Perfluoroalkyl-substituted pyrimido [1, 2-b] indazole ketone compound and preparation method thereof

Abstract

The invention discloses a perfluoroalkyl-substituted pyrimido [1, 2-b] indazole ketone compound and a preparation method thereof, and belongs to the technical field of compounds containing two or more heterocyclic rings. Comprising the following steps: with enaminone, a perfluoroalkane compound and aminoindazole as raw materials, carrying out a reaction under blue light irradiation in the presence of an organic solvent and alkali to prepare the perfluoroalkyl-substituted pyrimido [1, 2-b] indazole ketone compound; according to the invention, through visible light mediated dehalogenation and cyclization free radical addition, high-yield synthesis of the perfluoroalkyl substituted pyrimido [1, 2-b] indazole ketone compound is realized; the prepared perfluoroalkyl-substituted pyrimido [1, 2-b] indazolone compound has excellent antibacterial activity, can be used for preparing antibacterial drugs, and has outstanding industrial application value.

Description

Technical Field

[0001] This application relates to a perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone compound and its preparation method, belonging to the technical field of compounds containing two or more heterocycles. Background Technology

[0002] Pyrimido[1,2-b]inazole and its derivatives are a class of organic compounds with a unique triaza-fused-ring core structure. Due to their unique physicochemical properties and diverse biological activities, they exhibit great application potential in pharmaceuticals, pesticides, dyes, and polymer materials. For example, they are often regarded as a "privileged scaffold" in constructing drug molecules with antitumor, antiviral, and kinase inhibitory activities. However, the synthesis of these fused-ring systems often has high technical barriers. Early methods mainly relied on cumbersome multi-step linear synthesis or were limited to specific substitution modes. This not only led to harsh reaction conditions and low yields but also greatly limited the diversified modification and large-scale production of these compounds, hindering their in-depth application research.

[0003] With the continuous advancement of science and technology, especially the rapid development in fields such as materials science and computer-aided drug design, the demand for compounds containing specific fused-ring structures is becoming increasingly refined and growing. To meet this demand, researchers have begun actively exploring more efficient, environmentally friendly, and highly position-selective novel synthetic methods and technologies. Furthermore, thanks to the rapid development of advanced technologies such as computer-aided drug design and molecular simulation, researchers can more accurately predict and optimize the specific biological activities resulting from these fused-ring cores, thus providing strong theoretical support and an experimental platform for the rational design of new drugs and the development of high-performance materials. Summary of the Invention

[0004] In view of this, the first objective of this application is to provide a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound.

[0005] Specifically, this application is implemented through the following scheme: A perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, with the following structural formula: ; In the formula: R is selected from any one of ethoxy, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, m-chlorophenyl, methyl, p-fluorophenyl, phenyl, and cyclopropyl.

[0006] Specifically, the perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds of the above general formula are any of the following structural formulas: .

[0007] A perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, with the following structural formula: ; In the formula: R is selected from any one of fluorine, chlorine, bromine, trifluoromethyl, methoxy, cyano, and difluorobenzyl.

[0008] Specifically, the perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds of the above general formula are any of the following structural formulas: .

[0009] A perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, with the following structural formula:

[0010] In the formula: R is selected from any one of pentafluoroethyl, nonafluorobutyl, undecylfluoropentyl, pentadecylfluoroheptyl, and nonadecylfluorononyl.

[0011] Specifically, the perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds of the above general formula are any one of the following structural formulas: .

[0012] The second aspect of this application is to provide a method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, comprising the following steps: using enamine ketone, perfluoroalkane compound, and aminoindazole as raw materials, reacting them in the presence of an organic solvent and a base under blue light irradiation to prepare a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound.

[0013] Further settings are as follows: The enamino ketone is selected from (E)-3-(dimethylamino)ethyl acrylate, (E)-1-(4-chlorophenyl)-3-(dimethylamino)prop-2-en-1-one, (E)-1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one, (E)-1-(3-chlorophenyl) (E)-3-(dimethylamino)prop-2-en-1-one, (E)-4-(dimethylamino)but-3-en-2-one, (E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one

[0014] The perfluoroalkane compound is selected from any one of perfluoropropane, perfluoropentane, perfluorohexane, perfluorooctane, and perfluorodecane.

[0015] The aminoinazole is selected from any one of 6-fluoro-1H-indazole-3-amine, 6-chloro-1H-indazole-3-amine, 6-bromo-1H-indazole-3-amine, 6-(trifluoromethyl)-1H-indazole-3-amine, 6-methoxy-1H-indazole-3-amine, 3-amino-1H-indazole-5-carboxynitrile, and 5-(3,5-difluorobenzyl)-1H-indazole-3-amine.

