Indazole n-oxides, methods of synthesis and anticancer activity applications thereof

Abstract

The application discloses indazole nitrogen oxide and a synthesis method and anticancer activity application thereof, and belongs to the technical field of organic synthesis and drug discovery. N-nitrosoaniline compound 1, diazindione compound 2, a catalyst, an additive and hexafluoroisopropanol are mixed, and the mixture is reacted by temperature rising to obtain indazole nitrogen oxide. The chemical structure of the indazole nitrogen oxide is as follows: researches show that the indazole nitrogen oxide has the activity of inhibiting the proliferation of Hela, A549 and HCT-116 cancer cells, and has potential medicinal value. Meanwhile, the synthesis method provided by the application is completed by one-pot multi-step tandem reaction, and the process is simple and efficient. The synthesis method has the following remarkable characteristics: raw materials are cheap and easy to obtain, the product is valuable, the steps are economical and atomic economy is high.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and drug discovery technology, specifically relating to an indazole nitride, its synthesis method, and its anticancer activity. Background Technology

[0002] Indazole compounds often possess significant biological activity and unique physicochemical properties, thus playing an important role in fields such as synthetic chemistry, medicinal chemistry, and materials chemistry. On the other hand, organic molecules with nitrogen-oxygen structural units have received increasing attention in drug development because nitrogen-oxygen structural units can improve the water solubility of the parent compound or reduce its membrane permeability.

[0003] Indazole nitrides, obtained by introducing nitrogen-oxygen structural units onto the indazole ring, have been found to possess strong antiprotozoal activity, demonstrating potential application value. Furthermore, the nitrogen-oxygen structural units in indazole nitrides can also serve as directing groups, assisting in the selective mounting of desired functional group regions onto the indazole ring, thereby obtaining target molecules that cannot be synthesized by other methods.

[0004] Given its importance, several methods for synthesizing indazole nitrides have been developed in the existing literature. Although these methods are relatively reliable, they still have problems such as the difficulty in obtaining raw materials, cumbersome steps, poor atom economy, low efficiency, and harsh reaction conditions.

[0005] Therefore, synthesizing novel indazole nitrogen oxides, studying their biological activity and medicinal value, and developing simple, efficient, and sustainable atom-economical methods for synthesizing these novel indazole nitrogen oxides from readily available raw materials under mild reaction conditions are of significant theoretical and practical value. Summary of the Invention

[0006] In order to address the problems existing in the prior art, one of the objectives of this invention is to provide a new class of indazole nitrides, which studies have shown to have good anticancer activity.

[0007] The second objective of this invention is to provide the application of indazole nitride in the preparation of anticancer drugs.

[0008] A third objective of this invention is to provide a pharmaceutical composition for treating cervical cancer, lung cancer, and colon cancer, wherein the active ingredient is indazole nitride provided by this invention.

[0009] The fourth objective of this invention is to provide a method for synthesizing indazole nitrogen oxides.

[0010] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0011] Indazole nitrogen oxides have the following general chemical structural formula:

[0012]

[0013] Where: R 1 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkoxycarbonyl, phenyl, benzyl, trifluoromethyl, or halogen, R 1 Selected from mono- or multi-substitution; R 2 C 1-6 Chain alkyl, C 3-6 cycloalkyl or benzyl; R 3 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 3 Selected from mono- or multi-substitution.

[0014] Furthermore, in the above general formula structure, in the most preferred case, the following specific structure is selected:

[0015]

[0016] The aforementioned application of indazole nitride in the preparation of anticancer active drugs, wherein the anticancer activity is against cervical cancer, lung cancer and colon cancer.

[0017] Studies have shown that the indazole nitrides provided by this invention have inhibitory activity against the proliferation of three cancer cells: HeLa, A549, and HCT-116, suggesting that the compounds of this invention can serve as active ingredients in drugs for treating cervical cancer, lung cancer, and colon cancer. In particular, the aforementioned preferred compounds significantly inhibit the growth and proliferation of HeLa, A549, and HCT-116, suggesting that these compounds, as active ingredients in anticancer drugs, have preventive, therapeutic, and inhibitory effects on the progression of cervical cancer, lung cancer, and colon cancer.

[0018] A pharmaceutical composition for treating cervical cancer, lung cancer, and colon cancer, wherein the active ingredient is the aforementioned indazole nitride.

[0019] The above-mentioned method for synthesizing indazole nitrides uses N-nitrosoaniline compounds and diazonium dione compounds as raw materials; it includes the following steps: mixing N-nitrosoaniline compound 1, diazonium dione compound 2, catalyst, additives, and hexafluoroisopropanol (HFIP), and reacting at elevated temperature to obtain indazole nitrides 3. The reaction equation is as follows:

[0020]

[0021] Where: R 1 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C1-4 Alkoxycarbonyl, phenyl, benzyl, trifluoromethyl, or halogen, R 1 For mono- or multi-element substitution; R 2 C 1-6 Chain alkyl, C 3-6 cycloalkyl or benzyl; R 3 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 3 It can be replaced by a single or multiple elements.

[0022] Furthermore, in the above technical solution, the additive is copper acetate or a mixture of copper acetate and one or more of 2,2,6,6-tetramethylpiperidine oxide, silver acetate, silver oxide, silver carbonate, or silver nitrate.

