A nitrogen-containing heterocyclic compound and a preparation method thereof

Abstract

The present invention belongs to the technical field of organic synthesis, and discloses a nitrogen-containing heterocyclic compound and a preparation method thereof. The compound is mainly reacted with 2-pyridone compounds, hydrazone compounds or diazo compounds as raw materials. The method has mild reaction conditions, good functional group tolerance and substrate universality, and can be produced on a gram scale; and no additional ligand is required, and it has excellent chemical selectivity, and deuterated labeled products can be easily obtained. These research advances are 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 nitrogen-containing heterocyclic compound and a preparation method thereof. Background Art

[0002] Nitrogen-containing heterocycles are an important structural unit that are widely present in the structures of many biologically active natural products and pharmaceutical molecules [Q. Li, LA Mitscher, LL Shen, Med. Res. Rev. 2000, 20, 231; JL Medina-Franco, K. Martínez-Mayorga, C. Juárez-Gordiano, R. Castillo, Chem Med Chem, 2007, 2, 1141].

[0003] At present, there are many methods for synthesizing nitrogen-containing heterocyclic compounds, but there are few reports on methods for efficiently preparing nitrogen-containing heterocyclic compounds from simple raw materials. There are currently three main known synthesis methods: the first is to directly obtain nitrogen-containing heterocyclic compounds from 2-hydroxypyridone compounds and diazo ester compounds under the catalysis of metal rhodium [Jiahui S., Qiongya L., Ying S., Jiangtao S., Org. Lett. 2022, 24, 1637-1641], but this method has a limited substrate range, and diazo compounds are unstable, explosive, and neurotoxic; the second is to use the classic addition reaction [Y. Kawanaka et al. al.Bioorg.Med.Chem.11(2003)1723-1743], but the reaction conditions of this method are harsh and the substrate range is limited; the third method is to use non-cyclic precursors to construct nitrogen-containing heterocycles [Theisen, PD Heathcock, CH J, Org. Chem.1993,58,142; Francis, C J Jones, J B J Chem. Soc., Chem. Commun.1984,579.], but the substrate type of this method is special, the steps are numerous and the reaction conditions are harsh.

[0004] Therefore, how to efficiently synthesize nitrogen-containing heterocyclic compounds using simple and readily available raw materials is a problem that needs to be solved urgently. Summary of the invention

[0005] The purpose of the present invention is to provide a nitrogen-containing heterocyclic compound and a preparation method thereof, so as to solve the problems existing in the synthesis of existing nitrogen-containing heterocyclic compounds.

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

[0007] The present invention provides a nitrogen-containing heterocyclic compound having the following structure:

[0008]

[0009] Wherein, n is any positive integer from 1 to 4;

[0010] R 1 One selected from aryl, substituted aryl, heteroaryl, heterocycle, alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, sulfone;

[0011] R 2 One selected from alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, aryl, heteroaryl, nitro, halogen, cyano, sulfone, and deuterium;

[0012] R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0013] R 4 One selected from ester group, amide group, phospholipid group, sulfone group and sulfoxide group.

[0014] The present invention also provides a method for preparing a nitrogen-containing heterocyclic compound, comprising the following steps:

[0015] Under a protective atmosphere, a 2-pyridone compound, a nitrogen-containing compound and an organic solvent are mixed and reacted under visible light irradiation to obtain a nitrogen-containing heterocyclic compound.

[0016] Preferably, in the above-mentioned method for preparing a nitrogen-containing heterocyclic compound, the structure of the 2-pyridone compound is:

[0017] Wherein, n is any positive integer from 1 to 4;

[0018] R 1 One selected from aryl, substituted aryl, heteroaryl, heterocycle, alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, sulfone;

[0019] R 2 One selected from alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, aryl, heteroaryl, nitro, halogen, cyano, sulfone and deuterium.

[0020] Preferably, in the above-mentioned method for preparing nitrogen-containing heterocyclic compounds, the nitrogen-containing compound is a hydrazone compound or a diazo compound; when the nitrogen-containing compound is a hydrazone compound, it also includes adding a base and mixing it with the 2-pyridone compound, the nitrogen-containing compound and the organic solvent.

[0021] Preferably, in the above-mentioned method for preparing nitrogen-containing heterocyclic compounds, when the nitrogen-containing compound is a hydrazone compound, the molar volume ratio of the 2-pyridone compound, the hydrazone compound, the base, and the organic solvent is 1-1.5 mmol: 2-3 mmol: 4-6 mmol: 2-5 mL;

[0022] When the nitrogen-containing compound is a diazo compound, the molar volume ratio of the 2-pyridone compound, the diazo compound and the organic solvent is 1-1.5 mmol: 2-3 mmol: 2-5 mL.

[0023] Preferably, in the above-mentioned method for preparing nitrogen-containing heterocyclic compounds, the base is one of triethylenediamine, N,N-diisopropylethylamine, triethylamine, diisopropylamine, N,N-dimethylethylenediamine, N,N,N',N'-tetramethylethylenediamine, 2,6-dimethoxypyridine, 4-dimethylaminopyridine, cesium carbonate, cesium fluoride, sodium hydride, sodium hydroxide, and potassium hydroxide.

[0024] Preferably, in the above-mentioned method for preparing a nitrogen-containing heterocyclic compound, the structure of the hydrazone compound is:

[0025]

[0026] Among them, R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0027] R 4 One selected from the group consisting of an ester group, an amide group, a phospholipid group, a sulfone group, and a sulfoxide group;

[0028] R 5 One selected from 2-(trifluoromethyl)benzenesulfonyl, p-toluenesulfonyl, 2-(nitro)benzenesulfonyl, 2,4,6-triisopropylphenyl, and 2-naphthalenesulfonyl;

[0029] The structure of the diazo compound is:

[0030] Among them, R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0031] R 4 One selected from ester group, amide group, phospholipid group, sulfone group and sulfoxide group.

[0032] Preferably, in the above method for preparing nitrogen-containing heterocyclic compounds, the wavelength of the visible light is 400 to 800 nm.

[0033] Preferably, in the above-mentioned method for preparing nitrogen-containing heterocyclic compounds, the reaction temperature is 0 to 80° C.; and the reaction time is 1 to 50 hours.

[0034] In the present invention, when the nitrogen-containing compound is a hydrazone compound, the hydrazone compound generates a diazo compound in situ under the action of a base, and the diazo compound generates a carbene intermediate under the excitation of visible light, which selectively cycloadds with a 2-pyridone compound to obtain the target product.

[0035] It can be seen from the above technical solution that compared with the prior art, the present invention has the following beneficial effects:

[0036] (1) The main raw materials of the method of the present invention are readily available 2-pyridone compounds, hydrazone compounds or diazo compounds, and hydrazone compounds have good stability. Most of the raw materials can be commercial reagents, no special treatment is required, the price is low, the preparation method is simple, and it is convenient for industrial production;

[0037] (2) The wavelength of the light used in the present invention is within 400-800 nm, which is a kind of natural light, saving costs and reducing pollution to the environment, which is in line with the development concept of green chemistry;

[0038] (3) The reaction conditions of the present invention have good functional group tolerance and substrate universality, and can be produced on a gram scale;

[0039] (4) The preparation method of the present invention is efficient and diverse, and the six-three-membered ring structure is constructed in one step, which has extremely high step economy;

[0040] (5) The method of the present invention does not require the addition of additional ligands, has excellent chemical selectivity, and can easily obtain deuterated labeled products. These research advances are expected to be applied in related medicinal chemistry and natural product synthesis. DETAILED DESCRIPTION

[0041] The present invention provides a nitrogen-containing heterocyclic compound having the following structure:

[0042]

[0043] Wherein, n is any positive integer from 1 to 4;

[0044] R 1 One selected from aryl, substituted aryl, heteroaryl, heterocycle, alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, sulfone;

[0045] R 2 One selected from alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, aryl, heteroaryl, nitro, halogen, cyano, sulfone, and deuterium;

[0046] R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0047] R 4 One selected from ester group, amide group, phospholipid group, sulfone group and sulfoxide group.

[0048] In the present invention, the R 1 and R 3 The structures of the substituted aryl groups in are independently:

[0049] Among them, R 6 Independently selected from one of alkyl, halogen, ester, methoxy, acetal and cyano.

[0050] The present invention also provides a method for preparing a nitrogen-containing heterocyclic compound, comprising the following steps:

[0051] Under a protective atmosphere, a 2-pyridone compound, a nitrogen-containing compound and an organic solvent are mixed and reacted under visible light irradiation to obtain a nitrogen-containing heterocyclic compound.

[0052] In the present invention, the structure of the 2-pyridone compound is:

[0053] Wherein, n is any positive integer from 1 to 4;

[0054] R 1 One selected from aryl, substituted aryl, heteroaryl, heterocycle, alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, sulfone;

[0055] R 2 One selected from alkyl, alkoxy, hydrogen, ester, alkynyl, alkenyl, aryl, heteroaryl, nitro, halogen, cyano, sulfone and deuterium.

[0056] In the present invention, the nitrogen-containing compound is a hydrazone compound or a diazo compound;

[0057] When the nitrogen-containing compound is a hydrazone compound, the method further comprises adding a base to mix with the 2-pyridone compound, the nitrogen-containing compound and the organic solvent.

[0058] In the present invention, when the nitrogen-containing compound is a hydrazone compound, the molar volume ratio of the 2-pyridone compound, the hydrazone compound, the base, and the organic solvent is preferably 1-1.5 mmol: 2-3 mmol: 4-6 mmol: 2-5 mL, more preferably 1-1.3 mmol: 2-2.7 mmol: 4-5.4 mmol: 2.1-4.2 mL, and more preferably 1 mmol: 2 mmol: 4 mmol: 2.5 mL;

[0059] When the nitrogen-containing compound is a diazo compound, the molar volume ratio of the 2-pyridone compound, the diazo compound and the organic solvent is preferably 1-1.5 mmol: 2-3 mmol: 2-5 mL, more preferably 1-1.2 mmol: 2-2.5 mmol: 2.3-3.6 mL, and more preferably 1 mmol: 2 mmol: 2.5 mL.

[0060] In the present invention, the base is preferably one of triethylenediamine, N,N-diisopropylethylamine, triethylamine, diisopropylamine, N,N-dimethylethylenediamine, N,N,N',N'-tetramethylethylenediamine, 2,6-dimethoxypyridine, 4-dimethylaminopyridine, cesium carbonate, cesium fluoride, sodium hydride, sodium hydroxide, and potassium hydroxide, and is further preferably one of triethylenediamine, triethylamine, N,N-dimethylethylenediamine, 4-dimethylaminopyridine, cesium carbonate, and potassium hydroxide, and is more preferably triethylamine or cesium carbonate.

