A pyrazolopyrimidinone derivative containing an aniline unit, its preparation method and application

Abstract

This invention belongs to the field of pesticides and discloses a compound having the structure of Formula I. The preparation method is as follows: ethyl 5-amino-1-methylpyrazole-4-carboxylate undergoes three reactions in sequence: hydrolysis, amidation, and cyclization, to obtain the pyrazolopyrimidinone derivative containing the aniline unit. This pyrazolopyrimidinone derivative containing the aniline unit is a novel compound that has inhibitory effects on Fusarium wilt, Sheath blight, and Botrytis cinerea, and can be used to control plant diseases caused by fungi.

Description

Technical Field

[0001] This invention belongs to the field of pesticides, and specifically relates to a pyrazolopyrimidinone derivative containing an aniline unit, its preparation method, and its application. Background Technology

[0002] Plant fungal diseases are a significant factor affecting crop yield and quality, causing enormous agricultural losses globally. Therefore, timely and effective control of crop fungal diseases is crucial for ensuring smooth agricultural production. Currently, chemical control remains the primary method for controlling plant fungal diseases. However, the long-term use of fungicides such as boscalid, azoxystrobin, and carbendazim has led to severe resistance in plant pathogenic fungi. Therefore, there is an urgent need to develop novel, green fungicides with novel molecular structures and unique mechanisms of action. Summary of the Invention

[0003] Objectives of the Invention: The first objective of this invention is to provide a pyrazolopyrimidinone derivative containing an aniline unit that has an inhibitory effect on plant pathogenic fungal diseases; the second objective of this invention is to provide a method for preparing the pyrazolopyrimidinone derivative containing an aniline unit; and the third objective of this invention is to provide the application of the pyrazolopyrimidinone derivative containing an aniline unit in the prevention and control of plant pathogenic fungal diseases.

[0004] Technical solution: The present invention provides a pyrazolopyrimidinone derivative containing an aniline unit, the structural formula of which is shown in Figure I:

[0005]

[0006] Among them, R 1 It is selected from hydrogen, 2-methyl, 3-methyl, 4-methyl, 2,4-dimethyl, 2-chloro, 3-chloro, 4-chloro, 2,4-dichloro, 3,4-dichloro, 3,5-dichloro, 2-fluoro, 4-fluoro, 2,4-difluoro, 2-bromo, or 2-methoxy.

[0007] The method for preparing pyrazolopyrimidinone derivatives containing aniline units according to the present invention involves hydrolyzing ethyl 5-amino-1-methylpyrazol-4-carboxylate in 5% sodium hydroxide solution, followed by reaction with substituted phenylhydrazine in dichloromethane containing triethylamine and TBTU. The resulting hydrazine molecule undergoes a cyclization reaction with triethyl orthoformate in hot ethanol to obtain the pyrazolopyrimidinone derivatives containing aniline units. The synthetic route is as follows:

[0008]

[0009] The application of the pyrazolopyrimidinone derivative containing aniline units described in this invention in the prevention and control of plant pathogenic fungal diseases.

[0010] The plant pathogenic fungi mentioned are Fusarium graminearum, Rhizoctonia solani, and Gray mold of tomato.

[0011] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) The pyrazolopyrimidinone derivative containing aniline unit of the present invention is a new type of compound that has an inhibitory effect on wheat scab, rice sheath blight or tomato gray mold; (2) The preparation method of the pyrazolopyrimidinone derivative containing aniline unit of the present invention is simple, the raw materials are readily available, and the reaction is novel and efficient; (3) The pyrazolopyrimidinone derivative containing aniline unit of the present invention can significantly inhibit wheat scab, and its optimal inhibition rate at a dose of 50 μg / mL is 91.63%, which has the application prospect of being developed as a potential agricultural fungicide. Attached Figure Description

[0012] Figure 1 The photon spectrum of the pyrazolopyrimidinone derivative containing an aniline unit prepared in Example 1;

[0013] Figure 2 The carbon spectrum of the pyrazolopyrimidinone derivative containing an aniline unit prepared in Example 1;

[0014] Figure 3 Here is a high-resolution mass spectrum of the pyrazolopyrimidinone derivative containing an aniline unit prepared in Example 1;

[0015] Figure 4 The graph shows the effect of the pyrazolopyrimidinone derivative containing aniline units prepared in Example 13 on inhibiting wheat scab at different dosage concentrations. Detailed Implementation

[0016] The technical solution of the present invention will be further described below with reference to the embodiments.

