2-aryl-3-trifluoroethyl indole compounds, processes for their preparation and use

Abstract

The application discloses a 2-aryl-3-trifluoroethyl indole compound with a structure as shown in formula A and a preparation method and application thereof. 3 The target object A is obtained through the reaction of the aromatic aldehyde, the azacyclic carbene (NHC) and the o-amino styrene, 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1 lambda The 2-aryl-3-trifluoroethyl indole compound disclosed by the application has excellent antibacterial activity, is a novel material with a novel structure, raw materials are easy to obtain, reaction conditions are mild, green and environment-friendly, and operation is simple.

Description

Technical Field

[0001] This invention belongs to the fields of compound technology and medicinal chemistry, specifically a 2-aryl-3-trifluoroethylindole compound, its preparation method, and its application. Background Technology

[0002] The indole skeleton is widely found in natural products and synthetic drugs, and related studies have shown that compounds containing the indole skeleton possess a variety of important biological activities and pharmacological effects. Trifluoromethyl groups are also present in many drug molecules. However, there is limited research on substances that simultaneously possess both indole rings and trifluoromethyl groups. Studies have shown that combining these two skeleton structures in the same molecule yields novel substances with certain antibacterial activity, which can be used as drugs or drug lead compounds. Summary of the Invention

[0003] The purpose of this invention is to provide a novel 2-aryl-3-trifluoroethylindole compound, its preparation method, and its applications, the structure of which is shown in Formula A:

[0004]

[0005] In the above chemical structural formula: R 1 Selected from any one of the atoms or groups of hydrogen, fluorine, chlorine, and methyl; R 2 It is selected from any one of the following groups: phenyl and substituted phenyl, thiophene, pyrazolyl, imidazolyl, pyridinyl, pyrazinyl, indolyl, and quinoxalinyl.

[0006] This invention provides a method for preparing the above-described compound of formula A:

[0007]

[0008] Take o-aminostyrene (B), aromatic aldehyde (C), and 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1λ. 3 -Benzo[1,2]iodooxacyclopentene (D) was dissolved in an organic solvent under the protection of an inert gas using a nitrogen-heterocyclic carbene (NHC) as a catalyst, and then a base was added and post-treated to obtain A;

[0009] Furthermore, the molar ratio of compound (B) to compound (C) is 5:1-1:5, a more preferred ratio is 3:1-1:3, and a more preferred ratio is 1:1.5;

[0010] Furthermore, the reaction temperature is 0℃-100℃, preferably 55℃-60℃;

[0011] Furthermore, the base used is one or more of the following: triethylamine (TEA), diisopropylethylamine (DIPEA), DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), DABCO (1,4-diazabicyclo[2,2,2]octane), sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, and potassium phosphate; preferably potassium carbonate and / or DABCO.

[0012] Furthermore, the inert gas used is one or more of nitrogen and argon; argon is preferred.

[0013] Furthermore, the reaction time is 8-16 hours, with 11-13 hours being preferred;

[0014] Furthermore, the 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1λ used 3 The amount of benzo[1,2]iodooxacyclopentene (D) is 1-3 eq, with a preferred amount of 1.5 eq;

[0015] Furthermore, the amount of alkali used is 1-3 eq, with a preferred amount being 1.5 eq;

[0016] Furthermore, the organic solvent used is one or more of acetonitrile, dichloromethane, chloroform, toluene, acetone, dimethyl sulfoxide, and 1,2-dichloroethane, with acetone being preferred.

[0017] Furthermore, based on the above preparation method, the present invention provides compounds with the following structures:

[0018]

[0019]

[0020] This invention also provides the application of compound A as an antibacterial active substance.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] This invention yields a new compound with a 2-aryl-3-trifluoroethylindole skeleton structure. Experimental results show that most of these new compounds have certain antibacterial activity. Detailed Implementation

[0023] The technical solution of the present invention will be further described in detail below through specific embodiments, but the present invention is not limited to these embodiments. All reagents used in the present invention are commercially available; unless otherwise specified, they are all produced using existing technology or under natural conditions of room temperature and pressure.

