Synthesis method for substituted iminostilbene compound

Abstract

The present invention provides a synthesis method for a substituted iminostilbene compound. When the substituent is hydrogen, the substituted iminostilbene compound is an iminostilbene compound and is a carbamazepine intermediate. A preparation method provided by the present invention comprises the following steps: (1) performing coupling reaction on indole and halobenzene under the action of alkali and a solvent to obtain 1-phenylindole; (2) carrying out rearrangement reaction on the 1-phenylindole under the action of a catalyst and protonic acid to obtain iminostilbene; and (3) carrying out substitution reaction on iminostilbene and chlorosulfonyl isocyanate to obtain carbamazepine. The present invention has the characteristics of high yield, short reaction time, less waste water, waste gas and solid wastes, low costs, and a simple process, and is suitable for industrial production.

Description

Synthesis method of substituted iminostilbene compounds

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on August 10, 2023, with application number 202311002571.4 and invention name “Method for the synthesis of substituted iminostilbene compounds”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present invention belongs to the field of drug synthesis. The present invention relates to the synthesis of iminostilbene and substituted iminostilbene compounds, and the present invention relates to a method for synthesizing iminostilbene and substituted iminostilbene in one step using an indole compound as a starting material. Background Art

[0003] Substituted iminostilbenes are important pharmaceutical intermediates, such as those used in the synthesis of the antiepileptic drug carbamazepine and the antidepressant clomipramine.

[0004] Currently, the most widely used synthesis method for substituted iminostilbene is to use iminodibenzyl as the raw material and prepare it through bromination and dehydrobromination. Patent CN1616433 reports that o-nitrotoluene is used as the starting material, and iminodibenzyl is obtained through condensation, reduction, and high-temperature cyclization. Then, 5-formyl iminostilbene chloride is obtained through chloroformylation, bromination, and dehydrobromination. This route not only has many steps and low yield, but also has harsh reaction conditions and is prone to explosion. In addition, it produces a large amount of three wastes and causes serious pollution.

[0005] Patent CN101307021 reports the use of iminodibenzyl as a raw material, and catalytic dehydrogenation under high temperature and high pressure conditions to obtain iminostilbene. The catalytic dehydrogenation process has strict requirements on equipment, large equipment investment, expensive catalysts, high reaction risk, and high product cost.

[0006] Patent CN103113302 reports that 1-phenylindole is used as a raw material and an intramolecular rearrangement is carried out under acidic conditions such as sulfuric acid, phosphoric acid, and polyphosphoric acid to obtain iminostilbene in one step. However, the yield is extremely low, only about 30%, and industrial production is not possible.

[0007] Patents CN115724800 and CN112457253 improve the method of patent CN103113302 by using mixed acids or using super acids such as trifluoromethanesulfonic acid and fluoroantimonic acid alone to increase the acidity of the system and thus improve the reaction conversion rate. This method has the following disadvantages: 1. The amount of acid used is extremely large, and a large amount of three wastes is generated during post-treatment, causing great pollution; 2. The super acids are expensive, resulting in high product prices and cannot be used in actual production.

[0008] In general, the prior art focuses on achieving rearrangement reactions using strong acids, teaching those skilled in the art to use strong acids to complete rearrangement reactions. It is necessary to develop a process with greater industrial advantages to overcome the shortcomings of the prior art.

[0009] Summary of the Invention

[0010] In view of the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a method for preparing substituted iminostilbene to solve the problems of high energy consumption, harsh reaction conditions and long reaction steps in the existing process.

[0011] To achieve the above-mentioned and other related objectives, the present invention is implemented through the following technical solutions:

[0012] In one aspect, the present invention provides a method for preparing a substituted iminostilbene compound, which is prepared by a rearrangement reaction of a substituted phenylindole compound in the presence of a catalyst and a protonic acid, as shown in the following reaction formula:

[0013] wherein X1 and X2 are identical or different and are one or more halogen, C1-C6 alkyl, alkoxy or hydrogen.

