Preparation method of light-mediated aryl / heteroaryl sulfonamide and derivative thereof

Abstract

The invention discloses a preparation method of light-mediated aryl / heteroaryl sulfonamide and derivatives thereof, the reaction route is shown in the following formula, and the reaction comprises the following steps: (1) under the irradiation of blue light, reacting carboxylic acid active ester shown in the formula I with a sulfur dioxide source under the catalysis of a photocatalyst; and (2) acidifying the reaction product obtained in the step (1) to obtain the aryl / heteroaryl sulfonamide product as shown in the formula II. The method for catalyzing the reaction of the carboxylic acid active ester and the sulfur dioxide source under the action of the photocatalyst and the blue light to obtain the corresponding sulfonamide derivative has the advantages of simple reaction process operation, mild reaction conditions, recoverable raw materials, strong compatibility and adaptability, and wide substrate range and universality. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing aryl / heteroaryl sulfonamides and their derivatives mediated by light. Technical Background

[0002] Sulfonamide compounds are extremely important components in the fields of medicine, veterinary medicine, pesticides, and organic chemical synthesis. So far, the US Food and Drug Administration (FDA) has approved approximately 166 drugs containing sulfonamide structures. The sulfonamide moiety is usually used as a bioisostere of carboxylic acid and amide groups to improve drug efficacy and bioavailability. More and more sulfonamide drugs have been developed as candidate drugs with a wide range of biological activities, and they have a wide range of uses in the fields of antibacterial, antifungal, antioxidant, antiviral, anti-inflammatory, antidiabetic, and anticancer. In the field of organic synthesis, due to their acidity and weak self-aggregation properties, bifunctional sulfonamide reagents can be widely used as hydrogen bond catalysts in asymmetric organic catalysis. In addition, sulfonamide herbicides (such as: flumetsulam, cloransulam-methyl, florasulam, penoxsulam, pyrazosulfuron-ethyl, diclosulam, amidosulfuron) are a major class of pesticides.

[0003] The traditional methods for synthesizing these structures usually involve first preparing sulfonyl chloride, and then reacting the sulfonyl chloride with an amine to obtain the desired target product. However, this method does have many limitations, such as the tricky preparation and storage of sulfonyl chloride, as well as environmental pollution problems such as waste liquid and waste gas generated during this process, the weak nucleophilicity of specific amine substrates, and the tolerance problems of various functional groups.

[0004] Recently, photocatalysis has been applied to the synthesis of sulfonamides, but it mainly focuses on the synthesis of alkyl sulfonamides. There are few reports on the synthesis method of photocatalytic aryl sulfonamides. There are only three reports on the preparation of aryl sulfonamides by photocatalysis from substrates without sulfonyl groups (Chem. Commun. 2019, 55(17), 2489 - 2492; ACS Catal. 2023, 13(17), 11580 - 11588; J. Am. Chem. Soc. 2023, 145(39), 21189 - 21196), but it has the following problems: (1) using strong bases and performing the synthesis of sulfonamides in two steps; (2) the substrates are diazonium salts, thioxanthium salts, diaryliodonium salts, etc., and the preparation is relatively complex; (3) using toxic sulfur dioxide gas and copper metal as catalysts. Therefore, studying a general, practical, and effective method for synthesizing aryl / heteroaryl sulfonamide compounds under mild conditions remains a challenge and has practical application value. Summary of the Invention

[0005] In view of this, the object of the present invention is to provide a novel method for directly synthesizing aryl / heteroaryl sulfonamides with environmental friendliness, mild reaction conditions, simple process operation, recyclable raw materials and high catalytic efficiency.

