An aryl urea compound, a preparation method and application thereof

Abstract

The present application relates to the technical field of pesticide chemicals, in particular to an aryl urea compound, a preparation method and application thereof. The aryl urea compound has the structural general formula: the aryl urea compound has excellent noctuidae control activity and outstanding miticidal activity, the mortality of the compound to Spodoptera exigua is up to 80% or more in the concentration range of 50 ppm to 200 ppm, the mortality of the compound to Tetranychus urticae is significantly better than that of the parent compound bromofenpyr-ethyl, and the compound still has good crop safety at high concentration, effectively overcoming the technical defects of the existing anthranilamide compounds, such as weak activity on leaf mite pests and easy to produce phytotoxicity at high concentration, and realizing efficient, low-toxic and environmentally friendly control on pests such as Spodoptera exigua, Prodenia litura, Tetranychus urticae and red spider mites.

Description

Technical Field

[0001] This invention relates to the field of pesticide chemicals technology, specifically to an arylurea compound, its preparation method, and its application. Background Technology

[0002] m-Diamide insecticides belong to the class of allosteric inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels. After GABA is released from synaptic cells, it binds to insect GABA receptors (GABA-R), activating chloride channels and causing chloride ion influx, thereby inhibiting insect neural activity. m-Diamide insecticides act on the allosteric sites of GABA-gated chloride channels, altering the channel conformation and preventing normal opening. This prevents chloride ion influx, leading to excessive excitation and convulsions in pests, ultimately resulting in death. A classic example of this insecticidal molecule is broflanilide (CAS 1207727-04-5), jointly developed by Mitsui Chemicals and BASF. In 2017, broflanilide was designated as a new category, Group 30, by the International Resistant Pesticides Action Committee (IRAC), primarily for controlling lepidopteran pests such as the beet armyworm, diamondback moth, cotton bollworm, and rice stem borer.

[0003] However, existing diamide compounds still have relatively weak activity against spider mites, with a mortality rate of only about 10% at a concentration of 50 ppm, which is far from meeting the needs of agricultural production. At the same time, when the application concentration is increased to 100 ppm or above, it is easy to cause phytotoxicity to crops, resulting in adverse consequences such as leaf burn and growth inhibition, which seriously restricts its application in integrated pest management. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides an arylurea compound, its preparation method, and its applications. The arylurea compounds of this invention are arylurea compounds formed by strategically introducing urea (-NH-CO-NH-) structural units into a m-diamid parent skeleton. An amide-urea hybrid system is constructed through a two-step reaction of "phenyl chloroformate activation-amine nucleophilic substitution." The effects of the urea nitrogen substituent (R) on the urea group are systematically investigated. 1 R 2 ), aromatic ring substituents (R) 3 R 4 ) and benzoyl substituent (R 5The structure-activity relationship of the aryl urea compounds in this invention was clearly established to influence their insecticidal and acaricidal activity. These compounds exhibit both excellent activity against beet armyworms and outstanding acaricidal activity. At concentrations ranging from 50 ppm to 200 ppm, they achieve a mortality rate of over 80% against beet armyworms and a significantly higher mortality rate against two-spotted spider mites than the parent compound bromonitrile dibenzodiamide (increasing the mortality rate from approximately 10% to over 80% at 50 ppm). Furthermore, they maintain good crop safety even at high concentrations. This effectively overcomes the technical shortcomings of existing meta-diamide compounds, which exhibit weak activity against spider mites and are prone to phytotoxicity at high concentrations. This invention achieves highly efficient, low-toxicity, and environmentally friendly control of pests such as beet armyworms, cotton bollworms, two-spotted spider mites, and spider mites.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The first objective of this invention is to provide an arylurea compound with the following general structural formula: , where R 1 R 2 Independently selected from hydrogen, C1~C5 alkyl, heteroaryl, R 1a Substituted C1~C5 alkyl or R 1a Substituted heteroaryl groups; wherein the heteroatom in the heteroaryl group is selected from at least one of N, O, and S; R 1a Selected from halogen, hydroxyl, cyano, nitro, -OR 1b -NR 1b -S(O)2R 1b or ;R 1b Selected from C1~C3 alkyl groups.

[0006] or R 1 R 2 It can be linked with N to form a 5-6 membered heteroalkyl ring or a substituted 5-6 membered heteroalkyl ring, wherein the substituents of the substituted 5-6 membered heteroalkyl ring are selected from methyl, oxygen or halogen.

[0007] R 3 Selected from hydrogen, C1~C5 alkyl or R 1c Substituted C1~C5 alkyl groups; wherein, R 1c Selected from halogens, cyano groups, C1-C3 alkoxy groups, and C3-C6 cycloalkyl groups; R 4 Selected from halogens or C1~C3 alkyl groups.