[0014] Furthermore, a method for preparing iminostilbene, an intermediate of carbamazepine, is provided. 1-phenylindole is subjected to a rearrangement reaction in the presence of a catalyst and a protonic acid to obtain iminostilbene. The reaction formula is as follows:

[0015] Preferably, in the rearrangement reaction step, the catalyst is selected from one or more of boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, aluminum chloride, ferric chloride, titanium tetrachloride, zinc chloride, nickel chloride, zinc acetate, nickel acetate, phosphorus pentoxide, silicon tetrachloride, cuprous iodide, cuprous bromide, or Lewis acids formed by scandium, yttrium, and lanthanide elements. Preferred are boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, and titanium tetrachloride.

[0016] Preferably, in the rearrangement reaction step, the protonic acid is selected from one or more of trifluoromethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, benzenesulfonic acid and its derivatives (such as p-nitrobenzenesulfonic acid, p-trifluoromethylbenzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, etc.), 5-isoquinolinesulfonic acid, 1-chloro-5-isoquinolinesulfonic acid, 3-pyridinesulfonic acid, 6-chloropyridine-3-sulfonic acid, 2-pyridinesulfonic acid, and 6-chloropyridine-2-sulfonic acid. Methanesulfonic acid and trifluoromethanesulfonic acid are preferred.

[0017] Preferably, in the rearrangement reaction step, the solvent is selected from chlorobenzene, bromobenzene, toluene, xylene, acetic acid, formic acid or n-heptane, preferably chlorobenzene.

[0018] Preferably, in the rearrangement reaction step, the reaction temperature is 70-120°C, preferably 85-100°C.

[0019] Preferably, in the rearrangement reaction step, the reaction time is 2 to 16 hours, preferably 6 to 8 hours.

[0020] Preferably, in the rearrangement reaction step, the molar ratio of 1-phenylindole, catalyst, and protonic acid is 1:(0.5-5.0):(0.5-5.0), preferably 1:(0.5-3.0):(0.5-3.0).

[0021] Furthermore, the preparation method of the substituted iminostilbene provided by the present invention comprises the following steps:

[0022] (1) Substituted indole and substituted halogenated benzene undergo coupling reaction in the presence of a base and a solvent to prepare phenylindole;

[0023] (2) The substituted phenylindole undergoes rearrangement reaction under the action of a catalyst and a protonic acid to prepare a substituted iminostilbene;

[0024] The reaction formula is as follows:

[0025] Wherein, X is chlorine or bromine, and X1 and X2 are the same or different and are one or more halogens, C1-C6 alkyls, alkoxys or hydrogens.

[0026] Specifically, the present invention provides a method for preparing a carbamazepine intermediate iminostilbene, comprising the following steps:

[0027] (1) Indole and halogenated benzene are subjected to a coupling reaction under the action of a base and a solvent to prepare 1-phenylindole;

[0028] (2) 1-phenylindole undergoes rearrangement reaction under the action of catalyst and protonic acid to prepare iminostilbene;

[0029] The reaction formula is as follows:

[0030] wherein X is Br or I.

[0031] Preferably, in the coupling reaction step, the base is selected from one or more of K2CO3, Na2CO3, Cs2CO3, CaCO3, NiCO3, MgCO3, Li2CO3, TEA, DIPEA, TBU, and NaH. K2CO3 is preferred. The coupling reaction is carried out using potassium carbonate, and the reaction yield is greater than 98%, and the product can be carried to the next step without purification.

[0032] Preferably, in the coupling reaction step, the solvent is selected from one or more of dimethyl sulfoxide, xylene, N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide, acetonitrile, toluene, chlorobenzene, bromobenzene, and n-heptane, preferably dimethyl sulfoxide.

[0033] Preferably, in the rearrangement reaction step, the catalyst is selected from one or more of boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, aluminum chloride, ferric chloride, titanium tetrachloride, zinc chloride, nickel chloride, zinc acetate, nickel acetate, phosphorus pentoxide, silicon tetrachloride, cuprous iodide, cuprous bromide, or Lewis acids formed by scandium, yttrium, and lanthanide elements. Preferred are boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, and titanium tetrachloride.

[0034] Preferably, in the rearrangement reaction step, the protonic acid is selected from one or more of trifluoromethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, benzenesulfonic acid and its derivatives (such as p-nitrobenzenesulfonic acid, p-trifluoromethylbenzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, etc.), 5-isoquinolinesulfonic acid, 1-chloro-5-isoquinolinesulfonic acid, 3-pyridinesulfonic acid, 6-chloropyridine-3-sulfonic acid, 2-pyridinesulfonic acid, and 6-chloropyridine-2-sulfonic acid. Methanesulfonic acid and trifluoromethanesulfonic acid are preferred.