[0024] Example 1. Preparation of compound A

[0025] Add 0.15 mmol of compound C (aromatic aldehyde) and compound D (3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1λ) to a dry Schlenk test tube. 3 0.15 mmol of benzo[1,2]iodooxetine, 0.02 mmol of thiazole-type nitrogen-containing heterocyclic carbene catalyst (NHC), and 0.15 mmol of potassium carbonate were added. Subsequently, 0.1 mmol of compound B (o-aminostyrene) was dissolved in 1 mL of acetone and injected into a Schlenk tube under argon protection. The reaction was then stirred at 60 °C for 12 h. After the reaction was completed by TLC, the product was concentrated under reduced pressure and then purified by silica gel column chromatography with petroleum ether:dichloromethane = 5:1-3:1 as the eluent. The product was collected, concentrated, and dried to obtain the target compound A.

[0026] The following compounds were prepared according to the method in Example 1:

[0027] Compound 1: 2-Phenyl-3-(2,2,2-trifluoroethyl)-1H-indole

[0028]

[0029] White solid, yield: 66%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.21 (s, 1H), 7.70 (d, J = 7.8Hz, 1H), 7.58 (d, J = 6.6Hz, 2H), 7.53-7.50 (m, 2H), 7.4 5(t,J=6.6Hz,1H),7.41(d,J=7.2Hz,1H),7.27(t,J=6.6Hz,1H),7.22(t,J=6.6Hz,1H),3.62(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 137.8, 135.6, 132.0, 130.1, 129.0, 128.8, 128.5, 126 .6(q,J=271.8Hz,1C),122.8,120.4,119.5,110.9,101.8,30.2(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.79 (t, J = 8.5Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 16 H 12 F3NH + :276.0995,found276.1001.

[0030] Compound 2: 2-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0031]

[0032] White solid, yield 76%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.18 (s, 1H), 7.67 (d, J = 7.8Hz, 1H), 7.56-7.53 (m, 2H), 7.41(d,J=8.4Hz,1H),7.28-7.25(m,1H),7.22-7.19(m,3H),3.57(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 162.9 (d, J = 241.6Hz, 1C), 136.9, 135.5, 130.4 (d, J = 9.1Hz, 1C), 128.7, 128.1, 1 26.6(q,J=286.9Hz,1C),122.9,120.5,119.5,116.1(d,J=30.2Hz,1C),110.9,102.0,30.2(q,J=30.2Hz,1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-64.88(t,J=10.7Hz,3F),-111.45--111.50(m,1F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 11 F4NH + :294.0900,found:294.0898.

[0033] Compound 3: 2-(4-bromophenyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0034]

[0035] Yellow solid, yield: 97%. 1H NMR (600MHz, CDCl3) δ (ppm): 8.19 (s, 1H), 7.68 (d, J = 7.8Hz, 1H), 7.65 (s, 1H), 7.64 (s, 1H), 7.45 (s, 1H), 7.44(s,1H),7.41(d,J=8.4Hz,1H),7.28(t,J=7.2Hz,1H),7.22(t,J=6.6Hz,1H),3.58(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 136.5, 135.7, 132.2, 130.9, 123.0, 128.7, 126.5, (q, J=271.8Hz,1C),123.1,122.9,120.6,119.5,110.9,102.3,30.2(q,J=30.2Hz,1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-64.82(t,J=10.7Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 17 79 BrF3NH + :354.0100, found:354.0105; calculated for C 16 H 17 81 BrF3NH + :356.0079,found:356.0072.

[0036] Compound 4: 3-(2,2,2-trifluoroethyl)-2-(4-(trifluoromethyl)phenyl)-1H-indole

[0037]

[0038] Transparent semi-solid, yield: 78%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.26 (s, 1H), 7.77 (d, J = 8.4Hz, 2H), 7.71-7.64 (m, 3H), 7.4 4(d,J=7.8Hz,1H),7.30(t,J=8.4Hz,1H),7.23(t,J=6.6Hz,1H),3.61(q,J=10.2Hz,2H). 13C NMR (151MHz, CDCl3) δ (ppm): 135.9 (q, J = 30.2Hz, 1C), 135.6, 130.4, 128.7, 126.4 (q, J = 271.8Hz, 1C) ,126.03(q,J=30.2Hz,1C),124.8,123.5,123.0,120.8,119.7,111.0,103.1,30.2(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -63.01 (s, 3F), -64.78 (t, J = 10.8Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + calculated for C 17 H 11 F6NH + :344.0868,found:344.0864.

