Monofluoroazidone compound as well as preparation and application thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to a monofluoro azidone compound as well as preparation and application thereof. The preparation method comprises the following steps: dissolving a first compound and an azide source, uniformly mixing, reacting under the protection of nitrogen, and performing post-treatment to obtain the monofluoro azidone compound. The preparation method of the monofluoro azidone compound provided by the invention has the characteristics of short reaction time and low reaction temperature; in this way, in the production process, a large amount of energy and time cost can be saved, the production efficiency is improved, and energy consumption and the requirement for equipment in the production process are reduced; according to the preparation method provided by the invention, the monofluoro azidone compound can be efficiently synthesized, and the yield is relatively high; the utilization rate of the raw materials is increased, the waste is reduced, and large-scale industrial production becomes possible; the structure of the monofluoro azidone compound is brand new, a new direction and possibility are provided for chemical research and application, and innovation and development in related fields are promoted.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a monofluoroazidoketone compound and its preparation and application. Background Art

[0002] Azide compounds can be used as versatile intermediates for further reactions. For example, these structures can be used to synthesize 1,2,3-triazole compounds through cycloaddition reactions with alkynes. 1,2,3-Triazole compounds are an important class of nitrogen-containing heterocyclic compounds, which have important applications in medicine, pesticides, materials, and synthetic chemistry. Their synthesis methods and application research have received extensive attention, especially the discovery that some compounds containing 1,2,3-triazole rings have special biological activities. Therefore, the synthesis of novel azides is beneficial to the synthesis of more novel nitrogen-containing heterocyclic compounds.

[0003] Introducing fluoroalkyl groups on nitrogen-containing heterocyclic scaffolds can usually improve adsorption, hydrophobicity, and metabolism to enhance the pharmacokinetic properties of lead drugs. Therefore, the synthesis of fluoroazide compounds is beneficial to the subsequent synthesis of fluoro-containing drug analogs with 1,2,3-triazole ring structures.

[0004] In 2020, Petr Beier et al. first used sodium azide to replace bromofluoromethane to prepare azidopolyfluoromethane. This volatile and unstable compound was separated by low-temperature vacuum distillation, characterized, and subjected to [3+2] cycloaddition with alkynes, 1,3-diketones, and β-ketoesters to obtain 1-fluoromethyl-1,2,3-triazole. However, this route involves a relatively cumbersome three-step synthesis, and the intermediates are unstable, making separation difficult.

[0005]

[0006] In 2020, the research group of Ning Yongquan reported a new strategy for the fluorocyclization of 3-azidoheterocycles through readily available vinyl azides. This transformation proceeds under mild conditions and provides a wide range of 3-azidoheterocycles in high yields. Among them, the azide group plays an indispensable role in promoting rapid and regioselective fluorocyclization. However, this two-step synthesis method is relatively cumbersome and has a low cumulative yield.

[0007]

[0008] In 2021, the research group of Liu Zhaohong achieved an effective method for preparing oxetanes and azetidines by the fluoro-cyclization of readily available 2-azidoalkenols and amines. This is the first example of applying the fluoro-cyclization strategy to construct four-membered heterocycles. Through DFT and experimental studies, it was confirmed that the pendant electron-donating group (-N3) plays a crucial role in the polarization of the C=C double bond and the promotion of cyclization. However, the two-step synthesis of this route is relatively cumbersome, the reaction conditions are harsh, and Py·HF and by-products increase the cost and difficulty of post-treatment.

[0009]

[0010] The work reported by David Philip Day in 2021 demonstrated a new approach to obtain α-fluoro-α-triazol-1-yl ketones from sulfonylureas through an α-azido-α-fluoro ketone intermediate. In a one-pot two-step process, the ketone sulfoxide was initially subjected to the insertion of F+ and N3-, and then underwent a CuAAC reaction with arylacetylene to obtain the 1,2,3-triazole group. However, this route using a two-step method is relatively cumbersome, requires multiple purifications, uses a large amount of solvents, and causes serious waste.

[0011]

[0012] In summary, it is crucial to provide a technical solution that can solve the above-mentioned technologies. Summary of the Invention

[0013] To solve the above problems, the purpose of the present invention is to provide a monofluoroazidoketone compound and its preparation and application. The structure of the monofluoroazidoketone compound in the present invention is completely new and has potential biological activity.

[0014] The purpose of the present invention can be achieved by the following technical solutions:

[0015] The first purpose of the present invention is to provide a monofluoroazidoketone compound with a structural formula shown in Formula (1):

[0016]

[0017] Wherein, R1 and R2 are each independently selected from any one of alkyl, phenyl, substituted phenyl, fused-ring aryl or heterocyclic substituent; m is an integer from 0 to 3; Ar is selected from one of aryl or heteroaryl.

[0018] In an embodiment of the present invention, when R1 or R2 is a substituted phenyl, the substituent in the substituted phenyl is selected from any one or more of phenyl, hydrogen, fluorine, bromine, chlorine, C1-C4 alkyl, p-methoxy, trifluoromethyl, p-1,3-benzodioxole, p-halogen-substituted benzene or benzyl.

[0019] The second object of the present invention is to provide a method for preparing monofluoroazidoketone compounds, comprising the following steps:

[0020] Dissolve the first compound and the azide source and then carry out a reaction, and perform post-treatment to obtain monofluoroazidoketone compounds;

[0021] Wherein, the chemical structural formula of the first compound is shown in formula (2):

[0022]

[0023] Wherein, Y is Cl, Br or I, and R1 and R2 are each independently selected from any one of alkyl, phenyl, substituted phenyl, polycyclic aryl or heterocyclic substituents; m is an integer from 0 to 3; Ar is selected from one of aryl or heteroaryl.

