A 2-bromotetrafluoroethyl-substituted benzimidazoloisoquinolinone compound and a preparation method thereof

Abstract

The application discloses a 2-bromotetrafluoroethyl-substituted benzimidazoisoquinolinone compound and a preparation method thereof, and belongs to the technical field of organic synthesis. The application first uses BrCF2CF2Br in an intramolecular free radical cascade reaction of N-(2-methyl) acryloyl-2-aryl benzimidazole compounds, and synthesizes the 2-bromotetrafluoroethyl-substituted benzimidazoisoquinolinone compound. The method constructs the benzimidazoisoquinolinone while directly introducing the 2-bromotetrafluoroethyl group into the benzimidazoisoquinolinone compound, and provides a new method for synthesizing the 2-bromotetrafluoroethyl-substituted benzimidazoisoquinolinone compound.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a 2-bromotetrafluoroethyl substituted benzimidazoloisoquinolinone compound and a preparation method thereof. Background Art

[0002] Benzimidazoloisoquinolinones are an important class of nitrogen-containing heterocyclic compounds, whose structural units are widely found in drugs, bioactive molecules, and advanced materials. Due to their excellent biological activity, potential therapeutic potential, and broad application prospects, they have attracted the attention of numerous organic chemists and biologists in recent years. For example, compounds with the following A-H chemical structures:

[0003]

[0004] Studies have shown that compounds A and B, as a class of polysubstituted benzimidazole isoquinolinone compounds, have strong anti-cancer effects (PloS, Pathog. 2020, 16, e1008716.); compound C is mainly used to regulate potassium ion flux (WO2005002503 A22005); compound D is often used as a peripheral benzodiazepine (TSPO) receptor ligand in medicine (US4413126A, 1983); compound E is an antidiabetic drug used to treat diabetes (Aust. J. Chem. 2001, 54, 529.), compounds F and G are anti-inflammatory drugs and candidate drugs for the treatment of hemoglobinopathies (J. Med. Chem., 2021.21.439.); compound H, as a good conductive material, is widely used in the preparation of organic electronics, organic solar cells and organic transistor materials (J Photoch. Photobio. A Chem. 2017, 332, 515.). Therefore, in order to further study the potential application value of benzimidazoloisoquinolinone compounds, it is very necessary to explore various new methods to efficiently synthesize benzimidazoloisoquinolinone derivatives.

[0005] Currently, the synthesis of benzimidazoloisoquinolinone derivatives is mainly achieved through the condensation reaction of o-phenylenediamine and 2-(cyanomethyl)benzoic acid, the [4+2] cyclization reaction of 2-arylbenzimidazole and α-diazoketoester, and the free radical tandem cyclization reaction involving N-(2-methyl)acryloyl-2-arylbenzimidazole. The specific method is as follows:

[0006] (1) Synthesis of benzimidazolidinone by condensation reaction of o-phenylenediamine and 2-(cyanomethyl)benzoic acid

[0007] In 1969, Schefczik's group first proposed the use of o-phenylenediamine and 2-(cyanomethyl)benzoic acid at >200°C to produce the corresponding benzimidazoloisoquinolinone derivatives in good yields through an addition / condensation reaction (Liebigs Ann. Chem. 1969, 729, 83). Unfortunately, the group reported only a few successful examples, and the high temperature reaction conditions further limited its wider synthetic application. The reaction formula is:

[0008]

[0009] (2) Synthesis of benzimidazole-isoquinolinones via the [4+2] cyclization reaction of 2-arylbenzimidazoles and α-diazoketoesters

[0010] In 2018, Song Qiuling's research group proposed a transition metal-catalyzed [4+2] cyclization reaction of 2-arylbenzimidazoles with α-diazoketoesters using (Cp*RhCl2)2 (dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer) as a catalyst, resulting in a 98% yield of benzimidazole-isoquinolinone compounds (Chem. Commun. 2018, 54, 10240). In this reaction, not only a precious metal catalyst (rhodium) was used, but also a diazo compound with potential safety risks. The reaction formula is:

[0011]

[0012] (3) Synthesis of Benzimidazoloisoquinolinones by Free Radical Tandem Cyclization of N-(2-Methyl)acryloyl-2-arylbenzimidazole