[0016] The organic solvent is selected from any one of acetonitrile (MeCN), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and dichloromethane (DCM).

[0017] The base is selected from any one of dicycloamidinium (DBU), triethylenediamine (DABCO), tetramethylethylenediamine (TMEDA), and N,N-diisopropylethylamine (DIPEA).

[0018] The molar ratio of the enamine ketone, perfluoroalkane compound, and aminoinazole is 2-5: 2-4:1, preferably 4:3:1.

[0019] A third objective of this application is to provide the use of the above-mentioned perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds in the preparation of antibacterial drugs.

[0020] Compared with the prior art, this application has the following advantages: (1) This application prepares a novel perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, which has excellent antibacterial activity and can be used in the preparation of antibacterial drugs, and has outstanding industrial application value.

[0021] (2) This application provides a method for preparing perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds. This method achieves high-yield synthesis of perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds through visible light-mediated dehalogenation and cyclization radical addition. The reaction conditions are mild, no photocatalyst is required, and it is easy to implement for industrial production. Furthermore, the method generates less waste during the reaction process. Compared with traditional methods, it not only reduces energy consumption and production costs but also effectively reduces waste generation, demonstrating good environmental friendliness.

[0022] The present application will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0023] Figure 1This is the UV absorption spectrum of the reaction involved in this application.

[0024] Figure 2 The image shows the antibacterial effect of the product prepared in Example 1 against Escherichia coli.

[0025] Figure 2 In the table: 1 is DMSO; 2 is a 20 mg / mL sample solution; 3 is a 40 mg / mL sample solution; 4 is an 80 mg / mL sample solution. Detailed Implementation

[0026] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the technical solutions in the embodiments of this application will be further described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are only used to explain this application and are not intended to limit the technical solutions of this application. Unless otherwise specified, the raw materials and reagents used in the embodiments are all known in the art or commercially available products.

[0027] This application discloses a method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound. Using enamine ketone, perfluoroalkane compounds, and aminoindazole as raw materials, the method involves visible light-mediated dehalogenation and cyclization radical addition in the presence of an organic solvent and a base to synthesize the perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound. This method does not require a photocatalyst and is a typical EDA reaction. To verify the initiation mechanism of the photoinduced reaction in this application, ultraviolet-visible absorption spectroscopy (UV-Vis) was performed on the reaction system.

[0028] Ultraviolet-Vis absorption spectroscopy (UV-Vis) testing The specific test sample preparation process is as follows: using acetonitrile as solvent, (1) perfluoroiodobutane solution: dissolve 0.3 mmol perfluoroiodobutane in 1.0 mL acetonitrile, transfer 100 µL of the solution and dilute with acetonitrile to 2 mL; (2) DABCO solution: dissolve 0.4 mmol DABCO in 1.0 mL acetonitrile, transfer 100 µL of the solution and dilute with acetonitrile to 2 mL; (3) mixed solution: dissolve 0.3 mmol IC4F9 and 0.4 mmol DABCO together in 1.0 mL acetonitrile, transfer 100 µL of the mixed solution and dilute with acetonitrile to 2 mL.

[0029] Test results are as follows Figure 1 As shown: a single electron acceptor IC4F9 solution ( Figure 1 (Black line) and electron donor DABCO solution ( Figure 1 The middle red line shows no significant absorption in the wavelength range greater than 350 nm. When the two are mixed, the resulting solution (…) Figure 1The spectrum of the blue line (in the middle) shows a significant red shift, and a new charge transfer (CT) absorption band appears in the 350 nm to 500 nm band.

[0030] The spectral characteristics, which are not superpositions of single-monomer absorption spectra, definitively confirm that electron-deficient IC4F9 and electron-rich DABCO spontaneously assemble in the ground state to form an electron donor-acceptor (EDA) complex. The formation of this complex introduces a visible light absorption region into the reaction system, allowing the excited-state EDA complex to undergo single-electron transfer (SET) under illumination. This SET triggers homolytic cleavage of the CI bond, releasing a perfluorobutyl radical, thus smoothly driving the subsequent radical conversion reaction without the need for an external photocatalyst.

[0031] Based on the above mechanism, the following embodiments were prepared.

[0032] Example 1

[0033] In a glass reaction flask, 1H-indazole-3-amine (0.0133 g, 0.1 mmol), ethyl (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol), perfluoroiodobutane (IC4F9, 0.1040 g, 0.3 mmol), triethylenediamine (DABCO, 0.0337 g, 0.3 mmol), and acetonitrile (MeCN, 1.5 ml) were added sequentially and mixed thoroughly. A magnetic stir bar was placed inside, and the reaction was carried out at room temperature for 3 hours under the illumination of a 3W blue LED. After the reaction was complete, the solution was washed with ethyl acetate, concentrated, and the product was separated using a petroleum ether:ethyl acetate ratio of 4:1 as the developing solvent. Finally, the separated product was dried, with a yield of 86%.