[0035] Preferably, in the rearrangement reaction step, the solvent is selected from chlorobenzene, bromobenzene, toluene, xylene, acetic acid, formic acid or n-heptane, preferably chlorobenzene.

[0036] Preferably, in the rearrangement reaction step, the reaction temperature is 70-120°C, preferably 85-100°C.

[0037] Preferably, in the rearrangement reaction step, the reaction time is 2 to 16 hours, preferably 6 to 8 hours.

[0038] Preferably, in the rearrangement reaction step, the molar ratio of 1-phenylindole, catalyst, and protonic acid is 1:(0.5-5.0):(0.5-5.0), preferably 1:(0.5-3.0):(0.5-3.0).

[0039] In addition, the present invention provides a method for preparing carbamazepine, comprising the following steps:

[0040] (1) 1-phenylindole undergoes rearrangement reaction under the action of catalyst and protonic acid to obtain iminostilbene;

[0041] (2) Carbamazepine is obtained by substitution reaction of iminostilbene and chlorosulfonyl isocyanate;

[0042] The reaction formula is as follows:

[0043] Preferably, in the rearrangement reaction step, the catalyst is selected from one or more of boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, aluminum chloride, ferric chloride, titanium tetrachloride, zinc chloride, nickel chloride, zinc acetate, nickel acetate, phosphorus pentoxide, silicon tetrachloride, cuprous iodide, cuprous bromide, or Lewis acids formed by scandium, yttrium, and lanthanide elements. Preferred are boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, and titanium tetrachloride.

[0044] Preferably, in the rearrangement reaction step, the protonic acid is selected from one or more of trifluoromethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, benzenesulfonic acid and its derivatives (such as p-nitrobenzenesulfonic acid, p-trifluoromethylbenzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, etc.), 5-isoquinolinesulfonic acid, 1-chloro-5-isoquinolinesulfonic acid, 3-pyridinesulfonic acid, 6-chloropyridine-3-sulfonic acid, 2-pyridinesulfonic acid, and 6-chloropyridine-2-sulfonic acid. Methanesulfonic acid and trifluoromethanesulfonic acid are preferred.

[0045] Preferably, in the rearrangement reaction step, the solvent is selected from chlorobenzene, bromobenzene, toluene, xylene, acetic acid, formic acid or n-heptane, preferably chlorobenzene.

[0046] Preferably, in the rearrangement reaction step, the reaction temperature is 70-120°C, preferably 85-100°C.

[0047] Preferably, in the rearrangement reaction step, the reaction time is 2 to 16 hours, preferably 6 to 8 hours.

[0048] Preferably, in the rearrangement reaction step, the molar ratio of 1-phenylindole to the catalyst to the protonic acid is 1:(0.5-5.0):(0.5-5.0), preferably 1:(0.5-3.0):(0.5-3.0).

[0049] The present invention provides a method for preparing carbamazepine, which preferably comprises the following steps:

[0050] (1) Indole and halogenated benzene are subjected to a coupling reaction under the action of a base and a solvent to prepare 1-phenylindole;

[0051] (2) 1-phenylindole undergoes rearrangement reaction under the action of catalyst and protonic acid to prepare iminostilbene;

[0052] (3) Carbamazepine is prepared by substitution reaction of iminostilbene and chlorosulfonyl isocyanate;

[0053] The synthetic route is as follows:

[0054] wherein X is Br or I.

[0055] Preferably, in the coupling reaction step, the base is selected from one or more of K2CO3, Na2CO3, Cs2CO3, CaCO3, NiCO3, MgCO3, Li2CO3, TEA, DIPEA, TBU, and NaH, preferably K2CO3.

[0056] Preferably, in the coupling reaction step, the solvent is selected from one or more of dimethyl sulfoxide, xylene, N,N-dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide, acetonitrile, toluene, chlorobenzene, bromobenzene, and n-heptane, preferably dimethyl sulfoxide.