[0039] Compound 5: Methyl 4-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)benzoate

[0040]

[0041] Pale yellow solid, yield: 90%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.48 (s, 1H), 8.15 (d, J = 8.4Hz, 2H), 7.70 (d, J = 7.8Hz, 1H), 7.65 (d, J = 7.8Hz, 2H ),7.43(d,J=7.2Hz,1H),7.29(t,J=8.4Hz,1H),7.23(t,J=7.8Hz,1H),3.96(s,3H),3.63(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 166.7, 136.4, 135.9, 130.2, 129.7, 128.8, 128.2, 126.5 (q, J =286.9Hz, 1C), 123.3, 120.6, 119.6, 111.1, 102.89, 102.87, 52.3, 30.2 (q, J = 30.2Hz, 1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.75 (t, J=11.3Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 18 H14 F3NO2H + :334.1050; found:334.1060.

[0042] Compound 6: 2-(4-methoxyphenyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0043]

[0044] Yellow solid, yield: 80%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.17 (s, 1H), 7.67 (d, J = 7.2Hz, 1H), 7.50 (d, J = 9.0Hz, 2H), 7.39 (d, J = 7.8Hz, 1H ),7.25(t,J=6.6Hz,1H),7.20(t,J=7.2Hz,1H),7.04(d,J=9.0Hz,2H),3.88(s,3H),3.58(q,J=10.8Hz,2H). 13 C NMR-(151MHz, CDCl3) δ (ppm): 159.8, 137.8, 135.4, 129.8, 128.8, 126.7 (q, J=286.9Hz ,1C),124.3,122.5,120.3,119.3,114.4,110.8,101.1,55.4,30.2(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.83, (t, J=8.5Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + calculated for C 17 H 14 F3NOH + :306.1100,found:306.1095.

[0045] Compound 7: N,N-dimethyl-4-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)aniline

[0046]

[0047] Yellow solid, yield: 60%. 1 H NMR (600MHz, CDCl) 3)δ(ppm):8.11(s,1H),7.67(d,J=6.6Hz,1H),7.46(d,J=7.8Hz,2H),7.37(d,J=7.2Hz ,1H),7.26-7.19(m,2H),6.84(d,J=7.2Hz,2H),3.62(q,J=10.2Hz,2H),3.04(s,6H). 13 C NMR (151MHz, CDCl3) δ (ppm): 150.4, 138.7, 135.4, 129.3, 129.1, 126.8 (q, J = 271.8Hz ,1C),122.1,120.1,119.6,119.1,112.4,110.6,100.4,40.3,30.3(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.74 (t, J = 11.3Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 18 H 17 F3N2H + :319.1417,found:319.1420.

[0048] Compound 8: 3-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)benzonitrile

[0049]

[0050] White solid, yield: 60%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.34 (s, 1H), 7.85 (s, 1H), 7.84-7.82 (m, 1H), 7.73-7.72 (m, 1H), 7.69 (d, J = 8.4Hz, 1H) ,7.63(t,J=8.4Hz,1H),7.44(d,J=7.2Hz,1H),7.31(t,J=8.4Hz,1H),7.24(t,J=8.4Hz,1H),3.59(q,J=10.8Hz,2H). 13 C NMR(151MHz,CDCl3)δ(ppm):135.9,135.0,133.5,132.7,131.8,131.8,130.0,128.6,126.3( q,J=271.8Hz,1C),123.6,120.9,119.7,118.2,113.4,111.1,103.2,30.1(q,J=30.2Hz,1C).19 F NMR (565MHz, CDCl3) δ (ppm): -64.85 (t, J = 8.5Hz, 3F). HRMS (ESI-TOF) m / z: [M+Na] + Calculated for C 17 H 11 F3N2Na + :323.0767,found:323.0770.

[0051] Compound 9: 2-Methoxy-6-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)phenol

[0052]

[0053] Yellow solid, 45% 1 H NMR (600MHz, CDCl3) δ (ppm): 8.74 (s, 1H), 7.69 (d, J = 7.8Hz, 1H), 7.40 (d, J = 7.8Hz, 1H), 7.25 (t, J = 7.8Hz, 1H), 7. 20-7.16(m,2H),6.99(t,J=8.4Hz,1H),6.95(d,J=7.8Hz,1H),6.08(s,1H),3.97(s,3H),3.68(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 146.9, 143.3, 135.6, 133.8, 128.4, 126.7 (q, J = 271.8Hz, 1C), 1 22.6,122.5,120.2,120.0,119.2,117.8,110.9,110.7,102.7,56.2,30.4(q,J=30.2Hz,1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-64.78(t,J=10.7Hz,1H).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 17 H 14 F3N2O2H + :322.1049,found:322.1059.