[0034] The reaction equations involved are as follows: .

[0035] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.37 (s, 1H), 8.31 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.70 (t, J = 7.7 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 4.50 (q, J = 7.3 Hz, 2H), 1.45 (t, J= 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.0, 153.3, 141.4, 138.9, 135.9,131.4, 123.4, 121.0, 117.2, 117.0, 114.2, 63.2, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.66 (t, J = 9.7 Hz), -106.01 (p, J = 9.4, 8.6 Hz), -122.79 (d, J = 7.3 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 13 F7NO + 416.0880; Found 416.0880.

[0036] Replacement Examples 2 to 4 This example mainly examines the effect of solvent selection on the reaction.

[0037] The preparation method is the same as in Example 1, except that the type of solvent is adjusted as shown in Table 1, and the effect of each solvent on the reaction is tested.

[0038] Table 1: Effect of different solvents on the reaction .

[0039] As can be seen from Table 1, under the same reaction conditions, the yield is optimal when MeCN (acetonitrile) is used as the solvent.

[0040] Replacement Examples 5 to 7 This example mainly examines the effect of the choice of base on the reaction.

[0041] The preparation method is the same as in Example 1, except that the type of alkali is adjusted as shown in Table 2, and its effect on the reaction is tested respectively.

[0042] Table 2: Effect of base on reaction .

[0043] As can be seen from Table 2, under the same reaction conditions, the yield of the reaction is much lower when DIPEA (N,N-diisopropylethylamine), DBU (dicycloamidine), and TMEDA (tetramethylethylenediamine) are used as bases.

[0044] Replacement Examples 8 to 12 This embodiment mainly examines the effect of the molar ratio of reactants on the reaction.

[0045] The preparation method is the same as in Example 1, except that the molar ratio of the raw materials is adjusted as shown in Table 3, and their effects on the reaction are tested respectively.

[0046] Table 3: Effect of reactant molar ratio on the reaction .

[0047] As can be seen from Table 3, under the same reaction conditions, the yield is highest when the molar ratio of (E)-3-(dimethylamino)acrylate: perfluoroiodobutane: 1H-indazole-3-amine is 4:3:1, reaching 86%.

[0048] To test the effect of different (substituent) enamine ketones on the reaction, the experiments shown in Examples 2 to 9 were conducted.

[0049] Example 2

[0050] This embodiment is set up the same as in Example 1, except that when the raw materials are added, (E)-1-(4-chlorophenyl)-3-(dimethylamino)prop-2-en-1-one (0.0839 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 67%.

[0051] The reaction equation is as follows: .

[0052] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.02 (s, 1H), 8.44 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.82 – 7.76 (m, 1H), 7.76 – 7.66 (m, 4H), 7.55– 7.49 (m, 1H). 13 C NMR (101 MHz, Chloroform- d ) δ 188.7, 153.2, 141.8, 134.9, 132.8,132.5, 131.6, 130.6, 123.6, 122.9, 121.2, 117.2, 114.4. 19 F NMR (376 MHz, Chloroform- d ) δ -79.75 (t, J = 9.7 Hz), -106.11 (q, J = 9.9 Hz), -123.78. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 10 ClF7N3O + 476.0395; Found476.0409.

[0053] Example 3

[0054] This embodiment has the same setup as Example 1, except that when adding the raw materials, (E)-1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-one (0.1017 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 56%.

[0055] The reaction equation is as follows: .

[0056] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.02 (s, 1H), 8.44 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.83 – 7.77 (m, 3H), 7.52 (dd, J = 8.5, 6.6Hz, 3H). 13 C NMR (101 MHz, Chloroform-d ) δ 188.5, 153.2, 141.8, 141.7, 138.6,134.5, 132.8, 131.6, 131.6, 129.5, 123.6, 123.0, 121.2, 117.1, 114.4. 19 F NMR (376 MHz, Chloroform- d ) δ -79.75 (t, J = 9.7 Hz), -106.12 (q, J = 9.9 Hz), -123.78. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 10 BrF7N3O + 519.9890; Found 519.9892.

[0057] Example 4

[0058] This embodiment has the same setup as Example 1, except that when adding the raw materials, (E)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (0.0821 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 58%.

[0059] The reaction equation is as follows: .