[0017] Example 1

[0018] The pyrazolopyrimidin-4-one derivative I1 containing an aniline unit described in this invention, R1=H, has the chemical name 1-methyl-5-(phenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(phenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0019]

[0020] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0021]

[0022] Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (18 mmol) and 5% NaOH solution (10 mL) were added to 100 mL of ethanol and heated to 75–80 °C for about 4–5 h. After the starting material disappeared as monitored by TLC, the mixture was allowed to stand overnight, producing a large amount of white flocculent matter. After filtration, the filter cake was dissolved in water, and the pH of the system was adjusted to 5–6 with 5% HCl solution, precipitating a large amount of white solid. After filtration and drying, the resulting filter cake yielded 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A).

[0023] Step 2: Synthesis of 5-amino-1-methyl-N′-phenyl-1H-pyrazole-4-carboxylhydrazide (intermediate B1)

[0024]

[0025] In a 100 mL round-bottom flask, 7 mmol of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid, 7 mmol of phenylhydrazine, 8 mmol of TBTU condensing agent, and 30 mL of dichloromethane were added sequentially, and the mixture was stirred at room temperature for about 30 min. Then, 1 mL of triethylamine was added dropwise to the mixture, and stirring continued at room temperature. After the reactants disappeared as monitored by TLC, excess solvent was removed by vacuum distillation. The residue was purified by thin-layer chromatography to obtain 5-amino-1-methyl-N′-phenyl-1H-pyrazole-4-carboxyhydrazide (intermediate B1).

[0026] Step 3: Synthesis of 1-methyl-5-(aniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I1)

[0027] 5-Amino-1-methyl-N′-phenyl-1H-pyrazole-4-carboxylhydrazide (2 mmol) and triethyl orthoformate (6 mmol) were dissolved in anhydrous ethanol (30 mL), and then heated to 75–80 °C for about 4–5 h. After the starting material disappeared as monitored by TLC, the mixture was allowed to stand overnight, and a large amount of white solid precipitated. The solid was filtered, and the resulting filter cake was recrystallized from the filter cake with an appropriate amount of ethanol to give the target compound I1.

[0028] The target compound I1 is a white solid; yield 61%; mp 216-218℃; 1 H NMR (400MHz, DMSO-d6) δ9.28 (s, 1H), 8.50 (s, 1H), 8.15 (s, 1H), 7.19 (t, J=7.8Hz, 2H), 6.85 (t, J=7.3Hz, 1H), 6.64 (d, J=7.9Hz, 2H), 3.96 (s, 3H); 13C NMR (100MHz, DMSO-d6) δ156.09, 153.34, 151.25, 148.16, 135.00, 129.57, 121.02, 113.18, 106.22, 34.63; HRMS (ESI) m / z [M+H] + calcd forC 12 H 11 N5O: 242.1036, found: 242.1038.

[0029] Example 2

[0030] The pyrazolopyrimidin-4-one derivative I2 containing an aniline unit described in this invention, with R1 = 4-Cl, has the chemical name 1-methyl-5-(4-chloroaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(4-chlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0031]

[0032] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0033] As in the first step of Example 1.

[0034] Step 2: Synthesis of 5-amino-1-methyl-N′-(4-chlorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B2)

[0035]

[0036] As in the second step of Example 1, the difference is that 4-chlorophenylhydrazine is used as the reactant.

[0037] Step 3: Synthesis of 1-methyl-5-(4-chloroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I2)

[0038] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(4-chlorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0039] The target compound I2 is a white solid; yield 67%; mp 242-244℃; 1H NMR (400MHz, DMSO-d6) δ9.43 (s, 1H), 8.50 (s, 1H), 8.15 (s, 1H), 7.23 (d, J = 8.4Hz, 2H), 6.68 (d, J = 8.4Hz, 2H), 3.96 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.97, 153.18, 151.22, 147.13, 135.05.129.35, 124.58, 114.92, 106.17, 34.63; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 ClN5O: 276.0647, found: 276.0648.

[0040] Example 3

[0041] The pyrazolopyrimidin-4-one derivative I3 containing an aniline unit described in this invention, with R1 = 4-Me, has the chemical name 1-methyl-5-(4-methylaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(4-methylphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0042]

[0043] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0044] As in the first step of Example 1.

