A 7-phenylvinyl-1H-indole derivative and preparation method thereof

Abstract

This application belongs to the field of fine organic chemical industry and relates to a 7-styryl-1H-indole derivative and a preparation method thereof. The C7 position of the indole derivative has a terminal alkenyl structure, and there are no any substituents on the indole nitrogen atom. In the chemical structure general formula, the substituent R<supgt;1< / supgt> is selected from hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, halogen, and the position of the substituent R<supgt;1< / supgt> is selected from the 3, 4, 5, 6 positions on the indoline ring. The substituent R<supgt;2< / supgt> is selected from phenyl, second-substituted phenyl, alkyl, aryl-substituted alkyl, naphthalene ring, and the substituents in the second-substituted phenyl are selected from C1-C6 alkyl, fluoroalkoxy, fluoroalkyl, alkoxycarbonyl, halogen, phenyl, phenoxy, and the position of the substituents in the second-substituted phenyl is selected from the para position or meta position on the benzene ring. This indole derivative can effectively solve the problems in the prior art that the C7 position of the indole compound cannot have a terminal alkenyl structure and it is not easy to be substituted by other groups when there are substituents on the indole nitrogen atom.

Description

Technical Field

[0001] The present invention relates to the field of fine organic chemical industry, and in particular to an indole derivative having a terminal alkenyl structure at the C7 position and no substituent on the nitrogen atom and a preparation method thereof. Background Art

[0002] There are six CH bonds on the indole ring of indole compounds. Compared with indole derivatives substituted at C2, C3, C5, and C6, indole derivatives substituted at C7 are more difficult to obtain. And the obtained indole derivatives substituted at C7 are mainly indole derivatives with non-terminal olefinic structures and other substituent groups on the nitrogen atom of indole. Indole compounds with non-terminal olefinic structures are not conducive to the further transformation of olefin functional groups, which to a certain extent limits the conversion of indole compounds into other more valuable indole derivatives. In addition, when there are other substituent groups on the nitrogen atom of indole, other reactions will be limited to modify the nitrogen atom to a certain extent, further limiting the conversion of indole compounds into other more valuable indole derivatives. Summary of the invention

[0003] The present application provides a 7-phenylvinyl-1H-indole derivative and a preparation method thereof, in order to solve the problem in the prior art that the C7 position of the indole compound cannot have a terminal olefin structure and the indole nitrogen atom is not easily replaced by other groups when there is a substituent on the indole nitrogen atom.

[0004] The indole derivative provided in the present application has a terminal alkenyl structure at the C7 position and has no substituent group on the nitrogen atom. In the chemical structure formula of the indole derivative, the substituent group R 1 is selected from hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, halogen, and the substituent R 1 The position of the substituent R is selected from the 3, 4, 5, and 6 positions on the indoline ring. 2 is selected from phenyl, a second substituted phenyl, an alkyl, an aryl substituted alkyl, and a naphthalene ring, wherein the substituent in the second substituted phenyl is selected from C1-C6 alkyl, a fluoroalkoxy, a fluoroalkyl, an alkoxycarbonyl, a halogen, a phenyl, and a phenoxy group, and the position of the substituent in the second substituted phenyl is selected from the para position or the meta position on the benzene ring.

[0005] In a first aspect, the present application provides an indole derivative having a terminal alkenyl structure at the C7 position and having no substituent on the nitrogen atom of the indole, and the general chemical formula is as follows:

[0006]

[0007] R 2 At least one selected from the following: phenyl, a second substituted phenyl, an alkyl group, an alkyl group substituted with an aryl group, and a naphthalene ring.

[0008] Optionally, the substituent in the second substituted phenyl group is selected from at least one of the following: C1-C6 alkyl, fluoroalkoxy, fluoroalkyl, alkoxycarbonyl, halogen, phenyl, phenoxy.

[0009] Optionally, the position of the substituent in the second substituted phenyl group is selected from the para position or meta position on the benzene ring.

[0010] Optionally, the chemical formula of the alkenyl indole derivative is as follows:

[0011]

[0012] In the formula, R 1 At least one selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, and halogen.

[0013] Optionally, the substituent R of the alkenyl indole 1 The position of the indoline ring is selected from the 3, 4, 5, and 6 positions.

[0014] In a second aspect, the present application provides a method for preparing the 7-phenylvinyl-1H-indole derivative described in the first aspect, the method comprising the following steps:

[0015] N-pyridindoline I, alkenyl borate II and a catalyst are subjected to alkenylation reaction under set conditions to generate N-pyridindoline III having a terminal alkenyl structure at the C7 position;

[0016] N-pyridindoline III is reacted with manganese dioxide to generate N-pyridindoline IV having a terminal alkenyl structure at the C7 position;

[0017] The N-pyridindole IV is reacted with MeOTf to remove the pyridyl group, thereby generating an indole derivative V having a terminal olefinic structure at the C7 position and no substituent on the nitrogen atom.

[0018] Optionally, the temperature set for the olefination reaction is 60° C. to 100° C., and the set time is 8 to 24 hours.

[0019] Optionally, the catalyst for the olefination reaction includes Ag2CO3 and / or [RhCp*Cl2]2.

[0020] Optionally, the molar ratio of the N-pyridine indoline I, alkenyl borate II, Ag2CO3 and [RhCp*Cl2]2 is 1:(1-4):(1-4):(0.5%-20%).