[0061] In the present invention, the structure of the hydrazone compound is:

[0062] Among them, R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0063] R 4 One selected from the group consisting of an ester group, an amide group, a phospholipid group, a sulfone group, and a sulfoxide group;

[0064] R 5 One selected from 2-(trifluoromethyl)benzenesulfonyl, p-toluenesulfonyl, 2-(nitro)benzenesulfonyl, 2,4,6-triisopropylphenyl, and 2-naphthalenesulfonyl;

[0065] The structure of the diazo compound is:

[0066] Among them, R 3 One selected from aryl, substituted aryl, heteroaryl, heterocyclic, naphthyl, acyl, sulfoxide, sulfone, and alkyl;

[0067] R 4One selected from ester group, amide group, phospholipid group, sulfone group and sulfoxide group.

[0068] In the present invention, the organic solvent is preferably one or more of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, 1,4-dioxane, chlorobenzene, trifluorotoluene, toluene, o-xylene, and n-heptane, and is further preferably one or more of acetonitrile, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, 1,4-dioxane, and toluene, and is more preferably dichloromethane.

[0069] In the present invention, the wavelength of the visible light is preferably 400 to 800 nm, more preferably 430 to 760 nm, and even more preferably 650 nm.

[0070] In the present invention, the reaction temperature is preferably 0-80°C, more preferably 20-64°C, more preferably 35°C; the reaction time is preferably 1-50h, more preferably 16-41h, more preferably 38h.

[0071] In the present invention, after the reaction is completed, the reaction product is subjected to post-treatment; the post-treatment includes one or more of suction filtration, concentration, recrystallization and column chromatography purification. The present invention does not limit the specific method of post-treatment, and methods well known to those skilled in the art are sufficient.

[0072] The present invention also provides an application of nitrogen-containing heterocyclic compounds in drug synthesis and natural product synthesis, specifically in the preparation of anti-inflammatory drugs.

[0073] 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.

[0074] Example 1

[0075] Preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0076]

[0077] Under nitrogen protection, add 1-benzylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 81%). 1 HNMR(400MHz, CDCl3)δ7.37(d,J=3.8Hz,4H),7.35–7.30(m,1H),7.30–7.25(m,3H),7.00–6.94(m,2H),6.65(dd,J=9.8,5.2Hz,1H),5 .70(d,J=9.9Hz,1H),5.52(d,J=14.7Hz,1H),4.17(d,J=14.6Hz,1H),3.89(d,J=8.9Hz,1H),3.63(s,3H),2.88(dd,J=8.9,5.3Hz,1H). 13 C NMR (126MHz, CDCl3) δ173.47,161.43,136.31,136.18,133.26,129.50,128.91 ,128.50,128.32,128.14,127.95,126.47,53.17,50.55,48.71,33.85,28.12.

[0078] Example 2

[0079] The preparation of methyl 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 1, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 1.

[0080] Example 3

[0081] Preparation of 3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0082]

[0083] Under nitrogen protection, add 2-hydroxypyridine (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 45%). 1 HNMR (400MHz, CDCl3): δ7.56–7.49(m,1H),7.34–7.27(m,3H),7.16–7.07(m,2H),6.75(ddd,J=10.0,5.5,0.8Hz ,1H),5.60(dd,J=10.0,1.6Hz,1H),3.92(ddd,J=8.7,3.6,0.7Hz,1H),3.62(s,3H),2.94(dd,J=8.6,5.4Hz,1H). 13 C NMR (126MHz, CDCl3) δ173.28,163.53,138.50,133.86,129.51,128.41,128.04,125.72,53.15,44.11,33.24,27.14.

[0084] Example 4

[0085] The preparation of 3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester is specifically described in Example 3, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 3.

[0086] Example 5

[0087] Preparation of 2-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0088]

[0089] Under nitrogen protection, add 1-methylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 84%). 1 H NMR (400MHz, CDCl3) δ7.31–7.26(m,2H),7.26–7.22(m,1H),7.02–6.97(m,2H),6.63(ddd,J=9.8,5.3,0.7Hz,1 H),5.62(d,J=9.8Hz,1H),3.84(dd,J=8.8,0.7Hz,1H),3.64(s,3H),3.21(s,3H),2.91(dd,J=8.8,5.3Hz,1H). 13 CNMR (126MHz, CDCl3) δ173.62,161.58,135.89,133.14,129.51,128.51,128.19,126.46,53.16,50.68,35.27,33.63,28.18.

[0090] Example 6

[0091] The preparation of methyl 2-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 5, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 5.

[0092] Example 7

[0093] Preparation of 3-oxo-2,7-diphenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0094]

[0095] Under nitrogen protection, add 1-phenylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 79%). 1 H NMR (400MHz, CDCl3) δ7.61–7.53(m,2H),7.51–7.44(m,2H),7.34–7.26(m,4H),7.19–7.09(m,2H),6.74(dd ,J=9.9,5.3Hz,1H),5.78(d,J=9.8Hz,1H),4.29(d,J=8.9Hz,1H),3.67(s,3H),3.06(dd,J=8.9,5.3Hz,1H). 13 C NMR (126MHz, CDCl3) δ173.37,160.90,141.55,136.53,133.45,129.48,129 .18,128.59,128.35,127.54,126.50,124.92,53.33,50.63,34.55,28.09.

[0096] Example 8

[0097] The preparation of methyl 3-oxo-2,7-diphenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 7, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 7.

[0098] Example 9

[0099] Preparation of 2-tert-butyl-7-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-2,7-dicarboxylate

[0100]

[0101] Under nitrogen protection, add tert-butyl 2-oxopyridine-1(2H)-carboxylate (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 71%). 1 H NMR (500MHz, CDCl3) δ7.29–7.27(m,2H),7.27(s,1H),7.11–7.05(m,2H),6.77(dd,J=9.8,5.2Hz,1H) ,5.63(d,J=9.8Hz,1H),4.42(d,J=8.9Hz,1H),3.66(s,3H),2.94(dd,J=8.9,5.2Hz,1H),1.61(s,9H). 13 C NMR (101MHz, CDCl3) δ172.69,160.20,152.27,137.99,133.26,129.22,128.59,128.32,127.16,84.19,53.21,46.14,35.48,28.10,26.43.

[0102] Example 10

[0103] The preparation of 2-tert-butyl-7-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-2,7-dicarboxylate is specifically described in Example 9, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 9.

[0104] Embodiment 11

[0105] Preparation of 3-oxo-7-phenyl-2-p-toluenesulfonyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0106]

[0107] Under nitrogen protection, add 1-toluenesulfonylpyridin-2(1H)-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 75%). 1 H NMR (400MHz, CDCl3): δ8.04–7.94(m,2H),7.35–7.27(m,5H),7.26–7.19(m,2H),6.81(ddd,J=9.8,5.3,0.7Hz, 1H), 5.52 (d, J=9.8Hz, 1H), 4.81 (dd, J=9.0, 0.7Hz, 1H), 3.70 (s, 3H), 3.00 (dd, J=9.0, 5.3Hz, 1H), 2.43 (s, 3H). 13 C NMR (100MHz, CDCl3): δ172.54,159.51,145.47,139.88,135.74,133.73,129.5 5,129.07,128.56,128.47,128.43,125.71,53.48,46.72,35.34,26.94,21.82.

[0108] Example 12

[0109] The preparation of 3-oxo-7-phenyl-2-toluenesulfonyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester is specifically described in Example 11, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The H NMR and C NMR spectra of the target product are the same as those in Example 11.

[0110] Embodiment 13

[0111] Preparation of 2-methoxy-2-oxoethyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0112]

[0113] Under nitrogen protection, add 2-(2-oxopyridin-1(2H)-yl)acetic acid methyl ester (0.1mmol, 1.0equiv), 2-diazo-2-phenylacetic acid methyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 51%). 1 H NMR (400MHz, CDCl3) δ7.33–7.28(m,2H),7.25(d,J=6.8Hz,1H),6.99(dd,J=7.4,2.0Hz,2H),6.73(dd,J=9.9,5.3Hz,1H),5.67(d,J=9. 9Hz,1H),4.95(d,J=17.1Hz,1H),3.99(d,J=9.0Hz,1H),3.78(s,3H),3.74(s,1H),3.64(d,J=1.1Hz,3H),2.98(dd,J=8.9,5.3Hz,1H). 13 CNMR (126MHz, CDCl3) δ173.21,169.02,161.46,137.13,133.16,129.48,128.59,128.25,125.86,53.22,52.59,49.99,48.57,34.00,28.03.

[0114] Embodiment 14

[0115] The preparation of 2-2-methoxy-2-oxoethyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester is specifically described in Example 13, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 13.

[0116] Embodiment 15

[0117] Preparation of 2-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo-6-isoquinolinol)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0118]

[0119] Under nitrogen protection, add 2-butyl-6-(2-oxopyridine-1-2H-yl)-1-benzisoquinoline-1,3-dione (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 52%). 1 H NMR (400MHz, CDCl3) δ8.72(t,J=8.5Hz,1H),8.63(dd,J=12.9,7.2Hz,1H),8.16(d,J=8.4Hz ,1H),7.91–7.76(m,2H),7.45–7.35(m,3H),7.34–7.26(m,2H),7.02(dd,J=10.1,5.6Hz,1H) ,5.94(d,J=10.0Hz,1H),4.28(d,J=8.7Hz,1H),4.24–4.18(m,2H),3.60(s,3H),3.19(dd,J =8.8,5.3Hz,1H),1.73(dd,J=8.8,6.4Hz,2H),1.46(q,J=7.5Hz,2H),0.99(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3): δ172.95,164.03,161.49,143.52,138.42,133.79,131.72,131.22,128.97, 128.66,127.83,126.57,123.70,122.73,53.42,52.09,40.44,35.31,30.28,27.70,20.46,13.96.

[0120] Example 16

[0121] The preparation of methyl 2-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo-6-isoquinolinol)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 15, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 15.