[0045] Step 2: Synthesis of 5-amino-1-methyl-N′-(4-methylphenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B3)

[0046]

[0047] As in the second step of Example 1, the difference is that 4-methylphenylhydrazine is used as the reactant.

[0048] Step 3: Synthesis of 1-methyl-5-(4-methylaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I3)

[0049] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(4-methylphenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0050] The target compound I3 is a white solid; yield 63%; mp 243-245℃; 1 H NMR (400MHz, DMSO-d6) δ9.13 (s, 1H), 8.48 (s, 1H), 8.13 (s, 1H), 6.99 (d, J = 7.4Hz, 2H), 6.55 (d, J = 7.5Hz, 2H), 3.96 (s, 3H), 2.18 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ156.11, 153.32, 151.25, 145.84, 134.96, 129.93, 129.83, 113.41, 106.23, 34.61, 20.59; HRMS (ESI) m / z [M+H] + calcd for C 13 H 13 N5O: 256.1193, found: 256.1195.

[0051] Example 4

[0052] The pyrazolopyrimidin-4-one derivative I4 containing an aniline unit described in this invention, with R1 = 2-Cl, has the chemical name 1-methyl-5-(2-chloroaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(2-chlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0053]

[0054] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0055] As in the first step of Example 1.

[0056] Step 2: Synthesis of 5-amino-1-methyl-N′-(2-chlorophenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B4)

[0057]

[0058] As in the second step of Example 1, the difference is that 2-chlorophenylhydrazine is used as the reactant.

[0059] Step 3: Synthesis of 1-methyl-5-(2-chloroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I4)

[0060] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2-chlorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0061] The target compound I4 is a white solid; yield 59%; mp 237-239℃; 1 H NMR (400MHz, DMSO-d6) δ8.96 (s, 1H), 8.53 (s, 1H), 8.16 (s, 1H), 7.41 (d, J=7.8Hz, 1H ), 7.11 (t, J=7.6Hz, 1H), 6.88 (t, J=7.5Hz, 1H), 6.44 (d, J=8.0Hz, 1H), 3.97 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.67, 153.28, 151.18, 143.67, 135.10, 130.07, 128.51, 121.90, 118.40, 113.72, 106.11, 34.66; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 ClN5O: 276.0647, found: 276.0645.

[0062] Example 5

[0063] The pyrazolopyrimidin-4-one derivative I5 containing an aniline unit described in this invention, with R1 = 2-Br, has the chemical name 1-methyl-5-(2-bromoanilino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(2-bromophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0064]

[0065] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0066] As in the first step of Example 1.

[0067] Step 2: Synthesis of 5-amino-1-methyl-N′-(2-bromophenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B5)

[0068]

[0069] As in the second step of Example 1, the difference is that 2-bromophenylhydrazine is used as the reactant.

[0070] Step 3: Synthesis of 1-methyl-5-(2-bromoanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I5)

[0071] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2-bromophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0072] The target compound I5 is a white solid; yield 51%; mp 205-207℃; 1 H NMR (400MHz, DMSO-d6) δ8.74 (s, 1H), 8.52 (s, 1H), 8.16 (s, 1H), 7.56 (d, J=7.7Hz, 1H ), 7.15 (t, J=7.6Hz, 1H), 6.82 (t, J=7.4Hz, 1H), 6.40 (d, J=8.0Hz, 1H), 3.97 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.66, 153.27, 151.18, 144.69, 135.10, 133.27, 129.08, 122.43, 113.84, 107.90, 106.13, 34.66; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 BrN5O: 320.0142, found: 320.0143.

[0073] Example 6

[0074] The pyrazolopyrimidin-4-one derivative I6 containing an aniline unit described in this invention, R1 = 2,4-di-Cl, has the chemical name 1-methyl-5-(2,4-dichloroanilino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and the English name 1-methyl-5-(2,4-dichlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0075]

[0076] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0077] As in the first step of Example 1.

[0078] Step 2: Synthesis of 5-amino-1-methyl-N′-(2,4-dichlorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B6)

[0079]

[0080] As in the second step of Example 1, the difference is that 2,4-dichlorophenylhydrazine is used as the reactant.

