Method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds

Abstract

The present invention discloses a method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamides, belonging to the technical field of organic synthesis. The present invention provides a new route for the synthesis of tetrahydrobenzene-1-carboxamides, which reacts 2-(hetero)arylmethyl-2-bromocarbonyl compounds, N-(hetero)arylacrylamides and a photocatalyst under visible light and an inert environment to obtain tetrahydrobenzene-1-carboxamides. The method of the present invention is simple to operate, mild in conditions, efficient in reaction, wide in substrate scope and good in functional group tolerance. Through visible light catalysis without the participation of metal and additives, [4+2] cyclization reaction is carried out to prepare tetrahydrobenzene-1-carboxamides with diverse structures that are not easily obtained, breaking through the structural limitations of natural tetrahydrobenzene-1-carboxamides, and having low production cost and being suitable for large-scale production.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for photocatalytic synthesis of tetrahydronaphthalene-1-carboxamide compounds. Background Art

[0002] Tetrahydronaphthalene-1-carboxamide is the core structure of many natural products and important bioactive molecules, and has a wide range of physiological activities, such as: sedative hypnotic drug aronizide, C5aR antagonist W-54011, antiarrhythmic agent spirosuccinimide derivatives, HsFPPS inhibitor rosmarinic acid derivatives, 20S proteasome inhibitor bortezomib analogs, and anti-oomycete compound diamides and other bioactive molecules (Org. Lett. 2018, 20, 4499-4503; J. Biol. Chem. 2002, 277, 49403; J. Med. Chem. 1981, 24, 47; J. Med. Chem. 2019, 62, 10867; J. Med. Chem. 2009, 52, 4192; Bioorg. Med. Chem. 2015, 23, 2129). In addition, during the process of drug discovery and design, tetrahydronaphthalene-1-carboxamide skeleton compounds are important intermediates or synthetic building blocks in the synthesis of lead compounds. Its structural general formula is as follows (IV):

[0003]

[0004] The classical preparation method of tetrahydronaphthalene-1-carboxamide relies on the formation of an amide bond between tetrahydronaphthalene-1-carboxylic acid and an amine, while tetrahydronaphthalene-1-carboxylic acid needs to be obtained through multiple-step chemical synthesis. In addition, there are also some other preparation methods, such as: alkaline hydrolysis of tetrahydronaphthalene-1-carbonitrile in the H2O2-DMSO system, C-C bond coupling of tetrahydronaphthalene-1-ol and tosylmethyl isocyanide (TosMIC) mediated by InCl3, electrochemically promoted benzyl C-H bond carbamoylation of tetrahydronaphthalene and isocyanate, and polar radical cross-coupling of tetrahydronaphthalene-1-ethenone and arylsulfonamides (Org. Lett. 2022, 24, 536; WO2014106238, 2014; Tetrahedron Lett. 2007, 48, 9048; Org. Lett. 2022, 24, 2125; Nat. Commun. 2022, 13, 3083). However, the existing methods have more or less some disadvantages (such as: cumbersome steps, low yield, harsh reaction conditions, narrow substrate scope, and environmental problems), and all are prepared based on non-linear tetrahydronaphthalene derivatives that are not easily obtained. Therefore, there is an urgent need to develop a general, efficient and green method to prepare structurally diverse tetrahydronaphthalene-1-carboxamide compounds from simple and readily available linear substrates under mild, metal-free and additive-free conditions. SUMMARY OF THE INVENTION

[0005] The object of the present invention is to provide a synthesis method of tetrahydrobenzene-1-carboxamide compounds which is simple to operate, mild in conditions, highly efficient in reaction, wide in substrate range, good in functional group tolerance, and free of metal and additives in view of the problems existing in the preparation methods of existing tetrahydronaphthalene-1-carboxamide compounds.

[0006] The present invention provides a method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds, which comprises the following steps: placing a 2-cycloA (cycloA is an aryl or heteroaryl) methyl-2-bromocarbonyl compound represented by formula I, an N-cycloB (cycloB is an aryl or heteroaryl) acrylamide compound represented by formula II, and a photocatalyst in an organic solvent, and carrying out a cyclization reaction under visible light irradiation and inert gas protection. After the reaction is completed, through post-treatment, a tetrahydrobenzene-1-carboxamide compound represented by formula III is obtained;

[0007]

[0008] Wherein,

[0009] CycloA is selected from 6- to 14-membered aryls, 5- to 10-membered heteroaryls; in cycloA, the 5- to 10-membered heteroaryl contains 1 heteroatom, and the heteroatom is selected from N, NH, NC(O)OR6, S, O; R6 is selected from C1-C8 alkyls;

[0010] CycloB is selected from aryls, heteroaryls;

[0011] R3 is selected from 3- to 8-membered cycloalkyls, C1-C 10 alkyls, 6- to 10-membered aryls;

[0012] R4 is selected from cyano, -C(O)R 18 , -C(O)OR 19 ; R 18 , R 19 are each independently selected from C1-C 10 alkyls;

[0013] R5 is selected from hydrogen, 3- to 6-membered cycloalkyls, C1-C4 alkyls.

[0014] In the present invention, the reaction principle is that photocatalysis of formula I and formula II undergoes a [4+2] cyclization reaction. In this reaction, there is great compatibility with the R1 substituent on cycloA and the R2 substituent on cycloB. As can be seen from the examples of the present invention, common simple substituents in the organic field, such as alkyls, alkoxys, hydroxyls, aryls, etc., can all be compatible with the reaction of the present invention; in addition, carboxyl groups, ester groups, aldehyde groups, etc. can also be compatible with the reaction of the present invention; in addition, the present invention can also be used for direct cyclization synthesis of active molecules with complex structures, such as etc. Therefore, in the present invention, the R1 substituent on ring A and the R2 substituent on ring B basically do not affect the progress of the reaction, and those skilled in the art can select suitable R1 and / or R2 according to needs.

[0015] In addition, ring A has four reaction sites, which are selected from the 6- to 14-membered aryl groups and 5- to 10-membered heteroaryl groups as described above. Preferably, 6- to 14-membered aryl groups are used to synthesize standard tetrahydronaphthalene-1-carboxamide compounds; and as the substituent on ring A, R1 must ensure that there is at least one CH with an aromatic or heteroaromatic structure adjacent to the one connected to ring A, so that the cyclization reaction can proceed. For example, if is then the 2-position of indole must be CH. Another example is that if is then at least one of the 2- or 6-positions of the benzene ring needs to be CH. Ring B is far from the reaction site and has a relatively small influence on the reaction. Therefore, a wider variety of aromatic rings and heteroaromatic rings are applicable to ring B, and those skilled in the art can select a suitable ring B according to needs.

[0016] Among them, in the above method, ring A is selected from phenyl, naphthyl, anthryl, phenanthryl, pyrrolyl, pyridyl, indolyl, quinolinyl, isoquinolinyl; in ring A, the N on the pyrrolyl and indolyl is connected to H or C(O)OR6; R6 is selected from C1-C6 alkyl.

[0017] Preferably, in the above method, ring A is selected from phenyl, naphthyl, anthryl, phenanthryl, pyrrolyl, pyridyl, indolyl, quinolinyl, isoquinolinyl; in ring A, the N on the pyrrolyl and indolyl is connected to H or C(O)OR6; R6 is selected from tert-butyl.

[0018] Among them, in the above method, R3 is selected from 3- to 6-membered cycloalkyl, C1-C6 alkyl, 6- to 10-membered aryl; R4 is selected from cyano, -C(O)R 18 , -C(O)OR 19 ; R 18 , R 19 are each independently selected from C1-C6 alkyl.

[0019] Preferably, in the above method, R3 is selected from 3- to 6-membered cycloalkyl, methyl, ethyl, phenyl; R4 is selected from cyano, methoxycarbonyl, ethoxycarbonyl, acetyl.

[0020] Among them, in the above method, R1 represents 1 to 3 substituents on the connected ring A, and each substituent is independently selected from hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted C1-C 10 alkyl, substituted or unsubstituted C1-C 10 alkoxy, substituted or unsubstituted C1-C 10alkylthio, substituted or unsubstituted C1-C 10 alkoxycarbonyl, substituted or unsubstituted 3- to 8-membered cycloalkyl, substituted or unsubstituted 3- to 8-membered cycloalkoxy, substituted or unsubstituted 3- to 8-membered cycloalkanecarbonyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 6- to 10-membered aryloxy, substituted or unsubstituted 6- to 10-membered arylcarbonyl, -Bpin, -NHC(O)OR7, -C(O)R8, -C(O)NHR9, -SO2NHR 10 -OC(O)R 11 , or any two adjacent substituents are joined together and, together with the carbon atom on ring A connecting the two substituents, form a 5- to 6-membered cyclic structure which may or may not contain a heteroatom, the heteroatom being N, O or S, and the number of heteroatoms being 1 to 3;

[0021] In R1, the substituents of the substituted C1-C 10 alkyl, substituted C1-C 10 alkoxy, substituted C1-C 10 alkylthio, substituted C1-C 10 alkoxycarbonyl, substituted 3- to 8-membered cycloalkyl, substituted 3- to 8-membered cycloalkoxy, substituted 3- to 8-membered cycloalkanecarbonyl, substituted 6- to 10-membered aryl, substituted 6- to 10-membered aryloxy, substituted 6- to 10-membered arylcarbonyl are each independently selected from halogen, 6- to 10-membered aryl;

[0022] R7, R8, R9 are each independently selected from C1-C6 alkyl;

[0023] R 10 is selected from C1-C6 alkanecarbonyl, 6- to 10-membered aryl, 5- to 6-membered heteroaryl;

[0024] R 11 is selected from C1-C6 alkyl, 6- to 10-membered aryl substituted or unsubstituted with C1-C6 alkanecarbonyloxy, 5- to 6-membered heteroaryl.

[0025] Preferably, in the above method, R1 represents 1 to 2 substituents on the connected ring A, and each substituent is independently selected from hydrogen, halogen, cyano, hydroxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted 3- to 6-membered cycloalkyl, substituted or unsubstituted 3- to 6-membered cycloalkoxy, substituted or unsubstituted 3- to 6-membered cycloalkanecarbonyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 6- to 10-membered aryloxy, substituted or unsubstituted 6- to 10-membered arylcarbonyl, -Bpin, -NHC(O)OR7, -C(O)R8, -C(O)NHR9, -SO2NHR10 、 -OC(O)R 11 、 or any two adjacent substituents are joined together and, together with the carbon atom on ring A connecting the two substituents, form (wherein, the double dashed line represents the fused ring structure with ring A);

[0026] In R1, the substituents of the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C1-C6 alkylthio, substituted C1-C6 alkoxycarbonyl, substituted 3-6 membered cycloalkyl, substituted 3-6 membered cycloalkoxy, substituted 3-6 membered cycloalkanecarbonyl, substituted 6-10 membered aryl, substituted 6-10 membered aryloxy, and substituted 6-10 membered arylcarbonyl are each independently selected from fluorine, chlorine, bromine, 6-10 membered aryl;

[0027] R7, R8, and R9 are each independently selected from C1-C4 alkyl;

[0028] R 10 is selected from C1-C4 alkanecarbonyl, 6-10 membered aryl, 5-6 membered heteroaryl;

[0029] R 11 is selected from C1-C4 alkyl, 6-10 membered aryl which is substituted or unsubstituted with C1-C4 alkanecarbonyloxy, 5-6 membered heteroaryl.

[0030] More preferably, in the above method, R1 represents 1-2 substituents on the connected ring A, and each substituent is independently selected from H, fluorine, chlorine, bromine, cyano, hydroxy, methyl, tert-butyl, trifluoromethyl, benzyl, methoxy, trifluoromethoxy, methylthio, ethoxycarbonyl, phenyl, phenoxy, phenylcarbonyl, -Bpin, -NHBoc, -SO2NHAc, or any two adjacent substituents are joined together and, together with the carbon atom on ring A connecting the two substituents, form (wherein, the double dashed line represents the fused ring structure with ring A).

