CN110183450B - Synthetic method of 2-arylindazolo maleimide fused polycyclic compound - Google Patents
Synthetic method of 2-arylindazolo maleimide fused polycyclic compound Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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Abstract
The invention discloses a synthesis method of a 2-aryl indazole maleimide fused polycyclic compound, belonging to the technical field of organic synthesis. The synthesis method comprises the following steps: 2-aryl indazole compounds 1 and maleimide 2 are heated to generate dehydrocyclization tandem reaction in the presence of a rhodium catalyst and an oxidant, and 2-aryl indazole maleimide fused polycyclic compounds 3 are obtained. The method has the advantages of mild reaction conditions, good atom economy, wide substrate application range and no need of inert gas protection, and provides a novel efficient and practical method for synthesizing the 2-arylindazole maleimide fused polycyclic compound.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a 2-aryl indazole maleimide fused polycyclic compound.
Background
Indazoles are not only the core structural skeleton of various natural products, but also important constituent units of many artificially synthesized active drugs for cancer resistance, virus resistance, depression resistance, inflammation resistance and the like. Meanwhile, the indazole fused pi-conjugated system has good application prospect in the fields of biology, chemistry, material science and the like. On the other hand, maleimide derivatives have recently received a wide attention from synthetic and medicinal chemists due to their unique optical properties and diverse pharmaceutical activities.
Given the importance of indazole and maleimide compounds, we expect that fused polycyclic compounds containing both pharmacophores may have greater biological activity or superior optical properties than their parent structures. It should be noted that no synthesis method of 2-arylindazolo-maleimide fused polycyclic compounds has been reported.
Therefore, research and development of a method for synthesizing the 2-arylindazolo-maleimide fused polycyclic compound from cheap, easily available and safe reagents through simple and convenient operation steps have important theoretical significance and important application value.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a synthesis method of a 2-aryl indazole maleimide condensed polycyclic compound, the method utilizes dehydrocyclization tandem reaction of the 2-aryl indazole compound and maleimide under the catalysis of transition metal to efficiently synthesize the indazole maleimide condensed polycyclic compound, and the method has the advantages of simple and convenient operation, mild conditions, wide substrate application range and the like.
The invention adopts the following technical scheme for solving the technical problems, and the synthesis method of the 2-aryl indazole maleimide condensed polycyclic compound is characterized in that: the 2-arylindazole compound 1 and maleimide 2 react at elevated temperature in the presence of a rhodium catalyst and an oxidant to obtain a 2-arylindazolo-maleimide fused polycyclic compound 3.
The reaction equation in the synthesis method is as follows:
wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy, methylenedioxy, and the like; r2Selected from hydrogen, halogen, alkyl, alkoxy, and the like; r3Selected from aryl, alkyl, benzyl, and the like. The aryl group includes phenyl and substituted phenyl, and the alkyl group includes straight chain alkyl, branched chain alkyl or cycloalkyl.
Further, in the above technical solution, R1Is hydrogen, fluorine, chlorine, C1-4Alkyl radical, C1-4Alkoxy or methylenedioxy, R2Is hydrogen, trifluoromethyl, fluorine, chlorine, C1-4Alkyl or C1-4Alkoxy radical, R3Is phenyl, C1-4Alkyl, benzyl or cyclohexyl.
Further, in the above technical scheme, the reaction is carried out in an organic solvent, wherein the organic solvent is toluene, chlorobenzene, tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, acetonitrile, dioxane or hexafluoroisopropanol.
Further, in the above technical scheme, the rhodium catalyst is [ RhCp Cl [ ]2]2Or [ RhCp (MeCN)3](SbF6)2(ii) a Oxidizing agentIs acetate, and is selected from one or two of copper acetate, copper acetate monohydrate, zinc acetate, and cesium acetate.
Furthermore, in the technical scheme, the molar ratio of the 2-arylindazole compound 1, the maleimide 2, the rhodium catalyst and the oxidant is 1:1-3:0.005-0.06: 0.5-3.