[0023] Furthermore, in the above technical solution, the catalyst is dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([RhCp*Cl2]2) or tri(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III) di(hexafluoroantimonate) ([RhCp*(MeCN)3](SbF6)2).

[0024] Furthermore, in the above technical solution, the molar ratio of N-nitrosoaniline compound 1, diazonium dione compound 2, catalyst and additive is 1:1-1.5:0.04-0.06:1-5.

[0025] Furthermore, in the above technical solution, the reaction temperature is 60-100℃.

[0026] Furthermore, in the above technical solution, the reaction is carried out in an atmosphere of air, oxygen, or an inert gas.

[0027] Beneficial effects of the invention:

[0028] (1) The indazole nitrogen oxide provided by the present invention, through screening of compounds with various substituents and verification by anti-cancer cell activity test, shows that the compound provided by the present invention has significant inhibitory activity on the proliferation of three cancer cells, namely HeLa, A549 and HCT-116, suggesting that the compound of the present invention has anti-cancer activity against cervical cancer, lung cancer and colon cancer, and has potential medicinal value.

[0029] (2) The synthesis method provided by the present invention is completed by a one-pot multi-step tandem reaction of N-nitrosoaniline compounds, diazonium dione compounds and hexafluoroisopropanol, which is simple and efficient.

[0030] (3) The synthesis method provided by the present invention has the significant advantages of cheap and readily available raw materials, valuable products, economical steps and high atom economy. Attached Figure Description

[0031] Figure 1 This is the X-ray single-crystal diffraction pattern of compound 3u in Example 3. Detailed Implementation

[0032] The following examples further illustrate the above-described content of the present invention, but it should not be construed as limiting the scope of the subject matter of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention.

[0033] Example 1

[0034]

[0035] Compounds 1a, 2a, catalyst, additive, and hexafluoroisopropanol were added sequentially to a 15 mL reaction tube. The reaction tube was sealed and placed in an oil bath with heating and stirring. After the reaction was completed, the mixture was cooled to room temperature, filtered through diatomaceous earth, concentrated, and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain a yellow solid product 3a.

[0036] By changing the reaction conditions such as catalyst, additives, material ratio, temperature, and gas atmosphere, a series of results were obtained, as shown in Table 1.

[0037] Table 1 Synthesis of 3a under different conditions a

[0038]

[0039]

[0040] a Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), catalyst (5 mol%), additive 1 (0.4 mmol).

[0041] mmol), Additive 2 (0.1 mmol), Additive 3 (0.2 mmol), hexafluoroisopropanol (2 mL), 80 °C, oxygen atmosphere, 0.5 h; b Separation yield; c Atmosphere; d Argon atmosphere; e Additive 1 (0.2 mmol); f Additive 1 (0.6 mmol), Additive 2 (0.2 mmol), Additive 3 (0.2 mmol); g 60℃;

[0042] h 100℃; i 2a (0.2 mmol);j 2a (0.3 mmol).

[0043] Example 2

[0044]

[0045] Add 1a (27.2 mg, 0.2 mmol), 2a (41.3 mg, 0.24 mmol), [RhCp*Cl2]2 (6.2 mg, 0.01 mmol), copper acetate (72.7 mg, 0.4 mmol), 2,2,6,6-tetramethylpiperidine oxide (15.6 mg, 0.1 mmol), silver oxide (46.3 mg, 0.2 mmol), and hexafluoroisopropanol (2 mL) sequentially to a 15 mL pressure-resistant tube. Seal the tube and place it in an oil bath at 80 °C for 0.5 h. After the reaction, cool the reaction system to room temperature, filter through diatomaceous earth, concentrate the filtrate, and separate by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain a yellow solid product 3a (66.6 mg, 75%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl3): δ8.38(d,J=8.0Hz,1H),8.16(dd,J1=7.6Hz,J2=0.4Hz,1H),7.76(td,J1=7.2Hz,J2=0.8Hz,1H),7.62( td,J1=8.0Hz, J2=1.2Hz,1H),7.50-7.46(m,2H),7.42-7.38(m,1H),7.19(d,J=8.4Hz,1H),5.86-5.80(m,1H),3.74(s,3H). 13 C{ 1 H}NMR (150MHz, CDCl3): δ186.0,162.8,143.0,134.5,130.7,130.0,129.8,127.7,127.0,125.5,124.9,122.0,121.3,120.4(q, 1 J C-F =278.0Hz),118.0,107.1,67.5-66.6(m),28.7. 19 F NMR (376MHz, CDCl3): δ-73.07 (d, J = 6.8Hz). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 12 F6N2NaO4 + 469.0593; Found 469.0601.

[0046] Example 3

[0047] According to the method and steps of Example 2 a,b By changing reactant 1 and reactant 2, various indazole nitrides 3 can be synthesized, as shown in the following results:

[0048]

[0049] a Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol), [RhCp*Cl2]2 (0.01 mmol), copper acetate (0.4 mmol), 2,2,6,6-tetramethylpiperidine oxide (0.1 mmol), silver oxide (0.2 mmol), hexafluoroisopropanol (2 mL), 80 °C, 0.5 h, oxygen atmosphere; b Separation yield.

