1,2,3-benzotriazine-4(3h)-one selenide and preparation method and application thereof

Abstract

The application provides a 1,2,3-benzotriazine-4(3H)-ketone selenide and a preparation method and application thereof, and belongs to the field of organic synthesis. The 1,2,3-benzotriazine-4(3H)-ketone selenide has anti-schistosome activity. The preparation method has the advantages of mild conditions, easy control, high reaction efficiency, economical steps, cheap and easily available raw materials, no use of oxidants, good functional group tolerance and the like, and the prepared 1,2,3-benzotriazine-4(3H)-ketone selenide has high purity, the purity is 98.5-99.9%, and has great market promotion value. Compared with a multi-step synthesis reaction, the target product can be obtained through one-step reaction, the reaction yield reaches 90%, and the reaction has the advantages of high reaction efficiency and economical steps.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and in particular to a 1,2,3-benzotriazine-4(3H)-one seleno compound, a preparation method thereof and an application thereof. Background Art

[0002] 1,2,3-Benzotriazin-4(3H)-one is an important class of nitrogen-containing heterocyclic compounds, a key component of numerous bioactive compounds, and has attracted considerable attention in bioorganic and medicinal chemistry. This class of compounds has been shown to exhibit a range of pharmacological properties, including sedative, diuretic, anesthetic, anti-arthritic, and anti-tumor activities. However, 1,2,3-Benzotriazin-4(3H)-one has not been shown to have anti-schistosomal activity. Summary of the Invention

[0003] The present invention provides a 1,2,3-benzotriazine-4(3H)-one seleno compound, a preparation method and an application thereof. The 1,2,3-benzotriazine-4(3H)-one seleno compound has anti-schistosomal activity.

[0004] The present invention provides a 1,2,3-benzotriazine-4(3H)-one seleno compound having a structure shown in Formula I:

[0005]

[0006] The R 1 including phenyl, first substituted phenyl, first substituted alkyl or cycloalkyl;

[0007] The R 2 This includes phenyl, a second substituted phenyl, or a second substituted alkyl.

[0008] The 1,2,3-benzotriazine-4(3H)-one selenoside of the present invention has anti-schistosomal activity after the introduction of selenium.

[0009] Currently, the methods for synthesizing 1,2,3-benzotriazine-4(3H)-one derivatives are mainly:

[0010] (a) Synthesis of 3-aryl-1,2,3-benzotriazine-4(3H)-ones by copper-catalyzed Ullmann-type coupling reaction of 1,2,3-benzotriazine-4(3H)-one with aryl iodide (or aryl boronic acid):

[0011]

[0012] (b) Synthesis of 3-aryl-1,2,3-benzotriazole-4(3H)-ones via oxidative cyclization reaction of C-N bond cleavage and N-N bond formation:

[0013]

[0014] (c) using tert-butyl nitrite and 2-aminobenzamide as raw materials, TBAI as a catalyst, and synthesizing 3-aryl-1,2,3-benzotriazine-4(3H)-one under acid-free conditions:

[0015]

[0016] Compared with the above preparation method, the preparation method has the advantages of mild conditions, easy control, high reaction efficiency, economical steps, cheap and easily available raw materials, no use of oxidants, good functional group tolerance, and the prepared 1,2,3-benzotriazine-4(3H)-one selenide has high purity, the purity is 98.5-99.9%, and has great market promotion value. Compared with a multi-step synthesis reaction, the target product can be obtained by one-step reaction, and the reaction yield reaches 90%, which has the advantages of high reaction efficiency and economical steps. DETAILED DESCRIPTION

[0017] The application provides a 1,2,3-benzotriazine-4(3H)-one selenide with the structure shown in formula I:

[0018]

[0019] The R 1 including a phenyl group, a first substituted phenyl group, a first substituted alkyl group or a cycloalkyl group;

[0020] The R 2 including a phenyl group, a second substituted phenyl group or a second substituted alkyl group.

[0021] In the application, the first substituted phenyl group preferably includes a halophenyl group, and the halophenyl group preferably includes a fluorophenyl group;

[0022] The cycloalkyl group preferably includes a cyclohexane group;

[0023] The substituent group of the first substituted alkyl group preferably includes a phenyl group, a benzyl group, a halophenyl group, an adamantyl group, a furanyl group or a thienyl group.

[0024] In the application, the 1,2,3-benzotriazine-4(3H)-one selenide preferably has the structure shown in any one of formula I-1 to formula I-30:

[0025]

[0026]

[0027] The application further provides a preparation method of the 1,2,3-benzotriazine-4(3H)-one selenide in the above technical solution, comprising the following steps:

[0028] Mixing an o-aminobenzyl arylamine compound having a structure of formula II, a diselenide compound having a structure of formula III, a nitrate, a ligand of the nitrate, a basic compound, and a polar organic solvent, and performing a CN coupling reaction to obtain the 1,2,3-benzotriazine-4(3H)-one seleno compound;

[0029]

[0030] In the present invention, the molar ratio of the o-aminobenzamide compound to the diselenide compound is preferably 1:1 to 1.5. In a specific embodiment of the present invention, the molar ratio of the o-aminobenzamide compound to the diselenide compound can be 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.