[0031] Most preferably, in the above method, the formula I is selected from:

[0032] Among them, in the above method, ring B is selected from 6-14 membered aryl, 5-10 membered heteroaryl; in ring B, the 5-10 membered heteroaryl contains 1 heteroatom, and the heteroatom is selected from N, NH, NC(O)OR 12 、 S, O; R 12 is selected from C1-C8 alkyl.

[0033] Preferably, in the above method, ring B is selected from phenyl, naphthyl, anthryl, phenanthryl, pyrrolyl, pyridyl, indolyl, quinolinyl, isoquinolinyl; in ring B, the N on the pyrrolyl and indolyl is connected to H or C(O)OR 12 is connected; R 12 is selected from C1-C6 alkyl.

[0034] More preferably, in the above method, ring B is selected from phenyl, naphthyl, anthryl, phenanthryl, pyrrolyl, pyridyl, indolyl, quinolinyl, isoquinolinyl; in ring B, the N on the pyrrolyl and indolyl is connected to H or C(O)OR 12 is connected; R 12 is selected from tert-butyl.

[0035] Among them, in the above method, R5 is selected from hydrogen, 3-6 membered cycloalkyl, C1-C4 alkyl.

[0036] Preferably, in the above method, R5 is selected from hydrogen, methyl.

[0037] Among them, in the above method, R2 represents 1-3 substituents on the connected ring B, and each substituent is independently selected from hydrogen, halogen, cyano, hydroxy, substituted or unsubstituted C1-C 10 alkyl, substituted or unsubstituted C1-C 10 alkoxy, substituted or unsubstituted C1-C 10 alkylthio, substituted or unsubstituted C1-C 10 alkoxycarbonyl, substituted or unsubstituted 3-8 membered cycloalkyl, substituted or unsubstituted 3-8 membered cycloalkoxy, substituted or unsubstituted 3-8 membered cycloalkanecarbonyl, substituted or unsubstituted 6-10 membered aryl, substituted or unsubstituted 6-10 membered aryloxy, substituted or unsubstituted 6-10 membered arylcarbonyl, -Bpin, -NHC(O)OR 13 , -C(O)R 14 , -C(O)NHR 15 , -SO2NHR 16 , -OC(O)R 17 , or any two adjacent substituents are joined and together with the carbon atoms on ring B connecting the two substituents form a 5-6 membered cyclic structure with or without heteroatoms, the heteroatoms are N, O or S, and the number of heteroatoms is 1-3;

[0038] In R2, the substituted C1-C 10 alkyl, substituted C1-C 10 alkoxy, substituted C1-C 10 alkylthio, substituted C1-C 10The substituents of alkoxycarbonyl, substituted 3- to 8-membered cycloalkyl, substituted 3- to 8-membered cycloalkoxy, substituted 3- to 8-membered cycloalkanecarbonyl, substituted 6- to 10-membered aryl, substituted 6- to 10-membered aryloxy, and substituted 6- to 10-membered arylcarbonyl are each independently selected from halogen and 6- to 10-membered aryl;

[0039] R 13 、R 14 、R 15 are each independently selected from C1-C6 alkyl;

[0040] R 16 is selected from C1-C6 alkanecarbonyl, 6- to 10-membered aryl, and 5- to 6-membered heteroaryl;

[0041] R 17 is selected from C1-C6 alkyl, 6- to 10-membered aryl which is substituted or unsubstituted by C1-C6 alkanecarbonyloxy, and 5- to 6-membered heteroaryl.

[0042] Preferably, in the above method, R2 represents 1 to 2 substituents on the linked ring B, and each substituent is independently selected from hydrogen, halogen, cyano, hydroxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted 3- to 6-membered cycloalkyl, substituted or unsubstituted 3- to 6-membered cycloalkoxy, substituted or unsubstituted 3- to 6-membered cycloalkanecarbonyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 6- to 10-membered aryloxy, substituted or unsubstituted 6- to 10-membered arylcarbonyl, -Bpin, -NHC(O)OR 13 、-C(O)R 14 、-C(O)NHR 15 、-SO2NHR 16 、-OC(O)R 17 、 or any two adjacent substituents are joined and together with the carbon atom on ring B connecting the two substituents form (wherein, the double dashed line represents the fused ring structure with ring B);

[0043] In R2, the substituents of the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C1-C6 alkylthio, substituted C1-C6 alkoxycarbonyl, substituted 3- to 6-membered cycloalkyl, substituted 3- to 6-membered cycloalkoxy, substituted 3- to 6-membered cycloalkanecarbonyl, substituted 6- to 10-membered aryl, substituted 6- to 10-membered aryloxy, and substituted 6- to 10-membered arylcarbonyl are each independently selected from fluorine, chlorine, bromine, and 6- to 10-membered aryl;

[0044] R 13 、R 14 、R15 Each independently selected from C1-C4 alkyl;

[0045] R 16 Selected from C1-C4 alkoxycarbonyl, 6-10 membered aryl, 5-6 membered heteroaryl;

[0046] R 17 Selected from C1-C4 alkyl, 6-10 membered aryl substituted or unsubstituted with C1-C4 alkoxycarbonyloxy, 5-6 membered heteroaryl.

[0047] More preferably, in the above method, R2 represents 1-2 substituents on the linked ring B, and each substituent is independently selected from H, fluorine, chlorine, bromine, cyano, hydroxy, methyl, tert-butyl, trifluoromethyl, benzyl, methoxy, trifluoromethoxy, methylthio, ethoxycarbonyl, phenyl, phenoxy, benzoyl, -Bpin, -NHBoc, -SO2NHAc, Or any two adjacent substituents are joined and together with the carbon atom on ring B connecting the two substituents form (wherein, the double dashed line represents the fused ring structure with ring B).

[0048] Most preferably, in the above method, the formula II is selected from:

[0049] Most preferably, in the above method, the formula III is selected from:

[0050]

[0051] Wherein, in the above method, the molar ratio of the 2-benzyl-2-bromocarbonyl compound, N-arylacrylamide and photocatalyst is 1:1-2:0.01-0.05.

[0052] Preferably, in the above method, the molar ratio of the 2-benzyl-2-bromocarbonyl compound, N-arylacrylamide and photocatalyst is 1:1.2-1.8:0.01-0.03.

[0053] Wherein, in the above method, the photocatalyst is selected from 3DPAFIPN, 3DPA2FBN or 4CzIPN.

[0054] Preferably, in the above method, the photocatalyst is 3DPA2FBN.

[0055] Among them, in the above method, the organic solvent is selected from at least one of N,N-dimethylformamide, 1,4-dioxane, diethyl ether, ethyl acetate, methanol, acetone, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, and acetonitrile.

[0056] Preferably, in the above method, the organic solvent is N,N-dimethylformamide.

[0057] Among them, in the above method, the dosage of the organic solvent is 5 - 30 mL / mmol of formula I.

[0058] Preferably, in the above method, the dosage of the organic solvent is 15 - 25 mL / mmol of formula I.

[0059] Among them, in the above method, the light source used for visible light irradiation is selected from a blue light source, a green light source, an ultraviolet light source, or a white light source.

[0060] Preferably, in the above method, the light source used for visible light irradiation is a blue light source.

[0061] Among them, in the above method, the wavelength used for visible light irradiation is 455 - 465 nm;

[0062] Among them, in the above method, the temperature of the cyclization reaction is 0 - 80 °C.

[0063] Preferably, in the above method, the temperature of the cyclization reaction is 20 - 30 °C.

[0064] Among them, in the above method, the time of the cyclization reaction is 1 - 6 hours.

[0065] Preferably, in the above method, the time of the cyclization reaction is 1 - 2 hours.

[0066] In the present invention, after the reaction is completed, the post-treatment is a conventional operation in the art, that is: quenching the reaction with an appropriate amount of water and extracting with an appropriate amount of an appropriate organic solvent (such as ethyl acetate, dichloromethane, etc.), then the organic layer is washed with saturated brine and dried over Na2SO4, the solvent is removed under reduced pressure, and the obtained residue is separated by column chromatography using an organic solvent with an appropriate polarity according to the polarity of the product to obtain the target product.

[0067] Advantages of the present invention: The present invention uses 2-(hetero)arylmethyl-2-bromocarbonyl compounds (such as 2-benzyl-2-bromocarbonyl compounds) and N-(hetero)arylacrylamide compounds (such as N-arylacrylamide) as raw materials, and performs a [4+2] cycloaddition reaction through visible light catalysis without the participation of metals and additives, to prepare a novel class of tetrahydrobenzene-1-carboxamide compounds. The obtained compounds are confirmed by nuclear magnetic resonance spectrometer, breaking through the structural limitations of tetrahydronaphthalene-1-carboxamide compounds in nature, and providing a new way for the industrial production of tetrahydrobenzene (naphthalene)-1-carboxamide compounds; the method of the present invention is easy to operate, has mild reaction conditions, stable process conditions, easy product purification, wide substrate range, good functional group tolerance, low production cost, and is suitable for large-scale production. Description of the Drawings

[0068] Figure 1 1H NMR spectrum of the compound prepared in Example 1 of the present invention 1 spectrum.

[0069] Figure 2 13C NMR spectrum of the compound prepared in Example 1 of the present invention 13 spectrum. Detailed Embodiments

[0070] The following will explain the solution of the present invention in combination with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the embodiments, the techniques or conditions described in the literature in the art or according to the product specifications are followed.

[0071] Example 1: Preparation of Diethyl 4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0072]

[0073] Under argon atmosphere, N-phenylacrylamide (44.6 mg, 0.3 mmol), 3DPA2FBN (2.6 mg, 0.004 mmol), diethyl 2-benzyl-2-bromomalonate (65.8 mg, 0.2 mmol) and N,N-dimethylformamide (4 mL) were successively added to a dry Schlenk tube (10 mL), and irradiated with a blue LED light source (wavelength 455-465 nm), and reacted at 25 °C for 1 hour. After the reaction was completed, the reaction was quenched with H2O (6 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over Na2SO4, and the solvent was removed under reduced pressure and separated by column chromatography to obtain the compound. The obtained product was a white solid, with a melting point of 145.7-147.0 °C and a yield of 80%.Figure 1 and Figure 2 It can be seen that the product characterization is as follows: 1 H NMR(400MHz,CDCl3)δ8.05(d,J=7.5Hz,1H),7.83(d,J=7.8Hz,1H),7.74(s,1H),7.66(d,J=8.2Hz,1H),7.51–7.25(m,8H),4.23–4.01(m,5H),3.42(d,J=16.1Hz,1H),3.32(d,J=16.2Hz,1H),3.01–2.90(m,1H),2.77(dd,J=14.0,7.6Hz,1H),1.20(t,J=7.3Hz,3H),1.18(t,J=7.3Hz,3H); 13 C NMR(101MHz,CDCl3)δ172.4,171.3,170.6,134.9,134.0,132.4,132.1,129.7,129.0,128.8,128.0,127.3,126.7,126.3,125.9,125.7,125.6,120.2,119.9,62.0,61.7,53.4,46.3,35.1,32.1,14.0,13.9;HRMS(ESI)calcd for C 23 H 26 NO5[M+H] + :396.1085,found:396.1800。

[0074] The screening results of other reaction parameters are shown in Table 1 below:

[0075]

[0076] Table 1 Screening Results of Reaction Parameters

[0077] Number Single-factor condition change Yield (%) 1 Example 1 80 2 4CzIPN replaces 3DPA2FBN 68 3 3DPAFIPN replaces 3DPA2FBN 66 4 Rhodamine B replaces 3DPA2FBN 0 5 Dichloromethane replaces N,N-dimethylformamide 34 6 Tetrahydrofuran replaces N,N-dimethylformamide 28 7 Acetonitrile replaces N,N-dimethylformamide 30 8 The reaction substrate equivalents are exchanged with each other 77 9 1.3 equivalents of N-phenylacrylamide replaces 1.5 equivalents of N-phenylacrylamide 76 10 0.01 equivalent of 3DPA2FBN replaces 0.02 equivalent of 3DPA2FBN 71 11 2 hours replaces 1 hour 80 12 No light irradiation 0 13 No photocatalyst 0

[0078] Example 2: Preparation of Diethyl 6-methyl-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0079]

