Fluoromethyl substituted 2H-benzopyran and benzofuran compound with anti-cancer activity and synthesis method of fluoromethyl substituted 2H-benzopyran and benzofuran compound

Abstract

The invention discloses fluoromethyl substituted 2H-benzopyran and benzofuran compounds with anticancer activity and a synthesis method thereof, and belongs to the technical field of organic synthesis and drug discovery. The structural general formulas of the fluoromethyl substituted 2H-benzopyran compound and the fluoromethyl substituted benzofuran compound are respectively as follows: # imgabs0. The preparation method comprises the following steps: taking an N-aryloxy amide compound 1 and a fluoromethyl alkynyl ketone compound 2 as raw materials, and respectively reacting in the presence of a catalyst, an additive and an organic solvent; the fluoromethyl substituted 2H-benzopyran compound is obtained; reacting in the presence of an additive and dimethyl sulfoxide to obtain the fluoromethyl substituted benzofuran compound. Screening and anti-cancer cell activity tests prove that the compound provided by the invention has the activity of obviously inhibiting proliferation of two cancer cells, namely Hela and DU145, so that the compound provided by the invention has anti-cancer activity on cervical cancer and prostate cancer, and has potential medicinal value.

Description

Technical Field

[0001] The present invention belongs to the technical fields of organic synthesis and drug discovery, and particularly relates to fluoromethyl-substituted 2H-benzopyran and benzofuran compounds with anti-cancer activity and their synthesis methods. Background Art

[0002] The structural units of 2H-benzopyran and benzofuran widely exist in natural products and drug molecules. Among them, 2H-benzopyran derivatives not only have significant biological activities such as anti-tumor, anti-diabetic, anti-viral, anti-allergic, anti-inflammatory and bactericidal activities, but also have unique optical properties, and are the core structural units of organic functional materials such as laser dyes, fluorescent whitening agents, fluorescent probes, organic light-emitting devices, triplet sensitizers, etc.; the benzofuran structural framework is commonly found in clinical drugs and candidate drugs in phase II or III clinical trials, and is one of the advantageous structures for drug discovery. On the other hand, the introduction of fluoromethyl into organic molecules usually has a significant impact on the physicochemical properties and metabolic stability of the parent compound, can greatly enhance drug activity, improve the absorption and metabolism of drugs in vivo, etc., and is one of the commonly used and effective strategies in new drug design.

[0003] Based on their importance, researchers have developed some synthesis methods for these compounds. The synthesis methods of 2H-benzopyran compounds mainly include: intramolecular cyclization of functionalized arynes, electrocyclization of o-vinylidenequinones, oxycyclization of propargyl alcohols and azalactones, coupling cyclization of 1,3-diketones and 2-naphthols, electrochemical oxidative cyclization of unactivated alkynes, etc. The commonly used synthesis methods of benzofuran derivatives include condensation of hydroxy- or halogen-substituted acetophenones with ketones, condensation of salicylaldehyde with α-haloacetates, α-haloketones or ketones, etc. Most of these literature methods are effective and reliable, but there are still problems such as many reaction steps, difficult-to-obtain substrates, limited substrate scope, generation of toxic wastes and low atom economy.

[0004] Therefore, there is an urgent need to develop more efficient, concise and sustainable methods to construct libraries of 2H-benzopyran and benzofuran compounds to meet the requirements of drug development for compound structural diversity. At the same time, study their biological activities to meet the needs of people for drug discovery. Summary of the Invention

[0005] In order to solve the problems existing in the prior art, one of the purposes of the present invention is to provide fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds, and these compounds have anti-cancer activity.

[0006] Another purpose of the present invention is to provide the use of fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds in the preparation of anti-cancer drugs.

[0007] A third object of the present invention is to provide a pharmaceutical composition for treating cervical cancer and / or prostate cancer, and the active ingredient thereof is the fluoromethyl-substituted 2H-benzopyran compound and / or fluoromethyl-substituted benzofuran compound provided by the present invention.

[0008] A fourth object of the present invention is to provide a synthesis method for fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds.

[0009] In order to achieve the above objects, the technical solutions adopted by the present invention are as follows:

[0010] The fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds have the following general structural formulas respectively:

[0011]

[0012] Wherein, R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, phenyl, C 1-4 alkoxycarbonyl, trifluoromethoxy or halogen; R 2 is C 1-6 chain alkyl, halogenated C 1-6 chain alkyl, phenoxy C 1-6 chain alkyl or C 3-6 cyclic alkyl; R 3 is naphthyl, thienyl, phenyl or substituted phenyl, and the substituents on the benzene ring of the substituted phenyl are monosubstituted or polysubstituted C 1-4 alkyl, C 1-4 alkoxy, amino, methylamino, dimethylamino or halogen; R 4 is hydrogen, fluorine or methyl; R 5 is hydrogen, fluorine or methyl.

[0013] Furthermore, in the above general formula structure, in the most preferred case, it is selected from the following specific structures:

[0014]

[0015] The present invention designs experiments to verify that the compounds provided by the present invention have the activity of inhibiting the proliferation of two cancer cells, Hela and DU145, indicating that the compounds of the present invention can be used as the active ingredient of drugs for treating cancers such as cervical cancer and prostate cancer. In particular, the above-mentioned preferred compounds can significantly inhibit the growth and proliferation of Hela and DU145, indicating that these compounds, as the active ingredient of anti-cancer drugs, have the effects of preventing, treating and inhibiting the progression of cervical cancer and prostate cancer.

[0016] The application of the aforementioned fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds in the preparation of anticancer drugs, wherein the anticancer effect is against cervical cancer and prostate cancer.

[0017] A pharmaceutical composition for treating cervical cancer and / or prostate cancer, the active ingredient of which comprises the aforementioned fluoromethyl-substituted 2H-benzopyran compounds and / or fluoromethyl-substituted benzofuran compounds.

[0018] The present invention also provides a synthesis method for the aforementioned fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds, and the technical solution adopted is as follows:

[0019] A synthesis method for fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds, comprising the following steps: Using N-aryloxyamide compounds 1 and fluoromethyl alkynyl ketone compounds 2 as raw materials, reacting in the presence of a catalyst, an additive and an organic solvent to obtain fluoromethyl-substituted 2H-benzopyran compounds 3; reacting in the presence of an additive and dimethyl sulfoxide to obtain fluoromethyl-substituted benzofuran compounds 4.

[0020] The reaction equation is expressed as:

[0021]

[0022] Among them, R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, phenyl, C 1-4 alkoxycarbonyl, trifluoromethoxy or halogen; R 2 is C 1-6 chain alkyl, halogenated C 1-6 chain alkyl, phenoxy C 1-6 chain alkyl or C 3-6 cyclic alkyl; R 3 is naphthyl, thiophenyl, phenyl or substituted phenyl, and the substituents on the benzene ring of the substituted phenyl are monosubstituted or polysubstituted C 1-4 alkyl, C 1-4 alkoxy, amino, methylamino, dimethylamino or halogen; R 4 is hydrogen, fluorine or methyl; R 5 is hydrogen, fluorine or methyl.

[0023] Furthermore, in the above technical solution, the catalyst is tris(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III) bis(hexafluoroantimonate) ([RhCp*(MeCN) 3 (SbF 6 ) 2 ) or dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([RhCp*Cl2 2 )

[0024] Further, in the above technical solution, the additive is selected from acetate or a mixture of acetate and silver bis(trifluoromethanesulfonyl)imide, silver hexafluoroantimonate or silver tetrafluoroborate; the acetate is selected from copper acetate, zinc acetate, sodium acetate, silver acetate, potassium acetate or cesium acetate.

[0025] Further, in the above technical solution, the molar ratio of the N-aryloxyamide compound 1, the fluoromethyl alkynyl ketone compound 2, the catalyst and the additive is 1:1 - 3:0.03 - 0.06:0.5 - 1.1.

[0026] Further, in the above technical solution, the organic solvent is selected from methanol, toluene or 1,4-dioxane.

[0027] Further, in the above technical solution, the reaction temperature is 20 - 80 °C.

[0028] Further, in the above technical solution, the reaction is carried out under an air atmosphere.

[0029] Advantages of the invention:

[0030] (1) The fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds provided by the present invention, through screening compounds with various substituents and verifying by anti-cancer cell activity tests, the compounds provided by the present invention have obvious activity of inhibiting the proliferation of two cancer cells, Hela and DU145, indicating that the compounds of the present invention have anti-cancer activity against cervical cancer and prostate cancer, have potential medicinal value, and provide a new structural unit for drug screening;

[0031] (2) The synthesis method provided by the present invention is completed through a one-pot tandem reaction between an N-aryloxyamide compound and a fluoromethyl alkynyl ketone compound, and the process is simple and efficient;

[0032] (3) The synthesis method provided by the present invention has cheap and easily available raw materials, mild reaction conditions, simple operation, wide substrate applicability, good functional group tolerance and high atom economy. Description of the drawings

[0033] Figure 1 is the X-ray single crystal diffraction pattern of compound 3d in Example 4;

[0034] Figure 2 is the X-ray single crystal diffraction pattern of compound 4r in Example 4;

[0035] Figure 3 is the X-ray single crystal diffraction pattern of compound 5 in Example 5;​

[0036] Figure 4 X-ray single crystal diffraction pattern of compound 6 in Example 5;

[0037] Figure 5 X-ray single crystal diffraction pattern of compound 8 in Example 5. Detailed implementation mode

[0038] The above content of the present invention will be further described in detail through the following examples, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0039] Example 1

[0040]

[0041] Compound 1a, catalyst, additive, compound 2a and solvent were successively added to a 15 mL reaction tube. The reaction tube was sealed and stirred for 12 h. After the reaction was completed, it was extracted three times with ethyl acetate. The organic layers were combined and dried over anhydrous Na 2 SO 4 dried, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain a white solid product 3a or a yellow liquid product 4a.

[0042] By changing the reaction conditions such as reaction solvent, additive, catalyst, material ratio and reaction temperature, a series of results were obtained, as shown in Table 1.

[0043] Table 1 Synthesis of 3a and 4a under various conditions a

[0044]

[0045]

[0046] Example 2

[0047]

[0048] 1a (30.2 mg, 0.2 mmol), [RhCp*Cl 2 2 (6.2 mg, 0.01 mmol), copper acetate (18.2 mg, 0.1 mmol), silver tetrafluoroborate (3.9 mg, 0.02 mmol), 2a (39.6 mg, 0.2 mmol) and methanol (2.0 mL) were successively added to a 15 mL reaction flask. The flask was stoppered and sealed, and then placed in a 25 °C module and stirred for 12 h. After the reaction was completed, it was extracted three times with ethyl acetate. The organic layers were combined and dried over anhydrous Na 2 SO​4 It was dried, concentrated under reduced pressure, and separated by silica gel column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain the white solid product 3a (50.0 mg, 72%). 1 1H NMR (600 MHz, CDCl 3 3): δ 7.49 - 7.45 (m, 3H), 7.38 (s, 1H), 7.32 - 7.29 (m, 1H), 7.24 (d, J = 7.2 Hz, 1H), 7.17 - 7.14 (m, 2H), 6.93 (td, J 1 = 7.2 Hz, J 2 = 0.6 Hz, 1H), 6.78 (dd, J 1 = 7.8 Hz, J 2 = 1.8 Hz, 1H), 6.68 (s, 1H), 1.92 (s, 3H). 13 13C NMR (150 MHz, CDCl 3 3): δ 174.8, 149.3, 138.1, 132.8, 131.0, 129.2, 129.0, 128.9, 128.8, 128.5, 127.0, 122.5, 122.1 (q, 1 J C-F = 286.5 Hz), 120.0, 119.8, 116.9, 94.5 (q, 2 J C-F = 32.7 Hz), 22.2. 19 19F NMR (565 MHz, CDCl 3 3): δ -81.59 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 19H 14 19F 3 1NNaO 3 372.0818; Found 372.0832.

