CN113929635B - 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and preparation method and application thereof - Google Patents

1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and preparation method and application thereof Download PDF

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CN113929635B
CN113929635B CN202111323770.6A CN202111323770A CN113929635B CN 113929635 B CN113929635 B CN 113929635B CN 202111323770 A CN202111323770 A CN 202111323770A CN 113929635 B CN113929635 B CN 113929635B
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trimethoxyphenyl
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张为革
黄明鑫
关奇
刘润来
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Shenyang Pharmaceutical University
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Abstract

The invention belongs to the technical field of medicines, and relates to a 1, 6-diphenyl-1H-benzo [ d ]][1,2,3]Triazole compounds, and a preparation method and application thereof. The structural general formula of the target product is shown as follows, wherein R in the general formula M 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, C 1 ‑C 6 Alkyl, C 1 ‑C 6 An alkyl oxy group; r is R 5 ～R 9 Each independently is hydrogen, C 1 ‑C 6 Alkyl, C 1 ‑C 6 Alkyloxy, halogen, acetyl, nitro, amino, C 1 ‑C 6 Alkyl monosubstituted amino, C 1 ‑C 6 Alkyl disubstituted amino, hydroxy, trifluoromethyl. The compound has the effect of inhibiting tumor proliferation and has good prospect in the development of anti-tumor medicaments.

Description

1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medicines, relates to a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and a preparation method and application thereof, and particularly relates to the compound and pharmaceutically acceptable salts, solvates or hydrates thereof and a preparation method thereof, and application of the compound as a tumor cell proliferation inhibitor in an anti-tumor drug aspect.
Background
The malignant tumor seriously threatens the life health of human beings, and the existing clinical common antitumor drugs have the problems of unsatisfactory activity, serious adverse reaction and the like, so that the search for more efficient and safer antitumor drugs is important.
1H-benzo [ d ] [1,2,3] triazole is an important nitrogen-containing heterocycle, and compounds containing the heterocycle exhibit wide biological activities such as antifungal, hypoglycemic and the like, and related reports are found in: faggyas, et al European Journal of Organic chemistry.2019,5344-5353; S.Hamed, et al European Journal of Medicinal chemistry.2019,183,111677.
1, 6-diphenyl-1H-benzo [ d ] as concerns][1,2,3]Triazole compounds are less reported, wherein reports on the synthesis method of the compounds are shown in the following formula: ramachary, et al chem. Eur.j.2013,19, 13175-13181; E.SYNLETT.2014,25,1987-1990; for research literature on the biological activity of the compounds, see: eric, et al preparation of heterocyclic compounds for the treatment of arenavirus infection:WO 2020117794 (2020-06-11); representative compounds of this patent (as follows) are useful in the treatment of arenavirus infections and arenavirus glycoprotein mediated viral infections.
The invention relates to an anti-tumor activity research of 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compounds, which is not reported in the literature at present.
Disclosure of Invention
The invention aims to design and synthesize a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound with good anti-tumor activity, and the prepared compound shows good results in an in-vitro anti-tumor activity test.
The invention relates to a target product 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and salts and hydrates thereof, wherein the target product is defined as the following formula M:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, C 1 -C 6 Alkyl, C 1 -C 6 An alkyl oxy group; r is R 5 ～R 9 Each independently is hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkyloxy, halogen, acetyl, nitro, amino, C 1 -C 6 Alkyl monosubstituted amino, C 1 -C 6 Alkyl disubstituted amino, hydroxy, trifluoromethyl.
The present invention preferably relates to compounds of the general formula M defined below:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, C 1 -C 3 Alkyl, C 1 -C 3 An alkyl oxy group; r is R 5 ～R 9 Each independently is hydrogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkyloxy, halogen, acetyl, nitro, amino, C 1 -C 3 Alkyl monosubstituted amino, C 1 -C 3 Alkyl disubstituted amino, hydroxy, trifluoromethyl.
The invention more preferably relates to compounds of the general formula M defined below:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; r is R 5 ～R 9 Each independently is hydrogen, methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, iodo, acetyl, nitro, amino, methylamino, ethylamino, dimethylamino, diethylamino, hydroxy, trifluoromethyl.
The compound also comprises pharmaceutically acceptable nontoxic salts and hydrates thereof formed by the derivatives shown in the structural formula M, wherein the pharmaceutically acceptable nontoxic salts comprise salts formed by the derivatives and acid. The acid may be inorganic acid such as hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid or organic acid selected from acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid, and malic acid. The number of the crystal water of the hydrate is any real number from 0 to 16.
The preferred partial compounds of the present invention have the following structure:
compound 1
6- (4-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 2
6- (3-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 3
6- (4-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 4
6- (3-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 5
6- (3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 6
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 7
6- (4-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 8
6- (4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 9
6- (3-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 10
6- (4-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 11
6- (3-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 12
6- (4- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 13
6- (4-Nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 14
6- (3-Nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 15
6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 16
6- (4-Acetylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 17
6- (4-ethoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 18
6- (3-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 19
6- (4-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 20
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 21
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 22
6- (2-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 23
6- (2-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 24
1, 6-bis (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 25
6- (2, 4-dichlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 26
6- (2-fluoro-4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 27
6- (3-fluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 28
6- (3, 5-difluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 29
6- (4-nitro-3- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 30
6- (4-amino-3-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 31
6- (2-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 32
6- (2-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 33
6- (2-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 34
4-fluoro-6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
The 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound can be synthesized according to the following reaction route:
the reaction reagent: (a) Et (Et) 3 N,DMSO；(b)N 2 H 4 ·H 2 O(80％),FeCl 3 ·6H 2 O,AC,CH 3 CH 2 OH；(c)NaNO 2 , conc.H 2 SO 4 ,THF,H 2 O；(d)substituted phenylboronic acids or substituted phenylboronic acid pinacol esters,K 2 CO 3 ,Pd(PPh 3 ) 4 ,1,4-dioxane,H 2 O.