[0021] Optionally, the molar ratio of the N-pyridindoline III to the manganese dioxide is 1:(10-20).

[0022] The above technical solution provided by the embodiment of the present application has the following advantages compared with the prior art:

[0023] On the one hand, the 7-phenylvinyl-1H-indole derivatives provided in the embodiments of the present application directly obtain indole derivatives with a terminal alkenyl structure at the C7 position. Such indole derivatives can be converted into epoxides, alcohols, ketones, halides, etc. through various chemical reactions due to the presence of terminal alkenyl functional groups, thereby obtaining other more valuable indole derivatives. On the other hand, since there is no substituent on the pyridine nitrogen atom of the derivative, it can be more easily modified on the nitrogen atom by reactions such as aromatization, alkylation, allylation, acylation, carbonylation, and carboxylation, and converted into indoles substituted with other groups. This is of great significance for the preparation of drugs with indole structures and the activity research of their compounds, and the preparation method is simple and efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0025] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0026] Figure 1 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route for phenyl is shown below;

[0027] Figure 2 is a substituent R in the examples of this application 1 is 3-methyl, R 2 The synthetic route for phenyl is shown below;

[0028] Figure 3 is a substituent R in the examples of this application 1 is 4-methyl, R 2 The synthetic route for phenyl is shown below;

[0029] Figure 4 is a substituent R in the examples of this application 1 is 4-benzyloxy, R 2 The synthetic route for phenyl is shown below;

[0030] Figure 5 is a substituent R in the examples of this application 1 is 4-chloro, R 2 The synthetic route for phenyl is shown below;

[0031] Figure 6 is a substituent R in the examples of this application 1 is 4-methoxycarbonyl, R 2 The synthetic route for phenyl is shown below;

[0032] Figure 7 is a substituent R in the examples of this application 1 is 5-methyl, R 2 The synthetic route for phenyl is shown below;

[0033] Figure 8 is a substituent R in the examples of this application 1 is 5-methoxy, R 2 The synthetic route for phenyl is shown below;

[0034] Fig. 9 is a substituent R in the examples of this application 1 is 5-benzyloxy, R 2 The synthetic route for phenyl is shown below;

[0035] Fig.10 is a substituent R in the examples of this application 1 is 5-cyano, R 2 The synthetic route for phenyl is shown below;

[0036] Fig.11 is a substituent R in the examples of this application 1 is 5-nitro, R 2 The synthetic route for phenyl is shown below;

[0037] Fig.12 is a substituent R in the examples of this application 1 is 5-chloro, R 2 The synthetic route for phenyl is shown below;

[0038] Fig.13 is a substituent R in the examples of this application 1 is 5-bromo, R 2 The synthetic route for phenyl is shown below;

[0039] Fig.14 is a substituent R in the examples of this application 1 is 6-fluoro, R 2 The synthetic route for phenyl is shown below;

[0040] Fig.15 is a substituent R in the examples of this application 1 is 6-chloro, R 2 The synthetic route for phenyl is shown below;

[0041] Fig.16 is a substituent R in the examples of this application 1is 3-methyl, 5-methoxy, R 2 The synthetic route for phenyl is shown below;

[0042] Fig.17 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-methylphenyl is shown in FIG.

[0043] Fig.18 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 3-methylphenyl is shown below:

[0044] Fig.19 is the substituent RR in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-isopropylphenyl is shown in FIG.

[0045] Fig. 20 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-tert-butylphenyl is shown in FIG.

[0046] Fig.21 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-trifluoromethoxyphenyl is shown in FIG.

[0047] Fig. 22 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-methoxycarbonylphenyl is shown in FIG.

[0048] Fig.23 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-fluorophenyl is shown in FIG.

[0049] Fig.24 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 4-chlorophenyl is shown in FIG.

[0050] Fig.25 is a substituent R in the examples of this application 1 is hydrogen, R 2 is a synthetic route for 4-phenylphenyl;

[0051] Fig.26 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 3-phenoxyphenyl is shown in FIG.

[0052] Fig. 27 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route for methyl;

[0053] Fig.28 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route for n-butyl is shown below;

[0054] Fig.29 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 2-phenylethyl is shown below;

[0055] Fig.30 is a substituent R in the examples of this application 1 is hydrogen, R 2 The synthetic route of 2-naphthyl is shown below;

[0056] Fig.31 is a substituent R in the examples of this application 1 is hydrogen, R 2 The H NMR spectrum of the final product of phenyl group;

[0057] Fig.32 is a substituent R in the examples of this application 1 is hydrogen, R 2 The carbon NMR spectrum of the final product of phenyl group;

[0058] Fig.33 is a substituent R in the examples of this application 1 is hydrogen, R 2 The high-resolution mass spectrum of the final product of phenyl group;

[0059] Fig.34 is a substituent R in the examples of this application 1 is hydrogen, R 2 This is a partially enlarged high-resolution mass spectrum of the final product of phenyl.

[0060] Fig.35 FIG. 1 is a general chemical formula diagram of the alkenyl indole derivatives of the present application. DETAILED DESCRIPTION

[0061] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0062] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in this application can be purchased from the market or prepared by existing methods.

[0063] The present application will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are intended only to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods for which specific conditions are not specified in the following examples are usually measured according to national standards. If there is no corresponding national standard, then the conditions recommended by the manufacturer are followed.