[0060] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.02 (s, 1H), 8.42 (d, J = 8.3 Hz, 1H), 7.93 (d, J = 8.7 Hz, 1H), 7.83 (d, J = 8.9 Hz, 2H), 7.76 (t, J = 7.8 Hz,1H), 7.51 – 7.45 (m, 1H), 7.00 – 6.95 (m, 2H), 3.90 (s, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 188.0, 165.0, 153.0, 141.7, 132.8,132.8, 131.4, 129.2, 123.8, 123.3, 121.1, 117.0, 114.4, 114.3, 55.7. 19 F NMR (376 MHz, Chloroform- d ) δ -79.82 (t, J = 9.6 Hz), -106.40 (q, J = 9.8 Hz), -123.83. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 21 H 13 F7N3O2 + 472.0891; Found 472.0890.

[0061] Example 5

[0062] This embodiment is set up the same as in Example 1, except that when the raw materials are added, (E)-1-(3-chlorophenyl)-3-(dimethylamino)prop-2-en-1-one (0.0839 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 58%.

[0063] The reaction equation is as follows: .

[0064] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.04 (s, 1H), 8.43 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.87 (s, 1H), 7.79 (ddd, J = 8.5, 6.8, 1.2 Hz,1H), 7.72 – 7.63 (m, 2H), 7.55 – 7.44 (m, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 188.5, 153.2, 141.8, 137.7, 135.6,134.8, 132.9, 131.6, 130.4, 129.9, 128.5, 123.7, 122.8, 121.2, 117.2, 114.4. 19 F NMR (376 MHz, Chloroform- d ) δ -80.06 (t, J = 9.7 Hz), -106.30 (q, J = 9.9 Hz), -124.05. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H9ClF7N3O + 476.0395; Found476.0398.

[0065] Example 6

[0066] This embodiment is set up the same as in Example 1, except that (E)-4-(dimethylamino)but-3-en-2-one (0.0453 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 37%.

[0067] The reaction equation is as follows: .

[0068] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.11 (s, 1H), 8.34 (d, J = 8.3 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.76 – 7.71 (m, 1H), 7.45 (t, J = 7.6 Hz, 1H), 2.73 (s, 3H). 13C NMR (101 MHz, Chloroform- d ) δ 195.7, 153.2, 141.4, 137.8, 132.8,131.4, 125.6, 123.5, 121.0, 117.0, 114.3, 31.3. 19 F NMR (377 MHz, Chloroform- d ) δ -79.70 (t, J = 9.8 Hz), -105.80 (q, J = 9.8 Hz), -123.33 (d, J = 3.6 Hz), -123.36, -123.38 (d, J = 3.6 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 15 H9F7N3O + 380.0628; Found380.0619.

[0069] Example 7

[0070] This embodiment has the same setup as Example 1, except that when adding the raw materials, (E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (0.0773 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 61%.

[0071] The reaction equation is as follows: .

[0072] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.03 (s, 1H), 8.42 (d, J = 8.3 Hz,1H), 7.96 – 7.88 (m, 3H), 7.81 – 7.74 (m, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.20(t, J = 8.5 Hz, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 188.1, 168.1, 165.5, 153.2, 141.8,138.7, 133.1, 133.0, 132.8, 132.7, 131.6, 123.6, 123.2, 121.2, 117.1, 116.6,116.3, 114.4. 19 F NMR (376 MHz, Chloroform- d ) δ -79.79 (t, J = 9.7 Hz), -101.31 (tt, J = 8.3, 5.1 Hz), -106.17 (q, J = 9.9 Hz), -123.80. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 10 F8N3O + 460.0696; Found460.0706.

[0073] Example 8

[0074] This embodiment is set up the same as in Example 1, except that when the raw materials are added, (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one (0.0701 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 67%.

[0075] The reaction equation is as follows: .

[0076] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.04 (s, 1H), 8.40 (d, J = 8.3 Hz, 1H), 7.91 (d, J= 8.7 Hz, 1H), 7.88 – 7.85 (m, 2H), 7.77 – 7.72 (m, 1H), 7.70– 7.65 (m, 1H), 7.50 (dt, J = 15.7, 7.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 189.6, 153.1, 141.8, 138.9, 136.1,134.8, 133.0, 131.4, 130.3, 129.0, 123.5, 123.4, 121.1, 117.0, 114.4. 19 F NMR (376 MHz, Chloroform- d ) δ -79.84 (t, J = 9.6 Hz), -106.16 (q, J = 9.8 Hz), -123.79. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 11 F7N3O + 442.0785; Found442.0785.

[0077] Example 9

[0078] This embodiment is set up the same as in Example 1, except that when the raw materials are added, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one (0.0557 g, 0.4 mmol) is used instead of (E)-3-(dimethylamino)acrylate (0.0573 g, 0.4 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 58%.

[0079] The reaction equation is as follows: .