[0050] The representative product characterization data are as follows: 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-inda zole 2-oxide(3b)

[0051] 1 H NMR (600 MHz, CDCl3): δ8.39 (d, J = 7.8 Hz, 1H), 8.16 (d, J = 7.2 Hz, 1H), 7.76 (td, J1 = 7.2 Hz, J2 = 0.6 Hz, 1H), 7.62 (td, J1 = 7.8 Hz, J2 = 1.2 Hz,1H),7.48-7.46(m,2H),7.40(t,J=7.2 Hz,1H),7.21(d,J=8.4 Hz,1H),5.84-5.80(m,1H),4.31(q,J=7.2Hz,2H),1.31(t,J=7.8 Hz,3H). 13 C{ 1 H}NMR (150 MHz, CDCl3): δ186.2,162.8,143.3,134.6,130.1,130.0,129.8,127.6,126.9,125.3,124.8,122.0,121.3,120.4(q, 1 J C-F =276.8 Hz),118.2,107.0,67.5-66.6(m),37.7,12.7. 19F NMR(565MHz,CDCl3):δ-73.08(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 14 F6N2NaO4 + 483.0750;Found 483.0748.

[0052] 3-(2-(((1,1,1,3,3,3-Hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-propyl-1H-indazole 2-oxide(3c)

[0053] 1 H NMR(400 MHz,CDCl3):δ8.40(d,J=7.6 Hz,1H),8.18-8.16(m,1H),7.76.(td,J1=7.6 Hz,J2=1.2 Hz,1H),7.62(td,J1=8.0 Hz,J2=1.2 Hz,1H),7.49-7.45(m,2H),7.40(t,J=7.6 Hz,1H),7.21(d,J=8.0 Hz,1H),5.85-5.78(m,1H),4.21(t,J=7.2 Hz,2H),1.81-1.72(m,2H),0.91(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.3,162.7,143.3,134.6,130.5,130.1,129.8,127.6,126.9,125.2,124.7,121.9,121.2,120.4(q, 1 J C-F =281.1 Hz),118.0,107.2,67.5-66.6(m),44.3,21.2,11.1. 19 F NMR(565 MHz,CDCl3):δ-73.08(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 16 F6N2NaO4 + 497.0906;Found 497.0902.

[0054] 1-Butyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3d)

[0055] 1 H NMR(400 MHz,CDCl3):δ8.40(d,J=8.0 Hz,1H),8.17(d,J=7.6 Hz,1H),7.76.(td,J1=7.6 Hz,J2=1.2 Hz,1H),7.62(td,J1=8.0 Hz,J2=1.2 Hz,1H),7.49-7.45(m,2H),7.41-7.38(m,1H),7.21(d,J=8.0 Hz,1H),5.85-5.79(m,1H),4.24(t,J=7.2Hz,2H),1.74-1.66(m,2H),1.38-1.28(m,2H),0.90(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.2,162.8,143.4,134.6,130.4,130.1,129.8,127.6,126.9,125.2,124.7,121.9,121.2,120.4(q, 1 J C-F =281.1 Hz),118.0,107.2,67.5-66.6(m),42.7,29.8,20.0,13.5. 19 F NMR(565 MHz,CDCl3):δ-73.08(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd forC 22 H 18 F6N2NaO4 + 511.1063;Found 511.1060.1-Benzyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3e)

[0056] 1H NMR(600 MHz,CDCl3):δ8.40(dd,J1=7.2 Hz,J2=1.2 Hz,1H),8.16(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.77.(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.63(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.49(dd,J1=7.8 Hz,J2=1.2 Hz,1H),7.43-7.37(m,2H),7.30-7.25(m,3H),7.19-7.17(m,2H),7.14-7.13(m,1H),5.80-5.76(m,1H),5.44(s,2H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ186.3,162.8,143.2,134.6,133.9,130.6,130.1,129.9,129.0,128.4,127.7,127.5,127.1,125.3,124.9,121.9,121.4,120.4(q, 1 J C-F =284.4 Hz),118.1,107.6,67.5-66.6(m),45.7. 19 F NMR(565 MHz,CDCl3):δ-73.04(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 25 H 16 F6N2NaO4 + 545.0906;Found 545.0910.

[0057] 1-Cyclohexyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3f)

[0058] 1H NMR(600 MHz,CDCl3):δ8.44(d,J=8.4 Hz,1H),8.16(dd,J1=7.8 Hz,J2=0.6Hz,1H),7.76.(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.62(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.47-7.42(m,3H),7.39-7.37(m,1H),5.84-5.80(m,1H),5.02-4.97(m,1H),2.08(qd,J1=12.6 Hz,J2=3.0 Hz,2H),1.93-1.75(m,5H),1.45-1.37(m,2H),1.31-1.23(m,1H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.5,162.8,143.4,134.6,130.0,129.7,127.6,126.5,125.3,124.3,121.7,121.4,120.4(q, 1 J C-F =281.1 Hz),118.2,108.6,67.5-66.6(m),54.2,30.0,25.9,25.1. 19 F NMR(565 MHz,CDCl3):δ-73.07(d,J=5.7 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 24 H 20 F6N2NaO4 + 537.1219;Found 537.1209.