[0080] Referring to Example 1, diethyl 2-benzyl-2-bromomalonate was replaced with diethyl 2-bromo-2-(4-methylbenzyl)malonate, and the resulting product was a white solid with a melting point of 138.0-139.0 °C and a yield of 76%. The product characterization is as follows: 11H NMR (400 MHz, CDCl3) δ 7.55–7.44 (m, 3H), 7.30 (t, J = 7.9 Hz, 2H), 7.14–7.06 (m, 2H), 7.04 (d, J = 8.0 Hz, 1H), 7.00 (s, 1H), 4.20–4.01 (m, 4H), 3.98 (t, J = 7.8 Hz, 1H), 3.32 (d, J = 16.0 Hz, 1H), 3.23 (d, J = 16.0 Hz, 1H), 2.85–2.74 (m, 1H), 2.62 (dd, J = 14.0, 8.0 Hz, 1H), 2.27 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.21, 170.40, 169.67, 136.83, 135.76, 130.88, 130.26, 128.31, 127.97, 127.91, 127.65, 123.33, 118.69, 60.87, 60.61, 52.31, 45.23, 33.58, 31.07, 20.07, 12.94, 12.90; HRMS (ESI) calcd for C 24 H 28 NO5 [M + H] + : 410.1962, found: 410.1951。

[0081] Example 3: Preparation of Diethyl 6-Methoxy-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0082]

[0083] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-methoxybenzyl)malonate. The resulting product is a white solid with a melting point of 119.0 - 120.0 °C and a yield of 72%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.49 (d, J = 7.3 Hz, 2H), 7.29 (t, J = 7.9 Hz, 2H), 7.13–7.06 (m, 2H), 6.79 (dd, J = 8.5, 2.6 Hz, 1H), 6.73 (d, J = 2.6 Hz, 1H), 4.19–4.02 (m, 4H), 4.00 (t, J = 7.9 Hz, 1H), 3.72 (s, 3H), 3.29 (d, J = 15.8 Hz, 1H), 3.21 (d, J = 15.9 Hz, 1H), 2.85–2.74 (m, 1H), 2.61 (dd, J = 14.0, 8.1 Hz, 1H), 1.20 (t, J = 6.4 Hz, 3H), 1.16 (t, J = 6.4 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.04, 171.45, 170.70, 158.55, 137.81, 133.25, 130.46, 128.95, 126.39, 124.43, 119.83, 114.03, 113.24, 61.93, 61.67, 55.31, 53.48, 46.53, 34.24, 32.00, 13.99, 13.95; HRMS (ESI) calcd for C 24 H 28 NO6 [M + H] + : 426.1911, found: 426.1897。

[0084] Example 4: Preparation of Diethyl 6-(tert-butyl)-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0085]

[0086] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-tert-butylbenzyl)malonate. The obtained product is a white solid with a melting point of 148.0 - 149.0 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.7 Hz, 2H), 7.35 (s, 1H), 7.33–7.25 (m, 3H), 7.21 (d, J = 2.4 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 4.18–3.99 (m, 5H), 3.34 (d, J = 16.2 Hz, 1H), 3.22 (d, J = 16.2 Hz, 1H), 2.87–2.77 (m, 1H), 2.67 (dd, J = 14.0, 7.6 Hz, 1H), 1.26 (s, 9H), 1.19 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.2, 171.4, 170.7, 150.1, 137.7, 131.7, 131.3, 129.3, 129.0, 125.7, 125.1, 124.4, 119.8, 61.9, 61.7, 53.2, 46.4, 34.5, 34.5, 32.1, 31.3, 14.0, 13.9; HRMS (ESI) calcd for 27 C 34 H + NO5 [M + H]

[0087] Example 5: Preparation of Diethyl 6-Fluoro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0088]

[0089] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-fluorobenzyl)malonate. The resulting product is a white solid with a melting point of 167.0 - 168.8 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.52 (d, J = 7.7 Hz, 2H), 7.32 (t, J = 7.9 Hz, 2H), 7.19–7.14 (m, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.97–6.89 (m, 2H), 4.23–4.06 (m, 4H), 3.99 (t, J = 8.0 Hz, 1H), 3.32 (d, J = 16.0 Hz, 1H), 3.26 (d, J = 16.0 Hz, 1H), 2.84–2.74 (m, 1H), 2.60 (dd, J = 14.0, 8.5 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.36, 171.24, 170.52, 161.62 (d, J = 245.8 Hz), 137.64, 134.24 (d, J = 7.2 Hz), 130.90 (d, J = 8.0 Hz), 129.92 (d, J = 3.0 Hz), 129.03, 124.64, 119.83, 115.01 (d, J = 21.3 Hz), 114.88 (d, J = 21.7 Hz), 62.08, 61.81, 53.35, 46.36, 34.31, 31.80, 13.97, 13.95; 19 19F NMR (376 MHz, CDCl3) δ -114.90; HRMS (ESI) calcd for C 23 H 25 FNO5 [M + H] + : 414.1711, found: 414.1717.

[0090] Example 6: Preparation of Diethyl 6-chloro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0091]

[0092] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-chlorobenzyl)malonate. The resulting product is a white solid with a melting point of 151.0 - 152.8 °C and a yield of 65%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.52 (d, J = 7.7 Hz, 2H), 7.32 (t, J = 7.9 Hz, 2H), 7.23–7.16 (m, 2H), 7.17–7.08 (m, 2H), 4.21–4.06 (m, 4H), 3.97 (t, J = 8.1 Hz, 1H), 3.31 (d, J = 16.2 Hz, 1H), 3.25 (d, J = 16.3 Hz, 1H), 2.84–2.73 (m, 1H), 2.60 (dd, J = 14.0, 8.7 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.32, 171.14, 170.48, 137.64, 134.22, 132.84, 132.73, 130.72, 129.04, 128.24, 127.92, 124.66, 119.89, 62.12, 61.86, 53.22, 46.11, 34.43, 31.86, 13.98, 13.96; HRMS (ESI) calcd for C 23 H 25 ClNO5 [M + H] + : 430.1416, found: 430.1423.

[0093] Example 7: Preparation of Diethyl 6-Bromo-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0094]

[0095] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-bromobenzyl)malonate. The resulting product is a white solid with a melting point of 138.0 - 140.4 °C and a yield of 64%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.7 (s, 1H), 7.5 (d, J = 7.9 Hz, 2H), 7.4–7.3 (m, 4H), 7.1 (t, J = 7.4 Hz, 1H), 7.1 (d, J = 8.1 Hz, 1H), 4.2–4.1 (m, 4H), 4.0 (t, J = 8.1 Hz, 1H), 3.3 (d, J = 16.2 Hz, 1H), 3.2 (d, J = 16.3 Hz, 1H), 2.8–2.7 (m, 1H), 2.6 (dd, J = 14.0, 8.7 Hz, 1H), 1.2 (t, J = 7.1 Hz, 3H), 1.2 (t, J = 7.1 Hz, 3H);13 CNMR(101MHz,CDCl3)δ171.3,171.1,170.5,137.7,134.7,133.4,131.1,131.0,130.8,129.0,124.7,120.7,119.9,62.1,61.9,53.2,46.0,34.5,31.9,14.0(overlapped,2C); HRMS(ESI) calcd for C 23 H 24 BrNNaO5[M+Na] + : 496.0730, found: 496.0726。

[0096] Example 8: Preparation of Diethyl 4-(phenylcarbamoyl)-6-(trifluoromethyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0097]

[0098] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-(trifluoromethyl)benzyl)malonate. The resulting product is a white solid with a melting point of 157.0 - 158.0 °C and a yield of 63%. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.78(s,1H),7.50(d,J = 7.7Hz,2H),7.48–7.44(m,2H),7.35–7.27(m,3H),7.12(t,J = 7.4Hz,1H),4.23–4.07(m,4H),4.04(t,J = 8.1Hz,1H),3.40(d,J = 16.7Hz,1H),3.35(d,J = 16.9Hz,1H),2.89–2.78(m,1H),2.63(dd,J = 13.9,9.0Hz,1H),1.22(t,J = 7.1Hz,3H),1.15(t,J = 7.1Hz,3H); 13 C NMR(101MHz,CDCl3)δ171.23,170.96,170.45,138.56,137.56,133.36,129.96,129.44(q,J = 32.6Hz),129.0,125.27(q,J = 3.8Hz),124.77,124.33(q,J = 3.8Hz),123.90(d,J = 272.0Hz),119.84,62.21,61.94,53.12,46.03,34.86,31.99,13.95,13.91; 1919F NMR (376 MHz, CDCl3) δ -62.40; HRMS (ESI) calcd for C 24 H 25 F3NO5 [M + H] + : 464.1679, found: 464.1674。

[0099] Example 9: Preparation of Diethyl 6-acetyl-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0100]

[0101] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-(4-acetylbenzyl)-2-bromomalonate. The resulting product is a white solid with a melting point of 133.0 - 134.0 °C and a yield of 66%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.84–7.73 (m, 3H), 7.50 (d, J = 7.6 Hz, 2H), 7.34–7.27 (m, 3H), 7.11 (t, J = 7.4 Hz, 1H), 4.21–4.09 (m, 4H), 4.06 (t, J = 8.0 Hz, 1H), 3.41 (d, J = 16.6 Hz, 1H), 3.35 (d, J = 16.8 Hz, 1H), 2.88–2.79 (m, 1H), 2.64 (dd, J = 13.9, 8.7 Hz, 1H), 2.53 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 197.6, 171.5, 171.0, 170.4, 140.2, 137.6, 136.1, 133.0, 129.8, 129.0, 128.5, 127.5, 124.7, 120.0, 62.2, 61.9, 53.2, 46.1, 35.1, 32.0, 26.6, 14.0 (overlapped, 2C); HRMS (ESI) calcd for C 25 H 28 O6 [M + H] + : 438.1911, found: 438.1912。

[0102] Example 10: Preparation of Diethyl 6-cyano-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0103]

[0104] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-cyanobenzyl)malonate. The resulting product is a white solid with a melting point of 137.0 - 138.0 °C and a yield of 75%. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.95(s,1H),7.55(d,J=1.3Hz,1H),7.52(d,J=9.2Hz,2H),7.47(dd,J=7.9,1.7Hz,1H),7.33(t,J=7.9Hz,2H),7.28(d,J=7.6Hz,1H),7.14(t,J=7.4Hz,1H),4.25–4.08(m,4H),4.00(t,J=8.3Hz,1H),3.37(s,2H),2.87–2.77(m,1H),2.59(dd,J=13.9,9.5Hz,1H),1.23(t,J=7.1Hz,3H),1.16(t,J=7.1Hz,3H); 13 C NMR(101MHz,CDCl3)δ170.89,170.75,170.25,140.13,137.51,134.31,132.09,130.78,130.24,129.10,124.88,119.97,118.60,110.90,62.30,62.03,52.98,45.71,35.04,31.81,13.98,13.96; HRMS(ESI)calcd for C 24 H 25 N2O5[M+H] + :421.1758,found:421.1767.

[0105] Example 11: Preparation of Diethyl 8-Methyl-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0106]

[0107] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(2-methylbenzyl)malonate. The resulting product is a white solid with a melting point of 137.0 - 138.0 °C and a yield of 75%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.6 Hz, 2H), 7.33–7.26 (m, 3H), 7.14–7.03 (m, 4H), 4.21–4.01 (m, 4H), 3.99 (t, J = 7.7 Hz, 1H), 3.26–3.14 (m, 2H), 2.79 (dd, J = 13.9, 7.4 Hz, 1H), 2.68 (dd, J = 13.9, 7.7 Hz, 1H), 2.33 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.1, 171.5, 170.9, 137.8, 137.0, 133.2, 131.9, 129.4, 128.9, 126.6, 126.6, 124.4, 119.7, 62.0, 61.7, 53.2, 46.5, 31.8, 31.5, 19.9, 14.0, 13.9; HRMS (ESI) calcd for C 24 H 28 NO5[M + H] + : 410.1962, found: 410.1965.

