A 4-aryl-2-pyridone compound and preparation method thereof

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a 4-aryl-2-pyridone compound and a preparation method thereof. The preparation method is prepared by reacting a 2-pyridone compound, an aryl bromide, a palladium catalyst, an oxidant, a base, and a derivative of norbornene as main raw materials, has good functional group tolerance and substrate universality, can be produced on a gram scale, does not require additional ligand addition, has excellent chemical selectivity, can easily obtain a deuterated labeled product, and is expected to be applied in related medicinal chemistry and natural product synthesis.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a 4-aryl-2-pyridone compound and a preparation method thereof. Background Art

[0002] In recent years, 4-aryl-2-pyridone scaffolds based on 2-pyridone have attracted much attention, and their various drug activities have been deeply studied. It has been found that 4-aryl-2-pyridone scaffolds exhibit multiple biological activities (Amer M. MK; Aziz MA; Shehab WS; Abdellattif M. H.; Mouneir SM; Recent Advances in Chemistry and Pharmacological Aspects of 2-Pyridone Scaffolds. J. Saudi Chem. Soc. 2021, 25, 101259–101305.).

[0003] Currently, there are many methods for synthesizing 4-aryl-2-pyridone compounds, but there are few reports on methods for efficiently preparing nitrogen-containing heterocyclic compounds from simple raw materials. There are four main strategies for the synthesis of 4-aryl-2-pyridone derivatives: 1) intermolecular condensation strategy of aromatic formaldehyde, α-substituted acetonitrile and α-substituted acetamide (Helal, MH; El-Awdan, SA; Salem, MA; Abd-elaziz, TA; Moahamed, YA; El-Sherif, AA; Mohamed, GAM Synthesis, Biological Evaluation and Molecular Modeling of novel Series of Pyridine Derivatives as Anticancer, Anti-inflammatory and Analgesic Agents, Spectrochim. Acta Part A. Mol. Biomol. Spectrosc. 2015, 135, 764–773.); 2) condensation strategy of aromatic formaldehyde, methyl ketone, α-substituted ethyl acetate and ammonium acetate (Keshavarz, N.; Behbahani, FK Synthesis of 4-Aryl-6-phenyl-3-cyano-2-pyridones Using L-proline as an Organocatalyst. Chem. Africa 2018, 1, 113–117.); 3) Palladium-catalyzed coupling reaction strategy of cinnamamides with allenyltin compounds (Cherry, K.; Abarbri, M.; Parrain, J.-L.; Duchêne, A. Regio-and Selective Synthesis of 4,6-Disubstituted-2-Pyridones. Tetrahedron Lett. 2003, 44, 5791–5794.); 4) Suzuki coupling strategy of 2-pyridone derivatives substituted with I, Br or OTf at the 4-position with arylboronic acid (Wysocki, J.; Schlepphorst, C.; Glorius, F. Asymmetric Homogeneous Hydrogenation of 2-Pyridones. Synlett. 2015, 26, 1557–1562.). These methods provide important strategies for the synthesis of 4-aryl 2-pyridones to a certain extent, but are greatly limited by the substrates.In particular, the introduction of some special functional groups has certain limitations and is difficult to regulate in a regionally selective manner, resulting in low reaction efficiency. This is very unfavorable for the supplementation of the database of such compounds and has brought a lot of resistance to their in-depth activity research.

[0004] How to efficiently synthesize 4-aryl-2-pyridone compounds using simple and readily available raw materials is a problem that needs to be solved urgently. Summary of the invention

[0005] The object of the present invention is to provide a 4-aryl-2-pyridone compound and a preparation method thereof. The preparation method has good functional group tolerance and substrate universality, can be produced on a gram scale, does not require the addition of additional ligands, has excellent chemical selectivity, and can solve the problems existing in the synthesis of existing 4-aryl-2-pyridone compounds.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] In one aspect of the present invention, a method for preparing a 4-aryl-2-pyridone compound is provided. The method comprises contacting a compound represented by formula (1), a compound represented by formula (2), an oxidant, a base, a palladium catalyst, a derivative of norbornene and an organic solvent to react to obtain a compound represented by formula (3), namely the 4-aryl-2-pyridone compound.

[0008]

[0009] Where: R 1 is selected from benzyl, C1-C6 alkoxy substituted benzyl, C1-C6 alkyl, C1-C6 alkoxy substituted C1-C6 alkyl, halogen substituted C1-C6 alkyl, -CH2R 10 OR 11 、-CH2CH2CH2CO2R 12 , a C1-C6 alkyl substituted with a C2-C6 ester group, or a C2-C6 alkenyl substituted with a C2-C6 ester group;

[0010] R 2 One selected from C1-C6 alkyl, halogen, phenylhydroxy C1-C6 alkyl;

[0011] R 3 One selected from hydrogen and halogen;

[0012] R 4 , R 8 Each independently selected from C2-C6 ester group, C2-C6 alkanoyl group, carboxyl group, nitro group, C1-C6 alkyl sulfone group, C1-C6 alkyl phosphate group, CO2R 13, hydrogen, C1-C6 alkyl, halogen;

[0013] R 5 , R 6 , R 7 Each is independently selected from one of hydrogen, C1-C6 alkyl, halogen, C1-C6 alkoxy, and C2-C6 ester;

[0014] R 9 One selected from hydrogen and deuterium;

[0015] R 10 is one of benzyl and C1-C6 alkyl;

[0016] R 11 is an aromatic or heterocyclic group, C1-C 20 Alkyl, C1-C 20 One of the alkanoyloxy groups;

[0017] R 12 C1-C 20 Alkyl, C1-C 20 One of alkanoyl and aroyl;

[0018] R 13 is a cyclohexyl group substituted with a C1-C6 alkyl group, a C1-C 20 One of the alkyl groups;

[0019] or R 1 , R 2 , and R 1 The nitrogen atom bonded to R 2 The bonded carbon atoms join together to form a heterocyclic ring;

[0020] or R 7 , R 8 , and R 7 , R 8 Two adjacent carbon atoms that are bonded are joined together to form an aromatic ring.

[0021] As a specific embodiment of the present invention, the R 1 is selected from benzyl, C1-C3 alkoxy substituted benzyl, C1-C3 alkyl, C1-C3 alkoxy substituted C1-C3 alkyl, fluorine substituted C1-C3 alkyl, CH2R 10 OR 11 、CH2CH2CH2CO2R 12 , one of C1-C3 alkyl substituted with a C2-C4 ester group, and C2-C4 alkenyl substituted with a C2-C4 ester group;

[0022] R 2One selected from C1-C3 alkyl, fluorine, chlorine, bromine, phenylhydroxy C1-C3 alkyl;

[0023] R 3 One selected from hydrogen, fluorine, chlorine and bromine;

[0024] R 4 , R 8 Each independently selected from C2-C4 ester group, C2-C4 alkanoyl group, carboxyl group, nitro group, C1-C3 alkyl sulfone group, C1-C4 alkyl phosphate group, CO2R 13 , hydrogen, C1-C3 alkyl, fluorine, chlorine, bromine;

[0025] R 5 , R 7 Each is independently selected from one of hydrogen, C1-C3 alkyl, fluorine, chlorine, bromine, hydrogen, C1-C3 alkoxy, and C2-C4 ester;

[0026] R 6 One selected from hydrogen, C1-C3 alkoxy, fluorine, chlorine, and bromine;

[0027] R 9 is hydrogen;

[0028] R 10 is one of benzyl and C1-C3 alkyl;

[0029] R 11 It is one of a C1-C3 alkyl-substituted pyridyl group and an adamantyl C1-C3 alkanoyloxy group;

[0030] R 12 It is one of a C1-C3 alkyl-substituted cyclohexyl group and a C1-C3 alkanoyl C1-C3 alkyl-substituted cyclopentaphenanthryl group;

[0031] R 13 is a cyclohexyl group substituted with a C1-C3 alkyl group, a C1-C 10 One of the alkyl-substituted cyclopentaphenanthryl groups;

[0032] or R 1 , R 2 , and R 1 The nitrogen atom bonded to R 2 The bonded carbon atoms join together to form a C4 heterocyclic ring;

[0033] or R 7 , R 8 , and R 7 , R 8 The two adjacent carbon atoms that are bonded are combined together to form a C6 aromatic ring.

