,1H),3.58-3.14(m,2H),1.46(s,3H). 13 C NMR (151MHz, CDCl3) δ196.05,177.60,173.80,142.27,136.09,135.88,129.01 ,128.68,127.45,126.34,123.29,119.88,116.08,54.23,46.04,39.57,25.31.

[0071] Example 11

[0072]

[0073] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2The starting material 1f was obtained from CH2CO2Et. 1f is a known compound (Org. Chem. Front., 2024, 11, 4436-4441) with a yield of 95%. The reaction system differs in that 1f (27.2 mg, 0.1 mmol) is added to the reaction system instead of the reaction substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to obtain a white solid 2f. The target product 2f was an unknown compound and was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters obtained were 2-(1-(2-ethoxy-2-oxoethyl)-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2f): New compound. Colorless solid (14.36 mg, 45%). 1 H NMR (600MHz, CDCl3) δ8.02(dd,J=7.7,1.6Hz,1H),7.58(ddd,J=8.7,7.4,1.7Hz,1H),7.18(dd,J=11.1,3.9Hz,1H),6.90(d,J=8.3Hz,1H),5.2 0(d,J=17.8Hz,1H),4.39(d,J=17.8Hz,1H),4.19(qq,J=10.9,7.1Hz,2H),3.28(dd,J=39.0,17.7Hz,2H),1.39(s,3H),1.21(t,J=7.1Hz,3H). 13 C NMR (151MHz, CDCl3) δ195.64,176.88,173.28,168.28,142.18,136.18,12 8.82,123.54,119.65,114.32,61.94,54.17,44.14,39.12,25.06,14.16.

[0074] Example 12

[0075]

[0076] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the aromatic group of 2-cyanoaniline selected in the preparation of the raw materials is different. 1 4-Me, R 2Me was obtained by adding 1g of the starting material, which is a known compound (Org. Chem. Front., 2024, 11, 4436-4441), with a yield of 75%. The reaction system differs in that 1g (21.4mg, 0.1mmol) of the starting material was added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465nm) for 24 hours and then post-processed to obtain 2g of a white solid. The target product 2g was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The obtained product parameters are 2-(1,3,7-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2g): New compound. Colorless solid (19.58mg, 75%). 1 H NMR (600MHz, CDCl3) δ7.90(d,J=7.8Hz,1H),6.98(d,J=8.3Hz,1H),6.97(s,1H),3.45(s,3H),3.26(q,J=17.7Hz,2H),2.45(s,3H),1.32(s,3H). 13 C NMR (151MHz, CDCl3) δ195.81,176.87,173.74,147.58,143.30,128.58,124.24,117.45,115.55,53.94,39.52,30.02,25.43,22.54.

[0077] Example 13

[0078]

[0079] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the aromatic group of 2-cyanoaniline selected in the preparation of the raw materials is different. 1 6-Me, R 2Me was used to obtain the starting material 1h, a known compound (Org. Chem. Front., 2024, 11, 4436-4441), with a yield of 76%. The reaction system differed in that 1h (21.4 mg, 0.1 mmol) was added instead of the substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to yield 2h, a white solid. The target product 2h was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were: 2-(1,3,5-trimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2h): New compound. Colorless solid (11.75 mg, 45%). 1 H NMR (600MHz, CDCl3) δ7.45 (s, 1H), 7.06 (d, J = 8.3Hz, 1H), 6.99 (d, J = 7.6Hz, 1H), 3.46 (s, 3H), 3.27-3.16 (m, 2H), 2.62 (s, 3H), 1.32 (s, 3H). 13 C NMR (151MHz, CDCl3) δ197.23,176.67,172.85,144.07,142.94,134.23,127.02,118.77,113.27,54.92,38.72,30.78,24.71,22.80.

[0080] Example 14

[0081]

[0082] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the aromatic group of 2-cyanoaniline selected in the preparation of the raw materials is different. 1 4-OMe, R 2Me was used to obtain the starting material 1i, a known compound (Org. Chem. Front., 2024, 11, 4436-4441), with a yield of 70%. The reaction system differed in that 1i (23.0 mg, 0.1 mmol) was added instead of the reaction substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-processed to yield a white solid 2i. The target product 2i was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were: 2-(6-methoxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2i): New compound. Colorless solid (20.78 mg, 75%). 1 H NMR(600MHz, CDCl3) δ7.98(d,J=8.7Hz,1H),6.69(dd,J=8.7,2.0Hz,1H),6.61(d,J =2.0Hz,1H),3.90(s,3H),3.43(s,3H),3.26(dd,J=40.3,17.6Hz,2H),1.33(s,3H). 13 C NMR (151MHz, CDCl3) δ194.74,176.81,173.98,166.05,145.19,130.95,113.49,108.44,101.07,55.89,53.65,39.54,30.03,25.62.