[0081] Step 3: Synthesis of 1-methyl-5-(2,4-dichloroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I6)

[0082] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2,4-dichlorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0083] The target compound I6 is a white solid; yield 56%; mp 217-219℃; 1 H NMR (400MHz, DMSO-d6) δ9.12 (s, 1H), 8.53 (s, 1H), 8.16 (s, 1H), 7.56 (d, J = 2.2Hz, 1H), 7.17 (dd, J = 8.8, 2.1Hz, 1H), 6.51 (d, J = 8.8Hz, 1H), 3.97 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.58, 153.10, 151.14, 142.91, 135.14, 129.35, 128.42, 124.68, 119.05, 115.13, 106.06, 34.66; HRMS (ESI) m / z [M+H] + calcd for C 12 H9Cl2N5O: 310.0257, found: 310.0257.

[0084] Example 7

[0085] The pyrazolopyrimidin-4-one derivative I7 containing an aniline unit described in this invention, with R1 = 2-F, has the chemical name 1-methyl-5-(2-fluoroaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(2-fluorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0086]

[0087] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0088] As in the first step of Example 1.

[0089] Step 2: Synthesis of 5-amino-1-methyl-N′-(2-fluorophenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B7)

[0090]

[0091] As in the second step of Example 1, the difference is that 2-fluorophenylhydrazine is used as the reactant.

[0092] Step 3: Synthesis of 1-methyl-5-(2-fluoroaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I7)

[0093] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2-fluorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0094] The target compound I7 is a white solid; yield 51%; mp 235-237℃; 1 H NMR (400MHz, DMSO-d6) δ9.23 (s, 1H), 8.57 (s, 1H), 8.16 (s, 1H), 7.24-7.15 (m, 1H), 6. 98 (t, J=7.5Hz, 1H), 6.88 (dd, J=12.5, 6.4Hz, 1H), 6.56 (t, J=7.9Hz, 1H), 3.97 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.82, 153.25, 150.98 (d, J=240.1Hz), 135.52 (d, J=10.8Hz), 135.04, 125.26 (d, J= 3.0Hz), 121.62 (d, J=6.9Hz), 115.95 (d, J=17.8Hz), 114.96 (d, J=2.5Hz), 106.05, 34.63; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 FN5O: 260.0942, found: 260.0943.

[0095] Example 8

[0096] The pyrazolopyrimidin-4-one derivative I8 containing an aniline unit described in this invention, with R1 = 2-Me, has the chemical name 1-methyl-5-(2-methylaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one and the English name 1-methyl-5-(2-methylphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0097]

[0098] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0099] As in the first step of Example 1.

[0100] Step 2: Synthesis of 5-amino-1-methyl-N′-(2-methylphenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B8)

[0101]

[0102] As in the second step of Example 1, the difference is that 2-methylphenylhydrazine is used as the reactant.

[0103] Step 3: Synthesis of 1-methyl-5-(2-methylaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I8)

[0104] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2-methylphenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0105] The target compound I8 is a white solid; yield 72%; mp 222-224℃; 1 H NMR (400MHz, DMSO-d6) δ8.65 (s, 1H), 8.51 (s, 1H), 8.16 (s, 1H), 7.12 (d, J=7.3Hz, 1H), 6.9 7 (t, J=7.6Hz, 1H), 6.78 (t, J=7.3Hz, 1H), 6.17 (d, J=8.0Hz, 1H), 3.97 (s, 3H), 2.30 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.94, 153.35, 151.25, 145.65, 135.02, 130.94, 127.16, 123.17, 120.92, 111.37, 106.16, 34.64, 17.76; HRMS (ESI) m / z [M+H]+ calcd for C 13 H 13 N5O: 256.1193, found: 256.1195.

[0106] Example 9

[0107] The pyrazolopyrimidinone derivative I9 ​​containing an aniline unit described in this invention, R1 = 3,5-di-Cl, has the chemical name 1-methyl-5-(3,5-dichloroanilino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and the English name 1-methyl-5-(3,5-dichlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0108]

[0109] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0110] As in the first step of Example 1.

[0111] Step 2: Synthesis of 5-amino-1-methyl-N′-(3,5-dichlorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B9)

[0112]

[0113] As in the second step of Example 1, the difference is that 3,5-dichlorophenylhydrazine is used as the reactant.

[0114] Step 3: Synthesis of 1-methyl-5-(3,5-dichloroaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I9)

[0115] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(3,5-dichlorophenyl)-1H-pyrazole-4-formylhydrazine is used as the reactant.