[0064] There are six CH bonds on the indole ring of the indole compound. Compared with the indole derivatives substituted at C2, C3, C5, and C6, the indole derivatives substituted at C7 are more difficult to obtain, and the obtained indole derivatives substituted at C7 are mainly indole derivatives with non-terminal olefinic structures. This non-terminal olefinic structure is not conducive to the further transformation of the olefin functional group, which limits the conversion of terminal olefinic indole into other more valuable indole derivatives to a certain extent. On the other hand, 1H-indole, that is, indole without a substituent on the nitrogen atom, can be converted into indole substituted with other groups by some modifications on the nitrogen atom through reactions such as aromatization, alkylation, allylation, acylation, carbonylation, and carboxylation. Considering the particularity of the terminal olefinic substituted indole at C7 and the important role of 1H-indole, the present application provides an indole derivative having a terminal olefinic structure at C7 and no substituent on the nitrogen atom and a preparation method thereof, so as to solve the problem that the C7 position of the indole compound in the prior art cannot have a terminal olefinic structure, and the indole nitrogen atom is not easily replaced by other groups when there is a substituent.

[0065] In a first aspect, this embodiment provides an alkenyl indole derivative, characterized in that the C7 position has a terminal alkenyl structure, and there is no substituent on the nitrogen atom of the indole, and the general chemical formula is as follows:

[0066]

[0067] R 2 At least one selected from the following: phenyl, a second substituted phenyl, an alkyl group, an alkyl group substituted with an aryl group, and a naphthalene ring.

[0068] In this embodiment, the second substituted phenyl group refers to a phenyl group containing a substituent, and the substituent is not necessarily at the second position, but can be at the 3rd position or the 4th position, such as 4-methylphenyl, 4-fluorophenyl, and the like.

[0069] In some embodiments, the substituent in the second substituted phenyl group is selected from at least one of the following: C1-C6 alkyl, fluoroalkoxy, fluoroalkyl, alkoxycarbonyl, halogen, phenyl, phenoxy.

[0070] In the present embodiment, the main reason for selecting these substituents is: containing alkyl, fluoroalkyl, alkoxy, alkoxycarbonyl, halogen, cyano, nitro, etc. on the benzene ring of some active drug molecules and pesticide compounds. Usually, the possible reason for the high activity of a drug molecule is that it contains a certain group in its structure. Therefore, when a certain product reported as a synthetic method has a new structure, the substrates of these groups are generally used in the synthetic method to illustrate that the universality of the synthetic method is very good, and it is also hoped that the synthetic method can provide help for the preparation of candidate drug molecules. In addition, there are also some groups that can carry out functional group conversion to prepare products with the same structure and different substituents. For example, alkoxycarbonyl can be converted into carboxyl, cyano can also be converted into carboxyl, halogen can be further converted into aryl, and nitro can be converted into amino, etc.

[0071] In some embodiments, the position of the substituent in the second substituted phenyl group is selected from the para position or the meta position on the benzene ring.

[0072] In this embodiment, the second substituted phenyl group refers to a phenyl group containing a substituent, and the substituent is located at position 3 or 4 of the benzene ring. For example, the second substituted phenyl group is formed by replacing position 3 or 4 of the benzene ring with a C1-C6 alkyl group, a fluoroalkoxy group, a fluoroalkyl group, an alkoxycarbonyl group, a halogen group, a phenyl group, a phenoxy group, or the like.

[0073] In some embodiments, the chemical formula of the alkenyl indole derivative is as follows:

[0074]

[0075] In the formula, R 1 At least one selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, and halogen.

[0076] In this embodiment, the alkoxy group is a type of substituent consisting of an alkyl group and an oxygen atom. According to the size of the alkyl group, the alkoxy group can be further divided into: methoxy (CH3O-), ethoxy (C2H5O-), propoxy (C3H7O-), etc. Generally, the alkoxy group exhibits an electron-withdrawing inductive effect because the electronegativity of the oxygen atom is stronger than that of the carbon atom directly connected. However, if it is connected to a benzene ring (or a carbon-carbon double bond) as in this embodiment, it behaves as an electron donor because there is p-π conjugation here, and the oxygen atom supplies electrons to the benzene ring (or carbon-carbon double bond) through p-π conjugation.

[0077] In some embodiments, the substituent R of the alkenyl indole 1 The position of the indoline ring is selected from the 3, 4, 5, and 6 positions.

[0078] The present application also provides a method for preparing an alkenyl indole derivative, which uses at least one of the alkenyl indole derivatives of the above embodiments. Since the method uses the alkenyl indole derivatives of some or all of the above embodiments, it has at least all the beneficial effects brought by the above embodiments, which will not be described one by one here.

[0079] In a second aspect, the present invention provides a method for preparing an alkenyl indole derivative, which is used to prepare the alkenyl indole derivative according to any one of claims 1 to 5, and the method comprises:

[0080] N-pyridindoline I, alkenyl borate II and a catalyst undergo an alkenylation reaction under set conditions to generate N-pyridindoline III having a terminal alkenyl structure at the C7 position;

[0081] N-pyridindoline III reacts with manganese dioxide to generate N-pyridindole IV having a terminal olefinic structure at the C7 position;

[0082] N-pyridindole IV reacts with MeOTf to remove the pyridyl group, generating an indole derivative V having a terminal olefinic structure at the C7 position and no substituent on the nitrogen atom.

[0083] In some embodiments, the olefination reaction is set at a temperature of 60° C. to 100° C., and the set time is 8 h to 24 h.