[0083] Example 15

[0084]

[0085] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the aromatic group of 2-cyanoaniline selected in the preparation of the raw materials is different. 1 5-OCF3, R 2The starting material 1j was obtained from Bn. 1j is a known substance (Org. Chem. Front., 2024, 11, 4436-4441) with a yield of 60%. The reaction system differs in that 1j (36.0 mg, 0.1 mmol) is added to the reaction system instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 24 hours and then post-processed to obtain a white solid 2j. The target product 2j is an unknown substance and was further confirmed by nuclear magnetic resonance spectroscopy. The obtained product parameters are 2-(1-benzyl-6-methoxy-3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2j): New compound, White solid (12.28 mg, yield: 40%). 1 H NMR(600MHz, CDCl3) δ7.99(d,J=8.7Hz,1H),7.27-7.13(m,5H),6.64(dd,J=8.7,2.1Hz,1H),6.51(d,J=2.1 Hz,1H),5.44(d,J=14.3Hz,1H),5.11(d,J=15.3Hz,1H),3.74(s,3H),3.39(q,J=17.6Hz,2H),1.45(s,3H). 13 C NMR (151MHz, CDCl3) δ194.63,177.13,174.41,165.87,144.22,136.06,130.98,12 9.07,127.49,126.43,113.68,109.00,101.91,55.71,53.79,46.20,39.63,25.67.

[0086] Example 16

[0087]

[0088] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the aromatic group of 2-cyanoaniline selected in the preparation of the raw materials is different. 1 2OMe, R 2Me was used to obtain the raw material 1k, which is a known substance (Org.Chem.Front., 2024, 11, 4436-4441), with a yield of 65%. The difference in the reaction system is that the raw material added to the reaction system is 1k (26.0 mg, 0.1 mmol) instead of the reaction substrate (1a). The reaction was stopped under blue light (465 nm) for 24 hours and then post-treated to obtain a white solid 2k. The target product 2k was an unknown substance, and the target product was further confirmed by nuclear magnetic resonance detection. The parameters of the obtained product are

[0089] 2-(6,7-dimethoxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetic acid (2k): New compound, White solid (27.63 mg, yield: 90%). 1 H NMR (600MHz, DMSO) δ7.30 (s, 1H), 6.86 (s, 1H), 3.95 (s, 3H), 3.78 (s, 3H), 3.42 (s, 3H), 3.04 (dd, J = 35.5, 17.3Hz, 2H), 1.19 (s, 3H). 13 C NMR (151MHz, DMSO) δ194.57,173.42,172.57,155.54,144.77,139.23,111.25,108.32,99.60,56.29,55.76,52.82,29.72,25.19.

[0090] Example 17

[0091]

[0092] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the protective group of 2-cyanoaniline is different in the preparation of the raw materials. 1 H, R 2The starting material 11 was obtained from H. 11 is a known substance (Org. Chem. Front., 2024, 11, 4436-4441) with a yield of 65%. The reaction system differs in that the starting material 11 (18.6 mg, 0.1 mmol) is added to the reaction system instead of the reaction substrate (1a). The reaction is terminated under blue light (465 nm) for 24 hours and then post-processed to obtain a white solid 21. The target product 21 is an unknown substance. Nuclear magnetic resonance analysis further confirmed the target product. The obtained product parameters are 4-((2-cyanophenyl)amino)-3-methyl-4-oxobutanoic acid (21): New compound, White solid (19.72 mg, yield: 85%). 1 H NMR (600MHz, CDCl3) δ8.31(d,J=8.7Hz,1H),8.16(s,1H),7.57(ddd,J=7.4,4.2,2.8Hz,2H),7.17(t,J=7.6H z,1H),3.16-2.95(m,1H),2.91(dd,J=17.5,9.2Hz,1H),2.54(dd,J=17.5,4.4Hz,1H),1.34(d,J=7.0Hz,3H). 13 C NMR (151MHz, CDCl3) δ176.73,174.09,140.69,134.21,132.48,124.48,122.16,116.43,102.92,38.01,37.86,17.80.