Further, in the above technical scheme, an additive is added during the reaction, the additive is an organic acid or an organic base, the organic acid is selected from one or more of acetic acid, trifluoroacetic acid, p-toluenesulfonic acid monohydrate, 1-adamantanecarboxylic acid (ADA) and other acids, and the organic base is selected from one or more of N, N-diisopropylethylamine, N-dicyclohexylmethylamine, triethylamine and other bases.
The additive is not necessary, but the yield is very significantly improved in the presence of the acid additive, and particularly in the presence of p-toluenesulfonic acid, p-toluenesulfonic acid monohydrate and 1-adamantanecarboxylic acid, the formation of by-products is suppressed to the greatest extent. The additive is added in a proportion not exceeding 3 equivalents of the 2-arylindazole-based compound 1.
Further, in the above technical scheme, the reaction temperature is selected from 60-140 ℃, and preferably the reaction temperature is 120 ℃.
Furthermore, in the technical scheme, the reaction can be smoothly carried out in air, nitrogen or oxygen without being finished under the protection of inert gas.
During the study, 1a (2-phenylindazole) and 2a (N-methylmaleimide) were added to [ RhCp Cl ]2]2For the example of the reaction of the catalyst, the ketone acetate as the oxidant and the additive 1-adamantane carboxylic acid to generate 3a, the mechanism in the reaction process is presumed as follows: first 1a with in situ ion exchange formed [ RhCp (OAc)2]Coordination to form intermediate I, followed by C-H metallation to form rhodium ring II, followed by coordination with 2a and migratory insertion to form rhodium ring III, followed by inversion of III under acidic conditions to form intermediate IV, followed by reductive elimination of IV to give intermediate V and Rh (I). Next, oxidative dehydroaromatization of V yields product 3a, while rh (i) regenerates rh (iii) under cu (ii) oxidation, the reaction being represented as follows:
the invention has the following advantages: 1) the synthesis process is simple and efficient, and the indazole maleimide fused polycyclic compound is efficiently synthesized through the dehydrocyclization tandem reaction of the 2-arylindazole compound and maleimide under the catalysis of transition metal, so that the synthesis efficiency is high; 2) the reaction can be carried out in the air atmosphere, the condition is mild, and the operation is simple and convenient; (3) the application range of the substrate is wide. Therefore, the invention provides a novel efficient and practical method for synthesizing the 2-aryl indazole maleimide fused polycyclic compound.
Detailed Description
The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.
Example 1
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying, detection of only product 3a from the crude product, and separation on silica gel column (dichloromethane as eluent) gave product 3a as a red solid (81mg, 90%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.57(s,3H),7.98(t,J＝7.2Hz,1H),8.13(d,J＝8.4Hz,1H),8.24-8.29(m,2H),8.48(t,J＝7.2Hz,1H),8.91(d,J＝8.4Hz,1H),9.42(d,J＝8.4Hz,1H),9.45(d,J＝7.8Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.6,110.6,116.0,119.2,121.9,125.0,127.1,127.9,130.9,131.3,132.6,133.2,136.2,136.5,140.8,165.9,167.5.HRMS calcd for C18H12N3O2:302.0924[M+H]+,found:302.0918.
example 2
To a 15mL reaction tube were added 1a (0.3mmol,58.3mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp Cl ] dimer) in that order2]20.015mmol,9.3mg) and copper acetate (0.6mmol,109mg), the reaction tube was sealed under air conditions and then placed in a 120 ℃ oil bath to stir for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel (dichloromethane: ethyl acetate 50:1) gave product 3a as a red solid (44mg, 49%). In addition, white solid 4a (34.5mg, 38%) was also obtained, characterized as follows:1H NMR(400MHz,CDCl3):δ3.24(s,3H),3.37(d,J＝18.4Hz,1H),3.46(d,J＝18.4Hz,1H),7.14(t,J＝7.6Hz,1H),7.32-7.39(m,3H),7.44(d,J＝8.4Hz,1H),7.54-7.58(m,1H),7.83(d,J＝9.2Hz,1H),7.90(d,J＝7.6Hz,1H).13C NMR(100MHz,CDCl3):δ26.2,39.4,52.0,113.0,116.1,117.8,119.2,123.2,123.3,127.0,127.3,130.5,136.9,137.7,140.2,153.6,174.3,174.5.HRMS calcd for C18H14N3O2:304.1081[M+H]+,found:304.1082.