[0006] The object of the present invention is achieved by the following technical methods:

[0007] A method for preparing aryl / heteroaryl sulfonamides and their derivatives mediated by light, the reaction route is as follows:

[0008]

[0009] Wherein:

[0010] Ar is selected from substituted or unsubstituted C6-C14 aryl groups, substituted or unsubstituted 5-15 membered heteroaryl groups; the 5-15 membered heteroaryl group refers to a 5-15 membered, especially 5-13 membered, more especially 5-7 membered or 5-6 membered aromatic ring system containing 1-4, especially 1-3, more especially 1-2 ring heteroatoms selected from N, O or S (especially N), including monocyclic, bicyclic or fused polycyclic rings, and the remaining ring atoms are carbon atoms; the substitution means being substituted by one or more substituents selected from the following group A: halogen (such as -F, -Cl, -Br), hydroxyl, cyano (-CN), C1-C6 alkyl (such as methyl, n-butyl), C1-C6 alkyl substituted by one or more halogens (such as trifluoromethyl), C1-C6 alkoxy (such as methoxy), C1-C6 alkoxy substituted by one or more halogens (such as difluoromethoxy), -SO2R a 、-NHCOR a 、-COOR a 、-SR a 、oxo (=O, -O-), phenyloxy substituted by one or more R b substituents,

[0011] Wherein, R a is selected from H, C1-C6 alkyl (such as methyl), C1-C6 alkyl substituted by one or more halogens; R b is selected from H, halogen, hydroxyl, cyano (-CN), C1-C6 alkyl, C1-C6 alkyl substituted by one or more halogens (such as trifluoromethyl), C1-C6 alkoxy (such as methoxy), C1-C6 alkoxy substituted by one or more halogens;

[0012] R1 and R2 are each independently a substituted or unsubstituted benzene, or R1 and R2 cyclize to form a fluorenyl group; the substitution means being substituted by one or more substituents selected from the following group B: halogen (such as -Cl, -F,), C1-C6 alkyl (such as tert-butyl), C1-C6 alkoxy (such as methoxy);

[0013] The reaction includes the following steps:

[0014] (1) Under blue light irradiation, the carboxylic acid active ester shown in formula I reacts with a sulfur dioxide source under the catalysis of a photocatalyst;

[0015] (2) Acidifying the reaction product obtained in step (1) to obtain the aryl / heteroaryl sulfonamide product shown in formula II.

[0016] In a specific embodiment, Ar is selected from a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-13 membered heteroaryl group; in particular, Ar is selected from the following substituted or unsubstituted groups: phenyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, quinoxalinyl, pyridoindolyl, phthalazinyl; the definition of the substitution is as described above.

[0017] In a specific embodiment, the Ar is selected from the structures shown below:

[0018]

[0019] Among them, R3 is 0, one or more (such as 2, 3, 4, especially 2) substituents selected from the following: halogen (such as -F, -Cl, -Br), cyano (-CN), C1-C4 alkyl (such as methyl, n-butyl), C1-C4 alkyl substituted by one or more halogens (such as trifluoromethyl), C1-C4 alkoxy (such as methoxy), C1-C4 alkoxy substituted by one or more halogens (such as difluoromethoxy), -SO2R a , -NHCOR a , -COOR a , -SR a , Among them, R a is selected from H, C1-C4 alkyl (such as methyl).

[0020] In a specific embodiment, in step (1), the wavelength of the blue light is 450-435 nm, especially 445-435 nm, such as 440 nm.

[0021] In a specific embodiment, in step (1), the sulfur dioxide source can be sulfur dioxide or a substance that releases sulfur dioxide. For example, it can be one or a combination of bis(sulfur dioxide)-1,4-diazabicyclo[2.2.2]octane adduct (DABSO), sodium metabisulfite, potassium metabisulfite, and sodium sulfite. Preferably, it is bis(sulfur dioxide)-1,4-diazabicyclo[2.2.2]octane adduct (DABSO), which can control the reaction equivalent compared with directly using SO2 gas, and the reaction operation is convenient, green and environmentally friendly.

[0022] In a specific embodiment, in step (1), the photocatalyst includes but is not limited to: (4,4'-di-tert-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl-κN]phenyl-κN]phenyl-κC]iridium(III) hexafluorophosphate (Ir(dF(CF3)ppy)2(dtbbpy)](PF6)), (OC-6-22)-tris[2-(2,4-difluorophenyl)pyridine]iridium (fac-Ir(dFppy)3), 9-thioxanthone, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), especially Ir(dF(CF3)ppy)2(dtbbpy)](PF6).

