1, 2, 3-benzotriazine-4 (3H)-ketone seleno compound as well as preparation method and application thereof

Abstract

The invention provides a 1, 2, 3-benzotriazine-4 (3H)-ketone seleno compound as well as a preparation method and application thereof, and belongs to the field of organic synthesis. The 1, 2, 3-benzotriazine-4 (3H)-ketone seleno compound disclosed by the invention has the activity of resisting schistosome. The preparation method has the advantages that conditions are mild, control is easy, reaction efficiency is high, steps are economical, raw materials are cheap and easy to obtain, an oxidizing agent is not used, functional group tolerance is good and the like, the prepared 1, 2, 3-benzotriazine-4 (3H)-ketone seleno compound has high purity, the purity ranges from 98.5% to 99.9%, and the 1, 2, 3-benzotriazine-4 (3H)-ketone seleno compound has high market popularization value. Compared with a multi-step synthesis reaction, a target product can be obtained through one-step reaction, the reaction yield reaches 90%, and the method has the advantages of being high in reaction efficiency and economical in step.

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 and a preparation method and application thereof. Background Art

[0002] 1,2,3-Benzotriazine-4(3H)-one is an important class of nitrogen-containing heterocyclic compounds and an important component of many biologically active substances. It has attracted great attention in the fields of bioorganic chemistry and medicinal chemistry. This is exemplified by the reported pharmacological properties of this class of compounds, including sedative, diuretic, anesthetic, anti-arthritic and anti-tumor activities. However, 1,2,3-Benzotriazine-4(3H)-one currently has no anti-schistosomal activity. Summary of the invention

[0003] The invention provides a 1,2,3-benzotriazine-4(3H)-one seleno compound and a preparation method and application thereof. The 1,2,3-benzotriazine-4(3H)-one seleno compound has anti-schistosoma 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 Includes phenyl, a second substituted phenyl or a second substituted alkyl.

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

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

[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)-ones with aryl iodides (or aryl boronic acids):

[0011]

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

[0013]

[0014] (c) Using tert-butyl nitrite and 2-aminobenzamide as raw materials and TBAI as catalyst, 3-aryl-1,2,3-benzotriazole-4(3H)-one was synthesized under acid-free conditions:

[0015]

[0016] Compared with the above-mentioned preparation methods, the preparation method of the present invention has the advantages of mild conditions, easy control, high reaction efficiency, economical steps, cheap and easy-to-obtain raw materials, no use of oxidants, good functional group tolerance, etc., and the prepared 1,2,3-benzotriazine-4(3H)-one selenoside has a high purity of 98.5-99.9%, and has great market promotion value. Compared with multi-step synthesis reactions, the present invention can obtain the target product in one-step reaction, and the reaction yield reaches 90%, which has the advantages of high reaction efficiency and economical steps. DETAILED DESCRIPTION

[0017] The present invention provides a 1,2,3-benzotriazine-4(3H)-one seleno compound having a structure shown in Formula I:

[0018]

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

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

[0021] In the present invention, the first substituted phenyl group preferably includes a halogen phenyl group, and the halogen phenyl group preferably includes a fluorophenyl group;

[0022] The cycloalkyl group preferably includes cyclohexyl group;

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

[0024] In the present invention, the 1,2,3-benzotriazine-4(3H)-one seleno compound preferably has a structure shown in any one of Formula I-1 to Formula I-30:

[0025]

[0026]

[0027] The present invention also provides a method for preparing the 1,2,3-benzotriazine-4(3H)-one seleno compound described in the above technical solution, comprising the following steps:

[0028] The o-aminobenzoyl arylamine compound having a structure of formula II, the diselenide compound having a structure of formula III, nitrate, a ligand of the nitrate, an alkaline 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;

[0029]

[0030] In the present invention, the molar ratio of the o-aminobenzoyl aryl amine compound to the diselenide compound is preferably 1:1-1.5. In a specific embodiment of the present invention, the molar ratio of the o-aminobenzoyl aryl amine 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 invention, the o-aminobenzamide aromatic compounds preferably include 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-adamantanemethyl-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)benzamide]

[0063] one of 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 invention, the o-aminobenzoyl aromatic amine compound is prepared with reference to the content of “Li-Yan Zeng, Wen-Bin Yi, Chun Cai. (2012), Three-Component Domino Synthesis of 2-Arylquinazoline-4-amines in One Pot by Activating ansp3 CH Bond in a Nonmetal Catalytic Oxidation System. Eur. J. Org. Chem., 2012: 559-566. DOI: 10.1002 / ejoc.201101315.”

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

[0033] In the present invention, the molar ratio of the nitrate to the o-aminobenzoyl aromatic amide compound is preferably 1-2:1. In a specific embodiment of the present invention, the molar ratio of the nitrate to the o-aminobenzoyl aromatic amide 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 preferably includes silver nitrate.

