An amide compound containing iodinated aryl or iodinated heteroaryl, and preparation method and application thereof

Abstract

The present invention provides an amide compound containing an iodinated aryl group or an iodinated heteroaryl group, and a preparation method and application thereof. The amide compound containing an iodinated aryl group or an iodinated heteroaryl group of the present invention can be used to prepare an X-ray developing embolic material, thereby improving the developing modification efficiency and increasing the iodine content of the X-ray developing embolic material.

Description

Technical Field

[0001] The invention belongs to the technical field of material synthesis and relates to an amide compound containing an iodinated aryl group or an iodinated heteroaryl group and a preparation method and application thereof. Background Art

[0002] Due to the strong absorption of X-rays by iodine atoms, iodine-containing compounds, especially iodine-containing organic compounds, can be visualized in the human body under X-ray detection. Currently, commonly used contrast agent molecules in clinical practice, such as diatrizoate, iohexol, iodixanol, iopamidol, iotrolan, etc., have the characteristics of high water solubility and high iodine content. They are used for angiography of blood vessels and organs under X-ray detection such as CT in clinical interventional surgery, which greatly facilitates clinical surgical operations.

[0003] The commonly used liquid embolic material iodized oil in clinical TACE (Transhepatic Arterial Chem Otherapy And Embolization) surgery has iodized poppy oil as its main component. As an embolic material, iodized oil is visible in the human body under X-ray detection, which is helpful for clinicians to directly judge the embolic effect. CN102781974B discloses the use of 2,3,5-triiodobenzyl bromide modification, forming an ether bond with polyethylene glycol (PVA) under the action of a strong base, and then obtaining iodine-containing nanoparticles through emulsion precipitation, which can be used as an embolic material for X-ray development. CN104717983B discloses a poly 2-hydroxypropionic acid solution modified with triiodophenol and iohexol, which is used to produce an in-situ developable embolic precipitate during blood injection. CN113651906A discloses the grafting of iodinated phenyl ether compounds with PVA to obtain a liquid embolic material similar to ONYX glue. After the embolic material is injected into a blood vessel, a solid precipitate is generated in situ to form an embolism that can be visualized under X-rays.

[0004] In addition, the use of gel microspheres modified with iodine-containing organic compound molecules as solid embolic agents developed under X-rays has also achieved rapid development in recent years. CN105517582B and CN112334497A of BTG Company of the United Kingdom disclose the use of iodinated aryl aldehyde or acetal compounds to modify polyvinyl alcohol microspheres under acidic conditions to obtain developing microspheres for embolization. The modified molecules synthesized in the patent application use alkyl chains or alkoxy chains to connect iodinated aryls and aldehyde groups, resulting in a limited range of this type of molecule, requiring multi-step synthesis and difficult synthesis. CN111821503A discloses the use of iodinated aryl acyl chloride or sulfonyl chloride compounds to modify PVA microspheres to obtain embolic microspheres with an iodine content of 31.9-52.6%. The use of acyl chloride or sulfonyl chloride to modify microspheres has harsh conditions and is not conducive to process amplification. CN105517580A discloses the use of imidazole carbonate to react with PVA microspheres first, and then react with iodine-containing alcohols or amines to achieve iodine modification of gel microspheres. This method has mild reaction conditions, but requires two steps of reaction and is cumbersome. In addition, the developer molecules and microspheres are connected by carbonate bonds, which have poor stability.

[0005] Therefore, it is of great significance to further develop X-ray imaging materials in this field. Summary of the invention

[0006] In view of the deficiencies of the prior art, the object of the present invention is to provide an amide compound containing an iodinated aryl or iodinated heteroaryl group, and a preparation method and application thereof. The amide compound containing an iodinated aryl or iodinated heteroaryl group of the present invention can be used to prepare an X-ray developing embolic material. The compound of the present application is simple to synthesize, has an amide structure in the molecule, has a stable structure, and has good hydrophilicity. The microspheres after development modification have better hydrophilicity, elasticity and stability.

[0007] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0008] In one aspect, the present invention provides an amide compound containing an iodinated aryl group or an iodinated heteroaryl group, wherein the compound has a structure shown in Formula I:

[0009]

[0010] Wherein X is C substituted with at least one iodine 5-12 Aryl or at least one iodine-substituted C 5-12 Heteroaryl; R is C 1-6 Alkyl; n is an integer greater than or equal to 1.