example 3
To a 15mL reaction tube were added 1a (0.3mmol,58mg), chlorobenzene (3mL), 2a (0.45mmol,50mg), [ RhCp (MeCN)3](SbF6)2(0.015mmol,12.5mg) and copper acetate (0.6mmol,109mg), sealing the reaction tube under air, and then placing in oil at 60 deg.CThe reaction was stirred in the bath for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (27mg, 30%). In addition, white solid 4a was also obtained (24mg, 26%).
Example 4
To a 15mL reaction tube were added 1a (0.3mmol,58mg), tetrahydrofuran (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg) and copper acetate monohydrate (0.6mmol,120mg), the reaction tube was sealed under air conditions, and then placed in an oil bath at 140 ℃ to stir for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (26mg, 29%). In addition, white solid 4a (15mg, 16%) was obtained.
Example 5
To a 15mL reaction tube were added 1a (0.3mmol,58mg), 1, 2-dichloroethane (3mL), 2a (0.33mmol,37mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] in that order2]20.015mmol,9.3mg), zinc acetate (0.6mmol,110mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying, TLC detected only product 3a and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (77mg, 85%).
Example 6
To a 15mL reaction tube were added 1a (0.3mmol,58mg), dichloromethane (3mL), 2a (0.9mmol,100mg), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer(s) ((III))[[RhCp*Cl2]20.015mmol,9.3mg), cesium acetate (0.6mmol,115mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (54mg, 60%).
Example 7
To a 15mL reaction tube were added 1a (0.3mmol,58mg), acetonitrile (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.0015mmol,1mg), copper acetate (0.6mmol,109mg) and trifluoroacetic acid (0.3mmol, 22. mu.L), the reaction tube was sealed under air conditions, and then placed in a 120 ℃ oil bath and stirred for reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (18mg, 20%). In addition, white solid 4a (14mg, 15%) was obtained.
Example 8
To a 15mL reaction tube were added 1a (0.3mmol,58mg), hexafluoroisopropanol (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp Cl ] Cl) in that order2]20.018mmol,11mg), copper acetate (0.6mmol,109mg) and acetic acid (0.3mmol, 17. mu.L), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (37mg, 40%). In addition, white solid 4a was also obtained (23mg, 26%).
Example 9
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and p-toluenesulfonic acid monohydrate (0.3mmol,57mg), the reaction tube was sealed under oxygen conditions, and then placed in a 120 ℃ oil bath to stir for reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (72mg, 80%).
Example 10
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.15mmol,27mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under nitrogen, and then placed in a 120 ℃ oil bath to stir the reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (41mg, 45%). In addition, white solid 4a was also obtained (9mg, 10%).
Example 11
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.9mmol,164mg) and 1-adamantanecarboxylic acid (0.15mmol,27mg), the reaction tube was sealed under oxygen, and then placed in a 100 ℃ oil bath and stirred for reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtering, spin-drying, separating with silica gel column (washing with dichloromethane)Reagent removal) to yield product 3a as a red solid (56mg, 60%). In addition, white solid 4a (10mg, 11%) was obtained.
Example 12
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.9mmol, 162mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on a silica gel column (eluent dichloromethane) gave product 3a as a red solid (81mg, 90%).
Example 13
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg), zinc acetate (0.3mmol,55mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath and stirred for reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3a as a red solid (79mg, 87%).
Example 14
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg), acetic acid (0.3mmol, 17. mu.L) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath and stirred for reaction for 16 h. After the reaction is finished, after the reaction tube is cooled to room temperature, 10mL of water is added, and then ethyl acetate is usedThe ester was extracted (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on a silica gel column (eluent dichloromethane) gave product 3a as a red solid (74mg, 82%).