The substituted aniline I and the like are used as starting materials, and are subjected to substitution, reduction, cyclization, coupling and other reactions to obtain the 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound, which comprises the following steps:
(1) Dissolving substituted aniline I and compound II in dimethyl sulfoxide, adding triethylamine to perform substitution reaction, extracting with dichloromethane after the reaction, washing with saturated saline solution, and anhydrous Na 2 SO 4 Drying, and removing the solvent under reduced pressure to obtain a compound III; wherein, the molar ratio of the compound II to the substituted aniline I to the triethylamine is 1:1-1.5:3-10; the reaction temperature is 50-80 ℃, and the reaction time is 5-24 hours;
(2) Dissolving compound III, ferric trichloride hexahydrate and active carbon in absolute ethanol, adding 80% hydrazine hydrate for reduction reaction, filtering after the reaction, removing solvent in the filtrate under reduced pressure, adding ethyl acetate for dissolving and extracting, washing with saturated saline solution, and anhydrous Na 2 SO 4 Drying, and removing the solvent under reduced pressure to obtain a compound IV; wherein, the molar ratio of the compound III to the ferric trichloride hexahydrate to the active carbon to the 80% hydrazine hydrate is 1:0.05-0.5:5-50:5-50; the reaction temperature is 60-78 ℃, and the reaction time is 1-24h;
(3) Dissolving compound IV in tetrahydrofuran, adding concentrated sulfuric acid and NaNO 2 After the completion of the cyclization reaction, the solvent was removed under reduced pressure, dissolved in ethyl acetate, extracted, washed with saturated brine, and dried over Na 2 SO 4 Drying, removing the solvent under reduced pressure, and recrystallizing with ethanol to obtain compound V; wherein, compound IV, concentrated sulfuric acid and NaNO 2 The molar ratio of the materials is 1:1-30:1-5; the reaction temperature is-10-25 ℃, and the reaction time is 0.1-24h; tetrahydrofuran and NaNO 2 The volume ratio of water in the aqueous solution of (2) is 10-100:1;
(4) Dissolving a compound V and unsubstituted phenylboric acid or substituted phenylboric acid or unsubstituted phenylboric acid pinacol ester or substituted phenylboric acid pinacol ester in 1, 4-dioxane and water, adding potassium carbonate and tetraphenylphosphine palladium, performing coupling reaction, extracting the mixture with ethyl acetate, washing with saturated saline solution, and anhydrous Na 2 SO 4 Drying, removing solvent under reduced pressure, column chromatography or recrystallizing to obtain 1, 6-diphenyl-1H-benzo [ d ] with structural formula M][1,2,3]Triazole compounds; wherein, the molar ratio of the compound V, the substituted phenylboric acid or the substituted phenylboric acid pinacol ester to the potassium carbonate to the tetraphenylphosphine palladium is 1:1-3:1-10:0.03-0.3, the reaction temperature is 70-100 ℃, and the reaction time is 6-48h; the volume ratio of the 1, 4-dioxane to the water is 2-10:1.
The substituted phenylboronic acid of the present invention is preferably 4-fluorobenzeneboronic acid, 3-fluorobenzeneboronic acid, 4-chlorophenylboronic acid, 3-hydroxybenzeneboronic acid, 3-hydroxy-4-methoxyphenylboronic acid, 4-methylphenylboronic acid, 3-methylphenylboronic acid, 4-methoxyphenylboronic acid, 4-trifluoromethylphenylboronic acid, 4-nitrophenylboronic acid, 4-acetylphenylboronic acid, 4-ethoxyphenylboronic acid, 3-aminophenylboronic acid, 4-hydroxyphenylboronic acid, 3-hydroxy-4-methoxyphenylboronic acid, 2-chlorophenylboronic acid, 2-methoxyphenylboronic acid, 3,4, 5-trimethoxyphenylboronic acid, 2, 4-dichlorobenzoboronic acid, 2-fluoro-4-methylphenylboronic acid, 3-fluoro-4-nitrophenylboronic acid, 3, 5-difluoro-4-nitrophenylboronic acid, 3-trifluoromethyl-4-nitrophenylboronic acid, 3-nitro-4-aminophenylboronic acid, 2-fluorobenzeneboronic acid or 2-methylphenylboronic acid, and the pinacol ester of the substituted phenylboronic acid is preferably 4-aminophenylboronic acid or pinacol ester.
The invention also provides a pharmaceutical composition which comprises the 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound, salts and hydrates thereof and a pharmaceutically acceptable carrier.
The preparation method of the 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound provided by the invention is simple and feasible, and the yield is higher.
The invention further provides application of the 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound and salts and hydrates thereof or the pharmaceutical composition in preparation of medicines for treating tumor diseases, wherein the tumor is a human breast cancer, gastric cancer or lung cancer tumor strain.
The 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound has the effect of inhibiting tumor proliferation, can better treat tumor diseases, and has good development prospect in the development of anti-tumor medicaments.
Detailed Description
The invention will be further understood by the following examples, but the content of the invention is not limited to the examples.
The reagents used in the invention are all commercially available, and the nuclear magnetic resonance spectrum is determined by a Bruker AVANCE 400 nuclear magnetic resonance spectrometer, and the high resolution Mass spectrum is determined by an Agilent Accurate-Mass Q-TOF 6530 (Agilent, santa Clara, calif., USA) Mass spectrometer.
Example 1: preparation of 6-bromo-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
3,4, 5-trimethoxyaniline (54.60 mmol) and 4-bromo-2-fluoronitrobenzene (45.50 mmol) were dissolved in dimethyl sulfoxide (50 mL), and triethylamine (227.50 mmol) was added and reacted overnight at 65 ℃. After completion of the reaction, the mixture was extracted with methylene chloride (70 mL. Times.3), washed with saturated brine, and dried over anhydrous Na 2 SO 4 Drying and decompressing to remove the solvent to obtain the N- (5-bromo-2-nitrophenyl) -3,4, 5-trimethoxyaniline. The product was used in the next step without purification.
N- (5-bromo-2-nitrophenyl) -3,4, 5-trimethoxyaniline (7.83 mmol), ferric trichloride hexahydrate (300 mg), activated carbon (300 mg) were dissolved in absolute ethanol (30 mL), and then 80% hydrazine hydrate (78.3 mmol) was added to reflux for 4 hours. After the completion of the reaction, the mixture was filtered, the solvent was removed from the filtrate under reduced pressure, dissolved and extracted with ethyl acetate (30 mL. Times.3), washed with saturated brine, and dried over Na 2 SO 4 Drying and reducingThe solvent is removed under pressure to obtain 5-bromo-N 1 - (3, 4, 5-trimethoxyphenyl) benzene-1, 2-diamine. The product was used in the next step without purification.