[0093] Example 18

[0094]

[0095] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(m-MePh)Ph, R 2Me was used to obtain the starting material 1m, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 85%. The reaction system differed in that the starting material 1m (29.0 mg, 0.1 mmol) was added to the reaction system under air or nitrogen atmosphere instead of the reaction substrate (1a). The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to obtain a white solid 2m. The target product 2m was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The obtained product parameters were methyl2-(4,6,10-trimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2m): a known compound, white solid (19.14 mg, yield: 55%). 1 H NMR (600MHz, CDCl3) δ8.38(d,J=8.1Hz,1H),8.26(d,J=8.3Hz,1H),7.81(t,J=8.1Hz,1H),7.59(d,J=7.0Hz,1H),7.54-7.50(m, 1H),7.24(d,J=7.8Hz,1H),3.96(d,J=17.1Hz,1H),3.63(s,3H),3.61(d,J=11.1Hz,1H),3.47(s,3H),2.81(s,3H),1.57(s,3H). 13 C NMR (151MHz, CDCl3) δ174.15,172.77,158.19,143.43,139.09,137.54,133.90,131.71,129.7 0,126.25,122.83,120.54,116.47,111.84,110.77,51.72,49.11,42.95,30.49,30.04,18.39.

[0096] Example 19

[0097]

[0098] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(3,5-2MePh)Ph, R 2Me was used to obtain the starting material 1n, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 75%. The reaction system differed in that 1n (30.4 mg, 0.1 mmol) was added instead of the substrate (1m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2n as a white solid. The target product 2n was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl 2-(4,6,8,10-tetramethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2n): a known compound, white solid (14.48 mg, yield: 40%). 1 H NMR (600MHz, CDCl3) δ7.34(d,J=7.6Hz,1H),7.11(s,2H),7.08(s,1H),7.06(d,J=7.6Hz,1H),3.6 9(s,3H),3.53(s,3H),3.08(d,J=16.9Hz,1H),2.90(d,J=16.9Hz,1H),2.39(s,6H),1.40(s,3H). 13 C NMR (151MHz, CDCl3) δ180.27,170.18,146.81,146.61,138.39,138.20,133.21,13 0.46,126.96,125.71,123.67,116.76,52.00,44.30,41.35,28.51,24.44,21.47.

[0099] Example 20

[0100]

[0101] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials, the gas atmosphere is different, and the subsequent treatment is different. 1 3-(4-SMePh)Ph, R 2Me was used to obtain the starting material 1o, a known compound (Org. Chem. Front., 2023, 10, 3995), in a 65% yield. The reaction system differed in that 1o (32.2 mg, 0.1 mmol) was added in place of the substrate (1 m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2o as a white solid. The target product 2o was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl 2-(4,6-dimethyl-9-(methylsulfonyl)-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl) acetate (2o): a known compound, white solid (12.36 mg, yield: 30%). 1 H NMR (600MHz, CDCl3) δ7.50-7.41(m,2H),7.34(d,J=7.6Hz,1H),7.05(d,J=7.6Hz,1H),7.00(d,J=8.7Hz, 2H),3.86(s,3H),3.69(s,3H),3.53(s,3H),3.08(d,J=17.0Hz,1H),2.90(d,J=17.0Hz,1H),1.40(s,3H). 13 C NMR (151MHz, CDCl3) δ180.28,170.24,160.17,146.92,146.00,132.97,130.79,13 0.41,125.81,123.62,116.99,114.16,55.48,52.01,44.29,41.32,28.52,24.46.

[0102] Example 21

[0103]

[0104] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(4-Ph)Ph, R 2Me was used to obtain the starting material 1p, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 85%. The reaction system differed in that 1p (32.2 mg, 0.1 mmol) was added instead of the substrate (1m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2p as a white solid. The target product 2p was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl 2-(4,6-dimethyl-5-oxo-9-phenyl-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl) acetate (2p): a known compound, a white solid (11.20 mg, yield: 32%). 1 H NMR (600MHz, CDCl3) δ7.71(d,J=8.4Hz,2H),7.66(dd,J=8.3,1.2Hz,2H),7.60(d,J=8.4Hz,2H),7.47(t,J=7.7Hz,2H),7.39(d ,J=7.5Hz,2H),7.13(d,J=7.6Hz,1H),3.71(s,3H),3.55(s,3H),3.11(d,J=17.0Hz,1H),2.93(d,J=17.0Hz,1H),1.42(s,3H). 13 C NMR (151MHz, CDCl3) δ180.25,170.24,147.06,145.84,141.69,140.51,137.31,133.56,129.60,12 9.11,129.00,127.78,127.43,127.32,125.89,123.76,116.84,52.04,44.32,41.33,28.56,24.47.