[0057] Preferably, in the rearrangement reaction step, the catalyst is selected from one or more of boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, aluminum chloride, ferric chloride, titanium tetrachloride, zinc chloride, nickel chloride, zinc acetate, nickel acetate, phosphorus pentoxide, silicon tetrachloride, cuprous iodide, cuprous bromide, or Lewis acids formed by scandium, yttrium, and lanthanide elements. Preferred are boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, and titanium tetrachloride.

[0058] Preferably, in the rearrangement reaction step, the protonic acid is selected from one or more of trifluoromethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, benzenesulfonic acid and its derivatives (such as p-nitrobenzenesulfonic acid, p-trifluoromethylbenzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, etc.), 5-isoquinolinesulfonic acid, 1-chloro-5-isoquinolinesulfonic acid, 3-pyridinesulfonic acid, 6-chloropyridine-3-sulfonic acid, 2-pyridinesulfonic acid, and 6-chloropyridine-2-sulfonic acid. Methanesulfonic acid and trifluoromethanesulfonic acid are preferred.

[0059] Preferably, in the rearrangement reaction step, the solvent is selected from chlorobenzene, bromobenzene, toluene, xylene, acetic acid, formic acid or n-heptane, preferably chlorobenzene.

[0060] Preferably, in the rearrangement reaction step, the reaction temperature is 70-120°C, preferably 85-100°C.

[0061] Preferably, in the rearrangement reaction step, the reaction time is 2 to 16 hours, preferably 6 to 8 hours.

[0062] Preferably, in the rearrangement reaction step, the molar ratio of 1-phenylindole, catalyst, and protonic acid is 1:(0.5-5.0):(0.5-5.0), preferably 1:(0.5-3.0):(0.5-3.0).

[0063] During the research of the present invention, it was unexpectedly discovered that when the acid is used in combination with a suitable catalyst, the yield can reach as high as 95.2% and the purity can exceed 99% under mild reaction conditions. At the same time, the research found that in the presence of the catalyst, only a very small amount of acid (less than 1 equivalent) is needed to achieve the above results.

[0064] The method for synthesizing iminostilbene provided by the present invention uses a catalyst and a protonic acid in combination to carry out a reaction, has obvious technical and industrial advantages, and has the characteristics of high yield, short reaction time, less three wastes, low cost, simple process, and suitability for industrial production. DETAILED DESCRIPTION

[0065] The present invention will be further described below with reference to specific embodiments. Those skilled in the art will be able to implement the present invention based on these descriptions. Furthermore, the embodiments of the present invention described below generally represent only a portion of the present invention, rather than all of the embodiments. Therefore, all other embodiments derived by those skilled in the art based on the embodiments of the present invention without inventive effort should fall within the scope of protection of the present invention.

[0066] Example 1: Synthesis of 1-phenylindole

[0067] To a 250 mL three-necked flask, 50 g (0.43 mol) of indole, 8.2 g (0.043 mol) of CuI, 59.6 g (0.43 mol) of potassium carbonate, 100.6 g (0.64 mol) of bromobenzene, and 200 g of DMSO were added in sequence. Stirring was started, the temperature was raised to 180 ° C, and the reaction was carried out for 2-3 hours. After the reaction was completed, the temperature was lowered to 20-30 ° C, 20 g of diatomaceous earth was added to the system, filtered, and the filter cake was rinsed with 200 g of ethyl acetate. 500 ml of water was added to the mother liquor, stirred, and the layers were separated. The organic layer was separated, and the aqueous layer was extracted with 200*2 ethyl acetate. The organic layers were combined and washed with 300 g of saturated brine. The organic layer was concentrated and evaporated to dryness under reduced pressure, and then heated to 60-80 ° C. and the excess bromobenzene was evaporated under reduced pressure to obtain 81.2 g of a light brown oil with a yield of 98.5%.

[0068] Example 2: Synthesis of 1-phenylindole

[0069] The experimental process was the same as that of Example 1, except that bromobenzene was replaced by iodobenzene. Other conditions and operating procedures were the same as those of Example 1, and a light brown oil was finally obtained with a yield of 97.2%.

[0070] Example 3: Synthesis of 1-phenylindole

[0071] The experimental process was the same as that of Example 1, except that dimethyl sulfoxide was replaced with N-methylpyrrolidone. Other conditions and operations were the same as those of Example 1, and a light brown oil was finally obtained with a yield of 91.8%.