[0011] In the present invention, when defining the groups in the amide compound containing iodinated aryl or iodinated heteroaryl, the number of carbon atoms in each group is defined. The numerical range of the defined number of carbon atoms means that the number of carbon atoms in the group can be all integers within the given numerical range, for example, C1-6 Alkyl means that the number of carbon atoms in the alkyl group can be 1, 2, 3, 4, 5 or 6.

[0012] Preferably, in the compound of formula I, n=1 or 2 or 3.

[0013] Preferably, X is at least one iodine-substituted C 5-7 Aryl, more preferably, X is at least one iodine-substituted phenyl group.

[0014] Preferably, X is selected from any one of the following groups:

[0015]

[0016] The wavy lines represent the attachment sites of the groups.

[0017] Preferably, R is methyl, ethyl, n-propyl, isopropyl, n-butyl or n-hexyl.

[0018] Preferably, the amide compound containing an iodinated aryl group or an iodinated heteroaryl group is any one of the following compounds:

[0019]

[0020] In another aspect, the present invention provides a method for preparing the amide compound containing an iodinated aryl group or an iodinated heteroaryl group as described above, the preparation method comprising the following steps:

[0021] The compound of formula V undergoes a condensation reaction with the compound of formula VI to obtain an amide compound containing an iodinated aryl group or an iodinated heteroaryl group as shown in formula I. The reaction formula is as follows:

[0022]

[0023] The definitions of X, R, and n are the same as those above.

[0024] Preferably, the molar ratio of the compound of formula VI to the compound of formula V is 1:1 to 10:1, for example 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1.

[0025] Preferably, the condensation reaction is carried out in the presence of a condensation agent.

[0026] Preferably, the condensing agent is 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).

[0027] Preferably, the condensation reaction is carried out in the presence of an alkaline substance, and the alkaline substance is triethylamine, diisopropylethylamine, triethylenediamine (DABCO) or N-methylmorpholine.

[0028] Preferably, the solvent for the condensation reaction is N,N-dimethylformamide or N,N-dimethylacetamide.

[0029] Preferably, the condensation reaction temperature is room temperature, and the reaction time is 2-48 h, for example 2 h, 5 h, 8 h, 10 h, 12 h, 15 h, 18 h, 20 h, 24 h, 28 h, 32 h, 36 h, 38 h, 40 h, 44 h or 48 h.

[0030] Preferably, the condensation reaction is carried out under the protection of a protective gas, and the protective gas is preferably nitrogen.

[0031] In another aspect, the present invention provides an X-ray developing material, the X-ray developing material comprising the amide compound containing an iodinated aryl group or an iodinated heteroaryl group as described above;

[0032] Preferably, the X-ray developing material is X-ray developing embolic microspheres.

[0033] The developing microspheres modified with the amide compound containing iodinated aryl or iodinated heteroaryl have better hydrophilicity and operating performance.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] The compound of the present invention connects an iodinated aryl or heteroaryl structure with an aldehyde or acetal structure of a specific length through an amide bond, thereby introducing a hydrophilic amide structure, which makes it easier to achieve development modification of the embolic material when the development embolic material is prepared therefrom, so that the prepared development embolic material has better hydrophilicity, better elasticity, and better stability, and improves the development modification efficiency, so that the iodine content of the X-ray development embolic material is increased. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 For compound I-1 1 H-NMR spectrum;

[0037] Figure 2 is the LCMS spectrum of compound I-1;

[0038] Figure 3 is the HPLC spectrum of compound I-1;

[0039] Figure 4 Compound I-2 1 H-NMR spectrum;

[0040] Figure 5 is the LCMS spectrum of compound I-2;

[0041] Figure 6 It is the HPLC spectrum of compound I-2. DETAILED DESCRIPTION

[0042] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0043] The compounds obtained in the examples of the present invention were analyzed by HPLC (high performance liquid chromatography), LCMS (liquid chromatography mass spectrometry) and 1 H-NMR (nuclear magnetic hydrogen spectrum) characterization. The method is as follows:

[0044] HPLC: The test instrument is Agilent 1260 high performance liquid chromatograph; the chromatographic column is octadecyl bonded silica column; the mobile phase is 0.1% phosphoric acid aqueous solution and methanol; the detector is VWD detector; take about 0.1 mg of sample into a sample bottle, add DMSO to dissolve and then directly inject for detection; determine the product purity based on the integrated area.