[0024] In one embodiment of the present invention, when R1 or R2 is a substituted phenyl, the substituents in the substituted phenyl are selected from any one or more of phenyl, hydrogen, fluorine, bromine, chlorine, C1-C4 alkyl, p-methoxy, trifluoromethyl, p-1,3-benzodioxole, p-halogen-substituted benzene or benzyl.

[0025] In one embodiment of the present invention, the azide source is selected from one or several of NaN3, TMSN3, TsN3, TBSnA, TMGA or AAE.

[0026] In one embodiment of the present invention, the first compound and the azide source are dissolved in a solvent, and the solvent is selected from one or several of DMSO, tert-butanol, DME, CH2Cl2, CH3OH, CH3CN, DMF, THF, H2O or 1,4-Dioxane.

[0027] In one embodiment of the present invention, the molar ratio of the first compound to the azide source is 0.15 to 0.25:1.

[0028] In one embodiment of the present invention, during the reaction, the temperature is 0 to 50 °C and the time is 0.25 to 2 h.

[0029] In one embodiment of the present invention, the post-treatment is to carry out column chromatography separation on the reaction product after the reaction ends;

[0030] A mixture of n-hexane and ethyl acetate is used during the column chromatography separation.

[0031] In one embodiment of the present invention, the volume ratio of n-hexane to ethyl acetate is 60 to 500:1.

[0032] The third object of the present invention is to provide an application of monofluoroazidoketone compounds in the field of skeleton editing.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] (1) The preparation method of the monofluoroazidoketone compound provided by the present invention is characterized by short reaction time and low reaction temperature; this means that a large amount of energy and time costs can be saved during the production process, the production efficiency can be improved, and the energy consumption and requirements for equipment during the production process can be reduced.

[0035] (2) The preparation method of the monofluoroazidoketone compound provided by the present invention can efficiently synthesize the monofluoroazidoketone compound with a high yield; this not only improves the utilization rate of raw materials, reduces waste, but also makes large-scale industrial production possible, bringing higher economic benefits to enterprises.

[0036] (3) The structures of the monofluoroazidoketone compounds prepared by the present invention are all brand new. This novel structure provides new directions and possibilities for chemical research and applications, and helps to promote innovation and development in related fields. In addition, these compounds may have a variety of different combinations of substituents and functional groups, thus exhibiting different chemical properties and reaction activities. This structural diversity provides a broad space for their applications in different fields. For example, in drug design, appropriate structures can be selected for optimization according to different therapeutic goals. Detailed implementation manners

[0037] In the following examples, for the monofluoroiodoketone compounds with the general structural formula shown in formula (2), their synthesis methods can refer to the literature: https: / / doi.org / 10.1002 / ejoc.202200137. Unless otherwise specified, the reagents used are all commercially available reagents, and the detection means and methods used are all conventional detection means and methods in this field.

[0038] Example 1

[0039] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 2,3 - dihydro - 1H - inden - 1 - one, including the following steps:

[0040] 2-Fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) and sodium azide (1.1 mmol) were added to a 10 mL standard reaction tube. After evacuation, the tube was backfilled with nitrogen three times. Under nitrogen protection, 4.0 mL of dimethyl sulfoxide was added to the above 10 mL standard reaction tube using a pipette. After the addition was complete, the tube was sealed with a sealing film and stirred at 25 °C for about 0.5 h. The reaction was monitored by TLC until completion. After the reaction was completed, the reaction was quenched with 3 mL of sodium hypochlorite solution. Water (4 mL) and ethyl acetate (10 mL) were added to the reaction system for extraction (extracted 3 times in total). After extraction, the aqueous layer was discarded, and the organic layers were combined. Anhydrous sodium sulfate (20 g) was added for drying (about 0.5 h). After drying, the mixture was filtered, and the filtrate was concentrated using a rotary evaporator (at a temperature of 40 °C for 0.5 h) to remove the organic solvent. The remaining product was separated by column chromatography (the volume ratio of n-hexane to ethyl acetate was 60:1) to obtain 0.1874 g of a pale yellow oily liquid (2-azido-2-fluoro-2,3-dihydro-1H-inden-1-one) with a yield of 98%;

[0041] Among them, the chemical structural formula of 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one is shown as follows:

[0042]

[0043] The chemical structural formula of 2-azido-2-fluoro-2,3-dihydro-1H-inden-1-one is shown as follows:

[0044]

[0045] 1 H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 7.7 Hz, 1H), 7.63 (t, J = 7.7 Hz, 1H), 7.37 (q, J = 7.7 Hz, 2H), 3.64 - 2.81 (m, 2H).

[0046] 13 C NMR (100 MHz, CDCl3): δ 194.00 (d, J = 29.6 Hz), 148.88 (d, J = 4.3 Hz), 137.29, 132.15 (d, J = 2.3 Hz), 128.82, 126.73, 125.82, 101.68 (d, J = 231.4 Hz), 38.68 (d, J = 24.6 Hz).

[0047] 19 F NMR (376 MHz, CDCl3): δ -127.64 (dd, J = 19.3, 10.5 Hz).

[0048] HRMS(ESI) m / z calcd [M+Na] + = for C9H6FN3O: 214.0387, found: 214.0381.

[0049] Example 2

[0050] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 4 - methyl - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 4 - methyl - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol), the others are the same as in Example 1.

[0051] In this example, 0.1874 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 4 - methyl - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 98%;

[0052] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 4 - methyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0053]

[0054] The chemical structural formula of 2 - azido - 2 - fluoro - 4 - methyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0055]

[0056] 1 1H NMR (500 MHz, CDCl3): δ 7.80 (dd, J = 6.7, 1.4 Hz, 1H), 7.36 - 6.98 (m, 2H), 3.43 - 3.04 (m, 2H), 2.22 (d, J = 0.7 Hz, 3H).