Example 15
To a 15mL reaction tube were added 1b (0.3mmol,62mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3b as a red solid (85.5mg, 90%). The characterization data for this compound are as follows:1H NMR(400MHz,CDCl3):δ2.58(s,3H),3.26(s,3H),7.40(t,J＝8.0Hz,1H),7.60-7.65(m,2H),7.95(d,J＝8.8Hz,1H),8.59(s,1H),8.73(d,J＝8.8Hz,1H),8.81(d,J＝8.4Hz,1H).13C NMR(150MHz,CDCl3):δ21.6,24.1,116.9,117.0,117.5,118.4,121.6,123.1,123.4,123.9,125.3,125.7,129.1,133.5,138.2,149.6,167.4,168.6.HRMS calcdfor C19H14N3O2:316.1081[M+H]+,found:316.1096.
example 16
To a 15mL reaction tube were added 1c (0.3mmol,67mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg)mg), the reaction tube was sealed under air conditions, and then placed in a 120 ℃ oil bath to stir the reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3c as a red solid (92mg, 93%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.47(s,3H),4.17(s,3H),7.85(t,J＝8.4Hz,1H),7.98-8.01(m,2H),8.11(t,J＝8.4Hz,1H),8.67(d,J＝2.4Hz,1H),8.72(d,J＝9.6Hz,1H),9.27(d,J＝7.8Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.5,55.5,106.1,110.3,115.9,116.8,121.3,122.1,124.7,126.8,127.8,128.1,129.5,131.7,135.4,140.3,165.9,167.8.HRMScalcd for C19H14N3O3:332.1030[M+H]+,found:332.1042.
example 17
To a 15mL reaction tube were added 1d (0.3mmol,64mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3d as a red solid (72mg, 75%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.44(s,3H),7.86(t,J＝7.8Hz,1H),8.01(d,J＝9.0Hz,1H),8.08(t,J＝7.2Hz,1H),8.13(t,J＝8.4Hz,1H),8.87(d,J＝9.0Hz,1H),8.95(d,J＝5.4Hz,1H),9.28(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.6,110.5,122.6(d,2JC-F＝25.8Hz),115.9,118.1(d,3JC-F＝8.7Hz),120.7(d,3JC-F＝11.0Hz),123.0,124.8,125.4(d,2JC-F＝25.5Hz),127.1,129.3,130.3,132.2(d,4JC-F＝4.7Hz),136.0,140.7,163.1(d,1JC-F＝257.1Hz),165.4,167.1.19F NMR(565MHz,CF3CO2D)δ:-78.2.HRMS calcd forC18H10FNaN3O2:342.0649[M+Na]+,found:342.0652.
example 18
To a 15mL reaction tube were added 1e (0.3mmol,69mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3e as a red solid (78mg, 78%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.64(s,3H),8.06(t,J＝7.2Hz,1H),8.21(d,J＝9.0Hz,1H),8.33(t,J＝7.2Hz,1H),8.48(d,J＝9.0Hz,1H),8.97(d,J＝9.0Hz,1H),9.48(s,2H).13CNMR(150MHz,CF3CO2D):δ23.7,110.7,116.1,116.9,120.0,123.2,125.0,126.8,127.3,130.7,131.1,131.9,136.3,136.8,139.0,141.1,165.6,167.2.HRMS calcd forC18H11ClN3O2:336.0534[M+H]+,found:336.0553.
example 19
To a 15mL reaction tube were added 1f (0.3mmol,79mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3f as a red solid (80mg, 72%). The characterization data for this compound are as follows:1H NMR(400MHz,CF3CO2D):δ3.57(s,3H),7.99(t,J＝7.2Hz,1H),8.17(d,J＝8.4Hz,1H),8.27(t,J＝7.6Hz,1H),8.64(d,J＝8.4Hz,1H),9.12(d,J＝8.8Hz,1H),9.42(d,J＝8.4Hz,1H),9.71(s,1H).13C NMR(100MHz,CF3CO2D):δ23.8,111.0,116.1,116.9,118.9,122.4(q,1J＝270.7Hz),123.6,125.0,125.3(q,3J＝3.8Hz),127.5,131.4,132.1(q,3J＝3.1Hz),132.5,133.90,133.92(q,2J＝34.8Hz),136.7,141.6,165.4,167.0.19F NMR(376MHz,CF3CO2D):δ-78.0.HRMS calcd for C19H11F3N3O2:370.0798[M+H]+,found:370.0806.