[0045] LCMS: The test instrument is an Agilent 1260-6125 high performance liquid chromatography-mass spectrometer; the chromatographic column is an octadecyl bonded silica column; the mobile phase is a 0.1% formic acid aqueous solution and methanol; the detector is a mass spectrometer detector; about 0.1 mg of sample is taken into a sample bottle, dissolved in DMSO and directly injected for detection to identify the main ion peaks.

[0046] 1 H-NMR: The test instrument is a Bruker 400M nuclear magnetic resonance tester; the probe used is a room temperature hydrogen spectrum probe; 20-30 mg of sample is added to a nuclear magnetic resonance tube, and 0.3-0.5 mL of deuterated DMSO is added to dissolve and then tested.

[0047] Preparation Example 1

[0048] Preparation of compound I-1:

[0049]

[0050] Under nitrogen protection, compound VI-1 (1.0 equivalent), compound V-1 (1.0 equivalent, 50 g), HATU (1.5 equivalent) and anhydrous DMF (5000 mL) were added to a single-mouth reaction bottle in sequence, and after stirring and dissolving, triethylamine (3.0 equivalent) was slowly added to keep the reaction at room temperature. After the reaction of the raw materials was complete as monitored by TLC, 5000 mL of water was added to the reaction solution to quench the reaction, and then 5000 mL of ethyl acetate (EA) was added to extract the layers. The organic phase was retained and washed three times with water (5000 mL × 3). After drying over anhydrous sodium sulfate, the organic phase was concentrated. After concentration to a certain extent (about 300 mL EA was left), a large amount of solid precipitated. The temperature was lowered to -5 to 0 ° C. The solid was precipitated by stirring and then filtered. The filter cake was rinsed with a small amount of cold EA. The filter cake was vacuum dried at 45 ° C for 2 h to obtain the target product I-1 (44 g, yield 75%, purity> 98%), which was a white to light pink solid with a melting point of 180-182 ° C.

[0051] Figure 1 For compound I-1 1 H-NMR spectrum, the data are summarized as follows: 1 H NMR (400 MHz, DMSO-d 6 )δ8.58(t,J=5.9Hz,1H),8.25(d,J=1.9Hz,1H),7.46(d,J=1.9Hz,1H),4.48(t,J=5.5Hz,1H),3.29(s,6H),3.28-3.25(m,2H).

[0052] Figure 2 LCMS spectrum of compound I-1, MS (ESI): m / z 588 (M+H + ),610(M+Na + ).

[0053] Figure 3 It is the HPLC spectrum of compound I-1.

[0054] Depend on Figure 1-3 It can be concluded that the synthesized compound is a single target compound I-1 with a purity of >98%.

[0055] Preparation of compound I-2:

[0056]

[0057] Under nitrogen protection, compound VI-2 (1.2 equivalents), compound V-1 (1.0 equivalents, 50 g), HATU (1.5 equivalents) and anhydrous DMF (5000 mL) were added to a single-mouth reaction bottle in sequence, and after stirring and dissolving, triethylamine (3.0 equivalents) was slowly added to keep the reaction at room temperature. After the reaction of the raw materials was complete as monitored by TLC, 5000 mL of water was added to the reaction solution to quench the reaction, and then 5000 mL of ethyl acetate (EA) was added to extract and separate the layers. The organic phase was retained, washed three times with water (5000 mL × 3), dried over anhydrous sodium sulfate, and concentrated. After concentrating to a certain extent (about 300 mL EA was left), a large amount of solid precipitated. The temperature was lowered to -5 to 0 ° C, stirred to precipitate the solid, and then filtered, and the filter cake was rinsed with a small amount of cold EA. The filter cake was vacuum dried at 45 ° C for 2 h to obtain the target product I-2 (44 g, yield 70%, purity> 98%), which was a white solid with a melting point of 157-160 ° C;

[0058] Figure 4 Compound I-2 1 H-NMR spectrum, the data are as follows: 1 H NMR (400 MHz, DMSO-d 6 )δ8.41(t,J=5.6Hz,1H),8.26(d,J=1.8Hz,1H),7.51(d,J=1.8Hz,1H),4.59(t,J=5.6Hz,1H),3. 62-3.54(m,2H),3.50-3.42(m,2H),3.23-3.18(m,2H),1.78-1.73(m,2H),1.12(t,J=7.0Hz,6H).