[0013] Free radical tandem cyclization reaction is an effective method for constructing complex molecular ring systems and has been successfully used in the synthesis of various complex molecules. N-(2-methyl)acryloyl-2-arylbenzimidazole, as a good free radical acceptor, is also widely used by chemists to synthesize complex molecular ring systems, especially for the synthesis of benzimidazole and isoquinolinone compounds. In 2021, Wei Wenting's research group summarized and summarized the free radical tandem cyclization reaction involving N-(2-methyl)acryloyl-2-arylbenzimidazole for the synthesis of benzimidazole and isoquinolinone (Org. Biomol. Chem., 2021, 19, 8874). This summary further proves that N-(2-methyl)acryloyl-2-arylbenzimidazole can be used as a good free radical acceptor for the synthesis of benzimidazole and isoquinolinone compounds. In this method, the fluoroalkyl radicals used include trifluoromethyl radical, perfluorobutyl radical, perfluoropentyl radical and perfluorodecyl radical, but tetrafluoroethyl radical has not yet been found. The reaction formula is:

[0014]

[0015] In summary, benzimidazoloquinolinones were successfully synthesized via the condensation reaction of o-phenylenediamine and 2-(cyanomethyl)benzoic acid, the [4+2] cyclization reaction of 2-arylbenzimidazole and α-diazoketoester, and the free radical tandem cyclization reaction involving N-(2-methyl)acryloyl-2-arylbenzimidazole. Literature review revealed that no synthetic methods for directly introducing tetrafluoroethyl groups into benzimidazoloquinolinones have been reported. Therefore, considering the important medicinal value of benzimidazoloquinolinones and the potential biological activity of introducing tetrafluoroethyl groups into heterocyclic compounds, it is highly desirable to explore a novel, efficient, and facile synthetic method for preparing 2-bromotetrafluoroethyl-substituted benzimidazoloisoquinolinones. Summary of the Invention

[0016] The present invention aims to provide a 2-bromotetrafluoroethyl-substituted benzimidazoloisoquinolinone compound and a preparation method thereof. Using N-(2-methyl)acryloyl-2-arylbenzimidazole compounds as raw materials and the inexpensive and readily available BrCF2CF2Br as a 2-bromotetrafluoroethyl source, a tetrafluoroethyl-containing benzimidazoloisoquinolinone compound is prepared in one step through an intramolecular free radical tandem cyclization reaction of an olefin under visible light induction, the action of a photocatalyst, and a base. This method introduces a 2-bromotetrafluoroethyl group into the benzimidazoloisoquinolinone molecule for the first time. This method is green and safe, with inexpensive and readily available raw materials, high atom economy, good regioselectivity, mild reaction conditions, high yield, and easily purified products, thus representing a green synthesis.

[0017] To achieve the above object, the present invention provides the following technical solutions:

[0018] One of the technical solutions of the present invention is to provide a 2-bromotetrafluoroethyl substituted benzimidazolidinone compound, the general structural formula of which is shown below:

[0019]

[0020] In the above formula, R 1 is -Br or -H, R 2 is -H, -Me or -OMe.

[0021] The second technical solution of the present invention is to provide a method for preparing the above-mentioned 2-bromotetrafluoroethyl substituted benzimidazolidinone compound, comprising the following steps:

[0022] A 2-bromotetrafluoroethyl-substituted benzimidazoisoquinolinone compound is prepared by reacting BrCF2CF2Br and N-(2-methyl)acryloyl-2-arylbenzimidazole compound as reactants, dissolving in a solvent, adding a base and a photocatalyst, and performing the reaction under visible light induction.

[0023] The N-(2-methyl)acryloyl-2-arylbenzimidazole compound has the following structural formula:

[0024]

[0025] In the above formula, R 1 is -Br or -H, and R 2 is -H, -Me or -OMe.

[0026] Preferably, the base is NaHCO3 or Na2CO3, and more preferably, Na2CO3.

[0027] More preferably, the molar ratio of BrCF2CF2Br, N-(2-methyl)acryloyl-2-arylbenzimidazole compound and base is (1.0-2.0):(1.0-2.0):(1.0-3.0), and the most preferred molar ratio is 1.0:1.5:2.0.