[0034] The molar ratio of the nitrate ligand to the anthranilamide compound is 0.1 to 0.5:1. In a specific embodiment of the present invention, the molar ratio of the nitrate ligand to the anthranilamide compound can be 0.1:1, 0.2:1, 0.3:1, 0.4:1,

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

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

[0037] One or more of] pyridine, tricyclohexylphosphine and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.

[0038] The molar ratio of the basic compound to the o-aminobenzoyl arylamine compound is 0.5 to 1.5:1; in a specific embodiment of the present invention, the molar ratio of the basic compound to the o-aminobenzoyl arylamine 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-lutidine, triethylamine, triethylenediamine, 1,8-

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

[0040] In the present invention, the polar organic solvent and the o-aminobenzoyl aryl amide compound are preferably used in a ratio of 1L: 0.1-0.2 mol. In a specific embodiment of the present invention, the polar organic solvent and the o-aminobenzoyl aryl amide compound can be used in a ratio of 1L: 0.1 mol,

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

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

[0043] In the present invention, the CN coupling reaction is preferably carried out under a protective atmosphere, and the gas in the protective atmosphere preferably includes nitrogen; the CN coupling reaction is preferably carried out under oil bath heating; and the CN coupling reaction is also preferably carried out under stirring conditions. The present invention has no particular limitation on the stirring rate, and the reaction can be carried out smoothly according to the process well known in the art.

[0044] In the present invention, after the CN coupling reaction, the present invention preferably further comprises: purifying the obtained product system.

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

[0046] The present invention also provides the use of the 1,2,3-benzotriazine-4(3H)-one selenoside described in the above technical scheme or the 1,2,3-benzotriazine-4(3H)-one selenoside prepared by the preparation method described in the above technical scheme in the preparation of anti-schistosomal drugs.

[0047] The 1,2,3-benzotriazine-4(3H)-one seleno compound provided by the present invention and its preparation method and application are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0048] Example 1

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

[0050]

[0051] 0.1 mmol o-aminobenzanilide, 0.11 mmol diphenyl diselenide and 2 mL acetonitrile were added to the reaction tube, and then 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine and 0.1 mmol pyridine were added, and 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. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 90% and a purity of 99.9%.

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

[0053] 1H NMR (400MHz, CDCl3, ppm) δ8.25(d,J=2.0Hz,1H),7.98(d,J=8.5Hz,1H),7.77(dd ,J=8.5,2.0Hz,1H),7.67-7.60(m,4H),7.53(t,J=7.5Hz,2H),7.49-7.37(m,4H).

[0054] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.67,141.99,141.64,138.78,136.09,135.8 4,130.18,129.50,129.06,128.98,128.84,127.23,126.03,125.40,120.71;

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

[0056] Example 2

[0057] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0058]

[0059] 0.1mmol 2-amino-N-p-tolylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 42% and a purity of 99.9%.

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

[0061] 1HNMR (400MHz, CDCl3, ppm) δ8.27(s,1H),7.99(d,J=8.5Hz,1H),7.78(d,J=8.5Hz,1H),7.66(d, J=9.7Hz,2H),7.48(d,J=8.2Hz,2H),7.42(d,J=7.3Hz,3H),7.33(d,J=8.0Hz,2H),2.44(s,3H).

[0062] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.74,142.07,141.40,139.08,136.27,136.09,1 35.79,130.14,129.65,129.44,128.81,127.30,125.79,125.51,120.73,21.27;

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

[0064] Example 3

[0065] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0066]

[0067] 0.1mmol 2-amino-N-m-tolylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 78% and a purity of 99.9%.

[0068] The structure of the obtained product was characterized, and the structural 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] 0.1mmol 2-amino-N-p-fluorophenylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-m-fluorophenylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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 (400MHz, CDCl3, ppm) δ8.25(d,J=2.0Hz,1H),8.00(d,J=8.5Hz,1H),7.79(dd,J =8.5,2.0Hz,1H),7.67(d,J=6.1Hz,2H),7.51-7.39(m,6H),7.18(t,J=7.5Hz,1H).

[0086] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ163.76,161.30,154.52,142.15,141.78,136.15,135.90,130.2 0,129.57,128.92,127.08,125.34,121.64,121.61,120.57,116.04,115.83,113.78,113.53;

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

[0088] Example 6

[0089] The 1,2,3-benzotriazine-4(3H)-one seleno compound obtained in this example has the following structure:

[0090]

[0091] 0.1mmol 2-amino-N-o-fluorophenylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 48% and a purity of 99.9%.