[0080] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.14 (s, 1H), 8.37 (d, J = 8.3 Hz, 1H), 7.92 (d,J = 8.7 Hz, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 2.41 (tt, J = 8.0, 4.4 Hz, 1H), 1.51 – 1.44 (m, 2H), 1.28 (dd, J = 7.6, 3.7 Hz, 2H). 13 C NMR (101 MHz, Chloroform- d ) δ 199.1, 153.2, 141.5, 138.0, 132.9,131.4, 126.2, 123.4, 121.1, 117.1, 114.3, 22.9, 14.3. 19 F NMR (376 MHz, Chloroform- d ) δ -79.97 (t, J = 9.8 Hz), -106.05 (q, J = 9.9 Hz), -123.67. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 17 H 10 F7N3O + 406.0785; Found406.0788.

[0081] analyze: Comparing Examples 1 to 9, it can be seen that the reaction yields of enamine ketones with different substituents are significantly different, and the synthetic effects are in the following order: (E)-3-(dimethylamino)acrylate ethyl ester > (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one ≈ (E)-1-(4-chlorophenyl)-3-(dimethylamino)prop-2-en-1-one > (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en- 1-Ketone ≈ (E)-1-(3-chlorophenyl)-3-(dimethylamino)prop-2-en-1-ketone ≈ (E)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-ketone > (E)-1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-ketone > (E)-4-(dimethylamino)but-3-en-2-ketone, wherein the ethyl (E)-3-(dimethylamino)acrylate of Example 1 is the most effective.

[0082] To test the effect of different (substituent) aminoinazoles on the reaction, the experiments shown in Examples 10 to 16 were conducted.

[0083] Example 10

[0084] The setup in this embodiment is the same as in Example 1, except that when the raw materials are added, 6-fluoro-1H-indazole-3-amine (0.0151g, 0.1mmol) is used instead of 1H-indazole-3-amine (0.0133g, 0.1mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 77%.

[0085] The reaction equation is as follows: .

[0086] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.42 (s, 1H), 8.39 (dd, J = 9.1, 5.3Hz, 1H), 7.55 (dd, J = 9.5, 2.1 Hz, 1H), 7.28 (dd, J = 10.3, 8.2 Hz, 1H), 4.54 (q, J = 7.2 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 166.1, 163.6, 162.8, 154.3, 154.1,141.5, 136.0, 123.4, 123.3, 117.2, 115.0, 114.7, 111.3, 101.3, 101.1, 63.4,13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.65 (t, J = 10.4 Hz), -104.76 (t, J = 7.9 Hz), -106.19 (q, J = 9.8 Hz), -122.76. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 16 H9F8N3O2 + 428.0640; Found428.0645.

[0087] Example 11

[0088] This embodiment is set up the same as in Example 1, except that when the raw materials are added, 6-chloro-1H-indazole-3-amine (0.0168 g, 0.1 mmol) is used instead of 1H-indazole-3-amine (0.0133 g, 0.1 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 72%.

[0089] The reaction equation is as follows: .

[0090] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.40 (s, 1H), 8.31 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.42 (dd, J = 8.8, 1.7 Hz, 1H), 4.51 (q, J =7.2 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 162.8, 153.7, 141.6, 137.8, 136.2,125.0, 122.4, 117.6, 116.4, 112.7, 63.4, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.64 (t, J = 9.9 Hz), -106.21 (q, J = 9.4 Hz), -122.75 (d, J = 15.9 Hz), -122.75. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 16 H9ClF7N3O2 + 444.0344; Found444.0341.

[0091] Example 12

[0092] The setup in this embodiment is the same as in Example 1, except that when the raw materials are added, 6-bromo-1H-indazole-3-amine (0.0212 g, 0.1 mmol) is used instead of 1H-indazole-3-amine (0.0133 g, 0.1 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 76%.

[0093] The reaction equation is as follows: .

[0094] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.43 (s, 1H), 8.27 (dd, J = 8.7, 0.7Hz, 1H), 8.16 (dd, J = 1.5, 0.7 Hz, 1H), 7.58 (dd, J = 8.8, 1.5 Hz, 1H), 4.54(q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 162.8, 153.9, 136.3, 127.3, 126.1,122.4, 119.7, 117.8, 112.9, 63.4, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.64 (t, J = 9.9 Hz), -106.20 (q, J = 10.0 Hz), -122.76 (d, J = 7.7 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 16 H9BrF7N3O2 + 487.9839; Found 487.9839.

[0095] Example 13

[0096] This embodiment is set up the same as in Example 1, except that when the raw materials are added, 6-(trifluoromethyl)-1H-indazole-3-amine (0.0201g, 0.1mmol) is used instead of 1H-indazole-3-amine (0.0133g, 0.1mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 84%.

[0097] The reaction equation is as follows: .