[0031] In the present application, the o-aminobenzamide arylamine compound preferably includes one of o-aminobenzamide, 2-amino-N-p-tolylbenzamide, 2-amino-N-(3-methylphenyl)benzamide, 2-amino-N-o-tolylbenzamide, 2-amino-N-p-fluorophenylbenzamide, 2-amino-N-m-fluorophenylbenzamide, 2-amino-N-o-fluorophenylbenzamide, 2-amino-N-adamantyl-benzamide, 2-amino-N-cyclopentylbenzamide, 2-amino-N-isopropylbenzamide, 2-amino-N-n-butylbenzamide, 2-amino-N-(3,4-dimethylphenyl)-benzamide, 2-amino-N-(3-phenylpropyl)-benzamide, 2-amino-N-[3-(trifluoromethyl)phenyl]benzamide, 2-amino-N-benzylbenzamide, 2-amino-N-(4-methylbenzyl)benzamide, 2-amino-N-(3-methylbenzyl)benzamide, 2-amino-N-(2-methylbenzyl)benzamide, 2-amino-N-(4-chlorobenzyl)benzamide, 2-amino-N-(3-chlorobenzyl)benzamide, 2-amino-N-(2-chlorobenzyl)benzamide, 2-amino-N-(4-fluorobenzyl)benzamide, 2-amino-N-(3-fluorobenzyl)benzamide, 2-amino-N-(2-fluorobenzyl)benzamide, 2-amino-N-(cyclohexylmethyl)benzamide, 2-amino-N-(2-thienylmethyl)benzamide, and 2-amino-N-(2-furylmethyl)benzamide. In a specific embodiment of the present application, the o-aminobenzamide arylamine compound is prepared with reference to the contents of "Li-Yan Zeng, Wen-Bin Yi, Chun Cai. (2012), Three-Component Domino Synthesis of 2-Arylquinazoline-4-amines in One Pot by Activating an sp3 C-H Bond in a Nonmetal Catalytic Oxidation System. Eur. J. Org. Chem., 2012: 559-566. DOI: 10.1002 / ejoc.201101315."

[0032] In the present application, the diselenide compound preferably includes one of diphenyl diselenide, dimethyl diselenide, (4-methylphenyl) diselenide, (3-fluorophenyl) diselenide, and (4-fluorophenyl) diselenide. In specific embodiments of the present application, the diselenide compound is prepared in reference to the content in “Tong-Yang Cao, Lin Qi, Yi-Chen Dong, Jie-Hui Cao, Li-Jing Wang. Visible-Light-Driven Selenyl-Radical-Mediated Cascade Spirocyclization of 3-(2-Isocyanobenzyl)indoles with Diselenides [J]. Synlett, 2023, 34(17): 2042-2046. DOI: 10.1055 / a-2131-3551.”

[0033] In the present application, the molar ratio of the nitrate salt to the o-aminobenzamide compound is preferably 1-2:1. In specific embodiments of the present application, the molar ratio of the nitrate salt to the o-aminobenzamide compound can be 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1; the nitrate salt preferably includes silver nitrate.

[0034] The molar ratio of the ligand of the nitrate salt to the o-aminobenzamide compound is 0.1-0.5:1. In specific embodiments of the present application, the molar ratio of the ligand of the nitrate salt to the o-aminobenzamide compound can be 0.1:1, 0.2:1, 0.3:1, 0.4:

[0035] 1, or 0.5:1; the ligand of the nitrate salt preferably includes one or more of 2,2'-bipyridine, 4,5-diazofluorene-9-

[0036] ketone, 6,6"-dimethoxy-2,2"-bipyridine, 1,10-phenanthroline, 2,6-bis[(4S)-4-tert-butyl-2-

[0037] oxazoline]pyridine, tricyclohexylphosphine, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.

[0038] The molar ratio of the basic compound to the anthranilic acid arylamide compound is 0.5-1.5:1; in specific embodiments of the present application, the molar ratio of the basic compound to the anthranilic acid arylamide compound can be 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, or 1.5:1; the basic compound preferably includes pyridine, 2,6-dimethylpyridine, triethylamine, triethylenediamine, 1,8-

[0039] one or more of diazabicyclo[5.4.0]undec-7-ene, K2CO3, and t-BuOK.

[0040] In the present application, the use amount ratio of the polar organic solvent to the anthranilic acid arylamide compound is preferably 1L:0.1-0.2 mol, in specific embodiments of the present application, the use amount ratio of the polar organic solvent to the anthranilic acid arylamide compound can be 1L:0.1 mol,

[0041] 1L:0.15 mol, or 1L:0.2 mol; the polar organic solvent preferably includes one or more of acetonitrile, dichloromethane, and ethyl acetate.

[0042] In the present application, the temperature of the C-N coupling reaction is preferably 20-60°C, in specific embodiments of the present application, the temperature of the C-N coupling reaction can be 20°C, 30°C, 40°C, 50°C, or 60°C; the time is preferably 6-24 h, in specific embodiments of the present application, the time of the C-N coupling reaction can be 6 h, 9 h, 12 h, 15 h, 18 h, 21 h, or 24 h.

[0043] In the present application, the C-N coupling reaction is preferably performed under a protective atmosphere, the gas in the protective atmosphere preferably includes nitrogen; the C-N coupling reaction is preferably performed under oil bath heating; the C-N coupling reaction is also preferably performed under stirring. The present application does not have special limitations on the rate of stirring, which can be ensured to proceed smoothly according to processes well known in the art.