[0092] The structure of the obtained product was characterized, and the structural 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] 0.1mmol 2-amino-N-adamantanemethylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-cyclopentylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-isopropylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-butylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 11

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

[0130]

[0131] 0.1mmol 2-amino-N-(3,4-dimethylphenyl)-benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-(3-phenylpropyl)-benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-[3-(trifluoromethyl)phenyl]benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 14

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

[0154]

[0155] 0.1mmol 2-amino-N-benzylbenzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 15

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

[0162]

[0163] 0.1mmol 2-amino-N-(4-methylbenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] 0.1mmol 2-amino-N-(3-methylbenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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 (400MHz, CDCl3, ppm) δ8.15(d,J=2.0Hz,1H),7.92(d,J=8.5Hz,1H),7.74(dd,J=8.5,2.1Hz,1H),7.63(d,J=7.8Hz,2H), 7.41(dd,J=10.7,7.2Hz,3H),7.28(d,J=7.7Hz,2H),7.21(t,J=7.5Hz,1H),7.09(d,J=7.5Hz,1H),5.53(s,2H),2.31(s,3H).

[0174] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.74,142.71,140.97,138.45,135.90,135.79,135.62,1 30.13,129.43,129.00,128.64,128.62,127.24,125.85,125.04,120.47,53.43,21.39;

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

[0176] Embodiment 17

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

[0178]

[0179] 0.1mmol 2-amino-N-(2-methylbenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 65% and a purity of 99.9%.

[0180] The structure of the obtained product was characterized, and the structural 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] Embodiment 18

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

[0186]

[0187] 0.1mmol 2-amino-N-(4-chlorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 19

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

[0194]

[0195] 0.1mmol 2-amino-N-(3-chlorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 20

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

[0202]

[0203] 0.1mmol 2-amino-N-(2-chlorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 21

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

[0210]

[0211] 0.1mmol 2-amino-N-(4-fluorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 22

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

[0218]

[0219] 0.1mmol 2-amino-N-(3-fluorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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 (400MHz, CDCl3, ppm) δ8.15(d,J=1.9Hz,1H),7.94(d,J=8.5Hz,1H),7.76(dd,J=8.6,2.0Hz,1H),7.63(d, J=6.4Hz,2H),7.45-7.37(m,3H),7.31-7.23(m,2H),7.17(d,J=9.6Hz,1H),6.98(t,J=7.8Hz,1H),5.55(s,2H).

[0222] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ164.07,161.62,154.76,142.64,141.40,138.01,137.93,135.98,135.85,130.33,1 30.24,130.16,129.50,128.73,127.11,124.92,124.39,124.36,120.35,115.81,115.59,115.35,115.14,52.84;

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

[0224] Embodiment 23

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

[0226]

[0227] 0.1mmol 2-amino-N-(2-fluorobenzyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 50% and a purity of 99.9%.

[0228] The structure of the obtained product was characterized, and the structural 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] Embodiment 24

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

[0234]

[0235] 0.1mmol 2-amino-N-(cyclohexylmethyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 25

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

[0242]

[0243] 0.1mmol 2-amino-N-(2-thienylmethyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 26

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

[0250]

[0251] 0.1mmol 2-amino-N-(2-furanylmethyl)benzamide, 0.11mmol diphenyl diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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 (400MHz, CDCl3, ppm) δ8.16(d,J=2.0Hz,1H),7.93(d,J=8.5Hz,1H),7.75(dd,J=8.6,2.1Hz,1H),7.63(d,J= 6.4Hz, 2H), 7.42 (dd, J = 11.0, 7.2Hz, 3H), 7.35 (s, 1H), 6.46 (d, J = 3.2Hz, 1H), 6.32 (d, J = 1.9Hz, 1H), 5.58 (s, 2H).

[0254] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.64,148.74,142.91,142.64,141.22,135.97,135.84,1 30.18,130.15,129.47,128.74,127.16,125.90,124.98,120.36,110.63,109.89,46.09;

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

[0256] Anti-schistosomal activity:

[0257] Live 45-day-old Schistosoma japonicum adults were collected and placed in RPMI-1640 culture medium (10 / 3mL / dish), and 3μL of the test compound was added to each dish, with a final concentration of 0.1mmol / L. Praziquantel was used as the positive control group: 3μL DMSO was added, and the mixture was shaken well after adding the drug, and placed in a 37°C, 5% CO2 incubator. After 16 hours of culture, the worms were washed 3 times with physiological saline, and fresh RPMI-1640 culture medium was added. The activity of Schistosoma japonicum after 24 to 72 hours of culture was observed under a stereomicroscope. The negative control was to add 3μL of solvent DMSO to the culture medium. The results are shown in Table 1.

[0258] Table 1 Anti-schistosomal activity results

[0259]

[0260] The experimental results show that when the concentration of the compound is 0.1mmol / L, the mortality rate of Schistosoma japonicum adults is 20% after 48 hours; at 72 hours, the compound has a 50% lethality rate to adults in vitro.