[0059] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-5-methyl-1H-indazole 2-oxide(3g)

[0060] 1H NMR(600 MHz,CDCl3):δ8.22(s,1H),8.16(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.76(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.62(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.46(dd,J1=7.8 Hz,J2=1.2 Hz,1H),7.30(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.11(d,J=7.8 Hz,1H),5.84-5.80(m,1H),4.29(q,J=7.2 Hz,2H),2.51(s,3H),1.29(t,J=7.2Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.3,162.8,143.4,134.9,134.6,130.0,129.7,128.5,128.3,127.6,125.3,121.8,120.7,120.4(q, 1 J C-F =282.3 Hz),118.3,106.8,67.5-66.5(m),37.7,21.6,12.7. 19 F NMR(565 MHz,CDCl3):δ-73.07(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 16 F6N2NaO4 + 497.0906;Found 497.0909.

[0061] 5-(tert-Butyl)-1-ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3h)

[0062] 1H NMR(600 MHz,CDCl3):δ8.38(d,J=1.2 Hz,1H),8.16(dd,J1=7.8 Hz,J2=0.6Hz,1H),7.76(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.62(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.56(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.47(dd,J1=7.2 Hz,J2=0.6 Hz,1H),7.16(d,J=8.4 Hz,1H),5.85-5.81(m,1H),4.30(q,J=6.6 Hz,2H),1.42(s,9H),1.30(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.3,162.8,148.3,143.5,134.6,130.0,129.7,128.2,127.6,125.3,125.2,122.1,120.4(q, 1 J C-F =278.9Hz),118.0,117.2,106.7,67.5-66.6(m),37.7,35.1,31.6,12.8. 19 F NMR(565 MHz,CDCl3):δ-73.06(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 24 H 22 F6N2NaO4 + 539.1376;Found 539.1374.

[0063] 5-Benzyl-1-ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3i)

[0064] 1H NMR(600 MHz,CDCl3):δ8.29(d,J=0.6 Hz,1H),8.15(dd,J1=7.8 Hz,J2=0.6Hz,1H),7.75(td,J1=7.2 Hz,J2=1.2 Hz,1H),7.61(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.45(dd,J1=7.2 Hz,J2=0.6 Hz,1H),7.31-7.28(m,3H),7.24-7.20(m,3H),7.11(d,J=8.4 Hz,1H),5.85-5.80(m,1H),4.27(q,J=7.2 Hz,2H),4.12(s,2H),1.28(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.3,162.8,143.3,141.1,138.2,134.6,130.0,129.8,128.9,128.6,128.3,127.6,126.3,125.3,121.9,121.0,120.4(q, 1 J C-F =283.4Hz),118.3,107.3,67.5-66.6(m),42.1,37.8,12.8. 19 FNMR(565 MHz,CDCl3):δ-73.04(d,J=5.7 Hz).HRMS(ESI)m / z:[M+Na] + Calcdfor C 27 H 20 F6N2NaO4 + 573.1219;Found 573.1214.

[0065] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-5-phenyl-1H-indazole 2-oxide(3j)

[0066] 1H NMR(600 MHz,CDCl3):δ8.64(d,J=1.2 Hz,1H),8.18(d,J=8.4 Hz,1H),7.78(td,J1=7.2 Hz,J2=0.6 Hz,1H),7.73(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.69(d,J=7.2Hz,2H),7.65-7.62(m,1H),7.50-7.47(m,3H),7.39(t,J=7.2 Hz,1H),7.29(d,J=8.4 Hz,1H),5.85-5.81(m,1H),4.34(q,J=7.2 Hz,2H),1.34(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ186.2,162.8,143.2,140.8,138.5,134.6,130.0,129.8,129.3,128.9,127.7,127.5,127.4,126.7,125.3,122.2,120.4(q, 1 J C-F =282.2Hz),119.5,118.7,107.4,67.5-66.6(m),37.9,12.8. 19 F NMR(565 MHz,CDCl3):δ-73.04(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 26 H 18 F6N2NaO4 + 559.1063;Found 559.1060.

[0067] 5-Chloro-1-ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3k)

[0068] 1H NMR(400 MHz,CDCl3):δ8.44(d,J=1.2 Hz,1H),8.17(d,J=8.0 Hz,1H),7.79-7.75(m,1H),7.66-7.62(m,1H),7.47-7.43(m,2H),7.15(d,J=8.8 Hz,1H),5.84-5.78(m,1H),4.29(q,J=7.2 Hz,2H),1.30(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.0,162.8,142.8,134.7,130.8,130.1,130.0,128.2,127.7,127.4,125.3,121.6,120.8,120.4(q, 1 J C-F =281.1 Hz),119.1,108.2,67.5-66.6(m),38.0,12.7. 19 F NMR(565MHz,CDCl3):δ-73.08(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 13 ClF6N2NaO4 + 517.0360;Found 517.0373.