[0044] In the present application, after the C-N coupling reaction, the present application preferably further includes purifying the obtained product system.

[0045] In the present application, the purification method is preferably column chromatography, and the eluent used in the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 1-15:1, and in specific embodiments of the present application, the volume ratio of petroleum ether to ethyl acetate can be 1:1, 5:1, 8:1, 12:1 or 15:1. The present application does not have any special limitation on the specific process of the column chromatography, and the method well known to those skilled in the art can be used. The present application uses petroleum ether and ethyl acetate as the eluent for purification, and can obtain the target compound with high purity.

[0046] The present application also provides the use of the 1,2,3-benzotriazine-4(3H)-one selenide in the above technical solution or the 1,2,3-benzotriazine-4(3H)-one selenide prepared by the preparation method in the above technical solution in the preparation of an anti-schistosome drug.

[0047] The 1,2,3-benzotriazine-4(3H)-one selenide provided by the present application, the preparation method and the application thereof will be described in detail in conjunction with the following examples, but they should not be understood as limiting the scope of protection of the present application.

[0048] Example 1

[0049] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the following structure:

[0050]

[0051] In the reaction tube, 0.1 mmol of o-aminobenzamide, 0.11 mmol of diphenyl diselenide and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine and 0.1 mmol of pyridine, and the reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography, and the eluent used in the column chromatography was a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product 1,2,3-benzotriazine-4(3H)-one selenide was obtained, and the yield was 90% and the purity was 99.9%;

[0052] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0053] 1H NMR (400 MHz, CDC13, ppm) δ 8.25 (d, J = 2.0 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.77 (dd, J = 8.5, 2.0 Hz, 1H), 7.67-7.60 (m, 4H), 7.53 (t, J = 7.5 Hz, 2H), 7.49-7.37 (m, 4H).

[0054] 13 C{ 1 H} NMR (100 MHz, CDC13, ppm) δ 154.67, 141.99, 141.64, 138.78, 136.09, 135.84, 130.18, 129.50, 129.06, 128.98, 128.84, 127.23, 126.03, 125.40, 120.71;

[0055] MS (EI, 70 eV) m / z 379, 271, 242, 152, 77.

[0056] Example 2

[0057] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the structure shown below:

[0058]

[0059] In the reaction tube, 0.1 mmol of 2-amino-N-p-tolylbenzamide, 0.11 mmol of diphenyl diselenide, and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine, and 0.1 mmol of pyridine. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product, 1,2,3-benzotriazine-4(3H)-one selenide, was obtained in a yield of 42% and a purity of 99.9%.

[0060] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0061] 1HNMR (400 MHz, CDC13, ppm) δ 8.27 (s, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.66 (d, J = 9.7 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 7.3 Hz, 3H), 7.33 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H).

[0062] 13 C{ 1 H}NMR (100 MHz, CDC13, ppm) δ 154.74, 142.07, 141.40, 139.08, 136.27, 136.09, 135.79, 130.14, 129.65, 129.44, 128.81, 127.30, 125.79, 125.51, 120.73, 21.27;

[0063] MS (EI, 70 eV) m / z 393, 285, 256, 152, 77.

[0064] Example 3

[0065] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the structure shown below:

[0066]

[0067] In the reaction tube, 0.1 mmol of 2-amino-N-m-tolylbenzamide, 0.11 mmol of diphenyl diselenide, and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine, and 0.1 mmol of pyridine. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product, 1,2,3-benzotriazine-4(3H)-one selenide, was obtained in a yield of 78% and a purity of 99.9%.

[0068] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0069] 1H NMR (400MHz, CDCl3, ppm) δ8.26 (d, J = 2.0Hz, 1H), 7.99 (d, J = 8.5Hz, 1H), 7.78 (dd, J = 8.5, 2.0Hz,1H),7.68-7.64(m,2H),7.41(d,J=7.2Hz,6H),7.28(d,J=7.2Hz,1H),2.44(s,3H).

[0070] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.72,142.03,141.57,139.13,138.67,136.06,135.84,1 30.17,129.83,129.49,128.89,128.82,127.23,126.65,125.40,123.15,120.72,21.43;

[0071] MS(EI,70eV)m / z 393,289,256,152,77.

[0072] Example 4

[0073] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0074]

[0075] 0.1 mmol 2-amino-N-(4-fluorophenyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 43% and a purity of 99.9%.

[0076] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0077] 1H NMR (400MHz, CDCl3, ppm) δ8.24 (s, 1H), 7.99 (d, J = 8.6Hz, 1H), 7.78 (d, J = 8.4 Hz,1H),7.69-7.57(m,4H),7.42(d,J=7.5Hz,3H),7.23(q,J=8.9,8.3Hz,2H).

[0078] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ163.74, 161.26, 154.63, 141.90 (d, J = 3.0Hz), 136.07, 135.88, 134.75,130.19,129.55,128.87,127.93,127.85,127.12,125.26,120.57,116.10,115.88;

[0079] MS(EI,70eV)m / z 397,289,261,152,77.

[0080] Example 5

[0081] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0082]

[0083] 0.1 mmol 2-amino-N-(3-fluorophenyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 54% and a purity of 99.9%.