[0008] Preferred, R 1 Selected from C1~C3 alkyl, heteroaryl, R 1a Substituted C1~C3 alkyl or R 1a Substituted heteroaryl groups; wherein the heteroatoms in the heteroaryl group are N and S; R 1aSelected from fluorine, hydroxyl, cyano, nitro, -OCH3, -N(CH3)2, -S(O)2CH3 or ;R 2 Selected from hydrogen or C1~C3 alkyl groups.

[0009] In addition to N, the heteroatom in the 5-6 membered heteroalkane ring includes 0 or 1 additional heteroatom, wherein the additional heteroatom is selected from N or S, and the substituents in the substituted 5-6 membered heteroalkane ring are selected from methyl, oxygen, or fluorine; R 3 For hydrogen, R 1c Substituted C1~C3 alkyl groups; wherein, R 1c Selected from fluorine, cyano, methoxy, or cyclopropyl; R 4 Selected from fluorine or methyl.

[0010] Preferably, the arylurea compound is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0011] A second objective of this invention is to provide a method for preparing the above-mentioned arylurea compounds, comprising the following steps: S1. Compound I is reacted with phenyl chloroformate in the presence of solvent and base to generate an active ester intermediate; wherein, compound I is selected from... , , , , , or .

[0012] S2. Under the presence of solvent and base, the active ester intermediate is subjected to a substitution reaction with an amine compound to obtain an arylurea compound; wherein the amine compound is selected from trifluoroethylamine, 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride, 2-furanmethylamine, 2-methylsulfonylethylamine hydrochloride, 3-methoxypropylamine, 3-hydroxypropylamine, N,N-dimethylethylenediamine, 3-aminopropionitrile, dimethylamine, aniline, 2-fluoroaniline, 2-aminothiazole, piperidine, 4-methylpiperidine, 3-methylpiperidine, 3,5-dimethylpiperidine, 1-methylpiperazine, tetrahydrothiazole, thiomorpholine, m-chloroperoxybenzoic acid, or 4,4-difluoropiperidine.

[0013] Preferably, the molar ratio of compound I to phenyl chloroformate is 1:1.05~1.5.

[0014] Preferably, the molar ratio of the active ester intermediate to the amine compound is 1:2 to 13.

[0015] Preferably, when compound I reacts with phenyl chloroformate, the substitution reaction conditions are: reacting at 0℃~5℃ for 1h~12h.

[0016] Preferably, when the active ester intermediate reacts with the amine compound, the substitution reaction conditions are: reacting at 60℃~80℃ for 1h~12h.

[0017] A third objective of the present invention is a pesticide composition comprising an active ingredient and a pesticide-acceptable formulation carrier, wherein the active ingredient comprises the above-mentioned arylurea compound, or its stereoisomers, tautomers, pesticide-acceptable salts, or pesticide-acceptable solvates.

[0018] Preferably, the insect includes at least one of two-spotted spider mite, red spider mite, beet armyworm, and cotton bollworm.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention provides an arylurea compound with the following general structural formula: The aryl urea compounds of this invention possess both excellent activity against beet armyworms and outstanding acaricidal activity. At concentrations ranging from 50 ppm to 200 ppm, the mortality rate against beet armyworms is over 80%, and the mortality rate against two-spotted spider mites is significantly superior to that of the parent compound, bromfenacin (the mortality rate at 50 ppm increases from approximately 10% to over 80%). Furthermore, it maintains good crop safety even at high concentrations. This effectively overcomes the technical shortcomings of existing meta-diamid compounds, which exhibit weak activity against spider mites and are prone to phytotoxicity at high concentrations. It achieves highly efficient, low-toxicity, and environmentally friendly control of pests such as beet armyworms, cotton bollworms, two-spotted spider mites, and spider mites.

[0020] This is because the present invention strategically introduces urea (-NH-CO-NH-) structural units into the meta-diamid parent skeleton to form an amide-urea hybrid system, thereby changing the hydrogen bond donor / acceptor mode, conformational flexibility and lipophilic partition coefficient of the molecule, and enhancing the binding affinity and selectivity to the allosteric sites of insect GABA-gated chloride ion channels.

[0021] 2. This invention also provides a method for preparing aryl urea compounds. This invention constructs an amide-urea hybrid system through a two-step reaction of "phenyl chloroformate activation-amine nucleophilic substitution," and systematically investigates the effects of substituents on the nitrogen atom of the urea group (R...). 1 R 2 ), aromatic ring substituents (R) 3 R 4 ) and benzoyl substituent (R 5 The effect of this invention on insecticidal and acaricidal activity was investigated, and a clear structure-activity relationship was established. The preparation method of this invention has mild reaction conditions, is simple to operate, and the product is easy to separate and purify. It is suitable for the synthesis of arylurea compounds with various substituents, with high yields (49%~91%), and is convenient for industrial production. Detailed Implementation

[0022] The technical solution of the present invention will be clearly and completely described below with reference to the data in the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0023] It should be noted that the technical terms used in this invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all raw materials, reagents, instruments and equipment used in the following embodiments of this invention can be purchased on the market or prepared by existing methods.