[0034] As a specific embodiment of the present invention, the compound represented by formula (1) is selected from 1-benzyl-6-methylpyridin-2(1H)-one, 1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one, 1-benzyl-6-fluoropyridin-2(1H)-one, 1,6-dimethylpyridin-2(1H)-one, 6-methyl-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one, 1-benzyl-6-chloro Pyridin-2(1H)-one, 2,3-dihydroindole-5(1H)-one, 1-benzyl-3-fluoro-6-methylpyridin-2(1H)-one, 1-(ethoxymethyl)-6-methylpyridin-2(1H)-one, 1-benzyl-6-(2-hydroxy-2-phenylethyl)pyridin-2(1H)-one, 6-methyl-1-(4-(((6-methylpyridin-2-yl)oxy)methyl)benzyl)pyridine-2(1H) -ketone, 4-(6-methyl-2-oxopyridin-1(2H)-yl)butyl 2-((3r,5r,7r)-adamantan-1-yl)acetate, (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-4-(6-methyl-2-oxopyridin-1(2H)-yl)butanoate, (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl One of 1-2,3,4,7,8,9,10,11,12,13,14,15,16,17-decahydrophenanthrene-1H-cyclopentaphenanthrene-3-yl-4-(6-methyl-2-pyridone-1(2H)-yl)butyric acid methyl ester, 4-(6-methyl-2-oxopyridine-1(2H)-yl)butyric acid methyl ester, (E)-3-(6-methyl-2-oxopyridine-1(2H)-yl)acrylate;

[0035] As a specific embodiment of the present invention, the compound represented by formula (2) is selected from methyl 2-bromobenzoate, 2-bromo-N, N-dimethylbenzamide, methyl 2-bromo-4,5-dimethoxybenzoate, tert-butyl 2-bromobenzoate, 2-bromo-benzoic acid, 2-bromonitrobenzene, 2-methylsulfonylbromobenzene, diethyl (2-bromophenyl)phosphonate, methyl 2-bromo-6-methylbenzoate, methyl 2-bromo-6-chlorobenzoate, methyl 2-bromo-5-methoxybenzoate, methyl 2-bromo-5-chlorobenzoate, methyl 2-bromo-5-fluorobenzoate, methyl 2-bromo-4-methoxybenzoate, methyl 2-bromo-4-fluorobenzoate, diethyl 2,5-dibromoterephthalate , methyl 2-bromo-3-methylbenzoate, methyl 2-bromo-3-fluorobenzoate, methyl 2-bromo-3-chlorobenzoate, methyl 2-bromonaphthoate, (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-2-bromobenzoate, (5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptane-2-yl)hexahydro-1H-cyclopentadien-3-yl 2-bromobenzoate, 2-bromo-4-fluoro-N,N-dimethylbenzamide, 2-bromo-5-chloro-N,N-dimethylbenzamide, 2-bromo-5-methoxy-N,N-dimethylbenzamide.

[0036] As a specific embodiment of the present invention, the base is at least one of copper acetate, silver acetate, potassium acetate, sodium acetate, cesium acetate, and sodium formate.

[0037] As a specific embodiment of the present invention, the oxidant is one of air, oxygen, silver carbonate, silver acetate, silver nitrate, potassium persulfate, copper acetate, copper sulfate, benzoquinone, and DDQ (2,3-dichloro-5,6-dicyanobenzoquinone).

[0038] As a specific embodiment of the present invention, the palladium catalyst is at least one of palladium pivalate, palladium bromide, palladium chloride, palladium acetate, palladium trifluoroacetate, bis(triphenylphosphine)palladium chloride, and tetrakis(triphenylphosphine)palladium.

[0039] As a specific embodiment of the present invention, the organic solvent is at least one of acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, 1,4-dioxane, chlorobenzene, trifluorotoluene, toluene and o-xylene.

[0040] As a specific embodiment of the present invention, the derivative of norbornene is a racemic body or a single-configuration optical isomer, preferably any one of the following:

[0041]

[0042] Wherein: R is selected from one of alkyl, aryl, heteroaryl, methoxy, hydrogen, ester, hydroxyl, cyano and nitro.

[0043] As a specific embodiment of the present invention, the molar volume ratio of the compound represented by formula (1), the compound represented by formula (2), the base, the palladium catalyst, the derivative of norbornene and the organic solvent is 0.1-0.15mmol:0.15-0.225mmol:0.2-0.3mmoL:0.01-0.015mmol:0.05-0.075mmol:0.5-0.75ml; preferably 0.1mmol:0.15mmol:0.2mmol:0.01mmol:0.05mmol:0.5ml.

[0044] As a specific embodiment of the present invention, the reaction temperature is 90-140°C, preferably 110-120°C, more preferably 120°C; the reaction time is 10-30h, preferably 10-30h; more preferably 24h.

[0045] As a specific embodiment of the present invention, the reaction product is further subjected to post-treatment; preferably, the post-treatment includes filtering, washing, removing the solvent under reduced pressure, and column chromatography separation and purification in sequence. The present invention does not limit the specific method of post-treatment, and methods well known to those skilled in the art are sufficient.

[0046] Another aspect of the present invention provides a 4-aryl-2-pyridone compound prepared by the above method. The 4-aryl-2-pyridone compound is used in the field of drug synthesis and natural product synthesis, specifically for preparing anti-inflammatory drugs.

[0047] Compared with the prior art, the present invention has the following beneficial effects:

[0048] The preparation method provided by the present invention has the following advantages: 1) most raw materials can be commercial reagents without special treatment, the raw materials are easily available and inexpensive, the preparation method is simple, and industrial production is convenient; 2) the reaction conditions have good functional group tolerance and substrate universality, and gram-scale production is possible; 3) it is efficient and diverse, and a 4-aryl-2-pyridone structure is constructed by a one-step reaction, which has extremely high step economy; 4) there is no need to add additional ligands, it has excellent chemical selectivity, and deuterated labeled products can be easily obtained, and it is expected to be applied in related medicinal chemistry and natural product synthesis. DETAILED DESCRIPTION

[0049] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0050] Example 1

[0051] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0052]

[0053] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 80%). 1 H NMR (400MHz, CDCl3): δ7.88(dd,J=7.8,1.4Hz,1H),7.55(td,J=7.5,1.4Hz,1H),7.46(td,J=7.6,1.3Hz,1H),7.33(dd,J=12 .4,7.3Hz,3H),7.28–7.25(m,1H),7.20(d,J=7.5Hz,2H),6.49(s,1H),6.01(s,1H),5.39(s,2H),3.76(s,3H),2.29(s,3H). 13 C NMR (100MHz, CDCl3): δ168.02,163.93,153.01,145.37,139.90,136.56,131.94,130.37 ,129.94,129.71,128.95,128.63,127.50,126.61,116.23,108.88,52.30,47.24,20.77.

[0054] Example 2

[0055] Methyl 2-(1-(4-methoxybenzyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0056]

[0057] Under nitrogen protection, 1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 53%). 1 H NMR (400MHz, CDCl3): δ7.87(dd,J=7.8,1.4Hz,1H),7.54(td,J=7.5,1.4Hz,1H),7.44(td,J=7.6,1.3Hz,1H),7.33(dd,J=7.6,1.4H z,1H),7.16(d,J=8.6Hz,2H),6.85(d,J=8.7Hz,2H),6.48(s,1H),5.98(s,1H),5.30(s,2H),3.77(s,3H),3.74(s,3H),2.30(s,3H). 13 C NMR (100MHz, CDCl3): δ.168.01,158.96,152.80,145.37,139.88,131.89,130.30,129.8 8,129.67,128.62,128.57,128.07,116.19,114.26,108.70,55.39,52.29,46.68,20.76.

[0058] Example 3

[0059] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-N,N-dimethylbenzamide

[0060]

[0061] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (black oil, 84%). 1 H NMR (400MHz, CDCl3): δ7.45–7.35(m,4H),7.33–7.27(m,2H),7.26–7.21(m,1H),7.17–7. 13(m,2H),6.57(s,1H),6.21(s,1H),5.35(s,2H),2.95(s,3H),2.68(s,3H),2.27(s,3H). 13 C NMR (126MHz, CDCl3): δ170.60,163.82,151.32,146.17,136.35,135.85,135.49,129.59,12 9.29,128.90,128.76,127.49,127.38,126.49,116.08,108.14,47.16,38.55,34.86,20.74.