[0084] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0085] 1H NMR (400 MHz, CDC13, ppm) δ 8.25 (d, J = 2.0 Hz, 1H), 8.00 (d, J = 8.5 Hz, 1H), 7.79 (dd, J = 8.5, 2.0 Hz, 1H), 7.67 (d, J = 6.1 Hz, 2H), 7.51-7.39 (m, 6H), 7.18 (t, J = 7.5 Hz, 1H).

[0086] 13 C{ 1 H} NMR (100 MHz, CDC13, ppm) δ 163.76, 161.30, 154.52, 142.15, 141.78, 136.15, 135.90, 130.20, 129.57, 128.92, 127.08, 125.34, 121.64, 121.61, 120.57, 116.04, 115.83, 113.78, 113.53;

[0087] MS (EI, 70 eV) m / z 397, 289, 261, 152, 77.

[0088] Example 6

[0089] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the structure shown below:

[0090]

[0091] In the reaction tube, 0.1 mmol of 2-amino-N-o-fluorophenyl benzamide, 0.11 mmol of diphenyl diselenide and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine and 0.1 mmol of pyridine, and the reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product, 1,2,3-benzotriazine-4(3H)-one selenide, was obtained in a yield of 48% and a purity of 99.9%.

[0092] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0093] 1H NMR (400MHz, CDCl3, ppm) δ8.25(d,J=2.0Hz,1H),8.01(d,J=8.5Hz,1H),7.80(dd,J=8.5,2.0Hz,1 H),7.67(dd,J=7.7,1.8Hz,2H),7.51(t,J=7.5Hz,3H),7.42(d,J=7.3Hz,2H),7.35-7.28(m,2H).

[0094] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ158.53,156.01,154.27,142.10,142.04,136.15,135.93,131.46,13 1.38,130.20,129.56,128.99,128.95,127.05,125.27,124.79,124.75,120.51,116.83,116.63;

[0095] MS(EI,70eV)m / z 397,289,261,152,77.

[0096] Example 7

[0097] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0098]

[0099] 0.1 mmol 2-amino-N-adamantanemethylbenzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the product was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 63% and a purity of 99.9%.

[0100] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0101] 1H NMR (400MHz, CDCl3, ppm) δ8.21(s,1H),7.92(d,J=8.5Hz,1H),7.74(d,J=8.7Hz,1H),7.64( d,J=7.1Hz,2H),7.40(d,J=7.9Hz,3H),4.16(s,2H),1.96(s,3H),1.63(d,J=20.5Hz,12H).

[0102] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ135.92,130.10,129.36,128.54,127.44,125.36,120.19,40.58,36.72;

[0103] MS(EI,70eV)m / z 451,288,232,135,79.

[0104] Example 8

[0105] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0106]

[0107] 0.1 mmol 2-amino-N-cyclopentylbenzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 69% and a purity of 99.9%.

[0108] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0109] 1HNMR (400MHz, CDCl3, ppm) δ8.19(d,J=2.0Hz,1H),7.90(d,J=8.5Hz,1H),7.74(dd,J=8.5,2.1Hz,1H),7.66-7.55(m ,2H),7.40(dd,J=9.4,7.0Hz,3H),5.46(t,J=7.5Hz,1H),2.21-2.02(m,5H),1.98-1.92(m,2H),1.76-1.70(m,2H).

[0110] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.83,142.40,140.26,136.03,135.59,130. 07,129.27,128.41,127.57,125.92,125.39,119.77,58.64,32.21,24.90;

[0111] MS(EI,70eV)m / z 371,261,232,152,77.

[0112] Example 9

[0113] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0114]

[0115] 0.1 mmol 2-amino-N-isopropylbenzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 64% and a purity of 99.9%.

[0116] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0117] 1H NMR (400MHz, CDCl3, ppm) δ8.19(d,J=2.0Hz,1H),7.92(d,J=8.5Hz,1H),7.75(dd,J=8.6,2 .0Hz,1H),7.66-7.58(m,2H),7.49-7.36(m,3H),5.40-5.33(m,1H),1.54(d,J=6.8Hz,6H).

[0118] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.45,142.42,140.28,136.06,130.08,129.30,128.44,127.53,125.92,125.36,119.96,49.66,21.57;

[0119] MS(EI,70eV)m / z 345,302,232,152,77.

[0120] Example 10

[0121] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0122]

[0123] 0.1 mmol 2-amino-N-butylbenzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 61% and a purity of 99.9%.

[0124] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0125] 1H NMR (400MHz, CDCl3, ppm) δ8.19(d,J=2.0Hz,1H),7.92(d,J=8.5Hz,1H),7.75(dd,J=8.5,2.0Hz,1H),7.64(dd,J=7.9,1.7 Hz,2H),7.45-7.37(m,3H),4.46-4.39(m,2H),1.85(q,J=7.5Hz,2H),1.40(dt,J=14.8,7.4Hz,2H),0.96(t,J=7.4Hz,3H).

[0126] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.88,142.73,140.64,135.92,135.72,130 .11,129.37,128.56,127.38,125.04,120.18,49.74,30.90,19.89,13.66;

[0127] MS(EI,70eV)m / z 359,288,232,152,77.

[0128] Example 11

[0129] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0130]

[0131] 0.1 mmol 2-amino-N-(3,4-dimethylphenyl)-benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 46% and a purity of 99.9%.