[0116] The target compound I9 is ​​a white solid; yield 55%; mp 237-239℃; 1 H NMR (400MHz, DMSO-d6) δ9.66 (s, 1H), 8.47 (s, 1H), 8.15 (s, 1H), 7.01 (s, 1H), 6.72 (d, J=1.6Hz, 2H), 3.95 (s, 3H); 13CNMR (100MHz, DMSO-d6) δ155.82, 152.86, 151.23, 150.69, 135.18, 135.13, 120.09, 111.76, 106.11, 34.64; HRMS (ESI) m / z[M+H] + calcd for C 12 H9Cl2N5O: 310.0257, found: 310.0259.

[0117] Example 10

[0118] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 10 R1 = 2,4-di-Me, chemically named 1-methyl-5-(2,4-dimethylphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the English name 1-methyl-5-(2,4-dimethylphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, and its structural formula is as follows:

[0119]

[0120] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0121] As in the first step of Example 1.

[0122] Step 2: 5-Amino-1-methyl-N′-(2,4-dimethylphenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B) 10 Synthesis of

[0123]

[0124] As in the second step of Example 1, the difference is that 2,4-dimethylphenylhydrazine is used as the reactant.

[0125] Step 3: 1-Methyl-5-(2,4-dimethylaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 10 Synthesis of )

[0126] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2,4-dimethylphenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0127] Target compound I 10 It is a white solid; yield 58%; mp 220-222℃;1 H NMR (400MHz, DMSO-d6) δ8.52 (s, 1H), 8.49 (s, 1H), 8.15 (s, 1H), 6.94 (s, 1H), 6.7 7 (d, J=8.1Hz, 1H), 6.07 (d, J=8.1Hz, 1H), 3.96 (s, 3H), 2.26 (s, 3H), 2.16 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.97, 153.31, 151.25, 143.34, 134.96, 131.60, 129. 67, 127.39, 123.29, 111.72, 106.17, 34.62, 20.51, 17.68; HRMS(ESI)m / z[M+H] + calcd for C 14 H 15 N5O: 270.1349, found: 270.1351.

[0128] Example 11

[0129] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 11 R1 = 2,4-di-F, chemically named 1-methyl-5-(2,4-difluorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0130]

[0131] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0132] As in the first step of Example 1.

[0133] Step 2: 5-Amino-1-methyl-N′-(2,4-difluorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B) 11 Synthesis of )

[0134]

[0135] As in the second step of Example 1, the difference is that 2,4-difluorophenylhydrazine is used as the reactant.

[0136] Step 3: 1-Methyl-5-(2,4-difluoroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 11 Synthesis of )

[0137] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2,4-difluorophenyl)-1H-pyrazole-4-formylhydrazine is used as the reactant.

[0138] Target compound I 11 It is a white solid; yield 48%; mp 230-232℃; 1 H NMR (400MHz, DMSO-d6) δ9.19 (s, 1H), 8.57 (s, 1H), 8.14 (s, 1H), 7.27 (ddd, J=11.7 , 8.9, 2.6Hz, 1H), 6.88 (t, J=8.5Hz, 1H), 6.67 (td, J=9.3, 5.6Hz, 1H), 3.96 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ156.67 (d, J=239.6Hz), 155.85, 153.14, 151.17, 150.75 (d, J=243.9Hz), 135.01, 132.22 (dd, J=10.7, 3. 1Hz), 116.24 (dd, J=9.6, 3.5Hz), 111.66 (dd, J=22.0, 3.8Hz), 106.02, 104.72 (dd, J=26.7, 22.7Hz), 34.61; HRMS (ESI) m / z [M+H] + calcd for C 12 H9F2N5O: 278.0848, found: 278.0850.

[0139] Example 12

[0140] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 12 R1 = 4-F, chemical name is 1-methyl-5-(4-fluorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, English name is 1-methyl-5-(4-fluorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, structural formula is as follows:

[0141]

[0142] Step 1: Synthesis of 5-amino-1-methyl-1H-lpyrazole-4-carboxylic acid (intermediate A)

[0143] As in the first step of Example 1.

[0144] Step 2: 5-Amino-1-methyl-N′-(4-fluorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B) 12 Synthesis of )

[0145]

[0146] As in the second step of Example 1, the difference is that 4-fluorophenylhydrazine is used as the reactant.