[0057] 13 13C NMR (125 MHz, CDCl3): δ 200.54 (d, J = 32.0 Hz), 145.18 (d, J = 6.2 Hz), 136.15, 134.58 (d, J = 1.9 Hz), 133.63 (d, J = 4.1 Hz), 127.03, 123.30 (d, J = 2.1 Hz), 109.03 (d, J = 268.1 Hz), 40.16 (d, J = 26.9 Hz), 18.17.

[0058] 1919F NMR (472 MHz, CDCl3): δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F).

[0059] HRMS (ESI) m / z calcd [M+Na] + = for C9H6FN3O: 228.0544, found: 228.0538.

[0060] Example 3

[0061] This example provides a method for preparing a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 5 - methyl - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 5 - methyl - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol), the others are the same as in Example 1.

[0062] In this example, 0.1886 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 5 - methyl - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 92%;

[0063] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 5 - methyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:[[]]

[0064]

[0065] The chemical structural formula of 2 - azido - 2 - fluoro - 5 - methyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:[[]]

[0066]

[0067] 1 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 8.1 Hz, 1H), 7.17 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.13 - 7.04 (m, 1H), 3.14 (dddd, J = 42.3, 25.2, 12.5, 1.1 Hz, 2H), 2.29 (s, 3H).

[0068] 13C NMR (125MHz, CDCl3): δ198.75, 198.49 (d, J = 30.0Hz), 146.74, 143.45, 132.83, 127.92 ,127.11,125.51,111.51,109.37(d,J=267.5Hz),42.62,42.40(d,J=27.5Hz),21.06.

[0069] 19 F NMR (376MHz, CDCl3): δ-127.64 (dd, J=19.3, 10.5Hz, 1F).

[0070] HRMS(ESI)m / z calcd[M+Na] + =for C9H6FN3O:228.0544,found:228.0545.

[0071] Example 4

[0072] This example provides a method for preparing a monofluoroazide ketone compound - 2-azido-2-fluoro-6-methyl-2,3-dihydro-1H-inden-1-one, which is the same as Example 1 except that 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) is replaced by 2-fluoro-2-iodo-6-methyl-2,3-dihydro-1H-inden-1-one (1 mmol).

[0073] In this example, 0.1970 g of a light yellow oily liquid (2-azido-2-fluoro-6-methyl-2,3-dihydro-1H-inden-1-one) was isolated, with a yield of 96%.

[0074] The chemical structure of 2-fluoro-2-iodo-6-methyl-2,3-dihydro-1H-inden-1-one is shown below:

[0075]

[0076] The chemical structure of 2-azido-2-fluoro-6-methyl-2,3-dihydro-1H-inden-1-one is shown below:

[0077]

[0078] 1 H NMR (500MHz, CDCl3): δ7.76(d,J=1.9Hz,1H),7.35-7.01(m,1H),6.85(d,J=7.6Hz,1H),3.67-3.05(m,2H),2.38(s,3H).

[0079] 13 13C NMR (125 MHz, CDCl3): δ 198.15 (d, J = 32.0 Hz), 144.34, 137.88, 135.32, 132.71 (d, J = 4.1 Hz), 126.09, 125.95, 110.44, 42.00 (d, J = 27.2 Hz), 21.01.

[0080] 19 19F NMR (376 MHz, CDCl3): δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F).

[0081] HRMS (ESI) m / z calcd [M+Na] + = for C9H6FN3O: 228.0544, found: 228.0549.

[0082] Example 5

[0083] This example provides a method for preparing a monofluoroazidoketone compound, 2-azido-2-fluoro-7-methyl-2,3-dihydro-1H-inden-1-one. Except that 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) is replaced by 2-fluoro-2-iodo-7-methyl-2,3-dihydro-1H-inden-1-one (mmol), the others are the same as in Example 1.

[0084] In this example, 0.1887 g of a pale yellow oily liquid (2-azido-2-fluoro-7-methyl-2,3-dihydro-1H-inden-1-one) was isolated, with a yield of 92%;

[0085] Among them, the chemical structural formula of 2-fluoro-2-iodo-7-methyl-2,3-dihydro-1H-inden-1-one is shown as follows:

[0086]

[0087] The chemical structural formula of 2-azido-2-fluoro-7-methyl-2,3-dihydro-1H-inden-1-one is shown as follows:

[0088]

[0089] 1 1H NMR (500 MHz, DMSO-d6): δ 7.58 - 7.18 (m, 2H), 7.09 (dq, J = 6.8, 1.0 Hz, 1H), 3.14 (dddd, J = 42.3, 25.3, 12.5, 1.1 Hz, 2H), 2.38 (d, J = 0.6 Hz, 3H).

[0090] 13 13C NMR (125 MHz, CDCl3): δ 201.13 (d, J = 32.0 Hz), 145.18 (d, J = 6.0 Hz), 138.15 (d, J = 2.1 Hz), 133.79, 131.95 (d, J = 4.1 Hz), 129.78, 125.40 (d, J = 2.1 Hz), 108.84 (d, J = 267.8 Hz), 41.30 (d, J = 26.9 Hz), 19.57.

[0091] 19 19F NMR (376 MHz, DMSO-d6): δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F).

[0092] HRMS (ESI) m / z calcd [M+Na] + = for C9H6FN3O: 228.0544, found: 228.0542.

[0093] Example 6

[0094] This example provides a method for preparing a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 5 - methoxy - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced with 2 - fluoro - 2 - iodo - 5 - methoxy - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol), the others are the same as in Example 1.

[0095] In this example, 0.1990 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 5 - methoxy - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 90%;

[0096] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 5 - methoxy - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0097]

[0098] The chemical structural formula of 2 - azido - 2 - fluoro - 5 - methoxy - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0099]

[0100] 11H NMR (500 MHz, CDCl3): δ 7.85 (d, J = 8.3 Hz, 1H), 6.89 (dd, J = 8.4, 2.0 Hz, 1H), 6.77 (dt, J = 2.1, 1.0 Hz, 1H), 3.80 (s, 3H), 3.47 - 3.08 (m, 2H).