[0054] Compound 10: 2-bromo-6-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)phenol

[0055]

[0056] Yellow solid, yield: 99%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.52 (s, 1H), 7.71 (d, J = 7.8Hz, 1H), 7.58 (dd, J = 7.8, 1.4Hz, 1H), 7.45 (dd, J = 7.2, 1.4Hz, 1H), 7. 41(d,J=8.4Hz,1H),7.28(t,J=6.0Hz,1H),7.22(t,J=6.6Hz,1H),6.96(t,J=7.8Hz,1H),5.85(s,1H),3.60(q,J=11.4Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 149.9, 135.7, 132.9, 132.8, 130.7, 128.1, 126.5 (q, J = 271.8 Hz, 1C), 123.0, 122.0, 120.4, 119.6, 119.4, 111.3, 111.0, 103.6, 30.3 (q, J = 30.2Hz, 1C). 19 FNMR(565MHz, CDCl3)δ(ppm):-64.89(t,J=10.7Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 11 79 BrF3NOH + :370.0049, found:370.0043; calculated for C 16 H 11 81 BrF3NOH + :372.0028,found:372.0029.

[0057] Compound 11: 5-chloro-2-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)phenol

[0058]

[0059] Pale yellow solid, yield: 81%. 1H NMR (600MHz, CDCl3) δ (ppm): 8.28 (s, 1H), 7.70 (d, J = 8.4Hz, 1H), 7.40 (d, J = 7.8Hz, 1H), 7.31 -7.29(m,2H),7.24(t,J=7.2Hz,1H),7.05-7.04(m,2H),5.57(s,1H),3.50(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 154.4, 136.2, 136.1, 131.8, 131.5, 128.2, 124.4 (q, J=28 6.9Hz, 1C), 123.4, 121.3, 120.8, 119.5, 116.6, 111.2, 104.8, 30.1 (q, J = 30.2Hz, 1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-66.20(t,J=11.3Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 11 35 ClF3NOH + :326.0554,found:326.0546.

[0060] Compound 12: 2-(3,4-dichlorophenyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0061]

[0062] Yellow solid, yield: 52%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.19 (s, 1H), 7.68 (d, J = 8.4Hz, 1H), 7.66 (s, 1H), 7.58 (d, J = 7.8Hz ,1H),7.43-7.40(m,2H),7.29(t,J=7.2Hz,1H),7.23(t,J=7.8Hz,1H),3.59(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 135.8, 135.1, 133.3, 132.9, 132.0, 131.1, 130.2, 128.7, 127 .6,126.4(q,J=286.9Hz,1C),123.4,120.8,119.7,111.0,103.0,30.1(q,J=30.2Hz,1C).19 F NMR (565MHz, CDCl3) δ (ppm): -64.83 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+Na] + Calculated for C 16 H 10 35 Cl 37 ClF3NNa + :366.0035,found:366.0034; calculated for C 16 H 10 37 Cl2F3NNa + :368.0005, found:368.0003; calculated for C 16 H 10 35 Cl2F3NH + :348.0156,found:348.0152.

[0063] Compound 13: 2-Methoxy-5-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)phenol

[0064]

[0065] Yellow solid, yield: 45% 1 H NMR (600MHz, CDCl3) δ (ppm): 8.15 (s, 1H), 7.66 (d, J = 8.4Hz, 1H), 7.39 (d, J = 8.4Hz, 1H), 7.26-7.22 (m, 1H), 7.20-7.1 8(m,1H),7.14-7.12(m,1H),7.09-7.07(m,1H),6.98-6.97(m,1H),5.74(s,1H),3.97(s,3H),3.61(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 146.9, 146.0, 137.7, 135.4, 128.9, 126.7 (q, J = 271.8Hz, 1C), 1 25.3,122.5,120.6,120.3,119.3,114.6,111.0,110.8,101.3,56.0,30.2(q,J=30.2Hz,1C). 19F NMR (565MHz, CDCl3) δ (ppm): -64.79 (t, J = 10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 14 H 17 F3N1O2H + :322.1049,found:322.1046.