[0023] In a specific embodiment, the reaction in step (1) is carried out in an organic solvent, and the organic solvent can be selected from one or a mixture of two or more of ethyl acetate, tetrahydrofuran, dichloromethane, acetonitrile, methyltetrahydrofuran, ethyl formate, ethyl propionate, ethyl isopropionate, ethyl n-butyrate, propionitrile, butyronitrile or chloroform; in particular, the organic solvent is acetonitrile.

[0024] In a specific embodiment, in step (1), the concentration of the carboxylic acid active ester shown in formula I in the organic solvent is 0.05 mol / L to 1 mol / L, for example, 0.1 mol / L.

[0025] In a specific embodiment, in step (1), the molar ratio of the carboxylic acid active ester shown in formula I: sulfur dioxide source: iridium catalyst is 1:0.5 - 2:0.005 - 0.02, and the preferred molar ratio is 1:0.5 - 1:0.005 - 0.015, for example, 1:0.75:0.01.

[0026] In a specific embodiment, the reaction in step (1) is carried out at 20 - 30 °C, and the reaction time is 6 - 48 h, preferably 8 - 16 h.

[0027] In a specific embodiment, the reaction in step (1) is carried out under the protection of an inert gas (such as argon).

[0028] In a specific embodiment, the reaction in step (1) can also be carried out in the presence of an additive to facilitate an increase in the reaction yield. The additive can be one or a combination of (NH4)2SO4, (NH4)2CO3, NH4Br, NH4Cl, NH4H2PO4, NaH2PO4, KHSO4, CH3COOH, KCl, or KH2PO4, etc., and is preferably NH4Cl.

[0029] In a specific embodiment, in step (1), in the presence of an additive, the molar ratio of the carboxylic acid active ester shown in formula I to the additive is 1:0.1 - 2; the preferred molar ratio is 1:1 - 2, such as 1:1.5.

[0030] In a specific embodiment, in step (2), the acidification can be carried out by removing the organic solvent from the reaction product obtained in step (1) and then adding an acid reagent for treatment to remove the substituted or unsubstituted benzophenone or fluorenone protecting group. The acid reagent can be an organic acid or an inorganic acid, including but not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, trifluoroacetic acid, or an organic solution of hydrogen chloride, such as a 1,4 - dioxane solution of hydrogen chloride with a hydrogen chloride concentration of 24 mol / L; the treatment temperature is 20 - 30 °C, and the treatment time is 0.5 - 2 h.

[0031] In a specific embodiment, in step (2), the crude product after the acidification treatment can be further purified. Specifically, the crude product after the acidification treatment can be treated with a basifying reagent until it is neutral, and then obtained a purified product through extraction, chromatography, or crystallization. In a specific implementation, the basifying reagent can be sodium carbonate or a methanol solution of ammonia with a concentration of 5 - 10 mol / L.

[0032] The beneficial effects of the present invention are as follows:

[0033] 1. The method for catalytically reacting a carboxylic acid active ester with a sulfur dioxide source to obtain a corresponding sulfonamide derivative under the action of a photocatalyst and blue light proposed by the present invention has a simple reaction process operation, mild reaction conditions, recyclable raw materials, strong compatibility and adaptability, and has a wide substrate range and universality.

[0034] 2. The active ester shown in formula I in the method of the present invention can be prepared from aryl / heteroaryl carboxylic acids as raw materials, which are cheap and rich in sources; the sulfur dioxide source (DABSO) and the additive (ammonium chloride) added during the reaction process are also cheap and easily available.

[0035] 3. The method of the present invention can avoid the use of sulfonyl chloride or sulfur dioxide gas in traditional methods, avoid the harm of toxic substances to the human body and environmental pollution, is economical, green, and environmentally friendly, and has strong practicability. Specific Embodiments

[0036] The preparation method of the photo-mediated aryl / heteroaryl sulfonamide and its derivatives proposed by the present invention has the following reaction principle: in the presence of an iridium catalyst and under blue light irradiation, a carboxylic acid active ester shown in Formula I cleaves to release one molecule of carbon dioxide, an aryl / heteroaryl radical and an imine radical. The aryl radical reacts with sulfur dioxide released from a sulfur dioxide source to form an aryl / heteroaryl sulfonyl radical, which then combines with the imine radical to generate an aryl / heteroaryl sulfonimide. Finally, the benzophenone / fluorenone group is removed under acidic conditions to obtain the corresponding sulfonamide derivative.