[0049] Example 3

[0050]

[0051] To a 15 mL reaction flask were successively added 1a (30.2 mg, 0.2 mmol), cesium acetate (38.4 mg, 0.2 mmol), 2a (118.9 mg, 0.6 mmol) and dimethyl sulfoxide (2.0 mL). The flask was stoppered and sealed, and then placed in a 25 °C module and stirred for 12 h. After the reaction was completed, it was extracted three times with ethyl acetate. The organic layers were combined, and anhydrous Na 2 2SO 4It was dried, concentrated under reduced pressure, and separated by silica gel column (petroleum ether / ethyl acetate = 30 / 1) to obtain the yellow liquid product 4a (40.1 mg, 61%). 1 H NMR (600 MHz, CDCl 3 ): δ 7.72 (d, J = 7.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.54 - 7.48 (m, 3H), 7.42 (t, J = 7.8 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 2.10 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ): δ 184.6, 155.1, 154.1, 139.3 (q, 2 J C-F =41.6 Hz), 135.6, 132.6, 128.9, 128.5, 128.2, 126.1, 124.9, 122.2, 119.1 (q, 1 J C-F =267.9 Hz), 117.7 (q, 3 J C-F =3.3 Hz), 112.3, 24.6. 19 F NMR (565 MHz, CDCl 3 ): δ -62.79 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 12 F 3 NNaO 2 354.0712; Found 354.0709.

[0052] Example 4

[0053] According to the methods and steps of Example 2 and Example 3, various fluoromethyl-substituted 2H-benzopyran compounds 3 and fluoromethyl-substituted benzofuran compounds 4 were synthesized by changing reactant 1, reactant 2, and other reaction conditions. The specific results are as follows:

[0054] Table 2 Synthesis of Fluoromethyl-Substituted 2H-Benzopyran Compounds 3 a,b

[0055]

[0056]

[0057] Table 3 Synthesis of Fluoromethyl-Substituted Benzofuran Compounds 4 a,b

[0058]

[0059] Representative product characterization data are as follows:

[0060] N-(2-Hydroxy-6-methyl-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3b): 1 HNMR(600MHz,CDCl 3 ):δ7.50 - 7.45(m,3H),7.31(s,1H),7.24(d,J=6.6Hz,1H),7.17(d,J=7.2Hz,1H),7.11(dd,J 1 =8.4Hz,J 2 =1.8Hz,1H),7.05(d,J=8.4Hz,1H),6.61(s,1H),6.55(d,J=1.2Hz,1H),2.17(s,3H),1.92(s,3H). 13 C NMR(150MHz,CDCl 3 ):δ174.7,147.1,138.2,133.0,131.9,131.6,129.2,129.0,128.9,128.8,128.5,127.1,122.2(q, 1 J C-F =287.7Hz),120.1,119.5,116.7,94.4(q, 2 J C-F =31.8Hz),22.2,20.7. 19 F NMR(565MHz,CDCl 3 ):δ - 81.58(s).HRMS(ESI)m / z:[M+Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974;Found 386.0977.N-(6-(tert-Butyl)-2-hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3c): 1 H NMR(600MHz,CDCl 3 ):δ7.48 - 7.44(m,3H),7.34(dd,J 1 =8.4Hz,J2 = 2.4 Hz, 1H), 7.30 (s, 1H), 7.25 (d, J = 6.6 Hz, 1H), 7.15 (d, J = 6.0 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 6.77 (d, J = 2.4 Hz, 1H), 6.74 (s, 1H), 1.92 (s, 3H), 1.14 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ 174.8, 147.0, 145.3, 138.4, 132.9, 129.2, 129.0, 128.8, 128.7, 128.5, 128.1, 123.7, 122.2 (q, 1 J C-F = 287.7 Hz), 119.8, 119.0, 116.4, 94.4 (q, 2 J C-F = 31.8 Hz), 34.3, 31.3, 22.1. 19 F NMR (565 MHz, CDCl 3 ): δ -81.46 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 22 F 3 NNaO 3 428.1444; Found 428.1447.

[0061] N-(2-Hydroxy-4,6-diphenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3d): 1 H NMR (600 MHz, CDCl 3 ): δ 7.53 (dd, J 1 = 8.4 Hz, J 2 = 2.4 Hz, 1H), 7.51 - 7.46 (m, 3H), 7.44 (s, 1H), 7.36 - 7.33 (m, 4H), 7.30 - 7.26 (m, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.22 (d, J = 6.0 Hz, 1H), 6.98 (d, J = 2.4 Hz, 1H), 6.61 (s, 1H), 1.95 (s, 3H). 13 C NMR (150 MHz, CDCl 3): δ 174.7, 148.8, 140.2, 138.1, 135.9, 132.7, 129.8, 129.4, 129.2, 129.0, 128.8, 128.5, 127.2, 126.9, 125.5, 122.1 (q, 1 J = 286.5 Hz), 120.5, 120.0, 117.4, 94.6 (q, 2 J = 31.7 Hz), 22.2. 19 F NMR (565 MHz, CDCl 3 ): δ -81.54 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 18 F 3 NNaO 3 448.1131; Found 448.1139. Ethyl-3-acetamido-2-hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromene-6-carboxylate (3e): 1 H NMR (600 MHz, CDCl 3 ): δ 7.99 (dd, J 1 = 8.4 Hz, J 2 = 1.8 Hz, 1H), 7.62 (s, 1H), 7.52 - 7.47 (m, 4H), 7.38 (d, J = 6.6 Hz, 1H), 7.19 (t, J = 7.8 Hz, 2H), 6.63 (s, 1H), 4.26 (q, J = 6.6 Hz, 2H), 1.94 (s, 3H), 1.29 (t, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ): δ 174.8, 165.7, 152.9, 137.7, 132.3, 132.1, 129.5, 129.4, 129.2, 128.8, 128.6, 128.4, 125.0, 122.0 (q, 1 J C-F = 287.6 Hz), 120.7, 119.6, 117.0, 94.9 (q, 2 J C-F = 32.9 Hz), 61.0, 22.2, 14.2. 19 F NMR (565 MHz, CDCl 3 ): δ -81.83 (s). HRMS (ESI) m / z: [M+Na] +Calcd for C 21 H 18 F 3 NNaO 5 444.1029; Found 444.1032. N-(2-Hydroxy-4-phenyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3f): 1 H NMR(600 MHz,CDCl 3 ): δ7.45 - 7.41(m,4H),7.18 - 7.17(m,1H),7.10 - 7.09(m,3H),6.68(s,1H),6.57(s,1H),1.87(s,3H). 13 C NMR(100 MHz,CDCl 3 ): δ173.7,146.5,142.9(q, 3 J C-F =2.1Hz),135.8,130.9,128.5,128.1,127.6,127.4,122.6,120.9(q, 1 J C-F =286.7 Hz),120.5,119.9,119.3(q, 1 J C-F =254.9 Hz),118.7,117.1,93.7(q, 2 J C-F =32.5 Hz),22.2. 19 F NMR(565 MHz,CDCl 3 ): δ - 58.45(s), - 81.59(s).HRMS(ESI)m / z:[M+Na] + Calcd forC 19 H 13 F 6 NNaO 4 456.0641; Found 456.0648.

[0062] N-(2-Hydroxy-7-methyl-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3g): 1 HNMR(400 MHz,CDCl 3): δ 7.44 - 7.43 (m, 3H), 7.33 (s, 1H), 7.22 - 7.21 (m, 1H), 7.12 (br s, 1H), 6.97 (s, 1H), 6.79 (s, 1H), 6.73 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 2.31 (s, 3H), 1.90 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.9, 149.2, 141.9, 138.2, 133.0, 129.1, 128.9, 128.8, 128.4, 126.8, 123.4, 122.2 (q, 1 J C-F =286.8 Hz), 118.9, 117.4, 117.2, 94.6 (q, 2 J C-F =32.5 Hz), 22.1, 21.4. 19 F NMR (376 MHz, CDCl 3 ): δ -81.60 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974; Found 386.0973.

[0063] N-(2-Hydroxy-7-isopropyl-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3h): 1 H NMR (400 MHz, CDCl 3 ): δ 7.48 - 7.41 (m, 3H), 7.37 (s, 1H), 7.21 (d, J = 6.8 Hz, 1H), 7.12 - 7.11 (m, 1H), 7.03 (d, J = 1.2 Hz, 1H), 6.94 (s, 1H), 6.80 (dd, J 1 =8.0 Hz, J 2 =1.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 2.91 - 2.81 (m, 1H), 1.90 (s, 3H), 1.21 (d, J = 6.8 Hz, 6H). 13 C NMR (100 MHz, CDCl 3): δ 175.0, 152.9, 149.2, 138.1, 133.0, 129.1, 128.9, 128.82, 128.80, 128.4, 126.9, 122.2 (q, 1 J C-F = 286.7 Hz), 121.0, 119.0, 117.5, 114.7, 94.5 (q, 2 J C-F = 32.5 Hz), 34.1, 23.7, 23.6, 22.1. 19 19F NMR (376 MHz, CDCl 3 ): δ -81.45 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 20 F 3 NNaO 3 414.1287; Found 414.1285.

[0064] N-(2-Hydroxy-4,7-diphenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3i): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.58 - 7.56 (m, 2H), 7.52 - 7.47 (m, 3H), 7.45 - 7.41 (m, 4H), 7.35 (t, J = 7.2 Hz, 1H), 7.27 (d, J = 6.4 Hz, 1H), 7.21 (d, J = 6.4 Hz, 1H), 7.17 (dd, J 1 = 8.0 Hz, J 2 = 1.6 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H), 1.94 (s, 3H). 13 13C NMR (100 MHz, CDCl 3 ): δ 174.8, 149.6, 144.2, 139.7, 137.9, 132.8, 129.3, 129.1, 128.9, 128.8, 128.5, 128.1, 127.3, 127.0, 122.2 (q, 1 J C-F = 287.5 Hz), 121.2, 119.8, 118.7, 115.4, 94.7 (q, 2 J C-F = 31.7 Hz), 22.2.19 F NMR (376 MHz, CDCl 3 ): δ -81.54 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 18 F 3 NNaO 3 448.1131; Found 448.1129.