[0108] Example 12: Preparation of Diethyl 8-Fluoro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0109]

[0110] Referring to Example 1, diethyl 2-bromo-2-(2-fluorobenzyl)malonate was used instead of diethyl 2-benzyl-2-bromomalonate. The resulting product was a white solid with a melting point of 132.0 - 133.4 °C and a yield of 49%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.6 Hz, 2H), 7.45 (s, 1H), 7.31 (t, J = 7.9 Hz, 2H), 7.22–7.15 (m, 1H), 7.11 (t, J = 7.4 Hz, 1H), 7.04–6.94 (m, 2H), 4.21–4.05 (m, 4H), 3.99 (t, J = 7.9 Hz, 1H), 3.38 (d, J = 17.0 Hz, 1H), 3.26 (d, J = 17.0 Hz, 1H), 2.83–2.75 (m, 1H), 2.63 (dd, J = 13.9, 8.6 Hz, 1H), 1.21 (t, J = 7.0 Hz, 3H), 1.19 (t, J = 7.0 Hz, 3H); 1313C NMR(101MHz,CDCl3)δ170.36,170.05,169.44,159.63(d,J=246.4Hz),136.59,133.48(d,J=4.1Hz),127.96,126.80(d,J=8.7Hz),123.55,122.99(d,J=3.4Hz),121.43(d,J=17.3Hz),118.73,113.00(d,J=21.7Hz),61.06,60.82,51.31,44.86(d,J=2.4Hz),30.58,26.44(d,J=4.9Hz),12.90,12.87; 19 19F NMR(376MHz,CDCl3)δ-117.07;HRMS(ESI)calcd for C 23 H 25 19FNO5[M+H] + :414.1711,found:414.1720。

[0111] Example 13: Preparation of Diethyl 8-chloro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0112]

[0113] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(2-chlorobenzyl)malonate. The resulting product is a white solid with a melting point of 128.0 - 133.0 °C and a yield of 61%. Product characterization: 1 1H NMR(400MHz,CDCl3)δ7.76(s,1H),7.61(d,J=7.7Hz,2H),7.48–7.37(m,3H),7.30–7.18(m,3H),4.36–4.18(m,4H),4.12(t,J=7.9Hz,1H),3.59(d,J=17.1Hz,1H),3.42(d,J=17.1Hz,1H),2.96–2.85(m,1H),2.75(dd,J=13.9,8.8Hz,1H),1.34(t,J=7.3Hz,3H),1.30(t,J=7.2Hz,3H); 1313C NMR (101 MHz, CDCl3) δ 170.5, 170.1, 169.5, 136.6, 133.7, 133.6, 131.6, 127.9, 127.5, 126.6, 126.0, 123.6, 118.8, 61.1, 60.8, 52.0, 45.4, 31.2, 30.5, 12.9 (overlapped, 2C); HRMS (ESI) calcd for C 23 H 25 ClNO5 [M+H] + : 430.1416, found: 430.1417。

[0114] Example 14: Preparation of Diethyl 8-bromo-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0115]

[0116] Referring to Example 1, diethyl 2-bromo-2-(2-bromobenzyl)malonate was used instead of diethyl 2-benzyl-2-bromomalonate. The obtained product was a white solid with a melting point of 133.8 - 135.4 °C and a yield of 60%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.56–7.43 (m, 4H), 7.31 (t, J = 7.9 Hz, 2H), 7.18 (d, J = 7.7 Hz, 1H), 7.15–7.03 (m, 2H), 4.23–4.05 (m, 4H), 3.99 (t, J = 7.9 Hz, 1H), 3.44 (d, J = 17.0 Hz, 1H), 3.31 (d, J = 17.0 Hz, 1H), 2.83–2.72 (m, 1H), 2.63 (dd, J = 13.9, 8.5 Hz, 1H), 1.22 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.5, 171.1, 170.5, 137.7, 134.9, 134.2, 132.0, 129.0, 128.1, 127.8, 125.6, 124.6, 119.8, 62.2, 61.9, 53.3, 46.6, 35.1, 31.7, 14.0, 13.9; HRMS (ESI) calcd for C 23 H 25 ClNO5 [M+H] + : 474.0911, found: 474.0915。

[0117] Example 15: Preparation of Diethyl 5-Fluoro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate and Diethyl 7-Fluoro-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0118]

[0119] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(3-fluorobenzyl)malonate. The resulting product is a white solid with a melting point of 123.0 - 125.0 °C, a yield of 73%, and rr = 2.1:1. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.68(s,1H),7.56–7.41(m,8.4H),7.33–7.26(m,6.3H),7.24–7.14(m,3.1H),7.13–7.05(m,3.1H),7.00(d,J=7.7Hz,2.1H),6.94–6.85(m,3.9H),4.21–4.03(m,14.5H),3.97(t,J=8.0Hz,1H),3.40(d,J=16.2Hz,2.1H),3.34(d,J=16.3Hz,1H),3.29(d,J=15.8Hz,2.1H),3.26(d,J=16.1Hz,1H),2.92–2.83(m,2.1H),2.83–2.75(m,1H),2.67–2.51(m,3.1H),1.25–1.14(m,12.6H),1.11(t,J=7.1Hz,6H); 1313C NMR(101MHz,CDCl3)δ171.92,171.30,171.12,170.89,170.45,170.31,161.85(d,J = 246.8Hz),160.93(d,J = 246.6Hz),137.82,137.74,137.28(d,J = 3.7Hz),136.80(d,J = 7.8Hz),130.24(d,J = 8.4Hz),128.97(d,J = 8.8Hz),128.98,128.93,128.07(d,J = 2.9Hz),125.00(d,J = 3.1Hz),124.52,124.41,120.27(d,J = 15.8Hz),119.90,119.78,115.77(d,J = 21.3Hz),114.43(d,J = 21.7Hz),113.51(d,J = 21.5Hz),62.09,62.05,61.82,61.73,53.29,53.09,45.59,41.12(d,J = 2.4Hz),34.98,34.64(d,J = 2.5Hz),32.05,31.83,13.96,13.93(overlapped,2C),13.91; 19 19F NMR(376MHz,CDCl3)δ - 114.10, - 114.70;HRMS(ESI)calcd for C 23 H 25 19FNO5[M + H] + :414.1711,found:414.1712。

[0120] Example 16: Preparation of Diethyl 5 - chloro - 4-(phenylcarbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate and Diethyl 7 - chloro - 4-(phenylcarbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate

[0121]

[0122] Referring to Example 1, replace diethyl 2 - benzyl - 2 - bromomalonate with diethyl 2 - bromo - 2-(3 - chlorobenzyl)malonate. The obtained product is a white solid, with a melting point of 118.5 - 120.0 °C, a yield of 72%, and rr = 1.5:1. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.68 (s, 1.5H), 7.49 (d, J = 7.3 Hz, 3H), 7.43 (d, J = 7.3 Hz, 2H), 7.32–7.26 (m, 5H), 7.25–7.04 (m, 11H), 4.24 (dd, J = 8.1, 5.9 Hz, 1H), 4.21–3.97 (m, 10H), 3.96 (t, J = 8.0 Hz, 1H), 3.47 (d, J = 16.1 Hz, 1H), 3.32 (d, J = 16.4 Hz, 1.5H), 3.29–3.16 (m, 2.5H), 2.89–2.74 (m, 2.5H), 2.73 (dd, J = 14.2, 5.9 Hz, 1H), 2.59 (dd, J = 13.9, 8.6 Hz, 1.5H), 1.25–1.13 (m, 12H), 1.13 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.63, 171.08, 170.89, 170.79, 170.43, 170.40, 137.71, 137.68, 136.35, 135.07, 133.30, 130.91, 130.49, 129.86, 129.21, 129.00 (overlapped, 2C), 128.91, 128.86, 128.25, 128.18, 127.38, 124.58, 124.43, 119.88, 119.81, 62.12, 62.05, 61.85, 61.75, 53.09, 53.06, 45.73, 44.66, 35.37, 34.73, 32.07, 31.96, 13.97, 13.94 (overlapped, 2C), 13.87; HRMS (ESI) calcd for C 23 H 25 ClNO5 [M+H] + : 430.1416, found: 430.1422.

[0123] Example 17: Preparation of Diethyl 5-bromo-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate and Diethyl 7-bromo-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0124]

[0125] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(3-bromobenzyl)malonate. The resulting product is a white solid with a melting point of 139.0 - 141.0 °C, a yield of 67%, and rr = 2.3:1. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.70(s,2.3H),7.53–7.46(m,5.3H),7.42(d,J=7.3Hz,2H),7.36–7.26(m,11.1H),7.24–7.03(m,9H),4.23(dd,J=7.4,5.8Hz,1H),4.23–4.03(m,13.2H),3.94(t,J=7.5Hz,2.3H),3.49(d,J=16.0Hz,1H),3.32(d,J=16.3Hz,2.3H),3.24(d,J=16.4Hz,2.3H),3.18(d,J=16.1Hz,1H),2.88–2.73(m,4.3H),2.59(dd,J=13.9,8.7Hz,2.3H),1.24–1.09(m,19.8H); 13 C NMR(101MHz,CDCl3)δ171.54(overlapped,2C),171.06,170.89,170.51,170.38,138.04,137.68(overlapped,2C),136.70,132.21,132.16,131.69,131.45,130.27,130.12,129.22,129.00,128.91,128.88,126.00,124.59,124.46,121.43,119.92,119.82,62.13,62.05,61.87,61.77,53.14,53.05,46.90,45.80,35.58,34.64,32.03,31.91,13.97,13.95(overlapped,2C),13.86;HRMS(ESI)calcd for C 23 H 25 BrNO5[M+H] + :474.0911,found:474.0919。

[0126] Example 18: Preparation of Diethyl 5,7-Dimethyl-4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0127]

[0128] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(3,5-dimethylbenzyl)malonate. The resulting product is a white solid with a melting point of 162.5 - 164.0 °C and a yield of 65%. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.41–7.33(m,2H),7.28–7.23(m,2H),7.06(t,J=7.4Hz,1H),6.93(s,1H),6.92(s,1H),6.85(s,1H),4.22–3.95(m,4H),3.90–3.77(m,1H),3.42(d,J=16.2Hz,1H),3.09(d,J=16.2Hz,1H),2.83(dd,J=14.2,8.3Hz,1H),2.75(dd,J=14.2,5.0Hz,1H),2.31(s,3H),2.19(s,3H),1.17(t,J=7.1Hz,3H),1.12(t,J=7.1Hz,3H); 13 C NMR(101MHz,CDCl3)δ172.0,171.3,170.8,137.8,137.6,137.5,135.0,130.3,128.9,128.2,127.0,124.4,119.7,61.9,61.6,52.7,44.2,35.4,32.3,21.0,19.4,14.0,13.8; HRMS(ESI)calcdfor C25H30NO5[M+H]+:424.2118,found:424.2122.

[0129] Example 19: Preparation of diethyl 1-(phenylcarbamoyl)-1,4-dihydrophenanthrene-3,3(2H)-dicarboxylate

[0130]

[0131] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(naphthalen-1-ylmethyl)malonate. The resulting product is a white solid with a melting point of 162.0 - 164.0 °C and a yield of 65%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.58 (td, J = 6.8, 1.5 Hz, 1H), 7.53 (td, J = 6.8, 1.2 Hz, 1H), 7.46 (d, J = 7.7 Hz, 2H), 7.36 (s, 1H), 7.31–7.22 (m, 3H), 7.08 (t, J = 7.4 Hz, 1H), 4.24–4.02 (m, 5H), 3.77 (d, J = 16.8 Hz, 1H), 3.70 (d, J = 16.8 Hz, 1H), 2.92 (dd, J = 13.7, 7.1 Hz, 1H), 2.73 (dd, J = 13.8, 8.2 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.1, 171.4, 170.7, 137.7, 132.8, 132.0, 130.4, 128.9, 128.9, 128.6, 127.6, 126.8, 126.5, 126.2, 124.5, 123.2, 119.7, 62.1, 61.8, 53.1, 47.1, 31.6, 31.0, 14.0, 13.9; HRMS (ESI) calcd for C27H28NO5 [M+H]+: 446.1962, found: 446.1961.

