Method for preparing 2-sulfenyl pyrrolo [1, 2-alpha] quinoxaline compound
Through photocatalytic reaction, 2-thiopyrrolo[1,2-α]quinoxaline compounds were synthesized by isonitrile compounds and diphenyl disulfide derivatives under visible light, solving the problems of harsh reaction conditions, high catalyst dependence and environmental pollution in the traditional methods, and achieving efficient and green synthesis effects.
Patent Information
- Application Number
- CN202510333824.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-20
- Publication Date
- 2025-06-20
AI Technical Summary
The traditional method of synthesizing pyrrolo[1,2-α]quinoxaline skeleton from N-(nitrophenyl)pyrrole has problems such as harsh reaction conditions, high catalyst dependence and environmental pollution.
The photocatalytic reaction was carried out under visible light irradiation by isonitrile compounds and diphenyl disulfide derivatives, and 2-thiopyrrolo[1,2-α]quinoxaline compounds were synthesized by homozygous cracking and tandem addition of sulfur radicals. The catalysts and solvents used in this method are non-toxic and harmless, with mild reaction conditions and are green and efficient.
It has achieved efficient synthesis at room temperature, with high yield, strong atomic economy, and environmentally friendly, with a wide range of application potential in the fields of medicinal chemistry, optoelectronic devices, fluorescent probes and chemical sensing.
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Figure CN120172979A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of organic synthesis, and particularly to a method for preparing 2-thiolated pyrrolo[1,2-α]quinoxaline compounds. Background Art
[0002] Pyrrolo[1,2-α]quinoxaline and its derivatives, as an important class of nitrogen heterocyclic compounds, have unique physical and chemical properties and have been widely used in the fields of medicinal chemistry, optoelectronic devices, fluorescent probes, and chemical sensing. Therefore, it is particularly important to rapidly construct the pyrrolo[1,2-α]quinoxaline fragment. Currently, the method of synthesizing the pyrrolo[1,2-α]quinoxaline skeleton starting from N-(nitrophenyl)pyrrole is a widely used method and has been extensively studied. However, this method still has some obvious disadvantages and deficiencies. Specifically as follows: (1) Harsh reaction conditions: Traditional synthesis methods often require high temperature, high pressure, or a specific solvent environment, which not only increases the difficulty and cost of synthesis but also may pose potential threats to the environment and the health of operators; (2) High catalyst dependence: In the process of synthesizing the pyrrolo[1,2-α]quinoxaline skeleton from N-(nitrophenyl)pyrrole, the selection and design of the catalyst are crucial. However, existing catalysts often have problems such as limited hydrogen storage and transfer hydrogen capabilities and narrow applicable ranges, which limit the generality and efficiency of the synthesis method; (3) Environmental impact: Traditional synthesis methods may involve toxic and harmful reagents and solvents, and improper handling may cause environmental pollution. In summary, the traditional method of synthesizing the pyrrolo[1,2-α]quinoxaline skeleton starting from N-(nitrophenyl)pyrrole has problems such as harsh reaction conditions, high catalyst dependence, and environmental pollution. Starting from the principles of organic reactions, it is very necessary to develop new synthesis methods with mild conditions, greenness, and high efficiency for the further research, development, and application of pyrrolo[1,2-α]quinoxaline compounds. Summary of the Invention
[0003] The purpose of the present invention is to provide a method for preparing 2-thiolated pyrrolo[1,2-α]quinoxaline compounds to solve the problems existing in the above-mentioned prior art.
[0004] To achieve the above purpose, the present invention provides the following scheme:
[0005] One of the technical solutions of the present invention: A method for preparing 2-thiolated pyrrolo[1,2-α]quinoxaline compounds, comprising the following steps:
[0006] Mix compound 1, compound 2, a catalyst, a base, and a solvent, and carry out a reaction under visible light irradiation to obtain compound 3, which is the 2-thiolated pyrrolo[1,2-α]quinoxaline compound;
[0007] The structural formulas of Compound 1, Compound 2, and Compound 3 are as follows:
[0008]
[0009] Among them, R is selected from one of H, methyl, isopropyl, tert-butyl, or halogen.
[0010] Compound 1 is an isocyanide compound, and Compound 2 is a diphenyl disulfide derivative. Under visible light promotion, the isocyanide compound and the diphenyl disulfide derivative can react at room temperature to synthesize 2-thiol pyrrolo[1,2-α]quinoxaline compounds. Specifically, the diphenyl disulfide derivative undergoes homolytic cleavage under photocatalytic conditions to generate sulfur radicals, and then the sulfur radicals carry out tandem radical addition to the isocyanide compound to form 2-thiol pyrrolo[1,2-α]quinoxaline compounds. The catalyst, solvent, etc. used in the reaction process of the present invention are all non-toxic and harmless, the reaction conditions are mild, and it is green and efficient.