[0122] Embodiment 17

[0123] Preparation of 3-oxo-7-phenyl-2-thiophen-2-yl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0124]

[0125] Under nitrogen protection, add 2-thiophene-2-pyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 62%). 1 H NMR(400MHz, CHLOROFORM-D) δ7.53(dd,J=5.2,1.5Hz,1H),7.49(dd,J=3.3,1.5Hz,1H),7.39–7.36(m,1H),7.23(dt,J=3.7,2.7Hz,3H),7.06– 7.01(m,2H),6.71(ddd,J=9.9,5.3,0.8Hz,1H),5.75(d,J=9.8Hz,1H),4.32(dd,J=9.0,0.8Hz,1H),3.70(s,3H),3.03(dd,J=9.0,5.2Hz,1H). 13 C NMR(101MHz,CHLOROFORM-D)δ173.35,159.93,140.12,136.09,133.07,129.26 ,128.63,128.35,127.19,124.85,123.21,114.07,53.38,49.75,34.34,28.03.

[0126] Embodiment 18

[0127] The preparation of methyl 3-oxo-7-phenyl-2-thiophen-2-yl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 17, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 17.

[0128] Embodiment 19

[0129] Preparation of 3-oxo-7-phenyl-2-pyridin-2-yl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0130]

[0131] Under nitrogen protection, add 2-pyridylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 86%). 1 H NMR (400MHz, CDCl3): δ8.57(ddd,J=4.9,2.0,0.9Hz,1H),7.94(dt,J=8.4,1.0Hz,1H),7.72(ddd,J=8.4,7.3,2.0Hz,1H),7.22–7.14(m ,5H),6.81(ddd,J=9.8,5.4,0.9Hz,1H),5.76(d,J=9.8Hz,1H),4.76(dd,J=8.8,0.9Hz,1H),3.69(s,3H),3.05(dd,J=8.8,5.3Hz,1H). 13C NMR (100MHz, CDCl3): δ173.63,161.53,153.05,148.34,137.77,137.15,133.63 ,129.67,128.38,128.07,127.09,120.87,120.16,53.23,47.82,34.67,27.78.

[0132] Embodiment 20

[0133] The preparation of 3-oxo-7-phenyl-2-pyridin-2-yl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester is specifically described in Example 19, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 19.

[0134] Embodiment 21

[0135] Preparation of 3-oxo-7-phenyl-2-phenylvinyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0136]

[0137] Under nitrogen protection, add 1-phenylvinylpyridin-2-1-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 70%). 1H NMR (400MHz, CDCl3): δ8.17(d,J=14.9Hz,1H),7.52–7.47(m,2H),7.39–7.32(m,3H),7.24(dd,J=5.3,2.4Hz,3H),7.04–6.99(m,2H),6.8 0(dd,J=9.9,5.2Hz,1H),6.33(d,J=14.9Hz,1H),5.77(d,J=9.9Hz,1H),4.25(d,J=8.9Hz,1H),3.74(s,3H),3.01(dd,J=8.9,5.2Hz,1H). 13 CNMR(101MHz,CHLOROFORM-D)δ173.40,159.01,137.16,136.26,132.85,128.94,12 8.67,128.50,127.22,126.58,126.30,125.99,113.10,53.46,44.82,35.05,27.46.

[0138] Embodiment 22

[0139] The preparation of methyl 3-oxo-7-phenyl-2-phenylvinyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 21, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 21.

[0140] Embodiment 23

[0141] Preparation of 3-methoxy-3-oxoprop-1-en-1-yl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0142]

[0143] Under nitrogen protection, add 2-oxopyridine-1-propenoic acid methyl ester (0.1mmol, 1.0equiv), 2-diazo-2-phenylacetic acid methyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 85%). 1 HNMR (400MHz, CDCl3): δ8.65(d,J=14.4Hz,1H),7.28(s,1H),7.26(d,J=6.3Hz,3H),6.96–6.91(m,2H),6.89(dd,J=9.9,5.2Hz,1 H),5.77(d,J=10.0Hz,1H),5.68(d,J=14.4Hz,1H),4.09(d,J=8.7Hz,1H),3.82(s,3H),3.70(s,3H),3.00(dd,J=8.8,5.3Hz,1H). 13 C NMR (126MHz, CDCl3) δ172.57,167.57,158.81,140.75,139.19,132.74,12 8.76,128.64,128.43,125.15,101.29,53.54,51.78,44.44,36.13,26.65.

[0144] Embodiment 24

[0145] The preparation of 3-methoxy-3-oxoprop-1-en-1-yl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester is specifically described in Example 23, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 23.

[0146] Embodiment 25

[0147] Preparation of 2-(benzoyloxy)-5-(benzoyloxy)methyl)-5-(methoxycarbonyl)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-2-yl)tetrahydrofuran-3,4-dialkyl dibenzoate

[0148]

[0149] Under nitrogen protection, add 2-benzoyloxymethyl-2-(benzoyloxy)methyl-5-(2-oxopyridin-1(2H)yl)tetrahydrofuran-3,4-dibenzoate (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 62%). 1 H NMR (400MHz, CDCl3): δ8.19–7.91(m,11H),7.59–7.34(m,16H),7.13–6.97(m,5H),6.71–6 .65(m,2H),6.33(d,J=5.7Hz,1H),6.02(t,J=5.2Hz,1H),5.95–5.89(m,2H),5.68(d,J=10 .0Hz,1H),5.61(d,J=9.9Hz,1H),4.80–4.72(m,2H),4.67(dq,J=10.7,5.2Hz,3H),4.23(d ,J=9.0Hz,1H),4.07(d,J=8.9Hz,1H),3.48(d,J=4.6Hz,5H),2.92(dt,J=8.7,5.8Hz,2H). 13C NMR (100MHz, CDCl3): δδ173.00,172.92,166.45,166.30,165.65,165.52,165.44,161.95,161.42,138.10,137.59, 133.87,133.77,133.70,133.60,133.45,133.39,133.31,130.09,130.06,130.00,129.96,129.91,129.76,129.59 ,129.52,129.28,129.02,128.88,128.80,128.69,128.59,128.54,128.37,128.19,127.99,127.92,126.42,126.13,86.43,79.96,79.67,73.05,71.85,71.63,71.60,64.76,53.18,46.33,44.91,34.13,34.06,29.83,27.48,26.99.

[0150] Embodiment 26

[0151] The preparation of 2-(benzoyloxy)-5-(benzoyloxy)methyl)-5-(methoxycarbonyl)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-2-yl)tetrahydrofuran-3,4-dialkyl dibenzoate is specifically described in Example 25, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The H NMR and C NMR spectra of the target product are the same as those in Example 25.

[0152] Embodiment 27

[0153] Preparation of methyl 2-(2S,3S,4R)-3-benzoyloxy-4-(tert-butyldimethylsilyloxy)tetrahydrofuran-2-yl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptyl-4-ene-7-carboxylate

[0154]

[0155] Under nitrogen protection, add 2-tert-butyldimethylsilyloxy-2-(2-oxo-tert-butyl)-2-(2-oxopyridin-1(2H)yl)tetrahydrofuran-3-ylbenzoate (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 87%). 1 H NMR (400MHz, CDCl3): δ8.10–8.02(m,2H),7.60–7.55(m,1H),7.44(d,J=5.7Hz,2H),7 .39–7.27(m,4H),7.23(d,J=7.3Hz,3H),6.68(dd,J=9.8,5.3Hz,1H),6.07(s,1H),5.5 9(d,J=9.8Hz,1H),5.24(s,1H),4.43(d,J=9.0Hz,1H),4.40–4.35(m,1H),4.27–4.18 (m,2H),3.65(s,3H),2.90(dd,J=9.0,5.4Hz,1H),0.94(s,9H),0.19(d,J=5.3Hz,6H). 13 C NMR (100MHz, CDCl3): δ173.57,165.26,161.33,136.76,133.66,133.51,130.17,130.01,129.50,128.86,128.54,128.3 6,127.89,127.81,126.28,90.13,82.99,76.83,74.52,53.05,52.55,45.10,33.43,27.83,25.72,18.04,-4.63,-5.22.

[0156] Embodiment 28

[0157] The preparation of methyl 2-(2S,3S,4R)-3-benzoyloxy-4-(tert-butyldimethylsilyloxy)tetrahydrofuran-2-yl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptyl-4-ene-7-carboxylate is specifically described in Example 27, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 27.

[0158] Embodiment 29

[0159] Preparation of (2S, 3S, 4S, 5S)-2-acetoxymethyl-5-(7-methoxycarbonyl)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-2-yl)tetrahydrofuran-3,4-diyl diacetate

[0160]

[0161] Under nitrogen protection, add (2S, 3S, 4S, 5S)-2-acetoxymethyl-5-(2-oxopyridin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 48%). 1 H NMR (400MHz, CDCl3): δ7.23 (q, J=2.9Hz, 3H), 7.13–7.07 (m, 2H), 6.66 (dd, J=9.9, 5. 1Hz,1H),6.22(d,J=6.6Hz,1H),5.65(d,J=9.9Hz,1H),5.52(t,J=6.2Hz,1H),5.45( dd,J=5.9,3.8Hz,1H),4.38–4.30(m,2H),4.28(p,J=3.1Hz,1H),4.15(d,J=9.1Hz,1 H),3.64(s,3H),2.94(dd,J=9.1,5.1Hz,1H),2.16(s,3H),2.15(s,3H),2.13(s,3H). 13C NMR (100MHz, CDCl3): δ173.18,170.87,169.91,169.87,162.02,137.96,133.06,129.63,128.28,128.0 4,126.39,86.56,79.17,71.56,71.05,63.97,53.36,45.67,33.78,29.84,27.52,20.89,20.77,20.68.

[0162] Embodiment 30

[0163] The preparation of (2S,3S,4S,5S)-2-acetoxymethyl-5-(7-methoxycarbonyl)-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-2-yl)tetrahydrofuran-3,4-diyl diacetate is specifically described in Example 29, except that methyl 2-diazo-2-phenylacetate is replaced by methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those of Example 29.

[0164] Embodiment 31

[0165] Preparation of 2-benzyl-4-chloro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0166]

[0167] Under nitrogen protection, add 1-benzyl-3-chloropyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 55%). 1H NMR (400MHz, CHLOROFORM-D) δ7.27(s,2H),7.24(d,J=2.6Hz,2H),7.22–7.12(m,4H),6.86–6.80(m,2H),6.70(d,J=5.8H z,1H),5.32(d,J=14.5Hz,1H),4.14(d,J=14.5Hz,1H),3.82(d,J=8.9Hz,1H),3.52(s,3H),2.79(dd,J=9.1,5.9Hz,1H). 13 C NMR(101MHz,CHLOROFORM-D)δ173.17,157.47,135.70,133.34,132.56,130.17,12 9.06,128.85,128.77,128.67,128.48,128.31,53.33,51.98,48.59,33.84,28.21.