[0132] Example 20: Preparation of 9-(tert-Butyl)-3,3-diethyl-1-(phenylcarbamoyl)-1,4-dihydro-3H-carbazole-3,3,9(2H)-tricarboxylate

[0133]

[0134] Referring to Example 1, replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-((1-(tert-butoxycarbonyl)-1H-indol-3-yl)methyl)malonate. The obtained product is a white solid with a melting point of 152.0 - 154.0 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.2 Hz, 1H), 7.55 (d, J = 7.2 Hz, 1H), 7.44 (dd, J = 8.6, 1.2 Hz, 2H), 7.35 (t, J = 7.1 Hz, 1H), 7.34–7.27 (m, 1H), 7.28–7.26 (m, 2H), 7.11–7.02 (m, 2H), 4.47 (t, J = 6.6 Hz, 1H), 4.27–4.02 (m, 3H), 3.96–3.84 (m, 1H), 3.50 (d, J = 16.4 Hz, 1H), 3.20 (d, J = 16.4 Hz, 1H), 2.90 (dd, J = 14.0, 7.2 Hz, 1H), 2.77 (dd, J = 14.0, 6.2 Hz, 1H), 1.57 (s, 9H), 1.22 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 170.8, 170.6, 170.4, 150.2, 137.7, 136.6, 129.6, 128.8, 128.5, 125.1, 124.2, 123.0, 119.8, 118.6, 117.8, 115.9, 84.9, 62.1, 61.8, 52.7, 43.2, 32.9, 28.1, 27.1, 14.0, 13.8; HRMS (ESI) calcd for C 30 H 35 N2O7 [M + H] + : 535.2439, found: 535.2439。

[0135] Example 21: Preparation of Dimethyl 4-(phenylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0136]

[0137] Referring to Example 1, the product obtained by replacing diethyl 2-benzyl-2-bromomalonate with dimethyl 2-benzyl-2-bromomalonate was a white solid, with a melting point of 140.6 - 142.3 °C and a yield of 75%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.5–7.4 (m, 3H), 7.3 (t, J = 7.9 Hz, 2H), 7.3–7.2 (m, 4H), 7.1 (t, J = 7.4 Hz, 1H), 4.0 (t, J = 7.7 Hz, 1H), 3.7 (s, 3H), 3.6 (s, 3H), 3.4 (d, J = 16.3 Hz, 1H), 3.3 (d, J = 16.9 Hz, 1H), 2.9–2.7 (m, 1H), 2.7 (dd, J = 14.0, 8.0 Hz, 1H); 13 13C NMR (101 MHz, CDCl3) δ 171.88, 171.72, 171.13, 137.70, 134.35, 131.96, 129.55, 128.98, 128.74, 127.88, 127.24, 124.49, 119.78, 53.12, 53.07, 52.96, 46.15, 34.93, 31.97; HRMS (ESI) calcd for C 21 H 21 NNaO5 [M+Na] + : 390.1312, found: 390.1310.

[0138] Example 22: Preparation of Ethyl 2-Acetyl-4-(phenylcarbamoyl)-1,2,3,4-tetrahydronaphthalene-2-carboxylate

[0139]

[0140] Referring to Example 1, replacing diethyl 2-benzyl-2-bromomalonate with ethyl 2-benzyl-2-bromo-3-oxobutyrate, the resulting product was a white solid, melting point 136.8 - 138.4 °C, yield 60%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.8 Hz, 2H), 7.36 (s, 1H), 7.34–7.26 (m, 2H), 7.27–7.17 (m, 4H), 7.11 (t, J = 7.4 Hz, 1H), 4.23–4.07 (m, 2H), 4.00 (t, J = 7.6 Hz, 1H), 3.28 (d, J = 16.2 Hz, 1H), 3.22 (d, J = 16.3 Hz, 1H), 2.87–2.76 (m, 1H), 2.57 (dd, J = 14.0, 7.9 Hz, 1H), 2.22 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13CNMR (101 MHz, CDCl3) δ 204.4, 171.9, 171.4, 137.6, 134.7, 132.3, 129.6, 129.0, 128.6, 127.9, 127.3, 124.6, 120.0, 61.9, 59.8, 46.3, 34.1, 31.3, 25.9, 14.0; HRMS (ESI) calcd for C 22 H 24 NO4 [M + H] + : 366.1700, found: 366.1702。

[0141] Example 23: Preparation of Ethyl 2-Cyano-4-(phenylcarbamoyl)-1,2,3,4-tetrahydronaphthalene-2-carboxylate

[0142]

[0143] Referring to Example 1, replacing diethyl 2-benzyl-2-bromomalonate with ethyl 2-bromo-2-cyano-3-phenylpropionate, the resulting product was a white solid with a melting point of 149.5 - 151.4 °C and a yield of 23%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.62–7.47 (m, 3H), 7.34 (t, J = 7.9 Hz, 2H), 7.32–7.25 (m, 3H), 7.24–7.15 (m, 1H), 7.14 (t, J = 7.5 Hz, 1H), 4.31 (q, J = 7.3 Hz, 2H), 4.14 (dd, J = 10.8, 6.4 Hz, 1H), 3.47 (d, J = 16.4 Hz, 1H), 3.29 (d, J = 16.4 Hz, 1H), 2.77–2.67 (m, 1H), 2.64 (dd, J = 13.6, 10.8 Hz, 1H), 1.35 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 170.7, 168.0, 137.4, 131.7, 131.5, 129.7, 129.1, 128.3, 128.2, 128.0, 124.9, 119.9, 118.6, 63.5, 46.4, 43.0, 36.4, 33.8, 14.0; HRMS (ESI) calcd for C 21 H 21 N2O3 [M + H] + : 349.1547, found: 349.1549。

[0144] Example 24: Preparation of Diethyl 4-(p-tolylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0145]

[0146] Referring to Example 1, replace N-phenylacrylamide with N-(p-tolyl)acrylamide. The resulting product is a white solid with a melting point of 168.8 - 170.0 °C and a yield of 70%. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.39(s,1H),7.36(d,J = 8.4Hz,2H),7.26–7.14(m,4H),7.09(d,J = 8.2Hz,2H),4.20–4.02(m,4H),4.00(t,J = 7.8Hz,1H),3.36(d,J = 16.1Hz,1H),3.27(d,J = 16.2Hz,1H),2.86–2.75(m,1H),2.64(dd,J = 13.9,8.1Hz,1H),2.30(s,3H),1.20(t,J = 7.1Hz,3H),1.17(t,J = 7.1Hz,3H); 13 CNMR(101MHz,CDCl3)δ171.9,171.4,170.7,135.2,134.5,134.0,132.3,129.5,129.4,128.6,127.7,127.2,119.8,61.9,61.7,53.3,46.2,35.0,32.0,20.9,14.0,13.9;HRMS(ESI)calcd for C24H28NO5[M + H] + :410.1962,found:410.1960。

[0147] Example 25: Preparation of Diethyl 4-((4-methoxyphenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0148]

[0149] Referring to Example 1, replace N-phenylacrylamide with N-(p-methoxyphenyl)acrylamide. The resulting product is a white solid with a melting point of 143.0 - 144.0 °C and a yield of 72%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.29–7.24 (m, 2H), 7.23–7.13 (m, 7H), 7.11 (d, J = 8.5 Hz, 2H), 4.20–4.02 (m, 4H), 3.99 (t, J = 7.8 Hz, 1H), 3.93 (s, 2H), 3.35 (d, J = 16.1 Hz, 1H), 3.26 (d, J = 16.1 Hz, 1H), 2.85–2.74 (m, 1H), 2.63 (dd, J = 13.9, 8.2 Hz, 1H), 1.19 (t, J = 6.4 Hz, 3H), 1.16 (t, J = 6.4 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.00, 171.38, 170.67, 141.13, 137.30, 135.90, 134.45, 132.27, 129.52, 129.43, 128.85, 128.59, 128.48, 127.72, 127.19, 126.10, 119.95, 61.97, 61.71, 53.29, 46.21, 41.34, 34.98, 32.04, 13.98, 13.96; HRMS (ESI) calcd for C30H32NO5 [M+H] + : 486.2275, found: 486.2271.

[0150] Example 26: Preparation of Diethyl 4-((4-benzylphenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0151]

[0152] Referring to Example 1, N-phenylacrylamide was replaced with N-(4-benzylphenyl)acrylamide, and the resulting product was a white solid with a melting point of 129.7 - 130.7 °C and a yield of 72%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.29–7.24 (m, 2H), 7.23–7.13 (m, 7H), 7.11 (d, J = 8.5 Hz, 2H), 4.20–4.02 (m, 4H), 3.99 (t, J = 7.8 Hz, 1H), 3.93 (s, 2H), 3.35 (d, J = 16.1 Hz, 1H), 3.26 (d, J = 16.1 Hz, 1H), 2.85–2.74 (m, 1H), 2.63 (dd, J = 13.9, 8.2 Hz, 1H), 1.19 (t, J = 6.4 Hz, 3H), 1.16 (t, J = 6.4 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.00, 171.38, 170.67, 141.13, 137.30, 135.90, 134.45, 132.27, 129.52, 129.43, 128.85, 128.59, 128.48, 127.72, 127.19, 126.10, 119.95, 61.97, 61.71, 53.29, 46.21, 41.34, 34.98, 32.04, 13.98, 13.96; HRMS (ESI) calcd for C 30 H 32 NO5[M + H] + : 486.2275, found: 486.2271。

[0153] Example 27: Preparation of Diethyl 4-((4-phenoxyphenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0154]

[0155] Referring to Example 1, replace N-phenylacrylamide with N-(4-phenoxyphenyl)acrylamide. The resulting product is a white solid with a melting point of 154.0 - 156.0 °C and a yield of 71%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.45 (d, J = 8.9 Hz, 2H), 7.35–7.27 (m, 2H), 7.25–7.17 (m, 4H), 7.07 (t, J = 7.4 Hz, 1H), 7.02–6.91 (m, 4H), 4.20–4.04 (m, 4H), 4.02 (t, J = 7.8 Hz, 1H), 3.37 (d, J = 16.1 Hz, 1H), 3.27 (d, J = 16.1 Hz, 1H), 2.87–2.77 (m, 1H), 2.65 (dd, J = 14.0, 8.0 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.0, 170.4, 169.6, 156.5, 152.4, 133.4, 132.4, 131.2, 128.7, 128.5, 127.4, 126.7, 126.1, 122.0, 120.5, 118.6, 117.3, 60.9, 60.6, 52.2, 45.0, 33.9, 31.0, 12.9 (overlapped, 2C); HRMS (ESI) calcd for C 29 H 30 NO6 [M + H] + : 488.2068, found: 488.2064.

[0156] Example 28: Preparation of Diethyl 4-((4-fluorophenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0157]

[0158] Referring to Example 1, N-phenylacrylamide was replaced with N-(p-fluorophenyl)acrylamide. The resulting product was a white solid with a melting point of 142.0 - 144.0 °C and a yield of 68%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.49–7.39 (m, 2H), 7.27–7.15 (m, 4H), 7.02–6.91 (m, 2H), 4.20–4.01 (m, 4H), 4.01 (t, J = 7.8 Hz, 1H), 3.35 (d, J = 16.2 Hz, 1H), 3.26 (d, J = 16.2 Hz, 1H), 2.84–2.73 (m, 1H), 2.64 (dd, J = 14.0, 8.0 Hz, 1H), 1.19 (t, J = 7.0 Hz, 3H), 1.16 (t, J = 7.0 Hz, 3H);13 13C NMR (101 MHz, CDCl3) δ 172.11, 171.43, 170.66, 159.39 (d, J = 243.6 Hz), 134.44, 133.84 (d, J = 2.9 Hz), 132.2, 129.54, 128.52, 127.78, 127.22, 121.56 (d, J = 7.8 Hz), 115.56 (d, J = 22.4 Hz), 61.99, 61.73, 53.24, 46.04, 34.95, 31.96, 13.96, 13.93; 19 19F NMR (376 MHz, CDCl3) δ -117.89; HRMS (ESI) calcd for C 23 H 25 FNO5 [M + H] + : 414.1711, found: 414.1711.