[0011] Furthermore, the halogen is preferably Cl.
[0012] Furthermore, the catalyst is iridium tris(2-phenylpyridine) or iridium bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)] bis(hexafluorophosphate).
[0013] Furthermore, the base is potassium carbonate, sodium carbonate, or potassium phosphate.
[0014] Furthermore, the solvent is tetrahydrofuran, toluene, or dichloroethane.
[0015] Furthermore, the dosage ratio of Compound 1, Compound 2, the base, and the solvent is 0.05 - 0.5 mmol:0.05 - 0.5 mmol:0.05 - 2 mmol:1 - 6 ml.
[0016] Furthermore, the molar dosage of the catalyst is 1 - 10% of the sum of the molar dosages of Compound 1, Compound 2, and the base.
[0017] Furthermore, the visible light is blue light.
[0018] Furthermore, the intensity of the visible light irradiation is 5 - 100 W.
[0019] Furthermore, the reaction time is 24 - 36 hours.
[0020] Furthermore, the reaction is carried out in an air atmosphere.
[0021] Furthermore, the reaction temperature is room temperature.
[0022] Further, after the reaction is completed, it further includes the steps of filtration, concentration, and purification.
[0023] Further, the purification is specifically carried out by silica gel flash column chromatography, and a mixed solvent of ethyl acetate / petroleum ether is used as the eluent during the purification process.
[0024] Further, the volume ratio of ethyl acetate to petroleum ether is 1:250.
[0025] The second technical solution of the present invention: 2-Thiopyrrolo[1,2-α]quinoxaline compounds prepared according to the above method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds.
[0026] The present invention discloses the following technical effects:
[0027] The present invention provides a new method for photocatalytic synthesis of 2-thiopyrrolo[1,2-α]quinoxaline compounds, specifically for the synthesis of polycyclic heterocyclic compounds - 2-thiopyrrolo[1,2-α]quinoxaline compounds by visible light promotion of isocyanide compounds and diphenyl disulfide derivatives. The synthesis method of the present invention has mild conditions, strong atom economy, high yield, is green and efficient, and the synthesized 2-thiopyrrolo[1,2-α]quinoxaline compounds have potential application values in the fields of medicinal chemistry, optoelectronic devices, fluorescent probes, and chemical sensing, etc. Description of the Drawings
[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.
[0029] Figure 1 1H NMR spectrum of the product prepared in Example 1;
[0030] Figure 2 13C NMR spectrum of the product prepared in Example 1;
[0031] Figure 3 1H NMR spectrum of the product prepared in Example 2;
[0032] Figure 4 13C NMR spectrum of the product prepared in Example 2;
[0033] Figure 5 1H NMR spectrum of the product prepared in Example 3;
[0034] Figure 6 13C NMR spectrum of the product prepared in Example 3;
[0035] Figure 7 1H NMR spectrum of the product prepared in Example 4;
[0036] Figure 8 13C NMR spectrum of the product prepared in Example 4;
[0037] Figure 9 1H NMR spectrum of the product prepared in Example 5;
[0038] Figure 10 13C NMR spectrum of the product prepared in Example 5. Detailed Description of the Invention
[0039] The various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be construed as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.
[0040] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.
[0041] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.
[0042] Without departing from the scope or spirit of the present invention, various modifications and variations can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the present invention specification are obvious to those skilled in the art. The present invention specification and examples are merely exemplary.
[0043] Regarding the terms "comprising", "including", "having", "containing", etc. used herein, they are all open-ended terms, meaning including but not limited to.
[0044] It should be noted that those aspects of the present invention not described in detail are all conventional operating means in the art and are not the focus of the present invention.
[0045] As a first aspect of the present invention, the present invention provides a method for preparing 2-thiolopyrrolo[1,2-α]quinoxaline compounds, comprising the following steps:
[0046] Mix compound 1, compound 2, a catalyst, a base and a solvent, and carry out a reaction under visible light irradiation to obtain compound 3, which is the 2-thiolopyrrolo[1,2-α]quinoxaline compound;
[0047] The structural formulas of compound 1, compound 2 and compound 3 are as follows:
[0048]
[0049] Wherein, R is selected from one of H, methyl, isopropyl, tert-butyl or halogen.