[0065] N-(7-Bromo-2-hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3j): 1 H NMR (400 MHz, CDCl 3 ): δ 7.50 - 7.44 (m, 4H), 7.33 (d, J = 2.0 Hz, 1H), 7.22 - 7.21 (m, 1H), 7.14 - 7.13 (m, 1H), 7.06 (dd, J 1 = 8.4 Hz, J 2 = 1.6 Hz, 1H), 6.76 (s, 1H), 6.65 (d, J = 8.4 Hz, 1H), 1.92 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.9, 149.7, 137.5, 132.3, 129.4, 129.3, 129.0, 128.7, 128.4, 128.0, 125.8, 124.3, 121.9 (q, 1 J C-F = 287.5 Hz), 120.3, 118.9, 94.7 (q, 2 J C-F = 32.5 Hz), 22.2. 19 F NMR (376 MHz, CDCl 3 ): δ -81.66 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 13 BrF 3 NNaO 3 449.9923; Found 449.9929.

[0066] N-(2-Hydroxy-8-methyl-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3k): 1 HNMR(400 MHz,CDCl 3 ):δ7.46-7.41(m,3H),7.32(s,1H),7.24-7.22(m,1H),7.18-7.16(m,2H),6.83(t,J=7.6 Hz,1H),6.68(s,1H),6.61(d,J=7.6 Hz,1H),2.36(s,3H),1.91(s,3H). 13 C NMR(100 MHz,CDCl 3 ):δ174.8,147.3,138.4,133.2,132.4,129.2,128.9,128.8,128.4,126.4,124.7,122.3(q, 1 J C-F =286.7 Hz),121.9,119.7,119.4,94.5(q, 2 J C-F =32.5 Hz),22.2,15.4. 19 F NMR(376 MHz,CDCl 3 ):δ-81.75(s).HRMS(ESI)m / z:[M+Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974;Found 386.0979.

[0067] N-(2-Hydroxy-6,7-dimethyl-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3l): 1 H NMR(600 MHz,CDCl 3 ):δ7.49-7.46(m,3H),7.26(br s,1H),7.24(d,J=7.2 Hz,1H),7.17(d,J=7.2 Hz,1H),6.97(s,1H),6.50(s,2H),2.24(s,3H),2.07(s,3H),1.92(s,3H). 13 C NMR(150 MHz,CDCl 3): δ 174.7, 147.3, 140.4, 138.3, 133.2, 130.7, 129.2, 128.9, 128.8, 128.7, 128.5, 127.4, 122.2 (q, 1 J C-F = 286.7 Hz), 119.0, 117.9, 117.2, 94.5 (q, 2 J C-F = 31.7 Hz), 22.2, 19.9, 19.0. 19 19F NMR (565 MHz, CDCl 3 ): δ -81.61 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 18 F 3 NNaO 3 400.1131; Found 400.1137.

[0068] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)propionamide (3m): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.55 (s, 1H), 7.49 - 7.43 (m, 3H), 7.32 - 7.28 (m, 1H), 7.23 - 7.22 (m, 1H), 7.16 - 7.14 (m, 2H), 6.95 - 6.91 (m, 1H), 6.78 (dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, 1H), 6.65 (s, 1H), 2.20 - 2.07 (m, 2H), 1.01 (t, J = 7.6 Hz, 3H). 13 13C NMR (100 MHz, CDCl 3 ): δ 178.4, 149.2, 137.9, 132.8, 130.9, 129.2, 129.0, 128.9, 128.7, 128.5, 126.9, 122.4, 122.2 (q, 1 J C-F = 286.7 Hz), 120.1, 119.8, 116.9, 94.5 (q, 2 J C-F = 32.5 Hz), 28.9, 9.4. 19 19F NMR (376 MHz, CDCl 3): δ -81.52 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974; Found 386.0973.

[0069] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)isobutyramide (3n): 1 H NMR (400 MHz, CDCl 3 ): δ 7.61 (br s, 1H), 7.49 - 7.46 (m, 3H), 7.33 - 7.29 (m, 1H), 7.24 - 7.23 (m, 1H), 7.20 - 7.15 (m, 2H), 6.93 (t, J = 7.6 Hz, 1H), 6.78 (dd, J 1 = 7.6 Hz, J 2 = 0.8 Hz, 1H), 6.54 (s, 1H), 2.34 - 2.24 (m, 1H), 1.03 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 181.2, 149.2, 138.0, 132.9, 130.9, 129.3, 129.0, 128.9, 128.7, 128.6, 126.9, 122.4, 122.2 (q, 1 J C-F = 287.5 Hz), 120.1, 119.8, 116.9, 94.5 (q, 2 J C-F = 33.2 Hz), 35.1, 19.0, 18.9. 19 F NMR (376 MHz, CDCl 3 ): δ -81.47 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 18 F 3 NNa O 3 400.1131; Found 400.1136.

[0070] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)cyclopropanecarboxamide(3o): 1 H NMR(400 MHz,CDCl 3 ):δ7.68(br s,1H),7.51-7.43(m,3H),7.31-7.27(m,1H),7.23-7.19(m,2H),7.14(d,J=8.0 Hz,1H),6.92(t,J=7.6 Hz,1H),6.79-6.78(m,2H),1.29-1.23(m,1H),1.01-0.96(m,2H),0.85-0.74(m,2H). 13 C NMR(100 MHz,CDCl 3 ):δ178.3,149.3,137.4,132.8,130.8,129.2,129.0,128.85,128.76,126.9,122.4,122.2(q, 1 J C-F =287.5 Hz),120.3,119.8,116.9,94.5(q, 2 J C-F =32.5 Hz),14.1,8.5,8.1. 19 F NMR(376 MHz,CDCl 3 ):δ-81.61(s).HRMS(ESI)m / z:[M+Na] + Calcd forC 20 H 16 F 3 NNaO 3 398.0974;Found 398.0972.

[0071] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)pentanamide(3p): 1 H NMR(400 MHz,CDCl 3 ):δ7.57(s,1H),7.47-7.44(m,3H),7.33-7.29(m,1H),7.25-7.23(m,1H),7.19-7.15(m,2H),6.95-6.91(m,1H),6.77(dd,J 1 =7.6 Hz,J 2= 1.2 Hz, 1H), 6.56 (s, 1H), 2.18 - 2.04 (m, 2H), 1.47 - 1.40 (m, 2H), 1.26 - 1.17 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 177.6, 149.3, 137.9, 132.9, 130.9, 129.3, 129.0, 128.9, 128.7, 128.6, 126.9, 122.4, 122.2 (q, 1 J C-F = 286.7 Hz), 120.1, 119.8, 116.9, 94.6 (q, 2 J C-F = 32.5 Hz), 35.4, 27.2, 22.1, 13.6. 19 F NMR (376 MHz, CDCl 3 ): δ -81.56 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 21 H 20 F 3 NNaO 3 414.1287; Found 414.1280.

[0072] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)cyclohexanecarboxamide (3q): 1 H NMR (400 MHz, CDCl 3 ): δ 7.64 (br s, 1H), 7.49 - 7.46 (m, 3H), 7.33 - 7.29 (m, 1H), 7.23 - 7.22 (m, 1H), 7.19 - 7.15 (m, 2H), 6.93 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 7.2 Hz, 1H), 6.52 (s, 1H), 2.05 - 1.99 (m, 1H), 1.71 - 1.68 (m, 3H), 1.57 - 1.53 (m, 2H), 1.31 - 1.14 (m, 5H). 13 C NMR (150 MHz, CDCl 3 ): δ 180.3, 149.2, 137.8, 132.9, 130.9, 129.3, 129.0, 128.9, 128.8, 128.7, 126.8, 122.4, 122.2 (q,1 J C-F = 286.5 Hz), 120.2, 119.8, 116.9, 94.5 (q, 2 J C-F = 31.7 Hz), 44.7, 29.1, 29.0, 25.43, 25.36, 25.2. 19 F NMR (376 MHz, CDCl 3 ): δ -81.38 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 22 F 3 NNaO 3 440.1444; Found 440.1442.

[0073] 2-Chloro-N-(2-hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3r): 1 H NMR (400 MHz, CDCl 3 ): δ 7.55 - 7.48 (m, 4H), 7.36 - 7.32 (m, 1H), 7.22 - 7.21 (m, 2H), 7.17 (d, J = 8.4 Hz, 1H), 6.95 (t, J = 7.2 Hz, 1H), 6.90 (s, 1H), 6.82 (d, J = 7.6 Hz, 1H), 4.06 (d, J = 15.2 Hz, 1H), 3.91 (d, J = 15.6 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 170.1, 149.4, 139.2, 132.4, 131.3, 129.4, 129.2, 129.0, 128.5, 128.2, 127.1, 122.6, 122.0 (q, 1 J C-F = 287.5 Hz), 119.6, 118.7, 116.9, 94.5 (q, 2 J C-F = 33.2 Hz), 41.7. 19 F NMR (376 MHz, CDCl 3 ): δ -81.83 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 13 ClF 3NNaO 3 406.0428; Found 406.0429.

[0074] N-(2-Hydroxy-4-phenyl-2-(trifluoromethyl)-2H-chromen-3-yl)-2-phenoxyacetamide(3s): 1 HNMR(400 MHz,CDCl 3 ): δ 7.71(s,1H), 7.47 - 7.42(m,4H), 7.34 - 7.30(m,1H), 7.26 - 7.20(m,4H), 7.17(d,J = 8.0 Hz,1H), 7.01(t,J = 7.2 Hz,1H), 6.93(t,J = 7.2 Hz,1H), 6.78(dd,J 1 = 7.6Hz,J 2 = 1.2 Hz,1H), 6.63(d,J = 8.0 Hz,2H), 4.56(d,J = 15.6 Hz,1H), 4.34(d,J = 15.6 Hz,1H). 13 C NMR(150 MHz,CDCl 3 ): δ 172.2, 156.8, 149.4, 138.0, 132.5, 131.1, 129.8, 129.4, 129.1, 129.0, 128.5, 128.4, 126.9, 122.6, 122.5, 122.2(q, 1 J C-F = 287.6 Hz), 119.7, 118.9, 116.8, 114.8, 94.6(q, 2 J C-F = 32.9 Hz), 67.2. 19 F NMR(376 MHz,CDCl 3 ): δ - 81.98(s).HRMS(ESI)m / z: [M+Na] + Calcd for C 24 H 18 F 3 NNaO 4 464.1080; Found 464.1075.