[0024] In existing technologies, m-diamide insecticides (such as brofenoxam) are allosteric inhibitors of γ-aminobutyric acid-gated chloride channels. Although they have good control effects on lepidopteran pests, the diamide skeleton in their molecular structure results in weak activity against spider mites. At a concentration of 50 ppm, their mortality rate is only about 10%, which is difficult to meet the needs of integrated pest management in agricultural production. At the same time, when the application concentration is increased to 100 ppm or above, it is easy to cause phytotoxicity to crops, resulting in adverse consequences such as leaf burn and growth inhibition, which seriously restricts the application scope of this type of compound.

[0025] To address the problems existing in the prior art, the present invention provides a structural formula as follows: This study focuses on aryl urea compounds with amide-urea hybrid skeletons and optimized substituent combinations. By strategically introducing urea (-NH-CO-NH-) structural units into the m-diamid parent compound, the hydrogen bond donor / acceptor mode, conformational flexibility, and lipophilic partition coefficient of the molecule are altered. A two-step reaction involving "phenyl chloroformate activation—amine nucleophilic substitution" is employed to achieve efficient urea bond construction. The effects of chain-like substituents on the nitrogen atom of the urea group (such as trifluoroethyl, methyl sulfone ethyl, furanyl methyl, etc.), cyclic amine groups (such as piperidine, piperazine, thiomorpholine, etc.), and aromatic ring / benzoyl substituents on the activity are systematically screened. A "R" model is established. 1 When the structure is chain-like, its acaricidal activity is superior to that of aromatic ring structures and R. 3 The introduction of this compound reduces acaricidal activity, thus overcoming the technical shortcomings of existing metadiamide compounds, such as weak activity against spider mites and easy phytotoxicity at high concentrations. This enables highly efficient, low-toxicity, and environmentally friendly control of pests such as beet armyworm, cotton bollworm, two-spotted spider mite, and spider spider.

[0026] To enable those skilled in the art to more clearly understand the technical solution of the present invention, the following will provide a detailed description in conjunction with specific embodiments: Example 1 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL01-01 (MW=540, 54.00 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL01-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL01-02 (MW=660, 42.00 g), with a yield of 64%.

[0027] S2. At room temperature, XL01-02 (MW=660, 6.60 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and trifluoroethylamine (MW=99, 1.29 g, 0.013 mol) was added. The temperature was raised to 40 °C. The reaction process was monitored by liquid chromatography. When the content of XL01-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL01 (MW=665, 4.23 g), with a yield of 64%.

[0028] MS (ESI, m / z): 664.00 [MH]- . 1 H NMR (400 MHz, DMSO) δ 10.64 (s, 1H), 8.41 (s, 1H), 8.09 (s, 1H), 7.95 (s, 1H), 7.85 (s, 1H), 7.29 (s, 2H), 7.15 (s, 1H), 3.95 (s, 2H), 2.28 (s, 3H).

[0029] Example 2 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL01-02 (MW=660, 6.60 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (MW=192, 2.50 g, 0.013 mol), and the mixture was heated to 40 °C. The reaction was monitored by liquid chromatography, and when the content of XL01-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL02 (MW=722, 5.67 g), with a yield of 79%.

[0030] MS (ESI, m / z): 721.00 [MH] - . 1 H NMR (400 MHz, DMSO)δ 10.62 (s, 1H),8.63 (s, 1H), 8.41 (s, 1H), 8.11 (s, 1H), 7.95 (s, 1H), 7.91 (d, J = 5.8 Hz,1H), 7.25 (s, 2H), 6.89 (s, 1H), 3.94 (s, 2H), 3.84 (s, 2H), 2.28 (s, 3H).

[0031] Example 3 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL01-02 (MW=660, 6.60 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methyl sulfone ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 40 °C. The reaction was monitored by liquid chromatography, and when the content of XL01-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL03 (MW=689, 4.10 g), with a yield of 60%.

[0032] MS (ESI, m / z): 688.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ 10.60 (s, 1H), 8.39 (s, 1H), 8.04 (s, 1H), 7.94 (s, 1H), 7.89 – 7.80 (m, 1H), 7.25 (d, J =4.5 Hz, 2H), 6.77 (t, J = 5.7 Hz, 1H), 3.54 (q, J = 6.2 Hz, 2H), 3.31 (d, J =6.4 Hz, 2H), 3.02 (s, 3H), 2.26 (s, 3H).