example 20
To a 15mL reaction tube were added 1g (0.3mmol,62mg), toluene (3mL), 2g (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After the reaction is finished, the reaction is carried outThe reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on a silica gel column (eluent dichloromethane) gave 3g (80mg, 85%) of the product as a red solid. The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ2.67(s,3H),3.27(s,3H),7.67(t,J＝7.8Hz,1H),7.83(d,J＝9.0Hz,2H),7.94(t,J＝7.8Hz,1H),8.39(s,1H),9.03(d,J＝8.4Hz,1H),9.11(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ21.4,23.7,110.7,114.8,116.1,117.4,120.7,125.2,127.1,127.5,131.3,133.0,133.36,133.40,136.2,141.0,150.9,166.2,167.7,HRMS calcd for C19H14N3O2:316.1081[M+H]+,found:316.1086.
example 21
To a 15mL reaction tube were added 1h (0.3mmol,67mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product as a red solid for 3h (89mg, 90%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.56(s,3H),4.34(s,3H),7.87(d,J＝9.0Hz,1H),7.95(t,J＝7.2Hz,1H),8.09(d,J＝7.8Hz,1H),8.20-8.23(m,2H),9.34(d,J＝9.0Hz,1H),9.39(d,J＝7.8Hz,1H).13C NMR(100MHz,CF3CO2D):δ23.6,56.1,97.0,110.5,113.9,116.0,117.7,122.6,125.2,126.7,129.3,132.1,133.2,135.3,136.1,141.2,166.4,167.4,167.8.HRMS calcd for C19H14N3O3:332.1030[M+H]+,found:332.1035.
example 22
To a 15mL reaction tube were added 1i (0.3mmol,69mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3i as a red solid (77mg, 77%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.54(s,3H),7.96(t,J＝7.8Hz,1H),8.11(d,J＝8.4Hz,1H),8.18-8.20(m,1H),8.24(t,J＝7.8Hz,1H),8.92(s,1H),9.35(d,J＝9.0Hz,1H),9.38(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.6,110.7,115.5,116.0,117.5,121.8,125.0,127.2,128.8,131.5,132.2,132.7,133.1,136.4,141.3,144.6,165.6,167.2.HRMScalcd for C18H11ClN3O2:336.0534[M+H]+,found:336.0528.
example 23
To a 15mL reaction tube were added 1j (0.3mmol,63mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, thenThen placing the mixture in an oil bath at 120 ℃ to stir for reaction for 16 h. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave product 3j (84mg, 89%) as a red solid. The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.62(s,3H),3.64(s,3H),8.06(t,J＝7.2Hz,1H),8.21-8.24(m,2H),8.30-8.34(m,2H),9.51(d,J＝7.8Hz,1H),9.57(d,J＝9.0Hz,1H).13C NMR(150MHz,CF3CO2D):δ21.3,23.7,111.1,115.6,121.2,121.6,125.1,126.2,127.3,127.4,131.0,133.3,133.8,134.5,136.2,140.2,141.3,165.7,167.4.HRMS calcd forC19H13N3NaO2:338.0900[M+Na]+,found:338.0883.
example 24
To a 15mL reaction tube were added 1k (0.3mmol,67mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3k as a red solid (81mg, 82%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.49(s,3H),4.20(s,3H),7.84(d,J＝9.0Hz,1H),7.97(d,J＝9.0Hz,1H),8.16(t,J＝7.2Hz,1H),8.36(t,J＝7.2Hz,1H),8.71(s,1H),8.76(d,J＝8.4Hz,1H),9.33(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.7,55.6,102.9,112.2,115.1,119.1,122.3,128.0,129.4,130.0,131.2,132.2,132.7,136.3,136.9,158.7,166.3,167.7.HRMS calcd for C19H14N3O3:332.1030[M+H]+,found:332.1047.