[0062] Example 4

[0063] Methyl 2-(1-benzyl-6-fluoro-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0064]

[0065] Under nitrogen protection, 1-benzyl-6-fluoropyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 75%). 1 H NMR (400MHz, CDCl3): δ7.91 (dd, J=7.7, 1.4Hz, 1H), 7.56 (td, J=7.5, 1.4Hz, 1H), 7.50–7.41 (m, 3H), 7.3 7–7.29(m,4H),6.37(d,J=1.7Hz,1H),5.83(dd,J=6.0,1.7Hz,1H),5.29(d,J=3.5Hz,2H),3.77(s,3H). 13 C NMR (126MHz, CDCl3): δ167.51, 161.44 (d, J = 4.5Hz), 155.44 (d, J = 267.5Hz), 154.21 (d, J = 12.9Hz), 139.46 (d, J = 3.3Hz), 135.89, 132.13 ,130.56,129.61,129.56,128.95(d,J=18.7Hz),128.37,128.16,114.28(d,J=4.4Hz),89.82(d,J=21.9Hz),52.42,44.88(d,J=5.1Hz). 19 FNMR (600MHz,CDCl3):-93.85.

[0066] Example 5

[0067] 2-(1,6-dimethyl-2-oxo-1,2-dihydropyridin-4-yl)-N,N-dimethylbenzamide

[0068]

[0069] Under nitrogen protection, 1,6-dimethylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 59%). 1 H NMR(400MHz,Chloroform-d)δ7.49–7.40(m,2H),7.39–7.31(m,2H),6.47(d,J=2.0Hz, 1H), 6.21 (dd, J = 2.1, 1.0Hz, 1H), 3.54 (s, 3H), 2.97 (s, 3H), 2.68 (s, 3H), 2.36 (s, 3H). 13 C NMR(101MHz,Chloroform-d)δ170.63,163.81,150.91,145.95,136.02,135.53 ,129.52,129.15,128.88,127.31,115.62,107.66,38.57,34.89,31.19,21.15.

[0070] Example 6

[0071] Methyl 2-(1-trifluoroethyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0072]

[0073] Under nitrogen protection, 6-methyl-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 50%). 1 HNMR (600MHz, CDCl3): δ7.90 (dd, J=7.8, 1.4Hz, 1H), 7.55 (td, J=7.6, 1.4Hz, 1H), 7.47 (td, J=7.6, 1.3Hz, 1H), 7.31(dd,J=7.6,1.3Hz,1H),6.42(d,J=1.9Hz,1H),6.06–5.98(m,1H),4.80(s,2H),3.75(s,3H),2.42(s,3H). 13 CNMR (150MHz, CDCl3): δ.167.73,163.29,153.77,144.21,139.61,132.09,130.50,129.70,129.59 ,128.87,123.89(q,J=280.9Hz),116.38,109.47,52.31,44.35(q,J=35.2Hz),20.69(q,J=2.2Hz). 19 F NMR (565MHz, CDCl3) δ-67.95.

[0074] Example 7

[0075] Methyl 2-(1-benzyl-6-chloro-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0076]

[0077] Under nitrogen protection, 1-benzyl-6-chloropyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 70%). 1 H NMR (400MHz, CDCl3): δ7.93 (dd, J=7.8, 1.4Hz, 1H), 7.57 (td, J=7.6, 1.5Hz, 1H), 7.49 (td, J=7.6,1.2Hz,1H),7.40–7.27(m,6H),6.50(s,1H),6.27(s,1H),5.51(s,2H),3.78(s,3H). 13 C NMR (100MHz, CDCl3): δ.167.41,163.01,153.03,138.90,136.83,136.03,132.13,130 .58,129.60,129.51,129.02,128.70,127.71,127.54,117.07,108.86,52.35,49.06.

[0078] Example 8

[0079] Methyl 2-(5-oxo-1,2,3,5-tetrahydroindolidin-7-yl)benzoate

[0080]

[0081] Under nitrogen protection, 2,3-dihydroindole-5(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (black oil, 84%). 1 H NMR (600MHz, CDCl3): δ7.87 (dd, J=7.8, 1.4Hz, 1H), 7.54 (td, J=7.5, 1.4Hz, 1H), 7.45 (td, J=7.6, 1.3Hz, 1H), 7.30 (dd, J=7.7, 1.3H z,1H),6.34(d,J=1.6Hz,1H),6.09(d,J=1.8Hz,1H),4.19(t,J=7.3Hz,2H),3.77(s,3H),3.11(t,J=7.8Hz,2H),2.31–2.20(m,2H). 13 C NMR (151MHz, CDCl3): δ.167.96,162.12,154.15,149.49,140.43,131.84,130.22,129.82,128.46,115.88,103.04,52.34,48.69,31.83,21.45.

[0082] Example 9

[0083] Methyl 2-(1-benzyl-3-fluoro-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0084]

[0085] Under nitrogen protection, 1-benzyl-3-fluoro-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (colorless solid, 62%). 1 H NMR (600MHz, CDCl3): δ7.93 (dd, J=7.8, 1.3Hz, 1H), 7.52 (td, J=7.6, 1.3Hz, 1H), 7.42 (td, J=7.7, 1.3Hz, 1H), 7.27 (dd, J= 11.2,7.5Hz,3H),7.22–7.19(m,1H),7.15(d,J=7.6Hz,2H),5.87(d,J=6.0Hz,1H),5.33(s,2H),3.72(s,3H),2.21(s,3H). 13 CNMR (151MHz, CDCl3): δ166.03, 156.12 (d, J = 25.4Hz), 145.55 (d, J = 243.7Hz), 139.10 (d, J = 5.8Hz), 134.9 5,132.92,131.03,129.48,129.12,129.01,127.88,127.86,126.56,125.66,105.60,51.26,46.75,19.16. 19 F NMR (565MHz, CDCl3) δ-137.58.

[0086] Example 10

[0087] 2-(1-(Ethoxymethyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-N,N-dimethylbenzamide

[0088]

[0089] Under nitrogen protection, 1-(ethoxymethyl)-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 41%). 1 H NMR (400MHz, CDCl3) δ7.47–7.41(m,2H),7.37(td,J=6.2,3.3Hz,2H),6.44(d,J=1.9Hz,1H),6.17(dd,J=2.0, 1.0Hz,1H),5.55(s,2H),3.66(q,J=7.0Hz,2H),2.97(s,3H),2.68(s,3H),2.46(s,3H),1.20(t,J=7.0Hz,3H). 13 CNMR(101MHz,CDCl3)δ170.55,164.13,151.97,146.25,135.81,135.51,129.57,1 29.34,128.75,127.41,116.30,108.15,72.31,65.14,38.55,34.88,19.68,15.25.

[0090] Embodiment 11

[0091] Methyl 4,5-dimethoxy-2-(5-oxo-1,2,3,5-tetrahydroindolizin-7-yl)benzoate

[0092]

[0093] Under nitrogen protection, 2,3-dihydroindole-5(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-4,5-dimethoxybenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (black oil, 87%). 1 H NMR (400MHz, CDCl3) δ7.44(s,1H),6.75(s,1H),6.34(d,J=1.6Hz,1H),6.08(d,J=1.5Hz,1H),4.2 3–4.16(m,2H),3.96(s,3H),3.92(s,3H),3.75(s,3H),3.12(t,J=7.7Hz,2H),2.32–2.19(m,2H). 13 C NMR (101MHz, CDCl3) δ167.05,162.05,154.41,151.46,149.05,148.36,134.84,12 1.09,115.65,112.89,112.50,103.40,56.12,56.09,52.00,48.51,31.65,21.34.