[0168] Embodiment 32

[0169] The preparation of methyl 2-benzyl-4-chloro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 31, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 31.

[0170] Embodiment 33

[0171] Preparation of 2-benzyl-4-bromo-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0172]

[0173] Under nitrogen protection, add 1-benzyl-3-bromopyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 98%). 1HNMR (400MHz, CDCl3): δ7.40–7.26(m,8H),7.09(dd,J=5.8,0.7Hz,1H),6.99–6.89(m,2H),5.44(d,J= 14.5Hz,1H),4.27(d,J=14.5Hz,1H),3.95(d,J=8.9Hz,1H),3.65(s,3H),2.87(dd,J=9.0,5.8Hz,1H). 13 C NMR (101MHz, CDCl3) δ173.03,157.14,137.16,135.66,133.29,128.98,128.77 ,128.67,128.60,128.38,128.21,121.41,53.27,52.19,48.79,33.74,29.50.

[0174] Embodiment 34

[0175] The preparation of methyl 2-benzyl-4-bromo-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 33, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 33.

[0176] Embodiment 35

[0177] Preparation of 2-benzyl-3-oxo-7-phenyl-4-trifluoromethyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0178]

[0179] Under nitrogen protection, add 1-benzyl-3-trifluoromethylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 86%). 1H NMR(400MHz,CHLOROFORM-D)δ7.39(d,J=3.0Hz,5H),7.32–7.27(m,3H),7.22(d,J=5.6Hz,1H),6.88(dd,J=6.6,3.0Hz ,2H),5.45(d,J=14.5Hz,1H),4.25(d,J=14.5Hz,1H),3.95(d,J=8.7Hz,1H),3.67(s,3H),2.98(dd,J=8.6,5.8Hz,1H). 13 C NMR (101MHz, CHLOROFORM-D) δ150.25,136.28,135.54,130.28,129.83,129.01,127.64,126.57,116.22,107.88,47.32,38.59,34.98,29.83,20.84.

[0180] Embodiment 36

[0181] The preparation of methyl 2-benzyl-3-oxo-7-phenyl-4-trifluoromethyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 35, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 35.

[0182] Embodiment 37

[0183] Preparation of 2-benzyl-4-nitro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0184]

[0185] Under nitrogen protection, add 1-benzyl-3-nitropyridine-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 54%). 1HNMR (400MHz, CDCl3): δ7.42(d,J=5.7Hz,1H),7.39–7.32(m,5H),7.28(dd,J=5.0,1.8Hz,3H),6.92(dd,J=6.6,2.9Hz,2H),5 .48(d,J=14.6Hz,1H),4.22(d,J=14.6Hz,1H),3.95(d,J=8.6Hz,1H),3.69(s,3H),3.65(s,3H),2.98(dd,J=8.6,5.7Hz,1H). 13 C NMR (100MHz, CDCl3): δ172.80,164.52,157.92,143.21,135.80,133.10,129.29,128.89,1 28.60,128.53,128.49,128.44,128.05,77.28,53.28,52.42,50.87,48.83,35.69,27.28.

[0186] Embodiment 38

[0187] The preparation of methyl 2-benzyl-4-nitro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 37, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 37.

[0188] Embodiment 39

[0189] Preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-4,7-dicarboxylic acid dimethyl ester

[0190]

[0191] Under nitrogen protection, add 1-benzyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid methyl ester (0.1mmol, 1.0equiv), 2-diazo-2-phenylacetic acid methyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 52%). 1 H NMR (400MHz, CDCl3) δ7.42(d,J=5.6Hz,1H),7.39–7.32(m,5H),7.28(dd,J=4.9,1.9Hz,3H),6.92(dd,J=6.6,2.9Hz,2H),5. 48(d,J=14.6Hz,1H),4.22(d,J=14.6Hz,1H),3.95(d,J=8.6Hz,1H),3.69(s,3H),3.65(s,3H),2.98(dd,J=8.6,5.7Hz,1H). 13 C NMR (126MHz, CDCl3) δ172.88,164.59,158.00,143.28,135.87,133.18,129.37,128.9 7,128.67,128.61,128.57,128.51,128.13,53.35,52.50,50.94,48.91,35.76,27.36.

[0192] Embodiment 40

[0193] The preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-4,7-dicarboxylic acid dimethyl ester is specifically described in Example 39, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 39.

[0194] Embodiment 41

[0195] Preparation of 2-benzyl-5-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0196]

[0197] Under nitrogen protection, add 1-benzyl-4-methylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 58%). 1 H NMR (400MHz, CDCl3): δ7.35(d,J=3.8Hz,3H),7.34–7.29(m,2H),7.29(d,J=1.7Hz,1H),7.28–7.25(m,2H),7.00–6.95(m,2H),5.58(d,J= 14.7Hz,1H),5.53–5.50(m,1H),4.13(d,J=14.7Hz,1H),3.85(d,J=8.9Hz,1H),3.63(s,3H),2.74(d,J=8.9Hz,1H),2.08(d,J=1.4Hz,3H). 13 C NMR (126MHz, CDCl3) δ173.64,162.19,146.65,136.48,131.88,130.03,128.88,12 8.62,128.29,128.27,127.86,122.42,53.14,50.22,48.65,33.78,32.12,23.53.

[0198] Embodiment 42

[0199] The preparation of methyl 2-benzyl-5-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 41, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 41.

[0200] Embodiment 43

[0201] Preparation of 2-benzyl-5-iodo-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0202]

[0203] Under nitrogen protection, add 1-benzyl-4-iodopyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 60%). 1 H NMR (400MHz, CDCl3): δ7.41–7.30(m,8H),7.11(dd,J=6.5,2.9Hz,2H),6.38(s,1H),5.50(d,J= 14.6Hz, 1H), 4.15 (d, J = 14.6Hz, 1H), 3.77 (d, J = 9.1Hz, 1H), 3.66 (s, 3H), 3.31 (d, J = 9.1Hz, 1H). 13 C NMR (126MHz, CDCl3) δ172.76,159.34,135.72,135.28,132.26,129.02,12 8.76,128.67,128.38,128.17,107.86,53.41,50.43,49.97,38.74,35.15.

[0204] Embodiment 44

[0205] The preparation of methyl 2-benzyl-5-iodo-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 43, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 43.

[0206] Embodiment 45

[0207] Preparation of 2-benzyl-5-benzyloxy-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0208]

[0209] Under nitrogen protection, add 1-benzyl-4-benzyloxypyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 54%). 1 H NMR (400MHz, CDCl3): δ7.46–7.39(m,5H),7.37(d,J=4.3Hz,4H),7.35–7.26(m,4H),7.08–7.02(m,2H),5.55(d,J=14.8Hz,1H),5.00(s,1H ), 4.83 (d, J = 11.3Hz, 1H), 4.72 (d, J = 11.3Hz, 1H), 4.17 (d, J = 14.8Hz, 1H), 3.88 (d, J = 9.5Hz, 1H), 3.61 (s, 3H), 2.98 (dd, J = 9.5, 1.2Hz, 1H). 13 C NMR(101MHz,CHLOROFORM-D)δ172.97,164.35,163.22,136.69,134.97,131.70,130.14,128.96,1 28.93,128.91,128.68,128.42,128.31,127.89,97.28,71.25,53.17,50.03,47.22,33.09,29.87.

[0210] Embodiment 46

[0211] The preparation of methyl 2-benzyl-5-benzyloxy-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 45, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 45.

[0212] Embodiment 47

[0213] Preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-5,7-dicarboxylic acid dimethyl ester

[0214]

[0215] Under nitrogen protection, add 1-benzyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester (0.1mmol, 1.0equiv), 2-diazo-2-phenylacetic acid methyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 84%). 1 H NMR (400MHz, CDCl3): δ7.41–7.26(m,7H),7.25(d,J=2.0Hz,1H),6.89(dd,J=6.5,3.0Hz,2H),6.46(s,1H),5.52( d,J=14.5Hz,1H),4.22(d,J=14.6Hz,1H),3.96(d,J=9.1Hz,1H),3.89(s,3H),3.66(s,3H),3.26(d,J=9.1Hz,1H). 13 C NMR(101MHz,CHLOROFORM-D)δ172.98,165.51,161.17,137.18,135.69,132.48,130.69,12 9.29,129.07,128.86,128.48,128.45,128.24,53.32,53.09,50.79,48.24,33.49,27.06.

[0216] Embodiment 48

[0217] The preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-5,7-dicarboxylic acid dimethyl ester is specifically described in Example 47, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 47.

[0218] Embodiment 49

[0219] Preparation of 2-benzyl-4-bromo-6-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0220]

[0221] Under nitrogen protection, add 1-benzyl-3-bromo-5-methylpyridin-2-one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 57%). 1 H NMR (400MHz, CDCl3): δ7.45–7.34(m,5H),7.24(dd,J=4.8,1.9Hz,3H),6.84(dd,J=6.3,2.5Hz,3H) ,5.25(d,J=14.3Hz,1H),4.44(d,J=14.4Hz,1H),4.01(d,J=1.2Hz,1H),3.64(s,3H),1.47(s,3H). 13 C NMR (126MHz, CDCl3) δ170.90,156.90,142.29,135.93,132.92,130.90,129.0 2,128.58,128.27,128.14,120.18,53.09,52.50,51.47,38.79,33.07,17.95.

[0222] Embodiment 50

[0223] The preparation of methyl 2-benzyl-4-bromo-6-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 49, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 49.

[0224] Embodiment 51

[0225] Preparation of 2-tert-butyl-7-methyl-5-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-2,7-dicarboxylate

[0226]

[0227] Under nitrogen protection, add tert-butyl 4-methyl-2-oxopyridine-1(2H)-carboxylate (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 64%). 1 H NMR (400MHz, CDCl3): δ7.29–7.26(m,3H),7.06(dd,J=6.5,3.1Hz,2H),5.48–5.43(m,1H ),4.39(d,J=9.0Hz,1H),3.66(s,3H),2.80(d,J=9.0Hz,1H),2.14(s,3H),1.60(s,9H). 13 CNMR (100MHz, CDCl3): δ172.54,159.51,145.47,139.88,135.74,133.73,129.5 5,129.07,128.56,128.47,128.43,125.71,53.48,46.72,35.34,26.94,21.82.

[0228] Embodiment 52

[0229] The preparation of 2-tert-butyl-7-methyl-5-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-2,7-dicarboxylate is specifically described in Example 51, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 51.