[0050] As a preferred embodiment of the present invention, the halogen is Cl.
[0051] As a preferred embodiment of the present invention, the catalyst is tris(2-phenylpyridine)iridium or bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate).
[0052] As a preferred embodiment of the present invention, the base is potassium carbonate, sodium carbonate or potassium phosphate.
[0053] As a preferred embodiment of the present invention, the solvent is tetrahydrofuran, toluene or dichloroethane.
[0054] As a preferred embodiment of the present invention, the dosage ratio of compound 1, compound 2, the base and the solvent is 0.05 - 0.5 mmol:0.05 - 0.5 mmol:0.05 - 2 mmol:1 - 6 ml.
[0055] As a preferred embodiment of the present invention, the molar dosage of the catalyst is 1 - 10% of the sum of the molar dosages of compound 1, compound 2 and the base.
[0056] As a preferred embodiment of the present invention, the visible light is blue light.
[0057] As a preferred embodiment of the present invention, the intensity of the visible light irradiation is 5 - 100 W.
[0058] As a preferred embodiment of the present invention, the reaction time is 24 - 36 hours.
[0059] As a preferred embodiment of the present invention, the reaction is carried out in an air atmosphere.
[0060] As a preferred embodiment of the present invention, the temperature of the reaction is room temperature.
[0061] As a preferred embodiment of the present invention, after the reaction, the steps of filtration, concentration, and purification are further included.
[0062] As a preferred embodiment of the present invention, the purification is specifically carried out by silica gel flash column chromatography, and a mixed solvent of ethyl acetate / petroleum ether is used as the eluent during the purification process.
[0063] As a preferred embodiment of the present invention, the volume ratio of ethyl acetate to petroleum ether is 1:250.
[0064] As the second aspect of the present invention, the present invention provides 2-thiopyrrolo[1,2-α]quinoxaline compounds prepared by the method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds as described above.
[0065] The technical solutions of the present invention will be further described below in conjunction with specific embodiments.
[0066] The room temperature involved in the specific embodiments of the present invention specifically refers to 20-30 °C;
[0067] All raw materials used in the specific embodiments of the present invention are ordinary commercially available products or prepared according to existing technologies. Among them, the CAS number of diphenyl disulfide is 882-33-7, the CAS number of p-tolyl disulfide is 103-19-5, the CAS number of bis[4-(1-methylethyl)phenyl] disulfide is 622407-64-1, the CAS number of bis[4-(1,1-dimethylethyl)phenyl] disulfide is 785013-30-1, and the CAS number of bis(4,4-dichlorophenyl) disulfide is 1142-19-4.
[0068] The reaction route for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds in the specific embodiments of the present invention is as follows:
[0069]
[0070] Example 1
[0071] A method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds, the reaction route refers to the reaction route given in the specific embodiment. Among them, compound 1 is 1-(2-isocyanophenyl)-1H-pyrrole, denoted as 1a; compound 2 is diphenyl disulfide (i.e., R in compound 2 is H), denoted as 2a; the obtained compound 3 is denoted as 3a;
[0072] The specific preparation steps are as follows:
[0073] In an oven-dried sealed test tube, add compound 1 (0.10 mmol), compound 2 (0.10 mmol), potassium carbonate (0.20 mmol), tris(2-phenylpyridine)iridium (5 mmol%, i.e., 5% of the sum of the molar amounts of compound 1, compound 2 and potassium carbonate) and tetrahydrofuran (2 ml) to obtain a mixture. Irradiate the mixture under a 50 W blue light-emitting diode and stir the reaction at room temperature in an air atmosphere for 24 hours. After cooling, filter the reaction mixture, and concentrate the filtrate under reduced pressure. The residue is purified by flash column chromatography on silica gel using a mixed solvent of ethyl acetate / petroleum ether (volume ratio 1:250) as the eluent to obtain product 3a (17 mg of white solid, yield 64%).
[0074] The 1H NMR spectrum and 13C NMR spectrum of the product obtained in this example are shown in Figure 1 and Figure 2 respectively, and the structural characterization data are as follows:
[0075] 1 H NMR (500 MHz, Chloroform-d) δ: 7.91 (dd, 1H), 7.81 (d, J = 1.0 Hz, 1H), 7.74 (dd, J = 8.1, 1.2 Hz, 1H), 7.72 - 7.70 (m, 2H), 7.47 - 7.43 (m, 4H), 7.37 (t, 1H), 6.95 (dd, J = 4.0, 1.2 Hz, 1H), 6.85 (dd, J = 3.9, 2.8 Hz, 1H).