[0094] Example 12

[0095] Methyl 2-(1-benzyl-6-(2-hydroxy-2-phenylethyl)-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0096]

[0097] Under nitrogen protection, 1-benzyl-6-(2-hydroxy-2-phenylethyl)pyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (white solid, 40%). 1 H NMR (400MHz, CDCl3): δ7.95 (dd, J=7.9, 1.4Hz, 1H), 7.58 (td, J=7.5, 1.4Hz, 1H), 7.49 (td, J=7.6, 1.4Hz, 1H), 7.33 (ddt, J=15.6, 9.1, 2.5Hz, 7H), 7.18–7.07(m,3H),6.58(d,J=1.9Hz,1H),6.15(d,J=2.0Hz,1H),5.50–5 .29(m,2H),4.81(dd,J=8.7,3.8Hz,1H),3.80(s,3H),2.99–2.84(m,2H). 13 CNMR (101MHz, CDCl3): δ167.97,164.03,152.55,144.98,142.96,140.15,136.87,132.26,130.64,129.8 7,129.03,128.87,128.77,128.23,127.52,126.48,125.62,116.94,110.66,73.18,52.53,46.75,43.17.

[0098] Example 13

[0099] 2-(6-methylpyridin-2-oxy)methyl)benzyl)-2-oxo-1,2-dihydropyridin-4-yl)benzoic acid methyl ester

[0100]

[0101] Under nitrogen protection, 6-methyl-1-(4-(((6-methylpyridin-2-yl)oxy)methyl)benzyl)pyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.25mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 140°C for 36h. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (black oil, 51%). 1 H NMR(600MHz, CDCl3) δ7.89(dd,J=7.8,1.4Hz,1H),7.55(td,J=7.6,1.4Hz,1H),7.48–7.42(m,4H),7.35(dd,J=7.6,1.3Hz,1H),7.21(d,J=7.9Hz,2H) ,6.72(d,J=7.2Hz,1H),6.57(d,J=8.2Hz,1H),6.50(d,J=2.0Hz,1H),6.00 (s,1H),5.39(s,2H),5.34(s,2H),3.76(s,3H),2.45(s,3H),2.30(s,3H). 13 C NMR (151MHz, CDCl3) δ168.03,163.87,163.22,156.37,152.94,145.33,140.05,138.99,137.18,136.24,131.88,13 0.39,130.17,129.73,128.76,128.60,126.82,116.41,116.07,108.74,107.77,67.16,52.24,47.10,29.85,20.77.

[0102] Embodiment 14

[0103] Methyl 2-(1-(4-(2-((3R,5R,7R)-adamantan-1-yl)acetoxy)butyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0104]

[0105] Under nitrogen protection, 4-(6-methyl-2-oxopyridin-1(2H)-yl)butyl 2-((3r,5r,7r)-adamantan-1-yl)acetate (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 61%). 1 H NMR (600MHz, CDCl3): δ7.44–7.40(m,2H),7.36–7.34(m,Hz,2H),6.46(s,1H),6.19(s,1H),4.09(t,J=6.2Hz,2H),4.05(t,J=7. 3Hz,2H),2.96(s,3H),2.67(s,3H),2.38(s,3H),2.05(s,2H),1.81–1.72(m,4.6Hz,4H),1.71–1.65(m,4H),1.62-1.59(m,11H). 13 C NMR (151MHz, CDCl3): δ171.91,170.63,163.47,150.99,145.20,135.91,135.51,129.56,129.21,128.87,12 7.34,116.20,108.16,63.43,49.04,44.22,42.51,38.60,36.81,34.89,32.86,28.69,26.45,25.32,20.54.

[0106] Embodiment 15

[0107] Methyl 2-(1-(4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)-4-oxobutyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0108]

[0109] Under nitrogen protection, (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-4-(6-methyl-2-oxopyridin-1(2H)-yl)butanoate (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (colorless oil, 64%). 1 H NMR (600MHz, CDCl3): δ7.45–7.41(m,2H),7.39–7.33(m,2H),6.55(s,1H),6.25(s,1H),4.70(td,J=1 0.9,4.4Hz,1H),4.09(tt,J=13.2,5.6Hz,2H),2.97(s,3H),2.69(s,3H),2.47–2.41(m,5H),2.02(p,J =7.3Hz,2H),1.99–1.95(m,1H),1.84(tt,J=7.2,3.6Hz,1H),1.68(dq,J=10.2,3.0Hz,2H),1.51-1.4 4(m,1H),1.08–1.01(m,1H),0.97(td,J=12.1,10.9Hz,1H),0.90–0.87(m,7H),0.75(d,J=7.0Hz,3H). 13 C NMR (151MHz, CDCl3): δ172.70,170.63,163.68,151.40,145.76,135.85,135.56,129.60,129.29,128.95,127.38,116 .07,74.65,47.08,44.13,41.08,38.68,34.95,34.32,31.67,31.52,26.44,23.60,23.53,22.13,20.88,20.55,16.46.

[0110] Example 16

[0111] Methyl 2-(1-(4-(((3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-decahydrophenanthrene-1H-cyclopentaphenanthrene-3-yl)oxy)-4-butanoyloxy)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0112]

[0113] Under nitrogen protection, (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl l-2,3,4,7,8,9,10,11,12,13,14,15,16,17-decahydrophenanthrene-1H-cyclopentadienylphenanthrene-3-yl-4-(6-methyl-2-pyridone-1(2H)-yl)butanoic acid methyl ester ( 0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), dry 1,4-dioxane (0.5mL). The above reaction solution was placed in a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 64%). 1H NMR (400MHz, CDCl3): δ7.86 (d, J=6.4Hz, 1H), 7.55–7.51 (m, 1H), 7.46–7.43 (m, 1H), 7.30 (d, J=7.7Hz, 1H), 6.39 (s, 1H),5.98(s,1H),5.39–5.36(m,1H),4.64(ddq,J=11.3,8.1,4.1Hz,1H),4.11–4.07(m,2H),3.76(s,3H),2.54(d,J= 9.1Hz,1H),2.47–2.44(m,5H),2.33(d,J=7.9Hz,2H),2.24–2.14(m,2H),2.12(s,3H),2.07–1.99(m,5H),1.89(q,J =3.1Hz,1H),1.87–1.85(m,1H),1.71–1.56(m,4H),1.52–1.41(m,3H),1.19–1.12(m,3H),1.02(s,3H),0.63(s,3H).

[0114] 13 C NMR (151MHz, CDCl3): δ209.72,172.58,167.98,163.54,152.62,144.76,139.98, 139.70,131.90,130.29,129.89,129.76,128.55,122.57,116.22,108.75,74.26, 63.82,56.97,52.35,50.03,44.12,43.85,38.92,38.22,37.13,36.74,31.94,31.89,31.82,31.69,29.83,27.89,24.61,23.68,22.96,21.17,20.54,19.44,13.36.

[0115] Embodiment 17

[0116] tert-Butyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0117]

[0118] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-benzoic acid tert-butyl ester (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 68%). 1 H NMR (400MHz, CDCl3): δ7.82 (dd, J=7.6, 1.5Hz, 1H), 7.51 (td, J=7.5, 1.5Hz, 1H), 7.44 (td, J=7.6, 1.4Hz, 1H), 7. 35–7.30(m,3H),7.26(dt,J=8.4,6.2Hz,3H),6.55(s,1H),6.02(s,1H),5.39(s,2H),2.30(s,3H),1.39(s,9H). 13 CNMR (100MHz, CDCl3): δ.167.20,163.89,153.10,145.09,139.12,136.60,132.08,131.27,1 30.09,129.49,128.86,128.55,127.52,126.85,116.13,109.30,81.98,47.20,27.88,20.68.

[0119] Embodiment 18

[0120] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoic acid

[0121]

[0122] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-benzoic acid (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (white solid, 63%). 1 H NMR (400MHz, CDCl3): δ7.88(d,J=7.7Hz,1H),7.52–7.45(m,1H),7.46–7.38(m,1H),7.34–7.28(m,3H ),7.25(d,J=6.3Hz,1H),7.18(d,J=7.5Hz,2H),6.76(s,1H),6.28(s,1H),5.38(s,2H),2.31(s,3H). 13 C NMR (100MHz, CDCl3): δ164.57,153.76,146.15,138.83,136.04,131.08,130.38 ,129.14,128.98,128.65,127.56,126.68,115.91,110.46,47.74,29.83,20.79.