[0059] Figure 5 LCMS spectrum of compound I-2, MS (EI): m / z 630 (M+H + ).

[0060] Figure 6 It is the HPLC spectrum of compound I-2.

[0061] Depend on Figure 4-6 It can be concluded that the synthesized compound is a single target compound I-2 with a purity of >98%.

[0062] Preparation of compound I-3:

[0063]

[0064] Under nitrogen protection, compound VI-3 (2.0 equivalents), compound V-1 (1.0 equivalents, 50 g), HATU (1.5 equivalents) and anhydrous DMF (5000 mL) were added to a single-mouth reaction bottle in sequence, and after stirring and dissolving, triethylamine (3.0 equivalents) was slowly added to keep the reaction at room temperature. After the reaction of the raw materials was complete as monitored by TLC, 5000 mL of water was added to the reaction solution to quench the reaction, and then 5000 mL of ethyl acetate (EA) was added to extract and separate the layers. The organic phase was retained, washed three times with water (5000 mL × 3), dried over anhydrous sodium sulfate, and concentrated. After concentrating to a certain extent (about 300 mL EA was left), a large amount of solid precipitated. The temperature was lowered to -5 to 0 ° C, stirred to precipitate the solid, and then filtered, and the filter cake was rinsed with a small amount of cold EA. The filter cake was vacuum dried at 45 ° C for 2 h to obtain the target product I-3 (51.2 g, yield 83.7%, purity> 99%), which was a white solid with a melting point of 153-157 ° C; 1 H NMR (400 MHz, DMSO-d 6 )δ8.41(t,J=5.6Hz,1H),8.26(d,J=1.8Hz,1H),7.51(d,J=1.8Hz,1H),4.57(t,J=5.6Hz ,1H),3.28(s,6H),3.21-3.17(m,2H),1.81-1.77(m,2H),1.75-1.72(m,2H); MS(EI):m / z 616(M+H + ).

[0065] Preparation of compound I-4:

[0066]

[0067] Under nitrogen protection, compound VI-4 (1.5 equivalents), compound V-1 (1.0 equivalents, 50 g), HATU (1.5 equivalents) and anhydrous DMF (5000 mL) were added to a single-mouth reaction bottle in sequence, and after stirring and dissolving, triethylamine (3.0 equivalents) was slowly added to keep the reaction at room temperature. After TLC monitoring of the complete reaction of the raw materials, 5000 mL of water was added to the reaction solution to quench the reaction, and then 5000 mL of ethyl acetate (EA) was added to extract the layers. The organic phase was retained, washed three times with water (5000 mL × 3), dried over anhydrous sodium sulfate, and concentrated. After concentrating to a certain extent (about 300 mL EA was left), a large amount of solid precipitated. The temperature was lowered to -5 to 0 ° C, stirred to precipitate solid, and then filtered, and the filter cake was rinsed with a small amount of cold EA. The filter cake was vacuum dried at 45 ° C for 2 hours to obtain the target product I-4 (44.7 g, yield 71%, purity> 97%), which was a white solid with a melting point of 154-156 ° C; 1 H NMR (400 MHz, DMSO-d6 )δ8.41(t,J=5.6Hz,1H),8.26(d,J=1.8Hz,1H),7.51(d,J=1.8Hz,1H),4.57(t,J=5.6Hz ,1H),3.28(s,6H),3.20-3.16(m,2H),1.81-1.77(m,2H),1.77-1.70(m,4H); MS(EI):m / z 630(M+H + ).

[0068] Preparation of compound I-5:

[0069]

[0070] Under nitrogen protection, compound VI-5 (10.0 equivalents), compound V-1 (1.0 equivalents, 50 g), HATU (1.5 equivalents) and anhydrous DMF (5000 mL) were added to a single-mouth reaction bottle in sequence, and after stirring and dissolving, triethylamine (3.0 equivalents) was slowly added to keep the reaction at room temperature. After TLC monitoring of the complete reaction of the raw materials, 5000 mL of water was added to the reaction solution to quench the reaction, and then 5000 mL of ethyl acetate (EA) was added to extract the layers. The organic phase was retained, washed three times with water (5000 mL × 3), dried over anhydrous sodium sulfate, and concentrated. After concentrating to a certain extent (about 300 mL EA was left), a large amount of solid precipitated. The temperature was lowered to -5 to 0 ° C, stirred to precipitate the solid, and then filtered, and the filter cake was rinsed with a small amount of cold EA. The filter cake was vacuum dried at 45 ° C for 2 h to obtain the target product I-5 (40.5 g, yield 63%, purity> 95%), which was a white solid with a melting point of 145-147 ° C; 1 H NMR (400 MHz, DMSO-d 6 )δ8.42(t,J=5.6Hz,1H),8.27(d,J=1.8Hz,1H),7.52(d,J=1.8Hz,1H),4.58(t,J=5.6Hz,1H),3.2 9(s,6H),3.20-3.16(m,2H),1.81-1.77(m,2H),1.77-1.75(m,2H),1.74-1.70(m,4H); MS(EI):m / z 630(M+H + ).