[0075] N-(2-Hydroxy-4-(p-tolyl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3t): 1 H NMR(600 MHz,CDCl3 ): δ 7.40 (broad singlet, 1H), 7.31 - 7.26 (multiplet, 3H), 7.15 - 7.12 (multiplet, 2H), 7.05 (doublet, J = 7.2 Hz, 1H), 6.92 (triplet, J = 7.2 Hz, 1H), 6.81 (doublet of doublets, J 1 = 7.2 Hz, J 2 = 0.6 Hz, 1H), 6.68 (singlet, 1H), 2.41 (singlet, 3H), 1.94 (singlet, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.8, 149.3, 139.0, 137.9, 130.9, 129.9, 129.7, 129.6, 128.7, 128.4, 127.0, 122.4, 122.2 (quartet, 1 J C-F = 287.4 Hz), 119.9, 116.9, 94.5 (quartet, 2 J C-F = 32.5 Hz), 22.2, 21.3. 19 F NMR (565 MHz, CDCl 3 ): δ -81.61 (singlet). HRMS (ESI) m / z: [M + Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974; Found 386.0973.

[0076] N-(2-Hydroxy-4-(4-methoxyphenyl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3u): 1 H NMR (600 MHz, CDCl 3 ): δ 7.37 (singlet, 1H), 7.32 - 7.29 (multiplet, 1H), 7.18 - 7.14 (multiplet, 2H), 7.10 (doublet, J = 7.2 Hz, 1H), 6.99 (doublet, J = 9.0 Hz, 2H), 6.94 (triplet, J = 7.8 Hz, 1H), 6.83 (doublet of doublets, J 1 = 7.8 Hz, J 2 = 1.2 Hz, 1H), 6.63 (singlet, 1H), 3.87 (singlet, 3H), 1.96 (singlet, 3H). 13 C NMR (100 MHz, CDCl 3): δ 174.7, 160.1, 149.3, 137.6, 130.9, 130.2, 129.9, 127.0, 124.6, 122.4, 122.2 (q, 1 J C-F = 287.4 Hz), 120.0, 116.9, 114.6, 114.3, 94.5 (q, 2 J C-F = 32.5 Hz), 55.4, 22.3. 19 1H NMR (565 MHz, CDCl 3 ): δ -81.57 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 16 F 3 NNaO 4 402.0924; Found 402.0918.

[0077] N-(4-(4-(Dimethylamino)phenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3v): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.46 (s, 1H), 7.31 - 7.26 (m, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.08 - 7.05 (m, 2H), 6.95 - 6.92 (m, 2H), 6.77 (d, J = 8.8 Hz, 2H), 6.65 (s, 1H), 3.02 (s, 6H), 1.99 (s, 3H). 13 13C NMR (150 MHz, CDCl 3 ): δ 174.8, 150.6, 149.4, 137.5, 130.6, 129.9, 129.6, 127.2, 122.3, 122.2 (q, 1 J C-F = 293.1 Hz), 120.3, 119.5, 119.4, 116.9, 112.4, 112.0, 94.5 (q, 2 J C-F = 31.8 Hz), 40.3, 22.4. 19 19F NMR (376 MHz, CDCl 3 ): δ -81.60 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C20 H 19 F 3 N 2 NaO 3 415.1240;Found 415.1237.

[0078] N-(4-(4-Fluorophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3w): 1 HNMR(600 MHz,CDCl 3 ):δ7.32(t,J=7.2 Hz,1H),7.26 - 7.24(m,2H),7.19 - 7.15(m,4H),6.95(t,J=7.2 Hz,1H),6.76(d,J=7.8 Hz,1H),6.69(s,1H),1.95(s,3H). 13 CNMR(100 MHz,CDCl 3 ):δ174.7,163.0(d, 1 J C-F =247.0 Hz),149.2,137.5,131.2,130.7(d, 3 J C-F =7.9 Hz),130.5(d, 3 J C-F =6.5 Hz),128.7(d, 4 J C-F =3.6 Hz),126.8,122.6,122.1(q, 1 J C-F =286.8 Hz),120.3,119.7,117.1,116.4(d, 2 J C-F =20.3 Hz),116.1(d, 2 J C-F =21.7Hz),94.5(q, 2 J C-F =31.8 Hz),22.2. 19 F NMR(565 MHz,CDCl 3 ):δ-81.49(s),-111.67– - 111.72(m).HRMS(ESI)m / z:[M+Na] + Calcd for C 18 H 13 F 4 NNaO 3390.0724; Found 390.0723.

[0079] N-(4-(4-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3x): 1 HNMR(600 MHz,CDCl 3 ):δ7.47(d,J = 8.4 Hz,2H),7.34 - 7.32(m,1H),7.21 - 7.19(m,2H),7.17(d,J = 7.8 Hz,1H),7.13(d,J = 7.8 Hz,1H),6.96 - 6.94(m,1H),6.76(dd,J 1 = 7.8 Hz,J 2 = 1.2Hz,1H),6.56(s,1H),1.97(s,3H). 13 C NMR(100 MHz,CDCl 3 ):δ174.7,149.2,137.4,135.2,131.3,131.2,130.3,130.0,129.5,129.2,126.7,122.6,122.1(q, 1 J C-F = 286.8 Hz),120.3,119.4,117.1,94.4(q, 2 J C-F = 32.5 Hz),22.2. 19 F NMR(565 MHz,CDCl 3 ):δ - 81.46(s).HRMS(ESI)m / z:[M+Na] + Calcd for C 18 H 13 ClF 3 NNaO 3 406.0428; Found406.0426.

[0080] N-(4-(4-Bromophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide(3y): 1 HNMR(600 MHz,CDCl 3): δ 7.63 (d, J = 8.4 Hz, 2H), 7.34 - 7.31 (m, 1H), 7.19 (s, 1H), 7.17 - 7.14 (m, 2H), 7.07 (d, J = 7.2 Hz, 1H), 6.96 - 6.94 (m, 1H), 6.76 (dd, J 1 = 7.8 Hz, J 2 = 1.2 Hz, 1H), 6.58 (s, 1H), 1.97 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.7, 149.2, 137.5, 132.5, 132.2, 131.8, 131.3, 130.6, 130.3, 126.7, 123.4, 122.6, 122.1 (q, 1 J C-F = 287.5 Hz), 120.2, 119.4, 117.1, 94.4 (q, 2 J C-F = 32.5 Hz), 22.3. 19 F NMR (565 MHz, CDCl 3 ): δ -81.46 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 18 H 13 BrF 3 NNaO 3 449.9923; Found 449.9925.

[0081] N-(2-Hydroxy-4-(m-tolyl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3z): 1 H NMR (600 MHz, CDCl 3 ): δ 7.47 (s, 0.5H), 7.44 (s, 0.5H), 7.37 - 7.33 (m, 1H), 7.29 (t, J = 7.2 Hz, 1H), 7.26 - 7.25 (m, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.04 - 7.02 (m, 1H), 6.96 - 6.91 (m, 2H), 6.80 (dd, J 1 = 7.8 Hz, J 2 = 0.6 Hz, 1H), 6.76 (s, 0.5H), 6.72 (s, 0.5H), 2.38 (s, 3H), 1.92 (s, 1.5H), 1.91 (s, 1.5H).13 C NMR (100 MHz, CDCl 3 ): δ 174.8, 149.2, 139.1, 138.7, 138.0, 132.7, 130.9, 129.8, 129.3, 129.1, 128.9, 128.8, 127.0, 125.8, 125.4, 122.4, 122.2 (q, 1 J C-F = 286.7 Hz), 119.93, 119.88, 119.85, 119.79, 116.9, 94.5 (q, 2 J C-F = 32.5 Hz), 22.2, 22.1, 21.40, 21.38. 19 F NMR (565 MHz, CDCl 3 ): δ -81.61 (s), -81.66 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974; Found 386.0978.

[0082] N-(4-(3-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3aa): 1 H NMR (600 MHz, CDCl 3 ): δ 7.44 - 7.39 (m, 4.8H), 7.32 - 7.29 (m, 3.8H), 7.26 - 7.24 (m, 2.4H), 7.15 - 7.12 (m, 4.8H), 7.05 (d, J = 7.2 Hz, 1H), 6.97 - 6.95 (m, 2.4H), 6.86 (s, 1.4H), 6.83 (s, 1H), 6.77 (d, J = 7.8 Hz, 2.4H), 1.96 (s, 3H), 1.93 (s, 4.2H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.8, 149.1, 137.2, 137.1, 135.2, 134.9, 134.7, 134.6, 131.3, 130.6, 130.2, 129.3, 128.9, 128.6, 127.1, 126.8, 126.7, 122.7, 122.0 (q, 1 J C-F= 286.7 Hz), 120.4, 119.3, 117.1, 94.4 (q, 2 J C-F = 32.5 Hz), 22.1. 19 F NMR (565 MHz, CDCl 3 ): δ -81.44 (s), -81.49 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 13 ClF 3 NNaO 3 406.0428; Found 406.0420.

[0083] N-(2-Hydroxy-4-(o-tolyl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3bb): 1 H NMR (400 MHz, CDCl 3 ): δ 7.87 (s, 1H), 7.61 (s, 1.3H), 7.39 - 7.35 (m, 3.3H), 7.33 - 7.28 (m, 5.9H), 7.16 - 7.11 (m, 3.6H), 7.02 (d, J = 7.6 Hz, 1H), 6.92 - 6.88 (m, 2.3H), 6.63 - 6.59 (m, 3.3H), 6.46 (s, 1.3H), 2.15 (s, 3H), 2.05 (s, 3.9H), 1.89 (s, 6.9H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.6, 173.9, 149.4, 149.3, 138.1, 137.1, 136.8, 135.8, 132.2, 131.01, 130.97, 130.96, 130.7, 129.3, 129.1, 128.4, 128.3, 126.8, 126.5, 126.4, 126.3, 122.6 122.5, 122.23 (q, 1 J C-F = 286.7 Hz), 122.21 (q, 1 J C-F = 288.2 Hz), 120.5, 120.3, 119.2, 119.0, 116.9, 116.7, 94.8 (q, 2 J C-F = 33.3 Hz), 94.7 (q, 2 J C-F= 32.5 Hz), 22.4, 22.3, 19.4, 19.0. 19 F NMR (376 MHz, CDCl 3 ): δ -82.05 (s), -82.12 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 16 F 3 NNaO 3 386.0974; Found 386.0977.

[0084] N-(4-(2-Chlorophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3cc): 1 H NMR (400 MHz, CDCl 3 ): δ 7.91 (s, 1H), 7.48 - 7.43 (m, 4H), 7.36 - 7.14 (m, 19H), 7.07 - 7.05 (m, 4H), 6.86 - 6.75 (m, 8H), 6.57 - 6.52 (m, 4H), 1.83 (s, 3H), 1.80 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): δ 173.7, 172.5, 148.4, 148.1, 136.0, 133.0, 132.8, 131.9, 130.8, 130.5, 130.2, 130.0, 129.8, 129.6, 129.4, 129.3, 129.1, 129.0, 126.6, 126.3, 125.3, 125.2, 121.51, 121.47, 121.1 (q, 1 J C-F = 287.5 Hz), 119.7, 119.3 (q, 1 J C-F = 270.2 Hz), 117.5, 115.80, 115.75, 93.9 (q, 2 J C-F = 33.2Hz), 93.4 (q, 2 J C-F = 33.2 Hz), 21.4, 21.1. 19 F NMR (376 MHz, CDCl 3 ): δ -81.91 (s), 81.96 (s). HRMS (ESI) m / z: [M+Na] +Calculated for C 18 H 13 ClF 3 NNaO 3 406.0428; Found 406.0431.