[0084] In this embodiment, when the temperature is lower than 60° C. or higher than 100° C., the reaction effect is not good; when the time is lower than 8 h or higher than 12 h, the reaction effect is not good.

[0085] In some embodiments, the catalyst for the olefination reaction comprises Ag2CO3 and / or [RhCp*Cl2]2.

[0086] In this embodiment, only Ag2CO3 and / or [RhCp*Cl2]2 can be used as catalysts. The expected product cannot be obtained by replacing other catalysts.

[0087] In some embodiments, the molar ratio of the N-pyridindoline I, alkenyl borate II, Ag2CO3 and / or [RhCp*Cl2]2 is 1:(1-4):(1-4):(0.5%-20%).

[0088] In this embodiment, a molar ratio of the compounds that is too high or too low is not conducive to a complete reaction, or the reaction does not occur.

[0089] In some embodiments, the molar ratio of the N-pyridindoline III to the manganese dioxide is 1:(10-20).

[0090] In this embodiment, a molar ratio of the compounds that is too high or too low is not conducive to a complete reaction, or the reaction does not occur.

[0091] In this embodiment, the molar ratio of the compounds is too high or too low, which is not conducive to the complete reaction. The reaction temperature is too high or too low, which is not conducive to the reaction or the complete reaction. Generally, the oil bath temperature is 1-2 degrees higher than the boiling point of the solvent used to ensure the reflux state.

[0092] In this embodiment, the compound I substituent R 1 is selected from hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, halogen, etc., and the substituent R 1 The position of the substituent R is selected from the 3, 4, 5, and 6 positions on the indoline ring. 2 The second substituted phenyl is selected from phenyl, a second substituted phenyl, an alkyl, an aryl substituted alkyl, a naphthalene ring, etc., the substituent in the second substituted phenyl is selected from C1-C6 alkyl, a fluoroalkoxy, a fluoroalkyl, an alkoxycarbonyl, a halogen, a phenyl, a phenoxy group, etc., and the position of the substituent in the second substituted phenyl is selected from the para position or the meta position on the benzene ring.

[0093] In the present embodiment, TLC (thin layer chromatography) is used to detect whether the reaction is completely reacted. After the reaction is completely carried out, purification treatment is carried out. During the treatment process, it is necessary to first cool to room temperature, and then concentrate under reduced pressure. For the product that needs to be extracted, the organic layer is first dried over anhydrous magnesium sulfate, and after removing moisture, it is then concentrated under reduced pressure. The crude product obtained is separated and purified by silica gel column chromatography. The solvent used for separation and purification by silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate.

[0094] The preparation method of a 7-phenylvinyl-1H-indole derivative of the present application will be described in detail below in combination with specific examples and experimental data.

[0095] Embodiment 1:

[0096] like Figure 1 As shown, in this embodiment: R 1 is hydrogen, R 2 It is phenyl.

[0097] Figure 1 The steps shown include:

[0098] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 8h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-processing and purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid with a yield of 95%.

[0099] Step 2: In a 25mL round-bottom bottle, add compound III-1 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 95%.

[0100] Step 3: Add compound IV-1 (2.0 mmol) to a 25 mL two-necked flask and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice bath cooling, and then naturally warm to room temperature for 12 h. TLC (thin layer chromatography) detection until the reaction is complete, cool to room temperature, and concentrate under reduced pressure. The residue is dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) is added, and the mixture is placed at 60 ° C for 12 h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL × 2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20: 1 ~ 10: 1, that is, a pure product is obtained, a light yellow liquid, and the yield is 90%.

[0101] like Figure 31-34 As shown, the data of compound V-1 tested by nuclear magnetic resonance hydrogen spectrum, carbon spectrum and mass spectrum are as follows:

[0102] 1 H NMR(400MHz, CDCl3)δ7.59(br,1H),7.55(d,J=7.8Hz,1H),7.37–7.26(m,2H),7.26– 7.17(m,3H),7.13–7.09(m,1H),7.05(t,J=7.5Hz,1H),6.92(t,J=2.8Hz,1H ), 6.44 (dd, J = 2.9, 2.3Hz, 1H), 5.62 (d, J = 1.2Hz, 1H), 5.47 (d, J = 1.2Hz, 1H).

[0103] 13 C NMR (100MHz, CDCl3) δ147.2,140.4,133.9,128.5,128.2,128.1,127.6,125.0,124.1,122.6, 120.5,119.9,115.5,102.4.

[0104] HRMS m / z:calcd for C 16 H 14 N[M+H + ]220.1121, found 220.1127.

[0105] The above spectral data results all indicate that compound V-1 is the expected product.

[0106] Embodiment 2:

[0107] like Figure 2 As shown, in this embodiment: R 1 is 3-methyl, R 2 It is phenyl.

[0108] Figure 2 The steps shown include:

[0109] Step 1: In a 25mL Schlenk tube, add compound I-2 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 18h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a light yellow liquid, with a yield of 82%.

[0110] Step 2: In a 25mL round-bottom bottle, add compound III-2 (1.0mmol), MnO2 (20mmol), 1,2-dichloroethane (15.0mL), and place the mixture at 85°C for 8h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 91%.

[0111] Step 3: Add compound IV-2 (2.0 mmol) to a 25 mL double-necked flask and dissolve in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice bath cooling, then naturally warm to room temperature and react for 12 h. TLC (thin layer chromatography) detection until the reaction is complete, cool to room temperature, and concentrate under reduced pressure. The residue is dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) is added, and the mixture is placed at 60 ° C for 12 h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL × 2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20: 1 ~ 10: 1, that is, a pure product is obtained, a yellow liquid, and the yield is 89%.