[0037] The technical solutions of the present invention will be further described and illustrated through specific embodiments below, but these embodiments are by no means any limitation to the present invention.

[0038] Regarding reagents and consumables: unless otherwise specified, all reagents are commercially available. The silica gel for purification is the column chromatography silica gel with 200 - 300 mesh produced by Qingdao Marine Chemical Factory, and the blue light lamp is manufactured by Company, model PR160 - 440;

[0039] Regarding analytical instruments: the hydrogen spectrum is recorded by Bruker Avance III 600 type, Bruker Avance III 500 type, and Bruker Avance III 400 type nuclear magnetic resonance spectrometers, and the chemical shift is expressed in δ (ppm); the mass spectrum is recorded by an Agilent1200 - 6110 type single quadrupole liquid chromatography - mass spectrometry combined instrument or an Agilent 1290 - 6545UHPLC - QTOF mass spectrometer.

[0040] The active esters used in the following examples are prepared by the following method:

[0041]

[0042] According to the method reported in the literature (J. Am. Chem. Soc. 2023, 145, 30, 16630 - 16641), the oxime (1.0 mmol) b and the aromatic carboxylic acid a (1.0 mmol) are dissolved in a dichloromethane (10 mL) solution, and then 4 - dimethylaminopyridine (DMAP, 10 mol%, 0.1 mmol) and carbodiimide hydrochloride (EDCI, 2.5 mmol) are added. After stirring the mixture at room temperature for 4 hours, it is diluted with distilled water (20 mL), the organic phase is separated, dried over anhydrous sodium sulfate and concentrated. The crude product is purified by silica gel column chromatography (petroleum ether / ethyl acetate as the eluent) to obtain the corresponding compound.

[0043] Preparation of pyridine - 2 - sulfonamide (Compound 1) in Example 1

[0044]

[0045] (1) In a 10 mL vial, add different 2-pyridinecarboxylic acid active esters (0.2 mmol) shown in Table 1, bis(sulfur dioxide)-1,4-diazabicyclo[2.2.2]octane adduct (DABSO, 0.15 mmol), ammonium chloride (0.3 mmol), (4,4′-di-tert-butyl-2,2′-bipyridine)bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κN]phenyl-κC]iridium(III) hexafluorophosphate ([Ir(dF(CF3)ppy)2(dtbbpy)](PF6), 0.002 mmol), dissolve them in 2 mL of anhydrous acetonitrile. Under argon protection, irradiate with the company's PR160-440 blue light lamp (440 nm, 40 W), and use an electric fan to cool the reaction flask to keep the reaction at room temperature for 12 hours. After the reaction is completed, evaporate the organic solvent to dryness by a rotary evaporator, dissolve the obtained mixture in 1,4-dioxane containing 4 mol / L hydrochloric acid, stir at room temperature for one hour, and then add an appropriate amount of sodium carbonate or 7 mol / L ammonia methanol solution to keep the pH neutral.

[0046] (2) After the reaction is completed, evaporate the organic solvent to dryness by a rotary evaporator, and then purify the product by a silica gel column. The eluent ratio is petroleum ether∶ethyl acetate = 10∶1 to 7∶1. The yields of the obtained product pyridine-2-sulfonamide are shown in Table 1. At the same time, the recovered by-products benzophenone or fluorenone can be reused for the synthesis of active esters.

[0047] (3) After alkalization, evaporate the solvent of the reaction solution by a rotary evaporator, and then purify the product by a silica gel column. The eluent ratio is petroleum ether∶ethyl acetate = 10∶1 to 7∶1. The yields of the obtained product pyridine-2-sulfonamide are shown in Table 1. At the same time, the recovered by-products benzophenone or fluorenone can be reused for the synthesis of active esters.

[0048] Table 1

[0049]

[0050]

[0051] a Ammonium chloride not added

[0052] Characterization data:

[0053] 1 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 4.8 Hz, 1H), 8.07 (td, J = 7.7, 1.8 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.64 (dd, J = 7.7, 4.6 Hz, 1H), 7.46 (s, 2H);

[0054] 1313C NMR (126 MHz, DMSO-d6) δ 159.81, 149.61, 138.51, 126.60, 120.40.