[0085] N-(4-(3,5-Dichlorophenyl)-2-hydroxy-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3dd): 1 H NMR (400 MHz, CDCl 3 ): δ 7.45 - 7.44 (m, 1H), 7.32 - 7.27 (m, 1H), 7.22 (s, 1H), 7.16 - 7.12 (m, 2H), 7.03 (s, 1H), 6.99 - 6.96 (m, 2H), 6.76 (dd, J 1 = 7.6 Hz, J 2 = 1.2 Hz, 1H), 1.97 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.9, 149.0, 136.2, 135.9, 135.6, 131.5, 129.3, 127.4, 126.9, 126.6, 122.8, 121.9 (q, 1 J C-F = 286.8 Hz), 120.8, 118.9, 117.2, 94.3 (q, 2 J C-F = 32.7 Hz), 22.0. 19 F NMR (376 MHz, CDCl 3 ): δ -81.37 (s). HRMS (ESI) m / z: [M+Na] + Calculated for C 18 H 12 Cl 2 F 3 NNaO 3 440.0039; Found 440.0040.

[0086] N-(2-Hydroxy-4-(naphthalen-2-yl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3ee): 1 H NMR (600 MHz, CDCl 3): δ 7.95 - 7.90 (m, 3.6H), 7.86 - 7.81 (m, 1.8H), 7.74 (s, 0.8H), 7.65 (s, 1H), 7.59 - 7.53 (m, 3.6H), 7.45 - 7.40 (m, 1.8H), 7.32 - 7.29 (m, 2.8H), 7.25 - 7.24 (m, 0.8H), 7.17 (d, J = 7.8 Hz, 1.8H), 6.91 (t, J = 7.2 Hz, 1.8H), 6.83 (d, J = 7.2 Hz, 1H), 6.77 (d, J = 7.8 Hz, 0.8H), 6.73 - 6.71 (m, 1.8H), 1.87 (s, 3H), 1.85 (s, 2.4H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.9, 174.8, 149.29, 149.25, 138.1, 138.0, 133.4, 133.2, 133.1, 131.0, 130.3, 130.1, 129.1, 128.8, 128.3, 128.1, 128.02, 127.98, 127.91, 127.85, 127.11, 127.06, 127.0, 126.9, 126.1, 126.0, 122.5, 122.2 (q, 1 J C-F = 286.8 Hz), 120.3, 119.9, 119.8, 117.0, 94.55 (q, 2 J C-F = 32.5 Hz), 94.52 (q, 2 J C-F = 32.5 Hz), 22.23, 22.17. 19 F NMR (565 MHz, CDCl 3 ): δ -81.44 (s), -81.56 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 22 H 16 F 3 NNaO 3 422.0974; Found 422.0963.

[0087] N-(2-Hydroxy-4-(thiophen-3-yl)-2-(trifluoromethyl)-2H-chromen-3-yl)acetamide (3ff): 1 H NMR (400 MHz, CDCl 3): δ 7.50 - 7.48 (m, 1H), 7.34 - 7.27 (m, 3H), 7.15 (d, J = 8.4 Hz, 1H), 7.00 - 6.92 (m, 3H), 6.72 (s, 1H), 2.01 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.7, 149.2, 133.4, 132.4, 131.0, 128.0, 126.9, 126.7, 125.2, 122.5, 122.1 (q, 1 J C-F = 286.7 Hz), 120.6, 119.6, 117.0, 94.4 (q, 2 J C-F = 32.5 Hz), 22.3. 19 F NMR (376 MHz, CDCl 3 ): δ -81.50 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 16 H 12 F 3 NNaO 3 S 378.0382; Found 378.0384.

[0088] N-(2-(Fluoromethyl)-2-hydroxy-4-phenyl-2H-chromen-3-yl)acetamide (3gg): 1 H NMR (400 MHz, CDCl 3 ): δ 7.46 - 7.44 (m, 3H), 7.29 - 7.26 (m, 2H), 7.19 - 7.17 m, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.90 (t, J = 7.2 Hz, 1H), 6.80 - 6.78 (m, 1H), 6.71 (br s, 1H), 6.15 (s, 1H), 4.57 (d, J = 47.2 Hz, 2H), 1.97 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 173.6, 150.3, 134.8, 133.6, 130.2, 129.2, 129.1, 128.9, 128.8, 126.6, 123.8, 121.9, 120.6, 117.1, 95.2 (d, 2 J C-F = 19.6 Hz), 83.7 (d, 1 JC-F = 180.5 Hz), 22.5. 19 F NMR (565 MHz, CDCl 3 ): δ -220.12 (t, J = 46.9 Hz). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 16 FNNaO 3 336.1006; Found 336.0995.

[0089] N-(2-(Difluoromethyl)-2-hydroxy-4-phenyl-2H-chromen-3-yl)acetamide (3hh): 1 H NMR (400 MHz, CDCl 3 ): δ 7.48 - 7.45 (m, 3H), 7.30 - 7.26 (m, 2H), 7.17 (br s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.92 - 6.89 (m, 2H), 6.79 (d, J = 7.6 Hz, 1H), 6.70 (br s, 1H), 5.86 (t, J = 54.8 Hz, 1H), 1.92 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 174.4, 149.5, 137.0, 133.1, 130.6, 129.1, 129.0, 128.9, 128.8, 126.9, 122.2, 121.3, 120.2, 116.9, 114.3 (t, 1 J C-F = 249.2 Hz), 94.2 (t, 2 J C-F = 25.3 Hz), 22.3. 19 F NMR (376 MHz, CDCl 3 ): δ -129.22 (dd, J 1 = 279.7 Hz, J 2 = 55.3 Hz), -133.39 (dd, J 1 = 279.7 Hz, J 2 = 55.3 Hz). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 15 F 2 NNaO 3354.0912; Found 354.0904.

[0090] N-(2-(1,1-Difluoroethyl)-2-hydroxy-4-phenyl-2H-chromen-3-yl)acetamide (3ii): 1 H NMR (400 MHz, CDCl 3 ): δ 7.48 - 7.41 (m, 3H), 7.28 - 7.24 (m, 2H), 7.19 - 7.18 (m, 1H), 7.07 (d, J = 8.0 Hz, 1H), 7.00 (s, 1H), 6.88 (t, J = 7.6 Hz, 1H), 6.76 - 6.74 (m, 1H), 6.58 (brs, 1H), 1.93 - 1.74 (m, 6H). 13 C NMR (150 MHz, CDCl 3 ): δ 174.3, 149.9, 138.1, 133.6, 130.4, 129.1, 128.8, 128.7, 128.6, 126.8, 123.3 (t, 1 J = 246.0 Hz), 121.94, 121.88, 120.4, 116.6, 96.1 (dd, 2 J C-F = 32.7 Hz, 29.4 Hz), 22.3, 17.9 (t, 2 J C-F = 25.1 Hz). 19 F NMR (565 MHz, CDCl 3 ): δ -102.69 (dq, J 1 = 245.2 Hz, J 2 = 20.3 Hz), -103.36 (dq, J 1 = 245.2 Hz, J 2 = 20.3 Hz). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 17 F 2 NNaO 3 368.1069; Found 368.1070.

[0091] N-(Phenyl(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4a): 1 H NMR (600 MHz, CDCl3 ): δ 7.72 (d, J = 7.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.54 - 7.48 (m, 3H), 7.42 (t, J = 7.8 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 2.10 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ): δ 184.6, 155.1, 154.1, 139.3 (q, 2 J C-F = 41.6 Hz), 135.6, 132.6, 128.9, 128.5, 128.2, 126.1, 124.9, 122.2, 119.1 (q, 1 J C-F = 267.9 Hz), 117.7 (q, 3 J C-F = 3.3 Hz), 112.3, 24.6. 19 F NMR (565 MHz, CDCl 3 ): δ -62.79 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 18 H 12 F 3 NNaO 2 354.0712; Found 354.0709.

[0092] N-((5-Isopropyl-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4b): 1 H NMR (400 MHz, CDCl 3 ): δ 7.75 - 7.73 (m, 2H), 7.55 - 7.51 (m, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.38 (d, J = 8.8 Hz, 1H), 7.29 (s, 1H), 3.01 - 2.94 (m, 1H), 2.09 (s.3H), 1.23 (d, J = 6.8 Hz, 6H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.6, 155.3, 152.8, 146.0, 139.4 (q, 2 J C-F= 41.2 Hz), 135.7, 132.6, 128.9, 128.6, 127.2, 126.0, 119.11 (q, 1 J C-F = 268.0 Hz), 119.10, 117.6 (q, 3 J C-F = 2.9 Hz), 111.9, 34.1, 24.6, 24.3. 19 F NMR (376 MHz, CDCl 3 ): δ -62.77 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 18 F 3 NNaO 2 396.1182; Found 396.1184.

[0093] N-((5-(tert-Butyl)-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4c): 1 H NMR (400 MHz, CDCl 3 ): δ 7.76 - 7.74 (m, 2H), 7.57 (dd, J 1 = 9.2 Hz, J 2 = 1.6 Hz, 1H), 7.54 - 7.51 (m, 2H), 7.45 - 7.41 (m, 3H), 2.09 (s, 3H), 1.31 (s.9H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.5, 155.3, 152.5, 148.3, 139.4 (q, 2 J C-F = 41.2 Hz), 135.8, 132.6, 128.8, 128.6, 126.4, 125.7, 119.1 (q, 1 J C-F = 265.1 Hz), 118.1, 117.8 (q, 3 J C-F = 2.9 Hz), 111.5, 35.0, 31.6, 24.5. 19 F NMR (376 MHz, CDCl 3 ): δ -62.74 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C22 H 20 F 3 NNaO 2 410.1338; Found 410.1333.

[0094] N-(Phenyl(5-phenyl-2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4d): 1 H NMR (400 MHz, CDCl 3 ): δ 7.76 (s, 1H), 7.73 (d, J = 10.0 Hz, 2H), 7.66 (d, J = 10.0 Hz, 2H), 7.55 - 7.51 (m, 3H), 7.44 - 7.39 (m, 4H), 7.33 (t, J = 7.6 Hz, 1H), 2.12 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.6, 155.0, 153.7, 140.3, 139.8 (q, 2 J C-F = 41.2 Hz), 138.8, 135.6, 132.7, 128.9, 128.5, 128.0, 127.60, 127.55, 126.7, 120.4, 119.0 (q, 1 J C-F = 267.9 Hz), 117.9, (q, 3 J C-F = 2.9 Hz), 112.4, 24.6. 19 F NMR (376 MHz, CDCl 3 ): δ -62.80 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 16 F 3 NNaO 2 430.1025; Found 430.1027.