[0098] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.47 (s, 1H), 8.51 (d, J = 8.7 Hz,1H), 8.29 (s, 1H), 7.65 (d, J = 8.7 Hz, 1H), 4.53 (q, J = 7.2 Hz, 2H), 1.46(t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 162.6, 152.1, 136.4, 122.6, 119.4,118.4, 115.7, 115.5, 63.6, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -62.59, -79.67 (t, J = 9.8 Hz), -106.30 (q, J = 9.4 Hz), -122.80 (d, J = 7.9 Hz). HRMS (ESI-TOF) m / z: [M + H] +Calcd for C 17 H 10 F 10 N3O2 + 478.0608; Found478.0592.

[0099] Example 14

[0100] The setup in this embodiment is the same as in Example 1, except that when the raw materials are added, 6-methoxy-1H-indazole-3-amine (0.0163g, 0.1mmol) is used instead of 1H-indazole-3-amine (0.0133g, 0.1mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 85%.

[0101] The reaction equation is as follows: .

[0102] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.35 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.14 (d, J = 2.1 Hz, 1H), 7.10 (dd, J = 9.0, 2.1 Hz, 1H), 4.49 (q, J =7.1 Hz, 2H), 3.98 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.1, 163.0, 155.6, 141.4, 135.9,122.0, 118.1, 115.8, 109.1, 94.6, 63.1, 55.7, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.58 (t, J = 9.8 Hz), -106.01 (q, J = 9.5 Hz), -122.69 (d, J = 15.9 Hz), -122.69. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 17 H 13 F7N3O3 + 440.0840; Found440.0840.

[0103] Example 15

[0104] The setup in this embodiment is the same as in Example 1, except that when the raw materials are added, 3-amino-1H-indazole-5-carboxynitrile (0.0158 g, 0.1 mmol) is used instead of 1H-indazole-3-amine (0.0133 g, 0.1 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 73%.

[0105] The reaction equation is as follows: .

[0106] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.47 (s, 1H), 8.82 (t, J = 1.2 Hz,1H), 8.07 – 7.99 (m, 1H), 7.88 (dd, J = 9.0, 1.6 Hz, 1H), 4.53 (q, J = 7.2Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 162.4, 153.4, 142.1, 136.8, 132.3,128.4, 119.1, 118.9, 118.7, 113.7, 106.8, 63.8, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -79.70 (t, J = 9.9 Hz), -106.45 (q, J = 9.4 Hz), -122.76 (d, J = 16.3 Hz), -122.76. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 17 H 10 F7N4O2 + 435.0686; Found435.0688.

[0107] Example 16

[0108] This embodiment is set up the same as in Example 1, except that when the raw materials are added, 5-(3,5-difluorobenzyl)-1H-indazole-3-amine (0.0259 g, 0.1 mmol) is used instead of 1H-indazole-3-amine (0.0133 g, 0.1 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 69%.

[0109] The reaction equation is as follows: .

[0110] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.40 (s, 1H), 8.20 (s, 1H), 7.90 (d, J = 8.9 Hz, 1H), 7.55 (dd, J = 8.9, 1.7 Hz, 1H), 6.78 – 6.72 (m, 2H), 6.67(tt, J = 9.0, 2.4 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 4.18 (s, 2H), 1.45 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 164.5, 163.0, 152.6, 144.6, 141.2,139.1, 136.1, 135.0, 133.4, 120.3, 117.7, 117.2, 114.5, 111.9, 111.8, 111.7,111.7, 102.3, 102.0, 101.8, 63.3, 41.8, 13.9. 19F NMR (376 MHz, Chloroform- d ) δ -79.66 (t, J = 10.0 Hz), -106.12 (q, J = 9.6 Hz), -109.91 (t, J = 8.2 Hz), -122.74 (d, J = 8.4 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 23 H 15 F9N3O2 + 536.1021; Found536.1024.

[0111] analyze: Comparing Examples 1 and 10-16, it can be seen that when different (substituent) aminoindazoles are used for the reaction, the synthesis effect is as follows: 1H-indazole-3-amine > 6-methoxy-1H-indazole-3-amine > 6-(trifluoromethyl)-1H-indazole-3-amine > 6-fluoro-1H-indazole-3-amine > 6-bromo-1H-indazole-3-amine > 3-amino-1H-indazole-5-carboxynitrile > 6-chloro-1H-indazole-3-amine > 5-(3,5-difluorobenzyl)-1H-indazole-3-amine, among which the 1H-indazole-3-amine of Example 1 has the best effect.

[0112] To test the effect of different perfluoroiodoalkanes on the reaction, the experiments shown in Examples 17 to 21 were conducted.