[0159] Example 29: Preparation of Diethyl 4-((4-chlorophenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0160]

[0161] Referring to Example 1, N-phenylacrylamide was replaced with N-(4-chlorophenyl)acrylamide, and the resulting product was a white solid with a melting point of 164.0 - 166.0 °C and a yield of 72%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.51 (s, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.27–7.16 (m, 6H), 4.21–3.95 (m, 5H), 3.37 (d, J = 16.1 Hz, 1H), 3.25 (d, J = 16.2 Hz, 1H), 2.84–2.74 (m, 1H), 2.66 (dd, J = 14.1, 7.5 Hz, 1H), 1.19 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.2, 171.4, 170.7, 136.4, 134.4, 132.0, 129.6, 129.3, 128.9, 128.5, 127.8, 127.3, 121.0, 62.0, 61.8, 53.2, 46.1, 35.0, 31.9, 14.0, 13.9; HRMS (ESI) calcd for C 23 H 25 ClNO5 [M + H] +: 430.1416, found: 430.1417。

[0162] Example 30: Preparation of Diethyl 4 - ((4 - bromophenyl)carbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate

[0163]

[0164] Referring to Example 1, replace N - phenylacrylamide with N - (p - bromophenyl)acrylamide. The obtained product is a white solid with a melting point of 183.0 - 184.8 °C and a yield of 73%. Product characterization: 1 H NMR(400MHz, CDCl3) δ 7.67(s, 1H), 7.41–7.36(m, 4H), 7.26–7.13(m, 4H), 4.19–4.02(m, 4H), 4.00(t, J = 7.0Hz, 1H), 3.36(d, J = 16.2Hz, 1H), 3.25(d, J = 16.2Hz, 1H), 2.83–2.72(m, 1H), 2.64(dd, J = 14.0, 7.8Hz, 1H), 1.19(t, J = 7.1Hz, 3H), 1.16(t, J = 7.1Hz, 3H); 13 C NMR(101MHz, CDCl3) δ 172.2, 171.4, 170.7, 136.9, 134.4, 132.0, 131.9, 129.6, 128.5, 127.8, 127.3, 121.3, 116.9, 62.0, 61.8, 53.2, 46.2, 34.9, 31.9, 14.0, 13.9; HRMS(ESI) calcd for C 23 H 25 BrNO5[M + H] + : 474.0911, found: 474.0913。

[0165] Example 31: Preparation of Diethyl 4 - ((4 - benzoylphenyl)carbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate

[0166]

[0167] Referring to Example 1, replace N - phenylacrylamide with N - (p - benzoylphenyl)acrylamide. The obtained product is a white solid with a melting point of 149.0 - 150.3 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.78 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 7.0 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.27–7.16 (m, 4H), 4.19–4.03 (m, 5H), 3.36 (d, J = 16.1 Hz, 1H), 3.26 (d, J = 16.1 Hz, 1H), 2.85–2.75 (m, 1H), 2.67 (dd, J = 14.0, 7.9 Hz, 1H), 1.20 (t, J = 6.5 Hz, 3H), 1.16 (t, J = 6.4 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 195.70, 172.56, 171.49, 170.62, 141.86, 137.82, 134.39, 133.06, 132.27, 131.98, 131.58, 129.90, 129.59, 128.40, 128.29, 127.87, 127.33, 118.82, 62.07, 61.80, 53.25, 46.30, 34.98, 31.92, 13.98, 13.96; HRMS (ESI) calcd for C 30 H 30 NO6[M + H] + : 500.2068, found: 500.2072。

[0168] Example 32: Preparation of Diethyl 4-(4-(N-acetylaminosulfonyl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0169]

[0170] Referring to Example 1, N-phenylacrylamide was replaced with N-(4-(N-acetylaminosulfonyl)phenyl)acrylamide, and the resulting product was a white solid with a melting point of 127.0 - 128.5 °C and a yield of 63%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 9.36 (s, 1H), 8.65 (s, 1H), 7.90 (d, J = 8.9 Hz, 2H), 7.68 (d, J = 8.9 Hz, 2H), 7.24–7.12 (m, 4H), 4.20–4.05 (m, 5H), 3.35 (d, J = 16.1 Hz, 1H), 3.29 (d, J = 16.2 Hz, 1H), 2.86–2.75 (m, 1H), 2.60 (dd, J = 13.9, 8.6 Hz, 1H), 1.95 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.36, 170.51, 169.73, 167.75, 142.07, 133.16, 132.13, 130.89, 128.56, 128.47, 127.21, 126.76, 126.30, 118.35, 61.17, 60.88, 52.37, 45.03, 33.87, 30.92, 22.42, 12.92, 12.89; HRMS (ESI) calcd for C 25 H 29 N2O8S [M + H] + : 517.1639, found: 517.1635.

[0171] Example 33: Preparation of Diethyl 4-(3-(trifluoromethoxy)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)dicarboxylate

[0172]

[0173] Referring to Example 1, replace N-phenylacrylamide with N-(3-(trifluoromethoxy)phenyl)acrylamide. The resulting product is a white solid with a melting point of 118.8 - 119.6 °C and a yield of 71%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.59 (s, 1H), 7.33–7.27 (m, 2H), 7.27–7.15 (m, 4H), 6.99–6.92 (m, 1H), 4.21–3.98 (m, 5H), 3.38 (d, J = 16.2 Hz, 1H), 3.25 (d, J = 16.1 Hz, 1H), 2.84–2.74 (m, 1H), 2.68 (dd, J = 14.1, 7.4 Hz, 1H), 1.19 (t, J = 7.1 Hz, 6H); 1313C NMR (101 MHz, CDCl3) δ 171.2, 170.4, 169.6, 148.49 (q, J = 2.1 Hz), 138.2, 133.4, 130.8, 128.9, 128.5, 127.5, 126.8, 126.3, 119.38 (q, J = 257.2 Hz), 116.7, 115.4, 111.5, 61.0, 60.7, 52.2, 45.1, 33.9, 30.8, 12.9, 12.8; 19 19F NMR (376 MHz, CDCl3) δ -57.74; HRMS (ESI) calcd for C 24 H 25 F3NO6 [M + H] + : 480.1628, found: 480.1635.

[0174] Example 34: Preparation of Diethyl 4-(3-(methylthio)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)dicarboxylate

[0175]

[0176] Referring to Example 1, N-phenylacrylamide was replaced with N-(3-(methylthio)phenyl)acrylamide, and the resulting product was a white solid with a melting point of 141.0 - 142.5 °C and a yield of 67%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 7.64–7.45 (m, 2H), 7.27–7.13 (m, 6H), 7.03–6.92 (m, 1H), 4.21–4.03 (m, 4H), 4.01 (t, J = 7.9 Hz, 1H), 3.36 (d, J = 16.1 Hz, 1H), 3.2b7 (d, J = 16.2 Hz, 1H), 2.85–2.75 (m, 1H), 2.63 (dd, J = 13.9, 8.1 Hz, 1H), 2.46 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.18, 171.38, 170.64, 139.58, 138.37, 134.43, 132.10, 129.55, 129.17, 128.55, 127.79, 127.26, 122.34, 117.22, 116.20, 62.00, 61.73, 53.26, 46.28, 34.97, 32.01, 15.63, 13.97, 13.95; HRMS (ESI) calcd for C 24H 28 NO5S[M+H] + : 442.1683, found: 442.1690。

[0177] Example 35: Preparation of Diethyl 4-(3-(tert-butyl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)dicarboxylate

[0178]

[0179] Referring to Example 1, N-phenylacrylamide was replaced with N-(3-(tert-butyl)phenyl)acrylamide, and the resulting product was a white solid with a melting point of 152.7 - 154.5 °C and a yield of 70%. Product characterization: 1 H NMR(400MHz, CDCl3) δ 7.54(t, J = 2.0Hz, 1H), 7.48(s, 1H), 7.30(ddd, J = 7.9, 2.2, 1.2Hz, 1H), 7.25–7.16(m, 5H), 7.13(dt, J = 7.9, 1.4Hz, 1H), 4.21–4.04(m, 4H), 4.02(t, J = 7.9Hz, 1H), 3.37(d, J = 16.2Hz, 1H), 3.29(d, J = 16.0Hz, 1H), 2.88–2.77(m, 1H), 2.63(dd, J = 13.9, 8.5Hz, 1H), 1.30(s, 9H), 1.20(t, J = 7.1Hz, 3H), 1.16(t, J = 7.1Hz, 3H); 13 C NMR(101MHz, CDCl3) δ 170.99, 170.29, 169.61, 151.19, 136.50, 133.40, 131.18, 128.47, 127.61, 127.53, 126.67, 126.13, 120.50, 115.99, 115.89, 60.90, 60.64, 52.25, 45.29, 33.92, 33.74, 31.07, 30.23, 12.92, 12.90; HRMS(ESI) calcd for C 27 H 34 NO5[M+H] + : 452.2431, found: 452.2435。

[0180] Example 36: Preparation of Diethyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0181]

[0182] Referring to Example 1, replace N-phenylacrylamide with N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acrylamide. The resulting product is a white solid with a melting point of 148.0 - 149.0 °C and a yield of 69%. Product characterization: 1 H NMR(400MHz,CDCl3)δ7.92(ddd,J=8.2,2.4,1.2Hz,1H),7.59–7.48(m,2H),7.38–7.27(m,2H),7.26–7.16(m,4H),4.22–4.02(m,4H),4.01(t,J=7.9Hz,1H),3.35(d,J=16.2Hz,1H),3.29(d,J=16.2Hz,1H),2.89–2.79(m,1H),2.60(dd,J=13.9,8.3Hz,1H),1.32(s,12H),1.21(t,J=7.1Hz,3H),1.17(t,J=7.1Hz,3H); 13 C NMR(101MHz,CDCl3)δ172.05,171.26,170.52,137.26,134.55,131.99,130.81,129.60,128.77,128.59,127.87,127.30,125.46,122.92,83.98,61.96,61.68,53.29,46.40,35.00,32.18,24.88,24.84,13.98,13.96;HRMS(ESI)calcd for C 29 H 37 BNO7[M+H] + :522.2658,found:522.2661。

[0183] Example 37: Preparation of Diethyl 4-((2-bromophenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0184]

[0185] Referring to Example 1, replace N-phenylacrylamide with N-(2-bromophenyl)acrylamide. The resulting product is a white solid with a melting point of 78.9 - 79.3 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 8.36 (dd, J = 8.2, 1.6 Hz, 1H), 7.72 (s, 1H), 7.46 (dd, J = 8.0, 1.5 Hz, 1H), 7.32–7.27 (m, 1H), 7.26–7.19 (m, 4H), 6.95 (td, J = 7.7, 1.6 Hz, 1H), 4.18–4.04 (m, 5H), 3.36 (d, J = 16.2 Hz, 1H), 3.31 (d, J = 16.3 Hz, 1H), 2.97–2.86 (m, 1H), 2.64 (dd, J = 13.9, 7.9 Hz, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.1, 171.0, 170.5, 135.5, 134.8, 132.2, 131.7, 129.6, 129.2, 128.3, 128.0, 127.4, 125.3, 121.6, 113.4, 61.9, 61.7, 53.4, 46.6, 35.0, 32.1, 14.0 (overlapped, 2C); HRMS (ESI) calcd for C 23 H 25 BrNO5 [M + H] + : 474.0911, found: 474.0914.

[0186] Example 38: Preparation of Diethyl 4 - ((2 - ((tert - butoxycarbonyl)amino)phenyl)carbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate

[0187]

[0188] Referring to Example 1, replace N - phenylacrylamide with tert - butyl (2 - acrylamidophenyl)carbamate, and the obtained product is a yellow oily liquid with a yield of 71%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.50 (dd, J = 7.8, 1.8 Hz, 1H), 7.44 (dd, J = 7.8, 1.7 Hz, 1H), 7.23–7.08 (m, 6H), 6.83 (s, 1H), 4.20–3.98 (m, 5H), 3.37 (d, J = 16.3 Hz, 1H), 3.28 (d, J = 16.3 Hz, 1H), 2.86–2.75 (m, 1H), 2.64 (dd, J = 13.8, 8.4 Hz, 1H), 1.47 (s, 9H), 1.20 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.8, 171.5, 170.5, 154.0, 134.4, 132.1, 130.5, 129.7, 129.5, 128.6, 127.8, 127.1, 126.3, 125.4, 124.9, 124.5, 80.6, 62.0, 61.7, 53.2, 45.8, 34.9, 31.8, 28.3, 14.0, 13.9; HRMS (ESI) calcd for C 28 H 35 N2NaO7 [M+Na] + : 533.2258, found: 533.2257.