[0028] Preferably, the solvent includes acetonitrile (CH3CN), N,N-dimethylformamide (DMF) or acetone, and more preferably, acetonitrile.

[0029] Preferably, the photocatalyst is a noble metal catalyst or an organic dye catalyst, and the amount of photocatalyst added is 1-3% of the molar amount of BrCF2CF2Br.

[0030] More preferably, the noble metal catalyst is tris(2-phenylpyridine)iridium (fac-Ir III (ppy)3), and the organic dye catalyst is 2,4,5,6-tetra(9-carbazolyl)-1,3-dicyanobenzene (4CzIPN). The most preferred is 4CzIPN.

[0031] Preferably, the wavelength of the visible light is 390-460 nm (blue light), and the power is 5-10 W, and more preferably, the power is 10 W.

[0032] Preferably, the reaction time is 12-36 h, and more preferably, the reaction time is 24 h.

[0033] The beneficial technical effects of the present application are as follows:

[0034] (1) This invention first uses BrCF2CF2Br in an intramolecular free radical tandem cyclization reaction involving N-(2-methyl)acryloyl-2-arylbenzimidazole compounds to synthesize 2-bromotetrafluoroethyl-substituted benzimidazolidinone compounds. This method directly introduces a 2-bromotetrafluoroethyl group into the benzimidazolidinone compound while constructing the benzimidazolidinone compound, providing a new method for the synthesis of 2-bromotetrafluoroethyl-substituted benzimidazolidinone compounds.

[0035] (2) The BrCF2CF2Br used in the present invention is a non-toxic, odorless, cheap and readily available industrial raw material. Compared with other fluorination reagents, its greatest advantages are low price, easy availability and high atom economy.

[0036] (3) The synthesis method provided by the present invention has a high regioselectivity. 1 H NMR, 13 C NMR, 19 F NMR and high-resolution mass spectrometry revealed that the resulting compounds were all 2-bromotetrafluoroethyl-substituted benzimidazoloisoquinolinones with high purity. This synthetic method also offers advantages such as short reaction steps, high atom utilization, simple operation, mild reaction conditions, and high yield. Furthermore, the use of visible light irradiation to generate free radicals enables green synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a) synthesized in Example 1 1 H NMR spectrum;

[0038] Figure 2 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a) synthesized in Example 1 13 C NMR spectrum;

[0039] Figure 3 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a) synthesized in Example 1 19 F NMR spectrum;

[0040] Figure 4This is a high-resolution mass spectrometry monitoring diagram of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a) synthesized in Example 1;

[0041] Figure 5 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b) synthesized in Example 2 1 H NMR spectrum;

[0042] Figure 6 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b) synthesized in Example 2 13 C NMR spectrum;

[0043] Figure 7 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b) synthesized in Example 2 19 F NMR spectrum;

[0044] Figure 8 This is a high-resolution mass spectrometry monitoring diagram of 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b) synthesized in Example 2;

[0045] Figure 9 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3c) synthesized in Example 3 1 HNMR spectrum;

[0046] Figure 10 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3c) synthesized in Example 3 13 C NMR spectrum;

[0047] Figure 11 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3c) synthesized in Example 3 19 F NMR spectrum;

[0048] Figure 12This is a high-resolution mass spectrometry monitoring diagram of 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3c) synthesized in Example 3;

[0049] Figure 13 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d) synthesized in Example 4 1 HNMR spectrum;

[0050] Figure 14 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d) synthesized in Example 4 13 C NMR spectrum;

[0051] Figure 15 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d) synthesized in Example 4 19 F NMR spectrum;

[0052] Figure 16 This is a high-resolution mass spectrometry monitoring chart of 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d) synthesized in Example 4. DETAILED DESCRIPTION

[0053] Various exemplary embodiments of the present invention are now described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention.

[0054] In addition, for numerical ranges in the present invention, it is understood that each intervening value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any stated value or stated range, and any other stated value or intervening value in the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.

[0055] Unless otherwise indicated, all technical and scientific terms have the same meaning as those one of ordinary skill in the art of the invention would understand. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.