[0055] HRMS (ESI) (m / z): [M+H] + calculated for C5H7N2O2S: 159.0223, found: 159.0223.

[0056] Preparation of Compound 2-32 in Example 2-32

[0057] The synthesis procedure was the same as that in Example 1, except that the carboxylic acid active ester was different. The structure of the carboxylic acid active ester used was as follows. The structures, yields, and characterization data of the corresponding sulfonamide products are shown in Table 2.

[0058] Where Ar corresponds to the corresponding structure of the sulfonamide product.

[0059] Table 2

[0060]

[0061]

[0062]

[0063]

[0064]

[0065] As can be seen from Table 2, the method of the present invention has good compatibility with various heterocyclic carboxylic acids and substituted benzoic acids, has a wide application range, good isolation yields, and some even reach up to 87%.

[0066] Preparation of Compound 33-40 in Example 33-40

[0067] The synthesis procedure was the same as that in Example 1, except that the carboxylic acid active ester was different. The structure of the carboxylic acid active ester used was as follows. The structures, yields, and characterization data of the corresponding sulfonamide products are shown in Table 3.

[0068] Where Ar corresponds to the corresponding structure of the sulfonamide product.

[0069] Table 3

[0070]

[0071]

[0072]

[0073] As can be seen from Table 3, the method of the present invention has good compatibility with the complex structures related to natural products and drugs, has a wide application range, and has good separation yields, and some are even as high as 94%, and can be used for the late modification of drug structures.

[0074] The above embodiments are only used to further illustrate the preparation method of a sulfonamide and its derivatives of the present invention, but the present invention is not limited to the embodiments. Any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention all fall within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing a photo-mediated aryl / heteroaryl sulfonamide and its derivatives, and the reaction route is as follows: Wherein: Ar is selected from a substituted or unsubstituted C6-C14 aryl group, a substituted or unsubstituted 5-15 membered heteroaryl group; said substitution means being substituted by one or more substituents selected from the following group A: halogen (e.g., -F, -Cl, -Br), hydroxyl, cyano, C1-C6 alkyl (e.g., methyl, n-butyl), C1-C6 alkyl substituted by one or more halogens (e.g., trifluoromethyl), C1-C6 alkoxy (e.g., methoxy), C1-C6 alkoxy substituted by one or more halogens (e.g., difluoromethoxy), -SO2R a , -NHCOR a , -COOR a , -SR a , oxo (=O, -O-), phenyloxy substituted by one or more Rb, wherein, R a is selected from H, C1-C6 alkyl (e.g., methyl), C1-C6 alkyl substituted by one or more halogens; R b is selected from H, halogen, hydroxyl, cyano, C1-C6 alkyl, C1-C6 alkyl substituted by one or more halogens (e.g., trifluoromethyl), C1-C6 alkoxy (e.g., methoxy), C1-C6 alkoxy substituted by one or more halogens; R1 and R2 are each independently a substituted or unsubstituted benzene, or R1 and R2 are cyclized into a fluorenyl group; the substitution means being substituted by one or more substituents selected from the following group B: halogen (such as -Cl, -F), C1-C6 alkyl (such as tert-butyl), C1-C6 alkoxy (such as methoxy); The reaction includes the following steps: (1) Under blue light irradiation, the carboxylic acid active ester shown in formula I reacts with a sulfur dioxide source under the catalysis of a photocatalyst; (2) The reaction product obtained in step (1) is acidified to obtain the aryl / heteroaryl sulfonamide product shown in formula II.

2. The preparation method according to claim 1, characterized in that, Ar is selected from a substituted or unsubstituted C6-C10 aryl group, a substituted or unsubstituted 5-13 membered heteroaryl group; In particular, Ar is selected from the following substituted or unsubstituted groups: phenyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, quinoxalinyl, pyridoindolyl, phthalazinyl; the definition of substitution is as defined in claim 1.