[0112] Embodiment 3:

[0113] like Figure 3 As shown, in this embodiment: R 1 is 4-methyl, R 2 It is phenyl.

[0114] Figure 3 The steps shown include:

[0115] Step 1: In a 25mL Schlenk tube, add compound I-3 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 12h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 30:1 to 10:1, and a pure product is obtained as a light yellow solid. The yield is 91%.

[0116] Step 2: In a 25mL round-bottom bottle, add compound III-3 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 25:1 to 15:1, and a pure product is obtained as a white solid with a yield of 95%.

[0117] Step 3: Add compound IV-3 (2.0 mmol) to a 25 mL double-necked flask and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice bath cooling, and then naturally warm to room temperature for 12 h. TLC (thin layer chromatography) detection until the reaction is complete, cool to room temperature, and concentrate under reduced pressure. The residue is dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) is added, and the mixture is placed at 60 ° C for 8 h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL × 2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20: 1 ~ 10: 1, that is, a pure product is obtained, a yellow liquid, and the yield is 92%.

[0118] Embodiment 4:

[0119] like Figure 4 As shown, in this embodiment: R 1 is 4-benzyloxy, R 2 It is phenyl.

[0120] Figure 4 The steps shown include:

[0121] Step 1: In a 25mL Schlenk tube, add compound I-4 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 12h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid. The yield is 92%.

[0122] Step 2: In a 25mL round-bottom bottle, add compound III-4 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 95%.

[0123] Step 3: Add compound IV-4 (2.0 mmol) to a 25 mL two-necked flask and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice bath cooling, and then naturally warm to room temperature for 12 h. TLC (thin layer chromatography) detection until the reaction is complete, cool to room temperature, and concentrate under reduced pressure. The residue is dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) is added, and the mixture is placed at 60 ° C for 12 h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL × 2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20: 1 ~ 10: 1, that is, a pure product is obtained as a yellow solid, with a yield of 85%.

[0124] Embodiment 5:

[0125] like Figure 5 As shown, in this embodiment: R 1 is 4-chloro, R 2 It is phenyl.

[0126] Figure 5 The steps shown include:

[0127] Step 1: In a 25mL Schlenk tube, add compound I-5 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 18h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a white solid with a yield of 87%.

[0128] Step 2: In a 25mL round-bottom bottle, add compound III-5 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~15:1, and a pure product is obtained as a white solid with a yield of 93%.

[0129] Step 3: Add compound IV-5 (2.0 mmol) to a 25 mL two-necked flask and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice bath cooling, and then naturally warm to room temperature for 12 h. TLC (thin layer chromatography) detection until the reaction is complete, cool to room temperature, and concentrate under reduced pressure. The residue is dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) is added, and the mixture is placed at 60 ° C for 10 h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL × 2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20: 1 ~ 10: 1, that is, a pure product is obtained, a yellow liquid, and the yield is 85%.

[0130] Embodiment 6:

[0131] like Figure 6 As shown, in this embodiment: R 1 is 4-methoxycarbonyl, R 2 It is phenyl.

[0132] Figure 6 The steps shown include:

[0133] Step 1: In a 25mL Schlenk tube, add compound I-6 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 30:1 to 10:1 to obtain a pure product as a light yellow solid with a yield of 80%.

[0134] Step 2: In a 25mL round-bottom bottle, add compound III-6 (1.0mmol), MnO2 (12mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 5h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a yellow solid with a yield of 90%.

[0135] Step 3: Add compound IV-6 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0136] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 12 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a yellow solid with a yield of 88%.

[0137] Embodiment 7:

[0138] like Figure 7 As shown, in this embodiment: R 1 is 5-methyl, R 2 It is phenyl.

[0139] Figure 7 The steps shown include:

[0140] Step 1: In a 25mL Schlenk tube, add compound I-7 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a light yellow solid. The yield is 80%.

[0141] Step 2: In a 25mL round-bottom bottle, add compound III-7 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 25:1 to 15:1, and a pure product is obtained as a white solid with a yield of 96%.

[0142] Step 3: Add compound IV-7 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0143] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 10h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 87%.

[0144] Embodiment 8:

[0145] like Figure 8 As shown, in this embodiment: R 1 is 5-methoxy, R 2 It is phenyl.

[0146] Figure 8 The steps shown include:

[0147] Step 1: In a 25mL Schlenk tube, add compound I-8 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 12h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid with a yield of 92%.

[0148] Step 2: In a 25mL round-bottom bottle, add compound III-8 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 97%.

[0149] Step 3: Add compound IV-8 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0150] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 10h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a yellow liquid, with a yield of 87%.

[0151] Embodiment 9:

[0152] like Fig. 9 As shown, in this embodiment: R 1 is 5-benzyloxy, R 2 It is phenyl.

[0153] Fig. 9 The steps shown include:

[0154] Step 1: In a 25mL Schlenk tube, add compound I-9 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid. The yield is 67%.

[0155] Step 2: In a 25mL round-bottom bottle, add compound III-9 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 88%.

[0156] Step 3: Add compound IV-9 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0157] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 12 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a yellow solid with a yield of 90%.