[0189] Example 39: Preparation of Diethyl 4-(naphthalen-1-ylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0190]

[0191] Referring to Example 1, N-phenylacrylamide was replaced with N-(1-naphthyl)acrylamide, and the resulting product was a white solid with a melting point of 143.0 - 145.0 °C and a yield of 59%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.74 (s, 1H), 7.66 (d, J = 8.2 Hz, 1H), 7.51–7.25 (m, 8H), 4.23–4.01 (m, 5H), 3.42 (d, J = 16.1 Hz, 1H), 3.32 (d, J = 16.2 Hz, 1H), 3.01–2.90 (m, 1H), 2.77 (dd, J = 14.0, 7.6 Hz, 1H), 1.20 (t, J = 7.3 Hz, 3H), 1.18 (t, J = 7.3 Hz, 3H); 1313C NMR (101 MHz, CDCl3) δ 172.4, 171.3, 170.6, 134.9, 134.0, 132.4, 132.1, 129.7, 129.0, 128.8, 128.0, 127.3, 126.7, 126.3, 125.9, 125.7, 125.6, 120.2, 119.9, 62.0, 61.7, 53.4, 46.3, 35.1, 32.1, 14.0, 13.9; HRMS (ESI) calcd for C 27 H 28 NO5[M + H] + : 446.1962, found: 446.1962。

[0192] Example 40: Preparation of Diethyl 4-((1H-indol-4-yl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0193]

[0194] Referring to Example 1, replace N-phenylacrylamide with N-(1H-indol-4-yl)acrylamide. The obtained product is a white solid with a melting point of 57.0 - 58.0 °C and a yield of 65%. Product characterization: 1 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 7.89–7.80 (m, 1H), 7.58 (s, 1H), 7.35–7.24 (m, 4H), 7.20–7.11 (m, 2H), 7.10 (t, J = 2.9 Hz, 1H), 6.14–6.08 (m, 1H), 4.20–3.99 (m, 5H), 3.40 (d, J = 16.0 Hz, 1H), 3.28 (d, J = 16.1 Hz, 1H), 2.95–2.85 (m, 1H), 2.77 (dd, J = 14.0, 7.4 Hz, 1H), 1.18 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.9, 171.3, 170.7, 136.4, 134.8, 132.5, 129.8, 129.6, 129.1, 127.9, 127.3, 123.8, 122.6, 119.7, 111.0, 107.9, 98.2, 61.9, 61.7, 53.4, 46.3, 35.1, 32.0, 14.0, 13.9; HRMS (ESI) calcd for C 25 H 27 N2O5[M + H] +: 435.1914, found: 435.1907.

[0195] Example 41: Preparation of Diethyl 4-(quinolin-3-ylcarbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0196]

[0197] Referring to Example 1, replace N-phenylacrylamide with N-(quinolin-3-yl)acrylamide. The resulting product is a white solid with a melting point of 82.2 - 84.0 °C and a yield of 49%. Product characterization: 1 H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 2.5 Hz, 1H), 8.67 (d, J = 2.6 Hz, 1H), 8.35 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.78 (dd, J = 8.2, 1.5 Hz, 1H), 7.61 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.52 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.27–7.15 (m, 4H), 4.21–4.02 (m, 5H), 3.36 (d, J = 16.2 Hz, 1H), 3.28 (d, J = 16.2 Hz, 1H), 2.89–2.79 (m, 1H), 2.70 (dd, J = 14.0, 8.1 Hz, 1H), 1.19 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 173.0, 171.5, 170.7, 145.1, 143.9, 134.4, 132.0, 131.6, 129.6, 128.9, 128.4 (overlapped, 2C), 128.2, 127.9, 127.8, 127.4, 127.3, 123.9, 62.1, 61.8, 53.3, 46.1, 35.0, 32.0, 14.0, 13.9; HRMS (ESI) calcd for C 26 H 27 N2NaO5 [M+Na] + : 469.1734, found: 469.1727.

[0198] Example 42: Preparation of Diethyl 4-(methyl(phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0199]

[0200] Referring to Example 1, replace N-phenylacrylamide with N-methyl-N-phenylacrylamide. The resulting product is a white solid with a melting point of 84.6 - 86.2 °C and a yield of 61%. Product characterization: 1 H NMR (400 MHz, CDCl3) δ 7.48–7.41 (m, 2H), 7.38–7.30 (m, 3H), 7.16–6.99 (m, 4H), 4.27–4.14 (m, 2H), 3.96–3.84 (m, 2H), 3.65 (dq, J = 10.7, 7.1 Hz, 1H), 3.37 (s, 3H), 3.33 (dd, J = 16.2, 2.1 Hz, 1H), 3.18 (d, J = 16.3 Hz, 1H), 2.57 (ddd, J = 13.3, 5.9, 2.2 Hz, 1H), 2.45 (dd, J = 13.3, 11.6 Hz, 1H), 1.25 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 174.6, 171.2, 170.1, 144.0, 134.0, 133.9, 130.0, 129.1, 128.1, 127.4, 127.2, 126.8, 126.6, 61.7, 61.2, 53.4, 40.6, 37.9, 34.6, 32.1, 14.1, 13.8; HRMS (ESI) calcd for C 24 H 27 NNaO5 [M+Na] + : 432.1781, found: 432.1782.

[0201] Example 43: Preparation of Diethyl 6-Fluoro-4-Methyl(phenyl)carbamoyl)-3,4-Dihydronaphthalene-2,2(1H)-Dicarboxylate

[0202]

[0203] Referring to Example 1, replace N-phenylacrylamide with N-methyl-N-phenylacrylamide and replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(4-fluorobenzyl)malonate. The resulting product is a white solid with a melting point of 124.9 - 126.0 °C and a yield of 51%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.51–7.42 (m, 2H), 7.40–7.34 (m, 1H), 7.34–7.28 (m, 2H), 7.04 (dd, J = 8.5, 5.8 Hz, 1H), 6.83 (td, J = 8.5, 2.7 Hz, 1H), 6.70 (dd, J = 9.6, 2.5 Hz, 1H), 4.27–4.13 (m, 2H), 3.98–3.87 (m, 1H), 3.85 (dd, J = 11.8, 6.3 Hz, 1H), 3.66 (dq, J = 10.7, 7.1 Hz, 1H), 3.37 (s, 3H), 3.30 (dd, J = 16.1, 2.2 Hz, 1H), 3.11 (d, J = 15.9 Hz, 1H), 2.56 (ddd, J = 13.4, 6.0, 2.2 Hz, 1H), 2.42 (dd, J = 13.4, 11.5 Hz, 1H), 1.25 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 173.9, 171.0, 169.9, 161.4 (d, J = 244.2 Hz), 143.8, 135.7 (d, J = 7.1 Hz), 130.4 (d, J = 8.1 Hz), 130.1, 129.7 (d, J = 3.0 Hz), 128.2, 127.1, 114.1 (d, J = 21.3 Hz), 113.9 (d, J = 21.4 Hz), 61.8, 61.3, 53.4, 40.7 (d, J = 1.7 Hz), 38.0, 34.0, 31.8, 14.0, 13.8; 19 19F NMR (376 MHz, CDCl3) δ -116.28; HRMS (ESI) calcd for C 24 19 26 19FNNaO5 [M+Na] + : 450.1687, found: 450.1687。

[0204] Example 44: Preparation of Diethyl 8-chloro-4-methylcarbamoyl-3,4-dihydronaphthalene-2,2(1H)dicarboxylate

[0205]

[0206] Referring to Example 1, replace N-phenylacrylamide with N-methyl-N-phenylacrylamide and replace diethyl 2-benzyl-2-bromomalonate with diethyl 2-bromo-2-(2-chlorobenzyl)malonate. The obtained product is a white solid with a melting point of 112.9 - 114.6 °C and a yield of 37%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.49–7.41 (m, 2H), 7.39–7.34 (m, 1H), 7.33–7.28 (m, 2H), 7.22 (d, J = 7.9 Hz, 1H), 7.08 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 4.31–4.13 (m, 2H), 3.92 (dq, J = 10.7, 7.1 Hz, 1H), 3.82 (dd, J = 11.8, 5.7 Hz, 1H), 3.68–3.56 (m, 2H), 3.37 (s, 3H), 2.93 (d, J = 17.1 Hz, 1H), 2.54 (ddd, J = 13.3, 5.7, 2.2 Hz, 1H), 2.43 (dd, J = 13.3, 11.8 Hz, 1H), 1.26 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 174.0, 171.0, 169.9, 143.8, 136.2, 134.4, 132.3, 130.1, 128.2, 127.7, 127.2, 127.1, 126.0, 61.9, 61.4, 53.1, 40.8, 37.9, 32.1, 31.6, 14.0, 13.8; HRMS (ESI) calcd for C 24 H 27 ClNO5 [M + H] + : 444.1572, found: 444.1575.

[0207] Example 45: Preparation of Diethyl 4-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-4-yl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0208]

[0209] Referring to Example 1, replace N-phenylacrylamide with N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-4-yl)acrylamide. The resulting product is a white solid with a melting point of 236.0 - 238.0 °C and a yield of 33%. Product characterization: 11H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 10.33 (s, 1H), 7.87 (d, J = 7.5 Hz, 1H), 7.61–7.47 (m, 2H), 7.32–7.12 (m, 4H), 5.15 (dd, J = 13.2, 4.9 Hz, 1H), 4.48 (d, J = 17.5 Hz, 1H), 4.41 (d, J = 17.5 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 4.15–3.99 (m, 3H), 3.31 (d, J = 16.4 Hz, 1H), 3.17 (d, J = 16.1 Hz, 1H), 2.99–2.85 (m, 1H), 2.70–2.58 (m, 2H), 2.45–2.30 (m, 2H), 2.10–1.99 (m, 1H), 1.20 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H); 13 13C NMR (101 MHz, DMSO) δ 173.3, 172.6, 171.5, 171.2, 170.4, 168.2, 134.5, 134.3, 133.9, 133.8, 133.3, 129.5, 129.2, 127.8, 127.3, 127.0, 126.1, 120.0, 62.0, 61.6, 53.3, 52.1, 47.0, 44.2, 34.8, 31.9, 31.7, 23.1, 14.3, 14.2; HRMS (ESI) calcd for C 30 H 32 N3O8 [M + H] + : 562.2184, found: 562.2199.