[0066] Compound 14: 2-(2-thienyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0067]

[0068] Pale yellow solid, yield: 91%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.24 (s, 1H), 7.65 (d, J = 7.2Hz, 1H), 7.44 (d, J = 6.0Hz, 1H), 7.39 (d, J = 8.4Hz, 1H), 7.3 2(d,J=3.6Hz,1H),7.28-7.26(m,1H),7.21(t,J=7.2Hz,1H),7.18(dd,J=4.2,3.6Hz,1H),3.70(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 135.6, 133.1, 131.3, 128.9, 128.0, 126.5 (q, J = 271.8 Hz, 1C), 126.4, 126.3, 123.2, 120.6, 119.3, 110.8, 102.6, 30.4 (q, J = 30.2Hz, 1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.96 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + calculated for C 14 H 10 F3NSH + :282.0559,found:282.0554.

[0069] Compound 15: 2-(1H-3-pyrazolyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0070]

[0071] White solid, yield: 76%.1 H NMR (600MHz, CDCl3) δ (ppm): 9.29 (s, 1H), 8.98-8.97 (m, 2H), 8.57 (s, 1H), 7.71 (d, J = 8.4Hz, 1H),7.46(d,J=8.4Hz,1H),7.33(t,J=8.4Hz,1H),7.27-7.24(m,1H),3.59(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 158.1, 156.0, 136.4, 130.3, 128.5, 126.7, 126.1 ( q,J=271.8Hz,1C),124.0,121.1,119.8,111.3,104.7,30.1(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -65.03 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+Na] + Calculated for C 13 H 10 F3N3Na + :288.0719,found:288.0728.

[0072] Compound 16: 2-(1H-5-imidazolyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0073]

[0074] Brown semi-solid, yield: 75%. 1 H NMR (600MHz, CDCl3) δ (ppm): 9.29 (s, 1H), 7.78 (s, 1H), 7.60 (d, J = 7.2Hz, 1H), 7.39 -7.38(m,2H),7.21(t,J=7.2Hz,1H),7.16(t,J=8.4Hz,1H),3.69(q,J=10.8Hz,2H). 13 C NMR (151MHz, DMSO-d) 6 )δ(ppm):136.1,135.5,133.7,132.4,129.0,127.5(q,J=286.9Hz,1C),121.2,119.0,118.2,113.9,110.9,98.2,28.9(q,J=30.2Hz,1C). 19FNMR(565MHz, CDCl3)δ(ppm):-65.27(t,J=11.3Hz,3F).HRMS(ESI-TOF)m / z:[M+Na] + Calculated for C 13 H 10 F3N3Na + :288.2284,found:288.2286.

[0075] Compound 17: 2-(2-pyridyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0076]

[0077] White solid, yield: 78%. 1 H NMR (600MHz, CDCl3) δ (ppm): 9.69 (s, 1H), 8.68 (d, J = 4.8Hz, 1H), 7.83-7.79 (m, 2H), 7.67 (d, J = 7. 8Hz,1H),7.42(d,J=7.8Hz,1H),7.29-7.25(m,2H),7.19(t,J=7.8Hz,1H),3.91(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 149.8, 149.7, 137.0, 135.2, 134.9, 129.7, 126.6 (q, J=28 6.9Hz, 1C), 123.7, 122.4, 120.9, 120.3, 119.4, 111.3, 102.6, 30.5 (q, J = 30.2Hz, 1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-64.90--64.95(m,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 15 H 11 F3N2H + :277.0947,found:277.0947.

[0078] Compound 18: 2-(2-pyrazinyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0079]

[0080] White solid, yield: 82%. 1H NMR (600MHz, CDCl3) δ (ppm): 9.49 (s, 1H), 9.12 (s, 1H), 8.62-8.61 (m, 1H), 8.51 (d, J = 1.8Hz, 1H), 7.69 (d, J=8.4Hz,1H),7.44(d,J=8.4Hz,1H),7.31(t,J=6.6Hz,1H),7.21(t,J=7.2Hz,1H),3.96(q,J=10.2Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 146.1, 144.1, 142.8, 141.9, 135.8, 131.9, 129.6, 126 .3(q,J=286.9Hz,1C),124.5,120.8,119.7,111.4,104.6,30.5(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -65.08 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 14 H 10 F3N3H + :278.0900,found:278.0908.