[0230] Embodiment 53

[0231] Preparation of 2-benzyl-4-cyano-1-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester

[0232]

[0233] Under nitrogen protection, add 1-benzyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 39%). 1 H NMR (400MHz, CDCl3): δ7.54 (d, J=6.2Hz, 1H), 7.33 (ddd, J=9.9, 6.1, 1.3Hz, 6H), 7.28 (s, 2H), 7.10–7.06 (m,2H),5.42(d,J=15.5Hz,1H),4.28(d,J=15.5Hz,1H),3.69(s,3H),3.05(d,J=6.2Hz,1H),1.55(s,3H). 13 C NMR (126MHz, CDCl3) δ170.24,157.62,149.85,137.62,132.88,129.34,129.13,129.0 1,128.87,127.50,127.04,114.18,112.72,53.65,53.33,50.23,44.90,31.73,20.33.

[0234] Embodiment 54

[0235] The preparation of methyl 2-benzyl-4-cyano-1-methyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 53, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 53.

[0236] Embodiment 55

[0237] Preparation of 4-benzoyl-10-oxo-7-phenyl-1,2,3,4,5,6,7a,10-octahydro-7H-2,6-methylcyclopropyl[2,3]pyrido[1,2-a][1,5]diazoxizone-7-carboxylic acid methyl ester

[0238]

[0239] Under nitrogen protection, add 3-benzyl-1,2,3,4,5,6-hexahydro-8H-1,5-picoline (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a 4.0mL reaction bottle dried and equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 20%). 1 H NMR (600MHz, CDCl3): δ7.37–7.33(m,3H),7.28(dd,J=5.7,2.3Hz,3H),7.26–7.22(m,2 H),7.15–7.05(m,2H),6.78(s,1H),5.70(d,J=9.8Hz,1H),4.99(d,J=13.2Hz,1H),4.52 (d,J=14.0Hz,1H),3.85(d,J=12.8Hz,1H),3.66(s,3H),3.37–3.26(m,1H),3.18(d,J=1 2.6Hz,1H),3.07(s,1H),2.27(dt,J=12.8,2.6Hz,1H),2.05–2.00(m,1H),1.96(s,1H). 13 CNMR (100MHz, CDCl3): δ171.62,171.25,161.28,135.87,135.33,133.29,130.15,129.42,128.49,12 8.35,128.29,127.33,125.30,56.09,53.33,53.13,45.42,44.48,42.76,30.58,30.01,29.75,28.20.

[0240] Embodiment 56

[0241] The preparation of 4-benzoyl-10-oxo-7-phenyl-1,2,3,4,5,6,7a,10-octahydro-7H-2,6-methylcyclopropyl[2,3]pyrido[1,2-a][1,5]diazooxazine-7-carboxylic acid methyl ester is specifically described in Example 55, except that 2-diazo-2-phenylacetic acid methyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester (0.2mmol, 2.0equiv), chlorobenzene is replaced by trifluorotoluene (0.25mL), and cesium carbonate (0.4mmol, 4.0equiv) is added. The H NMR and C NMR spectra of the target product are the same as those in Example 55.

[0242] Embodiment 57

[0243] Preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylic acid methyl ester-4,6-d2

[0244]

[0245] Under nitrogen protection, add 1-benzylpyridin-2-one-3,5-d2 (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir to react for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 58%). 1 H NMR (400MHz, CDCl3): δ7.31–7.26(m,2H),7.26–7.21(m,2H),7.20–7.12(m,4H),6.89–6.84(m,2H),6.55(ddt,J=9.9,3.2,1.4Hz,1H),5.60(d,J =9.9Hz,1H),5.43(d,J=14.7Hz,1H),4.06(d,J=14.7Hz,1H),3.81–3.76(m,1H),3.53(s,3H),3.46(d,J=6.2Hz,1H),2.78(dd,J=8.9,5.3Hz,1H). 13C NMR (126MHz, CDCl3): δ173.46,161.43,136.26,136.17,133.30,129.57,129.56,128.94,128. 51,128.38,128.17,127.98,126.58,126.56,53.15,50.61,48.75,48.67,33.93,33.85,28.12.

[0246] Embodiment 58

[0247] The preparation of methyl 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]heptene-7-carboxylate-4,6-d2 is specifically described in Example 57, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon NMR spectra of the target product are the same as those in Example 57.

[0248] Embodiment 59

[0249] Preparation of ethyl 2-benzyl-3-oxo-7-o-tolyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0250]

[0251] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-o-tolylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 46%). 1H NMR (400MHz, CDCl3) δ7.38 (d, J=4.4Hz, 4H), 7.35–7.31 (m, 1H), 7.21–7.14 (m, 2H), 7.10 (td ,J=7.4,1.9Hz,1H),6.87(dd,J=7.7,1.4Hz,1H),6.58(ddd,J=9.9,5.2,0.8Hz,1H),5.69(d ,J=14.6Hz,1H),5.63(d,J=9.9Hz,1H),4.24–4.16(m,2H),4.03(dd,J=10.8,7.1Hz,1H),3. 86(dd,J=8.9,0.8Hz,1H),2.95(dd,J=8.9,5.2Hz,1H),2.18(s,3H),1.14(t,J=7.1Hz,3H). 13 CNMR (101MHz, CDCl3) δ172.88,161.73,139.16,136.23,134.53,131.90,130.80,128.95,128. 74,128.42,128.33,127.99,126.34,125.87,61.93,50.77,48.74,31.75,28.96,19.66,14.28.

[0252] Embodiment 60

[0253] The preparation of ethyl 2-benzyl-3-oxo-7-o-tolyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 59, except that ethyl 2-diazo-2-o-tolyl acetate is replaced with ethyl (Z)-2-o-tolyl-2-(2-toluenesulfonylhydrazine) acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 59.

[0254] Embodiment 61

[0255] Preparation of ethyl 2-benzyl-3-oxo-7-m-tolyl-2-azabicyclo[4.1.0]heptene-7-carboxylate

[0256]

[0257] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-methyltoluene acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 88%). 1 HNMR (400MHz, CDCl3) δ7.41–7.27(m,5H),7.15(t,J=7.5Hz,1H),7.04(ddt,J=7.6,1. 8,0.9Hz,1H),6.79–6.72(m,2H),6.64(ddd,J=9.9,5.3,0.7Hz,1H),5.69(d,J=9.9Hz ,1H),5.47(d,J=14.6Hz,1H),4.20(d,J=14.6Hz,1H),4.09(q,J=7.1Hz,2H),3.85(dd ,J=8.9,0.7Hz,1H),2.85(dd,J=8.9,5.3Hz,1H),2.28(s,3H),1.13(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.96,161.50,137.78,136.46,136.26,133.87,130.25,129.47,128.9 2,128.84,128.40,128.22,127.92,126.28,61.88,50.58,48.49,33.99,27.80,21.56,14.25.

[0258] Embodiment 62

[0259] The preparation of ethyl 2-benzyl-3-oxo-7-m-tolyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 61, except that ethyl 2-diazo-2-m-tolyl acetate is replaced with ethyl (Z)-2-m-tolyl-2-(2-toluenesulfonylhydrazine) acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon NMR spectra of the target product are the same as those in Example 61.

[0260] Embodiment 63

[0261] Preparation of ethyl 2-benzyl-3-oxo-7-p-tolyl-2-azabicyclo[4.1.0]heptene-7-carboxylate

[0262]

[0263] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-p-tolylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 76%). 1 HNMR(400MHz, CDCl3)δ7.40–7.30(m,5H),7.06(d,J=7.7Hz,2H),6.83(d,J=8 .1Hz,2H),6.64(ddd,J=9.8,5.3,0.8Hz,1H),5.70(d,J=9.9Hz,1H),5.50(d,J =14.6Hz,1H),4.17(d,J=14.7Hz,1H),4.09(q,J=7.1Hz,2H),3.85(dd,J=8.8 ,0.7Hz,1H),2.85(dd,J=8.8,5.3Hz,1H),2.30(s,3H),1.13(t,J=7.1Hz,3H). 13 C NMR (126MHz, CDCl3) δ173.07,161.54,137.68,136.44,136.29,133.07,129.22,128.9 1,128.41,127.93,126.47,126.42,61.87,50.59,48.49,33.75,27.92,21.36,14.26.

[0264] Embodiment 64

[0265] The preparation of ethyl 2-benzyl-3-oxo-7-p-tolyl-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 63, except that ethyl 2-diazo-2-p-tolyl acetate is replaced with ethyl (Z)-2-p-tolyl-2-(2-toluenesulfonylhydrazine) acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon NMR spectra of the target product are the same as those in Example 63.

[0266] Embodiment 65

[0267] Preparation of ethyl 2-benzyl-7-(4-chlorophenyl)-3-oxo-2-azabicyclo[4.1.0]heptene-7-carboxylate

[0268]

[0269] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-(4-chlorophenyl)-2-diazoacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 57%). 1 H NMR (400MHz, CDCl3) δ7.41–7.31(m,5H),7.25–7.19(m,2H),6.85–6.78(m,2H),6.64(ddd,J=9.8,5.3,0.8Hz,1H),5.74(d,J=9.9Hz,1H),5.38(d ,J=14.6Hz,1H),4.26(d,J=14.6Hz,1H),4.09(q,J=7.1Hz,2H),3.87(dd,J=8.9,0.8Hz,1H),2.87(dd,J=8.9,5.3Hz,1H),1.13(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.41,161.26,136.18,136.05,134.58,134.00,128.98,12 8.77,128.50,128.23,128.09,126.72,62.09,50.67,48.67,33.34,27.83,14.21.

[0270] Embodiment 66

[0271] The preparation of ethyl 2-benzyl-7-(4-chlorophenyl)-3-oxo-2-azabicyclo[4.1.0]heptene-7-carboxylate is specifically described in Example 65, except that ethyl 2-(4-chlorophenyl)-2-diazoacetate is replaced with ethyl (Z)-2-(4-chlorophenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 65.

[0272] Embodiment 67

[0273] Preparation of ethyl 2-benzyl-7-(4-methoxyphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0274]

[0275] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-(4-methoxyphenyl)acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 90%). 1 H NMR (400MHz, CDCl3) δ7.40–7.29(m,5H),6.85(d,J=8.8Hz,2H),6.78(d,J=8. 8Hz,2H),6.64(ddd,J=9.9,5.3,0.7Hz,1H),5.72(d,J=9.8Hz,1H),5.48(d,J =14.6Hz,1H),4.18(d,J=14.6Hz,1H),4.09(q,J=7.1Hz,2H),3.84(dd,J=8.9 ,0.8Hz,1H),3.77(s,3H),2.84(dd,J=8.9,5.3Hz,1H),1.13(t,J=7.1Hz,3H). 13C NMR (126MHz, CDCl3) δ173.23,161.55,159.05,136.42,136.26,134.36,128.92,128.4 1,127.95,126.49,121.37,113.92,61.88,55.18,50.60,48.58,33.39,28.09,14.25.