example 25
To a 15mL reaction tube were added 1l (0.3mmol,67mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on a silica gel column (eluent dichloromethane) gave 3l (72mg, 75%) of the product as a red solid. The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.53(s,3H),7.96-7.99(m,1H),8.13(dd,J1＝9.6Hz,J2＝3.0Hz,1H),8.25(t,J＝7.8Hz,1H),8.45(t,J＝7.8Hz,1H),8.89(d,J＝8.4Hz,1H),9.02-9.03(m,1H),9.41(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.4,109.1(d,2JC-F＝26.9Hz),113.0(d,3JC-F＝8.9Hz),115.4,116.6,116.7,119.3,121.9,126.3(d,2JC-F＝29.0Hz),127.8,130.5(d,3JC-F＝6.3Hz),131.4,132.7(d,4JC-F＝4.2Hz),136.4,137.9,160.1,165.8,167.4.19F NMR(376MHz,CF3CO2D)δ-78.1.HRMS calcd for C18H10FN3NaO2:342.0649[M+Na]+,found:342.0630.
example 26
To a 15mL reaction tube were added 1m (0.3mmol,69mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product as a red solid, 3m (80mg, 80%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.46(s,3H),7.98(d,J＝8.4Hz,1H),8.04(d,J＝7.8Hz,1H),8.18(t,J＝7.2Hz,1H),8.37(d,J＝7.2Hz,1H),8.81(d,J＝7.8Hz,1H),9.26(s,1H),9.33(d,J＝7.8Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.6,112.0,115.3,116.7,119.3,121.8,123.6,127.7,129.7,131.4,132.5,132.9,133.6,136.4,136.8,139.3,165.7,167.3.HRMS calcd for C18H11ClN3O2:336.0534[M+H]+,found:336.0541.
example 27
To a 15mL reaction tube were added 1n (0.3mmol,67mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtering, spin-drying, separating with silica gel column (with dichloromethane as eluent) to obtain redProduct 3n (85mg, 86%) as a colored solid. The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.51(s,3H),4.17(s,3H),7.38(s,1H),7.52(d,J＝9.6Hz,1H),8.16(t,J＝7.8Hz,1H),8.37(t,J＝7.8Hz,1H),8.73(d,J＝8.4Hz,1H),9.16(d,J＝9.0Hz,1H),9.34(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ23.5,55.3,90.4,110.4,114.7,118.4,120.1,121.4,126.0,127.8,130.4,130.5,132.8,133.3,136.4,143.6,166.1,166.9,167.7.HRMS calcd for C19H14N3O3:332.1030[M+H]+,found:332.1016
example 28
To a 15mL reaction tube were added 1o (0.3mmol,72mg), toluene (3mL), 2a (0.45mmol,50mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3o as a red solid (91mg, 88%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ3.40(s,3H),6.25(br s,2H),7.24(br s,1H),8.03-8.04(m,1H),8.24(br s,1H),8.43(br s,1H),8.55-8.56(m,1H),9.19-9.21(m,1H).13C NMR(150MHz,CF3CO2D):δ23.4,89.0,99.8,103.7,114.2,115.5,117.9,121.5,127.7,129.3,130.2,132.1,132.6,135.9,139.6,149.3,156.9,166.1,167.6.HRMS calcd forC19H12N3O4:346.0822[M+H]+,found:346.0835.