[0069] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-5-(methoxycarbonyl)-1H-indazole 2-oxide(3l)

[0070] 1 H NMR(600 MHz,CDCl3):δ9.10(d,J=1.2 Hz,1H),8.20-8.17(m,2H),7.78(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.65(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.48(dd,J1=7.2 Hz,J2=0.6 Hz,1H),7.26(d,J=8.4 Hz,1H),5.84-5.80(m,1H),4.33(q,J=7.2Hz,2H),3.98(s,3H),1.33(t,J=7.8 Hz,3H). 13 C{1 H}NMR(150 MHz,CDCl3):δ186.0,166.8,162.8,142.8,134.7,132.2,130.1,130.0,128.3,127.7,126.8,125.3,123.8,122.3,120.3(q, 1 J C-F =281.1 Hz),117.7,106.9,67.5-66.6(m),52.3,38.0,12.8. 19 F NMR(565 MHz,CDCl3):δ-73.09(d,J=5.7 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 22 H 16 F6N2NaO6 + 541.0805;Found541.0807.

[0071] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-6-methyl-1H-indazole 2-oxide(3m)

[0072] 1 H NMR(600 MHz,CDCl3):δ8.25(d,J=8.4 Hz,1H),8.16(dd,J1=8.4 Hz,J2=0.6Hz,1H),7.76(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.62(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.46(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.23(d,J=7.8 Hz,1H),7.01(s,1H),5.84-5.80(m,1H),4.28(q,J=7.8 Hz,2H),2.51(s,3H),1.30(t,J=6.6 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.2,162.8,143.3,137.5,134.6,130.3,130.1,129.7,127.6,126.5,125.3,122.0,121.0,120.4(q, 1 J C-F=282.2 Hz),115.9,106.9,67.5-66.5(m),37.6,22.0,12.7. 19 F NMR(565 MHz,CDCl3):δ-73.07(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd forC 21 H 16 F6N2NaO4 + 497.0906;Found 497.0903.6-Chloro-1-ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3n)

[0073] 1 H NMR(600 MHz,CDCl3):δ8.33(d,J=8.4 Hz,1H),8.17(d,J=7.2 Hz,1H),7.79-7.76(m,1H),7.65-7.63(m,1H),7.46(d,J=7.8 Hz,1H),7.37(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.23(d,J=1.2 Hz,1H),5.83-5.79(m,1H),4.27(q,J=7.2 Hz,2H),1.31(t,J=7.2Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.0,162.7,142.8,134.7,133.4,130.4,130.1,130.0,127.7,125.5,125.3,122.5,122.0,120.3(q, 1 J C-F =280.1 Hz),116.6,107.0,67.5-66.6(m),37.9,12.7. 19 F NMR(376 MHz,CDCl3):δ-73.08(d,J=5.6 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 13 ClF6N2NaO4 + 517.0360;Found 517.0364.

[0074] 4-Chloro-1-ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1H-indazole 2-oxide(3o)

[0075] 1 H NMR(400 MHz,CDCl3):δ8.03(d,J=7.6 Hz,1H),7.74(t,J=7.2 Hz,1H),7.66-7.61(m,2H),7.40-7.34(m,2H),7.12(dd,J1=7.2 Hz,J2=1.6 Hz,1H),5.85-5.79(m,1H),4.34(q,J=7.6 Hz,2H),1.31(t,J=7.6 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ184.4,163.1,142.7,134.0,131.5,130.7,130.1,128.8,127.3,126.3,126.1,125.8,122.2,120.4(q, 1 J C-F =281.1 Hz),116.3,105.6,67.5-66.6(m),38.0,12.7. 19 F NMR(376 MHz,CDCl3):δ-73.09(d,J=5.3 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 13 ClF6N2NaO4 + 517.0360;Found 517.0359.

[0076] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-7-methyl-1H-indazole 2-oxide(3p)

[0077] 1H NMR(600 MHz,CDCl3):δ8.30(d,J=7.8 Hz,1H),8.16(d,J=7.8 Hz,1H),7.78-7.75.(m,1H),7.64-7.61(m,1H),7.46(d,J=7.2 Hz,1H),7.29(t,J=7.2 Hz,1H),7.22(d,J=7.2 Hz,1H),5.84-5.80(m,1H),4.51(q,J=7.2 Hz,2H),2.67(s,3H),1.28(t,J=7.2Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.4,162.7,143.5,134.6,130.0,129.7,129.5,129.4,127.6,125.2,124.6,121.9,120.4(q, 1 J C-F =282.2 Hz),119.1,118.7,117.9,67.5-66.5(m),39.4,18.8,14.3. 19 F NMR(565 MHz,CDCl3):δ-73.06(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 16 F6N2NaO4 + 497.0906;Found 497.0907.

[0078] 5-Bromo-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-isobutyl-1H-indazole 2-oxide(3q)

[0079] 1H NMR(600 MHz,CDCl3):δ8.60(d,J=1.8 Hz,1H),8.17(dd,J1=7.8 Hz,J2=1.2Hz,1H),7.77.(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.64(td,J1=7.2 Hz,J2=0.6 Hz,1H),7.57(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.45(dd,J1=7.8 Hz,J2=1.2 Hz,1H),7.08(d,J=8.4 Hz,1H),5.82-5.78(m,1H),4.01(d,J=7.2 Hz,2H),2.23-2.18(m,1H),0.89(d,J=6.6Hz,6H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.1,162.7,143.0,134.7,130.2,130.0,129.9,129.5,127.6,125.1,123.6,121.2,120.3(q, 1 J C-F =283.4 Hz),119.3,118.1,111.2,108.9,67.5-66.6(m),50.2,27.8,19.9. 19 F NMR(565MHz,CDCl3):δ-73.06(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 22 H 17 BrF6N2NaO4 + 589.0168;Found 589.0164.