[0132] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0133] 1HNMR (400MHz, CDCl3, ppm) δ8.27(d,J=2.0Hz,1H),7.99(d,J=8.4Hz,1H),7.78(dd,J=8.5,2.0Hz,1 H),7.66(d,J=5.7Hz,2H),7.42(t,J=7.7Hz,3H),7.36(s,1H),7.29(t,J=7.6Hz,2H),2.33(s,6H).

[0134] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.79,142.10,141.35,137.84,137.60,136.44,136.06,1 35.79,130.15,129.44,128.80,127.31,126.97,125.50,123.36,120.74,19.92,19.62;

[0135] MS(EI,70eV)m / z 407,299,207,152,77.

[0136] Example 12

[0137] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0138]

[0139] 0.1 mmol 2-amino-N-(3-phenylpropyl)-benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 54% and a purity of 99.9%.

[0140] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0141] 1H NMR (400MHz, CDCl3, ppm) δ8.21(s,1H),7.95(d,J=8.6Hz,1H),7.77(d,J=8.4Hz,1H),7.67(d,J=7.5Hz,2H),7.44(d,J =6.5Hz,3H),7.23(td,J=17.1,16.6,7.3Hz,5H),4.49(t,J=7.3Hz,2H),2.77(t,J=7.7Hz,2H),2.27(p,J=7.6Hz,2H).

[0142] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.89,142.68,140.76,135.96,135.73,130.13,12 8.58,128.42(d,J=4.1Hz),127.39,126.05,125.04,120.12,49.59,32.91,30.15;

[0143] MS(EI,70eV)m / z 421,292,232,152,77.

[0144] Example 13

[0145] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0146]

[0147] 0.1 mmol 2-amino-N-[3-(trifluoromethyl)phenyl]benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 45% and a purity of 99.9%.

[0148] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0149] 1HNMR (400MHz, CDCl3, ppm) δ8.25 (d, J = 2.0Hz, 1H), 8.01 (d, J = 8.5Hz, 1H), 7.96 (s, 1H), 7.86 (d, J = 7.9Hz, 1H),7.81(dd,J=8.5,2.0Hz,1H),7.73(d,J=7.8Hz,1H),7.67(dd,J=8.0,1.6Hz,3H),7.48-7.40(m,3H).

[0150] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.59,142.50,141.79,139.16,136.19,135.96, 130.24,129.16,128.99,126.95,125.59,125.22,123.03(d,J=4.0Hz),120.50;

[0151] MS(EI,70eV)m / z 447,339,234,152,77.

[0152] Example 14

[0153] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0154]

[0155] 0.1 mmol 2-amino-N-benzylbenzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 60% and a purity of 99.9%.

[0156] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0157] 1H NMR (400MHz, CDCl3, ppm) δ8.15(s,1H),7.93(d,J=8.5Hz,1H),7.75(d,J=8.5Hz,1H),7.63(d,J =6.4Hz,2H),7.49(d,J=6.3Hz,2H),7.40(d,J=7.5Hz,3H),7.31(d,J=7.5Hz,3H),5.57(s,2H).

[0158] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.76,142.70,141.04,135.93,135.79,135.69,130.13, 129.44,128.81,128.69(d,J=7.7Hz),128.24,127.23,125.91,125.02,120.45,53.47;

[0159] MS(EI,70eV)m / z 393,336,208,152,91.

[0160] Example 15

[0161] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0162]

[0163] 0.1 mmol 2-amino-N-(4-methylbenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 70% and a purity of 99.9%.

[0164] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0165] 1H NMR (400MHz, CDCl3, ppm) δ8.59(s,1H),8.35(d,J=8.5Hz,1H),8.23(d,J=8.4Hz,1H),7.76-7.68( m,2H),7.52-7.43(m,3H),7.37(d,J=7.7Hz,2H),7.11(d,J=7.7Hz,2H),5.55(s,2H),2.28(s,3H).

[0166] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.40,147.75,145.38,142.07,138.29,131.92,1 31.13,130.14,130.04,129.45,128.91,125.91,123.80,120.48,53.50,21.17;

[0167] MS(EI,70eV)m / z 407299,222,152,77.

[0168] Example 16

[0169] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0170]

[0171] 0.1 mmol 2-amino-N-(3-methylbenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 75% and a purity of 99.9%.

[0172] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0173] 1H NMR (400 MHz, CDC13, ppm) δ 8.15 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.74 (dd, J = 8.5, 2.1 Hz, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.41 (dd, J = 10.7, 7.2 Hz, 3H), 7.28 (d, J = 7.7 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 7.5 Hz, 1H), 5.53 (s, 2H), 2.31 (s, 3H).

[0174] 13 C{ 1 H} NMR (100 MHz, CDC13, ppm) δ 154.74, 142.71, 140.97, 138.45, 135.90, 135.79, 135.62, 130.13, 129.43, 129.00, 128.64, 128.62, 127.24, 125.85, 125.04, 120.47, 53.43, 21.39;

[0175] MS (EI, 70 eV) m / z 407, 222, 152, 105, 77.

[0176] Example 17

[0177] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the following structure:

[0178]

[0179] In the reaction tube, 0.1 mmol of 2-amino-N-(2-methylbenzyl) benzamide, 0.11 mmol of diphenyl diselenide, and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine, and 0.1 mmol of pyridine. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in the column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product, 1,2,3-benzotriazine-4(3H)-one selenide, was obtained in a yield of 65% and a purity of 99.9%.