[0101] 13 13C NMR (125 MHz, CDCl3): δ 198.44 (d, J = 32.0 Hz), 164.28, 147.86 (d, J = 6.0 Hz), 130.37 (d, J = 4.1 Hz), 125.80 (d, J = 2.1 Hz), 113.70, 111.03 (d, J = 2.1 Hz), 110.64 (d, J = 268.1 Hz), 55.30, 42.55 (d, J = 26.9 Hz).

[0102] 19 19F NMR (376 MHz, CDCl3): δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F).

[0103] HRMS (ESI) m / z calcd [M + Na] + = for C 10 H8FN3O2: 244.0493, found: 244.0499.

[0104] Example 7

[0105] This example provides a method for preparing a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 5,6 - dimethoxy - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 5,6 - dimethoxy - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol), the others are the same as in Example 1.

[0106] In this example, 0.2136 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 5,6 - dimethoxy - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 85%;

[0107] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 5,6 - dimethoxy - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0108]

[0109] The chemical structural formula of 2-azido-2-fluoro-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one is shown as follows:

[0110]

[0111] 1 H NMR(400MHz,CDCl3):δ7.49(s,1H),6.82(t,J=1.0Hz,1H),3.86(s,4H),3.85(s,4H),3.22(dd,J=25.2,1.0Hz,2H).

[0112] 13 C NMR(100MHz,CDCl3):δ197.82(d,J=32.0Hz),152.97,149.49,144.12(d,J=6.0Hz),130.47(d,J=4.1Hz),110.79(d,J=267.8Hz),108.52(d,J=1.9Hz),107.97(d,J=1.9Hz),56.12(d,J=50.1Hz),42.55(d,J=26.9Hz).

[0113] 19 F NMR(376MHz,CDCl3):δ-127.64(dd,J=19.3,10.5Hz,1F).

[0114] HRMS(ESI)m / z calcd[M+Na] + =for C 11 H 10 FN3O3:274.0598,found:274.0592.

[0115] Example 8

[0116] This example provides a preparation method of a monofluoroazidoketone compound - 2-azido-5-chloro-2-fluoro-2,3-dihydro-1H-inden-1-one. Except that 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) is replaced with 5-chloro-2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol), the others are the same as in Example 1.

[0117] In this example, 0.1986 g of a pale yellow oily liquid (2-azido-5-chloro-2-fluoro-2,3-dihydro-1H-inden-1-one) was isolated, and the yield was 88%;

[0118] Among them, the chemical structural formula of 5-chloro-2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one is shown as follows:

[0119]

[0120] The chemical structural formula of 2-azido-5-chloro-2-fluoro-2,3-dihydro-1H-inden-1-one is shown as follows:

[0121]

[0122] 1 H NMR(400MHz,CDCl3): δ7.86(d,J = 8.3Hz,1H),7.36(dd,J = 8.2,2.2Hz,1H),7.29 - 7.07(m,1H),4.13 - 2.43(m,2H).

[0123] 13 C NMR(100MHz,CDCl3): δ198.01(d,J = 32.0Hz),147.44(d,J = 6.0Hz),136.08,133.48(d,J = 4.1Hz),127.27,126.10(d,J = 2.2Hz),125.46(d,J = 1.9Hz),110.16(d,J = 268.1Hz),42.31(d,J = 27.2Hz).

[0124] 19 F NMR(376MHz,CDCl3): δ - 127.64(dd,J = 19.3,10.5Hz,1F).

[0125] HRMS(ESI)m / z calcd[M+Na] + =for C9H5ClFN3O:274.9997,found:274.9991.

[0126] Example 9

[0127] This example provides a preparation method of a monofluoroazidoketone compound - 2-azido-5-bromo-2-fluoro-2,3-dihydro-1H-inden-1-one. Except for replacing 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) with 5-bromo-2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol), the others are the same as in Example 1.

[0128] In this example, 0.2485 g of a pale yellow oily liquid (2-azido-5-bromo-2-fluoro-2,3-dihydro-1H-inden-1-one) was isolated, and the yield was 92%;

[0129] Among them, the chemical structural formula of 5-bromo-2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one is shown as follows:

[0130]

[0131] The chemical structural formula of 2-azido-5-bromo-2-fluoro-2,3-dihydro-1H-inden-1-one is shown as follows:

[0132]

[0133] 1 H NMR(400MHz,CDCl3): δ7.77(d,J = 8.4Hz,1H),7.45(dd,J = 8.3,2.3Hz,1H),7.39(dt,J = 2.2,0.9Hz,1H),3.33 - 3.15(m,2H).

[0134] 13 C NMR(100MHz,CDCl3)δ198.11(d,J = 32.2Hz),147.57(d,J = 6.0Hz),134.64(d,J = 3.8Hz),130.09,128.68(d,J = 2.2Hz),126.02(d,J = 1.9Hz),125.19,110.79(d,J = 267.8Hz),42.30(d,J = 26.9Hz).

[0135] 19 F NMR(376MHz,CDCl3):δ - 127.64(dd,J = 19.3,10.5Hz,1F).

[0136] HRMS(ESI)m / z calcd[M+Na] + =for C9H5BrFN3O:291.9492,found:291.9498.

[0137] Example 10

[0138] This example provides a preparation method of a monofluoroazidoketone compound - 2-azido-2,5,6-trifluoro-2,3-dihydro-1H-inden-1-one. Except for replacing 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) with 2,5,6-trifluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol), the others are the same as in Example 1.