[0080] 3-(2-(((1,1,1,3,3,3-Hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1,5-dimethyl-1H-indazole 2-oxide(3r)

[0081] 1H NMR(600 MHz,CDCl3):δ8.21(s,1H),8.15(d,J=7.8 Hz,1H),7.75(td,J1=7.8Hz,J2=1.2 Hz,1H),7.61(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.46(d,J=7.2 Hz,1H),7.29(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.08(d,J=8.4 Hz,1H),5.85-5.80(m,1H),3.71(s,3H),2.50(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ186.2,162.8,143.2,135.0,134.5,130.0,129.8,129.1,128.6,127.6,125.5,121.7,120.4(q, 1 J C-F =278.9 Hz),120.6,118.2,106.9,67.5-66.6(m),28.8,21.6. 19 F NMR(565 MHz,CDCl3):δ-73.06(d,J=4.5 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 14 F6N2NaO4 + 483.0750;Found 483.0766.

[0082] 3-(2-(((1,1,1,3,3,3-Hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-methyl-5-(trifluoromethyl)-1H-indazole 2-oxide(3s)

[0083] 1H NMR(600 MHz,CDCl3):δ8.73(s,1H),8.17(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.78(td,J1=7.8 Hz,J2=1.8 Hz,1H),7.71(dd,J1=8.4 Hz,J2=1.2 Hz,1H),7.66(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.47(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.30(d,J=8.4 Hz,1H),5.83-5.79(m,1H),3.77(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ185.9,162.8,142.4,134.7,131.9,130.2,130.0,127.8,127.3(q, 2 J C-F =32.7 Hz),125.5,124.2(q, 1 J C-F =271.4Hz),123.7(q, 3 J C-F =3.3 Hz),122.1,120.3(q, 1 J C-F =280.1 Hz),119.2(q, 3 J C-F =4.4 Hz),117.6,107.6,67.6-66.6(m),29.0. 19 F NMR(565MHz,CDCl3):δ-61.41(s),-73.10(d,J=6.2Hz).HRMS(ESI)m / z:[M+Na] + Calcdfor C 20 H 11 F9N2NaO4 + 537.0467;Found 537.0471.

[0084] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)-4,5-dimethoxybenzoyl)-1H-indazole 2-oxide(3t)

[0085] 1H NMR(600 MHz,CDCl3):δ8.37(d,J=7.8 Hz,1H),7.60(s,1H),7.48-7.46(m,1H),7.41-7.38(m,1H),7.21(d,J=7.8 Hz,1H),6.93(s,1H),5.84-5.80(m,1H),4.33(q,J=7.2 Hz,2H),4.01(s,3H),3.95(s,3H),1.32(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ185.9,162.4,154.0,149.3,137.5,129.9,126.9,124.7,122.1,121.3,120.4(q, 1 J C-F =283.4 Hz),118.2,117.4,112.1,110.4,107.0,67.3-66.4(m),56.3,56.1,37.7,12.7. 19 F NMR(565 MHz,CDCl3):δ-73.14(d,J=5.7 Hz).HRMS(ESI)m / z:[M+Na] + Calcd forC 22 H 18 F6N2NaO6 + 543.0961;Found 543.0976.3-(4,5-Difluoro-2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-ethyl-1H-indazole 2-oxide(3u)

[0086] 1 H NMR(400 MHz,CDCl3):δ8.38(d,J=8.0 Hz,1H),7.97(dd,J1=10.4 Hz,J2=7.6 Hz,1H),7.52-7.48(m,1H),7.44-7.40(m,1H),7.31-7.22(m,2H),5.81-5.75(m,1H),4.33(q,J=7.2 Hz,2H),1.33(t,J=6.8 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ183.3,161.1,154.1(dd, 1 JC-F =260.4 Hz, 2 J C-F =13.2 Hz),150.2(dd, 1 J C-F =252.8 Hz, 2 J C-F =13.2 Hz),140.8-140.7(m),129.9,127.2,125.1,122.41-122.35(m),121.7,121.2,120.2(q, 1 J C-F =280.1 Hz),119.8(d, 2 J C-F =19.8 Hz),118.0,117.7(d, 2 J C-F =19.8 Hz),107.1,67.8-66.9(m),37.9,12.7. 19 F NMR(376 MHz,CDCl3):δ-73.09(d,J=5.3 Hz),-125.90--126.00(m),-133.31--133.41(m).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 12 F8N2NaO4 + 519.0562;Found 519.0574.