[0056] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” and the like are open-ended terms that are intended to permit but not limit the amount or number of steps, components, members, etc. to follow, and are not intended to exclude other additives, components, steps, or the like.

[0057] Example 1

[0058] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a):

[0059] The synthesis route is as follows:

[0060]

[0061] N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), 2 mL CH3CN were added into a 50 mL Schlenk flask. The Schlenk flask was evacuated and refilled with argon, repeated three times. The reaction mixture was placed on a 10 W blue light and stirred at room temperature for 24 h. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography with petroleum ether and ethyl acetate as eluent (PE:EA = 5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a): white solid, 36.7 mg, yield 78%.

[0062] The above-synthesized 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a) was subjected to 1 H NMR, 13 C NMR, 19 F NMR high resolution mass spectrometry (as shown in Figure 5-8 ), the results showed that the product was pure target compound. The characterization data of the corresponding product are as follows:

[0063] 1 H NMR (400MHz, CDCl3) δ = 8.48 (d, J = 8.8Hz, 1H), 8.33 (d, J = 8.8Hz, 2H), 7.80 (d, J = 8.0Hz, 1H), 7.46-7.39 (m, 2H ),7.08(dd,J=8.8,2.4Hz,1H),6.96(s,1H),3.93(s,3H),3.58-3.46(m,1H),2.94-2.81(m,1H),1.78(s,3H);

[0064] 13 C{ 1 H}NMR(150MHz, CDCl3)δ=171.0,162.4,149.4,140.9,131.3,128.3,126.0,125.3, 119.4,115.6,115.0,113.9,112.6,112.5,55.6,45.3,40.1(t,J=21.0Hz),31.7.;

[0065] 19 F NMR (376MHz, CDCl3)-66.26--67.44(m,2F),-104.44--105.25(m,1F),-109.30--110.08(m,1F);

[0066] HRMS(ESI):m / z[M+H] + calcd for C 20 H 16 O2N2BrF4:471.03259; found 471.03284.

[0067] Example 2

[0068] Synthesis of 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b):

[0069] The synthetic route is as follows:

[0070]

[0071] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-tolyl)benzimidazole 1b (41.4 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 24 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b): a colorless liquid, 35.0 mg, and a yield of 77%.

[0072] The above-synthesized 3,5-dimethyl-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3b) was 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry (such as Figure 5-8 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0073] 1 H NMR (400MHz, CDCl3) δ = 8.40 (d, J = 8.0Hz, 1H), 8.36-8.34 (m, 1H), 7.83-7.80 (m, 1H), 7.47-7.40 (m, 2H), 7 .35(dd,J=8.0,2.4Hz,1H),7.28(s,1H),3.58-3.46(m,1H),2.97-2.84(m,1H),2.48(s,3H),1.77(s,3H);

[0074] 13 C{ 1 H}NMR(150MHz, CDCl3)δ=171.2,149.5,144.0,142.1,138.8,131.3,129.4,126.9,1 26.2,126.0,125.5,119.7,119.6,115.6,45.1,40.0(t,J=19.5Hz,1H),31.5,21.9;

[0075] 19 F NMR (376 MHz, CDC13) δ = -66.18 - -67.42 (m, 2F), -104.45 - -105.26 (m, IF), -109.32 - -110.10 (m, IF);

[0076] HRMS (ESI): m / z [M+H]+calcd for C 20 H 16 BrF4N2O: 455.0377; found 455.0369.

[0077] Example 3

[0078] Synthesis of 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3c):

[0079] The synthesis route is as follows:

[0080]

[0081] N-(2-methyl)acryloyl-2-phenylbenzimidazole 1c (39.3 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), 2 mL CH3CN were added into a 50 mL Schlenk flask. The Schlenk flask was evacuated and refilled with argon, which was repeated three times. The reaction mixture was placed on a 10 W blue light and stirred at room temperature for 36 h. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography with petroleum ether and ethyl acetate as eluent (PE:EA = 5:1, volume ratio) to obtain 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3c): colorless liquid, 35.2 mg, yield 80%.