[0139] In this example, 0.2135 g of a pale yellow oily liquid (2-azido-2,5,6-trifluoro-2,3-dihydro-1H-inden-1-one) was isolated, with a yield of 94%;

[0140] Among them, the chemical structural formula of 2,5,6-trifluoro-2-iodo-2,3-dihydro-1H-inden-1-one is shown as follows:

[0141]

[0142] The chemical structural formula of 2-azido-2,5,6-trifluoro-2,3-dihydro-1H-inden-1-one is shown as follows:

[0143]

[0144] 1 H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 8.0, 5.0 Hz, 1H), 7.04 (ddt, J = 7.9, 4.9, 1.0 Hz, 1H), 4.41 - 2.58 (m, 2H).

[0145] 13 C NMR (101 MHz, CDCl3) δ 197.86 (dd, J = 32.0, 3.1 Hz), 152.85 (dd, J = 252.1, 20.0 Hz), 150.10 (dd, J = 252.0, 19.9 Hz), 145.93 (ddd, J = 8.1, 6.1, 3.1 Hz), 132.21 (ddd, J = 7.9, 4.1, 3.0 Hz), 115.44 (ddd, J = 19.8, 7.9, 1.9 Hz), 113.65 (ddd, J = 20.0, 8.0, 2.0 Hz), 110.78 (d, J = 268.1 Hz), 42.16 (dd, J = 27.1, 3.9 Hz).

[0146] 19 F NMR (376 MHz, CDCl3) δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F), -131.16, -138.76.

[0148] HRMS (ESI) m / z calcd [M+Na] + = for C9H4F3N3O: 250.0199, found: 250.0196.

[0149] Example 11

[0150] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 5 - (trifluoromethyl) - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 5 - trifluoromethyl - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol), the others are the same as in Example 1.

[0151] In this example, 0.2410 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 5 - (trifluoromethyl) - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 93%;

[0152] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 5 - trifluoromethyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0153]

[0154] The chemical structural formula of 2 - azido - 2 - fluoro - 5 - (trifluoromethyl) - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0155]

[0156] 1 H NMR(400MHz,CDCl3): δ7.85(d,J = 11.0Hz,1H),7.73(dd,J = 10.9,2.3Hz,1H),7.46(dt,J = 2.2,1.1Hz,1H),3.88 - 2.71(m,2H).

[0157] 13 C NMR(125MHz,CDCl3): δ198.47(d,J = 32.0Hz),146.78(dt,J = 6.0,2.0Hz),135.13(d,J = 3.8Hz),133.04(q,J = 32.1Hz),125.47(p,J = 2.2Hz),124.70(q,J = 4.1Hz),124.21(q,J = 267.5Hz),123.79(qd,J = 4.1,2.0Hz),110.45(d,J = 268.1Hz),42.61(d,J = 27.2Hz).

[0158] 19 F NMR(376MHz,CDCl3): δ - 65.56,δ - 127.64(dd,J = 19.3,10.5Hz,1F).

[0159] HRMS(ESI) m / z calcd [M+Na] + = for C 10 H5F4N3O: 282.0261, found: 282.0269.

[0160] Example 12

[0161] This example provides a preparation method of a monofluoroazidoketone compound - 6 - azido - 6 - fluoro - 6,7 - dihydro - 5H - indeno[5,6 - d][1,3]dioxol - 5 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - indene - 1 - one (1 mmol) is replaced by 6 - fluoro - 6 - iodo - 6,7 - dihydro - 5H - indeno[5,6 - d][1,3]dioxol - 5 - one (1 mmol), the others are the same as in Example 1.

[0162] In this example, 0.2187 g of a pale yellow oily liquid (6 - azido - 6 - fluoro - 6,7 - dihydro - 5H - indeno[5,6 - d][1,3]dioxol - 5 - one) was isolated, and the yield was 93%;

[0163] Among them, the chemical structural formula of 6 - fluoro - 6 - iodo - 6,7 - dihydro - 5H - indeno[5,6 - d][1,3]dioxol - 5 - one is shown as follows:

[0164]

[0165] The chemical structural formula of 6 - azido - 6 - fluoro - 6,7 - dihydro - 5H - indeno[5,6 - d][1,3]dioxol - 5 - one is shown as follows:

[0166]

[0167] 1 H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H), 6.68 (t, J = 1.1 Hz, 1H), 5.94 (d, J = 2.6 Hz, 3H), 3.61 - 2.83 (m, 2H).

[0168] 13 C NMR (125 MHz, CDCl3) δ 197.82 (d, J = 32.0 Hz), 150.11, 147.47, 144.16 (d, J = 6.0 Hz), 129.62 (d, J = 4.1 Hz), 110.78 (d, J = 268.1 Hz), 104.39 (d, J = 2.2 Hz), 104.08 (d, J = 1.9 Hz), 101.19, 42.55 (d, J = 26.9 Hz).

[0169] 19 19F NMR (376 MHz, CDCl3) δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F).

[0170] HRMS (ESI) m / z calcd [M+Na] + = for C 10 H6FN3O3: 258.0285, found: 258.0288.

[0171] Example 13

[0172] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 3,4 - dihydronaphthalen - 1(2H) - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - indene - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 3,4 - dihydronaphthalen - 1(2H) - one (1 mmol), the others are the same as in Example 1.

[0173] In this example, 0.1765 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 3,4 - dihydronaphthalen - 1(2H) - one) was isolated, with a yield of 86%;

[0174] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 3,4 - dihydronaphthalen - 1(2H) - one is shown as follows:

[0175] [[ID=2%]]

[0176] The chemical structural formula of 2 - azido - 2 - fluoro - 3,4 - dihydronaphthalen - 1(2H) - one is shown as follows:

[0177]

[0178] 1 1H NMR (500 MHz, CDCl3): δ 8.15 (dd, J = 7.0, 1.8 Hz, 1H), 7.75 - 6.95 (m, 3H), 3.84 - 1.48 (m, 4H).