[0276] Embodiment 68

[0277] The preparation of ethyl 2-benzyl-7-(4-methoxyphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 67, except that ethyl 2-diazo-2-(4-methoxyphenyl)acetate is replaced with ethyl (Z)-2-(4-methoxyphenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 67.

[0278] Embodiment 69

[0279] Preparation of ethyl 2-benzyl-7-(4-fluorophenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0280]

[0281] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-(4-fluorophenyl)acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 60%). 1H NMR (400MHz, CDCl3) δ7.40–7.31(m,5H),6.96–6.90(m,2H),6.90–6.84(m,2H),6.65(ddd,J=9.8,5.3,0.8Hz,1H),5.73(d,J=9.9Hz,1H),5.41(d ,J=14.6Hz,1H),4.24(d,J=14.5Hz,1H),4.09(q,J=7.1Hz,2H),3.87(dd,J=8.9,0.8Hz,1H),2.87(dd,J=8.9,5.3Hz,1H),1.13(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.62,163.42,161.29,160.96,136.25,136.07,135.00,134.92,128.93,12 8.44,128.03,126.63,125.43,125.39,115.64,115.43,61.99,50.62,48.64,33.22,27.88,14.16. 19 F NMR(471MHz, CDCl3)δ-113.42–-113.48(m).

[0282] Embodiment 70

[0283] The preparation of ethyl 2-benzyl-7-(4-fluorophenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 69, except that ethyl 2-diazo-2-(4-fluorophenyl)acetate is replaced with ethyl (Z)-2-(4-fluorophenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen, carbon and fluorine NMR spectra of the target product are the same as those in Example 69.

[0284] Embodiment 71

[0285] Preparation of ethyl 2-benzyl-3-oxo-7-(4-trifluoromethylphenyl)-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0286]

[0287] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-(4-trifluoromethylphenyl)acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 42%). 1 H NMR (400MHz, CDCl3) δ7.50(d,J=8.0Hz,2H),7.42–7.32(m,5H),7.00(d,J=8.0Hz,2H),6.67(dd,J=9.9,5.2Hz,1H),5.73(d,J=9.9Hz,1H),5.3 6(d,J=14.5Hz,1H), 4.33(d,J=14.6Hz,1H), 4.10(q,J=7.1Hz,2H), 3.92(d,J=8.8Hz,1H), 2.91(dd,J=8.9,5.2Hz,1H), 1.12(t,J=7.1Hz,3H). 13 C NMR (126MHz, CDCl3) δ172.06,161.16,136.09,135.99,133.98,133.64,130.22,129.0 6,128.59,128.22,126.81,125.45,125.42,62.24,50.76,48.73,33.61,27.73,14.22. 19 F NMR (376MHz,CDCl3)δ-62.60.

[0288] Embodiment 72

[0289] The preparation of ethyl 2-benzyl-3-oxo-7-(4-trifluoromethylphenyl)-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 71, except that ethyl 2-diazo-2-(4-trifluoromethylphenyl)acetate is replaced with ethyl (Z)-2-(2-toluenesulfonylhydrazine)-2-(4-(trifluoromethyl)phenyl)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen, carbon and fluorine NMR spectra of the target product are the same as those in Example 71.

[0290] Embodiment 73

[0291] Preparation of ethyl 2-benzyl-7-(4-ethoxycarbonylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0292]

[0293] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 4-(1-diazo-2-ethoxy-2-oxoethyl)benzoate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 38%). 1 H NMR (400MHz, CDCl3) δ7.96–7.90(m,2H),7.42–7.30(m,5H),7.04–6.94(m,2H),6.66 (ddd,J=9.8,5.3,0.8Hz,1H),5.70(d,J=9.9Hz,1H),5.41(d,J=14.6Hz,1H),4.36(qd ,J=7.2,1.1Hz,2H),4.27(d,J=14.6Hz,1H),4.09(q,J=7.1Hz,2H),3.91(dd,J=8.8,0 .7Hz,1H),2.90(dd,J=8.9,5.3Hz,1H),1.38(t,J=7.1Hz,3H),1.11(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.22,166.32,161.20,136.18,136.06,134.88,133.30,130.08,129. 64,129.01,128.52,128.13,126.68,62.17,61.16,50.67,48.72,33.82,27.84,14.47,14.20.

[0294] Embodiment 74

[0295] The preparation of ethyl 2-benzyl-7-(4-ethoxycarbonylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 73, except that ethyl 4-(1-diazo-2-ethoxy-2-oxoethyl)benzoate is replaced with ethyl (Z)-4-(2-ethoxy-2-oxo-1-(2-toluenesulfonylhydrazine)ethyl)benzoate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 73.

[0296] Embodiment 75

[0297] Preparation of 2-benzyl-7-(4-bromophenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0298]

[0299] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), 2-bromophenyl-2-diazoacetic acid methyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 62%). 1 H NMR (400MHz, CHLOROFORM-D) δ7.39(d,J=6.6Hz,2H),7.38–7.29(m,5H),6.81–6.73(m,2H),6.63(dd,J=9.9,5.3Hz,1H),5.75(d ,J=9.9Hz,1H),5.41(d,J=14.6Hz,1H),4.24(d,J=14.6Hz,1H),3.89(d,J=8.9Hz,1H),3.63(s,3H),2.88(dd,J=8.9,5.3Hz,1H). 13 C NMR(101MHz,CHLOROFORM-D)δ172.91,161.24,136.08,136.00,134.94,131.84,12 9.01,128.68,128.49,128.12,126.90,122.51,53.25,50.70,48.85,33.33,28.04.

[0300] Embodiment 76

[0301] The preparation of methyl 2-benzyl-7-(4-bromophenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 75, except that methyl 2-bromophenyl-2-diazoacetate is replaced with methyl (Z)-2-(4-bromophenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon NMR spectra of the target product are the same as those in Example 75.

[0302] Embodiment 77

[0303] Preparation of ethyl 2-benzyl-7-(3,4-dimethylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0304]

[0305] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-(3,4-dimethylphenyl)acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 32%). 1 H NMR (400MHz, CDCl3): δ7.39–7.29(m,5H),7.01(d,J=7.6Hz,1H),6.69(d,J=7.4H z,2H),6.63(ddd,J=9.9,5.3,0.7Hz,1H),5.69(d,J=9.8Hz,1H),5.48(d,J=14.7 Hz,1H),4.17(d,J=14.7Hz,1H),4.10(q,J=7.1Hz,2H),3.83(dd,J=8.8,0.7Hz,1 H), 2.83 (dd, J = 8.9, 5.3Hz, 1H), 2.19 (s, 3H), 2.17 (s, 3H), 1.14 (t, J = 7.1Hz, 3H). 13C NMR (101MHz, CDCl3) δ173.15,161.60,136.51,136.42,136.36,136.29,134.31,130.55,129.70,1 28.90,128.36,127.89,126.74,126.26,61.84,50.55,48.46,33.76,27.88,19.99,19.68,14.30.

[0306] Embodiment 78

[0307] The preparation of ethyl 2-benzyl-7-(3,4-dimethylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 77, except that ethyl 2-diazo-2-(3,4-dimethylphenyl)acetate is replaced with ethyl (Z)-2-(3,4-dimethylphenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 77.

[0308] Embodiment 79

[0309] Preparation of ethyl 2-benzyl-7-(3,5-dimethylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0310]

[0311] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-(3,5-dimethylphenyl)acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 54%). 1H NMR(400MHz, CDCl3)δ7.40–7.30(m,5H),6.86(d,J=1.7Hz,1H),6.63(ddd,J= 9.9,5.3,0.7Hz,1H),6.55(d,J=1.6Hz,2H),5.70(d,J=9.8Hz,1H),5.44(d,J =14.6Hz,1H),4.21(d,J=14.6Hz,1H),4.10(q,J=7.1Hz,2H),3.84(dd,J=8.9 ,0.7Hz,1H),2.83(dd,J=8.9,5.3Hz,1H),2.23(s,6H),1.15(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3): δ173.06,161.59,137.56,136.51,136.31,130.94,129.84,129. 30,128.93,128.42,127.91,126.18,61.86,50.61,48.50,33.98,27.75,21.45,14.30.

[0312] Embodiment 80

[0313] The preparation of ethyl 2-benzyl-7-(3,5-dimethylphenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 79, except that ethyl 2-diazo-2-(3,5-dimethylphenyl)acetate is replaced with ethyl (Z)-2-(3,5-dimethylphenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 79.

[0314] Embodiment 81

[0315] Preparation of ethyl 2-benzyl-7-naphth-1-yl-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0316]

[0317] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-diazo-2-naphthalene-1-yl acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 66%). 1 HNMR (400MHz, CDCl3) δ7.84 (dd, J=7.3, 2.0Hz, 1H), 7.77 (d, J=8.0Hz, 2H), 7.51–7 .33(m,8H),7.06(d,J=7.1Hz,1H),6.36(dd,J=9.9,5.1Hz,1H),5.67(d,J=14.5Hz ,1H),5.33(d,J=9.9Hz,1H),4.32(d,J=14.5Hz,1H),4.11(ddd,J=10.6,7.2,3.6H z, 1H), 3.99 (t, J = 8.1Hz, 2H), 3.20 (dd, J = 8.9, 5.2Hz, 1H), 0.99 (t, J = 7.1Hz, 3H). 13 C NMR (100MHz, CDCl3): δ173.16,161.87,136.29,135.46,134.23,133.40,131.08,129.25,129.13,129.0 3,128.51,128.10,126.56,125.68,125.23,125.18,123.78,61.98,50.87,48.83,30.87,29.25,14.15.

[0318] Embodiment 82

[0319] The preparation of ethyl 2-benzyl-7-naphthalen-1-yl-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 81, except that ethyl 2-diazo-2-naphthalen-1-yl acetate is replaced with ethyl (Z)-2-(1-naphthyl)-2-(2-toluenesulfonylhydrazine) acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 81.