[0082] The above-synthesized 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3c), was subjected to 1 H NMR, 13 C NMR, 19 F NMR high resolution mass spectrometry detection (as shown in Figure 5-8 , the results showed that the product was pure target compound. The corresponding product characterization data are:

[0083] 1 H NMR (400 MHz, CDC13) δ = 8.53 (dd, J = 8.0, 1.6 Hz, 1H), 8.38-8.35 (m, 1H), 7.85-7.83 (m, 1H), 7.60 (td, J = 7.2, 1.2 Hz, 1H), 7.55-7.49 (m, 2H), 7.47-7.42 (m, 2H), 3.59-3.47 (m, 1H), 2.98-2.86 (m, 1H), 1.78 (s, 3H).

[0084] 13 C{ 1 H} NMR (150 MHz, CDC13) δ = 171.0, 149.3, 144.0, 138.8, 131.5, 131.4, 128.3, 126.6, 126.3, 126.1, 125.7, 122.3, 119.9, 115.7, 45.2, 40.0 (t, J = 19.5 Hz), 31.5;

[0085] 19 F NMR (376 MHz, CDC13) δ = -66.29 - -67.47 (m, 2F), -104.55 - -105.36 (m, 1F), -109.43 - -110.20 (m, 1F);

[0086] HRMS (ESI): m / z [M + Na] calcd for C + calcd for C 19 H 13 BrF4N2ONa: 463.0040; found 463.0021.

[0087] Example 4

[0088] Synthesis of 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromo- benzo[4,5]imidazo[2,l-a]isoquinolin-6(5H)-one (3d):

[0089] The synthesis route is as follows:

[0090]

[0091] N-(2-Methyl)acryloyl-2-phenyl-5,6-dibromobenzimidazole 1d (62.7 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d): a colorless liquid, 38.7 mg, and a yield of 65%.

[0092] The above-synthesized 5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methyl-9,10-dibromobenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3d) was 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry (such as Figure 5-8 The results show that the product is a pure target compound. The characterization data of the corresponding product are:

[0093] 1 H NMR(400MHz, CDCl3)8.67(s,1H),8.48(dd,J=7.2,1.2Hz,1H).8.10(s,1H),7.64(td,J=7.6,1.2Hz,1H),7.55 (td,J=7.6,1.2Hz,1H),7.51(d,J=8.4Hz,1H),3.50(dd,J=31.6,15.2Hz,1H),2.99-2.86(m,1H),1.79(s,3H);

[0094] 13 C{ 1 H}NMR(150MHz, CDCl3)δ=170.9,150.8,143.4,138.9,132.1,130.3,130.2,129 .6,128.5,126.7,126.5,121.7,121.1,117.1,45.2,40.2(t,J=19.5Hz),31.4;

[0095] 19 F NMR (376MHz, CDCl3) δ=-66.38--67.59(m,2F),-104.60--105.41(m,1F),-109.31--110.09(m,1F);

[0096] HRMS(ESI):m / z[M+H] + calcd for C 19 H 12 Br3F4N2O:596.8430; found 596.8438.

[0097] Example 5

[0098] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0099] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (29.2 mg, 0.1 mmol, 1.0 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 24.9 mg, and a yield of 53%.

[0100] Example 6

[0101] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0102] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (58.4 mg, 0.2 mmol, 2.0 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 30.1 mg, and a yield of 64%.

[0103] Example 7

[0104] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0105] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (3.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (39.0 mg, 0.15 mmol, 1.5 equiv), 4CzIPN (3.56 mg, 0.0045 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 21.6 mg, and a yield of 31%.

[0106] Example 8

[0107] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0108] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (3.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (52.0 mg, 0.2 mmol, 2.0 equiv), 4CzIPN (4.74 mg, 0.006 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 23.0 mg, and a yield of 33%.

[0109] Example 9

[0110] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0111] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (3.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (52.0 mg, 0.2 mmol, 2.0 equiv), 4CzIPN (4.74 mg, 0.006 mmol), Na2CO3 (10.6 mg, 0.1 mmol, 1.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 19.3 mg, and a yield of 27%.

[0112] Example 10

[0113] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0114] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (3.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (52.0 mg, 0.2 mmol, 2.0 equiv), 4CzIPN (4.74 mg, 0.006 mmol), Na2CO3 (31.8 mg, 0.3 mmol, 3.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 18.3 mg, and a yield of 26%.