5-bromo-N 1 - (3, 4, 5-trimethoxyphenyl) benzene-1, 2-diamine (5.66 mmol) was dissolved in tetrahydrofuran (20 mL) and stirred at 0 ℃. Concentrated sulfuric acid (28.30 mmol) and 1mL NaNO were then added 2 (6.23 mmol) in water at 0deg.C for 2 hours. After the reaction was completed, the solvent was removed under reduced pressure, dissolved and extracted with ethyl acetate (30 mL ×3), washed with saturated brine, and dried Na 2 SO 4 Drying, removing the solvent under reduced pressure, and recrystallizing with ethanol to obtain 6-bromo-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ]][1,2,3]Triazole. Brown solid; yield 68%; MP is 133-135 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.17(d,J＝1.20Hz, 1H),8.15(d,J＝8.80Hz,1H),7.65(dd,J 1 ＝1.68Hz,J 2 ＝8.80Hz,1H),7.12(s,2H), 3.90(s,6H),3.78(s,3H)；HRMS calcd for C 15 H 14 BrN 3 NaO 3 [M+Na] + :388.0090, found:388.0113。
example 2: preparation of 6-bromo-1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Preparation of 6-bromo-1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] in the same manner as in example 1 except that 3, 5-trimethoxyaniline (54.60 mmol) was used as a starting material][1,2,3]Triazole; the yield thereof was found to be 59%; mp is 136-138 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.15(d,J＝6.08Hz,1H),8.14(d,J＝ 0.36Hz,1H),7.66(dd,J 1 ＝1.56Hz,J 2 ＝8.92Hz,1H),6.99(d,J＝2.24Hz,2H), 6.74-6.72(m,1H),3.87(s,6H)；HRMS calcd for C 14 H 13 BrN 3 O 2 [M+H] + :334.0186, found:334.0191；C 14 H 12 BrN 3 NaO 2 [M+Na] + :356.0005,found:356.0013。
example 3: preparation of 6-bromo-1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Preparation of 6-bromo-1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] in the same manner as in example 1 except that 3, 4-trimethoxyaniline (54.60 mmol) was used as a starting material][1,2,3]Triazole; the yield is 50%; mp is 126-128 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.14(d,J＝9.08Hz,1H),8.08(d,J＝ 1.20Hz,1H),7.64(dd,J 1 ＝1.68Hz,J 2 ＝8.80Hz,1H),7.40(d,J＝2.44Hz,1H), 7.36(dd,J 1 ＝2.48Hz,J 2 ＝8.52Hz,1H),7.21(d,J＝8.56Hz,1H),3.88(s,3H),3.87 (s,3H)；HRMS calcd for C 14 H 12 BrN 3 NaO 2 [M+Na] + :356.0005,found:356.0022。
example 4: preparation of 6-bromo-4-fluoro-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
The same procedures used in example 1 were repeated except for using 5-bromo-1, 3-difluoro-2-nitrobenzene (45.50 mmol) as a starting material to prepare 6-bromo-4-fluoro-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ]][1,2,3]Triazole; the yield thereof was found to be 51%; mp is 159-161 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.04(d,J＝1.20Hz,1H),7.68 (dd,J 1 ＝1.20Hz,J 2 ＝9.92Hz,1H),7.12(s,2H),3.89(s,6H),3.78(s,3H)；HRMS calcd for C 15 H 13 BrFN 3 NaO 3 [M+Na] + :405.9996,found:405.9990。
example 5:6- (4-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 1)
The 6-bromo-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] prepared in example 1][1,2,3]Triazole (0.50 mmol) and 4-fluorophenylboronic acid (0.50 mmol) were dissolved in 6mL1, 4-dioxane and 2mL water, followed by the addition of potassium carbonate (2.00 mmol) and palladium tetraphenylphosphine (0.05 mmol) to react overnight at 100 ℃. After the completion of the reaction, the mixture was extracted with ethyl acetate (20 mL. Times.3), and the organic layers were combined, washed with saturated brine, and dried over Na 2 SO 4 Drying and removing the solvent under reduced pressure. Finally, column chromatography or recrystallization is carried out to obtain the target compound 1; yield 45%; mp is 164-166 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ8.17(d,J＝8.64Hz,1H), 7.78(s,1H),7.63-7.57(m,3H),7.19-7.15(m,2H),6.98(s,2H),3.94(s,9H)； 13 C-NMR(100MHz,CDCl 3 ):δ162.9(d,J＝246.67Hz),154.1(2C),145.7,141.1, 138.6,136.6(d,J＝3.10Hz),133.2,132.5,129.4,129.3,124.7,120.6,116.1,115.9, 108.1,101.3(2C),61.1,56.6(2C)；HRMS calcd for C 21 H 18 FN 3 NaO 3 [M+Na] + : 402.1224,found:402.1235。
example 6:6- (3-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 2)
Compound 2 was produced in the same manner as in example 5 except that 3-fluorobenzeneboronic acid (0.50 mmol) was used as a starting material; yield 62%; mp is 153-155 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ8.19(dd,J 1 ＝ 0.68Hz,J 2 ＝8.68Hz,1H),7.82-7.81(m,1H),7.65(dd,J 1 ＝1.52Hz,J 2 ＝8.68Hz, 1H),7.47-7.39(m,2H),7.34-7.30(m,1H),7.13-7.08(m,1H),6.98(s,2H),3.94(s, 9H)； 13 C-NMR(100MHz,CDCl 3 ):δ163.2(d,J＝245.24Hz),154.2(2C),146.0, 142.7(d,J＝7.70Hz),140.7(d,J＝2.09Hz),138.7,133.2,132.4,130.6(d,J＝8.40 Hz),124.6,123.4(d,J＝2.74Hz),120.7,114.9(d,J＝21.02Hz),114.7(d,J＝21.99 Hz),108.4,101.3(2C),61.1,56.6(2C)；HRMS calcd for C 21 H 18 FN 3 NaO 3 [M+Na] + : 402.1224,found:402.1236。
example 7:6- (4-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 3)
Compound 3 was prepared in the same manner as in example 5 except that 4-chlorophenylboronic acid (0.50 mmol) was used as a starting material; yield 41%; mp is 148-150 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ8.18(d,J＝ 8.64Hz,1H),7.79(s,1H),7.63(dd,J 1 ＝1.44Hz,J 2 ＝8.68Hz,1H),7.56(d,J＝8.52 Hz,2H),7.45(d,J＝8.52Hz,2H),6.98(s,2H),3.94(s,3H),3.93(s,6H)； 13 C-NMR (100MHz,CDCl 3 ):δ154.1(2C),145.9,140.8,139.0,138.6,134.4,133.2,132.4, 129.2(2C),128.9(2C),124.6,120.7,108.2,101.3(2C),61.1,56.6(2C)；HRMS calcd for C 21 H 18 ClN 3 NaO 3 [M+Na] + :418.0929,found:418.0948。
example 8:6- (3-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 4)