[0072] Example 4: Synthesis of chlorine-substituted iminostilbene:

[0073] 28.8 g (0.3 mol) of methanesulfonic acid was added to 100 g of chlorobenzene, and after stirring evenly, 22.7 g (0.1 mol) of chlorobenzene indole compound was added, and then 14.2 g (0.1 mol) of boron trifluoride etherate was added. The temperature was raised to 85-100 ° C. and the reaction was closed for 6-8 hours. The reaction was cooled to room temperature, 100 g of water was added dropwise, the layers were separated, and the aqueous layer was extracted with 50 g * 2 ethyl acetate. The organic layers were combined and washed with 50 g of saturated brine. The organic phase was evaporated to dryness under reduced pressure and crystallized with 100 g of n-heptane to prepare chlorine-substituted iminostilbene (20.6 g, yield 91.0%).

[0074] Example 5: Synthesis of Chloro-Substituted Iminostilbene

[0075] Referring to the operation of Example 4, different catalyst and protonic acid combinations were used, and the experimental results were as follows:

[0076] Example 6: Synthesis of Methoxy-Substituted Iminostilbene

[0077] 28.8 g (0.3 mol) of methanesulfonic acid was added to 100 g of chlorobenzene, and after stirring evenly, 22.3 g (0.1 mol) of methoxyphenylindole compound was added, and then 14.2 g (0.1 mol) of boron trifluoride etherate was added. The temperature was raised to 85-100 ° C. and the reaction was closed for 6-8 hours. The reaction was cooled to room temperature, 100 g of water was added dropwise, the layers were separated, and the aqueous layer was extracted with 50 g * 2 ethyl acetate. The organic layers were combined and washed with 50 g of saturated brine. The organic phase was evaporated to dryness under reduced pressure and crystallized with 100 g of n-heptane to prepare methoxy-substituted iminostilbene (19.0 g, yield 85.2%).

[0078] Example 7:

[0079] Referring to the operation of Example 6, different catalyst and protonic acid combinations were used, and the experimental results were as follows:

[0080] Example 8:

[0081] To a 250 mL three-necked flask, 50 g (0.33 mol) of a chloro-substituted indole compound, 6.3 g (0.033 mol) of CuI, 45.7 g (0.33 mol) of potassium carbonate, 62.4 g (0.40 mol) of bromobenzene, and 200 g of DMSO were added in sequence. Stirring was started, the temperature was raised to 180 ° C, and the reaction was carried out for 2-3 hours. After the reaction was completed, the temperature was lowered to 20-30 ° C. 20 g of diatomaceous earth was added to the system, filtered, and the filter cake was rinsed with 200 g of ethyl acetate. 500 ml of water was added to the mother liquor, stirred, and the layers were separated. The organic layer was separated, and the aqueous layer was extracted with 200*2 ethyl acetate. The organic layers were combined, washed with 300 g of saturated brine, and the organic layer was concentrated under reduced pressure and evaporated to dryness to obtain 71.1 g of a light brown oily substance as a chloro-substituted phenyl indole compound with a yield of 95%.

[0082] Example 9:

[0083] To a 250 mL three-necked flask, 50 g (0.33 mol) of a chloro-substituted indole compound, 6.3 g (0.033 mol) of CuI, 45.7 g (0.33 mol) of potassium carbonate, 74.8 g (0.40 mol) of m-methoxybromobenzene, and 200 g of DMSO were added in sequence. Stirring was started, the temperature was raised to 180°C, and the reaction was carried out for 2-3 hours. After the reaction was completed, the temperature was lowered to 20-30°C. 20 g of diatomaceous earth was added to the system, and the mixture was filtered. The filter cake was rinsed with 200 g of ethyl acetate. 500 ml of water was added to the mother liquor, stirred, and the layers were separated. The organic layer was separated, and the aqueous layer was extracted with 200*2 ethyl acetate. The organic layers were combined, washed with 300 g of saturated brine, and the organic layer was concentrated under reduced pressure and evaporated to dryness to obtain 74.8 g of a light brown oil as the target compound with a yield of 88%.