[0123] Embodiment 19

[0124] 1-Benzyl-6-methyl-4-(2-nitrophenyl)pyridin-2(1H)one

[0125]

[0126] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromonitrobenzene (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 32%). 1 H NMR(400MHz,Chloroform-d)δ7.99(dd,J=8.1,1.3Hz,1H),7.68(td,J=7.6,1.3Hz,1H),7.57(td,J=7.8,1.5Hz,1H),7 .45(dd,J=7.7,1.5Hz,1H),7.38–7.27(m,3H),7.25–7.17(m,2H),6.54(s,1H),5.95(s,1H),5.38(s,2H),2.29(s,3H). 13 CNMR(101MHz,Chloroform-d)δ149.37,146.55,136.20,134.08,133.29,131 .03,129.70,129.03,127.59,126.61,124.75,116.37,107.20,47.35,20.90.

[0127] Embodiment 20

[0128] 1-Benzyl-6-methyl-4-(2-methylsulfonyl)phenylpyridin-2(1H)one

[0129]

[0130] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-methylsulfonylbromobenzene (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.1mmol, 100mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 43%). 1 H NMR (400MHz, CDCl3): δ8.18(dd,J=8.0,1.4Hz,1H),7.70–7.66(m,1H),7.63–7.59(m,1H)7.39–7.32(m,3H), 7.29(d,J=7.2Hz,1H),7.24–7.18(m,2H),6.50(s,1H),6.22(s,1H),5.39(s,2H),3.01(s,3H),2.33(s,3H). 13 CNMR (100MHz, CDCl3): δ163.28,151.20,145.75,138.72,138.37,136.17,133.68,13 1.25,129.33,129.29,129.05,127.65,126.65,117.37,110.41,47.45,44.95,20.90.

[0131] Embodiment 21

[0132] Diethyl (2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)phosphonate

[0133]

[0134] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), diethyl (2-bromophenyl)phosphonate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 15%). 1 H NMR(600MHz, CDCl3)δ7.96(ddd,J=14.3,7.7,1.4Hz,1H),7.53–7.49(m,1H),7.42(tdd,J=7.8,6.5,3.6,1.9Hz,1H),7.28–7.2 3(m,4H),7.15(d,J=7.6Hz,2H),6.49(s,1H),6.18(s,1H),5.33(s,2H),4.04–3.91(m,4H),2.25(s,3H),1.20–1.15(m,6H).13C NMR(151MHz,Chloroform-d)δ151.61,143.80,141.63,135.45,132.99(d,J=9.3Hz),131.31,128.88,128.79,1 27.77, 127.08, 126.98, 126.39, 125.57, 116.26, 108.70, 61.19 (d, J = 6.1Hz), 46.09, 19.61, 15.22 (d, J = 6.6Hz).

[0135] Embodiment 22

[0136] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methylbenzoate

[0137]

[0138] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-6-methylbenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 50%). 1 H NMR (400MHz, CDCl3): δ7.37(t,J=7.7Hz,1H),7.32(t,J=7.3Hz,2H),7.28–7.24(m,2H),7.21(d,J=7.6Hz ,1H),7.19–7.15(m,2H),6.54(s,1H),6.05(s,1H),5.37(s,2H),3.73(s,3H),2.40(s,3H),2.28(s,3H). 13 C NMR (100MHz, CDCl3): δ169.61,163.75,152.02,146.09,137.33,136.47,136.22,132.30,13 0.77,129.88,128.92,127.49,126.53,126.17,116.13,108.06,52.23,47.13,20.77,19.85.

[0139] Embodiment 23

[0140] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-chlorobenzoate

[0141]

[0142] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-6-chlorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 56%). 1 H NMR (400MHz, CDCl3): δ7.47 (dd, J=8.1, 1.3Hz, 1H), 7.42 (t, J=7.8Hz, 1H), 7.36–7.27 (m, 4H),7.20–7.14(m,2H),6.55(s,1H),6.06(s,1H),5.36(s,2H),3.81(s,3H),2.30(s,3H). 13 C NMR (100MHz, CDCl3): δ167.04,163.61,150.30,146.69,138.77,136.30,132.51,131.83 ,130.85,129.94,129.01,127.63,127.10,126.64,116.61,107.67,52.85,47.33,20.89.

[0143] Embodiment 24

[0144] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-methoxybenzoate

[0145]

[0146] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-5-methoxybenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (colorless oil, 69%). 1 H NMR (400MHz, CDCl3): δ7.37 (d, J=2.8Hz, 1H), 7.36–7.24 (m, 4H), 7.23–7.17 (m, 2H), 7.08 (dd, J= 8.5,2.7Hz,1H),6.48(s,1H),5.99(s,1H),5.38(s,2H),3.87(s,3H),3.76(s,3H),2.28(s,3H). 13 C NMR (100MHz, CDCl3): δ.168.05,163.90,159.61,152.55,145.18,136.58,132.07,131.14,13 1.01,128.90,127.43,126.52,117.80,116.08,115.09,108.98,55.71,52.41,47.09,20.74.

[0147] Embodiment 25

[0148] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-chlorobenzoate

[0149]

[0150] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-5-chlorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 55%). 1 H NMR (400MHz, CDCl3): δ7.87(s,1H),7.52(dd,J=8.2,2.2Hz,1H),7.36–7.29(m,3H),7.28(d,J=2 .0Hz,1H),7.22–7.16(m,2H),6.46(s,1H),5.96(s,1H),5.38(s,2H),3.77(s,3H),2.29(s,3H). 13 C NMR (100MHz, CDCl3): δ166.70,163.71,151.72,145.70,138.30,136.43,134.74,131.94 ,131.33,131.07,130.39,128.96,127.53,126.57,116.33,108.40,52.61,47.22,20.80.

[0151] Embodiment 26

[0152] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-fluorobenzoate

[0153]

[0154] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-5-fluorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 69%). 1 H NMR (500MHz, CDCl3): δ7.59 (dd, J=8.9, 2.7Hz, 1H), 7.37–7.30 (m, 4H), 7.29–7.23 (m, 5H) ),7.21–7.16(m,2H),6.45(s,1H),5.97(s,1H),5.37(s,2H),3.77(s,3H),2.29(s,3H).

[0155] 13 C NMR (500MHz, CDCl3): δ.166.75, 171.23 (d, J = 249.48Hz), 163.80, 151.98, 145.57, 136.46, 136.03 (d, J = 3.8Hz), 131.66 ( d,J=7.4Hz),128.98,127.55,126.58,119.03(d,J=21.4Hz),117.45(d,J=23.8Hz),116.41,108.75,52.61,47.22,20.79. 19 FNMR (471MHz, CDCl3): δ-112.24.

[0156] Embodiment 27

[0157] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-methoxybenzoate

[0158]

[0159] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-4-methoxybenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 74%). 1 H NMR (400MHz, CDCl3): δ7.93(d,J=8.8Hz,1H),7.33(dd,J=8.1,6.5Hz,2H),7.27(dd,J=4.9,2.4Hz,1H),7.21(dd,J=7.1,1.8Hz,2H) ,6.95(dd,J=8.7,2.6Hz,1H),6.81(d,J=2.6Hz,1H),6.49(s,1H),6.00(s,1H),5.39(s,2H),3.87(s,3H),3.73(s,3H),2.29(s,3H). 13 C NMR (100MHz, CDCl3): δ.167.18,163.92,162.24,153.37,145.07,142.61,136.57,132.86,12 8.92,127.46,126.58,121.44,116.03,115.14,113.90,108.89,55.72,52.01,47.18,20.77.

[0160] Embodiment 28

[0161] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-methylbenzoate

[0162]

[0163] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-4-methylbenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 62%). 1 H NMR (400MHz, CDCl3): δ7.82(d,J=7.9Hz,1H),7.36–7.31(m,2H),7.29–7.23(m,2H),7.22–7.18(m,2H) ,7.15(d,J=1.8Hz,1H),6.49(s,1H),6.00(s,1H),5.39(s,2H),3.75(s,3H),2.42(s,3H),2.29(s,3H). 13 C NMR (100MHz, CDCl3): δ167.84,163.87,153.27,145.14,142.63,140.15,136.61,130.60,13 0.49,129.23,128.91,127.43,126.82,126.55,116.10,108.87,52.13,47.13,21.57,20.74.