[0071] Example 2 Analysis of stability in acid environment

[0072] High performance liquid analysis method: Agilent C18 alkyl silica gel column was used, the mobile phase was 0.1% phosphoric acid / methanol, the column was flushed at a flow rate of 1.0 ml / ml, and the detection wavelength was 245 nm.

[0073] Standard curve preparation:

[0074] Synthesis of Amide Impurity IV

[0075]

[0076] In a 500mL single-mouth reaction bottle, 2,3,5-triiodobenzoic acid (10g, 20.01mmol, 1.0eq) and anhydrous THF (200mL) were added in sequence and stirred to dissolve. Then, thionyl chloride (11.9g, 100.04mmol, 5.0eq) was slowly added dropwise under the condition of temperature control at 0℃. The temperature was raised to 55℃ and refluxed for 4h. After TLC monitoring (a small amount of the reaction solution was quenched with methanol), the reaction solution was directly concentrated to dryness to obtain an off-white acyl chloride solid. At the same time, in another 500mL single-mouth flask, ammonium hydroxide (30mL, relative density ρ=0.879(15℃, 28%NH 3 ), 26.37g, 1.56mol, 78eq), then cooled to -5~0℃, slowly dripped the prepared acyl chloride solution (dissolved the prepared acyl chloride solid with 200mL of anhydrous THF), precipitated solid while dripping, and after addition, a large amount of solid precipitated, continued to stir and react for 30min, sampled the reaction solution, sent to LC-MS, the reaction was complete, filtered, the filter cake was rinsed with water 1-2 times, the filtrate was evaporated to remove THF, solid precipitated, continued to filter, the solids filtered twice were combined, DCM refluxed and slurried, filtered again, and dried to obtain the target product 10.6g (yield ~100%). Compound IV is a white solid (purity 98.94%), melting point 275-277℃; 1 H NMR (400 MHz, DMSO-d 6 )δ8.25(d,J=1.9Hz,1H),7.89(s,1H),7.60(s,1H),7.52(d,J=1.9Hz,1H); MS(EI):m / z 500(M+H + ).

[0077] Compound IV of different concentrations was prepared and analyzed by the above-mentioned HPLC method, and a standard curve was prepared with the peak area as the abscissa and the compound concentration as the ordinate.

[0078] Sample treatment: Weigh 0.5 mg of the above-prepared compounds I-1 to I-5, dissolve in 10 ml of DMSO acid solution (9.9 ml DMSO + 0.1 ml methanesulfonic acid), place on a rotary mixer, mix and incubate for 6 h.

[0079] Analysis: Take 10 μL of the sample prepared by the above sample treatment, dilute the reaction solution 100 times with DMSO and test it with a high performance liquid chromatography, and convert the impurity amide content using the standard curve.

[0080] result:

[0081] Table 1: Compound stability test

[0082]

[0083] Analysis: From the results in Table 1, it can be concluded that when n=0, since there is only one C atom between the acetal and the nitrogen atom, the acetal group is relatively active and is hydrolyzed by acid to form compound III, which is further hydrolyzed by acid to form amide compound IV. As the C chain is extended, aldehyde compound III tends to be stable and is not easily decomposed into compound IV.

[0084] The mechanism of its hydrolysis reaction is as follows:

[0085]

[0086] Example 3 Preparation of embolic microspheres

[0087] In a 250mL three-necked flask equipped with an overhead mechanical stirrer, add 100mL of purified water, add about 15g of PVA (model 1888), heat to 95°C to dissolve, and cool to room temperature; add 0.7654g of N-(2,2-dimethoxyethyl)-2-acrylamide (NAAADA), followed by 10mL of concentrated hydrochloric acid, react at room temperature for 14 hours, and then use 2.5M sodium hydroxide solution to neutralize to pH = 7 to obtain a macromolecular polyvinyl alcohol monomer solution.