[0113] Example 17 This embodiment is set up the same as in Example 1, except that: when adding raw materials, perfluoroiodopropane (0.0888 g, 0.3 mmol) is used instead of perfluoroiodobutane (0.104 g, 0.3 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds with a yield of 60%.

[0114] The reaction equation is as follows: .

[0115] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.46 (s, 1H), 8.34 (d, J = 8.4 Hz, 1H), 7.93 (d,J = 8.7 Hz, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.49 – 7.42 (m, 1H), 4.52 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 162.8, 153.4, 141.2, 139.2, 136.5,131.6, 123.5, 121.1, 117.2, 116.7, 114.4, 63.2, 14.0. 19 F NMR (376 MHz, Chloroform- d ) δ -80.01, -80.03, -80.09, -108.01. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 15 H 11 F5N3O2 + 360.0771; Found360.0772.

[0116] Example 18 This embodiment has the same setup as Example 1, except that: when adding raw materials, perfluoroiodopentane (0.1188g, 0.3mmol) is used instead of perfluoroiodobutane (0.104g, 0.3mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 71%.

[0117] The reaction equation is as follows: .

[0118] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.46 (s, 1H), 8.40 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 8.7 Hz, 1H), 7.83 – 7.75 (m, 1H), 7.54 – 7.47 (m, 1H), 4.54(q,J = 7.1 Hz, 2H), 1.48 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.0, 153.4, 141.4, 139.2, 136.0,131.6, 123.6, 121.2, 117.2, 117.2, 114.4, 63.3, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -80.92 (t, J = 10.1 Hz), -105.48 (t, J = 12.7 Hz), -118.92 – -119.20 (m), -124.42 (d, J = 13.8 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 17 H 11 F9N3O2 + 460.0708; Found460.0706.

[0119] Example 19 This embodiment has the same setup as Example 1, except that: when adding raw materials, perfluoroiodopentane (0.1338 g, 0.3 mmol) is used instead of perfluoroiodobutane (0.104 g, 0.3 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone with a yield of 68%.

[0120] The reaction equation is as follows: .

[0121] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.42 (s, 1H), 8.38 (d, J = 8.3 Hz, 1H), 7.95 (d, J= 8.7 Hz, 1H), 7.80 – 7.74 (m, 1H), 7.52 – 7.45 (m, 1H), 4.51(q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.1, 153.4, 141.5, 135.9, 131.6,123.6, 121.2, 117.3, 117.2, 114.4, 63.3, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -80.64 (t, J = 10.3 Hz), -105.47 (t, J = 14.5 Hz), -118.41 (t, J = 14.4 Hz), -121.35 (q, J = 13.0 Hz), -126.09 (t, J = 14.9 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 18 H 11 F 11 N3O2 + 510.0676; Found510.0673.

[0122] Example 20 The setup in this embodiment is the same as in Example 1, except that perfluoroiodooctane (0.1638 g, 0.3 mmol) was used instead of perfluoroiodobutane (0.104 g, 0.3 mmol) when the raw materials were added, to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone with a yield of 71%.

[0123] The reaction equation is as follows: .

[0124] Product confirmation: 1 H NMR (400 MHz, Chloroform- d) δ 9.41 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.1, 153.4, 141.5, 135.9, 131.6,123.6, 121.2, 117.3, 117.2, 114.4, 63.3, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -80.74 (d, J = 10.8 Hz), -105.45 (d, J = 15.3 Hz), -118.21 (d, J = 16.8 Hz), -120.43, -121.87, -122.56, -126.10(d, J = 16.6 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 20 H 11 F 15 N3O2 + 610.0612; Found610.0609.

[0125] Example 21 This embodiment has the same setup as Example 1, except that: when adding raw materials, perfluoroiododecane (0.1938 g, 0.3 mmol) is used instead of perfluoroiodobutane (0.104 g, 0.3 mmol) to obtain perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone with a yield of 54%.

[0126] The reaction equation is as follows: .

[0127] Product confirmation: 1 H NMR (400 MHz, Chloroform- d ) δ 9.40 (s, 1H), 8.38 (d, J = 8.3 Hz,1H), 7.95 (d, J = 8.7 Hz, 1H), 7.76 (t, J = 7.7 Hz, 1H), 7.51 – 7.45 (m, 1H),4.51 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 163.1, 153.5, 141.5, 135.8, 131.6,123.6, 121.2, 117.4, 117.2, 114.4, 63.3, 13.9. 19 F NMR (376 MHz, Chloroform- d ) δ -80.72 (t, J = 10.2 Hz), -105.44 (t, J = 14.4 Hz), -118.16, -120.37, -121.73 (d, J = 93.1 Hz), -122.66, -126.08(td, J = 15.0, 14.2, 6.7 Hz). HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 22 H 11 F 19 N3O2 + 710.0542; Found710.0536。

[0128] Analysis: Comparing Examples 1 and 17 to 21, it can be seen that when different perfluoroiodoalkanes are used for the reaction, the synthesis effect is as follows: perfluoroiodobutane > perfluoroiodopentane ≈ perfluoroiodooctane > perfluoroiodopentane > perfluoroiodopropane > perfluoroiododecane, among which the effect of perfluoroiodobutane in Example 1 is the best.