[0105] Example 22

[0106]

[0107] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(4-nPrPh)Ph, R 2Me was used to obtain the starting material 1q, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 85%. The reaction system differed in that the starting material 1q (31.8 mg, 0.1 mmol) was added in place of the substrate (1 m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2q, a white solid. The target product 2q was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl 2-(4,6-dimethyl-5-oxo-9-propyl-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl) acetate (2q): a known compound, a white solid (16.92 mg, yield: 45%). 1 H NMR (600MHz, CDCl3) δ8.42(d,J=8.4Hz,1H),8.23(d,J=8.2Hz,1H),7.89(d,J=1.3Hz ,1H),7.80(t,J=8.1Hz,1H),7.47(dd,J=8.4,1.7Hz,1H),7.21(d,J=7.8Hz,1H),3.9 8(d,J=17.2Hz,1H),3.98(d,J=17.2Hz,1H),3.61(s,3H),3.58(d,J=17.2Hz,1H),3. 47(s,3H),2.89-2.76(m,2H),1.89-1.74(m,2H),1.57(s,3H),1.02(t,J=7.3Hz,3H). 13 C NMR (151MHz, CDCl3) δ174.14,172.73,159.62,145.01,144.10,139.04,133.63,131.80,128.76,127. 76,122.52,121.02,116.07,111.84,110.57,51.75,48.81,42.85,38.12,30.11,30.03,24.56,14.07.

[0108] Example 23

[0109]

[0110] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-[(4-OPh)Ph]Ph, R2 Me was used to obtain the starting material 1r, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 80%. The reaction system differed in that 1r (31.8 mg, 0.1 mmol) was added to the reaction system under air or nitrogen atmosphere instead of the substrate (1m). The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2r as a white solid. The target product 2r was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl2-(4,6-dimethyl-5-oxo-9-phenoxy-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2r): a known compound, white solid (17.04 mg, yield: 40%). 1 H NMR (600MHz, CDCl3) δ8.47(d,J=9.0Hz,1H),8.18(d,J=8.3Hz,1H),7.80(t,J=8.1Hz,1H),7.54(d,J=2.5Hz,1H),7.42(t,J=7.9Hz,2H),7.37(dd, J=8.9,2.6Hz,1H),7.22-7.18(m,2H),7.17-7.13(m,2H),3.91(d,J=17. 2Hz,1H),3.61(s,3H),3.55(d,J=17.2Hz,1H),3.47(s,3H),1.55(s,3H). 13 C NMR (151MHz, CDCl3) δ174.01,172.73,160.59,158.52,156.58,146.29,139.15,133.54,132.10,130.10,12 4.34,124.18,119.97,119.06,118.84,116.10,115.90,111.55,110.43,51.75,48.85,42.78,30.05,30.02.

[0111] Example 24

[0112]

[0113] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(4-naphthyl)Ph, R 2Me was used to obtain the starting material 1s, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 78%. The reaction system differed in that 1s (32.6 mg, 0.1 mmol) was added instead of the substrate (1m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2s as a white solid. The target product 2s was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were methyl 2-(4,6-dimethyl-5-oxo-5,6-dihydro-4H-benzo[b]pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2s): a known compound, a white solid (24.96 mg, yield: 65%). 1 H NMR (600MHz, CDCl3) δ9.04(d,J=8.4Hz,1H),8.75(d,J=8.5Hz,1H),8.00(d,J=9.0Hz,1H),7.99(s,2H),7.83(t,J=8.2Hz,1H),7.70-7.66(m ,1H),7.62(t,J=7.3Hz,1H),7.24(d,J=5.2Hz,1H),3.99(d,J=17.3Hz,1H),3.64(s,3H),3.61(d,J=17.3Hz,1H),3.46(s,3H),1.59(s,3H). 13 C NMR (151MHz, CDCl3) δ173.97,172.72,158.91,144.79,138.90,133.58,133.19,131.53,130.02,129.99,12 8.87,128.33,127.60,126.70,126.31,120.99,119.55,113.40,110.21,51.77,48.60,42.84,30.17,30.07.