[0088] In a 1L three-necked flask equipped with an overhead mechanical stirrer, add 600mL of butyl acetate and 18g of cellulose acetate butyrate to dissolve to obtain an oil phase;

[0089] 8.61 g of acrylamido-2-methylpropanesulfonic acid sodium salt (AMPS sodium) was dissolved in 60 mL of water, 160 g of macromolecular polyvinyl alcohol monomer solution was added, and 1.5 g of potassium persulfate was added to obtain an aqueous phase.

[0090] The rotation speed was set to 400 rpm, and the aqueous phase was added dropwise to the oil phase; after the addition was completed, the temperature was raised to 55°C, 2.2 mL of tetramethylethylenediamine was added, and the reaction was continued for 8 hours. After a series of purification and drying, PVA embolic microspheres were obtained.

[0091] Example 4 Preparation of X-ray imaging microspheres

[0092] In a 250mL three-necked round-bottom flask equipped with an overhead stirrer and a thermometer, 4.0g of dry polyvinyl alcohol microspheres were added and swollen with 120mL of DMSO; 8g of compound I-1 or I-2 or I-3 or I-4 or I-5 were added, and 1mL of methanesulfonic acid was added to react at 60°C for 24h to obtain developing microspheres (i.e., wet microspheres). The iodine content of the obtained microspheres is shown in Table 2:

[0093] Table 2 Iodine content of microspheres

[0094]

[0095] By comparison, it can be seen that by increasing the carbon chain length, the amount of amide impurity IV generated during the reaction is significantly reduced, and the difficulty of cleaning is reduced. Due to the reduction of side reactions, more developers are bonded to the microspheres, thereby significantly increasing the iodine content of the developed microspheres. The carbon chain of compound I-5 is too long (n≥4), and due to the large volume of the developer molecule, the development modification efficiency is reduced, resulting in a decrease in the dry ball iodine content and the wet ball iodine content.

[0096] The applicant declares that the present invention uses the above-mentioned embodiments to illustrate the amide compounds containing iodinated aryl or iodinated heteroaryl groups and the preparation method and application thereof, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. An amide compound containing an iodinated aryl group, characterized in that: The compound has a structure shown in Formula I: Where R is C 1-6 Alkyl; n=1 or 2 or 3; X is selected from any one of the following groups: The wavy lines represent the attachment sites of the groups.

2. The amide compound containing an iodoaryl group according to claim 1, characterized in that: R is methyl, ethyl, n-propyl, isopropyl, n-butyl or n-hexyl.

3. The amide compound containing an iodoaryl group according to claim 1, characterized in that: The amide compound containing an iodinated aryl group is any one of the following compounds:

4. The method for preparing an amide compound containing an iodinated aryl group according to any one of claims 1 to 3, characterized in that: The preparation method comprises the following steps: The compound of formula V undergoes a condensation reaction with the compound of formula VI to obtain an amide compound containing an iodoaryl group as shown in formula I. The reaction formula is as follows: wherein the definitions of X, R, and n are the same as those in formula I.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the compound of formula VI to the compound of formula V is 1:1 to 10:

1.

6. The preparation method according to claim 4, characterized in that: The condensation reaction is carried out in the presence of a condensation agent.

7. The preparation method according to claim 6, characterized in that: The condensing agent is 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

8. The preparation method according to claim 4, characterized in that: The condensation reaction is carried out in the presence of an alkaline substance, and the alkaline substance is triethylamine, diisopropylethylamine, triethylenediamine or N-methylmorpholine.

9. The preparation method according to claim 4, characterized in that: The solvent for the condensation reaction is N,N-dimethylformamide or N,N-dimethylacetamide.

10. The preparation method according to claim 4, characterized in that: The temperature of the condensation reaction is room temperature, and the reaction time is 2-48 hours.

11. The preparation method according to claim 4, characterized in that: The condensation reaction is carried out under the protection of protective gas.

12. The preparation method according to claim 11, characterized in that: The condensation reaction was carried out under nitrogen protection.

13. An X-ray developing material, characterized in that: The X-ray developing material is prepared by using the amide compound containing iodinated aromatic groups as described in any one of claims 1 to 3 as developing molecules.

14. The X-ray developing material according to claim 13, characterized in that: The X-ray developing material is X-ray developing embolic microspheres.

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