[0076] 13 C NMR (126 MHz, CDCl3) δ: 153.6, 135.8, 134.8, 129.3, 129.2, 129.0, 128.7, 126.9, 126.8, 125.1, 124.5, 114.5, 113.6, 113.6, 106.5.
[0077] HRMS (ESI) m / z calcd for C 17 H 13 N2S + [M + H] + : 277.07939, found 277.07910.
[0078] Example 2
[0079] A method for preparing 2-thiolpyrrolo[1,2-α]quinoxaline compounds, the reaction route refers to the reaction route given in the specific implementation manner. Among them, compound 1 is 1-(2-isocyanophenyl)-1H-pyrrole, denoted as 1a; compound 2 is p-tolyl disulfide (that is, R in compound 2 is methyl (-CH3), and the methyl is in the para position of the -S-S- group), denoted as 2b; the obtained compound 3 is denoted as 3b.
[0080] The specific preparation steps are as follows:
[0081] In a sealed test tube dried in an oven, add compound 1 (0.10 mmol), compound 2 (0.10 mmol), potassium carbonate (0.20 mmol), tris(2-phenylpyridine)iridium (5 mmol%, that is, 5% of the sum of the molar amounts of compound 1, compound 2 and potassium carbonate) and tetrahydrofuran (2 ml) to obtain a mixture. Irradiate the mixture with a 50W blue light-emitting diode and stir the reaction at room temperature in an air atmosphere for 24 hours. After cooling, filter the reaction mixture, and concentrate the filtrate under reduced pressure. The residue is purified by silica gel flash column chromatography using a mixed solvent of ethyl acetate / petroleum ether (volume ratio 1:250) as the eluent to obtain product 3b (16 mg of light yellow oil, yield 53%).
[0082] The hydrogen NMR spectrum and carbon NMR spectrum of the product obtained in this example are respectively as Figure 3 and Figure 4 shown, and the structure characterization data are as follows:
[0083] 1 H NMR(500MHz,Chloroform-d)δ:7.90(d,1H),7.79(d,J=8.1Hz,1H),7.74(d,J=8.0Hz,1H),7.60(d,J=8.1Hz,2H),7.43(t,J=7.1Hz,1H),7.35(t,J=7.6Hz,1H),7.27(d,J=8.1Hz,2H),6.94(d,J=3.9Hz,1H),6.84(t,1H),2.45(s,3H).
[0084] 13 C NMR(126MHz,CDCl3)δ154.1,139.0,135.8,135.0,129.8,129.3,126.9,126.7,125.4,125.0,124.4,114.4,113.5,106.4,21.4.
[0085] HRMS(ESI)m / z calcd for C 18 H15 N2S + [M+H] + : 291.09504, found 291.09451.
[0086] Example 3
[0087] A method for preparing 2-thiol pyrrolo[1,2-α]quinoxaline compounds. The reaction route refers to the reaction route given in the specific implementation manner. Among them, compound 1 is 1-(2-isocyanophenyl)-1H-pyrrole, denoted as 1a; compound 2 is bis[4-(1-methylethyl)phenyl] disulfide (that is, R in compound 2 is isopropyl (-CH(CH3)2), and the isopropyl group is in the para position of the -S-S- group), denoted as 2c; the obtained compound 3 is denoted as 3c;
[0088] The specific preparation steps are as follows:
[0089] In a sealed test tube dried in an oven, add compound 1 (0.10 mmol), compound 2 (0.10 mmol), potassium carbonate (0.20 mmol), tris(2-phenylpyridine)iridium (5 mmol%, that is, 5% of the sum of the molar amounts of compound 1, compound 2 and potassium carbonate) and tetrahydrofuran (2 ml) to obtain a mixture. Irradiate the mixture with a 50W blue light-emitting diode and stir the reaction at room temperature in an air atmosphere for 24 hours. After cooling, filter the reaction mixture, and concentrate the filtrate under reduced pressure. The residue is purified by flash column chromatography on silica gel, using a mixed solvent of ethyl acetate / petroleum ether (volume ratio 1:250) as the eluent to obtain product 3c (30 mg of light yellow oil, yield 93%).