[0115] Example 11

[0116] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0117] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), NaHCO3 (16.8 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 28.7 mg, and a yield of 61%.

[0118] Example 12

[0119] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0120] N-(2-Methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of DMF were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 33.4 mg, and a yield of 71%.

[0121] Example 13

[0122] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0123] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of acetone. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 28.2 mg, and a yield of 60%.

[0124] Example 14

[0125] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a):

[0126] N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (0.79 mg, 0.001 mmol), Na2CO3(21.2 mg, 0.2 mmol, 2.0 equiv), 2 mL CH3CN were added into a 50 mL Schlenk flask. The Schlenk flask was evacuated and backfilled with argon for three times. The reaction mixture was placed on 10 W blue light and stirred at room temperature for 36 h. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography with petroleum ether and ethyl acetate as eluent (PE:EA = 5:1, volume ratio) to give 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a): white solid, 15.5 mg, yield 33%.

[0127] Example 15

[0128] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1- a]isoquinolin-6(5H)-one (3a):

[0129] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (1.58 mg, 0.002 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 24 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 28.7 mg, and a yield of 61%.

[0130] Example 16

[0131] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0132] N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), fac-Ir III (ppy)3 (1.97 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 24 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA = 5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 11.3 mg, in a 24% yield.

[0133] Example 17

[0134] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0135] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 5 W blue light and stirred at room temperature for 24 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 25.9 mg, and a yield of 55%.

[0136] Example 18

[0137] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0138] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 12 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 16.5 mg, and a yield of 35%.

[0139] Example 19

[0140] Synthesis of 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a):

[0141] A 50 mL Schlenk flask was charged with N-(2-methyl)acryloyl-2-(p-methoxy)phenylbenzimidazole 1a (43.8 mg, 0.15 mmol, 1.5 equiv), BrCF2CF2Br (26.0 mg, 0.1 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 0.003 mmol), Na2CO3 (21.2 mg, 0.2 mmol, 2.0 equiv), and 2 mL of CH3CN. The Schlenk flask was evacuated and then filled with argon three times. The reaction mixture was placed under 10 W blue light and stirred at room temperature for 36 h. After the reaction, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE:EA=5:1, volume ratio) to obtain 3-methoxy-5-(3-bromo-2,2,3,3-tetrafluoropropyl)-5-methylbenzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3a): a white solid, 33.8 mg, and a yield of 72%.

[0142] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A method for preparing a 2-bromotetrafluoroethyl substituted benzimidazolidinone compound, characterized in that: The following steps are involved: BrCF2CF2Br and N-(2-methyl)acryloyl-2-arylbenzimidazole compounds are used as reactants, dissolved in a solvent, and a base and a photocatalyst are added. The reaction is induced by visible light to prepare 2-bromotetrafluoroethyl-substituted benzimidazole-isoquinolinone compounds. Wherein, the structural formula of the N-(2-methyl)acryloyl-2-arylbenzimidazole compound is as follows: ； In the above formula, R 1 is -Br or -H, R 2 is -H, -Me or -OMe; The general structural formula of the 2-bromotetrafluoroethyl substituted benzimidazolidinone compound is as follows: ； In the above formula, R 1 is -Br or -H, R 2 is -H, -Me or -OMe; The photocatalyst is a noble metal catalyst or an organic dye catalyst, and the amount of the photocatalyst added is 1-3% of the molar amount of the BrCF2CF2Br; The noble metal catalyst is tris(2-phenylpyridine)iridium; and the organic dye catalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile.

2. The preparation method according to claim 1, characterized in that The base is NaHCO3 or Na2CO3.

3. The preparation method according to claim 2, characterized in that The molar ratio of the BrCF2CF2Br, N-(2-methacryloyl)-2-arylbenzimidazole compound and the base is (1.0-2.0):(1.0-2.0):(1.0-3.0).

4. The preparation method according to claim 1, characterized in that The solvent is acetonitrile, N,N-dimethylformamide or acetone.

5. The preparation method according to claim 1, characterized in that The wavelength of the visible light is 390-460 nm, and the power is 5-10 W.

6. The preparation method according to claim 1, characterized in that The reaction time is 12 to 36 hours.

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