[0033] Example 4 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL01-02 (MW=660, 6.60 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-furanylamine (MW=97, 1.26 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL01-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL04 (MW=663, 4.66 g), with a yield of 70%.

[0034] MS (ESI, m / z): 662.00 [MH] - . 1H NMR (400 MHz, DMSO)δ 10.62 (s, 1H), 8.40 (s, 1H), 7.95 (s, 2H), 7.88 (s, 1H), 7.60 (s, 1H), 7.25 (s, 2H), 6.99 (s, 1H), 6.40 (s, 1H), 6.29 (s, 1H), 4.31 (d, J = 3.8 Hz, 2H), 2.27 (s, 3H).

[0035] Example 5 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL05-01 (MW=544, 54.40 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL05-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL05-02 (MW=664, 46.10 g), with a yield of 69%.

[0036] S2. At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and trifluoroethylamine (MW=99, 1.29 g, 0.013 mol) was added. The temperature was raised to 60 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL05 (MW=669, 4.76 g), with a yield of 71%.

[0037] MS (ESI, m / z): 668.00 [MH] - . 1 H NMR (400 MHz, DMSO)δ 10.68 (s, 1H),8.81 (s, 1H), 8.40 (s, 1H), 8.27 (s, 1H), 7.95 (s, 1H), 7.37 – 7.14 (m, 3H),4.14 – 3.85 (m, 2H).

[0038] Example 6 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (MW=192, 2.50 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL06 (MW=726, 5.88 g), with a yield of 81%.

[0039] MS (ESI, m / z): 725.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.68 (s, 1H), 8.85 (d, J = 2.4 Hz, 1H), 8.65 (t, J = 6.3 Hz, 1H), 8.40 (s, 1H), 8.30 (td, J= 7.6, 4.1 Hz, 1H), 7.94 (s, 1H), 7.31 – 7.12 (m, 2H), 7.02 (t, J = 5.5 Hz, 1H), 4.00 – 3.87 (m, 2H), 3.85 (d, J = 5.5 Hz, 2H).

[0040] Example 7 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL07 (MW=693, 4.10 g), with a yield of 60%.

[0041] MS (ESI, m / z): 692.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.65 (s, 1H),8.80 (d, J = 1.9 Hz, 1H), 8.40 (s, 1H), 8.37 – 8.28 (m, 1H), 7.95 (s, 1H),7.29 – 7.15 (m, 2H), 6.91 (t, J = 5.9 Hz, 1H), 3.56 (q, J = 6.2 Hz, 2H), 3.32 (d, J = 6.4 Hz, 2H), 3.02 (s, 3H).

[0042] Example 8 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 3-methoxypropylamine (MW=89, 1.16 g, 0.013 mol) was added. The mixture was heated to 60 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL08 (MW=659, 3.89 g), with a yield of 59%.

[0043] MS (ESI, m / z): 658.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ 10.66 (s, 1H),8.52 (s, 1H), 8.40 (s, 1H), 8.32 (dd, J = 10.4, 5.1 Hz, 1H), 7.94 (s, 1H),7.27 – 7.12 (m, 2H), 6.68 (t, J = 5.6 Hz, 1H), 3.35 (t, J = 6.2 Hz, 2H), 3.23(s, 3H), 3.14 (q, J = 6.5 Hz, 2H), 1.65 (p, J = 6.5 Hz, 2H).

[0044] Example 9 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 3-hydroxypropylamine (MW=75, 0.98 g, 0.013 mol) was added. The mixture was heated to 60 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL09 (MW=645, 3.77 g), with a yield of 58%.

[0045] MS (ESI, m / z): 645.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ 10.66 (s, 1H), 8.54 (s, 1H), 8.40 (s, 1H), 8.33 (t, J = 6.8 Hz, 1H), 7.94 (s, 1H), 7.31 –7.09 (m, 2H), 6.68 (t, J = 5.4 Hz, 1H), 4.49 (t, J = 5.1 Hz, 1H), 3.45 (q, J= 6.0 Hz, 2H), 3.16 (q, J = 6.4 Hz, 2H), 1.58 (p, J = 6.4 Hz, 2H).

[0046] Example 10 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by N,N-dimethylethylenediamine (MW=88, 1.14 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL10 (MW=658, 3.96 g), with a yield of 60%.

[0047] MS (ESI, m / z): 659.00 [M+H] + .1 H NMR (400 MHz, DMSO) δ 10.64 (s, 1H), 8.69 (s, 1H), 8.40 (s, 1H), 8.32 (t, J = 6.8 Hz, 1H), 7.94 (s, 1H), 7.27 –7.09 (m, 2H), 6.73 (t, J = 5.1 Hz, 1H), 3.18 (q, J = 5.8 Hz, 2H), 2.31 (t, J= 6.1 Hz, 2H), 2.16 (s, 6H).