[0095] N-((5-Bromo-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4e): 1 H NMR (400 MHz, CDCl 3): δ 7.70 (d, J = 7.6 Hz, 2H), 7.62 - 7.59 (m, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 2.12 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.5, 154.5, 152.9, 140.4 (q, 2 J C-F =41.9 Hz), 135.2, 132.9, 131.4, 129.0, 128.5, 128.0, 124.8, 118.7 (q, 1 J C-F =267.9 Hz), 118.1, 117.2 (q, 3 J C-F =2.9 Hz), 113.8, 24.6. 19 F NMR (376 MHz, CDCl 3 ): δ -62.90 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 18 H 11 BrF 3 NNaO 2 431.9817; Found 431.9824.

[0096] Ethyl-3-((acetylimino)(phenyl)methyl)-2-(trifluoromethyl)benzofuran-5-carboxylate (4f): 1 H NMR (400 MHz, CDCl 3 ): δ 8.25 - 8.22 (m, 2H), 7.73 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 8.8 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.6 Hz 2H), 4.37 (q, J = 6.8 Hz, 2H), 2.12 (s. 3H), 1.37 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.5, 165.6, 156.3, 154.6, 140.5 (q, 2 J C-F= 41.1 Hz), 135.3, 132.8, 129.6, 129.0, 128.5, 127.9, 126.2, 124.5, 118.8 (q, 1 J C-F = 268.7 Hz), 118.1 (q, 3 J C-F = 2.9 Hz), 112.3, 61.5, 24.6, 14.3. 19 F NMR (376 MHz, CDCl 3 ): δ -62.99 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 16 F 3 NNaO 4 426.0924; Found 426.0928.

[0097] N-(Phenyl(5-(trifluoromethoxy)-2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4g): 1 H NMR (400 MHz, CDCl 3 ): δ 7.72 - 7.70 (m, 2H), 7.64 (d, J = 9.2 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.39 (d, J = 9.2 Hz, 1H), 7.36 (s, 1H), 2.12 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.4, 154.4, 152.1, 146.2 (q, 3 J C-F = 2.1 Hz), 141.2 (q, 2 J C-F = 41.1 Hz), 135.2, 132.9, 129.0, 128.5, 127.0, 122.1, 120.4 (q, 1 J C-F = 256.4 Hz), 118.7 (q, 1 J C-F = 268.7 Hz), 117.9 (q, 3 J C-F = 2.2 Hz), 114.9, 113.5, 24.5. 19 F NMR (376 MHz, CDCl3 ): δ -58.37 (s), -62.98 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 19 H 11 F 6 NNaO 3 438.0535; Found 438.0530.

[0098] N-((6-Isopropyl-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4h): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.73 (d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.45 (s, 1H), 7.43 - 7.37 (m, 3H), 7.22 (d, J = 8.4 Hz, 1H), 3.10 - 3.00 (m, 1H), 2.09 (s, 3H), 1.31 (d, J = 7.2 Hz, 6H). 13 13C NMR (100 MHz, CDCl 3 ): δ 184.7, 155.3, 154.7, 150.2, 138.7 (q, 2 J C-F = 41.2 Hz), 135.7, 132.5, 128.8, 128.5, 124.3, 124.0, 121.7, 119.2 (q, 1 J C-F = 267.9 Hz), 117.6 (q, 3 J C-F = 2.9 Hz), 109.5, 34.5, 24.6, 24.1. 19 19F NMR (376 MHz, CDCl 3 ): δ -62.74 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 21 H 18 F 3 NNaO 2 396.1182; Found 396.1183.

[0099] N-((6-Fluoro-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide(4i): 1 H NMR(400 MHz,CDCl 3 ):δ7.72-7.70(m,2H),7.56-7.52(m,1H),7.47-7.41(m,3H),7.33(dd,J 1 =8.4 Hz,J 2 =2.4 Hz,1H),7.11(td,J 1 =8.8 Hz,J 2 =2.4 Hz,1H),2.11(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ184.6,162.8(d, 1 J C-F =247.7 Hz),154.6,154.2(d, 3 J C-F =13.8 Hz),139.9(q, 2 J C-F =41.2 Hz),135.4,132.8,128.9,128.5,123.2(d, 3 J C-F =10.2 Hz),122.5(d, 4 J C-F =2.1 Hz),118.8(q, 1 J C-F =268.7 Hz),117.7(q, 3 J C-F =1.5 Hz),114.0(d, 2 J C-F =24.6 Hz),100.0(d, 2 J C-F =26.8 Hz),24.5. 19 F NMR(376 MHz,CDCl 3 ):δ-62.88(s),-110.46--110.51(m).HRMS(ESI)m / z:[M+Na] + Calcd forC 18 H 11 F 4 NNaO 2 372.0618;Found 372.0617.

[0100] N-((7-Methyl-2-(trifluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4j): 1 H NMR (400 MHz, CDCl 3 ): δ 7.74 - 7.72 (m, 2H), 7.54 - 7.50 (m, 1H), 7.43 - 7.39 (m, 2H), 7.29 (d, J=7.2 Hz, 2H), 7.24 - 7.20 (m, 1H), 2.58 (s, 3H), 2.09 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.7, 155.3, 153.4, 139.0 (q, 2 J C-F =41.2 Hz), 135.6, 132.6, 128.9, 128.8, 128.5, 125.7, 125.0, 122.8, 119.2 (q, 1 J C-F =266.6 Hz), 119.4, 117.8 (q, 3 J C-F =2.1 Hz), 24.6, 14.9. 19 F NMR (376 MHz, CDCl 3 ): δ - 62.74 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 19 H 14 F 3 NNaO 2 368.0869;Found 368.0860.

[0101] N-(Phenyl(2-(trifluoromethyl)benzofuran-3-yl)methylene)propionamide (4k): 1 H NMR (400 MHz, CDCl 3 ): δ 7.73 - 7.71 (m, 2H), 7.62 - 7.60 (m, 1H), 7.55 - 7.49 (m, 3H), 7.44 - 7.40 (m, 2H), 7.36 - 7.32 (m, 1H), 2.37 (q, J=7.2 Hz, 2H), 1.01 (t, J=7.2 Hz, 3H). 13 C NMR (150 MHz, CDCl 3): δ 187.9, 155.3, 154.1, 139.4 (q, 2 J C-F = 40.5 Hz), 135.8, 132.5, 128.8, 128.5, 128.1, 126.2, 124.9, 122.2, 119.1 (q, 1 J C-F = 268.1 Hz), 117.9 (q, 3 J C-F = 2.3 Hz), 112.3, 30.6, 8.2. 19 19F NMR (376 MHz, CDCl 3 ): δ -62.77 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 14 F 3 NNaO 2 368.0869; Found 368.0868.

[0102] N-(Phenyl(2-(trifluoromethyl)benzofuran-3-yl)methylene)cyclohexanecarboxamide (4l): 1 1H NMR (600 MHz, CDCl 3 ): δ 7.73 - 7.71 (m, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.53 - 7.48 (m, 3H), 7.41 (t, J = 7.8 Hz, 2H), 7.33 (d, J = 7.8 Hz, 1H), 2.27 - 2.22 (m, 1H), 1.74 - 1.69 (m, 4H), 1.59 (br s, 1H), 1.39 - 1.34 (m, 2H), 1.21 - 1.14 (m, 3H). 13 13C NMR (100 MHz, CDCl 3 ): δ 189.9, 155.1, 154.0, 139.5 (q, 2 J C-F = 41.2 Hz), 136.0, 132.5, 128.8, 128.5, 128.0, 126.2, 124.8, 122.4, 119.1 (q, 1 J C-F = 268.0 Hz), 118.1 (q, 3 J C-F = 2.9 Hz), 112.2, 46.7, 28.9, 25.7, 25.5.19 F NMR (376 MHz, CDCl 3 ): δ -62.76 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 20 F 3 NNaO 2 422.1338; Found 422.1332. N-(p-Tolyl(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4m): Eluent: petroleum ether / ethyl acetate (30:1). Yellow liquid (42.1 mg, 61%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.62 - 7.59 (m, 3H), 7.52 - 7.47 (m, 2H), 7.32 (td, J 1 = 8.0 Hz, J 2 = 0.8 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H), 2.09 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.8, 154.8, 154.1, 143.5, 139.2 (q, 2 J C-F = 41.2 Hz), 133.0, 129.6, 128.6, 128.1, 126.2, 124.9, 122.2, 119.1 (q, 1 J C-F = 268.0 Hz), 117.9 (q, 3 J C-F = 2.9 Hz), 112.2, 24.6, 21.6. 19 F NMR (376 MHz, CDCl 3 ): δ -62.79 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 14 F 3 NNaO 2 368.0869; Found 368.0872.

[0103] N-((4-Methoxyphenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide(4n): 1 H NMR(400 MHz,CDCl 3 ):δ7.70-7.66(m,2H),7.61-7.59(m,1H),7.51-7.48(m,2H),7.35-7.31(m,1H),6.92-6.88(m,2H),3.84(s,3H),2.08(s,3H). 13 C NMR(100 MHz,CDCl 3 ):δ184.9,163.3,154.2,154.1,139.1(q, 2 J C-F =40.5 Hz),130.6,128.3,128.1,126.2,124.8,122.2,119.1(q, 1 J C-F =268.0 Hz),117.9(q, 3 J C-F =2.9 Hz),114.2,112.2,55.5,24.7. 19 F NMR(376 MHz,CDCl 3 ):δ-62.83(s).HRMS(ESI)m / z:[M+Na] + Calcd forC 19 H 14 F 3 NNaO 3 384.0818;Found384.0813.

[0104] N-((4-Fluorophenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide(4o): 1 H NMR(400 MHz,CDCl3):δ7.77-7.72(m,2H),7.62(d,J=8.8 Hz,1H),7.54-7.52(m,1H),7.49(d,J=7.6 Hz,1H),7.37-7.33(m,1H),7.13-7.07(m,2H),2.09(s,3H). 1313C NMR (100 MHz, CDCl3): δ 184.5, 165.5 (d, 1JC-F = 252.8 Hz), 154.2, 153.9, 139.2 (q, 2JC-F = 41.1 Hz), 131.9 (d, 4JC-F = 2.9 Hz), 130.9 (d, 3JC-F = 8.6 Hz), 128.3, 126.0, 125.0, 122.1, 119.0 (q, 1JC-F = 268.0 Hz), 117.3 (q, 3JC-F = 2.9 Hz), 116.1 (d, 2JC-F = 21.6 Hz), 112.4, 24.6. 19 19F NMR (376 MHz, CDCl 3 ): δ -62.84 (s), -105.82--105.89 (m). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 11 F 4 NNaO372.0618; Found 372.0624.