[0087] 3-(4,5-Dichloro-2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-ethyl-1H-indazole 2-oxide(3v)

[0088] 1 H NMR(600 MHz,CDCl3):δ8.39(d,J=7.8 Hz,1H),8.19(s,1H),7.55(s,1H),7.51-7.49(m,1H),7.44-7.41(m,1H),7.23(d,J=8.4 Hz,1H),5.80-5.77(m,1H),4.33(q,J=7.2 Hz,2H),1.33(t,J=6.6 Hz,3H). 13 C{ 1H}NMR(150 MHz,CDCl3):δ183.4,161.3,142.1,139.5,134.3,131.6,130.0,129.9,127.2,125.10,125.07,121.8,121.2,120.2(q, 1 J C-F =279.9 Hz),117.9,107.2,67.8-66.8(m),37.9,12.7. 19 F NMR(565 MHz,CDCl3):δ-73.02(d,J=6.2 Hz).HRMS(ESI)m / z:[M+Na] + Calcd forC 20 H 12 Cl2F6N2NaO4 + 550.9971;Found550.9977.

[0089] 3-(2-(((1,1,1,3,3,3-Hexafluoropropan-2-yl)oxy)carbonyl)-4,5-dimethoxybenzoyl)-5-methoxy-1-methyl-1H-indazole 2-oxide(3w)

[0090] 1 H NMR(600 MHz,CDCl3):δ7.86(s,1H),7.59(s,1H),7.13-7.10(m,2H),6.92(s,1H),5.85-5.81(m,1H),4.01(s,3H),3.95-3.94(m,6H),3.73(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ186.0,162.4,158.0,153.9,149.3,137.4,125.4,122.3,120.4(q, 1 J C-F =279.5Hz),119.0,118.0,117.5,112.0,110.3,108.4,101.6,67.6-66.2(m),56.3,56.2,55.9,28.9. 19 F NMR(376 MHz,CDCl3):δ-73.10(d,J=5.6 Hz).HRMS(ESI)m / z:[M+Na] + Calcd forC 22 H18 F6N2NaO7 + 559.0910;Found 559.0922.3-(4,5-Difluoro-2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-5-methoxy-1-methyl-1H-indazole 2-oxide(3x)

[0091] 1 H NMR(400 MHz,CDCl3):δ7.96(dd,J1=10.0 Hz,J2=7.2 Hz,1H),7.82(s,1H),7.30-7.26(m,1H),7.130-7.127(m,2H),5.82-5.76(m,1H),3.94(s,3H),3.73(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ183.4,161.1,158.3,154.0(dd, 1 J C-F =259.3 Hz, 2 J C-F =13.0Hz),150.2(dd, 1 J C-F =252.8 Hz, 2 J C-F =13.0 Hz),140.6(dd, 3 J C-F =5.8Hz, 4 J C-F =4.4 Hz),125.4,122.5(dd, 3 J C-F =5.7 Hz, 4 J C-F =4.3 Hz),121.8,120.2(q, 1 J C-F =281.0 Hz),119.7(d, 2 J C-F =20.2 Hz),118.8,118.3,117.7(d, 2 J C-F =19.5 Hz),108.6,101.5,68.0-66.6(m),55.9,29.0. 19F NMR(376 MHz,CDCl3):δ-73.05(d,J=6.8 Hz),-126.07--126.17(m),-133.34--133.44(m).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 12 F8N2NaO5 + 535.0511;Found535.0514.

[0092] 3-(3,6-Dichloro-2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-1-ethyl-1H-indazole 2-oxide(3y)

[0093] 1 H NMR(400 MHz,CDCl3):δ8.29(d,J=8.0 Hz,1H),7.55-7.52(m,2H),7.50-7.47(m,1H),7.41(t,J=7.6 Hz,1H),7.25(d,J=8.0 Hz,1H),5.82-5.76(m,1H),4.43-4.37(m,2H),1.35(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ181.4,161.6,141.5,133.5,132.2,132.0,129.94,129.85,127.9,127.1,125.0,122.3,121.0,120.0(q, 1 J C-F =281.1Hz),117.9,107.2,67.9-66.9(m),38.0,12.6. 19 F NMR(376 MHz,CDCl3):δ-72.56(d,J=5.6Hz),-72.85(d,J=5.6 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 12 Cl2F6N2NaO4 + 550.9971;Found 550.9973.

[0094] 1-Ethyl-3-(2-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)benzoyl)-5-(2-(2-isopropyl-5-methylphenoxy)-2-oxoethyl)-1H-indazole 2-oxide(3z)

[0095] 1 H NMR(600MHz,CDCl3):δ8.46(d,J=0.6Hz,1H),8.17(dd,J1=7.8Hz,J2=0.6Hz,1H),7.76.(td,J1=7.8Hz,J2=1.2Hz,1H),7.62(td,J1=7.8Hz,J2=1.2Hz,1H),7.54(dd,J1=8.4Hz,J2=1.8Hz,1H),7.46(dd,J1=7.2Hz,J2=0.6Hz,1H),7.23(d,J=8.4Hz,1H),7.17(d,J=7.8Hz,1H),7.01(dd,J1=8.4Hz,J2=0.6Hz,1H),6.82(d,J=0.6Hz,1H),5.84-5.80(m,1H),4.31(q,J=7.2Hz,2H),4.04(s,2H),2.91-2.86(m,1H),2.29(s,3H),1.30(t,J=7.2Hz,3H),1.12(d,J=6.6Hz,6H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ186.2,170.2,162.8,147.9,143.2,137.0,136.6,134.6,130.5,130.0,129.8,129.2,128.4,127.6,127.2,126.4,125.3,122.6,122.0,121.9,120.4(q, 1 J C-F =283.2Hz),118.4,107.4,67.5-66.6(m),41.4,37.8,27.0,22.9,20.8,12.7. 19 F NMR(565MHz,CDCl3):δ-73.05(d,J=6.2Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 32 H 28 F6N2NaO6 +673.1744; Found 673.1743.