[0164] Embodiment 29

[0165] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-fluorobenzoate

[0166]

[0167] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-4-fluorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 53%). 1 H NMR (500MHz, CDCl3): δ7.93(dd,J=8.7,5.7Hz,1H),7.35–7.30(m,2H),7.28–7.23(m,1H),7.22–7.17(m,2H),7.13(t d,J=8.3,2.6Hz,1H),7.04(dd,J=9.0,2.6Hz,1H),6.46(s,1H),5.98(s,1H),5.38(s,2H),3.75(s,3H),2.29(s,3H). 13 C NMR (126MHz, CDCl3): δ.166.83, 164.34 (d, J = 254.7Hz), 163.68, 151.78, 145.71, 142.94 (d, J = 8.6Hz), 136.45, 133.14 (d, J = 9.3Hz) ,128.96,127.52,126.57,125.87(d,J=3.2Hz),116.98(d,J=22.7Hz),116.23,115.56(d,J=21.2Hz),108.22,52.34,47.22,20.78. 19 FNMR (376MHz, CDCl3): δ-106.53.

[0168] Embodiment 30

[0169] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-bromoterephthalic acid diethyl ester

[0170]

[0171] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), diethyl 2,5-dibromoterephthalate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 46%). 1 HNMR (400MHz, CDCl3): δ8.15(s,1H),7.74(s,1H),7.36–7.31(m,2H),7.29–7.25(m,1H),7.24–7.18(m,2H),6.50(s,1H),5.99 (s,1H),5.38(s,2H),4.43(q,J=7.1Hz,2H),4.25(q,J=7.1Hz,2H),2.31(s,3H),1.43(t,J=7.2Hz,3H),1.21(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3): δ165.53,165.17,163.58,150.80,145.96,138.52,136.30,135.88,135.21,133.5 3,132.19,128.94,127.59,126.66,121.65,116.44,108.18,62.36,62.10,47.28,20.78,14.30,13.95.

[0172] Embodiment 31

[0173] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4,5-dimethoxybenzoic acid methyl ester

[0174]

[0175] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-4,5-dimethoxybenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (white solid, 71%). 1 H NMR (400MHz, CDCl3): δ7.45 (s, 1H), 7.34 (t, J = 7.3Hz, 2H), 7.28 (d, J = 5.9Hz, 1H), 7.21 (d, J = 7.0Hz, 2H), 6.79(s,1H),6.50(s,1H),5.99(s,1H),5.39(s,2H),3.96(s,3H),3.94(s,3H),3.74(s,3H),2.30(s,3H). 13 C NMR (100MHz, CDCl3): δ167.33,163.99,153.36,151.67,148.61,144.97,136.60,134.42,128.9 3,127.49,126.60,121.29,116.18,113.08,112.46,109.29,56.32,56.29,52.14,47.18,20.77.

[0176] Embodiment 32

[0177] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-methylbenzoate

[0178]

[0179] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-3-methylbenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 31%). 1 HNMR (400MHz, CDCl3): δ7.75(dd,J=7.7,1.4Hz,1H),7.41(d,J=7.6Hz,1H),7.33(t,J=7.6Hz,3H),7.29–7.2 3(m,2H),7.22–7.17(m,2H),6.34(s,1H),5.95(s,1H),5.40(s,2H),3.71(s,3H),2.30(s,3H),2.21(s,3H). 13 C NMR (100MHz, CDCl3): δ.167.78,163.97,152.58,145.52,139.21,136.59,136.19,133.87,12 9.95,128.95,128.01,127.76,127.44,126.46,116.66,109.18,52.15,47.15,20.81,20.47.

[0180] Embodiment 33

[0181] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-fluorobenzoate

[0182]

[0183] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-3-fluorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 42%). 1 H NMR(400MHz, CDCl3):7.73–7.69(m,1H),7.44(td,J=8.1,5.2Hz,1H),7.37–7.30(m,3H),7.29–7 .24(m,2H),7.23–7.18(m,2H),6.47(s,1H),6.02(s,1H),5.40(s,2H),3.76(s,3H),2.31(s,3H). 13 C NMR (151MHz, CDCl3): δ166.72 (d, J=3.2Hz), 163.64, 159.32 (d, J=248.2Hz), 146.07, 145.61, 136.54, 132.23 (d, J= 2.3Hz),129.94(d,J=8.5Hz),127.51,126.59,126.02(d,J=3.6Hz),119.56,119.41,117.98,108.96,52.50,20.81. 19 F NMR (376MHz, CDCl3): δ-113.23.

[0184] Embodiment 34

[0185] Methyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-chlorobenzoate

[0186]

[0187] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromo-3-chlorobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 34%). 1 H NMR (400MHz, CDCl3): δ7.82(dd,J=7.8,1.3Hz,1H),7.62(dd,J=8.1,1.2Hz,1H),7.40(t,J=7.9Hz,1H),7.34(t,J=7.3Hz,2H),7 .29–7.24(m,1H),7.21–7.17(m,2H),6.39(d,J=1.9Hz,1H),6.03–5.98(m,1H),5.41(d,J=9.8Hz,2H),3.74(s,3H),2.32(s,3H). 13 C NMR (100MHz, CDCl3): δ166.66,163.78,149.98,145.60,138.07,136.46,133.65,133.17 ,132.15,129.31,128.95,128.62,127.45,126.44,117.37,109.05,52.50,47.20,20.83.

[0188] Embodiment 35

[0189] 1-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-naphthoic acid methyl ester

[0190]

[0191] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromonaphthoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 47%). 1 H NMR (400MHz, CDCl3): δ7.99–7.89(m,3H),7.78(dd,J=8.6,1.2Hz,1H),7.59(ddd,J=8.1,6.8,1.2Hz,1H),7.51(ddd,J=8.3,6 .8,1.3Hz,1H),7.41–7.35(m,2H),7.32–7.25(m,3H),6.52(s,1H),6.09(s,1H),5.59–5.35(m,2H),3.79(s,3H),2.34(s,3H). 13 C NMR (100MHz, CDCl3): δ167.66,163.69,151.29,145.42,138.60,136.53,134.84,130.91,128.92,128.60 ,128.12,128.02,127.45,127.19,127.15,126.56,126.53,125.60,117.80,109.96,52.24,47.20,20.76.

[0192] Embodiment 36

[0193] (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0194]

[0195] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow solid, 62%). 1 H NMR (400MHz, CDCl3): δ7.86 (dd, J=7.7, 1.4Hz, 1H), 7.53 (td, J=7.5, 1.5Hz, 1H), 7.50–7.44 (m, 1H) ,7.35–7.31(m,3H),7.30–7.22(m,3H),6.54(s,1H),5.98(s,1H),5.47–5.27(m,2H),4.81(td,J=1 0.9,4.4Hz,1H),2.27(s,3H),2.04–1.97(m,1H),1.81(pd,J=7.0,2.7Hz,1H),1.77–1.61(m,3H),1 .51–1.41(m,1H),1.36–1.24(m,2H),1.11–0.98(m,1H),0.85-0.81(m,6H),0.73(d,J=6.9Hz,3H). 13 C NMR (100MHz, CDCl3): δ.167.32,163.92,152.99,145.01,139.63,136.67,131.62,130.78,130.16,129.82,128.97,128.5 7,127.53,126.86,116.26,109.28,75.60,47.30,47.09,40.67,34.22,31.42,26.36,23.38,22.14,20.92,20.77,16.33.