[0105] N-((3-Fluorophenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4p): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.63 (d, J = 8.8 Hz, 1H), 7.54-7.49 (m, 3H), 7.44-7.42 (m, 1H), 7.41-7.34 (m, 2H), 7.25-7.21 (m, 1H), 2.10 (s, 3H). 13 13C NMR (100 MHz, CDCl 3 ): δ 184.3, 163.0 (d, 1 J C-F = 246.3 Hz), 154.2, 154.1 (d, 4 J C-F = 2.9 Hz), 139.3 (q, 2 J C-F = 41.2 Hz), 137.9 (d, 3 J C-F = 7.2 Hz), 130.5 (d, 3 J C-F = 8.0 Hz), 128.3, 125.9, 125.1, 124.5 (d, 4 JC-F = 2.9 Hz), 122.0, 119.7 (d, 2 J C-F = 21.7 Hz), 119.0 (q, 1 J C-F = 259.7 Hz), 117.1 (q, 3 J C-F = 2.9 Hz), 115.0 (d, 2 J C-F = 23.1 Hz), 112.4, 24.5. 19 F NMR (376 MHz, CDCl 3 ): δ -62.84 (s), -111.50--111.56 (m). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 11 F 4 NNaO 2 372.0618; Found 372.0615.

[0106] N-((3-Bromophenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4q): 1 H NMR (400 MHz, CDCl 3 ): δ 7.98 (t, J = 1.6 Hz, 1H), 7.67 - 7.64 (m, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.56 - 7.48 (m, 3H), 7.38 - 7.34 (m, 1H), 7.28 (t, J = 8.0 Hz, 1H), 2.09 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.2, 154.2, 153.9, 139.3 (q, 2 J C-F = 41.9 Hz), 137.6, 135.6, 131.0, 130.4, 128.4, 127.4, 125.8, 125.1, 123.2, 122.0, 119.0 (q, 1 J C-F = 268.0 Hz), 116.9 (q, 3 J C-F = 2.1 Hz), 112.4, 24.5. 19 F NMR (376 MHz, CDCl 3): δ - 62.79 (s). HRMS(ESI) m / z: [M+Na] + Calcd for C 18 H 11 BrF 3 NNaO 2 431.9817; Found 431.9816.

[0107] N - ((3,5 - Dimethoxyphenyl)(2 - (trifluoromethyl)benzofuran - 3 - yl)methylene)acetamide(4r): 1 H NMR(400 MHz, CDCl 3 ): δ 7.60 (d, J = 8.8 Hz, 1H), 7.52 - 7.48 (m, 2H), 7.34 (t, J = 7.2 Hz, 1H), 6.86 (d, J = 2.4 Hz, 2H), 6.61 (t, J = 2.4 Hz, 1H), 3.78 (s, 6H), 2.09 (s, 3H). 13 C NMR(100 MHz, CDCl 3 ): δ 184.5, 161.0, 154.8, 154.1, 139.3 (q, 2 J C-F = 41.1 Hz), 137.6, 128.2, 126.1, 124.9, 122.2, 119.1 (q, 1 J C-F = 268.0 Hz), 117.6 (q, 3 J C-F = 2.1 Hz), 112.3, 106.6, 104.7, 55.5, 24.6. 19 F NMR(376 MHz, CDCl 3 ): δ - 62.77 (s). HRMS(ESI) m / z: [M+Na] + Calcd for C 20 H 16 F 3 NNaO 4 414.0924; Found 414.0931.

[0108] N - ((3,5 - Dichlorophenyl)(2 - (trifluoromethyl)benzofuran - 3 - yl)methylene)acetamide(4s): 1 H NMR(400 MHz, CDCl3 ): δ 7.64 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 2.0 Hz, 2H), 7.57 - 7.55 (m, 1H), 7.52 (t, J = 2.0 Hz, 1H), 7.50 (d, J = 7.6, 1H), 7.40 - 7.36 (m, 1H), 2.09 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 183.9, 154.2, 153.0, 139.4 (q, 2 J C-F = 41.2 Hz), 138.5, 135.9, 132.4, 128.6, 126.7, 125.6, 125.3, 121.9, 118.9 (q, 1 J C-F = 268.7 Hz), 116.3 (q, 3 J C-F = 2.9 Hz), 112.5, 24.4. 19 F NMR (376 MHz, CDCl 3 ): δ -62.78 (s). HRMS (ESI) m / z: [M + Na] + Calcd for C 18 H 10 Cl 2 F 3 NNaO 2 421.9933; Found 421.9925.

[0109] N-((2-Fluorophenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4t): 1 H NMR (400 MHz, CDCl 3 ): δ 7.66 (td, J 1 = 7.6 Hz, J 2 = 1.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.53 - 7.47 (m, 2H), 7.36 - 7.32 (m, 1H), 7.24 (td, J 1 = 7.6 Hz, J 2 = 0.8 Hz, 1H), 7.11 - 7.06 (m, 1H), 2.14 (s, 3H). 13 C NMR (100 MHz, CDCl 3): δ 183.7, 160.4 (d, 1 J C-F = 252.8 Hz), 154.0, 152.4, 140.4 (q, 2 J C-F = 41.2 Hz), 133.7 (d, 3 J C-F = 8.6 Hz), 130.5 (d, 4 J C-F = 1.5 Hz), 127.9, 125.5, 124.8, 124.6 (d, 3 J C-F = 3.6 Hz), 124.0 (d, 2 J C-F = 11.6 Hz), 122.2, 120.0 (q, 3 J C-F = 2.1 Hz), 119.0 (q, 1 J C-F = 268.0 Hz), 116.6 (d, 2 J C-F = 21.7 Hz), 112.2, 24.6. 19 F NMR (376 MHz, CDCl 3 ): δ -62.17 (s), -111.94 - 112.00 (m). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 11 F 4 NNaO 2 372.0618; Found 372.0624.

[0110] N-((2-Chlorophenyl)(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4u): 1 H NMR (400 MHz, CDCl 3 ): δ 7.59 (d, J = 8.4 Hz, 1H), 7.55 - 7.37 (m, 6H), 7.33 - 7.29 (m, 1H), 2.11 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 183.7, 155.2, 153.8, 142.5 (q, 2 J C-F= 41.9 Hz), 134.6, 131.9, 131.6, 131.0, 130.2, 127.7, 127.1, 125.5, 124.9, 122.6, 120.2 (q, 3 J C-F = 2.9 Hz), 119.0 (q, 1 J C-F = 268.7 Hz), 112.2, 24.7. 19 F NMR (376 MHz, CDCl 3 ): δ -61.19 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 18 H 11 ClF 3 NNaO 2 388.0323; Found 388.0326.

[0111] N-(Naphthalen-2-yl(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4v): 1 H NMR (400 MHz, CDCl 3 ): δ 8.06 (dd, J 1 = 8.4 Hz, J 2 = 2.0 Hz, 1H), 7.95 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.60 - 7.47 (m, 4H), 7.36 - 7.32 (m, 1H), 2.13 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.8, 155.0, 154.2, 139.4 (q, 2 J C-F = 41.9 Hz), 135.4, 133.2, 132.7, 130.9, 129.3, 128.9, 128.5, 128.2, 127.9, 126.9, 126.3, 125.0, 123.6, 122.3, 119.1 (q, 1 J C-F = 286.0 Hz), 117.6 (q, 3 J C-F = 2.1 Hz), 112.4, 24.7. 1919F NMR (376 MHz, CDCl 3 ): δ -62.76 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 14 F 3 NNaO 2 404.0869; Found 404.0862.

[0112] N-(Thiophen-3-yl(2-(trifluoromethyl)benzofuran-3-yl)methylene)acetamide (4w): 1 1H NMR (400 MHz, CDCl 3 ): δ 7.61 (d, J = 8.4 Hz, 1H), 7.56 - 7.49 (m, 4H), 7.38 (dd, J 1 = 5.2 Hz, J 2 = 3.2 Hz, 1H), 7.37 - 7.33 (m, 1H), 2.11 (s, 3H). 13 13C NMR (100 MHz, CDCl 3 ): δ 184.4, 154.1, 149.7, 139.9, 139.2 (q, 2 J C-F = 41.1 Hz), 132.3, 128.2, 127.2, 126.5, 125.9, 124.9, 122.2, 119.1 (q, 1 J C-F = 268.7 Hz), 118.3 (q, 3 J C-F = 2.9 Hz), 112.3, 24.7. 19 19F NMR (376 MHz, CDCl 3 ): δ -62.66 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 16 H 10 F 3 NNaO 2 S 360.0277; Found 360.0276.

[0113] N-((2-(Difluoromethyl)benzofuran-3-yl)(phenyl)methylene)acetamide (4x): 1 1H NMR (400 MHz, CDCl3 ): δ 7.68 - 7.66 (m, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.56 - 7.53 (m, 1H), 7.47 - 7.42 (m, 3H), 7.35 (d, J = 7.6 Hz, 1H), 7.29 - 7.25 (m, 1H), 6.70 (t, J = 52.4 Hz, 1H), 2.05 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 184.8, 156.2, 154.3, 146.7 (t, 2 J C-F = 25.3 Hz), 135.7, 132.3, 129.0, 128.5, 127.3, 125.9, 124.5, 121.9, 117.6 (t, 3 J C-F = 5.0 Hz), 112.3, 107.8 (t, 1 J C-F = 236.9 Hz), 24.9. 19 F NMR (565 MHz, CDCl 3 ): δ -116.84 (dd, J 1 = 98.3 Hz, J 2 = 50.9 Hz). HRMS (ESI) m / z: [M + Na] + Calcd for C 18 H 13 F 2 NNaO 2 336.0807; Found 336.0798.

[0114] N - ((2 - (1,1 - Difluoroethyl)benzofuran - 3 - yl)(phenyl)methylene)acetamide (4y): 1 H NMR (400 MHz, CDCl 3 ): δ 7.76 - 7.74 (m, 2H), 7.57 - 7.55 (m, 1H), 7.52 - 7.48 (m, 1H), 7.44 - 7.38 (m, 4H), 7.30 - 7.26 (m, 1H), 2.09 - 1.99 (m, 6H). 13 C NMR (100 MHz, CDCl 3 ): δ 185.3, 156.5, 153.9, 146.8 (t, 2 J C-F= 35.4 Hz), 136.2, 132.3, 128.7, 128.6, 126.9, 126.8, 124.4, 121.4, 117.8 (t, 1 J C-F = 235.5 Hz), 114.1 (t, 3 J C-F = 2.1 Hz), 112.0, 24.7, 23.6 (t, 2 J C-F = 26.7 Hz). 19 F NMR (376 MHz, CDCl 3 ): δ -87.74 (q, J = 17.7 Hz). HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 15 F 2 NNaO 2 350.0963; Found 350.0955.