[0210] Example 46: Preparation of Diethyl 4-(4-(3-ethyl-2,6-dioxopiperidin-3-yl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0211]

[0212] Referring to Example 1, N-phenylacrylamide was replaced with N-(4-(3-ethyl-2,6-dioxopiperidin-3-yl)phenyl)acrylamide, and the resulting product was a white solid with a melting point of 139.0 - 141.0 °C and a yield of 69%. Product characterization: 11H NMR(400MHz,CDCl3)δ8.09(s,1H),7.78(s,1H),7.51(d,J = 8.6Hz,2H),7.26–7.12(m,6H),4.20–4.04(m,4H),4.03(t,J = 7.8Hz,1H),3.35(d,J = 16.2Hz,1H),3.27(d,J = 16.2Hz,1H),2.79(dd,J = 14.0,7.6Hz,1H),2.66–2.52(m,2H),2.44–2.29(m,2H),2.19(td,J = 14.1,4.4Hz,1H),2.01(dq,J = 14.7,7.4Hz,1H),1.88(dq,J = 14.6,7.4Hz,1H),1.19(t,J = 7.1Hz,3H),1.16(t,J = 7.1Hz,3H),0.85(t,J = 7.4Hz,3H); 13 13C NMR(101MHz,CDCl3)δ175.2,172.4,172.4,171.4,170.7,137.4,134.5,134.3,132.2,129.5,128.4,127.7,127.2,126.8,120.2,62.0,61.8,53.3,50.7,46.1,34.9,32.8,32.0,29.3,27.0,13.9(overlapped,2C),9.0;HRMS(ESI)calcd for C 30 H 35 N2O7[M + H] + :535.2439,found:535.2447。

[0213] Example 47: Preparation of Diethyl 4-((4-(Ethoxycarbonyl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0214]

[0215] Referring to Example 1, replace N-phenylacrylamide with ethyl 4-acrylamidobenzoate. The resulting product is a white solid with a melting point of 136.0 - 137.0 °C and a yield of 68%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.8 Hz, 2H), 7.72 (s, 1H), 7.56 (d, J = 8.8 Hz, 2H), 7.26–7.16 (m, 4H), 4.35 (q, J = 7.1 Hz, 2H), 4.21–3.98 (m, 5H), 3.38 (d, J = 16.1 Hz, 1H), 3.25 (d, J = 16.1 Hz, 1H), 2.85–2.74 (m, 1H), 2.68 (dd, J = 14.1, 7.5 Hz, 1H), 1.38 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 6H); 13 13C NMR (101 MHz, CDCl3) δ 172.2, 171.4, 170.6, 166.1, 141.9, 134.5, 131.9, 130.7, 129.6, 128.6, 127.9, 127.3, 126.1, 118.8, 62.0, 61.8, 60.9, 53.2, 46.4, 35.0, 31.9, 14.3, 14.0, 13.9; HRMS (ESI) calcd for C 26 H 30 NO7 [M + H] + : 468.2017, found: 468.2026。

[0216] Example 48: Preparation of Diethyl 4-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0217]

[0218] Referring to Example 1, N-phenylacrylamide was replaced with N-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)acrylamide. The resulting product was a white solid with a melting point of 148.0 - 150.0 °C and a yield of 55%. Product characterization: 11H NMR (400 MHz, DMSO) δ 10.69 (s, 1H), 8.36 (d, J = 4.8 Hz, 2H), 7.83 (d, J = 8.9 Hz, 2H), 7.69 (d, J = 8.9 Hz, 2H), 7.10–6.94 (m, 4H), 6.91 (t, J = 4.9 Hz, 1H), 4.02 (q, J = 7.1 Hz, 2H), 3.98–3.86 (m, 3H), 3.15 (d, J = 16.2 Hz, 1H), 3.02 (d, J = 16.0 Hz, 1H), 2.52–2.42 (m, 1H), 2.22 (dd, J = 13.5, 10.7 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H), 0.92 (t, J = 7.0 Hz, 3H); 13 13C NMR (101 MHz, DMSO) δ 173.0, 171.1, 170.3, 158.8, 157.4, 143.3, 134.9, 134.3, 133.6, 129.6, 129.4, 127.7, 127.3, 127.0, 119.3, 116.3, 62.0, 61.6, 53.2, 44.9, 34.8, 31.8, 14.3, 14.2; HRMS (ESI) calcd for C 27 H 29 N4O7 [M + H] + : 553.1751, found: 553.1752.

[0219] Example 49: Preparation of Diethyl 4-((4-((2-acetoxybenzoyl)oxy)phenyl)carbamoyl)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate

[0220]

[0221] Referring to Example 1, N-phenylacrylamide was replaced with 4-acrylamidophenyl 2-acetoxybenzoate. The resulting product was a white solid with a melting point of 153.0 - 155.0 °C and a yield of 72%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 7.9, 1.7 Hz, 1H), 7.72 (s, 1H), 7.63 (td, J = 7.8, 1.7 Hz, 1H), 7.55 (d, J = 8.9 Hz, 2H), 7.38 (td, J = 7.6, 1.2 Hz, 1H), 7.26–7.18 (m, 4H), 7.16 (dd, J = 8.1, 1.2 Hz, 1H), 7.10 (d, J = 9.0 Hz, 2H), 4.20–4.05 (m, 4H), 4.02 (t, J = 7.9 Hz, 1H), 3.36 (d, J = 16.2 Hz, 1H), 3.27 (d, J = 16.2 Hz, 1H), 2.86–2.74 (m, 1H), 2.64 (dd, J = 13.9, 8.1 Hz, 1H), 2.29 (s, 3H), 1.21 (t, J = 7.3 Hz, 3H), 1.17 (t, J = 7.3 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.1, 171.4, 170.7, 169.8, 163.1, 151.2, 146.7, 135.8, 134.6, 134.4, 132.2, 132.2, 129.5, 128.5, 127.8, 127.2, 126.2, 124.0, 122.5, 122.1, 120.8, 62.0, 61.7, 53.3, 46.2, 35.0, 32.0, 21.0, 14.0, 13.9; HRMS (ESI) calcd for C 32 H 32 NO9 [M + H] + : 574.2072, found: 574.2063.

[0222] Example 50: Preparation of Diethyl 4 - ((4 - hydroxyphenyl)carbamoyl)-3,4 - dihydronaphthalene - 2,2(1H)-dicarboxylate

[0223]

[0224] Referring to Example 1, N - phenylacrylamide was replaced with N - (4 - hydroxyphenyl)acrylamide, and the obtained product was a white solid with a melting point of 95.0 - 97.0 °C and a yield of 40%. Product characterization: 11H NMR (400 MHz, CDCl3) δ 7.39 (s, 1H), 7.28–7.17 (m, 6H), 6.71 (d, J = 8.8 Hz, 2H), 6.12 (s, 1H), 4.23–4.03 (m, 4H), 4.00 (t, J = 7.8 Hz, 1H), 3.36 (d, J = 16.2 Hz, 1H), 3.27 (d, J = 16.2 Hz, 1H), 2.87–2.75 (m, 1H), 2.63 (dd, J = 13.9, 8.1 Hz, 1H), 1.20 (t, J = 7.0 Hz, 3H), 1.16 (t, J = 7.0 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 172.3, 171.4, 170.7, 153.2, 134.5, 132.1, 130.2, 129.5, 128.7, 127.8, 127.2, 122.2, 115.7, 62.0, 61.8, 53.3, 46.0, 34.9, 32.0, 14.0, 13.9; HRMS (ESI) calcd for C 23 H 26 NO6 [M + H] + : 412.1755, found: 412.1758。

Claims

1. A method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds, characterized in that: Comprising the following steps: A 2-cyclo-A-ylmethyl-2-bromocarbonyl compound shown in Formula I, an N-cyclo-B-ylacrylamide compound shown in Formula II, and a photocatalyst are placed in an organic solvent, and a cyclization reaction is carried out under visible light irradiation and inert gas protection. After the reaction is completed, through post-treatment, a tetrahydrobenzene-1-carboxamide compound shown in Formula III is obtained; Wherein, Cyclo-A is selected from phenyl, naphthyl, anthracenyl, phenanthryl, indolyl; in cyclo-A, the N on the indolyl is connected to C(O)OR6; R6 is selected from C1-C6 alkyl; Ring B is selected from phenyl, naphthyl, anthryl, phenanthryl, pyridyl, indolyl, quinolinyl, isoquinolinyl; in Ring B, the N on the indolyl is connected to H or C(O)OR 12 is connected; R 12 is selected from C1-C6 alkyl; R1 represents 1 to 2 substituents on the connected cyclo-A, and each substituent is independently selected from halogen, cyano, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, -C(O)R8; In R1, the substituents of the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, and substituted C1-C6 alkylthio are each independently selected from fluorine, chlorine, bromine; R8 is selected from C1-C4 alkyl; R2 represents 1 to 2 substituents on the linked ring B, and each substituent is independently selected from halogen, cyano, hydroxy, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylthio, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted 3- to 6-membered cycloalkyl, substituted or unsubstituted 3- to 6-membered cycloalkoxy, substituted or unsubstituted 3- to 6-membered cycloalkanecarbonyl, substituted or unsubstituted 6- to 10-membered aryl, substituted or unsubstituted 6- to 10-membered aryloxy, substituted or unsubstituted 6- to 10-membered arylcarbonyl, -Bpin, -NHC(O)OR 13 , -C(O)R 14 , -C(O)NHR 15 , -SO2NHR 16 , -OC(O)R 17 , or any two adjacent substituents are joined and together with the carbon atoms on ring B connecting the two substituents form In R2, the substituents of the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C1-C6 alkylthio, substituted C1-C6 alkoxycarbonyl, substituted 3-6-membered cycloalkyl, substituted 3-6-membered cycloalkoxy, substituted 3-6-membered cycloalkanecarbonyl, substituted 6-10-membered aryl, substituted 6-10-membered aryloxy, and substituted 6-10-membered arylcarbonyl are each independently selected from fluorine, chlorine, bromine, 6-10-membered aryl; R 13 、R 14 、R 15 Each independently selected from C1-C4 alkyl; R 16 Selected from C1-C4 alkanoyl groups, 6-10 membered aryl groups, 5-6 membered heteroaryl groups; R 17 selected from C1-C4 alkyl, a 6-10 membered aryl group which is substituted or unsubstituted with C1-C4 alkoxycarbonyloxy, and a 5-6 membered heteroaryl group; R3 is selected from C1-C6 alkyl; R4 is selected from cyano, -C(O)R 18 , -C(O)OR 19 ; R 18 , R 19 are each independently selected from C1-C6 alkyl; R5 is selected from hydrogen, C1-C4 alkyl; The photocatalyst is selected from 3DPAFIPN, 3DPA2FBN or 4CzIPN.

2. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: R6 is selected from tert-butyl.

3. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: R3 is selected from methyl, ethyl; R4 is selected from cyano, methoxycarbonyl, ethoxycarbonyl, acetyl.

4. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: R1 represents 1 to 2 substituents on the connected cyclo-A, and each substituent is independently selected from fluorine, chlorine, bromine, cyano, methyl, tert-butyl, trifluoromethyl, methoxy, trifluoromethoxy, methylthio.

5. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: The formula I is selected from:

6. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, characterized in that: R 12 selected from tert-butyl.

7. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, characterized in that: R5 is selected from hydrogen, methyl.

8. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: R2 represents 1 to 2 substituents on the linked ring B, and each substituent is independently selected from fluorine, chlorine, bromine, cyano, hydroxy, methyl, tert-butyl, trifluoromethyl, benzyl, methoxy, trifluoromethoxy, methylthio, ethoxycarbonyl, phenyl, phenoxy, benzoyl, -Bpin, -NHBoc, -SO2NHAc, or any two adjacent substituents are joined together and, together with the carbon atoms on ring B to which the two substituents are attached, form 9. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: The formula II is selected from:

10. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 1, wherein: The formula III is selected from:

11. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The molar ratio of the 2-cyclo-A-ylmethyl-2-bromocarbonyl compound shown in Formula I, the N-cyclo-B-ylacrylamide compound shown in Formula II, and the photocatalyst is 1:1-2:0.01-0.

05.

12. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 11, wherein: The molar ratio of the 2-cyclo-A-ylmethyl-2-bromocarbonyl compound shown in Formula I, the N-cyclo-B-ylacrylamide compound shown in Formula II, and the photocatalyst is 1:1.2-1.8:0.01-0.

03.

13. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The photocatalyst is 3DPA2FBN.

14. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The organic solvent is selected from at least one of N,N-dimethylformamide, 1,4-dioxane, diethyl ether, ethyl acetate, methanol, acetone, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, and acetonitrile.

15. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 14, characterized in that: The organic solvent is N,N-dimethylformamide.

16. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The dosage of the organic solvent is 5 - 30 mL / mmol of formula I.

17. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 16, wherein: The dosage of the organic solvent is 15 - 25 mL / mmol of formula I.

18. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The light source used for the visible light irradiation is selected from a blue light source, a green light source, an ultraviolet light source, or a white light source.

19. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 18, characterized in that: The light source used for the visible light irradiation is a blue light source.

20. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The wavelength used for the visible light irradiation is 455 - 465 nm.

21. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The temperature of the cyclization reaction is 0 - 80 °C.

22. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 21, wherein: The temperature of the cyclization reaction is 20 - 30 °C.

23. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to any one of claims 1 to 10, characterized in that: The time of the cyclization reaction is 1 - 6 hours.

24. The method for photocatalytic synthesis of tetrahydrobenzene-1-carboxamide compounds according to claim 23, wherein: The time of the cyclization reaction is 1 - 2 hours.

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