[0261] Embodiment 27

[0262] The 1,2,3-benzotriazine-4(3H)-one seleno compound 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 the reaction tube, and then 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine and 0.1 mmol pyridine were added, and 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. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside 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] Embodiment 28

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

[0271]

[0272] 0.1mmol o-aminobenzanilide, 0.11mmol (4-methylphenyl) diselenide and 2mL acetonitrile were added to the reaction tube, and then 0.2mmol silver nitrate, 0.03mmol 2,2'-bipyridine and 0.1mmol pyridine were added, and the mixture was stirred in an oil bath at 40°C for 12h. After the reaction, the mixture was separated and purified by column chromatography. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 41% and a purity of 99.9%.

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

[0274] 1 H NMR (400MHz, CDCl3, ppm) δ8.69(d,J=1.8Hz,1H),8.42(dd,J=8.5,1.8Hz,1H),8.32(d,J =8.4Hz,1H),7.64-7.58(m,4H),7.56-7.48(m,3H),7.29(d,J=7.9Hz,2H),2.36(s,3H).

[0275] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ154.36,148.66,144.71,138.89,138.39,131.5 4,130.85,130.18,129.30,129.18,125.98,125.92,124.21,120.81,21.43;

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

[0277] Embodiment 29

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

[0279]

[0280] 0.1 mmol o-aminobenzanilide, 0.11 mmol (3-fluorophenyl) diselenide and 2 mL acetonitrile were added to the reaction tube, and then 0.2 mmol silver nitrate, 0.03 mmol 2,2'-bipyridine and 0.1 mmol pyridine were added, and 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. The eluent used for the column chromatography was a mixed solvent of petroleum ether and ethyl acetate. 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 selenoside was obtained with a yield of 38% and a purity of 99.9%.

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

[0282] 1 HNMR (400MHz, CDCl3, ppm) δ8.33(d,J=2.0Hz,1H),8.05(d,J=8.5Hz,1H),7.85(dd,J=8.5,2.0Hz,1H),7. 62(d,J=7.8Hz,2H),7.55(t,J=7.5Hz,2H),7.48(t,J=7.3Hz,1H),7.44-7.31(m,3H),7.15-7.08(m,1H).

[0283] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ164.22,161.72,154.60,142.28,140.03,138.70,136.84,131.42,13 1.34,130.90,130.86,129.09,129.05,126.48,126.00,122.21,121.99,120.86,116.57,116.36.;

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

[0285] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A 1,2,3-benzotriazine-4(3H)-one seleno compound, characterized in that: It has the structure shown in Formula I: The R 1 including phenyl, first substituted phenyl, first substituted alkyl or cycloalkyl; The R 2 Includes phenyl, a second substituted phenyl or a second substituted alkyl.

2. The 1,2,3-benzotriazine-4(3H)-one seleno compound according to claim 1, characterized in that: The first substituted phenyl group includes a halophenyl group; The cycloalkyl group includes cyclohexyl; The substituent of the first substituted alkyl group includes a phenyl group, a benzyl group, a halogenphenyl group, an adamantyl group, a furyl group or a thienyl group.

3. The 1,2,3-benzotriazine-4(3H)-one seleno compound according to claim 1 or 2, characterized in that: It has a structure shown in any one of Formula I-1 to Formula I-30:

4. The method for preparing the 1,2,3-benzotriazine-4(3H)-one seleno compound according to any one of claims 1 to 3, characterized in that: The following steps are involved: The o-aminobenzoyl arylamine compound having a structure of formula II, the diselenide compound having a structure of formula III, nitrate, a ligand of the nitrate, an alkaline 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; 5. The preparation method according to claim 4, characterized in that: The o-aminobenzamide aromatic amine compounds include o-aminobenzanilide, 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-adamantanemethyl-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 amide, 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.

6. The preparation method according to claim 4, characterized in that: The diselenide compound includes one of diphenyl diselenide, dimethyl diselenide, (4-methylphenyl) diselenide, (3-fluorophenyl) diselenide and (4-fluorophenyl) diselenide.

7. The preparation method according to any one of claims 4 to 6, characterized in that: The molar ratio of the o-aminobenzoyl aromatic amine compound to the diselenide compound is 1:1-1.

5.

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

1.

9. The preparation method according to claim 4, characterized in that: The temperature of the CN coupling reaction is 20-60°C ， The time is 6 to 24 hours.

10. Use of the 1,2,3-benzotriazine-4(3H)-one seleno compound according to any one of claims 1 to 3 or the 1,2,3-benzotriazine-4(3H)-one seleno compound prepared by the preparation method according to any one of claims 4 to 9 in the preparation of anti-schistosomal drugs.

Images