[0158] Embodiment 10:

[0159] like Fig.10 As shown, in this embodiment: R 1 is 5-cyano, R 2 It is phenyl.

[0160] Fig.10 The steps shown include:

[0161] Step 1: In a 25mL Schlenk tube, add compound I-10 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 15:1 to 5:1, and a pure product is obtained as a white solid with a yield of 42%.

[0162] Step 2: In a 25mL round-bottom bottle, add compound III-10 (1.0mmol), MnO2 (15mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 4h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 10:1 to 5:1, and a pure product is obtained as a yellow solid with a yield of 92%.

[0163] Step 3: Add compound IV-10 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0164] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a yellow solid with a yield of 83%.

[0165] Embodiment 11:

[0166] like Fig.11 As shown, in this embodiment: R 1 is 5-nitro, R 2 It is phenyl.

[0167] Fig.11 The steps shown include:

[0168] Step 1: In a 25mL Schlenk tube, add compound I-11 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 8:1, and a pure product is obtained as a yellow solid with a yield of 54%.

[0169] Step 2: In a 25mL round-bottom bottle, add compound III-11 (1.0mmol), MnO2 (15mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 4h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 10:1 to 5:1, and a pure product is obtained as a yellow solid with a yield of 90%.

[0170] Step 3: Add compound IV-11 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0171] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a yellow solid with a yield of 85%.

[0172] Embodiment 12:

[0173] like Fig.12 As shown, in this embodiment: R 1 is 5-chloro, R 2 It is phenyl.

[0174] Fig.12 The steps shown include:

[0175] Step 1: In a 25mL Schlenk tube, add compound I-12 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 12h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a white solid with a yield of 95%.

[0176] Step 2: In a 25mL round-bottom bottle, add compound III-12 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 92%.

[0177] Step 3: Add compound IV-12 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0178] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 90%.

[0179] Embodiment 13:

[0180] like Fig.13 As shown, in this embodiment: R 1 is 5-bromo, R 2 It is phenyl.

[0181] Fig.13 The steps shown include:

[0182] Step 1: In a 25mL Schlenk tube, add compound I-13 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid with a yield of 57%.

[0183] Step 2: In a 25mL round-bottom bottle, add compound III-13 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 ~ 10:1, and a pure product is obtained as a white solid with a yield of 91%.

[0184] Step 3: Add compound IV-13 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0185] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 12 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 91%.

[0186] Embodiment 14:

[0187] like Fig.14 As shown, in this embodiment: R 1 is 6-fluoro, R 2 It is phenyl.

[0188] Fig.14 The steps shown include:

[0189] Step 1: In a 25mL Schlenk tube, add compound I-14 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a yellow solid with a yield of 72%.

[0190] Step 2: In a 25mL round-bottom bottle, add compound III-14 (1.0mmol), MnO2 (12mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 93%.

[0191] Step 3: Add compound IV-14 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0192] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 10h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 89%.

[0193] Embodiment 15:

[0194] like Fig.15 As shown, in this embodiment: R 1 is 6-chloro, R 2 It is phenyl.

[0195] Fig.15 The steps shown include:

[0196] Step 1: In a 25mL Schlenk tube, add compound I-15 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a white solid with a yield of 54%.

[0197] Step 2: In a 25mL round-bottom bottle, add compound III-15 (1.0mmol), MnO2 (12mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~15:1, and a pure product is obtained as a white solid with a yield of 95%.

[0198] Step 3: Add compound IV-15 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0199] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 88%.

[0200] Embodiment 16:

[0201] like Fig.16 As shown, in this embodiment: R 1 is 3-methyl, 5-methoxy, R 2 It is phenyl.

[0202] Fig.16 The steps shown include:

[0203] Step 1: In a 25mL Schlenk tube, add compound I-16 (1.0mmol), compound II-1 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 40:1 to 20:1, and a pure product is obtained as a white solid with a yield of 83%.

[0204] Step 2: In a 25mL round-bottom bottle, add compound III-16 (1.0mmol), MnO2 (15mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 5h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 15:1 to 10:1, and a pure product is obtained as a yellow solid with a yield of 95%.

[0205] Step 3: Add compound IV-16 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0206] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 8h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 93%.

[0207] Embodiment 17:

[0208] like Fig.17 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-methylphenyl.

[0209] Fig.17 The steps shown include:

[0210] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-2 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a light yellow liquid, with a yield of 83%.

[0211] Step 2: In a 25mL round-bottom bottle, add compound III-17 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 99%.

[0212] Step 3: Add compound IV-17 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0213] TLC (thin layer chromatography) detected that the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 10 h. TLC (thin layer chromatography) detected that the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a yellow liquid, with a yield of 90%.

[0214] Embodiment 18:

[0215] like Fig.18 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 3-methylphenyl.

[0216] Fig.18 The steps shown include:

[0217] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-3 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-processing and purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a light yellow liquid, with a yield of 60%.

[0218] Step 2: In a 25mL round-bottom bottle, add compound III-18 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 98%.

[0219] Step 3: Add compound IV-18 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0220] TLC (thin layer chromatography) detected that the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 10 h. TLC (thin layer chromatography) detected that the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a yellow liquid, with a yield of 90%.

[0221] Embodiment 19:

[0222] like Fig.19 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-isopropylphenyl.

[0223] Fig.19 The steps shown include:

[0224] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-4 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a yellow liquid, with a yield of 85%.

[0225] Step 2: In a 25mL round-bottom bottle, add compound III-19 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 ~ 15:1, and a pure product is obtained as a light yellow solid with a yield of 98%.