[0180] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0181] 1H NMR (400MHz, CDCl3, ppm) δ8.17(d,J=2.0Hz,1H),7.93(d,J=8.6Hz,1H),7.75(dd,J=8.5,2.0Hz,1H),7.63(d,J=6.3Hz,2H),7.49-7.37 (m,3H),7.28(d,J=7.5Hz,1H),7.18(d,J=4.3Hz,2H),7.13(dq,J=8.7,4.6,4.1Hz,1H),5.62(d,J=14.8Hz,2H),2.51(d,J=4.6Hz,3H).

[0182] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.85,142.62,141.02,136.69,135.96,135.78,133.82,130.62,1 30.14,129.44,129.02,128.65,128.16,127.24,126.18,125.91,125.06,120.39,50.88,19.60;

[0183] MS(EI,70eV)m / z 407,379,232,152,77.

[0184] Example 18

[0185] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0186]

[0187] 0.1 mmol 2-amino-N-(4-chlorobenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 59% and a purity of 99.9%.

[0188] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0189] 1H NMR (400MHz, CDCl3, ppm) δ8.13(d,J=2.0Hz,1H),7.93(d,J=8.5Hz,1H),7.75(dd,J=8.5,2.0 Hz,1H),7.63(dd,J=8.0,1.6Hz,2H),7.45-7.37(m,5H),7.28(d,J=8.4Hz,2H),5.52(s,2H).

[0190] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.74,142.64,141.37,135.97,135.84,134.25,1 34.11,130.29,130.16,129.49,128.91,128.71,127.12,124.89,120.35,52.77;

[0191] MS(EI,70eV)m / z 427,242,152,125,77.

[0192] Example 19

[0193] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0194]

[0195] 0.1 mmol 2-amino-N-(3-chlorobenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 32% and a purity of 99.9%.

[0196] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0197] 1H NMR (400MHz, CDCl3, ppm) δ8.15(d,J=2.0Hz,1H),7.94(d,J=8.5Hz,1H),7.78- 7.74(m,1H),7.65-7.61(m,2H),7.47-7.39(m,4H),7.26(s,3H),5.53(s,2H).

[0198] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.75,142.64,141.43,137.53,135.99,135.85,134.58,130.1 6,130.01,129.50,128.83,128.74,128.49,127.11,126.97,125.90,124.93,120.35,52.78;

[0199] MS(EI,70eV)m / z 427,242,152,125,77.

[0200] Example 20

[0201] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0202]

[0203] 0.1 mmol 2-amino-N-(2-chlorobenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 36% and a purity of 99.9%.

[0204] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0205] 1H NMR (400MHz, CDCl3, ppm) δ8.17(d,J=2.0Hz,1H),7.96(d,J=8.5Hz,1H),7.77(dd,J=8 .5,2.0Hz,1H),7.68-7.62(m,2H),7.46-7.37(m,4H),7.25-7.17(m,3H),5.72(s,2H).

[0206] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.90,142.58,141.40,135.98,135.88,133.62,133.24,1 30.17,129.81,129.53,129.51,129.28,128.75,127.09,126.98,124.94,120.29,50.83;

[0207] MS(EI,70eV)m / z 427,392,242,152,77.

[0208] Example 21

[0209] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0210]

[0211] 0.1 mmol 2-amino-N-(4-fluorobenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 50% and a purity of 99.9%.

[0212] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0213] 1HNMR (400MHz, CDCl3, ppm) δ8.14(s,1H),7.92(d,J=8.5Hz,1H),7.74(d,J=8.5Hz,1H),7.63(d,J =7.1Hz,2H),7.51-7.46(m,2H),7.40(q,J=9.2,7.1Hz,3H),7.00(t,J=8.6Hz,2H),5.53(s,2H).

[0214] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ163.87,161.42,154.74,142.67,141.26,135.96,135.83,131.4 8,130.84,130.75,130.15,129.48,128.69,127.15,124.92,120.39,115.74,115.52,52.74;

[0215] MS(EI,70eV)m / z 411,226,152,109,77.

[0216] Example 22

[0217] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0218]

[0219] 0.1 mmol 2-amino-N-(3-fluorobenzyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 55% and a purity of 99.9%.

[0220] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0221] 1HNMR (400 MHz, CDC13, ppm) δ 8.15 (d, J = 1.9 Hz, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.76 (dd, J = 8.6, 2.0 Hz, 1H), 7.63 (d, J = 6.4 Hz, 2H), 7.45-7.37 (m, 3H), 7.31-7.23 (m, 2H), 7.17 (d, J = 9.6 Hz, 1H), 6.98 (t, J = 7.8 Hz, 1H), 5.55 (s, 2H).

[0222] 13 C{ 1 H}NMR (100 MHz, CDC13, ppm) δ 164.07, 161.62, 154.76, 142.64, 141.40, 138.01, 137.93, 135.98, 135.85, 130.33, 130.24, 130.16, 129.50, 128.73, 127.11, 124.92, 124.39, 124.36, 120.35, 115.81, 115.59, 115.35, 115.14, 52.84;

[0223] MS (EI, 70 eV) m / z 411, 226, 152, 109, 77.