[0081] Compound 19: 3-(2,2,2-trifluoroethyl)-1H,1'H-2,2'-biindole

[0082]

[0083] Brown solid, yield: 97%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.36 (s, 1H), 8.29 (s, 1H), 7.70 (d, J = 8.4Hz, 1H), 7.67 (d, J = 7.8Hz, 1H), 7.47 (d, J = 8.4Hz, 1H), 7. 42(d,J=8.4Hz,1H),7.29(q,J=6.6Hz,2H),7.24(t,J=8.4Hz,1H),7.21(t,J=7.2Hz,1H),6.79(s,1H),3.73(q,J=11.4Hz,2H). 13C NMR (151MHz, CDCl3) δ (ppm): 136.9, 135.8, 130.1, 129.2, 129.0, 128.6, 126.7 (q, J = 286.9Hz, 1C),123.4,123.1,120.9,120.8,119.2,111.3,111.0,103.0,102.4,30.3(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.94 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 18 H 13 F3N2H + :315.1104,found:315.1111.

[0084] Compound 20: 3-(2,2,2-trifluoroethyl)-1H,1'H-2,4'-biindole

[0085]

[0086] Reddish-brown solid, yield 45%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.39 (s, 1H), 8.36 (s, 1H), 7.74 (d, J = 7.8Hz, 1H), 7.51-7.48 (m, 1H), 7.43 (d, J = 8.4Hz ,1H),7.33(s,1H),7.32(s,1H),7.29-7.26(m,2H),7.25-7.22(m,1H),6.55-6.54(m,1H),3.64(q,J=10.8Hz,2H). 13 CNMR (151MHz, CDCl3) δ (ppm): 137.7, 136.17, 135.7, 128.7, 127.0, 126.7 (q, J = 271.8Hz, 1C), 125. 1,123.9,122.4,122.2,121.3,120.2,119.4,111.7,110.8,102.1,101.8,30.3(q,J=30.2Hz,1C). 19 FNMR(565MHz, CDCl3)δ(ppm):-64.88(t,J=10.7Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 18 H 13F3N2H + :315.1104,found:315.1112.

[0087] Compound 21: 3-(2,2,2-trifluoroethyl)-1H,1'H-2,6'-biindole

[0088]

[0089] Brown semi-solid, yield: 65%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.27 (s, 1H), 8.22 (s, 1H), 7.76 (d, J = 8.4Hz, 1H), 7.70 (d, J = 8.4Hz, 1H), 7.59 (s, 1H), 7.40 (d, J=8.4Hz,1H),7.31-7.29(m,2H),7.26(t,J=6.6Hz,1H),7.23-7.21(m,1H),6.63(t,J=2.1Hz,1H),3.64(q,J=10.8Hz,2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 139.2, 135.8, 135.5, 128.9, 128.0, 126.9 (q, J = 286.9Hz, 1C), 125.6 ,125.6,122.4,121.3,120.5,120.3,119.3,111.3,110.8,102.8,101.1,30.4(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -64.58 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 18 H 13 F3N2H + :315.1104,found:315.1111.

[0090] Compound 22: 2-(3-(2,2,2-trifluoroethyl)-1H-2-indolyl)quinoxaline

[0091]

[0092] Yellow solid, yield: 20%. 1H NMR (600MHz, CDCl3) δ (ppm): 9.69 (s, 1H), 9.41 (s, 1H), 8.13-8.11 (m, 2H), 7.81 (t, J = 6.6Hz, 1H), 7.77 (t, J = 6.0Hz, 1H ),7.72(d,J=7.8Hz,1H),7.50(d,J=7.8Hz,1H),7.35(t,J=8.4Hz,1H),7.23(t,J=6.6Hz,1H),4.07(q,J=10.8Hz,2H). 13 CNMR(151MHz, CDCl3)δ(ppm):145.2,142.7,142.1,141.4,136.1,132.5,130.8,129.9,129.7,12 9.3,129.0,126.2(q,J=286.9Hz,1C),124.9,120.9,119.9,111.5,105.6,30.8(q,J=30.2Hz,1C). 19 F NMR (565MHz, CDCl3) δ (ppm): -65.06 (t, J=10.7Hz, 3F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 18 H 12 F3N3O4H + :328.1056,found:328.1061.