[0048] Example 11 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 3-aminopropionitrile (MW=70, 0.91 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL11 (MW=640, 3.45 g), with a yield of 54%.

[0049] MS (ESI, m / z): 639.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.68 (s, 1H),8.74 (d, J = 1.6 Hz, 1H), 8.41 (s, 1H), 8.36 – 8.23 ​​(m, 1H), 7.95 (s, 1H),7.29 – 7.16 (m, 2H), 6.99 (t, J = 5.9 Hz, 1H), 3.37 (q, J = 6.2 Hz, 2H), 2.69 (t, J = 6.3 Hz, 2H).

[0050] Example 12 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL) at room temperature, anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 33% dimethylamine aqueous solution (MW=45, 5.00 g, 0.036 mol) was added. The reaction was carried out at room temperature. The reaction progress was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, water (20 mL) was slowly added to the reaction solution. The mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL12 (MW=615, 4.54 g), with a yield of 74%.

[0051] MS (ESI, m / z): 614.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.63 (s, 1H),8.40 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.67 (td, J = 7.8, 1.5 Hz, 1H),7.45 – 7.35 (m, 1H), 7.25 (t, J = 7.9 Hz, 1H), 2.93 (s, 6H).

[0052] Example 13 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-furanylamine (MW=97, 1.26 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL13 (MW=667, 4.32 g), with a yield of 65%.

[0053] MS (ESI, m / z): 666.00 [MH] - . 1H NMR (400 MHz, DMSO) δ10.67 (s, 1H),8.61 (d, J = 2.4 Hz, 1H), 8.41 (s, 1H), 8.32 (td, J = 7.5, 2.4 Hz, 1H), 7.95(s, 1H), 7.59 (d, J = 1.0 Hz, 1H), 7.29 – 7.16 (m, 2H), 7.06 (t, J = 5.6 Hz, 1H), 6.40 (dd, J = 3.0, 1.9 Hz, 1H), 6.27 (d, J = 3.0 Hz, 1H), 4.32 (d, J =5.6 Hz, 2H).

[0054] Example 14 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) and aniline (MW=93, 1.21 g, 0.013 mol) were added, and the mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL14 (MW=663, 5.46 g), with a yield of 82%.

[0055] MS (ESI, m / z): 662.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.70 (s, 1H),9.11 (s, 1H), 8.78 (d, J = 2.6 Hz, 1H), 8.41 (s, 1H), 8.36 (td, J = 7.6, 3.0Hz, 1H), 7.96 (s, 1H), 7.46 (d, J = 7.7 Hz, 2H), 7.34 – 7.22 (m, 4H), 6.99 (t, J = 7.4 Hz, 1H).

[0056] Example 15 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 2-fluoroaniline (MW=111, 1.44 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL15 (MW=681, 6.21 g), with a yield of 91%.

[0057] MS (ESI, m / z): 680.00 [MH] - . 1 H NMR (400 MHz, DMSO)δ 10.72 (s, 1H), 9.28 (d, J = 1.8 Hz, 1H), 9.11 (s, 1H), 8.47 – 8.33 (m, 2H), 8.18 (t, J = 7.7Hz, 1H), 7.96 (s, 1H), 7.34 – 7.26 (m, 2H), 7.24 (dd, J = 10.9, 8.9 Hz, 1H), 7.14 (t, J = 7.7 Hz, 1H), 7.07 – 6.95 (m, 1H).

[0058] Example 16 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-aminothiazole (MW=100, 1.30 g, 0.013 mol), and the mixture was heated to 80 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL16 (MW=670, 5.17 g), with a yield of 77%.

[0059] MS (ESI, m / z): 669.00 [MH] - . 1H NMR (400 MHz, DMSO)δ10.74 (s, 1H),9.19 (s, 1H), 8.41 (s, 1H), 8.34 (td, J = 7.5, 3.9 Hz, 1H), 7.96 (s, 1H),7.41 – 7.38 (m, 2H), 7.34 (s, 1H), 7.15 (t, J = 2.9 Hz, 2H).

[0060] Example 17 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL17-01 (MW=626, 62.60 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction was monitored by liquid chromatography. When the content of compound XL17-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL17-02 (MW=746, 49.31 g), with a yield of 66%.

[0061] S2. At room temperature, XL17-02 (MW=746, 7.46 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL17-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to give compound XL17 (MW=775, 4.41 g), with a yield of 57%. MS (ESI, m / z): 774.00 [MH] - .

[0062] Example 18 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL18-01 (MW=608, 60.80 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL18-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL18-02 (MW=728, 35.89 g), with a yield of 49%.

[0063] S2. At room temperature, XL18-02 (MW=728, 7.28 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography. When the content of XL18-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL18 (MW=757, 3.36 g), with a yield of 44%. MS (ESI, m / z): 756.00 [MH] - .