3. The preparation method according to claim 1 or 2, characterized in that, The Ar is selected from the following structures: Among them, R3 is zero, one or more substituents selected from the following: halogen (such as -F, -Cl, -Br), cyano (-CN), C1-C4 alkyl (such as methyl, n-butyl), C1-C4 alkyl substituted with one or more halogens (such as trifluoromethyl), C1-C4 alkoxy (such as methoxy), C1-C4 alkoxy substituted with one or more halogens (such as difluoromethoxy), -SO2R a , -NHCOR a , -COOR a , -SR a , Among them, R a is selected from H, C1-C4 alkyl (such as methyl).

4. The preparation method according to any one of claims 1-3, characterized in that, In step (1): The wavelength of the blue light is 450-435 nm, especially 445-435 nm; and / or The sulfur dioxide source is sulfur dioxide or a substance that releases sulfur dioxide; the substance that releases sulfur dioxide is selected from one or more combinations of bis(sulfur dioxide)-1,4-diazabicyclo[2.2.2]octane adduct, sodium metabisulfite, potassium metabisulfite, sodium sulfite, and is preferably bis(sulfur dioxide)-1,4-diazabicyclo[2.2.2]octane adduct; and / or The photocatalyst includes: (4,4'-di-tert-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-trifluoromethyl-2-pyridinyl-κN]phenyl-κN]phenyl-κC]iridium(III) hexafluorophosphate, (OC-6-22)-tris[2-(2,4-difluorophenyl)pyridine]iridium, 9-thioxanthone, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile; in particular, the photocatalyst is (4,4'-di-tert-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-trifluoromethyl-2-pyridinyl-κN]phenyl-κN]phenyl-κC]iridium(III) hexafluorophosphate.

5. The preparation method according to any one of claims 1-3, characterized in that, The reaction in step (1) is carried out in an organic solvent, and the organic solvent is selected from one or a mixture of two or more of ethyl acetate, tetrahydrofuran, dichloromethane, acetonitrile, methyltetrahydrofuran, ethyl formate, ethyl propionate, ethyl isopropionate, ethyl n-butyrate, propionitrile, butyronitrile or chloroform; in particular, the organic solvent is acetonitrile; and / or The concentration of the carboxylic acid active ester shown in formula I in the organic solvent is 0.05 mol / L to 1 mol / L.

6. The preparation method according to any one of claims 1 to 3, characterized in that, In step (1): The molar ratio of the carboxylic acid active ester shown in formula I: sulfur dioxide source: iridium catalyst is 1:0.5-2:0.005-0.02, and the preferred molar ratio is 1:0.5-1:0.005-0.

015.

7. The preparation method according to any one of claims 1 to 3, characterized in that, In step (1): The reaction is carried out at 20-30 °C, and the reaction time is 6-48 h, preferably 8-16 h; and / or The reaction is carried out under the protection of an inert gas.

8. The preparation method according to any one of claims 1-3, characterized in that, The reaction in step (1) is carried out in the presence of an additive, and the additive is one or a combination of (NH4)2SO4, (NH4)2CO3, NH4Br, NH4C1, NH4H2PO4, NaH2PO4, KHSO4, CH3COOH, KCl or KH2PO4, preferably NH4C1; and / or The molar ratio of the carboxylic acid active ester shown in formula I to the additive is 1:0.1-2; the preferred molar ratio is 1:1-2.

9. The preparation method according to any one of claims 1-3, characterized in that, In step (2), the acidification is carried out by removing the organic solvent from the reaction product obtained in step (1) and then adding an acid reagent for treatment; the acid reagent is an organic acid or an inorganic acid, including hydrochloric acid, hydrobromic acid, sulfuric acid, trifluoroacetic acid or an organic solution of hydrogen chloride, such as a 1,4-dioxane solution of hydrogen chloride, wherein the concentration of hydrogen chloride is 24 mol / L; the treatment temperature is 20-30 °C, and the treatment time is 0.5-2 h.

10. The preparation method according to any one of claims 1-3, characterized in that, Step (2) further includes: treating the crude product after the acidification treatment with a basifying reagent until it is neutral, and then obtaining a purified product through extraction, chromatography or crystallization; In particular, the basifying reagent is sodium carbonate or a methanol solution of ammonia; preferably, the concentration of the methanol solution of ammonia is 5-10 mol / L.

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