[0147] Step 3: 1-Methyl-5-(4-fluoroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 12 Synthesis of )

[0148] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(4-fluorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0149] Target compound I 12 It is a white solid; yield 57%; mp 224-226℃; 1 H NMR (400MHz, DMSO-d6) δ9.27 (s, 1H), 8.51 (s, 1H), 8.15 (s, 1H), 7.07-7.00 (m, 2H), 6.72-6.67 (m, 2H), 3.96 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ157.36 (d, J=235.8Hz), 156.08, 153.22, 151.25, 144.57 (d, J=2.0H z), 134.99, 116.05 (d, J=22.6Hz), 114.83 (d, J=7.8Hz), 106.21, 34.60; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 FN5O: 260.0942, found: 260.0944.

[0150] Example 13

[0151] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 13R1 = 2-OMe, chemically named 1-methyl-5-(2-methoxyphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0152]

[0153] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0154] As in the first step of Example 1.

[0155] Step 2: 5-Amino-1-methyl-N′-(2-methoxyphenyl)-1H-pyrazole-4-formylhydrazine (intermediate B) 13 Synthesis of )

[0156]

[0157] As in the second step of Example 1, the difference is that 2-methoxyphenylhydrazine is used as the reactant.

[0158] Step 3: 1-Methyl-5-(2-methoxyanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 13 Synthesis of )

[0159] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(2-methoxyphenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0160] Target compound I 13 It is a white solid; yield 56%; mp 219-221℃; 1 H NMR (400MHz, DMSO-d6) δ8.55 (s, 1H), 8.48 (s, 1H), 8.12 (s, 1H), 7.01-6.98 (m, 1H), 6.84 (td, J= 7.9, 1.4Hz, 1H), 6.73 (t, J=7.6Hz, 1H), 6.29 (dd, J=7.8, 1.2Hz, 1H), 3.96 (s, 3H), 3.87 (s, 3H); 13C NMR (100MHz, DMSO-d6) δ155.82, 153.50, 151.23, 147.29, 136.75, 134.94, 121.33, 121.21, 112.24, 111.50, 106.21, 56.05, 34.60; HRMS (ESI) m / z [M+H] + calcd for C 13 H 13 N5O2: 272.1142, found: 272.1144.

[0161] Example 14

[0162] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 14 R1 = 3-Cl, chemically named 1-methyl-5-(3-chlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0163]

[0164] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0165] As in the first step of Example 1.

[0166] Step 2: 5-Amino-1-methyl-N′-(3-chlorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B) 14 Synthesis of )

[0167]

[0168] As in the second step of Example 1, the difference is that 3-chlorophenylhydrazine is used as the reactant.

[0169] Step 3: 1-Methyl-5-(3-chloroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 14 Synthesis of )

[0170] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(3-chlorophenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0171] Target compound I 14 It is a white solid; yield 56%; mp 229-231℃;1 H NMR (400MHz, DMSO-d6) δ9.49 (s, 1H), 8.49 (s, 1H), 8.15 (s, 1H), 7.21 (t, J=8.1Hz, 1H), 6.8 9 (dd, J=7.9, 1.1Hz, 1H), 6.70 (t, J=1.8Hz, 1H), 6.62 (dd, J=8.2, 1.6Hz, 1H), 3.96 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.93, 153.12, 151.22, 149.76, 135.07, 134.21, 131.29, 120.68, 112.83, 111.90, 106.14, 34.64; HRMS (ESI) m / z [M+H] + calcd for C 12 H 10 ClN5O: 276.0647, found: 276.0649.

[0172] Example 15

[0173] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 15 R1 = 3-Me, chemical name 1-methyl-5-(3-methylaniline)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, English name 1-methyl-5-(3-methylphenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, structural formula as follows:

[0174]

[0175] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0176] As in the first step of Example 1.

[0177] Step 2: 5-Amino-1-methyl-N′-(3-methylphenyl)-1H-pyrazole-4-carboxylhydrazide (intermediate B) 15 Synthesis of )

[0178]

[0179] As in the second step of Example 1, the difference is that 3-methylphenylhydrazine is used as the reactant.

[0180] Step 3: 1-Methyl-5-(3-methylaniline)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 15 Synthesis of )

[0181] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(3-methylphenyl)-1H-pyrazole-4-formylhydrazide is used as the reactant.

[0182] Target compound I 15 It is a white solid; yield 59%; mp 223-225℃; 1 H NMR (400MHz, DMSO-d6) δ9.19 (s, 1H), 8.48 (s, 1H), 8.14 (s, 1H), 7.07 (t, J=7.6H z, 1H), 6.66 (d, J=7.4Hz, 1H), 6.44 (d, J=7.7Hz, 2H), 3.96 (s, 3H), 2.19 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ156.10, 153.35, 151.24, 148.19, 138.91, 135.00, 129.44, 121.85, 113.59, 110.49, 106.22, 34.62, 21.61; HRMS (ESI) m / z [M+H] + calcd for C 13 H 13 N5O: 256.1193, found: 256.1195.