[0064] Example 19 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL19-01 (MW=583, 58.30 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL19-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL19-02 (MW=703, 38.59 g), with a yield of 55%.

[0065] S2. At room temperature, XL19-02 (MW=703, 7.03 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography. When the content of XL19-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL19 (MW=732, 3.55 g), with a yield of 48%. MS (ESI, m / z): 731.00 [MH] - .

[0066] Example 20 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL20-01 (MW=602, 60.20 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 5 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL20-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL20-02 (MW=722, 33.23 g), with a yield of 46%.

[0067] S2. At room temperature, XL20-02 (MW=722, 7.22 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography. When the content of XL20-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL20 (MW=751, 3.35 g), with a yield of 45%. MS (ESI, m / z): 750.00 [MH] - .

[0068] Example 21 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: S1. At room temperature, compound XL21-01 (MW=598, 59.80 g, 0.10 mol) was dispersed in dichloromethane (200 mL), and pyridine (MW=79, 11.85 g, 0.15 mol) was added. The mixture was cooled to 0 °C, and phenyl chloroformate (MW=156, 18.72 g, 0.12 mol) was added dropwise. The reaction process was monitored by liquid chromatography. When the content of compound XL21-01 was less than 1%, the mixture was filtered, the filter cake was washed with water, and dried at 60 °C to obtain compound XL21-02 (MW=718, 41.55 g), with a yield of 58%.

[0069] S2. At room temperature, XL21-02 (MW=718, 7.18 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 2-methylsulfonyl ethylamine hydrochloride (MW=159, 2.08 g, 0.013 mol), and the mixture was heated to 60 °C. The reaction was monitored by liquid chromatography, and when the content of XL21-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL21 (MW=747, 4.61 g), with a yield of 62%. MS (ESI, m / z): 746.00 [MH] - .

[0070] Example 22 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and piperidine (MW=85, 1.11 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL22 (MW=655, 4.35 g), with a yield of 66%.

[0071] MS (ESI, m / z): 654.00 [MH] - . 1H NMR (400 MHz, DMSO) δ10.65 (s, 1H), 8.40 (d, J = 14.7 Hz, 2H), 7.95 (s, 1H), 7.62 (t, J = 7.7 Hz, 1H), 7.38 (d, J = 5.8 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 3.41 (s, 4H), 1.53 (d, J = 31.1 Hz, 6H).

[0072] Example 23 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 4-methylpiperidine (MW=99, 1.23 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL23 (MW=669, 4.77 g), with a yield of 71%.

[0073] MS (ESI, m / z): 668.00 [MH] - . 1 H NMR (400 MHz, DMSO)δ8.40 (d, J = 8.7Hz, 2H), 7.95 (s, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.38 (d, J = 5.9 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 4.07 (d, J = 13.4 Hz, 2H), 2.78 (t, J = 12.6 Hz,2H), 1.62 (d, J = 13.7 Hz, 2H), 1.56 (s, 1H), 1.04 (d, J = 12.8 Hz, 2H), 0.91(d, J = 6.0 Hz, 3H).

[0074] Example 24 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 3-methylpiperidine (MW=99, 1.23 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL24 (MW=669, 4.85 g), with a yield of 72%.

[0075] MS (ESI, m / z): 668.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.65 (s, 1H), 8.40 (d, J = 11.2 Hz, 2H), 7.95 (s, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.39 (t, J= 6.8 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 3.98 (t, J = 11.0 Hz, 2H), 3.15 (d,J = 5.0 Hz, 1H), 2.76 (t, J = 12.0 Hz, 1H), 1.75 (d, J = 12.2 Hz, 1H), 1.62(d, J = 13.7 Hz, 1H), 1.52 (s, 1H), 1.46 – 1.32 (m, 1H), 1.10 (t, J = 12.0Hz, 1H), 0.86 (d, J = 6.5 Hz, 3H).

[0076] Example 25 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 3,5-dimethylpiperidine (MW=113, 1.47 g, 0.013 mol), and the mixture was heated to 80 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL25 (MW=683, 4.26 g), with a yield of 62%.

[0077] MS (ESI, m / z): 682.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.64 (s, 1H), 8.40 (s, 2H), 7.94 (s, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.39 (t, J = 6.6 Hz, 1H), 7.24 (t, J = 7.7 Hz, 1H), 4.06 (d, J = 12.5 Hz, 2H), 3.15 (d, J = 5.2Hz, 1H), 2.25 (t, J = 12.2 Hz, 2H), 1.76 (d, J = 13.1 Hz, 1H), 1.53 (s, 2H), 0.85 (d, J = 6.5 Hz, 6H).