Claims

1. A method for preparing a substituted iminostilbene compound, characterized in that, In the presence of a catalyst and a protonic acid, a phenylindole compound is subjected to a rearrangement reaction to prepare a substituted iminostilbene compound, and the reaction formula is as follows: Wherein, X1 and X2 are the same or different and are one or more halogen, C1-C6 alkyl, alkoxy or hydrogen.

2. The preparation method according to claim 1, characterized in that: Iminostilbene is prepared by rearrangement reaction of 1-phenylindole in the presence of a catalyst and a protonic acid. The reaction formula is as follows:

3. The preparation method according to claim 1, characterized in that: The following steps are involved: (1) Substituted indole and substituted halogenated benzene are subjected to coupling reaction under the action of base and solvent to prepare substituted phenyl indole; (2) Substituted phenyl indole undergoes rearrangement reaction under the action of a catalyst and a protonic acid to prepare a substituted iminostilbene; The reaction formula is as follows: Wherein, X is Br or I, and X1 and X2 are the same as defined in claim 1.

4. The preparation method according to claim 2, characterized in that: Further preparing carbamazepine comprises the following steps: (1) 1-phenylindole undergoes a rearrangement reaction under the action of a catalyst and a protonic acid to prepare iminostilbene; (2) Carbamazepine is prepared by substitution reaction of iminostilbene and chlorosulfonyl isocyanate; The reaction formula is as follows:

5. The preparation method according to claim 2, characterized in that: Further preparing carbamazepine comprises the following steps: (1) Indole and halobenzene are subjected to a coupling reaction under the action of a base and a solvent to prepare 1-phenylindole; (2) 1-phenylindole undergoes a rearrangement reaction under the action of a catalyst and a protonic acid to prepare iminostilbene; (3) Carbamazepine is prepared by substitution reaction of iminostilbene and chlorosulfonyl isocyanate; The reaction formula is as follows: Wherein, X is Br or I.

6. The preparation method according to any one of claims 1 to 5, characterized in that: In the rearrangement reaction step, the catalyst is selected from one or more of boron trifluoride etherate, boron trifluoride, boron trifluoride tetrahydrofuran, boron trifluoride acetonitrile, boron chloride, boron bromide, aluminum chloride, ferric chloride, titanium tetrachloride, zinc chloride, nickel chloride, zinc acetate, nickel acetate, phosphorus pentoxide, silicon tetrachloride, cuprous iodide, cuprous bromide or Lewis acids formed by scandium, yttrium and lanthanide elements.

7. The preparation method according to any one of claims 1 to 5, characterized in that: In the rearrangement reaction step, the proton acid is selected from one or more of trifluoromethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, benzenesulfonic acid and its derivatives, 5-isoquinolinesulfonic acid, 1-chloro-5-isoquinolinesulfonic acid, 3-pyridinesulfonic acid, 6-chloropyridine-3-sulfonic acid, 2-pyridinesulfonic acid, and 6-chloropyridine-2-sulfonic acid, and the benzenesulfonic acid derivative is p-nitrobenzenesulfonic acid, p-trifluoromethylbenzenesulfonic acid, p-chlorobenzenesulfonic acid or p-toluenesulfonic acid.

8. The preparation method according to any one of claims 1 to 5, characterized in that The solvent in the rearrangement reaction step is selected from chlorobenzene, bromobenzene, toluene, xylene, acetic acid, formic acid or n-heptane.

9. The preparation method according to any one of claims 1 to 5, characterized in that: The reaction temperature of the rearrangement step reaction is 70-120°C, and the reaction time is 2-16h.

10. The preparation method according to any one of claims 1 to 5, characterized in that: In the rearrangement reaction step, the molar ratio of the indole compound, the catalyst and the protonic acid is 1:(0.5-5.0):(0.5-5.0).

11. The preparation method according to claim 3 or 5, characterized in that: In the coupling reaction step, the base is selected from one or more of K2CO3, Na2CO3, Cs2CO3, CaCO3, NiCO3, MgCO3, Li2CO3, TEA, DIPEA, TBU, and NaH, and the solvent is selected from one or more of dimethyl sulfoxide, xylene, N,N-dimethylamide, acetonitrile, N-methylpyrrolidone, N,N-dimethylacetamide, toluene, chlorobenzene, bromobenzene, and n-heptane.

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