Compound 4 was prepared in the same manner as in example 5 except that 3-chlorophenylboronic acid (0.50 mmol) was used as a starting material; yield 49%; mp is 149-151 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ8.19(dd,J 1 ＝ 0.48Hz,J 2 ＝8.68Hz,1H),7.80(d,J＝0.64Hz,1H),7.63(dd,J 1 ＝1.52Hz,J 2 ＝ 8.68Hz,1H),7.61-7.60(m,1H),7.52-7.49(m,1H),7.41-7.36(m,2H),6.98(s,2H), 3.95(s,3H),3.94(s,6H)； 13 C-NMR(100MHz,CDCl 3 ):δ154.2(2C),146.0,142.4, 140.6,138.7,135.0,133.2,132.4,130.3,128.1,127.8,125.9,124.6,120.7,108.4, 101.3(2C),61.1,56.6(2C)；HRMS calcd for C 21 H 18 ClN 3 NaO 3 [M+Na] + :418.0929, found:418.0957。
example 9:6- (3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 5)
Compound 5 was produced in the same manner as in example 5 except that 3-hydroxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield is 50%; mp is 198-200 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ9.59(s, 1H),8.22(d,J＝8.68Hz,1H),7.96(s,1H),7.75(dd,J 1 ＝1.20Hz,J 2 ＝8.68Hz,1H), 7.32-7.28(m,1H),7.21(d,J＝7.72Hz,1H),7.18(s,2H),7.16-7.15(m,1H),6.84 (dd,J 1 ＝1.60Hz,J 2 ＝7.96Hz,1H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ158.4,154.2(2C),145.5,141.5,141.4,138.3,133.4,132.4,130.6, 124.9,120.3,118.8,115.6,114.8,108.8,102.2(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 19 N 3 NaO 4 [M+Na] + :400.1268,found:400.1287。
example 10:6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 6)
Compound 6 was prepared in the same manner as in example 5 except that 3-hydroxy-4-methoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield was 60%; mp is 203-205 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 9.15(s,1H),8.18(d,J＝8.68Hz,1H),7.90(s,1H),7.73(d,J＝8.80Hz,1H), 7.23-7.21(m,2H),7.18(s,2H),7.04(d,J＝8.84Hz,1H),3.90(s,6H),3.83(s,3H), 3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C),148.5,147.4,145.2, 141.3,138.3,133.5,132.8,132.5,124.7,120.2,119.0,115.0,113.1,107.9,102.1(2C), 60.7,56.9(2C),56.2；HRMS calcd for C 22 H 22 N 3 O 5 [M+H] + :408.1554,found: 408.1543。
example 11:6- (4-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 7)
Compound 7 was prepared in the same manner as in example 5 except that 4-aminophenylboronic acid pinacol ester (0.50 mmol) was used as a starting material; the yield was 70%; mp is 212-214 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.12(d,J＝8.72Hz,1H),7.86(s,1H),7.72(d,J＝8.80Hz,1H),7.51(d,J＝8.40Hz, 2H),7.16(s,2H),6.68(d,J＝8.44Hz,2H),5.35(s,2H),3.90(s,6H),3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.1(2C),149.6,144.7,142.1,138.2,133.7, 132.6,128.7(2C),126.9,124.2,120.0,114.7(2C),106.4,102.0(2C),60.7,56.9(2C)； HRMS calcd for C 21 H 21 N 4 O 3 [M+H] + :377.1608,found:377.1622。
example 12:6- (4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 8)
Compound 8 was prepared in the same manner as in example 5 except that 4-methylphenylboronic acid (0.50 mmol) was used as a starting material; yield 71%; MP is 183-185 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.22(d,J ＝8.72Hz,1H),8.01(s,1H),7.79(d,J＝8.72Hz,1H),7.70(d,J＝8.04Hz,2H), 7.31(d,J＝7.92Hz,2H),7.18(s,2H),3.90(s,6H),3.79(s,3H),2.36(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C),145.3,141.3,138.3,138.0,137.1, 133.5,132.4,130.1(2C),127.9(2C),124.9,120.3,108.6,102.1(2C),60.7,56.9(2C), 21.1；HRMS calcd for C 22 H 21 N 3 NaO 3 [M+Na] + :398.1475,found:398.1499。
example 13:6- (3-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 9)
Compound 9 was produced in the same manner as in example 5 except that 3-methylphenylboronic acid (0.50 mmol) was used as a starting material; yield 78%; mp is 175-177 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.23(d,J ＝8.68Hz,1H),8.02(s,1H),7.79(dd,J 1 ＝1.20Hz,J 2 ＝8.68Hz,1H),7.62(s,1H), 7.59(d,J＝7.88Hz,1H),7.41-7.37(m,1H),7.24(d,J＝7.48Hz,1H),7.18(s,2H), 3.90(s,6H),3.79(s,3H),2.40(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2 (2C),145.4,141.5,140.0,138.7,138.3,133.5,132.4,129.4,129.2,128.7,125.2, 125.0,120.3,108.9,102.2(2C),60.7,56.9(2C),21.5；HRMS calcd for C 22 H 21 N 3 NaO 3 [M+Na] + :398.1475,found:398.1498。
example 14:6- (4-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 10)
Compound 10 was prepared in the same manner as in example 5 except that 4-methoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 63%; mp is 148-150 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.20 (d,J＝8.68Hz,1H),7.99(s,1H),7.79-7.75(m,3H),7.18(s,2H),7.06(d,J＝8.76 Hz,2H),3.90(s,6H),3.82(s,3H),3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ 159.9,154.2(2C),145.2,141.1,138.2,133.5,132.5,132.3,129.3(2C),124.7,120.2, 115.0(2C),108.1,102.0(2C),60.7,56.9(2C),55.7；HRMS calcd for C 22 H 21 N 3 NaO 4 [M+Na] + :414.1424,found:414.1447。
example 15:6- (3-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 11)
Compound 11 was produced in the same manner as in example 5 except that 3-methoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 51%; mp is 138-140 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.23 (d,J＝8.68Hz,1H),8.07(d,J＝0.56Hz,1H),7.81(dd,J 1 ＝1.48Hz,J 2 ＝8.72Hz, 1H),7.44-7.40(m,1H),7.37-7.34(m,2H),7.20(s,2H),7.01-6.99(m,1H),3.91(s, 6H),3.84(s,3H),3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ160.3,154.2(2C), 145.6,141.6,141.3,138.3,133.3,132.5,130.5,125.1,120.4,120.3,114.3,113.6, 109.3,102.0(2C),60.7,56.9(2C),55.7；HRMS calcd for C 22 H 21 N 3 NaO 4 [M+Na] + : 414.1424,found:414.1447。
example 16:6- (4- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 12)
Compound 12 was produced in the same manner as in example 5 except that 4-trifluoromethylphenyl boronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 68%; mp is 179-181 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.30(d,J＝8.68Hz,1H),8.17(d,J＝0.56Hz,1H),8.05(d,J＝8.12Hz,2H), 7.88-7.84(m,3H),7.20(s,2H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ154.2(2C),145.8,144.1,139.7,138.4,133.4,132.3,129.0(2C),128.7, 126.3(q,J＝3.73Hz),126.1,125.0,123.4,120.6,110.0,102.2(2C),60.7,56.9(2C)； HRMS calcd for C 22 H 18 F 3 N 3 NaO 3 [M+Na] + :452.1192,found:452.1223。