[0114] Example 25

[0115]

[0116] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(4-naphthyl)Ph, R 2Me was used to obtain the starting material 1s, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 78%. The reaction system differed in that 1s (32.6 mg, 0.1 mmol) was added instead of the substrate (1m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2t, a white solid. The target product 2t was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were ethyl 2-(4,6-dimethyl-5-oxo-5,6-dihydro-4H-benzo[b]pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2t): a known compound, white solid (24.68 mg, yield: 62%). 1 H NMR (600MHz, CDCl3) δ9.06(d,J=8.4Hz,1H),8.77(d,J=8.5Hz,1H),8.04-8.01(m,1H),8.02(s,2H),7.86(t,J=8.2Hz,1H),7.71(ddd,J=8.4,6.9,1 .4Hz,1H),7.66-7.62(m,1H),3.98(d,J=17.2Hz,1H),3.93-3.83(m,1H), 3.66(s,3H),3.62(d,J=17.2Hz,1H),1.61(s,3H),1.00(t,J=7.1Hz,3H). 13 C NMR (151MHz, CDCl3) δ174.03,172.08,159.05,144.82,138.95,133.57,133.20,131.52,130.04,130.00,128.8 9,128.35,127.61,126.70,126.31,120.96,119.52,113.43,110.16,60.53,48.63,43.30,30.17,30.07,14.04.

[0117] Example 26

[0118]

[0119] The reaction steps and operating conditions are the same as those in Example 1. The difference from Example 1 is that the 3-phenyl group of 2-cyanoaniline is different in the preparation of the raw materials. 1 3-(4-naphthyl)Ph, R 2Me was used to obtain the starting material 1s, a known compound (Org. Chem. Front., 2023, 10, 3995), with a yield of 78%. The reaction system differed in that 1s (32.6 mg, 0.1 mmol) was added instead of the substrate (1m) in an air or nitrogen atmosphere. The reaction was terminated under blue light (465 nm) for 24 hours and then post-esterified to yield 2u as a white solid. The target product 2u was an unknown compound, which was further confirmed by nuclear magnetic resonance spectroscopy. The product parameters were cyclohexyl2-(4,6-dimethyl-5-oxo-5,6-dihydro-4H-benzo[b]pyrido[4,3,2-gh]phenanthridin-6-yl)acetate (2u): a known compound, white solid (14.46 mg, yield: 32%). 1 H NMR(600MHz, CDCl3)δ9.06(d,J=8.4Hz,1H),8.77(d,J=8.5Hz,1H),8.03(dd,J=7.9,0.9Hz,1H), 8.01(s,2H),7.86(t,J=8.2Hz,1H),7.73-7.68(m,1H),7.64(dd,J=10.9,3.9Hz,1H),7.27(d,J= 7.8Hz,1H),4.50-4.41(m,1H),3.94(d,J=17.1Hz,1H),3.66(s,3H),3.63(d,J=17.1Hz,1H),1.6 0(s,3H),1.55-1.49(m,1H),1.46(d,J=3.5Hz,2H),1.34(t,J=11.4Hz,2H),1.17-0.92(m,5H).δ 13 C NMR (151MHz, CDCl3) δ174.02,171.38,159.20,144.84,139.00,133.58,133.21,131.52,130.05,130.02,128.91,128.35,127 .60,126.70,126.31,120.94,119.47,113.42,110.12,72.85,48.72,43.61,31.44,31.28,30.18,30.08,25.34,23.54,23.48.

[0120] Application Examples

[0121]

[0122] In addition, a derivatization experiment was conducted on the target product 2a obtained in Example 1 to further demonstrate the synthetic application of this scheme. Product 2a (0.2 mmol) and TMSN2CH2 (0.4 mmol) were reacted at 0°C in CH3CN (2 mL) for 3 hours. Subsequently, MeNH2 (0.3 mmol) was added and the reaction was continued at 60°C in H2O (2 mL) for 12 hours to obtain the reduced product 3a. Nuclear magnetic resonance spectroscopy confirmed the target product, and the obtained product parameters were 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)-N-methylacetamide (3a): New compound, White solid (23.2 mg, yield: 90%). 1 H NMR (600 MHz, CDCl3) δ 8.07 (dd, J = 7.7, 1.6 Hz, 1H), 7.72-7.55 (m, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.18-7.15 (m, 1H), 5.46 (s, 1H), 3.51 (s, 3H), 3.27 (q, J = 15.8 Hz, 2H), 2.71 (d, J = 4.9 Hz, 3H), 1.35 (s, 3H). Further reference (Bioorg. Med. Chem. 2010, 18, 2872; J. Med. Chem. 2015, 58, 5751; J. Nat. Prod. 1996, 59, 469) can be converted into the corresponding drug molecular skeleton.