[0224] Example 23

[0225] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the following structure:

[0226]

[0227] In the reaction tube, 0.1 mmol of 2-amino-N-(2-fluorobenzyl) benzamide, 0.11 mmol of diphenyl diselenide, and 2 mL of acetonitrile were added, followed by 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine, and 0.1 mmol of pyridine. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in the column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product, 1,2,3-benzotriazine-4(3H)-one selenide, was obtained in a yield of 50% and a purity of 99.9%.

[0228] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0229] 1HNMR (400MHz, CDCl3, ppm) δ8.15(s,1H),7.94(d,J=8.5Hz,1H),7.76(d,J=8.6Hz,1H),7.63(d,J= 6.7Hz,2H),7.44-7.33(m,4H),7.27(d,J=6.8Hz,1H),7.07(dd,J=14.0,6.9Hz,2H),5.65(s,2H).

[0230] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.80,142.60,141.25,135.95,135.85,130.55(d,J=3.6Hz),130.15,130.0 1(d,J=8.1Hz),129.48,128.72,124.94,124.26(d,J=3.7Hz),120.34,115.81,115.60,47.12(d,J=4.0Hz);

[0231] MS(EI,70eV)m / z 411,354,226,152,77.

[0232] Example 24

[0233] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0234]

[0235] 0.1 mmol 2-amino-N-(cyclohexylmethyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 70% and a purity of 99.9%.

[0236] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0237] 1H NMR (400MHz, CDCl3, ppm) δ8.62(d,J=1.8Hz,1H),8.35(dd,J=8.5,1.8Hz,1H),8.23(d,J=8.5Hz,1H),7.7 7-7.70(m,2H),7.48(d,J=1.8Hz,3H),4.28(d,J=7.3Hz,2H),1.65(d,J=12.1Hz,5H),1.24-1.00(m,6H).

[0238] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.80,147.63,145.26,142.11,131.90,130.13,129.97,125.93,123.82,120.16,55.85,37.32,30.54,26.17,25.59;

[0239] MS(EI,70eV)m / z 399,288,232,152,77.

[0240] Example 25

[0241] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0242]

[0243] 0.1 mmol 2-amino-N-(2-thienylmethyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 37% and a purity of 99.9%.

[0244] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0245] 1H NMR (400MHz, CDCl3, ppm) δ8.18(d,J=2.0Hz,1H),7.92(d,J=8.5Hz,1H),7.74(dd,J=8.5,2.0Hz,1H),7.63(dd,J =8.0,1.6Hz,2H),7.42(dd,J=11.2,7.2Hz,3H),7.23(t,J=4.7Hz,2H),6.95(dd,J=5.1,3.5Hz,1H),5.74(s,2H).

[0246] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.52,142.70,141.22,137.13,136.00,135.80,1 30.14,129.46,128.74,128.39,126.91,126.56,125.92,125.03,120.36,47.77;

[0247] MS(EI,70eV)m / z 399,291,214,153,97.

[0248] Example 26

[0249] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0250]

[0251] 0.1 mmol 2-amino-N-(2-furylmethyl)benzamide, 0.11 mmol diphenyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 40% and a purity of 99.9%.

[0252] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0253] 1HNMR (400 MHz, CDC13, ppm) δ 8.16 (d, J = 2.0 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.75 (dd, J = 8.6, 2.1 Hz, 1H), 7.63 (d, J = 6.4 Hz, 2H), 7.42 (dd, J = 11.0, 7.2 Hz, 3H), 7.35 (s, 1H), 6.46 (d, J = 3.2 Hz, 1H), 6.32 (d, J = 1.9 Hz, 1H), 5.58 (s, 2H).

[0254] 13 C{ 1 H}NMR (100 MHz, CDC13, ppm) δ 154.64, 148.74, 142.91, 142.64, 141.22, 135.97, 135.84, 130.18, 130.15, 129.47, 128.74, 127.16, 125.90, 124.98, 120.36, 110.63, 109.89, 46.09;

[0255] MS (EI, 70 eV) m / z 383, 298, 198, 152, 81.

[0256] Antischistosomal activity:

[0257] Live 45-day-old S. japonicum adult worms were collected and placed in RPMI-1640 medium (10 worms / 3 mL / dish), and 3 μL of each test compound was added to each dish, and the final concentration of the compound was 0.1 mmol / L. Praziquantel was used as a positive control: 3 μL of DMSO was added, and after the addition of the drug, the mixture was shaken thoroughly and placed in a 37 °C, 5% CO2incubator, and after 16 h of incubation, the worms were washed with normal saline 3 times, fresh RPMI-1640 medium was added, and the viability of the schistosomes after 24-72 h of incubation was observed under a stereomicroscope. The negative control was the addition of 3 μL of solvent DMSO to the medium. The results are shown in Table 1.

[0258] Table 1 Antischistosomal activity results

[0259]

[0260] The experimental results show that at a concentration of 0.1 mmol / L, 20% of the schistosome adult worms died after 48 h, and the compound had a 50% lethal rate on adult worms in vitro after 72 h.

[0261] Example 27

[0262] The 1,2,3-benzotriazine-4(3H)-one selenide obtained in this example has the following structure:

[0263]

[0264] 0.1 mmol o-aminobenzanilide, 0.11 mmol dimethyl diselenide, and 2 mL acetonitrile were added to a reaction tube, followed by 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine, and 0.1 mmol pyridine. The mixture was stirred in an oil bath at 40°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1, and the purified target product, 1,2,3-benzotriazine-4(3H)-one selenoate, was obtained with a yield of 71% and a purity of 99.9%.