[0196] Embodiment 37

[0197] (5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-(R)-6-methylheptan-2-yl)hexahydro-1H-cyclopentylphenanthren-3-yl 2-(1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0198]

[0199] Under nitrogen protection, to a dried 10.0 mL reaction tube equipped with a magnetic stirrer were added 1-benzyl-6-methylpyridin-2(1H)-one (0.1 mmol, 1.0 equiv), (5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)hexahydro-1H-cyclopentadien-3-yl 2-bromobenzoate (0.15 mmol, 1.5 equiv), palladium chloride (0.01 mmol, 10 mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05 mmol, 50 mol%), anhydrous copper acetate (0.2 mmol, 2.0 equiv), and dry 1,4-dioxane (0.5 mL). The above reaction solution was placed in a magnetic stirrer reactor and heated and stirred at 120°C for 24 hours. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (white solid, 59%). 1 H NMR (400MHz, CDCl3): δ7.86 (dd, J=7.7, 1.4Hz, 1H), 7.53 (td, J=7.5, 1.5Hz, 1H), 7.45 (td, J=7.6, 1.4Hz ,1H),7.34(ddd,J=7.6,4.2,2.7Hz,3H),7.30–7.23(m,4H),6.53(s,1H),6.01(s,1H),5.36(q,J=15.6H z,2H),4.81(tt,J=10.9,4.8Hz,1H),2.29(s,3H),2.06–1.95(m,1H),1.85–1.77(m,1H),1.76–1.43(m, 10H),1.43–0.95(m,25H),0.90(d,J=6.5Hz,3H),0.86(dd,J=6.6,1.9Hz,6H),0.74(s,3H),0.65(s,3H). 13C NMR (100MHz, CDCl3): δ167.39,163.94,152.98,145.04,139.52,136.67,131.62,130.82,1 30.29,129.69,128.98,128.58,127.51,126.88,116.35,109.20,75.10,56.53,56.40,54. 29,47.35,44.68,42.72,40.10,39.65,36.77,36.30,35.94,35.59,35.57,33.84,32.08,28.77,28.38,28.15,27.20,24.34,23.98,22.96,22.70,21.32,20.77,18.81,12.33,12.21.

[0200] Embodiment 38

[0201] Methyl 2-(1-(ethoxymethyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0202]

[0203] Under nitrogen protection, 1-(ethoxymethyl)-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a dry 10.0mL reaction tube equipped with a magnetic stirrer. The above reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, it was cooled to room temperature, the product was filtered with diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 76%). 1 H NMR (600MHz, CDCl3) δ7.87(d,J=7.8Hz,1H),7.53(t,J=8.2Hz,1H),7.44(t,J=7.6Hz,1H),7.30(d,J=8.9Hz,1H) ,6.36(s,1H),5.96(s,1H),5.57(s,2H),3.75(s,3H),3.68(q,J=7.0Hz,2H),2.46(s,3H),1.20(t,J=7.0Hz,3H).13 C NMR (151MHz, CDCl3) δ167.78,164.06,153.48,145.28,139.76,131.82,130.23 ,129.71,129.52,128.54,116.25,108.71,72.19,65.01,52.20,19.58,15.19.

[0204] Embodiment 39

[0205] Methyl 4-(4-(2-(dimethylcarbamate)phenyl)-6-methyl-2-oxopyridin-1(2H)-yl)butanoate

[0206]

[0207] Under nitrogen protection, methyl 4-(6-methyl-2-oxopyridin-1(2H)-yl)butanoate (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 67%). 1 H NMR (600MHz, CDCl3) δ7.45–7.40(m,2H),7.37–7.32(m,2H),6.44(s,1H),6.18(s,1H),4.07(t,J=7.9H z,2H),3.68(s,3H),2.96(s,3H),2.66(s,3H),2.46(t,J=6.9Hz,2H),2.43(s,3H),2.05–1.99(m,2H). 13 CNMR(151MHz,CDCl3)δ173.49,170.63,163.52,151.06,145.57,135.94,135.54,129.54,1 29.19,128.86,127.37,116.07,108.11,51.82,43.75,38.58,34.90,31.13,23.56,20.44.

[0208] Embodiment 40

[0209] Methyl (E)-2-(1-(3-methoxy-3-oxopropyl-1-en-1-yl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzoate

[0210]

[0211] Under nitrogen protection, methyl (E)-3-(6-methyl-2-oxopyridin-1(2H)-yl)acrylate (0.1mmol, 1.0equiv), methyl 2-bromobenzoate (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), butyl (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 23%). 1 H NMR (400MHz, CDCl3) δ7.93(dd,J=7.8,1.4Hz,1H),7.79(d,J=14.3Hz,1H),7.57(td,J=7.5,1.4Hz,1H),7.48(td,J=7.6,1.4Hz,1H),7.31( dd,J=7.7,1.3Hz,1H),7.00(d,J=14.3Hz,1H),6.41(d,J=1.9Hz,1H),6.05(dd,J=2.0,1.0Hz,1H),3.82(s,3H),3.80(s,3H),2.42(s,3H). 13 C NMR (151MHz, CDCl3) δ166.42,166.37,162.35,151.88,141.47,138.33,136.69,131 .00,129.41,128.54,128.45,127.81,116.52,116.05,108.90,51.28,50.91,20.44.

[0212] Embodiment 41

[0213] 2-(1-(4-methoxybenzyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-N,N-dimethylbenzamide

[0214]

[0215] Under nitrogen protection, 1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 50%). 1 H NMR (400MHz, CDCl3) δ7.50–7.31(m,5H),7.15–7.10(m,2H),6.87–6.82(m,2H),6.54( s,1H),6.18(s,1H),5.28(s,2H),3.76(s,3H),2.95(s,3H),2.67(s,3H),2.30(s,3H). 13 C NMR (101MHz, CDCl3) δ170.62,163.86,159.03,151.23,146.18,135.90,135.53,129.59,129.28 ,128.79,128.48,128.06,127.40,116.15,114.30,108.09,55.38,46.72,38.56,34.88,20.77.

[0216] Embodiment 42

[0217] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-fluoro-N,N-dimethylbenzamide

[0218]

[0219] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-4-fluoro-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 45%). 1 H NMR (400MHz, CDCl3) δ7.39–7.28(m,3H),7.25(d,J=6.2Hz,1H),7.17–7.09(m,4H ),6.54(s,1H),6.17(s,1H),5.35(s,2H),2.94(s,3H),2.68(s,3H),2.28(s,3H). 13 C NMR (101MHz, CDCl3) δ169.83, 136.69, 162.90 (d, J = 250.1Hz), 148.39 (d, J = 345.5Hz), 138.34 (d, J = 7.6Hz), 136.26, 131.75 ,129.62(d,J=8.6Hz),129.00,127.63,126.55,116.25,116.08(dd,J=46.9,22.1Hz),107.66,47.29,38.66,35.02,20.83.

[0220] Embodiment 43

[0221] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-chloro-N,N-dimethylbenzamide

[0222]

[0223] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-5-chloro-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 40%). 1 H NMR(400MHz, CDCl3)δ7.42(dd,J=8.3,2.2Hz,1H),7.37–7.22(m,6H),7.18–7.09(m, 2H),6.56(s,1H),6.18(s,1H),5.35(s,2H),2.95(s,3H),2.70(s,3H),2.28(s,3H). 13 C NMR (101MHz, CDCl3) δ169.06,150.19,146.54,137.02,136.22,135.48,134.29,130.22,12 9.77,128.95,128.55,127.58,126.52,116.16,107.82,47.26,38.53,34.92,29.77,20.78.

[0224] Embodiment 44

[0225] 2-(1-Benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl)-5-methoxy-N,N-dimethylbenzamide

[0226]

[0227] Under nitrogen protection, 1-benzyl-6-methylpyridin-2(1H)-one (0.1mmol, 1.0equiv), 2-bromo-5-methoxy-N,N-dimethylbenzamide (0.15mmol, 1.5equiv), palladium chloride (0.01mmol, 10mol%), (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester (0.05mmol, 50mol%), anhydrous copper acetate (0.2mmol, 2.0equiv), and dry 1,4-dioxane (0.5mL) were added to a 10.0mL reaction tube dried and equipped with a magnetic stirrer. The reaction solution was placed on a magnetic stirrer reactor and heated and stirred at 120°C for 24h. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature and the product was filtered through celite and washed with ethyl acetate. The solvent was removed under reduced pressure and the crude product was directly separated and purified by column chromatography to obtain the target product (yellow oil, 47%). 1 H NMR (400MHz, CDCl3) δ7.36–7.26(m,3H),7.26–7.20(m,1H),7.14(d,J=7.5Hz,2H),6.97(dd,J=8.6,2.6Hz,1H),6 .88(d,J=2.6Hz,1H),6.57(s,1H),6.20(s,1H),5.35(s,2H),3.83(s,3H),2.94(s,3H),2.67(s,3H),2.26(s,3H). 13 C NMR (101MHz, CDCl3) δ170.48,164.00,160.42,151.09,146.01,136.80,136.50,130.34,128.96 ,128.16,127.54,126.56,115.74,115.63,112.57,108.28,55.65,47.18,38.50,34.94,20.77.