[0183] Example 16

[0184] The pyrazolopyrimidinone derivative I containing an aniline unit described in this invention 16 R1 = 34-di-Cl, chemically named 1-methyl-5-(3,4-dichlorophenylamino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, with the following structural formula:

[0185]

[0186] Step 1: Synthesis of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid (intermediate A)

[0187] As in the first step of Example 1.

[0188] Step 2: 5-Amino-1-methyl-N′-(3,4-dichlorophenyl)-1H-pyrazole-4-carboxylhydrazine (intermediate B) 16 Synthesis of )

[0189]

[0190] As in the second step of Example 1, the difference is that 3,4-dichlorophenylhydrazine is used as the reactant.

[0191] Step 3: 1-Methyl-5-(3,4-dichloroanilino)-1,5-dihydro-4H-pyropyrazole[3,4-d]pyrimidin-4-one (target compound I) 16 Synthesis of )

[0192] As in step 3 of Example 1, the difference is that 5-amino-1-methyl-N′-(3,4-dichlorophenyl)-1H-pyrazole-4-formylhydrazine is used as the reactant.

[0193] Target compound I 16 It is a white solid; yield 71%; mp 262-264℃; 1 H NMR (400MHz, DMSO-d6) δ9.57 (s, 1H), 8.49 (s, 1H), 8.15 (s, 1H), 7.41 (d, J = 8.8Hz, 1H), 6.92 (d, J = 2.6Hz, 1H), 6.69 (dd, J = 8.8, 2.7Hz, 1H), 3.95 (s, 3H); 13 C NMR (100MHz, DMSO-d6) δ155.87, 152.98, 151.22, 148.37, 135.11, 132.03, 131.40, 122.34, 114.73, 113.75, 106.12, 34.64; HRMS (ESI) m / z [M+H] + calcd for C 12 H9Cl2N5O: 310.0257, found: 310.0260.

[0194] Application performance testing

[0195] Test methods for inhibiting the activity of plant pathogenic fungi:

[0196] The inhibitory effects of the target molecule on *Fusarium graminearum*, *Rhizoctonia solanis*, *Botrytis cinerea*, and *Alternaria solani* at a concentration of 50 μg / mL were determined using the mycelial growth rate method. 200 g of potato slices were added to 800 mL of boiled secondary water and boiled until easily broken with a glass rod. The solution was filtered through gauze and the filtrate was reserved. Separately, 200 mL of secondary water was taken, 20 g of agar powder was added, and the mixture was stirred well. The filtrate from the previous step was then added, and the secondary water was added until a final volume of 1 L was reached. After boiling, 20 g of glucose was added, and the mixture was stirred well and dispensed into Erlenmeyer flasks to obtain PDA medium. After sterilizing freshly prepared PDA medium at 121℃ for 20 min, 100 μL of drug-containing DMSO was added to 45 mL of sterilized and still-warmed PDA medium using a 200 μL pipette. After mixing, the drug-containing medium was evenly transferred to three disposable culture dishes and allowed to cool naturally under UV light. Once cooled, 5 mm diameter mycelial discs were inoculated into the center of each disposable culture dish, and then transferred to a 25℃ incubator for inverted cultivation in the dark. When the colony diameter (C) of the blank control reached 70-80 mm, the colony diameter (T) of each treatment group was measured using the cross-sectional method. The inhibition rate (I) of the corresponding treatment group against plant pathogenic fungi was then calculated based on the colony diameters obtained from the blank and drug-treated groups. The calculation formula is as follows:

[0197]

[0198] Using the agricultural fungicide hymexazol as a positive control, the mycelial growth rate method was used to determine the target molecules I1-I2. 16 The inhibitory activity of the agent at a concentration of 50 μg / mL against plant pathogenic fungi Fusarium graminearum, rice sheath blight, tomato gray mold, and tomato early blight is shown in Table 1.