example 29
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2b (0.45mmol,56mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3p as a red solid (86mg, 91%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ1.47(t,J＝7.2Hz,3H),4.06(q,J＝7.2Hz,2H),7.89(t,J＝8.4Hz,1H),8.03-8.04(m,1H),8.15-8.20(m,2H),8.39(t,J＝7.8Hz,1H),8.82(d,J＝9.0Hz,1H),9.34(d,J＝8.4Hz,1H),9.37(d,J＝7.8Hz,1H).13C NMR(150MHz,CF3CO2D):δ11.9,34.1,110.5,115.2,116.0,119.2,121.9,125.1,127.0,127.8,130.9,131.2,132.6,133.1,136.1,136.4,140.8,165.6,167.2.HRMS calcd for C19H14N3O2:316.1081[M+H]+,found:316.1080.
example 30
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2c (0.45mmol,84mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After the reaction was completed, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order, anddried over sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3q as a red solid (104mg, 92%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ5.14(s,2H),7.32(t,J＝7.2Hz,1H),7.36(t,J＝7.2Hz,2H),7.50(d,J＝7.2Hz,2H),7.90(t,J＝7.8Hz,1H),8.05(d,J＝8.4Hz,1H),8.16-8.21(m,2H),8.40(t,J＝7.8Hz,1H),8.83(d,J＝9.0Hz,1H),9.36(d,J＝8.4Hz,1H),9.39(d,J＝8.4Hz,1H).13C NMR(150MHz,CF3CO2D):δ42.4,110.4,115.9,119.2,121.8,125.0,127.0,127.7,127.8,128.2,128.6,130.8,131.2,132.5,133.0,134.3,136.1,136.4,140.7,165.4,167.0,HRMS calcd for C24H15N3NaO2:400.1056[M+Na]+,found:400.1067.
example 31
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2d (0.45mmol,81mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3r as a red solid (101mg, 91%). The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ1.62-1.66(m,1H),1.74-1.76(m,2H),2.06-2.08(m,1H),2.19-2.20(m,2H),2.25-2.27(m,2H),2.60-2.62(m,2H),4.62-4.64(m,1H),8.09-8.10(m,1H),8.22-8.23(m,1H),8.36-8.41(m,2H),8.59-8.60(m,1H),9.00-9.02(m,1H),9.57-9.61(m,2H).13C NMR(150MHz,CF3CO2D):δ24.3,25.3,29.4,53.6,110.5,116.1,119.3,121.9,125.3,127.0,127.9,131.1,131.2,132.6,132.9,136.1,136.3,140.9,165.7,167.4.HRMS calcd for C23H20N3O2:370.1550[M+H]+,found:370.1543.
example 32
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2e (0.45mmol,69mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3s as a red solid (91mg, 88%). The characterization data for this compound are as follows:1H NMR(400MHz,CF3CO2D):δ1.90(s,9H),7.86(t,J＝7.6Hz,1H),8.01(d,J＝8.4Hz,1H),8.12-8.18(m,2H),8.34(t,J＝8.0Hz,1H),8.77(d,J＝8.4Hz,1H),9.39-9.42(m,2H).13C NMR(150MHz,CF3CO2D):δ27.4,60.6,110.3,115.0,116.0,119.2,122.0,125.6,126.8,128.0,131.0,132.4,132.6,135.8,135.9,140.8,166.3,168.1.HRMS calcd forC21H18N3O2:344.1394[M+H]+,found:344.1382.
example 33
To a 15mL reaction tube were added 1a (0.3mmol,58mg), toluene (3mL), 2f (0.45mmol,78mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air conditionsThen the mixture is placed in an oil bath at 120 ℃ to be stirred and reacted for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave 3t (93mg, 85%) of the product as a red solid. The characterization data for this compound are as follows:1H NMR(600MHz,CF3CO2D):δ7.56-7.59(m,2H),7.70-7.71(m,3H),7.95(t,J＝7.8Hz,1H),8.14(d,J＝8.4Hz,1H),8.24(t,J＝7.8Hz,1H),8.28(t,J＝7.8Hz,1H),8.49(t,J＝7.8Hz,1H),8.95(d,J＝9.0Hz,1H),9.37(d,J＝8.4Hz,1H),9.47(d,J＝7.8Hz,1H).13CNMR(150MHz,CF3CO2D):δ110.9,115.7,116.3,119.5,122.0,125.2,127.3,127.5,128.3,129.4,130.0,130.5,131.0,131.7,132.9,133.1,136.5,137.0,141.2,166.1,167.5.HRMScalcd for C23H14N3O2:364.1081[M+H]+,found:364.1098.