[0179] 13 13C NMR (125 MHz, CDCl3): δ 195.70 (d, J = 32.0 Hz), 144.08 (d, J = 16.0 Hz), 134.21 (d, J = 4.1 Hz), 133.46, 129.19, 128.55 (d, J = 2.1 Hz), 127.00, 102.46 (d, J = 268.1 Hz), 30.46 (d, J = 26.9 Hz), 25.40 (d, J = 10.0 Hz).

[0180] 19 19F NMR (376 MHz, CDCl3): δ -138.79 (s, 1F).

[0181] HRMS (ESI) m / z calcd [M+Na] + = for C 10 H8FN3O: 228.0544, found: 228.0549.

[0182] Example 14

[0183] This example provides a preparation method of a monofluoroazidoketone compound - 6 - azido - 6 - fluoro - 6,7,8,9 - tetrahydro - 5H - benzo[7]cyclohepten - 5 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - indene - 1 - one (1 mmol) is replaced by 6 - fluoro - 6 - iodo - 6,7,8,9 - tetrahydro - 5H - benzo[7]cyclohepten - 5 - one (1 mmol), the others are the same as in Example 1.

[0184] In this example, 0.1732 g of a pale yellow oily liquid (6 - azido - 6 - fluoro - 6,7,8,9 - tetrahydro - 5H - benzo[7]cyclohepten - 5 - one) was isolated, and the yield was 79%;

[0185] Among them, the chemical structural formula of 6 - fluoro - 6 - iodo - 6,7,8,9 - tetrahydro - 5H - benzo[7]cyclohepten - 5 - one is shown as follows:

[0186]

[0187] The chemical structural formula of 6 - azido - 6 - fluoro - 6,7,8,9 - tetrahydro - 5H - benzo[7]cyclohepten - 5 - one is shown as follows:

[0188]

[0189] 1 1H NMR (500 MHz, CDCl3): δ 7.63 (dd, J = 7.0, 1.8 Hz, 1H), 7.57 - 7.29 (m, 2H), 7.23 (ddt, J = 6.4, 2.2, 1.0 Hz, 1H), 3.79 - 2.45 (m, 4H), 2.37 - 1.39 (m, 2H).

[0190] 1313C NMR (125 MHz, CDCl3): δ 198.99 (d, J = 32.0 Hz), 143.05 (d, J = 2.2 Hz), 135.32 (d, J = 4.1 Hz), 132.67, 129.76, 128.96 (d, J = 1.9 Hz), 127.08, 104.37 (d, J = 268.1 Hz), 34.23 (d, J = 26.9 Hz), 33.90 (d, J = 1.9 Hz), 22.03 (d, J = 10.0 Hz).

[0191] 19 19F NMR (376 MHz, CDCl3): δ -91.04 (s, 1F).

[0192] HRMS (ESI) m / z calcd [M+Na] + = for C 11 H 10 FN3O: 242.0700, found: 242.0709.

[0193] Example 15

[0194] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 6 - methyl - 2,3 - dihydro - 1H - inden - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - cyclopenta[b]naphthalen - 1 - one (1 mmol), the others are the same as in Example 1.

[0195] In this example, 0.1930 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 6 - methyl - 2,3 - dihydro - 1H - inden - 1 - one) was isolated, with a yield of 80%;

[0196] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - cyclopenta[b]naphthalen - 1 - one is shown as follows:

[0197]

[0198] The chemical structural formula of 2 - azido - 2 - fluoro - 6 - methyl - 2,3 - dihydro - 1H - inden - 1 - one is shown as follows:

[0199]

[0200] 11H NMR (500 MHz, CDCl3): δ 8.35 (d, J = 1.8 Hz, 1H), 8.09 - 7.84 (m, 2H), 7.78 (dt, J = 8.1, 1.6 Hz, 1H), 7.54 (ddd, J = 8.1, 6.8, 1.3 Hz, 1H), 7.43 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 3.46 - 2.89 (m, 2H).

[0201] 13 13C NMR (125 MHz, CDCl3): δ 199.09 (d, J = 32.0 Hz), 143.97 (d, J = 6.0 Hz), 135.50, 133.28, 130.84 (d, J = 4.1 Hz), 128.39, 127.54, 126.18, 125.96, 123.41 (d, J = 1.9 Hz), 122.83 (d, J = 2.1 Hz), 110.29 (d, J = 268.1 Hz), 42.11 (d, J = 26.9 Hz).

[0202] 19 19F NMR (376 MHz, CDCl3): δ -127.64 (dd, J = 19.3, 10.5 Hz, 1F)

[0203] HRMS (ESI) m / z calcd [M+Na] + = for C 13 H8FN3O: 264.0544, found: 264.0548.

[0204] Example 16

[0205] This example provides a preparation method of a monofluoroazidoketone compound - 2 - azido - 2 - fluoro - 4 - methyl - 3,4 - dihydronaphthalen - 1 - one. Except that 2 - fluoro - 2 - iodo - 2,3 - dihydro - 1H - inden - 1 - one (1 mmol) is replaced by 2 - fluoro - 2 - iodo - 4 - methyl - 3,4 - dihydronaphthalen - 1 - one (1 mmol), the others are the same as in Example 1.

[0206] In this example, 0.2720 g of a pale yellow oily liquid (2 - azido - 2 - fluoro - 4 - methyl - 3,4 - dihydronaphthalen - 1 - one) was isolated, with a yield of 80%;

[0207] Among them, the chemical structural formula of 2 - fluoro - 2 - iodo - 4 - methyl - 3,4 - dihydronaphthalen - 1 - one is shown as follows:[[]]

[0208]

[0209] The chemical structural formula of 2-azido-2-fluoro-4-methyl-3,4-dihydronaphthalenone is shown as follows:

[0210]

[0211] 1 H NMR(500MHz,CDCl3)δ7.79(d,J=2.3Hz,2H),7.76(t,J=1.5Hz,3H),7.49-7.46(m,4H),7.45(t,J=4.2Hz,6H),7.36-7.23(m,5H),2.84(tq,J=16.2,12.8Hz,5H),2.41(ddd,J=50.3,24.8,16.3Hz,5H),1.94-1.70(m,5H),1.17(s,7H),1.15(s,7H).