[0320] Embodiment 83

[0321] Preparation of ethyl (7-benzo[1,3]dioxetyl-4-yl)-2-benzyl-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0322]

[0323] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), (2-benzo[1,3]dioxol-4-yl)-2-ethyldiazoacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 75%). 1 H NMR (400MHz, CDCl3): δ7.41–7.30(m,5H),6.69(d,J=8.6Hz,1H),6.67–6.61(m,1H),6.42–6.35(m,2H),5.94(s,2H),5.77(d,J=9.8Hz,1H),5.46( d,J=14.6Hz,1H),4.18(d,J=14.6Hz,1H),4.10(q,J=7.1Hz,2H),3.83(dd,J=8.8,0.7Hz,1H),2.83(dd,J=8.9,5.3Hz,1H),1.15(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3): δ172.98,161.61,147.50,147.34,136.38,136.19,129.62,128.97,128.42,128. 01,127.00,126.58,122.93,113.28,108.35,101.27,61.99,50.68,48.74,33.76,29.83,28.08,14.29.

[0324] Embodiment 84

[0325] The preparation of ethyl (7-benzo[1,3]dioxol-4-yl)-2-benzyl-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 83, except that ethyl (2-benzo[1,3]dioxol-4-yl)-2-diazoacetate is replaced with ethyl (Z)-2-(benzo[d][1,3]dioxol-4-yl)-2-(2-tosylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those of Example 83.

[0326] Embodiment 85

[0327] Preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid benzyl ester

[0328]

[0329] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), 2-diazo-2-phenylacetic acid benzyl ester (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 38%). 1 H NMR (400MHz, CDCl3): δ7.39–7.32(m,5H),7.29(td,J=4.3,1.9Hz,4H),7.28–7.26(m,2H),7.14–7.07(m,2H),7.00–6.93(m,2H),6.69–6.61(m ,1H),5.71(d,J=9.8Hz,1H),5.48(d,J=14.5Hz,1H),5.09(s,2H),4.19(d,J=14.5Hz,1H),3.88(d,J=8.8Hz,1H),2.90(dd,J=8.9,5.3Hz,1H). 13C NMR (100MHz, CDCl3): δ172.66,161.39,136.28,136.16,135.85,133.27,129.48,128.9 4,128.58,128.51,128.15,128.00,127.32,126.56,67.10,50.59,48.61,34.15,27.90.

[0330] Embodiment 86

[0331] The preparation of 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid benzyl ester is specifically described in Example 85, except that 2-diazo-2-phenylacetic acid benzyl ester is replaced by (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid benzyl ester (0.2 mmol, 2.0 equiv), chlorobenzene is replaced by trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 85.

[0332] Embodiment 87

[0333] Preparation of 2-benzyl-3,7-dimethyl-6-oct-1-yl-2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0334]

[0335] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), 3,7-dimethyl-6-octyl-2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 47%). 1H NMR (400MHz, CDCl3): δ7.41–7.31(m,5H),7.25–7.13(m,3H),7.00–6.87(m,2H),6.66(dd,J=9.9,5.3H z,1H),5.70(d,J=9.9Hz,1H),5.51(dd,J=14.6,7.0Hz,1H),5.07–4.98(m,1H),4.17(dd,J=14.6,6.5H z,1H),4.10–4.01(m,2H),3.86(d,J=8.8Hz,1H),2.86(dd,J=8.9,5.2Hz,1H),1.68(s,3H),1.58(s,3H ),1.30–1.28(m,1H),1.27–1.23(m,2H),1.13–0.96(m,2H),0.95–0.81(m,2H),0.77(d,J=5.9Hz,3H). 13 C NMR (100MHz, CDCl3): δ172.96,161.47,136.40,136.24,133.22,131.42,129.69,129.67,128.93,128.45,128.40,128.00,127.98,126.43 ,124.62,64.51,50.63,50.62,48.46,48.42,36.97,36.94,35.32,34 .10,29.62,29.60,27.81,27.79,25.84,25.53,25.51,19.36,17.77.

[0336] Embodiment 88

[0337] The preparation of 2-benzyl-3,7-dimethyl-6-oct-1-yl-2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 87, except that 3,7-dimethyl-6-octyl-2-diazo-2-phenylacetate is replaced with (S)-3,7-dimethyloct-6-en-1-yl-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 87.

[0338] Embodiment 89

[0339] Preparation of 2-isopropyl-5-methylcyclohexyl-2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0340]

[0341] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), 2-phenylacetic acid isopropyl-5-methylcyclohexyl-2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 59%). 1 H NMR (400MHz, CDCl3): δ7.40–7.30(m,5H),7.22(td,J=5.8,2.5Hz,3H),6.94–6.81(m,2H),6.66(dt,J=10 .8,5.7Hz,1H),5.70(dd,J=9.9,2.8Hz,1H),5.50–5.33(m,1H),4.58(tdd,J=10.8,8.0,4.4Hz,1H),4.31– 4.18(m,1H),3.82(d,J=8.9Hz,1H),2.85(ddd,J=14.3,8.9,5.3Hz,1H),2.00–1.86(m,1H),1.63(td,J=6. 9,2.9Hz,1H),1.59–1.52(m,1H),1.25(s,1H),1.16–1.07(m,1H),1.03–0.94(m,1H),0.91–0.62(m,12H). 13 C NMR (126MHz, CDCl3) δ172.35,172.13,161.43,136.53,136.50,136.22,133.21,133.14,129.85 ,129.72,128.96,128.78,128.69,128.32,128.26,128.05,127.88,127.84,126.37,126.32,76 .01,75.98,50.83,50.63,48.25,48.02,46.83,46.81,40.74,40.66,34.34,34.24,34.17,34.13,31.40,27.32,27.23,26.47,26.35,23.54,23.47,22.10,22.06,20.75,20.70,16.61,16.46.

[0342] Embodiment 90

[0343] The preparation of 2-isopropyl-5-methylcyclohexyl-2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 89, except that 2-phenylacetic acid isopropyl-5-methylcyclohexyl-2-diazo-2-phenylacetate is replaced with (1R, 2S, 5R)-2-isopropyl-5-methylcyclohexyl-2-phenyl-2-(2-tosylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 89.

[0344] Embodiment 91

[0345] Preparation of (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-methylheptane-2-ylhexahydro-1H-cyclopentane-2-yl 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0346]

[0347] Under nitrogen protection, 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10,13-dimethyl-17-methylheptane-2-yl-hexahydro-1H-cyclopentanoic acid phenanthroline 2-diazo-2-phenyl acetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) were added to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. The above reaction solution was placed on a blue light reactor with a wavelength of 470nm and stirred at room temperature for 48h. The reaction was monitored by TLC. After the reaction was complete, 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, 31%). 11H NMR (400 MHz, CDCl3): δ 7.39–7.33 (m, 5H), 7.24 (p, J = 2.4 Hz, 3H), 6.92 (dt, J = 6.7, 1.7 Hz, 2H), 6.64 (dd, J = 9.9, 5.3 Hz, 1H), 5.68 (d, J = 9.9 Hz, 1H), 5.46 (dd, J = 14.5, 2.3 Hz, 1H), 4.63 (tt, J = 11.0, 4.7 Hz, 1H), 4.20 (dd, J = 14.7, 2.2 Hz, 1H), 3.83 (d, J = 8.8 Hz, 1H), 2.84 (dd, J = 8.9, 5.3 Hz, 1H), 1.99–1.91 (m, 1H), 1.64 (s, 1H), 1.58 (s, 3H), 1.54–1.48 (m, 2H), 1.32 (d, J = 8.2 Hz, 5H), 1.26 (s, 3H), 1.14–1.03 (m, 8H), 1.01–0.94 (m, 4H), 0.91–0.83 (m, 13H), 0.73 (s, 3H), 0.63 (s, 4H). 13 13C NMR (100 MHz, CDCl3): δ 172.35, 161.50, 136.53, 136.30, 133.25, 129.87, 128.96, 128.58, 128.35, 128.01, 127.90, 126.39, 75.49, 56.53, 56.40, 54.29, 50.66, 48.32, 44.76, 42.71, 40.08, 39.65, 36.78, 36.30, 35.92, 35.57, 35.54, 34.28, 33.96, 32.10, 28.70, 28.36, 28.15, 27.65, 27.43, 24.32, 23.97, 22.95, 22.69, 21.33, 18.80, 12.36, 12.19.

[0348] Example 92

[0349] The preparation of (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-methylheptane-2-ylhexahydro-1H-cyclopentane-2-yl 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is as follows: Example 91, except that (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-methylheptane-2-ylhexahydro-1H-cyclopentane-2-yl 2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate H-cyclopentanoic acid phenanthrenyl 2-diazo-2-phenyl acetate was replaced with (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-(R)-6-methylheptane-2-yl-hexahydro-1H-cyclopentylphenanthren-2-yl-2-phenyl-2-(2-toluenesulfonylhydrazine) acetate (0.2 mmol, 2.0 equiv), chlorobenzene was replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) was added. The H NMR and C NMR spectra of the target product were the same as those in Example 91.

[0350] Embodiment 93

[0351] Preparation of dimethyl (2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-7-yl)phosphonate

[0352]

[0353] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), (phenyl) dimethyl methylphosphonate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 20%). 1 HNMR (400MHz, CDCl3): δ7.42–7.28(m,5H),7.26–7.18(m,3H),6.95(dt,J=7.4,2.0Hz,2H),6.62(dd,J=9.9,5.2Hz,1H),5.67(d,J =9.9Hz,1H),5.39(d,J=14.5Hz,1H),4.29(d,J=14.6Hz,1H),3.87(dd,J=11.0,8.6Hz,1H),3.69–3.59(m,6H),2.81–2.72(m,1H). 13C NMR (100MHz, CDCl3): δ161.43,136.27,135.89,135.87,133.96,128.95,128.61,128.59,128.26,128 .24,128.16,128.06,126.40,53.74,53.72,53.70,53.68,50.82,44.39,27.46,26.23,22.94,22.92. 31 P NMR (243MHz, CDCl3) δ26.50 (tq, J=20.8, 10.4Hz).

[0354] Embodiment 94

[0355] The preparation of dimethyl (2-benzyl-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-en-7-yl)phosphonate is specifically described in Example 93, except that dimethyl (phenyl)methylphosphonate is replaced with dimethyl (phenyl(2-tosylhydrazine)methyl)phosphonate (0.2mmol, 2.0equiv), chlorobenzene is replaced with trifluorotoluene (0.25mL), and cesium carbonate (0.4mmol, 4.0equiv) is added. The hydrogen, carbon and phosphorus NMR spectra of the target product are the same as those in Example 93.