example 17:6- (4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 13)
Compound 13 was prepared in the same manner as in example 5 except that 4-nitrobenzoic acid (0.50 mmol) was used as a starting material; yield 86%; mp is 228-230 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.33-8.31(m, 3H),8.22(s,1H),8.11(d,J＝8.04Hz,2H),7.90(d,J＝8.44Hz,1H),7.20(s,2H), 3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C),147.5, 146.4,146.0,138.8,138.4,133.3,132.3,129.4(2C),125.0,124.5(2C),120.7,110.5, 102.2(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 19 N 4 O 5 [M+H] + :407.1350,found: 407.1367。
example 18:6- (3-Nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 14)
In addition to using 3-nitrobenzoic acid (0.50 mmol) as a starting material, the following procedure was followedExample 5 compound 14 was prepared in the same manner; yield 78%; mp is 213-215 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.58(s, 1H),8.31-8.26(m,3H),8.23(s,1H),7.90(dd,J 1 ＝1.12Hz,J 2 ＝8.68Hz,1H), 7.82-7.78(m,1H),7.20(s,2H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ154.2(2C),148.9,145.9,141.7,138.9,138.4,134.8,133.4,132.3, 131.0,125.0,123.2,122.8,120.6,110.3,102.2(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 19 N 4 O 5 [M+H] + :407.1350,found:407.1370；C 21 H 18 N 4 NaO 5 [M+Na] + : 429.1169,found:429.1183。
example 19: 6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 15)
Compound 15 was produced in the same manner as in example 5 except that phenylboronic acid (0.50 mmol) was used as a raw material; the yield thereof was found to be 65%; mp is 163-165 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.24(d,J＝ 8.72Hz,1H),8.05(d,J＝0.48Hz,1H),7.82-7.80(m,3H),7.53-7.49(m,2H), 7.45-7.41(m,1H),7.19(s,2H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ154.2(2C),145.5,141.4,140.0,138.3,133.4,132.4,129.5(2C),128.5, 128.1(2C),125.0,120.3,109.0,102.1(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 19 N 3 NaO 3 [M+Na] + :384.1319,found:384.1342。
example 20:6- (4-Acetylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 16)
Compound 16 was produced in the same manner as in example 5 except that 4-acetylphenylboronic acid (0.50 mmol) was used as a starting material; yield 75%; mp is 178-180 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.28 (d,J＝8.68Hz,1H),8.16(d,J＝0.40Hz,1H),8.07(d,J＝8.48Hz,2H),7.97(d,J＝ 8.48Hz,2H),7.88(dd,J 1 ＝1.40Hz,J 2 ＝8.68Hz,1H),7.20(s,2H),3.91(s,6H), 3.79(s,3H),2.63(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ198.0,154.2(2C), 145.8,144.3,140.0,138.4,136.6,133.4,132.3,129.3(2C),128.4(2C),125.0,120.5, 109.8,102.1(2C),60.7,56.9(2C),27.3；HRMS calcd for C 23 H 21 N 3 NaO 4 [M+Na] + : 426.1424,found:426.1447。
example 21:6- (4-ethoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 17)
Compound 17 was prepared in the same manner as in example 5 except that 4-ethoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 51%; mp is 116-118 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.19 (d,J＝8.72Hz,1H),7.98(s,1H),7.78-7.73(m,3H),7.18(s,2H),7.04(d,J＝8.76 Hz,2H),4.08(q,J＝6.96Hz,2H),3.91(s,6H),3.79(s,3H),1.36(t,J＝6.92Hz, 3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ159.2,154.2(2C),145.1,141.1,138.3, 133.5,132.5,132.1,129.2(2C),124.7,120.2,115.4(2C),108.0,102.1(2C),63.6, 60.7,56.9(2C),15.1；HRMS calcd for C 23 H 24 N 3 O 4 [M+H] + :406.1761,found: 406.1785。
example 22:6- (3-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 18)
Compound 18 was prepared in the same manner as in example 5 except that 3-aminophenylboronic acid (0.50 mmol) was used as a starting material; yield 42%; mp is 206-208 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.21(d, J＝8.68Hz,1H),7.90(s,1H),7.73(d,J＝8.64Hz,1H),7.17(s,2H),7.14(d,J＝ 7.76Hz,1H),6.97(s,1H),6.92(d,J＝7.40Hz,1H),6.63(d,J＝7.64Hz,1H),5.21 (s,2H),3.90(s,6H),3.79(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C), 149.7,145.4,142.3,140.6,138.3,133.5,132.4,130.1,124.8,120.2,115.6,114.3, 113.2,108.3,102.2(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 21 N 4 O 3 [M+H] + : 377.1608,found:377.1624。
example 23:6- (4-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 19)
The procedure of example 5 was followed except that 4-hydroxyphenylboronic acid (0.50 mmol) was used as a starting materialCompound 19 was prepared in the same manner; the yield was 70%; MP is 286-288 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ9.74(s, 1H),8.17(d,J＝8.72Hz,1H),7.93(s,1H),7.75(dd,J 1 ＝1.40Hz,J 2 ＝8.76Hz,1H), 7.64(d,J＝8.64Hz,2H),7.17(s,2H),6.91(d,J＝8.60Hz,2H),3.91(s,6H),3.79(s, 3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ158.3,154.1(2C),145.0,141.5,138.2, 133.5,132.5,130.6,129.2(2C),124.6,120.1,116.4(2C),107.6,102.1(2C),60.7, 56.9(2C)；HRMS calcd for C 21 H 19 N 3 NaO 4 [M+Na] + :400.1268,found:400.1291。
example 24:6- (4-methoxy-3-hydroxyphenyl) -1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (compound 20)
Except for using 3-hydroxy-4-methoxyphenylboronic acid (0.50 mmol) and 6-bromo-1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] prepared in example 2][1,2,3]Compound 20 was produced in the same manner as in example 5 except that triazole (0.50 mmol) was used as a starting material; the yield thereof was found to be 82%; mp is 94-96 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 9.18(s,1H),8.19(d,J＝8.72Hz,1H),7.88(s,1H),7.73(d,J＝8.72Hz,1H), 7.22-7.19(m,2H),7.05(d,J＝1.88Hz,2H),6.74-6.73(m,1H),5.76(s,1H),3.88(s, 6H),3.83(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ161.8(2C),148.5,147.4,145.3, 141.5,138.4,133.1,132.7,124.8,120.3,119.0,115.0,113.1,108.0,102.0(2C),101.1, 56.2(3C)；HRMS calcd for C 21 H 19 N 3 NaO 4 [M+Na] + :400.1268,found:400.1269。