[0212] 13 C NMR(125MHz,CDCl3)δ189.78(d,J=31.5Hz),150.27(d,J=15.3Hz),135.00(s),132.14(d,J=3.7Hz),130.68(d,J=1.4Hz),128.93(s),128.04(s),41.13(s),40.91(s),32.55(d,J=9.5Hz),22.24(s).

[0213] 19 F NMR(472MHz,CDCl3)δ-144.80(s),-144.80(s).

[0214] HRMS(ESI)m / z calcd[M+Na] + =for C 11 H 10 FN3O:242.0813,found:242.0821.

[0215] Example 17

[0216] This example provides a preparation method of a monofluoroazidoketone compound - 2-azido-2-fluoro-4-methyl-6-(trifluoromethyl)-3,4-dihydronaphthalenone. Except that 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) is replaced by 2-fluoro-2-iodo-4-methyl-6-(trifluoromethyl)-3,4-dihydronaphthalenone (1 mmol), the others are the same as in Example 1.

[0217] In this example, 0.3330 g of a pale yellow oily liquid (2-azido-2-fluoro-4-methyl-6-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one) was obtained by separation, with a yield of 75%;

[0218] Among them, the chemical structural formula of 2-fluoro-2-iodo-4-methyl-6-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one is shown as follows:

[0219]

[0220] The chemical structural formula of 2-azido-2-fluoro-4-methyl-6-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one is shown as follows:

[0221]

[0222] 1 H NMR (500 MHz, CDCl3) δ 7.77 (s, 5H), 7.74 (s, 6H), 7.50 (d, J = 2.9 Hz, 6H), 7.47 (d, J = 2.9 Hz, 5H), 7.34 (d, J = 2.9 Hz, 12H), 2.89 - 2.76 (m, 12H), 2.55 (ddd, J = 15.8, 11.3, 5.8 Hz, 12H), 2.42 (ddd, J = 31.9, 15.8, 5.8 Hz, 12H), 1.16 (d, J = 12.7 Hz, 35H).

[0223] 13 C NMR (125 MHz, CDCl3) δ 189.78 (d, J = 31.5 Hz), 145.67 (dd, J = 16.2, 1.5 Hz), 138.77 (q, J = 31.5 Hz), 130.30 (s), 127.76 - 126.36 (m), 124.37 (s), 122.23 (s), 120.08 (s), 117.54 (q, J = 3.7 Hz), 41.02 (d, J = 27.7 Hz), 32.44 (d, J = 9.5 Hz), 22.24 (d, J = 1.4 Hz).

[0224] 19 F NMR (472 MHz, CDCl3) δ -63.60 (s), -144.80 (s).

[0225] HRMS (ESI) m / z calcd [M+Na] + = for C 12 H9F4N3O: 310.0713, found: 310.7221.

[0226] Example 18

[0227] This example provides a preparation method of a monofluoroazidoketone compound, 6-azido-6-fluoro-8-methyl-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one. Except that 2-fluoro-2-iodo-2,3-dihydro-1H-inden-1-one (1 mmol) is replaced by 6-fluoro-6-iodo-8-methyl-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one (1 mmol), the others are the same as in Example 1.

[0228] In this example, 0.3598 g of a pale yellow oily liquid (6-azido-6-fluoro-8-methyl-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one) was isolated, with a yield of 77%;

[0229] Among them, the chemical structural formula of 6-fluoro-6-iodo-8-methyl-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one is shown as follows:

[0230]

[0231] The chemical structural formula of 6-azido-6-fluoro-8-methyl-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one is shown as follows:

[0232]

[0233] 1 H NMR (500 MHz, CDCl3) δ 7.79 (s, 1H), 7.77 (s, 1H), 7.52 (d, J = 1.6 Hz, 1H), 7.50 (d, J = 1.4 Hz, 1H), 7.25 (d, J = 1.4 Hz, 2H), 2.81 (dd, J = 11.9, 5.6 Hz, 2H), 2.67 - 2.51 (m, 5H), 2.30 (dd, J = 12.4, 7.6 Hz, 1H), 2.25 (dd, J = 12.4, 7.7 Hz, 1H), 1.84 (ddd, J = 25.1, 12.4, 7.7 Hz, 2H), 0.95 (d, J = 6.3 Hz, 7H).

[0234] 1313C NMR (125 MHz, CDCl3) δ 190.30 (d, J = 32.4 Hz), 155.80 (s), 140.28 (d, J = 3.7 Hz), 137.08 (q, J = 32.4 Hz), 133.02 (s), 132.44 - 131.48 (m), 126.51 (s), 125.30 (d, J = 3.8 Hz), 124.37 (s), 122.23 (s), 120.08 (s), 44.40 (d, J = 1.4 Hz), 40.58 (d, J = 26.7 Hz), 32.84 (d, J = 9.5 Hz), 20.18 (d, J = 1.4 Hz).

[0235] 19 19F NMR (472 MHz, CDCl3) δ -63.60 (s), -144.80 (s).

[0236] HRMS (ESI) m / z calcd [M+Na] + = for C 13 H 11 F4N3O: 324.0822, found: 324.0832.

[0237] Example 19

[0238] This example provides a preparation method of 2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydro-1H-inden-1-one, which is as follows:

[0239] Azide compounds can be used as multifunctional intermediates for further reactions. For example, these structures can be used to synthesize 1,2,3-triazole compounds through cycloaddition reactions with alkynes. In this Example 1, 2-azido-2-fluoro-2,3-dihydro-1H-inden-1-one prepared in Example 1 was used as the azide reagent, and phenylacetylene was used as the reaction raw material. Under the action of the catalyst CuSO4·5H2O and sodium ascorbate, the click reaction was realized to prepare 2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydro- 1H-inden-1-one.