[0093] Compound 23: 2-(4-chlorophenyl)-5-fluoro-3-(2,2,2-trifluoroethyl)-1H-indole

[0094]

[0095] White solid, yield: 71% 1 H NMR (600MHz, CDCl3) δ (ppm): 8.19 (s, 1H), 7.50-7.48 (m, 4H), 7.33-7.31 (m, 2H), 7.01 (td, J = 9.0, 2.8Hz, 1H), 3.53 (q, J = 10.8Hz, 2H). 13C NMR (151MHz, CDCl3) δ (ppm): 158.5 (d, J = 226.5Hz, 1C), 138.4, 135.1, 132.2, 130.2, 129.8, 129.5, 129.4 (d, J = 15.1Hz, 1C), 126.5 (q,J=271.8Hz,1C),111.83,(d,J=10.6Hz,1C),111.6(d,J=30.2Hz,1C),104.7(d,J=30.2Hz,1C),102.6,30.3(q,J=30.2Hz,1C). 19 F NMR(565MHz, CDCl3)δ(ppm):-55.1(t,J=10.8Hz,3F),-103.7(s,1F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 10 35 ClF4NH + :328.0511,found:328.0509;C 16 H 10 37 ClF4NH + :330.0481,found:330.0473.

[0096] Compound 24: 6-Chloro-2-(4-chlorophenyl)-3-(2,2,2-trifluoroethyl)-1H-indole

[0097]

[0098] Yellow solid, yield: 87%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.21 (s, 1H), 7.57 (d, J = 8.4Hz, 1H), 7.52-7.46 (m, 4H), 7.39 (s, 1H), 7.18 (d, J = 8.4Hz, 1H), 3.55 (q, J = 10.2Hz, 2H). 13 CNMR(151MHz,CDCl3)δ(ppm):137.2,136.0,135.0,129.9,129.7,129.4,128.9,127 .3,126.4(q,J=286.9Hz,1C),121.4,120.5,110.9,102.42,30.1(q,J=30.2Hz,1C). 19FNMR(565MHz, CDCl3)δ(ppm):-64.86(t,J=10.7Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 16 H 10 35 Cl2F3NH + :344.0215,found:344.0213; calculated forC 16 H 10 35 Cl 37 ClF3NH + :346.0186, found:346.0181; calculated for C 16 H 10 37 Cl2F3NH + :348.0156,found:348.0152.

[0099] Compound 25: 2-(4-chlorophenyl)-5,7-difluoro-3-(2,2,2-trifluoroethyl)-1H-indole

[0100]

[0101] White solid, yield: 99%. 1 H NMR (600MHz, CDCl3) δ (ppm): 8.34 (s, 1H), 7.53-7.48 (m, 4H), 7.13 (d, J = 9.0Hz, 1H), 6.80 (t, J = 10.8Hz, 1H), 3.52 (q, J = 11.4Hz, 2H). 13 C NMR (151MHz, CDCl3) δ (ppm): 157.5 (dd, J=226.5, 8.6Hz, 1C), 148.4 (dd, J=241.6, 14.5Hz, 1C), 138.9, 135.4, 131.1 (dd, J=11.6, 5.9Hz, 1C), 129.8, 12 9.5,129.0,126.3(q,J=286.9Hz,1C),120.8(d,J=15.1Hz,1C),103.3,100. 5(d,J=30.2Hz,1C),98.3(dd,J=30.4,15.1Hz,1C),30.2(q,J=30.2Hz,1C). 19F NMR (565MHz, CDCl3) δ (ppm): -64.88 (t, J = 11.3Hz, 3F), -112.34 (t, J = 9.04Hz, 1F), -132.07 (d, J = 13.8Hz, 1F). HRMS (ESI-TOF) m / z: [M+H] + Calculated for C 16 H9 35 ClF5NNa + :368.0236, found:368.0236; calculated forC 16 H9 37 ClF5NNa + :370.0206,found:370.0212.