example 25:6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (compound 21)
Except for using 3-hydroxy-4-methoxyphenylboronic acid (0.50 mmol) and 6-bromo-1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] prepared in example 3][1,2,3]Compound 21 was prepared in the same manner as in example 5 except that triazole (0.50 mmol) was used as a starting material; yield 61%; mp is 186-188 ℃; 1 H-NMR(400MHz,DMSO-d 6 ): δ9.15(s,1H),8.17(d,J＝8.64Hz,1H),7.83(s,1H),7.72(d,J＝8.64Hz,1H),7.43 (d,J＝11.60Hz,2H),7.23(d,J＝8.64Hz,1H),7.20(d,J＝7.08Hz,2H),7.03(d,J ＝8.32Hz,1H),3.89(s,6H),3.83(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ150.0, 149.7,148.5,147.4,145.1,141.2,133.5,132.8,129.8,124.6,120.2,118.9,116.0, 115.0,113.1,112.6,108.3,107.8,56.4,56.3,56.2；HRMS calcd for C 21 H 19 N 3 NaO 4 [M+Na] + :400.1268,found:400.1272。
example 26:6- (2-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 22)
Compound 22 was prepared in the same manner as in example 5 except that 2-chlorobenzoic acid (0.50 mmol) was used as a starting material; the yield was 55%; mp is 140-142 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.25(d,J ＝8.56Hz,1H),7.95(s,1H),7.63-7.56(m,3H),7.48-7.44(m,2H),7.16(s,2H),3.89 (s,6H),3.77(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C),145.4,139.5 (2C),138.3,132.7,132.4,132.3,132.0,130.4,130.2,128.1,127.2,119.6,112.1, 102.0(2C),60.7,56.8(2C)；HRMS calcd for C 21 H 18 ClN 3 NaO 3 [M+Na] + :418.0929, found:418.0944。
example 27:6- (2-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 23)
Compound 23 was prepared in the same manner as in example 5 except that 2-methoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 63%; mp is 150-152 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.17 (d,J＝8.68Hz,1H),7.91(s,1H),7.63(dd,J 1 ＝1.24Hz,J 2 ＝8.64Hz,1H),7.45-7.38 (m,2H),7.17-7.16(m,3H),7.09-7.05(m,1H),3.89(s,6H),3.79(s,3H),3.77(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ156.7,154.1(2C),145.1,139.2,138.2,132.8, 132.5,131.4,130.0,129.5,127.5,121.4,119.2,112.4,111.4,101.8(2C),60.7,56.8 (2C),56.0；HRMS calcd for C 22 H 21 N 3 NaO 4 [M+Na] + :414.1424,found:414.1438。
example 28:1, 6-bis (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 24)
Compound 24 was produced in the same manner as in example 5 except that 3,4, 5-trimethoxyphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 59%; mp is 138-140 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.22(d,J＝8.68Hz,1H),8.11(s,1H),7.85(d,J＝8.68Hz,1H),7.23(s,2H),7.07(s, 2H),3.92(s,6H),3.88(s,6H),3.78(s,3H),3.72(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ154.2(2C),153.7(2C),145.5,141.6,138.1(2C),135.9,133.1,132.6, 125.3,120.1,109.3,105.8(2C),101.6(2C),60.7,60.5,56.8(2C),56.5(2C)；HRMS calcd for C 24 H 25 N 3 NaO 6 [M+Na] + :474.1636,found:474.1652。
example 29:6- (2, 4-dichlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 25)
Compound 25 was prepared in the same manner as in example 5 except that 2, 4-dichlorobenzoboric acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 64%; mp is 166-168 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.26 (d,J＝8.56Hz,1H),7.97(s,1H),7.77(d,J＝1.52Hz,1H),7.61-7.54(m,3H),7.16 (s,2H),3.89(s,6H),3.77(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.2(2C), 145.5,138.5,138.4,138.3,133.9,133.7,133.1,132.6,132.3,129.8,128.2,127.0, 119.7,112.3,101.9(2C),60.7,56.8(2C)；HRMS calcd for C 21 H 17 Cl 2 N 3 NaO 3 [M+Na] + :452.0539,found:452.0560。
example 30:6- (2-fluoro-4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 26)
Compound 26 was prepared in the same manner as in example 5 except that 2-fluoro-4-methylphenylboronic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 63%; mp is 161-163 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.24(d,J＝8.68Hz,1H),7.97(s,1H),7.68-7.65(m,1H),7.59-7.55(m,1H), 7.20-7.14(m,4H),3.89(s,6H),3.78(s,3H),2.38(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ159.5(d,J＝244.70Hz),154.2(2C),145.3,141.0(d,J＝8.26Hz), 138.3,136.1,133.0,132.3,131.5(d,J＝3.25Hz),126.5(d,J＝2.65Hz),126.2(d,J ＝2.84Hz),125.0(d,J＝12.84Hz),119.9,117.0(d,J＝22.30Hz),111.2(d,J＝3.05 Hz),102.0(2C),60.7,56.8(2C),21.0；HRMS calcd for C 22 H 21 FN 3 O 3 [M+H] + : 394.1561,found:394.1582；C 22 H 20 FN 3 NaO 3 [M+Na] + :416.1381,found:416.1405。
example 31:6- (3-fluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 27)
Compound 27 was prepared in the same manner as in example 5 except that 3-fluoro-4-nitrobenzoic acid (0.50 mmol) was used as a starting material; the yield thereof was found to be 44%; mp is 199-201 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.32-8.30(m,2H),8.27-8.23(m,1H),8.14(dd,J 1 ＝1.48Hz,J 2 ＝12.92Hz,1H), 7.93(d,J＝8.68Hz,2H),7.19(s,2H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100 MHz,DMSO-d 6 ):δ155.4(d,J＝256.76Hz),154.1(2C),147.9(d,J＝8.93Hz), 146.2,138.4,137.6,136.5(d,J＝7.41Hz),133.3,132.2,127.2(d,J＝1.93Hz), 125.0,124.7(d,J＝3.36Hz),120.7,117.9(d,J＝21.85Hz),110.9,102.3(2C),60.7, 56.9(2C)；HRMS calcd for C 21 H 18 FN 4 O 5 [M+H] + :425.1256,found:425.1227。
example 32:6- (3, 5-difluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 28)