[0129] Application Examples This embodiment mainly investigates the antibacterial properties of perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compounds.

[0130] The antibacterial properties of the product prepared in Example 1 were evaluated using the following method: 1. Sample preparation for testing antibacterial materials Accurately weigh the sample and prepare sample solutions (using DMSO) with concentrations of 20 mg / mL, 40 mg / mL, and 80 mg / mL, respectively, to test their inhibitory effect on Escherichia coli.

[0131] 2. Preparation of bacterial suspension Take a strain of *E. coli* and place it in a test tube. Add 5 mL of culture medium to the test tube and incubate at 37°C for 8 hours. Then, use an inoculation loop to streak the bacterial culture evenly onto nutrient broth agar medium. Incubate the medium in a constant temperature incubator for 16 hours to obtain a single *E. coli* colony. Pick a single *E. coli* colony with a pipette tip and place it in 5 mL of LB medium. Incubate at 37°C for 10 hours to obtain the OD. 600 =1.0 bacterial solution.

[0132] 3. Antibacterial zone experiment After turning on the ultra-clean hood for 30 minutes, perform aseptic operations. Immerse blank antibiotic susceptibility test strips in the aforementioned sample solution for 5 minutes. Take 40 μL of the test bacterial solution and spread it evenly on nutrient broth agar medium. Then, attach the antibiotic susceptibility test strips soaked in the solution to the medium. Incubate the medium overnight at 37°C. Observe the size of the inhibition zone afterward. Figure 2 As shown in Table 4.

[0133] Table 4: Antibacterial Properties

[0134] In the table: 1 is DMSO solution; 2 is 20 mg / mL sample solution; 3 is 40 mg / mL sample solution; 4 is 80 mg / mL sample solution.

[0135] Table 4 shows that different concentrations of the product solution from Example 1 have different antibacterial effects against Escherichia coli; the higher the concentration, the stronger the bactericidal effect. The perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound of this application has good antibacterial effects and can be used to prepare antibacterial drugs.

[0136] The embodiments described above are merely examples of several feasible implementations of this application. While the descriptions are specific and detailed, they should not be construed as limiting the scope of the patent application. Furthermore, the embodiments are not intended to limit the scope of protection outlined in the claims. Those skilled in the art can make various modifications and improvements without departing from the concept of this application. All equivalent implementations or changes that do not depart from the scope of this application should be included in the technology of this application.

Claims

1. A method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound, characterized in that, The process includes the following steps: using enamine ketones, perfluoroalkane compounds, and aminoindazoles as raw materials, the reaction is carried out in the presence of an organic solvent and a base under blue light irradiation to prepare perfluoroalkyl-substituted pyrimido[1,2-b]indazole methyl ketone compounds.

2. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The enamino ketone is selected from (E)-3-(dimethylamino)ethyl acrylate, (E)-1-(4-chlorophenyl)-3-(dimethylamino)prop-2-en-1-one, (E)-1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-one, (E)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one, (E)-1-(3-chlorophenyl) (E)-3-(dimethylamino)prop-2-en-1-one, (E)-4-(dimethylamino)but-3-en-2-one, (E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one, (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one 3. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The perfluoroalkane compound is selected from any one of perfluoropropane, perfluoropentane, perfluorohexane, perfluorooctane, and perfluorodecane.

4. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The aminoinazole is selected from any one of 6-fluoro-1H-indazole-3-amine, 6-chloro-1H-indazole-3-amine, 6-bromo-1H-indazole-3-amine, 6-(trifluoromethyl)-1H-indazole-3-amine, 6-methoxy-1H-indazole-3-amine, 3-amino-1H-indazole-5-carboxynitrile, and 5-(3,5-difluorobenzyl)-1H-indazole-3-amine.

5. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The molar ratio of the enamine ketone, perfluoroalkane compound, and aminoinazole is 2–5: 2–4:

1.

6. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The organic solvent is selected from any one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, and dichloromethane.

7. The method for preparing a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound according to claim 1, characterized in that: The base is selected from any one of dicycloamidinium, triethylenediamine, tetramethylethylenediamine, and N,N-diisopropylethylamine.

8. The use of a perfluoroalkyl-substituted pyrimido[1,2-b]indazole ketone compound prepared by the method of claim 1 in the preparation of antibacterial drugs.

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