[0102] Compound 26: 2-(4-chlorophenyl)-5,7-dimethyl-3-(2,2,2-trifluoroethyl)-1H-indole

[0103]

[0104] Pale yellow solid, yield: 51%. 1 H NMR (600MHz, CDCl3) δ (ppm): 7.99 (s, 1H), 7.52-7.47 (m, 4H), 7.30 (s, 1H), 6.92 (s, 1H), 3.55 (q, J = 10.2Hz, 2H), 2.49 (s, 3H), 2.47 (s, 3H). 13 CNMR(151MHz,CDCl3)δ(ppm):136.4,134.5,133.6,130.8,130.2,129.8,129.2,128.6,1 26.5(q,J=271.8Hz,1C),125.4,119.8,116.7,102.4,30.3(q,J=30.2Hz,1C),21.5,16.5. 19 FNMR(565MHz, CDCl3)δ(ppm):-64.81(t,J=11.3Hz,3F).HRMS(ESI-TOF)m / z:[M+H] + Calculated for C 18 H 15 35 ClF3NH + :338.0918,found:338.0919; calculated forC 18 H 15 37ClF3NH + :340.0888,found:340.0895.

[0105] Example 2. Preparation of compound A by changing the alkali

[0106] Replacing potassium carbonate in Example 1 with DABCO yielded A in almost the same yield.

[0107] Example 3. Preparation of compound A by changing the solvent

[0108] A was obtained in a slightly lower yield by replacing acetone with acetonitrile in Example 1.

[0109] Experimental Example 1: Study on Antibacterial Activity

[0110] The minimum inhibitory concentrations (MICs) of 2-aryl-3-trifluoroethylindole compound A against susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), susceptible Staphylococcus surface disease (MSSE), and methicillin-resistant Staphylococcus surface disease (MRSE) were determined using the microbroth 2-fold dilution method recommended by the Clinical and Laboratory Standards Institute (CLSI) antimicrobial susceptibility testing procedures (M02-A11, M07-A9, and M11-A8). The activity data are shown in Table 1.

[0111] Table 1. MIC test results of compound A

[0112]

[0113]

[0114] The results showed that compounds 1-4, 9-14, 19-21, and 23-26 exhibited good antibacterial activity against susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), susceptible Staphylococcus surface disease (MSSE), and methicillin-resistant Staphylococcus surface disease (MRSE). Among these, compounds 3, 12, 23, and 24 all had MIC values ​​less than 4 μg·mL against these four pathogenic bacteria. -1 It has excellent antibacterial effects.

[0115] The foregoing description illustrates and describes several preferred embodiments of the invention. However, as previously stated, it should be understood that the invention is not limited to the forms disclosed herein and should not be construed as excluding other embodiments. It can be used in various other combinations, modifications, and environments, and can be altered within the scope of the inventive concept described herein through the foregoing teachings or techniques or knowledge in related fields. Any modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the invention should be within the protection scope of the appended claims.

Claims

1. A 2-aryl-3-trifluoroethylindole compound, characterized in that, The compound has the following structural formula: The compound is selected from one of the following structural formulas: R 1 R 2 As defined in the specific compound.

2. The method for preparing the compound according to claim 1, characterized in that, Includes the following steps: With o-aminostyrene (B), aromatic aldehyde (C) and 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1λ 3 Using benzo[1,2]iodooxacyclopentene (D) as a starting material and nitrogen-containing heterocyclic carbene (NHC) as a catalyst, the mixture is dissolved in an organic solvent under inert gas protection. A base is then added, and a cyclization reaction occurs at a certain temperature to obtain A.

3. The preparation method according to claim 2, characterized in that: The base used is one or more of the following: triethylamine (TEA), diisopropylethylamine (DIPEA), DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), DABCO (1,4-diazabicyclo[2,2,2]octane), sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, and potassium phosphate; the organic solvent used is one or more of the following: acetonitrile, dichloromethane, chloroform, toluene, acetone, dimethyl sulfoxide, and 1,2-dichloroethane; the inert gas used is one or more of the following: nitrogen and argon.

4. The preparation method according to claim 3, characterized in that: The molar ratio of o-aminostyrene (B) to aromatic aldehyde (C) is 3:1 to 1:3; 3,3-dimethyl-1-(trifluoromethyl)-1,3-dihydro-1λ 3 The amount of benzo[1,2]iodooxetine (D) is 1-3 eq; the amount of nitrogen heterocyclic carbene catalyst used is 0.1-0.8 eq; and the amount of base used is 1-3 eq.

5. The preparation method according to claim 2, characterized in that: The reaction temperature is 0℃-100℃.

6. The 2-aryl-3-trifluoroethylindole compound according to claim 1, characterized in that, Use in the preparation of antibacterial drugs, wherein the compound is selected from one of the following structural formulas:

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