[0226] Step 3: Add compound IV-19 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0227] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 10 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 92%.

[0228] Embodiment 20:

[0229] like Fig. 20 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-tert-butylphenyl.

[0230] Fig. 20 The steps shown include:

[0231] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-5 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a yellow liquid, with a yield of 85%.

[0232] Step 2: In a 25mL round-bottom bottle, add compound III-20 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~15:1, and a pure product is obtained as a light yellow solid with a yield of 97%.

[0233] Step 3: Add compound IV-20 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0234] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 12 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 91%.

[0235] Embodiment 21:

[0236] like Fig.21 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-trifluoromethoxyphenyl.

[0237] Fig.21 The steps shown include:

[0238] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-6 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 12h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a yellow liquid, with a yield of 94%.

[0239] Step 2: In a 25mL round-bottom bottle, add compound III-21 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 98%.

[0240] Step 3: Add compound IV-21 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0241] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 8h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 86%.

[0242] Embodiment 22:

[0243] like Fig. 22 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-methoxycarbonylphenyl.

[0244] Fig. 22 The steps shown include:

[0245] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-7 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained, a yellow liquid, with a yield of 75%.

[0246] Step 2: In a 25mL round-bottom bottle, add compound III-22 (1.0mmol), MnO2 (15mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 3h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 15:1 to 10:1, and a pure product is obtained as a yellow solid with a yield of 90%.

[0247] Step 3: Add compound IV-22 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0248] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a light yellow solid with a yield of 88%.

[0249] Embodiment 23:

[0250] like Fig.23 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-fluorophenyl.

[0251] Fig.23 The steps shown include:

[0252] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-8 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a yellow liquid, with a yield of 73%.

[0253] Step 2: In a 25mL round-bottom bottle, add compound III-23 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 92%.

[0254] Step 3: Add compound IV-23 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0255] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 85%.

[0256] Embodiment 24:

[0257] like Fig.24 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-chlorophenyl.

[0258] Fig.24 The steps shown include:

[0259] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-9 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a yellow liquid, with a yield of 81%.

[0260] Step 2: In a 25mL round-bottom bottle, add compound III-24 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 92%.

[0261] Step 3: Add compound IV-24 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0262] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 10h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 86%.

[0263] Embodiment 25:

[0264] like Fig.25 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 4-phenylphenyl.

[0265] Fig.25 The steps shown include:

[0266] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-10 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a white solid with a yield of 75%.

[0267] Step 2: In a 25mL round-bottom bottle, add compound III-25 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 15:1 to 10:1, and a pure product is obtained as a white solid with a yield of 98%.

[0268] Step 3: Add compound IV-25 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0269] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 8h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a white solid with a yield of 90%.

[0270] Embodiment 26:

[0271] like Fig.26 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 3-phenoxyphenyl.

[0272] Fig.26 The steps shown include:

[0273] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-11 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.02mmol), MeOH (10.0mL), and place the mixture at 60°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 30:1 to 15:1 to obtain a pure product as a white solid with a yield of 73%.

[0274] Step 2: In a 25mL round-bottom bottle, add compound III-26 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 15:1 to 10:1, and a pure product is obtained as a white solid with a yield of 97%.

[0275] Step 3: Add compound IV-26 (2.0 mmol) to a 25 mL two-necked bottle and dissolve it in CH2Cl2 (20 mL). Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0276] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 8h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a white solid with a yield of 93%.

[0277] Embodiment 27:

[0278] like Fig. 27 As shown, in this embodiment: R 1 is hydrogen, R 2 It is methyl.

[0279] Fig. 27 The steps shown include:

[0280] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-12 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.05mmol), MeOH (10.0mL), and place the mixture at 100°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained, a light yellow liquid, with a yield of 64%.

[0281] Step 2: In a 25mL round-bottom bottle, add compound III-27 (1.0mmol), MnO2 (12mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 30:1 to 20:1, and a pure product is obtained as a yellow solid with a yield of 94%.

[0282] Step 3: Add compound IV-27 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0283] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a yellow liquid, with a yield of 83%.

[0284] Embodiment 28:

[0285] like Fig.28 As shown, in this embodiment: R 1 is hydrogen, R 2 It is n-butyl.

[0286] Fig.28 The steps shown include:

[0287] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-13 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.04mmol), MeOH (10.0mL), and place the mixture at 80°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a light yellow liquid with a yield of 65%.

[0288] Step 2: In a 25mL round-bottom bottle, add compound III-28 (1.0mmol), MnO2 (12mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 1h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 30:1 to 20:1, and a pure product is obtained as a light yellow solid with a yield of 95%.

[0289] Step 3: Add compound IV-28 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0290] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a light yellow liquid, with a yield of 85%.

[0291] Embodiment 29:

[0292] like Fig.29 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 2-phenylethyl.

[0293] Fig.29 The steps shown include:

[0294] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-14 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.04mmol), MeOH (10.0mL), and place the mixture at 80°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a light yellow liquid with a yield of 76%.

[0295] Step 2: In a 25mL round-bottom bottle, add compound III-29 (1.0mmol), MnO2 (10mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 2h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a light yellow solid with a yield of 96%.

[0296] Step 3: Add compound IV-29 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0297] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0mL), 2N NaOH solution (6.0mL) was added, and the mixture was placed at 60°C for 12h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30mL), extract with ethyl acetate (20mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained, a yellow liquid, with a yield of 83%.