[0078] Example 26 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and 1-methylpiperazine (MW=100, 1.30 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL26 (MW=670, 3.31 g), with a yield of 49%.

[0079] MS (ESI, m / z): 669.00 [MH] - . 1H NMR (400 MHz, DMSO) δ10.65 (s, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 7.95 (s, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.40 (t,J = 6.5 Hz, 1H), 7.26 (t, J = 7.7 Hz, 1H), 3.44 (s, 4H), 2.31 (s, 4H), 2.19 (s, 3H).

[0080] Example 27 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and tetrahydrothiazole (MW=89, 1.16 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL27 (MW=659, 3.20 g), with a yield of 49%.

[0081] MS (ESI, m / z): 658.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.69 (s, 1H), 8.56 (s, 1H), 8.42 (s, 1H), 7.95 (s, 1H), 7.68 (t, J = 7.6 Hz, 1H), 7.43 (t,J = 6.7 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H), 4.54 (s, 2H), 3.72 (t, J = 6.1 Hz, 2H), 3.05 (t, J = 6.2 Hz, 2H).

[0082] Example 28 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, and thiomorpholine (MW=103, 1.34 g, 0.013 mol) was added. The mixture was heated to 80 °C. The reaction process was monitored by liquid chromatography. When the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to obtain compound XL28 (MW=673, 3.89 g), with a yield of 58%.

[0083] MS (ESI, m / z): 672.00 [MH] - . 1 H NMR (400 MHz, DMSO) δ10.66 (s, 1H), 8.51 (s, 1H), 8.41 (s, 1H), 7.95 (s, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.42 (t,J = 6.5 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 3.73 (s, 4H), 2.60 (s, 4H).

[0084] Example 29 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: XL28 (MW=673, 0.673 g, 0.001 mol) was dissolved in dichloroethane (10 mL) at room temperature, and m-chloroperoxybenzoic acid (MW=172, 2.12 g, 0.0013 mol) was added. The reaction was carried out at room temperature. The reaction progress was monitored by liquid chromatography, and the reaction was terminated when the content of XL28 was less than 1%. The organic phase was filtered, washed with saturated sodium carbonate solution and water, concentrated to dryness, and dried at 60 °C to give compound XL29 (MW=689, 0.421 g), with a yield of 61%. MS (ESI, m / z): 688.00 [MH] - .

[0085] Example 30 A method for preparing arylurea compounds, the technical route of which is as follows: This includes the following steps: At room temperature, XL05-02 (MW=664, 6.64 g, 0.01 mol) was dissolved in N,N-dimethylformamide (10 mL), anhydrous sodium carbonate (MW=106, 2.12 g, 0.02 mol) was added, followed by 4,4-difluoropiperidine (MW=121, 1.57 g, 0.013 mol), and the mixture was heated to 80 °C. The reaction was monitored by liquid chromatography, and when the content of XL05-02 was less than 1%, the mixture was cooled to room temperature. Water (20 mL) was slowly added to the reaction solution, and the mixture was filtered. The filter cake was washed with water and dried at 60 °C to give compound XL30 (MW=691, 5.32 g), with a yield of 77%. MS (ESI, m / z): 690.00 [MH] - .

[0086] application: Taking the arylurea compounds of Examples 1 to 30 as examples, their properties were studied, as follows: ① Study on the activity of beet armyworm: Take 0.05g of the aryl urea compound to be tested, dissolve it in DMSO (1.00g) to prepare a stock solution with a concentration of 50,000ppm; dilute the stock solution with water to different concentrations (50ppm, 100ppm, 200ppm), immerse laboratory-cultured pakchoi leaves in it, remove the leaves and air dry them after about 5 to 10 seconds, and feed the leaves to beet armyworm larvae (4th instar), 10 larvae per group, and record the number of larvae that died after 24 hours.

[0087] ② Activity study of the two-spotted spider mite: Take 0.05 g of the aryl urea compound to be tested, dissolve it in DMSO (1.00 g) to prepare a stock solution with a concentration of 50,000 ppm. Dilute the stock solution with water to different concentrations (50 ppm, 100 ppm, 200 ppm), immerse laboratory-cultured kidney bean leaves in it, remove the leaves after about 5 to 10 seconds, and air dry them. Place the leaves in a petri dish (4 leaves / dish); place two-spotted spider mites on the leaf surface (5 mites / leaf), 20 mites per group, and record the number of dead two-spotted spider mites after 48 hours.

[0088] The bioactivity test results of the arylurea compounds in Examples 1 to 30 of this invention are shown in Table 1. The arylurea compounds exhibit significant killing activity against the two-spotted spider mite. 1 The group with a chain-like structure has better activity against mites than Broflanilide; R 1 The aromatic ring group has poor reactivity and can no longer meet the application requirements; R 3 The introduction of the group reduces the acaricidal activity, but still meets the usage requirements.