example 34
To a 15mL reaction tube were added 1b (0.3mmol,63mg), toluene (3mL), 2f (0.45mmol,78mg), and dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Cl ] dimer in that order2]20.015mmol,9.3mg), copper acetate (0.6mmol,109mg) and 1-adamantanecarboxylic acid (0.3mmol,54mg), the reaction tube was sealed under air, and then placed in a 120 ℃ oil bath to stir the reaction for 16 hours. After completion of the reaction, after the reaction tube was cooled to room temperature, 10mL of water was added, followed by extraction with ethyl acetate (10 mL. times.3), and then the organic phase was washed with water and saturated brine in this order and dried over anhydrous sodium sulfate. Filtration, spin-drying and separation on silica gel column (eluent dichloromethane) gave the product 3u as a red solid (99mg, 87%). The characterization data for this compound are as follows:1H NMR(400MHz,CF3CO2D):δ2.84(s,3H),7.54-7.55(m,2H),7.66-7.70(m,3H),7.90(t,J＝8.0Hz,1H),8.08(d,J＝8.4Hz,1H),8.18(t,J＝8.0Hz,1H),8.30(d,J＝8.4Hz,1H),8.79(d,J＝8.8Hz,1H),9.23(s,1H),9.32(d,J＝8.8Hz,1H).13C NMR(100MHz,CF3CO2D):δ19.8,110.5,115.0,115.9,119.4,121.6,124.8,126.9,127.0,129.1,129.7,130.2,131.1,132.2,135.9,138.6,140.6,144.1,166.1,167.4.HRMS calcd for C24H16N3O2:378.1237[M+H]+,found:378.1224.
the foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and the invention is intended to be covered by the appended claims.
Claims (7)
- A method for synthesizing a 2-arylindazolo-maleimide fused polycyclic compound, comprising the steps of: the 2-arylindazole compound 1 and maleimide 2 react at elevated temperature in the presence of a rhodium catalyst and an oxidant to obtain a 2-arylindazolo-maleimide fused polycyclic compound 3, and the reaction equation in the synthesis method is as follows:
wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy or methylenedioxy; r2Selected from hydrogen, halogen, alkyl or alkoxy; r3Selected from aryl, alkyl or benzyl; the rhodium catalyst is [ RhCpCl ]2]2Or [ RhCp (MeCN)3](SbF6)2(ii) a The oxidant is one or a mixture of two of copper acetate, copper acetate monohydrate, zinc acetate and cesium acetate; during the reaction, an additive is added, and the additive is organic acid. - 2. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: r1Is hydrogen, fluorine, chlorine, C1-4Alkyl radical, C1-4Alkoxy or methylenedioxy, R2Is hydrogen, fluorine, chlorine, C1-4Alkyl or C1-4Alkoxy radical, R3Is phenyl, C1-4Alkyl or benzyl.
- 3. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: the reaction is carried out in an organic solvent, wherein the organic solvent is toluene, chlorobenzene, tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, acetonitrile, dioxane or hexafluoroisopropanol.
- 4. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: the heating reaction temperature is 60-140 ℃.
- 5. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: the molar ratio of the 2-arylindazole compound 1, the maleimide 2, the rhodium catalyst and the oxidant is 1:1-3:0.005-0.06: 0.5-3.
- 6. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: the organic acid is selected from one or more of acetic acid, trifluoroacetic acid, p-toluenesulfonic acid monohydrate and 1-adamantanecarboxylic acid.
- 7. The method of synthesizing a 2-arylindazolo-maleimide fused polycyclic compound according to claim 1, wherein: the additive is p-toluenesulfonic acid, p-toluenesulfonic acid monohydrate or 1-adamantanecarboxylic acid, and the adding proportion of the additive is not more than 3 equivalents of 2-arylindazole compound 1.
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