[0298] Embodiment 30:

[0299] like Fig.30 As shown, in this embodiment: R 1 is hydrogen, R 2 It is 2-naphthyl.

[0300] Fig.30 The steps shown include:

[0301] Step 1: In a 25mL Schlenk tube, add compound I-1 (1.0mmol), compound II-15 (2.0mmol), Ag2CO3 (2.0mmol), [RhCp*Cl2]2 (0.04mmol), MeOH (10.0mL), and place the mixture at 80°C for 24h. TLC (thin layer chromatography) is used to detect the reaction until it is complete. Post-treatment purification: cool to room temperature and concentrate under reduced pressure. The crude product is separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 50:1 to 30:1, and a pure product is obtained as a white solid with a yield of 61%.

[0302] Step 2: In a 25mL round-bottom bottle, add compound III-30 (1.0mmol), MnO2 (15mmol), 1,2-dichloroethane (10.0mL), and place the mixture at 85°C for 4h. TLC (thin layer chromatography) detection until the reaction is complete. Post-processing purification: cool to room temperature and filter under reduced pressure. The filtrate is concentrated under reduced pressure and separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1 to 10:1, and a pure product is obtained as a white solid with a yield of 99%.

[0303] Step 3: Add compound IV-30 (2.0 mmol) and dissolve it in CH2Cl2 (20 mL) in a 25 mL two-necked bottle. Add MeOTf (3.0 mmol) under ice-bath cooling, and then naturally warm to room temperature to react for 12 h.

[0304] TLC (thin layer chromatography) detected until the reaction was complete, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in MeOH (8.0 mL), 2N NaOH solution (6.0 mL) was added, and the mixture was placed at 60°C for 8 h. TLC (thin layer chromatography) detected until the reaction was complete. Post-treatment purification: Cool to room temperature, add water (30 mL), extract with ethyl acetate (20 mL×2), dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate)] = 20:1~10:1, and a pure product was obtained as a white solid with a yield of 90%.

[0305] Various embodiments of the present application may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be understood as a rigid limitation on the scope of the present application; therefore, the range description should be considered to have specifically disclosed all possible sub-ranges and single numerical values ​​within the range. For example, the range description from 1 to 6 should be considered to have specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which apply regardless of the range. In addition, whenever a numerical range is indicated herein, it is meant to include any cited number (fractional or integer) within the indicated range.

[0306] In this application, unless otherwise specified, directional words such as "upper" and "lower" used refer specifically to the directions of the drawings in the accompanying drawings. In addition, in the description of the specification of this application, the terms "include", "comprise", etc. mean "including but not limited to".

[0307] In this article, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply that there is any such actual relationship or order between these entities or operations. In this article, "and / or" describes the association relationship of associated objects, indicating that there can be three relationships, for example, A and / or B, which can represent: A exists alone, A and B exist at the same time, and B exists alone. Wherein A, B can be singular or plural. In this article, "at least one" refers to one or more, and "multiple" refers to two or more. "At least one", "the following at least one (individual)" or similar expressions refer to any combination of these items, including any combination of single (individual) or plural (individual). For example, "at least one (individual) of a, b, or c", or "at least one (individual) of a, b, and c", can all represent: a, b, c, ab (i.e. a and b), ac, bc, or abc, wherein a, b, c can be single or multiple respectively.

[0308] The above description is only a specific implementation of the present application, so that those skilled in the art can understand or implement the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the embodiments shown herein, but will conform to the widest range consistent with the principles and novel features applied for herein.

Claims

1. A method for preparing an alkenyl indole derivative, characterized in that: The method comprises: N-pyridine indole I, alkenyl borate II and a catalyst are subjected to alkenylation reaction under set conditions to generate N-pyridine indole III having a terminal alkenyl structure at the C7 position; the temperature set for the alkenylation reaction is 60 to 100 o C, the set time is 8-24 h, the catalyst for the olefination reaction is selected from Ag2CO3 and [RhCp*Cl2]2, and the molar ratio of the N-pyridine indole I, olefin borate II, Ag2CO3 and [RhCp*Cl2]2 is 1:(1-4):(1-4):(0.5%-20%); Reacting N-pyridindoline III with manganese dioxide to generate N-pyridindole IV having a C7 terminal olefinic structure, wherein the molar ratio of the N-pyridindoline III to the manganese dioxide is 1:(10-20); Reaction of N-pyridindole IV with MeOTf to remove the pyridyl group, thereby generating an indole derivative V having a terminal olefinic structure at the C7 position and having no substituent on the nitrogen atom; The synthetic route is as follows: Among them, R 1 At least one selected from the following: hydrogen, alkyl, alkoxy, alkoxycarbonyl, cyano, nitro, halogen; R 2 At least one selected from the following: phenyl, substituted phenyl, alkyl, aryl-substituted alkyl, naphthyl; The substituent in the substituted phenyl group is selected from at least one of the following: C1-C6 alkyl, fluoroalkoxy, fluoroalkyl, alkoxycarbonyl, halogen, phenyl, and phenoxy.

2. The preparation method according to claim 1, characterized in that The position of the substituent in the substituted phenyl group is selected from the para position or the meta position on the benzene ring.

3. The preparation method according to claim 1, characterized in that: The substituent R of the alkenyl indole 1 The position of is selected from 3, 4, 5, 6 on the indoline ring.

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