[0089] Table 1. Results of bioactivity tests on the compounds in the examples. In the table, A represents a mortality rate of 80% to 100%, B represents a mortality rate of 50% to 79%, and C represents a mortality rate of 0% to 49%.

[0090] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range, as well as any value between the two endpoints, can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described here to avoid redundancy. Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of this invention.

Claims

1. An arylurea compound, characterized in that, The general structural formula of arylurea compounds is: , where R 1 R 2 Independently selected from hydrogen, C1~C5 alkyl, heteroaryl, R 1a Substituted C1~C5 alkyl or R 1a Substituted heteroaryl groups; wherein the heteroatom in the heteroaryl group is selected from at least one of N, O, and S; R 1a Selected from halogen, hydroxyl, cyano, nitro, -OR 1b -NR 1b -S(O)2R 1b or ;R 1b Selected from C1~C3 alkyl groups; or R 1 R 2 It can be connected with N to form a 5-6 membered heteroalkyl ring or a substituted 5-6 membered heteroalkyl ring, wherein the substituents of the substituted 5-6 membered heteroalkyl ring are selected from methyl, oxygen or halogen; R 3 Selected from hydrogen, C1~C5 alkyl or R 1c Substituted C1~C5 alkyl groups; wherein, R 1c Selected from halogens, cyano groups, C1-C3 alkoxy groups, and C3-C6 cycloalkyl groups; R 4 Selected from halogens or C1~C3 alkyl groups.

2. The arylurea compound according to claim 1, characterized in that, R 1 Selected from C1~C3 alkyl, heteroaryl, R 1a Substituted C1~C3 alkyl or R 1a Substituted heteroaryl groups; In this heteroaryl group, the heteroatoms are N and S; R 1a Selected from fluorine, hydroxyl, cyano, nitro, -OCH3, -N(CH3)2, -S(O)2CH3 or ; R 2 Selected from hydrogen or C1-C3 alkyl groups; In addition to N, the heteroatom in the 5-6 membered heteroalkane ring includes 0 or 1 additional heteroatom, wherein the additional heteroatom is selected from N or S, and the substituents in the substituted 5-6 membered heteroalkane ring are selected from methyl, oxygen, or fluorine; R 3 For hydrogen, R 1c Substituted C1~C3 alkyl groups; wherein, R 1c Selected from fluorine, cyano, methoxy, or cyclopropyl; R 4 Selected from fluorine or methyl.

3. The arylurea compound according to claim 1, characterized in that, The arylurea compounds are selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , or .

4. A method for preparing the arylurea compound according to claim 1, characterized in that, Includes the following steps: Compound I was subjected to a substitution reaction with phenyl chloroformate in the presence of solvent and base to generate an active ester intermediate. In the presence of solvent and base, the active ester intermediate is subjected to a substitution reaction with an amine compound to obtain arylurea compounds; Compound I is selected from , , , , , or ; The amine compounds are selected from trifluoroethylamine, 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride, 2-furanmethylamine, 2-methylsulfonylethylamine hydrochloride, 3-methoxypropylamine, 3-hydroxypropylamine, N,N-dimethylethylenediamine, 3-aminopropionitrile, dimethylamine, aniline, 2-fluoroaniline, 2-aminothiazole, piperidine, 4-methylpiperidine, 3-methylpiperidine, 3,5-dimethylpiperidine, 1-methylpiperazine, tetrahydrothiazole, thiomorpholine, m-chloroperoxybenzoic acid, or 4,4-difluoropiperidine.

5. The method for preparing arylurea compounds according to claim 4, characterized in that, The molar ratio of compound I to phenyl chloroformate is 1:1.05~1.

5.

6. The method for preparing arylurea compounds according to claim 4, characterized in that, The molar ratio of the active ester intermediate to the amine compound is 1:2~13.

7. The method for preparing arylurea compounds according to claim 4, characterized in that, When compound I reacts with phenyl chloroformate, the substitution reaction conditions are: reaction at 0℃~5℃ for 1h~12h.

8. The method for preparing arylurea compounds according to claim 4, characterized in that, When reactive ester intermediates react with amine compounds, the substitution reaction conditions are: reaction at 60℃~80℃ for 1h~12h.

9. A pesticide composition, characterized in that, The pesticide composition comprises an active ingredient and a pesticide-acceptable formulation carrier, wherein the active ingredient comprises an arylurea compound as described in any one of claims 1 to 3, or a stereoisomer, tautomer, pesticide-acceptable salt, or pesticide-acceptable solvate thereof.

10. The pesticide composition according to claim 9, characterized in that, The pesticide composition is used to control insects, and the insects are selected from at least one of two-spotted spider mites, spider mites, beet armyworms, and cotton bollworms.

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