Compound 28 was prepared in the same manner as in example 5 except that 3, 5-difluoro-4-nitrobenzoic acid (0.50 mmol) was used as a starting material; yield 23%; mp is 208-210 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ 8.19(d,J＝8.64Hz,1H),7.75(s,1H),7.54(dd,J 1 ＝0.96Hz,J 2 ＝8.64Hz,1H),7.28 (d,J＝9.04Hz,2H),6.88(s,2H),3.88(s,3H),3.87(s,6H)； 13 C-NMR(100MHz, CDCl 3 ):δ156.3(d,J＝2.59Hz),154.3(2C),153.7(d,J＝2.72Hz),146.6,146.2(t,J ＝9.24Hz,2C),139.0,137.5,133.2,132.0,123.9,121.5,112.2(d,J＝3.45Hz),112.0 (d,J＝3.44Hz),109.1,101.5(2C),61.1,56.6(2C)；HRMS calcd for C 21 H 17 F 2 N 4 O 5 [M+H] + :443.1162,found:443.1191。
example 33:6- (4-nitro-3- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 29)
Compound 29 was prepared in the same manner as in example 5 except that 3-trifluoromethyl-4-nitrobenzoic acid (0.50 mmol) was used as a starting material; yield 30%; mp is 175-177 ℃; 1 H-NMR(400MHz,CDCl 3 ):δ 8.20(d,J＝8.64Hz,1H),7.98(s,1H),7.96(d,J＝8.44Hz,1H),7.90-7.88(m,1H), 7.80(s,1H),7.60(dd,J 1 ＝1.16Hz,J 2 ＝8.64Hz,1H),6.90(s,2H),3.88(s,3H),3.87 (s,6H)； 13 C-NMR(100MHz,CDCl 3 ):δ154.3(2C),147.3,146.5,145.4,138.9,138.1, 133.2,132.1,131.9,127.2(q,J＝5.30Hz),126.0,124.6(d,J＝34.04Hz),124.3, 121.9(d,J＝272.19Hz),121.5,109.3,101.4(2C),61.1,56.6(2C)；HRMS calcd for C 22 H 18 F 3 N 4 O 5 [M+H] + :475.1224,found:475.1214。
example 34:6- (4-amino-3-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 30)
Compound 30 was prepared in the same manner as in example 5 except that 3-nitro-4-aminophenylboronic acid (0.50 mmol) was used as a starting material; the yield is 50%; mp 253-255 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ 8.35(d,J＝2.16Hz,1H),8.20(d,J＝8.72Hz,1H),8.02(s,1H),7.93(dd,J 1 ＝2.16 Hz,J 2 ＝8.84Hz,1H),7.78(dd,J 1 ＝1.36Hz,J 2 ＝8.76Hz,1H),7.59(s,2H),7.18(s, 2H),7.15(d,J＝8.92Hz,1H),3.91(s,6H),3.79(s,3H)； 13 C-NMR(100MHz, DMSO-d 6 ):δ154.1(2C),146.3,145.2,139.5,138.3,135.4,133.5,132.4,131.0, 127.1,124.3,124.2,120.5,120.4,108.0,102.1(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 20 N 5 O 5 [M+H] + :422.1459,found:422.1490。
example 35:6- (2-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 31)
Except forCompound 31 was prepared in the same manner as in example 5 except that 2-aminophenylboronic acid pinacol ester (0.50 mmol) was used as a starting material; the yield thereof was found to be 77%; mp is 201-203 ℃; 1 H-NMR(400MHz,DMSO-d 6 ): δ8.22(d,J＝8.60Hz,1H),7.94(s,1H),7.53(dd,J 1 ＝1.32Hz,J 2 ＝8.64Hz,1H), 7.22(s,2H),7.13(dd,J 1 ＝1.36Hz,J 2 ＝7.56Hz,1H),7.10-7.06(m,1H),6.80-6.78 (m,1H),6.68-6.64(m,1H),5.10(s,2H),3.88(s,6H),3.76(s,3H)； 13 C-NMR(100 MHz,DMSO-d 6 ):δ154.2(2C),146.0,145.1,140.5,138.1,133.1,132.5,130.9,129.2, 126.9,124.9,120.2,117.2,116.1,110.9,101.8(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 20 N 4 NaO 3 [M+Na] + :399.1428,found:399.1448。
example 36:6- (2-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 32)
Compound 32 was prepared in the same manner as in example 5 except that 2-fluorobenzeneboronic acid (0.50 mmol) was used as a starting material; yield 48%; mp is 158-160 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.26(d,J ＝8.64Hz,1H),8.02(s,1H),7.71-7.67(m,2H),7.52-7.46(m,1H),7.39-7.33(m,2H), 7.18(s,2H),3.90(s,6H),3.78(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ159.6(d, J＝244.96Hz),154.2(2C),145.4,138.3,136.0,133.0,132.3,131.9(d,J＝2.75Hz), 130.7(d,J＝8.40Hz),128.1(d,J＝12.68Hz),126.6(d,J＝2.51Hz),125.5(d,J＝ 3.33Hz),120.0,116.7(d,J＝22.27Hz),111.5(d,J＝2.86Hz),102.1(2C),60.7, 56.8(2C)；HRMS calcd for C 21 H 18 FN 3 NaO 3 [M+Na] + :402.1224,found:402.1238。
example 37:6- (2-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 33)
Compound 33 was produced in the same manner as in example 5 except that 2-methylphenylboronic acid (0.50 mmol) was used as a starting material; the yield was 55%; mp is 164-166 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ8.21(d, J＝8.56Hz,1H),7.80(s,1H),7.49(d,J＝8.60Hz,1H),7.35-7.29(m,4H),7.16(s, 2H),3.88(s,6H),3.76(s,3H),2.29(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ 154.1(2C),145.1,142.3,141.0,138.3,135.5,132.9,132.4,130.9,130.4,128.3,127.1, 126.5,119.5,111.2,102.0(2C),60.7,56.8(2C),20.7；HRMS calcd for C 22 H 21 N 3 NaO 3 [M+Na] + :398.1475,found:398.1496。
example 38: 4-fluoro-6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole (Compound 34)
Except that phenylboronic acid (0.50 mmol) and 6-bromo-4-fluoro-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] prepared in example 4 were used][1,2,3]Compound 34 was prepared in the same manner as in example 5 except that triazole (0.50 mmol) was used as a starting material; yield 30%; mp is 207-209 ℃; 1 H-NMR(400MHz,DMSO-d 6 ):δ7.89 (s,1H),7.83(d,J＝7.36Hz,2H),7.71(d,J＝11.84Hz,1H),7.52-7.42(m,3H),7.18 (s,2H),3.89(s,6H),3.78(s,3H)； 13 C-NMR(100MHz,DMSO-d 6 ):δ154.1(2C), 152.7(d,J＝253.73Hz),142.8(d,J＝6.64Hz),138.9,138.6,136.2(d,J＝6.97Hz), 135.2(d,J＝19.24Hz),131.9,129.5(2C),129.1,128.2(2C),109.4(d,J＝17.20Hz), 105.5(d,J＝3.98Hz),102.5(2C),60.7,56.9(2C)；HRMS calcd for C 21 H 18 FN 3 NaO 3 [M+Na] + :402.1224,found:402.1224。
example 39: in vitro antitumor Activity test of the Compounds of the invention
The in vitro activity test method and results are as follows: among them, colchicine (Colchicine) reported in the literature is a positive experimental group.
The screening method comprises the following steps: reduction of tetrazolium salts (MTT)
Cell lines: human breast cancer cell line (MCF-7 cell line), human gastric cancer cell line (SGC-7901 cell line), human lung cancer cell line (A549 cell line)
The action time is as follows: 72 hours
The inhibition rate (10. Mu.g/mL) of each compound against the growth of three tumor cells is shown in Table-1.