[0090] The 1H NMR spectrum and 13C NMR spectrum of the product obtained in this example are respectively as Figure 5 and Figure 6 shown, and the structure characterization data are as follows:
[0091] 1 H NMR(500MHz,Chloroform-d)δ:7.91 - 7.88(m,1H),7.77(dd,J = 15.4,8.1Hz,2H),7.66(d,J = 8.2Hz,2H),7.43(t,J = 7.7Hz,1H),7.39 - 7.32(m,3H),6.97(d,J = 4.0Hz,1H),6.87 - 6.82(m,1H),3.06 - 2.97(m,1H),1.35(d,J = 6.9Hz,6H).
[0092] 1313C NMR (126 MHz, CDCl3) δ: 154.0, 149.8, 135.9, 134.9, 129.3, 127.2, 126.9, 126.7, 125.7, 125.0, 124.4, 114.4, 113.5, 106.3, 34.0, 24.0.
[0093] HRMS (ESI) m / z calcd for C 20 H 19 N2S + [M + H] + : 319.12634, found 319.12592.
[0094] Example 4
[0095] A method for preparing 2 - mercapto - pyrrolo[1,2 - α]quinoxaline compounds. The reaction route refers to the reaction route given in the specific implementation manner. Among them, compound 1 is 1-(2 - isocyanophenyl)-1H - pyrrole, denoted as 1a; compound 2 is bis[4-(1,1 - dimethylethyl)phenyl] disulfide (i.e., R in compound 2 is tert - butyl (t - Bu), and the tert - butyl group is in the para - position of the - S - S - group), denoted as 2d; the obtained compound 3 is denoted as 3d;
[0096] The specific preparation steps are as follows:
[0097] In a sealed test tube dried in an oven, add compound 1 (0.10 mmol), compound 2 (0.10 mmol), potassium carbonate (0.20 mmol), tris(2 - phenylpyridine)iridium (5 mmol%, that is, 5% of the sum of the molar amounts of compound 1, compound 2 and potassium carbonate) and tetrahydrofuran (2 ml) to obtain a mixture. Irradiate the mixture with a 50 W blue light - emitting diode and stir the reaction at room temperature in an air atmosphere for 24 hours. After cooling, filter the reaction mixture, and concentrate the filtrate under reduced pressure. The residue is purified by silica gel flash column chromatography using a mixed solvent of ethyl acetate / petroleum ether (volume ratio 1:250) as the eluent to obtain product 3d (24 mg of light yellow oil, yield 71%).
[0098] The 1H NMR spectrum and 13C NMR spectrum of the product obtained in this example are respectively as Figure 7 and Figure 8 shown, and the structure characterization data are as follows:
[0099] 11H NMR (500 MHz, Chloroform-d) δ: 7.89 (dd, J = 2.5, 1.1 Hz, 1H), 7.81 - 7.74 (m, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.46 - 7.41 (m, 1H), 7.39 - 7.33 (m, 1H), 6.97 (dd, J = 4.0, 1.1 Hz, 1H), 6.88 - 6.83 (m, 1H), 1.42 (s, 9H).
[0100] 13 13C NMR (126 MHz, CDCl3) δ: 154.0, 152.0, 135.9, 134.6, 129.3, 126.9, 126.7, 126.1, 125.5, 125.0, 124.5, 114.4, 113.6, 106.3, 34.8, 31.3.
[0101] HRMS (ESI) m / z calcd for C 21 H 21 N2S + [M + H] + : 333.14199, found 333.14154.
[0102] Example 5
[0103] A method for preparing 2-thiolpyrrolo[1,2-α]quinoxaline compounds, the reaction route refers to the reaction route given in the specific implementation manner. Among them, compound 1 is 1-(2-isocyanophenyl)-1H-pyrrole, denoted as 1a; compound 2 is bis(4,4-dichlorodiphenyl) disulfide (i.e., R in compound 2 is -Cl, and -Cl is in the para position of the -S-S- group), denoted as 2e; the obtained compound 3 is denoted as 3e;
[0104] The specific preparation steps are as follows:
[0105] In a sealed test tube dried in an oven, add compound 1 (0.10 mmol), compound 2 (0.10 mmol), potassium carbonate (0.20 mmol), tris(2-phenylpyridine)iridium (5 mmol%, i.e., 5% of the sum of the molar amounts of compound 1, compound 2 and potassium carbonate) and tetrahydrofuran (2 ml) to obtain a mixture. Irradiate the mixture under a 50 W blue light-emitting diode and stir the reaction at room temperature in an air atmosphere for 24 hours. After cooling, filter the reacted mixture, and concentrate the filtrate under reduced pressure. The residue is purified by flash column chromatography on silica gel using a mixed solvent of ethyl acetate / petroleum ether (volume ratio 1:250) as the eluent to obtain product 3e (29 mg of white solid, yield 93%).