[0356] Embodiment 95

[0357] Preparation of ethyl 2-benzyl-7-(3,4-dichlorophenyl)-3-oxo-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate

[0358]

[0359] Under nitrogen protection, add 1-benzylpyridin-2-one (0.1mmol, 1.0equiv), ethyl 2-(3,4-dichlorophenyl)-2-(2-toluenesulfonylhydrazine)acetate (0.2mmol, 2.0equiv), cesium carbonate (0.4mmol, 4.0equiv), and dry trifluorotoluene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 42%). 1HNMR (400MHz, CDCl3): δ7.37(d,J=4.9Hz,5H),7.30(d,J=8.3Hz,1H),6.97(d,J=2.1Hz,1H),6.72–6.62(m,2H),5.79(d,J=9.9Hz,1H),5.32– 5.28(m,1H),4.33(d,J=14.5Hz,1H),4.10(qd,J=7.1,1.4Hz,2H),3.89(d,J=8.9Hz,1H),2.88(dd,J=8.9,5.2Hz,1H),1.14(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3): δ171.89,161.13,135.95,135.89,135.27,132.52,132.39,130.5 3,130.06,129.11,128.63,128.24,127.08,62.30,50.80,48.86,33.15,27.77,14.25.

[0360] Embodiment 96

[0361] Preparation of 2-benzyl-1-chloro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylic acid methyl ester

[0362]

[0363] Under nitrogen protection, add 1-benzyl-6-chloropyridin-2(1H)one (0.1mmol, 1.0equiv), methyl 2-diazo-2-phenylacetate (0.2mmol, 2.0equiv), and dry chlorobenzene (0.25mL) to a dry 4.0mL reaction bottle equipped with a magnetic stirrer. Place the above reaction solution on a blue light reactor with a wavelength of 470nm and stir at room temperature for 48h. Monitor the reaction by TLC. After the reaction is complete, filter the product with diatomaceous earth, wash with ethyl acetate, remove the solvent under reduced pressure, and directly separate and purify the crude product by column chromatography to obtain the target product (yellow solid, 31%). 1 H NMR (400MHz, CDCl3) δ7.39–7.28(m,7H),7.25–7.15(m,3H),6.86(dd,J=9.8,5.8Hz,1H),5.79(d, J=9.8Hz,1H),5.14(d,J=15.2Hz,1H),4.64(d,J=15.3Hz,1H),3.75(s,3H),3.55(d,J=5.8Hz,1H). 13C NMR (126MHz, CDCl3) δ168.82,137.64,135.37,132.48,128.71,128.44,127.13,125.46,71.23,53.75,51.11,34.10,32.35.

[0364] Embodiment 97

[0365] The preparation of methyl 2-benzyl-1-chloro-3-oxo-7-phenyl-2-azabicyclo[4.1.0]hept-4-ene-7-carboxylate is specifically described in Example 96, except that methyl 2-diazo-2-phenylacetate is replaced with methyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate (0.2 mmol, 2.0 equiv), chlorobenzene is replaced with trifluorotoluene (0.25 mL), and cesium carbonate (0.4 mmol, 4.0 equiv) is added. The hydrogen and carbon nuclear magnetic resonance spectra of the target product are the same as those in Example 96.

[0366] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a nitrogen-containing heterocyclic compound, characterized in that: The following steps are involved: Under a protective atmosphere, a 2-pyridone compound, a nitrogen-containing compound, and an organic solvent are mixed, and stirred at room temperature for 48 hours under visible light irradiation to obtain a nitrogen-containing heterocyclic compound; Wherein, the nitrogen-containing compound is a hydrazone compound or a diazo compound; When the nitrogen-containing compound is a hydrazone compound, the method further comprises adding a base to mix with the 2-pyridone compound, the nitrogen-containing compound, and the organic solvent; the molar volume ratio of the 2-pyridone compound, the hydrazone compound, the base, and the organic solvent is 1-1.5 mmol: 2-3 mmol: 4-6 mmol: 2-5 mL; When the nitrogen-containing compound is a diazo compound, the molar volume ratio of the 2-pyridone compound, the diazo compound, and the organic solvent is 1-1.5 mmol: 2-3 mmol: 2-5 mL; The 2-pyridone compounds are 1-benzylpyridin-2(1H)-one, 2-hydroxypyridine, 1-methylpyridin-2-one, 1-phenylpyridin-2-one, 2-oxopyridine-1(2H)-carboxylic acid tert-butyl ester, 1-toluenesulfonylpyridin-2(1H)-one, 2-(2-oxopyridine-1(2H)-yl)acetic acid methyl ester, 2-butyl-6-(2-oxopyridine-1-2H-yl)-1-benzisohexoquinoline-1,3-dione, 2-thiophene-2-pyridin-2-one, 2- Pyridylpyridin-2-one, 1-phenylvinylpyridin-2-1-one, 2-oxopyridine-1-propenoic acid methyl ester, 2-benzoyloxymethyl-2-(benzoyloxy)methyl-5-(2-oxopyridine-1(2H)yl)tetrahydrofuran-3,4-dibenzoate, 2-tert-butyldimethylsilyloxy-2-(2-oxopyridine-1(2H)yl)tetrahydrofuran-3-ylbenzoate, (2S,3S,4S,5S)-2-acetoxymethyl- 5-(2-oxopyridin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate, 1-benzyl-3-chloropyridin-2-one, 1-benzyl-3-bromopyridin-2-one, 1-benzyl-3-trifluoromethylpyridin-2-one, 1-benzyl-3-nitropyridin-2-one, 1-benzyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid methyl ester, 1-benzyl-4-methylpyridin-2-one, 1-benzyl-4-iodopyridin-2-one, 1-benzyl-4-benzyloxypyridin-2-one , 1-benzyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid methyl ester, 1-benzyl-3-bromo-5-methylpyridin-2-one, 4-methyl-2-oxopyridine-1(2H)-carboxylic acid tert-butyl ester, 1-benzyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile, 3-benzyl-1,2,3,4,5,6-hexahydro-8H-1,5-methylpyridine, 1-benzylpyridin-2-one-3,5-d2, 1-benzyl-6-chloropyridin-2(1H)one; The hydrazone compound is ( Z )-2-phenyl-2-(2-toluenesulfonylhydrazine)acetic acid methyl ester, (Z)-2-o-tolyl-2-(2-toluenesulfonylhydrazine)acetic acid ethyl ester, (Z)-2-m-tolyl-2-(2-toluenesulfonylhydrazine)acetic acid ethyl ester, (Z)-2-p-tolyl-2-(2-toluenesulfonylhydrazine)acetic acid ethyl ester, (Z)-2-(4-chlorophenyl)-2-(2-toluenesulfonylhydrazine)acetic acid ethyl ester, (Z)-2-(4-methoxyphenyl)-2-(2-toluenesulfonylhydrazine)acetic acid ethyl ester, (Z)-2-( ethyl (Z)-2-(2-toluenesulfonylhydrazine)acetate, ethyl (Z)-2-(2-toluenesulfonylhydrazine)-2-(4-(trifluoromethyl)phenyl)acetate, ethyl (Z)-4-(2-ethoxy-2-oxo-1-(2-toluenesulfonylhydrazine)ethyl)benzoate, methyl (Z)-2-(4-bromophenyl)-2-(2-toluenesulfonylhydrazine)acetate, ethyl (Z)-2-(3,4-dimethylphenyl)-2-(2-toluenesulfonylhydrazine)acetate, ethyl (Z)-2-(3,5-dimethylphenyl)-2-(2-toluenesulfonylhydrazine)acetate ethyl (Z)-2-(1-naphthyl)-2-(2-toluenesulfonylhydrazine)acetate, ethyl (Z)-2-(benzo[d][1,3]dioxol-4-yl)-2-(2-toluenesulfonylhydrazine)acetate, benzyl (Z)-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate, (S)-3,7-dimethyloct-6-en-1-yl-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate, (1R,2S,5R)-2-isopropyl one of 2-(2-toluenesulfonylhydrazine)acetate, (2R, 5S, 8R, 9S, 10S, 13R, 14S, 17R)-10, 13-dimethyl-17-(R)-6-methylheptane-2-yl-hexahydro-1H-cyclopentylphenanthrene-2-yl-2-phenyl-2-(2-toluenesulfonylhydrazine)acetate, (phenyl(2-toluenesulfonylhydrazine)methyl)phosphonic acid dimethyl ester, and ethyl 2-(3, 4-dichlorophenyl)-2-(2-toluenesulfonylhydrazine)acetate; The diazo compound is methyl 2-diazo-2-phenylacetate, ethyl 2-diazo-2-o-tolyl acetate, ethyl 2-diazo-2-m-tolyl acetate, ethyl 2-diazo-2-p-tolyl acetate, ethyl 2-(4-chlorophenyl)-2-diazoacetate, ethyl 2-diazo-2-(4-methoxyphenyl) acetate, ethyl 2-diazo-2-(4-fluorophenyl) acetate, ethyl 2-diazo-2-(4-trifluoromethylphenyl) acetate, ethyl 4-(1-diazo-2-ethoxy-2-oxoethyl) benzoate, methyl 2-bromophenyl-2-diazoacetate, ethyl 2-diazo-2-(3,4-dimethylphenyl) acetate, ethyl 2-diazo-2- One of (3,5-dimethylphenyl)acetic acid ethyl ester, 2-diazo-2-naphthalene-1-ylacetic acid ethyl ester, (2-benzo[1,3]dioxolan-4-yl)-2-diazoacetic acid ethyl ester, 2-diazo-2-phenylacetic acid benzyl ester, 3,7-dimethyl-6-octyl-2-diazo-2-phenylacetic acid ester, 2-phenylacetic acid isopropyl-5-methylcyclohexyl-2-diazo-2-phenylacetic acid ester, (2R,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-methylheptane-2-yl-hexahydro-1H-cyclopentanoic acid phenanthrenyl 2-diazo-2-phenylacetic acid ester, and dimethyl diazo-benzylphosphonate.

2. The method for preparing a nitrogen-containing heterocyclic compound according to claim 1, characterized in that: The base is one of triethylenediamine, N,N-diisopropylethylamine, triethylamine, diisopropylamine, N,N-dimethylethylenediamine, N,N,N',N'-tetramethylethylenediamine, 2,6-dimethoxypyridine, 4-dimethylaminopyridine, cesium carbonate, cesium fluoride, sodium hydride, sodium hydroxide, and potassium hydroxide.

3. The method for preparing a nitrogen-containing heterocyclic compound according to claim 1, characterized in that: The wavelength of the visible light is 400-800nm.

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