Claims

1. A method for preparing a 4-aryl-2-pyridone compound, characterized in that: The preparation method comprises reacting the compounds represented by formula (1) and formula (2), copper acetate, palladium chloride, and (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester in an organic solvent to obtain the compound represented by formula (3); Where: R 1 is selected from benzyl, C1-C6 alkoxy substituted benzyl, C1-C6 alkyl, C1-C6 alkoxy substituted C1-C6 alkyl, halogen substituted C1-C6 alkyl, -CH2R 10 OR 11 、-CH2CH2CH2CO2R 12 , C1-C6 alkyl substituted with a C2-C6 ester group or C2-C6 alkenyl substituted with a C2-C6 ester group; R 2 Selected from C1-C6 alkyl, halogen or phenylhydroxy C1-C6 alkyl; R 3 is selected from hydrogen or halogen; R 4 , R 8 Each independently selected from C2-C6 ester group, C2-C6 alkanoyl group, carboxyl group, nitro group, C1-C6 alkyl sulfone group, C1-C6 alkyl phosphate group, CO2R 13 , hydrogen, C1-C6 alkyl or halogen; R 5 、 R 6 、 R 7 Each is independently selected from hydrogen, C1-C6 alkyl, halogen, hydrogen, C1-C6 alkoxy or C2-C6 ester; R 9 is selected from hydrogen or deuterium; R 10 is benzyl or C1-C6 alkyl; R 11 is a pyridyl group or adamantyl C1-C3 alkanoyloxy group substituted with a C1-C3 alkyl group; R 12 is a cyclohexyl group substituted with a C1-C3 alkyl group or a cyclopentaphenanthryl group substituted with a C1-C3 alkanoyl group or a C1-C3 alkyl group; R 13 is a cyclohexyl group substituted with a C1-C3 alkyl group or a C1-C 10 Alkyl-substituted cyclopentaphenanthryl.

2. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The R 1 is selected from benzyl, C1-C3 alkoxy substituted benzyl, C1-C3 alkyl, C1-C3 alkoxy substituted C1-C3 alkyl, fluorine substituted C1-C3 alkyl, CH2R 10 OR 11 、CH2CH2CH2CO2R 12 , C1-C3 alkyl substituted with a C2-C4 ester group or C2-C4 alkenyl substituted with a C2-C4 ester group; R 2 Selected from C1-C3 alkyl, fluorine, chlorine, bromine or phenylhydroxy C1-C3 alkyl; R 3 is selected from hydrogen, fluorine, chlorine or bromine; R 4 , R 8 Each independently selected from C2-C4 ester group, C2-C4 alkanoyl group, carboxyl group, nitro group, C1-C3 alkyl sulfone group, C1-C4 alkyl phosphate group, CO2R 13 , hydrogen, C1-C3 alkyl, fluorine, chlorine or bromine; R 5 、 R 7 Each is independently selected from hydrogen, C1-C3 alkyl, fluorine, chlorine, bromine, hydrogen, C1-C3 alkoxy or C2-C4 ester; R 6 is selected from hydrogen, C1-C3 alkoxy, fluorine, chlorine or bromine; R 9 is hydrogen; R 10 It is benzyl or C1-C3 alkyl.

3. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The compound represented by formula (1) is selected from 1-benzyl-6-methylpyridin-2 (1H)-one, 1-(4-methoxybenzyl)-6-methylpyridin-2 (1H)-one, 1-benzyl-6-fluoropyridin-2 (1H)-one, 1,6-dimethylpyridin-2 (1H)-one, 6-methyl-1-(2,2,2-trifluoroethyl)pyridin-2 (1H)-one, 1-benzyl-6-chloropyridin-2 (1H)-one , 2,3-dihydroindole-5(1H)-one, 1-benzyl-3-fluoro-6-methylpyridin-2(1H)-one, 1-(ethoxymethyl)-6-methylpyridin-2(1H)-one, 1-benzyl-6-(2-hydroxy-2-phenylethyl)pyridin-2(1H)-one, 6-methyl-1-(4-(((6-methylpyridin-2-yl)oxy)methyl)benzyl)pyridin-2(1H)-one, 4-(6 -methyl-2-oxopyridin-1(2H)-yl)butyl 2-((3r,5r,7r)-adamantan-1-yl)acetate, (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-4-(6-methyl-2-oxopyridin-1(2H)-yl)butanoate, (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl 1-2 , one of the following: 3,4,7,8,9,10,11,12,13,14,15,16,17-decahydrophenanthrene-1H-cyclopentaphenanthrene-3-yl-4-(6-methyl-2-pyridone-1(2H)-yl)butyric acid methyl ester, 4-(6-methyl-2-oxopyridine-1(2H)-yl)butyric acid methyl ester, and (E)-3-(6-methyl-2-oxopyridine-1(2H)-yl)acrylate.

4. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The compound represented by formula (2) is selected from methyl 2-bromobenzoate, 2-bromo-N, N-dimethylbenzamide, methyl 2-bromo-4,5-dimethoxybenzoate, tert-butyl 2-bromobenzoate, 2-bromobenzoic acid, 2-bromonitrobenzene, 2-methylsulfonylbromobenzene, diethyl (2-bromophenyl)phosphonate, methyl 2-bromo-6-methylbenzoate, methyl 2-bromo-6-chlorobenzoate, methyl 2-bromo-5-methoxybenzoate, methyl 2-bromo-5-chlorobenzoate, methyl 2-bromo-5-fluorobenzoate, methyl 2-bromo-4-methoxybenzoate, methyl 2-bromo-4-fluorobenzoate, diethyl 2,5-dibromoterephthalate, 2-bromo-3- One of methyl methyl benzoate, methyl 2-bromo-3-fluorobenzoate, methyl 2-bromo-3-chlorobenzoate, methyl 2-bromonaphthoate, (1R, 2S, 5R)-2-isopropyl-5-methylcyclohexyl-2-bromobenzoate, (5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-((R)-6-methylheptane-2-yl)hexahydro-1H-cyclopentadien-3-yl 2-bromobenzoate, 2-bromo-4-fluoro-N, N-dimethylbenzamide, 2-bromo-5-chloro-N, N-dimethylbenzamide, and 2-bromo-5-methoxy-N, N-dimethylbenzamide.

5. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The organic solvent is at least one of acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, 1,4-dioxane, chlorobenzene, trifluorotoluene, toluene and o-xylene.

6. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The molar volume ratio of the compound represented by formula (1), the compound represented by formula (2), copper acetate, palladium chloride, (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester and the organic solvent is 0.1-0.15 mmol:0.15-0.225 mmol:0.2-0.3 mmol:0.01-0.015 mmol:0.05-0.075 mmol:0.5-0.75 ml.

7. The method for preparing 4-aryl-2-pyridone compounds according to claim 6, characterized in that: The molar volume ratio of the compound represented by formula (1), the compound represented by formula (2), copper acetate, palladium chloride, (1S, 4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylic acid butyl ester and the organic solvent is 0.1 mmol:0.15 mmol:0.2 mmol:0.01 mmol:0.05 mmol:0.5 ml.

8. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: The reaction temperature is 90-140°C; the reaction time is 10-30 h.

9. The method for preparing 4-aryl-2-pyridone compounds according to claim 8, characterized in that: The reaction temperature is 110-120°C; the reaction time is 10-30 h.

10. The method for preparing 4-aryl-2-pyridone compounds according to claim 9, characterized in that: The reaction temperature is 120°C and the reaction time is 24 h.

11. The method for preparing 4-aryl-2-pyridone compounds according to claim 1, characterized in that: It also includes post-processing the reaction product.

12. The method for preparing 4-aryl-2-pyridone compounds according to claim 11, characterized in that: The post-treatment includes filtering, washing, removing the solvent under reduced pressure, and column chromatography separation and purification in sequence.

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