[0265] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0266] 1 H NMR (400MHz, CDCl3, ppm) δ8.27 (s, 1H), 8.02 (s, 1H), 7.91 (d, J = 10.3Hz, 1H), 7.64 (d, J = 7.6Hz, 2H), 7.58-7.46 (m, 3H), 2.51 (s, 3H).

[0267] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.80,141.67,141.30,138.84,135.35,129.09,128.99,128.42,126.09,126.06,123.40,120.69,6.97;

[0268] MS(EI,70eV)m / z 317,274,246,166,77.

[0269] Example 28

[0270] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0271]

[0272] In the reaction tube, 0.1 mmol of anthranilic acid benzamide, 0.11 mmol of (4-methylphenyl) diselenide and 2 mL of acetonitrile were added, and then 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine and 0.1 mmol of pyridine were added. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product 1,2,3-benzotriazine-4(3H)-ketone selenide was obtained in a yield of 41% and a purity of 99.9%.

[0273] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0274] 1 H NMR (400 MHz, CDCl3, ppm) δ 8.69 (d, J = 1.8 Hz, 1H), 8.42 (dd, J = 8.5, 1.8 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.64-7.58 (m, 4H), 7.56-7.48 (m, 3H), 7.29 (d, J = 7.9 Hz, 2H), 2.36 (s, 3H).

[0275] 13 C{ 1 H} NMR (100 MHz, CDCl3, ppm) δ 154.36, 148.66, 144.71, 138.89, 138.39, 131.54, 130.85, 130.18, 129.30, 129.18, 125.98, 125.92, 124.21, 120.81, 21.43;

[0276] MS (EI, 70 eV) m / z 393, 285, 166, 91, 77.

[0277] Example 29

[0278] The 1,2,3-benzotriazine-4(3H)-ketone selenide obtained in this example has the following structure:

[0279]

[0280] In the reaction tube, 0.1 mmol of anthranilic acid benzamide, 0.11 mmol of (3-fluorophenyl) diselenide and 2 mL of acetonitrile were added, and then 0.2 mmol of silver nitrate, 0.03 mmol of 2,2'-bipyridine and 0.1 mmol of pyridine were added. The reaction was stirred at 40°C in an oil bath for 12 h. After the reaction was completed, the product was separated and purified by column chromatography. The eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the eluent was 8:1. The purified target product 1,2,3-benzotriazine-4(3H)-ketone selenide was obtained in a yield of 38% and a purity of 99.9%.

[0281] The structure of the obtained product was characterized, and the structure characterization data are as follows:

[0282] 1 HNMR (400MHz, CDCl3, ppm) δ 8.33 (d, J = 2.0 Hz, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.85 (dd, J = 8.5, 2.0 Hz, 1H), 7.62 (d, J = 7.8 Hz, 2H), 7.55 (t, J = 7.5 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.44-7.31 (m, 3H), 7.15-7.08 (m, 1H).

[0283] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ 164.22, 161.72, 154.60, 142.28, 140.03, 138.70, 136.84, 131.42, 131.34, 130.90, 130.86, 129.09, 129.05, 126.48, 126.00, 122.21, 121.99, 120.86, 116.57, 116.36.

[0284] MS (EI, 70 eV) m / z 397, 289, 207, 166, 77.

[0285] The above only describes the preferred embodiments of the present application. It should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered within the scope of protection of the present application.

Claims

1. A 1,2,3-benzotriazine-4(3H)-one seleno compound, characterized in that: It has the structure shown in formula I: Formula I; The formula I is selected from the following structural formula: I-13; I-15; I-16; I-17; I-18; I-19; I-20; I-21; I-22; I-23; I-24; I-26; I-27。 2. The method for preparing the 1,2,3-benzotriazine-4(3H)-one seleno compound according to claim 1, characterized in that: The following steps are involved: An o-aminobenzyl arylamine compound having a structure of formula II, a diselenide compound having a structure of formula III, a nitrate, a ligand of the nitrate, a basic compound, and a polar organic solvent are mixed and subjected to a CN coupling reaction to obtain the 1,2,3-benzotriazine-4(3H)-one seleno compound; the nitrate comprises silver nitrate; and the ligand of the nitrate comprises one or both of 2,2'-bipyridine and 6,6''-dimethoxy-2,2''-bipyridine; Formula II; Formula III.

3. The preparation method according to claim 2, characterized in that The molar ratio of the o-aminobenzoyl arylamine compound to the diselenide compound is 1:1-1.

5.

4. The preparation method according to claim 2, characterized in that The molar ratio of the nitrate to the o-aminobenzamide compound is 1-2:1; The molar ratio of the nitrate ligand to the o-aminobenzamide compound is 0.1-0.5:1; The molar ratio of the basic compound to the o-aminobenzamide compound is 0.5-1.5:

1.

5. The preparation method according to claim 2, characterized in that The temperature of the CN coupling reaction is 20-60° C., and the time is 6-24 hours.

6. Use of the 1,2,3-benzotriazine-4(3H)-one seleno compound according to claim 1 in the preparation of anti-schistosomal drugs.

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