[0106] The 1H NMR spectrum and 13C NMR spectrum of the product obtained in this example are respectively as shown in Figure 7 and Figure 8 as follows, and the structure characterization data are as follows:
[0107] 1 H NMR (500 MHz, Chloroform-d) δ: 7.91 (t, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.73 (d, 1H), 7.63 (d, J = 8.5 Hz, 2H), 7.47 - 7.41 (m, 3H), 7.37 (t, 1H), 6.96 (d, J = 4.0 Hz, 1H), 6.86 (t, 1H).
[0108] 13 C NMR (126 MHz, CDCl3) δ: 154.0, 136.1, 135.7, 135., 129.3, 129.2, 127.5, 127.0, 126.9, 125.2, 124.3, 114.7, 113.7, 113.6, 106.3.
[0109] HRMS (ESI) m / z calcd for C 17 H 12 N2ClS + [M + H] + : 311.04042, found 311.03989.
[0110] Test Example
[0111] Inhibitory performance test of the products prepared in Examples 1 - 5 against CK2 (Casein Kinase 2)
[0112] 10 μL of the test compound in aqueous solution at different concentrations was added to the reaction mixture, which contained: 10 μL of assay dilution buffer (ADB; consisting of 20 mM 3-morpholinopropanesulfonic acid (MOPS), pH 7.2, 25 mM β-glycerophosphate, 5 mM ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EGTA), 1 mM sodium orthovanadate and 1 mM dithiothreitol), 10 μL of substrate peptide (RRRDDDSDDD, dissolved in ADB at a concentration of 1 mM), 10 μL of recombinant human CK2 (25 ng, dissolved in ADB). The reaction was initiated by adding 10 μL of ATP solution. The ATP solution consisted of 90 wt% of a solution formed by dissolving 75 mM magnesium chloride and 75 mM ATP (adenosine triphosphate) in ADB and 10 wt% of [γ-33P]ATP. The reaction was maintained at 30 °C for 10 minutes. The reaction was terminated by adding 100 μL of 0.75 wt% phosphoric acid, and then the reaction solution was transferred to a phosphocellulose filter plate and filtered. After washing each well 5 times with 0.75 wt% phosphoric acid, the filter plate was dried in vacuo for 5 minutes. Subsequently, 15 μL of scintillation fluid was added to each well, and the residual radioactivity was measured using a Varian luminometer. An inhibition curve of CK2 activity against the compound concentration was plotted with the logarithm of the concentration on the abscissa and the inhibition rate at the corresponding concentration on the ordinate, and the IC 50 .
[0113] The test results are shown in Table 1 as follows.
[0114] Table 1
[0115]
[0116] As can be seen from Table 1, the products of Examples 1-5 have good inhibitory performance against CK2 and can be used as CK2 inhibitors.
[0117] The above-described embodiments are only descriptions of the preferred embodiments of the present invention and do not limit the scope of the present invention. Without departing from the spirit of the design of the present invention, various modifications and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.
Claims
1. A method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds, characterized in that: The following steps are involved: Compound 1, compound 2, a catalyst, a base and a solvent are mixed and reacted under visible light irradiation to obtain compound 3, which is the 2-thiopyrrolo[1,2-α]quinoxaline compound; The structural formulas of Compound 1, Compound 2 and Compound 3 are as follows: Wherein, R is selected from one of H, methyl, isopropyl, tert-butyl or halogen.
2. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The catalyst is tris(2-phenylpyridine)iridium or di[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate).
3. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The base is potassium carbonate, sodium carbonate or potassium phosphate.
4. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The solvent is tetrahydrofuran, toluene or ethylene dichloride.
5. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The usage ratio of the compound 1, the compound 2, the base and the solvent is 0.05-0.5 mmol: 0.05-0.5 mmol: 0.05-2 mmol: 1-6 ml.
6. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The molar amount of the catalyst is 1-10% of the sum of the molar amounts of the compound 1, the compound 2 and the base.
7. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The visible light is blue light.
8. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The intensity of the visible light irradiation is 5-100W.
9. The method for preparing 2-thiopyrrolo[1,2-α]quinoxaline compounds according to claim 1, characterized in that: The reaction time is 24 to 36 hours.
10. The 2-sulfanylpyrrolo[1,2-α]quinoxaline compound prepared by the method for preparing 2-sulfanylpyrrolo[1,2-α]quinoxaline compounds according to any one of claims 1 to 9.