[0115] Example 5

[0116] The products fluoromethyl-substituted 2H-benzopyran and benzofuran compounds 3 and 4 synthesized in the present invention were subjected to a series of reactions to synthesize further derivatives. For example:

[0117]

[0118] 3a (69.9 mg, 0.2 mmol) and 98% sulfuric acid (2.0 mL) were added to a reaction tube equipped with a stir bar. After the reaction tube was sealed, the mixture was stirred and reacted in an air atmosphere at 45 °C for 6 hours. Saturated Na 2 CO 3 aqueous solution was added to quench the reaction, and then the reaction system was extracted three times with ethyl acetate. The organic layers were combined, dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. Purification by silica gel column chromatography using petroleum ether / ethyl acetate (5:1) as the eluent gave the white solid product 5 (53.5 mg, 87%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.48 - 7.46 (m, 2H), 7.41 (d, J = 7.6 Hz, 1H), 7.38 - 7.25 (m, 2H), 7.06 - 7.02 (m, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.86 - 6.82 (m, 1H), 6.61 (dd, J 1 = 7.6 Hz, J 2= 1.2 Hz, 1H), 4.16 (br s, 1H), 3.67 (br s, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 147.6, 133.9, 130.3, 130.2, 130.15, 130.10, 129.5, 128.2, 128.1, 126.2, 123.8, 122.5, 122.4 (q, 1 J C-F = 290.3 Hz), 115.1, 112.2, 94.7 (q, 2 J C-F = 33.2 Hz). 19 F NMR (376 MHz, CDCl 3 ): δ -83.32 (s). HRMS (ESI) m / z: [M+Na] + Calcd for C 16 H 12 F 3 NNaO 2 330.0712; Found 330.0714.

[0119]

[0120] To a 15 mL pressure-resistant tube were successively added 4a (68.8 mg, 0.21 mmol), toluene (2.0 mL) and Lawesson's reagent (64.7 mg, 0.16 mmol), and then the mixture was stirred in an air atmosphere at 100 °C for 12 hours. After completion, it was filtered through diatomaceous earth, the filtrate was concentrated under reduced pressure, purified by silica gel column chromatography using petroleum ether as the eluent, and a yellow solid product 6 (29.2 mg, 40%) was obtained. 1 H NMR (600 MHz, CDCl 3 ): δ 7.52 - 7.51 (m, 2H), 7.45 - 7.41 (m, 3H), 7.15 - 7.13 (m, 1H), 6.92 - 6.90 (m, 2H), 6.71 (t, J = 7.8 Hz, 1H), 2.44 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ): δ 158.4, 152.3, 141.1, 136.3, 129.6, 128.7, 128.2, 127.8, 122.4 (q, 1 J C-F = 285.5 Hz), 122.1, 121.8, 121.5, 109.7, 107.1, 88.0 (q, 2 J C-F= 33.9 Hz), 26.1. 19 F NMR (565 MHz, CDCl 3 ): δ -85.72 (s). HRMS (ESI) m / z: [M+H] + Calcd for C 18 H 13 F 3 NOS 348.0664; Found 348.0673.

[0121]

[0122] 4a (76.2 mg, 0.23 mmol) and dilute HCl (2.0 mL) were added to a reaction flask equipped with a stir bar, and the resulting mixture was stirred at room temperature for 0.5 h. Then the reaction was quenched with saturated NaHCO 3 aqueous solution, and the reaction system was extracted three times with ethyl acetate. The organic layers were combined, dried over anhydrous Na 2 SO 4 and filtered and concentrated under reduced pressure. Purification by silica gel column chromatography with petroleum ether / ethyl acetate (5:1) as the eluent gave the yellow liquid product 7 (61.4 mg, 92%). 1 HNMR (400 MHz, CDCl 3 ): δ 7.84 - 7.81 (m, 2H), 7.58 - 7.54 (m, 2H), 7.44 - 7.39 (m, 3H), 7.37 (d, J = 8.0 Hz, 1H), 7.26 - 7.22 (m, 1H). 13 CNMR (150 MHz, CDCl 3 ): δ 188.8, 154.0, 141.6 (q, 2 J C-F = 42.6 Hz), 137.0, 134.4, 129.7, 128.8, 127.9, 125.8, 124.8, 122.2, 121.8 (q, 3 J C-F = 2.3 Hz), 119.1 (q, 1 J C-F = 268.1 Hz), 112.2. 19 FNMR (376 MHz, CDCl 3 ): δ -62.12 (s). HRS (ESI) m / z: [M+Na] + Calcd for C 16 H 9 F 3 Na O 2 313.0447; Found 313.0448.

[0123]

[0124] Compound 7 (123.3 mg, 0.42 mmol), PhNHNH 2 (45.4 mg, 0.42 mmol) and ethanol (2.0 mL) were added to a reaction flask under stirring, and then the mixture was stirred and refluxed in an oil bath for 12 h. After completion, it was concentrated under reduced pressure and purified by silica gel column chromatography with petroleum ether / ethyl acetate (3:1) as the eluent to obtain the white solid product 8 (108.8 mg, 68%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.30 (s, 5H), 7.22 - 7.17 (m, 2H), 7.16 - 7.12 (m, 3H), 7.04 - 7.02 (m, 2H), 6.86 (t, J = 7.2 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 5.16 (s, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 153.9, 143.6, 142.1 (q, 2 J C-F = 36.1 Hz), 141.5, 139.1, 130.1, 129.6, 129.14, 129.09, 128.6, 128.5, 128.2, 125.4, 121.4 (q, 1 J C-F = 269.4 Hz), 120.5, 116.8, 115.6, 115.4. 19 FNMR (376 MHz, CDCl 3 ): δ -60.74 (s). HRMS (ESI) m / z: [M + H] + Calcd for C 22 H 16 F 3 N 2 O 381.1209; Found 381.1211.

[0125] Example 6

[0126] The anti-cancer activity of the compounds provided by the present invention was evaluated by studying the anti-proliferation activity of cancer cells using the CCK-8 method. The specific method was as follows: First, DU145 or Hela cells were seeded into a 96-well plate containing 100 μL of medium at a density of 4000 cells per well and incubated at 37 °C and 5% CO 2Incubate overnight in the environment. After the cells adhered to the wall the next day, add 50 μL of the test compound diluted with the culture medium (concentration: 0.78 μM - 50 μM) to each well. Then, incubate the cells at 37 °C and 5% CO 2 environment for 48 hours. Then, add 10 μL of CCK8 to each well, and place the 96-well plate at 37 °C and 5% CO 2 environment for 1.5 hours. Measure the absorbance at 450 nm (using 630 nm as the reference wavelength) with a multi-functional microplate reader (Perkinermer), and calculate the IC 50 value using GraphPad Prism 6.0 software. All experiments are performed with two parallel samples and repeated twice. Use 5-fluorouracil (5-FU) as the positive control of the drug.

[0127] The anti-cancer activity results of the representative compounds are as follows:

[0128]

[0129] The activity results show that the fluoromethyl-substituted 2H-benzopyran compound 3 and the fluoromethyl-substituted benzofuran compound 4 provided by the present invention can inhibit the proliferation activities of two cancer cells, DU145 and Hela. Among them, 3q, 3s, and 4r have significant anti-DU145 cancer cell proliferation activities; compounds 3s, 4e, and 4r have significant effects on inhibiting the proliferation of Hela cancer cells, suggesting that this type of compound has medicinal value for preventing / treating / inhibiting the progression of cancer, especially prostate cancer and cervical cancer.

[0130] The above embodiments describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. Fluoromethyl substituted 2H-benzopyran compounds and fluoromethyl substituted benzofuran compounds, the general structural formulas of which are: in: R 1 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, phenyl, C 1-4 Alkoxycarbonyl, trifluoromethoxy or halogen; R 2 C 1-6 Chain alkyl, halogenated C 1-6 Chain alkyl, phenoxy C 1-6 Chain alkyl or C 3-6 Cyclic alkyl; R 3 is naphthyl, thienyl, phenyl or substituted phenyl, and the substituent on the phenyl ring of the substituted phenyl is a mono- or poly-substituted C 1-4 Alkyl, C 1-4 Alkoxy, amino, methylamino, dimethylamino or halogen; R 4 is hydrogen, fluorine or methyl; R 5 is hydrogen, fluorine or methyl.

2. The fluoromethyl-substituted 2H-benzopyran compound and the fluoromethyl-substituted benzofuran compound according to claim 1, characterized in that: Fluoromethyl substituted 2H-benzopyran compounds are Fluoromethyl substituted benzofuran compounds are 3. Use of the fluoromethyl substituted 2H-benzopyran compounds and fluoromethyl substituted benzofuran compounds as claimed in claim 1 or 2 in the preparation of drugs for treating cervical cancer and / or prostate cancer.

4. The use of the fluoromethyl substituted 2H-benzopyran compound and the fluoromethyl substituted benzofuran compound according to claim 3 in the preparation of an anti-cervical cancer and / or prostate cancer drug, characterized in that: The anti-cervical cancer effect is to inhibit the growth and proliferation of Hela, and the anti-prostate cancer effect is to inhibit the growth and proliferation of DU145.

5. A pharmaceutical composition for treating cervical cancer and / or prostate cancer, wherein the active ingredient comprises the fluoromethyl substituted 2H-benzopyran compound and / or the fluoromethyl substituted benzofuran compound as claimed in claim 1 or 2.

6. The method for synthesizing fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds as claimed in claim 1, characterized in that: The reaction equation is shown as follows: Where: R 1 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, phenyl, C 1-4 Alkoxycarbonyl, trifluoromethoxy or halogen; R 2 C 1-6 Chain alkyl, halogenated C 1-6 Chain alkyl, phenoxy C 1-6 Chain alkyl or C 3-6 Cyclic alkyl; R 3 is naphthyl, thienyl, phenyl or substituted phenyl, and the substituent on the phenyl ring of the substituted phenyl is a mono- or poly-substituted C 1-4 Alkyl, C 1-4 Alkoxy, amino, methylamino, dimethylamino or halogen; R 4 is hydrogen, fluorine or methyl; R 5 is hydrogen, fluorine or methyl; comprising the following steps: using an N-aryloxyamide compound 1 and a fluoromethyl alkynyl ketone compound 2 as raw materials, reacting in the presence of a catalyst, an additive and an organic solvent to obtain a fluoromethyl substituted 2H-benzopyran compound 3; reacting in the presence of an additive and dimethyl sulfoxide to obtain a fluoromethyl substituted benzofuran compound 4.

7. The method for synthesizing fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds according to claim 6, characterized in that: The catalyst is tris(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III)di(hexafluoroantimonate) or dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer.

8. The method for synthesizing fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds according to claim 6, characterized in that: The additive is selected from acetate or a mixture of acetate and silver bis(trifluoromethanesulfonyl)imide, silver hexafluoroantimonate or silver tetrafluoroborate; the acetate is selected from copper acetate, zinc acetate, sodium acetate, silver acetate, potassium acetate or cesium acetate.

9. The method for synthesizing fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds according to claim 6, characterized in that: The molar ratio of the N-aryloxyamide compound 1, the fluoromethyl alkynyl ketone compound 2, the catalyst and the additive is 1:1-3:0.03-0.06:0.5-1.

1.

10. The method for synthesizing fluoromethyl-substituted 2H-benzopyran compounds and fluoromethyl-substituted benzofuran compounds according to claim 6, characterized in that: The organic solvent is selected from methanol, toluene or 1,4-dioxane; the reaction temperature is 20-80° C.; and the reaction is carried out under air atmosphere.

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