[0240]

[0241] The specific preparation method is as follows:

[0242] Weigh CuSO4·5H2O (0.3 mmol) and sodium ascorbate (0.3 mmol), add them into a 10 mL standard reaction tube, and evacuate and backfill with nitrogen three times; under nitrogen protection, weigh the 2-azido-2-fluoro-2,3-dihydro-1H-inden-1-one (1 mmol) prepared in Example 1, phenylacetylene (1.2 mmol) and 4.0 mL of solvent in advance, and add them into the above 10 mL standard reaction tube with a pipette. After the feeding is completed, stir at 50 °C for 24 h (monitor the reaction by TLC after the consumption of azide and the appearance of triazole). After the reaction is completed, wash and extract with ethyl acetate (10 mL) (extract 3 times), discard the aqueous phase after separation, then dry with anhydrous Na2SO4 (20 g), remove the solvent under reduced pressure with a rotary evaporator (temperature is 40 °C, time is 0.5 h), purify the crude residue by recrystallization (petroleum ether / ethyl acetate = 60:1 (volume ratio)), and the filter cake obtained by suction filtration is the separated product; obtain a white solid: 2-fluoro-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydro-1H-inden-1-one (0.2842 g, yield 97%), m.p. = 94.0 °C.

[0243] 1 H NMR (500 MHz, CDCl3): δ 8.53 (s, 1H), 7.91 (dd, J = 6.7, 1.9 Hz, 1H), 7.87 - 7.70 (m, 2H), 7.62 - 7.36 (m, 5H), 7.32 - 7.14 (m, 1H), 3.56 (dt, J = 25.1, 1.1 Hz, 2H)..

[0244] 13 C NMR (125 MHz, CDCl3): δ 199.53 (d, J = 32.2 Hz), 148.57 (d, J = 4.1 Hz), 147.42 (d, J = 6.0 Hz), 134.86 (d, J = 4.1 Hz), 132.88, 130.44, 129.28, 129.10, 128.38, 127.49 (d, J = 2.2 Hz), 127.34 (d, J = 1.9 Hz), 125.19, 122.06 (d, J = 7.2 Hz), 109.46 (d, J = 268.1 Hz), 44.17 (d, J = 26.9 Hz).

[0245] 19 F NMR (376 MHz, CDCl3): δ -116.85 (dd, J = 21.4, 12.5 Hz).

[0246] HRMS (ESI) m / z calcd [M+Na] + =for C 17 H12 FN3O: 316.0857, found: 316.0862.

[0247] The above description of the embodiments is to enable those of ordinary skill in the art to understand and use the invention. It is obvious that those who are familiar with the technology in this field can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative efforts. Therefore, the present invention is not limited to the above embodiments, and the improvements and modifications made by those skilled in the art without departing from the scope of the present invention according to the interpretation of the present invention should be within the protection scope of the present invention.

Claims

1. A monofluoroazidoketone compound, characterized in that, It has a structural formula shown in formula (1): Wherein, R1 and R2 are each independently selected from any one of alkyl, phenyl, substituted phenyl, fused-ring aryl or heterocyclic substituent; m is an integer from 0 to 3; Ar is selected from one of aryl or heteroaryl.

2. The monofluoroazidoketone compound according to claim 1, characterized in that, When R1 or R2 is a substituted phenyl, the substituent in the substituted phenyl is selected from any one or more of phenyl, hydrogen, fluorine, bromine, chlorine, C1-C4 alkyl, p-methoxy, trifluoromethyl, p-1,3-benzodioxole, p-halogen-substituted benzene or benzyl.

3. A method for preparing a monofluoroazidoketone compound as described in any one of claims 1 to 2, characterized in that, It includes the following steps: Dissolve the first compound and the azide source and then react, and perform post-treatment to obtain monofluoroazidoketone compounds; Wherein, the chemical structural formula of the first compound is shown in formula (2): Wherein, Y is Cl, Br or I, R1 and R2 are each independently selected from any one of alkyl, phenyl, substituted phenyl, fused-ring aryl or heterocyclic substituent; m is an integer from 0 to 3; Ar is selected from one of aryl or heteroaryl.

4. The preparation method of a monofluoroazidoketone compound according to claim 3, characterized in that, When R1 or R2 is a substituted phenyl, the substituent in the substituted phenyl is selected from any one or more of phenyl, hydrogen, fluorine, bromine, chlorine, C1-C4 alkyl, p-methoxy, trifluoromethyl, p-1,3-benzodioxole, p-halogen-substituted benzene or benzyl.

5. The preparation method of a monofluoroazidoketone compound according to claim 3, characterized in that, The azide source is selected from one or several of NaN3, TMSN3, TsN3, TBSnA, TMGA or AAE.

6. The preparation method of a monofluoroazidoketone compound according to claim 3, characterized in that, The molar ratio of the first compound to the azide source is 0.15-0.25:

1.

7. The preparation method of a monofluoroazidoketone compound according to claim 3, characterized in that, The reaction is carried out under a nitrogen atmosphere, the temperature is 0-50 °C, and the time is 0.25-2 h.

8. The preparation method of a monofluoroazidoketone compound according to claim 3, characterized in that, The post-treatment is that after the reaction is completed, the reaction product is separated by column chromatography; A mixture of n-hexane and ethyl acetate is used in the process of column chromatography separation.

9. The preparation method of a monofluoroazidoketone compound according to claim 8, characterized in that, The volume ratio of n-hexane to ethyl acetate is 60-500:

1.

10. Use of a monofluoroazidoketone compound as described in any one of claims 1-2 in the field of framework editing.

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