[0096] Example 4

[0097] The anticancer activity of the compounds provided in this invention was evaluated using CCK-8 assays and through cell antiproliferative activity studies.

[0098] The specific method is as follows: First, HeLa, A549, or HCT-116 cells were seeded at a density of 4000 cells per well into 96-well plates containing 100 μL of culture medium per well, and incubated overnight at 37°C and 5% CO2. The next day, 100 μL of different concentrations of the test compound prepared with the culture medium was added to each well according to the plate plot. Then, the cells were incubated at 37°C and 5% CO2 for 48 hours. After the 96-well plates equilibrated to room temperature, 10 μL of CCK-8 was added to each well, and the plates were shaken for 2 minutes on a vortex mixer to induce cell lysis. After incubation at 37°C and 5% CO2 for 1.5 hours, the absorbance at 450 nm was measured using a Perkin Elmer microplate reader, and the IC50 was calculated using GraphPad Prism 6.0 software. 50 Values. All experiments were performed with two parallel samples and repeated twice. 5-Fluorouracil (5-FU) was used as a positive control for the drug.

[0099] The results of the anticancer activity of some compounds are as follows:

[0100]

[0101]

[0102] The activity results indicate that the indazole nitride 3 provided by this invention can inhibit the proliferation of three cancer cells: HeLa, A549, and HCT-116. Compounds 3b, 3c, 3d, 3e, 3m, and 3p have significant effects on all three cancer cell types. Compounds 3g and 3h significantly inhibit the proliferation of HeLa cancer cells. Compound 3i exhibits significant anti-proliferative activity against both HeLa and A-549 cancer cells. Compound 3j shows a strong inhibitory effect on the proliferation of HCT-116 cancer cells. These activity results suggest that these compounds have medicinal value in preventing / treating / inhibiting the progression of cancers, particularly cervical cancer, lung cancer, and colon cancer.

[0103] The above embodiments describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the present invention. Various changes and modifications can be made to the present invention without departing from its principles, and all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. Indazole nitroxide characterized in that, The chemical structure is as follows: wherein: R 1 is selected from hydrogen, C 1-4 alkyl, C 1-4 alkoxy, phenyl, benzyl, trifluoromethyl or halogen, R 1 is selected from mono- or poly- substitution; R 2 is selected from C 1-6 chain alkyl or benzyl; R 3 is selected from hydrogen, C 1-4 alkyl, C 1-4 alkoxy or halogen, R 3 is selected from mono- or poly- substitution.

2. The indazole N-oxide of claim 1, wherein: ###0001### The compound is selected from the following specific structures: 。 3. Use of the indazole N-oxide according to claim 1 or 2 for the preparation of a medicament with anticancer activity.

4. Use of an indazole N-oxide according to claim 3 for the preparation of a medicament with anticancer activity, characterized in that: The anticancer is against cervical cancer, lung cancer and colon cancer.

5. Use of indazole N-oxide according to claim 4 for the preparation of a medicament with anticancer activity, characterized in that: The anticancer against cervical cancer is to inhibit the proliferation of Hela cancer cells, the anticancer against lung cancer is to inhibit the proliferation of A549 cancer cells, and the anticancer against colon cancer is to inhibit the proliferation of HCT-116 cancer cells.

6. A pharmaceutical composition for treating cervical cancer, lung cancer and colon cancer, the active ingredient of which comprises the indazole N-oxide according to claim 1 or 2.

7. The method for synthesizing indazole nitrogen oxides as described in claim 1, characterized in that, comprising the steps of: N The nitrosoaniline compound 1, the diazindione compound 2, a catalyst, an additive and hexafluoroisopropanol are mixed and reacted at elevated temperature to obtain the indazol nitrogen oxide compound 3, and the reaction equation is as follows: wherein: R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, phenyl, benzyl, trifluoromethyl or halogen, R 1 is mono- or poly-substituted; R 2 is C 1-6 chain alkyl or benzyl; R 3 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy or halogen, R 3 is mono- or poly-substituted; the additive is selected from copper acetate or a mixture of copper acetate with one or more of 2,2,6,6-tetramethylpiperidine oxide, silver acetate, silver oxide, silver carbonate or silver nitrate; the catalyst is selected from dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer or tris(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III) bis(hexafluoroantimonate).

8. The method for synthesizing indazole nitride according to claim 7, characterized in that: The N - molar ratio of nitrosoaniline compound 1, diazindione compound 2, catalyst and additive is 1: 1-1.5: 0.04-0.06: 1-5.

9. The process for the synthesis of indazole N-oxide according to claim 7 or 8, characterized in that: The reaction temperature is 60-100℃; the reaction is carried out in an air, oxygen or inert gas atmosphere.

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