[0123] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing a carboxyl-substituted quinoline-2,4-dione or ester-substituted phenanthridine compound, characterized in that: N-(2-cyanoaryl)-N-alkylacrylamide is used as a substrate, formate is used as a C1 source, a photocatalyst is added, and the substrate is induced to synthesize carboxyl-substituted quinoline-2,4-dione compounds or ester-substituted phenanthridine compounds under visible light conditions.

2. The synthesis method according to claim 1, characterized in that: The specific preparation process is as follows: using formate as the C1 source, N-(2-cyanoaryl)-N-methylacrylamide is added to a solvent, a base, a hydrogen atom transfer agent and a photocatalyst are added, and carboxyl-substituted quinoline-2,4-dione compounds or ester-substituted phenanthridine compounds are sequentially generated through visible light-induced reactions.

3. The synthesis method according to claim 1, wherein: The structure of N-(2-cyanoaryl)-N-alkylacrylamide is as follows: The structures of carboxyl-substituted quinoline-2,4-dione compounds or ester-substituted phenanthridine compounds are as follows: Substituent R 1 is one or more of H, an alkyl group having 1 to 4 carbon atoms, an alkoxy group, a phenyl group, an ester group, and a thiomethyl group; the substituent R 2 is one or both of an alkyl group or a benzyl group having 1 to 4 carbon atoms; the substituent R 3 It is one or both of an alkyl group or a cycloalkyl group having 1 to 2 carbon atoms.

4. The synthesis method according to claim 1, wherein: The reaction is carried out under visible light of one or more of 1-18W white light (6500K), 1-18W violet light (400-405nm), 1-18W blue light (460-465nm), 1-18W green light (525-530nm) or 1-18W red light (700-705nm), with 18W blue light (460-465nm) being the best.

5. The synthesis method according to claim 2, wherein: The solvent is one or more of dichloromethane, ethanol, ethyl acetate, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide. The preferred solvent is dimethyl sulfoxide. 0.5-3 mL of solvent is added for every 0.1 mmol of N-(2-cyanoaryl)-N-methylacrylamide, and the optimal amount of solvent is 2 mL.

6. The synthesis method according to claim 1 or 2, wherein: The reaction is carried out in the presence of a base, which is any one or two of sodium carbonate, potassium carbonate, cesium carbonate, potassium tert-butoxide, potassium phosphate, and 1,8-diazacyclo[5,4,0]undecene-7 (DBU), preferably potassium phosphate; the molar concentration of the base in the solvent is 0.05-0.15 M, preferably 0.1-0.15 M, and most preferably 0.1 M.

7. The synthesis method according to claim 1, 2 or 3, wherein: The reaction is carried out in the presence of a photocatalyst, wherein the photocatalyst is any one or more of fac-Ir(ppy)3 (Shanghai Bid Pharmaceutical Technology Co., Ltd.), 4CzIPN, 4CzIPN-CH3, 4CzIPN-tBu, DCA, and Ru(bpy)Cl2·6H2O, with 4CzIPN being the preferred photocatalyst. The molar concentration of the photocatalyst in the solvent is preferably 0.0005-0.0020 M, and the optimal concentration is 0.0015 M.

8. The synthesis method according to claim 1, 2 or 3, wherein: The reaction is carried out in the presence of a hydrogen atom transfer agent (HAT), which is any one or more of p-MePhSH, triethylenediamine (DABCO), quinine, p-BuPhSH, nBuSH, and iPr3SiSH. The preferred hydrogen atom transfer agent (HAT) is DABCO. The molar concentration of the hydrogen atom transfer agent (HAT) in the solvent is preferably 0.0005-0.005 M, and most preferably 0.0025 M.

9. The synthesis method according to claim 2, wherein: The formate is any one or more of sodium formate, potassium formate, and cesium formate, and the preferred formate is sodium formate. The molar concentration of sodium formate in the solvent is preferably 0.5-10M, and the most preferred is 2.5M.

10. The synthesis method according to claim 1, 2 or 3, wherein: The reaction time under CO2 atmosphere is 12-36 hours, the optimal reaction time is 24 hours, the reaction temperature under visible light is 25-80°C, and the optimal reaction temperature under visible light is 25-35°C.

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