[0199] Table 1 Compounds I1~I 16 Inhibitory activity against plant pathogenic fungi at a concentration of 50 μg / mL

[0200] compound wheat scab Rice Rhizoctonia solani tomato gray mold Tomato early pathogen <![CDATA[I1]]> 5.95±1.18 4.56±1.01 7.15±0.46 6.16±0.49 <![CDATA[I2]]> 39.05±1.22 53.19±2.34 17.84±0.55 30.57±0.88 <![CDATA[I3]]> 15.29±1.09 6.97±1.53 11.02±1.29 8.27±0.88 <![CDATA[I4]]> 81.52±2.55 2.03±0.84 53.34±0.74 5.79±1.00 <![CDATA[I5]]> 83.11±0.45 1.17±1.27 70.98±2.51 4.72±0.58 <![CDATA[I6]]> 68.23±1.46 52.98±2.77 58.41±1.01 30.12±1.05 <![CDATA[I7]]> 20.75±2.06 5.53±0.82 7.54±1.18 3.81±0.65 <![CDATA[I8]]> 30.38±2.24 15.36±1.31 21.02±0.97 1.05±0.86 <![CDATA[I9]]> 7.64±1.03 39.22±3.33 10.88±1.43 3.40±0.46 <![CDATA[I 10 ]]> 13.06±0.75 7.66±1.31 5.76±1.43 4.58±0.44 <![CDATA[I 11 ]]> 8.91±1.05 10.35±1.16 7.10±1.29 8.71±0.44 <![CDATA[I 12 ]]> 35.67±2.16 23.68±2.11 12.25±0.99 23.02±0.35 <![CDATA[I 13 ]]> 91.63±1.65 20.02±2.32 12.25±0.99 1.00±0.63 <![CDATA[I 14 ]]> 10.02±1.09 12.37±1.12 11.36±1.22 6.65±0.42 <![CDATA[I 15 ]]> 8.14±0.54 16.23±0.99 17.54±1.22 6.37±0.28 <![CDATA[I 16 ]]> 25.86±1.52 55.58±1.25 12.63±0.23 14.22±0.33 Oxyphenidyl 48.66±3.15 36.90±2.30 64.01±2.49 37.05±2.17

[0201] Table 1 shows that some target molecules exhibited significant antibacterial activity against *Fusarium graminearum*, *Rhizoctonia solani*, and *Botrytis cinerea* at a concentration of 50 μg / mL. Among them, target molecules I4, I5, I6, and I... 13At 50 μg / mL, it significantly inhibited the growth of Fusarium graminearum mycelium, with inhibition rates of 81.52%, 83.11%, 68.23%, and 91.63%, respectively, which was superior to the inhibition rate of hymexazol against Fusarium graminearum at the same concentration (48.66%). Simultaneously, the target molecules I2, I6, and I... 16 At a concentration of 50 μg / mL, it also showed significant inhibitory activity against *Rhizoctonia solani*, the causal agent of rice sheath blight, with inhibition rates of 53.19%, 52.98%, and 55.58%, respectively. Furthermore, target molecules I4, I5, and I6 also showed significant inhibitory activity against *Botrytis cinerea*, the causal agent of tomato gray mold, at a concentration of 50 μg / mL, with inhibition rates of 53.34%, 70.98%, and 58.41%, respectively. Notably, compound I... 13 The inhibition rate against Fusarium graminearum at 50 μg / mL reached 91.63%, indicating its potential for development as a fungicide for agricultural use.

Claims

1. A pyrazolopyrimidinone derivative containing an aniline unit, characterized in that, The structural formula is shown in I: Among them, R 1 It is selected from hydrogen, 2-methyl, 3-methyl, 4-methyl, 2,4-dimethyl, 2-chloro, 3-chloro, 4-chloro, 2,4-dichloro, 3,4-dichloro, 3,5-dichloro, 2-fluoro, 4-fluoro, 2,4-difluoro, 2-bromo, or 2-methoxy.

2. The method for preparing the pyrazolopyrimidinone derivative containing an aniline unit according to claim 1, characterized in that, Ethyl 5-amino-1-methylpyrazole-4-carboxylate was hydrolyzed in 5% sodium hydroxide solution, and then reacted with a substituted phenylhydrazine in dichloromethane containing triethylamine and TBTU. The resulting hydrazine molecule underwent a cyclization reaction with triethyl orthoformate in hot ethanol to give the pyrazolopyrimidinone derivative I containing the aniline unit. The synthetic route is as follows:

3. The application of the pyrazolopyrimidinone derivative containing an aniline unit as described in claim 1 in the prevention and control of wheat scab, rice sheath blight, or tomato gray mold.

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