TABLE-1
Example 40: test of antitumor Activity in animals of Compounds of the invention
The compound 6 with better in vitro activity is selected for testing the anti-tumor activity in animals, the used model is a mouse S-180 sarcoma model, and the positive control drug is Fluorouracil (5-Fu) which is a clinically common anti-tumor drug.
The experimental method comprises the following steps: selecting 18-22 g female Kunming mice and well-grown 7-11 days S-180 tumor, preparing tumor tissue into cell suspension, inoculating into right side underarm of mice, and subcutaneously administering about 1.0-2.0X10 6 Cells/animals were randomly caged 24 hours after inoculation and given by intraperitoneal injection for 7 consecutive days. Animals were sacrificed 24 hours after drug withdrawal, weighed, tumor weights were calculated for each group, tumor inhibition was determined according to the following formula and t-test was performed.
Tumor inhibition ratio = [ (average tumor weight of blank control group-average tumor weight of treatment group)/(average tumor weight of blank control group) ]100%
The experimental results are shown in Table-2.
TABLE-2
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Claims (10)

1. 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound of formula M:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, C 1 -C 6 Alkyl, C 1 -C 6 An alkyl oxy group; r is R 5 ～R 9 Each independently is hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkyloxy, halogen, acetyl, nitro, amino, C 1 -C 6 Alkyl monosubstituted amino, C 1 -C 6 Alkyl disubstituted amino, hydroxy, trifluoromethyl.
2. A compound according to claim 1 and salts thereof, wherein:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, C 1 -C 3 Alkyl, C 1 -C 3 An alkyl oxy group; r is R 5 ～R 9 Each independently is hydrogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkyloxy, halogen, acetyl, nitro, amino, C 1 -C 3 Alkyl monosubstituted amino, C 1 -C 3 Alkyl disubstituted amino, hydroxy, trifluoromethyl.
3. A compound according to claim 1 or 2 and salts thereof, wherein:
wherein in the general formula M, R 1 ～R 3 Each independently is methoxy or hydrogen, but not simultaneously hydrogen; r is R 4 Independently hydrogen, fluorine, chlorine, methyl, ethyl, methoxy, ethoxy; r is R 5 ～R 9 Each independently is hydrogen, methyl, ethyl, methoxy, ethoxy, fluoro, chloro, bromo, iodo, acetyl, nitro, amino, methylamino, ethylamino, dimethylamino, diethylamino, hydroxy, trifluoromethyl.
4. A compound according to claim 1 or 2 and salts thereof, wherein:
the salt is formed by a compound with a general formula M and acid, and the acid is selected from hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid and malic acid.
5. A compound according to claim 1 or 2, and salts and hydrates thereof, characterized in that: the compound is selected from:
compound 1
6- (4-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 2
6- (3-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 3
6- (4-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 4
6- (3-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 5
6- (3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 6
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 7
6- (4-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 8
6- (4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 9
6- (3-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 10
6- (4-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 11
6- (3-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 12
6- (4- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 13
6- (4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 14
6- (3-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 15
6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 16
6- (4-Acetylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole Compound 17
6- (4-ethoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 18
6- (3-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 19
6- (4-hydroxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 20
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 5-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 21
6- (4-methoxy-3-hydroxyphenyl) -1- (3, 4-dimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 22
6- (2-chlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 23
6- (2-methoxyphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 24
1, 6-bis (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 25
6- (2, 4-dichlorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 26
6- (2-fluoro-4-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 27
6- (3-fluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 28
6- (3, 5-difluoro-4-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 29
6- (4-nitro-3- (trifluoromethyl) phenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 30
6- (4-amino-3-nitrophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 31
6- (2-aminophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 32
6- (2-fluorophenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole
Compound 33
6- (2-methylphenyl) -1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole compound 34
4-fluoro-6-phenyl-1- (3, 4, 5-trimethoxyphenyl) -1H-benzo [ d ] [1,2,3] triazole.
6. A process for the preparation of a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound according to any one of claims 1 to 5, characterized in that: the method comprises the following steps:
(1) Dissolving substituted aniline I and a compound II in dimethyl sulfoxide, adding triethylamine, and performing substitution reaction to obtain a compound III;
(2) Dissolving a compound III, ferric trichloride hexahydrate and active carbon in absolute ethyl alcohol, adding 80% hydrazine hydrate, and carrying out a reduction reaction to obtain a compound IV;
(3) Dissolving compound IV in tetrahydrofuran, adding concentrated sulfuric acid and NaNO 2 Carrying out cyclization reaction on the aqueous solution of (2) to obtain a compound V;
(4) Dissolving a compound V and unsubstituted phenylboric acid or substituted phenylboric acid or unsubstituted phenylboric acid pinacol ester or substituted phenylboric acid pinacol ester in 1, 4-dioxane and water, adding potassium carbonate and tetraphenylphosphine palladium, and carrying out a coupling reaction to obtain a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound with a structural general formula M;
the reaction route is as follows:
7. the method of manufacturing according to claim 6, wherein: in the step (1), the molar ratio of the compound II to the substituted aniline I to the triethylamine is 1:1-1.5:3-10; the reaction temperature is 50-80 ℃, and the reaction time is 5-24 hours;
in the step (2), the molar ratio of the compound III to the ferric trichloride hexahydrate to the active carbon to the 80% hydrazine hydrate is 1:0.05-0.5:5-50:5-50; the reaction temperature is 60-78 ℃, and the reaction time is 1-24h;
in the step (3), the compound IV, concentrated sulfuric acid and NaNO 2 The molar ratio of the materials is 1:1-30:1-5; the reaction temperature is-10-25 ℃, and the reaction time is 0.1-24h; tetrahydrofuran and NaNO 2 The volume ratio of water in the aqueous solution of (2) is 10-100:1;
in the step (4), the molar ratio of the compound V, the substituted phenylboronic acid or the substituted phenylboronic acid pinacol ester, the potassium carbonate and the tetraphenylphosphine palladium is 1:1-3:1-10:0.03-0.3, the reaction temperature is 70-100 ℃, and the reaction time is 6-48h; the volume ratio of the 1, 4-dioxane to the water is 2-10:1.
8. A pharmaceutical composition comprising a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound according to any one of claims 1 to 5 and salts thereof and a pharmaceutically acceptable carrier.
9. Use of a 1, 6-diphenyl-1H-benzo [ d ] [1,2,3] triazole compound according to any one of claims 1 to 5 or a salt thereof or a pharmaceutical composition according to claim 8 for the preparation of an antitumor drug.
10. The use according to claim 9, wherein the tumour is a human breast, gastric or lung cancer tumour strain.
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