CN110183450A - A kind of synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds - Google Patents
A kind of synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds Download PDFInfo
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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 the synthetic methods of a kind of 2- arylindazoles and maleimide fused-polycyclic compounds, belong to technical field of organic synthesis.The synthetic method uses: 2- arylindazoles class compound 1 and maleimide 2, and in the presence of rhodium catalyst and oxidant, dehydrocyclization tandem reaction occurs for heating, obtains 2- arylindazoles and maleimide fused-polycyclic compounds 3.Reaction condition of the present invention is mild, and Atom economy is good, wide application range of substrates, while can carry out without inert gas shielding, and the synthesis for 2- arylindazoles and maleimide fused-polycyclic compounds provides a kind of new method of highly effective.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of 2- arylindazoles and maleimide is condensed more
The synthetic method of cycle compound.
Background technique
Indazole is not only the nuclear structure skeleton of a variety of natural products, and is many anticancers, antiviral, antidepression and anti-
The important composition unit of the artificial synthesizing activity drug such as inflammation.Meanwhile the Pi-conjugated systems that indazole condenses are in biology, chemistry and material
The fields such as science show good application prospect.On the other hand, maleimide derivatives because of its unique optical property and
Multiplicity pharmaceutical activity and in the recent period by synthesis chemist and Pharmaceutical Chemist extensive concern.
In view of the importance of indazole and maleimide compound, it is anticipated that condensed more comprising both pharmacophores
Cycle compound may have bioactivity more stronger than its precursor structure or superior optical property.It is pointed out that mesh
The preceding report there has been no about 2- arylindazoles and maleimide fused-polycyclic compounds synthetic method.
Therefore, it studies and develops and 2- is synthesized as raw material, via easy operating procedure using reagent cheap and easy to get and safe
The method of arylindazoles and maleimide fused-polycyclic compounds not only has important theory significance, but also has weight
The application value wanted.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of 2- arylindazoles and maleimide fused polycycle chemical combination
The synthetic method of object, this method is using 2- arylindazoles class compound and maleimide in the de- of transition metal-catalyzed lower generation
Hydrogen is cyclized tandem reaction, efficiently synthesizes indazole and maleimide fused-polycyclic compounds, and this method has easy to operate, item
The advantages that part is mild, wide application range of substrates.
The present invention adopts the following technical scheme that simultaneously maleimide is condensed for 2- arylindazoles to solve above-mentioned technical problem
The synthetic method of polycyclic compound, it is characterised in that: 2- arylindazoles class compound 1 and maleimide 2, in rhodium catalyst and
In the presence of oxidant, temperature reaction obtains 2- arylindazoles and maleimide fused-polycyclic compounds 3.
Reaction equation in the synthetic method are as follows:
Wherein, R1Selected from hydrogen, halogen, alkyl, alkoxy, two oxygroup of methene etc.；R2Selected from hydrogen, halogen, alkyl, alkoxy
Deng；R3Selected from aryl, alkyl, benzyl etc..The aryl includes phenyl and substituted-phenyl, and the alkyl includes straight chained alkyl, branch
Alkyl group or naphthenic base.
Further, in the above-mentioned technical solutions, R1For hydrogen, fluorine, chlorine, C1-4Alkyl, C1-4Two oxygroup of alkoxy or methene,
R2For hydrogen, trifluoromethyl, fluorine, chlorine, C1-4Alkyl or C1-4Alkoxy, R3For phenyl, C1-4Alkyl, benzyl or cyclohexyl.
Further, in the above-mentioned technical solutions, reaction carries out in organic solvent, and organic solvent is toluene, chlorobenzene, four
Hydrogen furans, 1,2- dichloroethanes, methylene chloride, acetonitrile, dioxane or hexafluoroisopropanol.
Further, in the above-mentioned technical solutions, rhodium catalyst is [RhCp*Cl2]2Or [RhCp* (MeCN)3](SbF6)2；
Oxidant is acetate, is chosen in particular from the mixing of one or both of copper acetate, copper acetate monohydrate, zinc acetate, cesium acetate.
Further, in the above-mentioned technical solutions, 2- arylindazoles class compound 1, maleimide 2, rhodium catalyst with
Oxidant molar ratio is 1:1-3:0.005-0.06:0.5-3.
Further, in the above-mentioned technical solutions, additive is added when reaction, additive is organic acid or organic base, is had
Machine acid is selected from the acid such as acetic acid, trifluoroacetic acid, p-methyl benzenesulfonic acid, p-methyl benzenesulfonic acid monohydrate, 1- adamantanecarboxylic acid (ADA)
One or more, organic base is selected from n,N-diisopropylethylamine, N, one of alkali such as N- dicyclohexylmethylamine, triethylamine or more
Kind.
Additive is not necessary, but in the presence of acid additive, and yield has the raising of highly significant, especially to first
In the presence of benzene sulfonic acid, p-methyl benzenesulfonic acid monohydrate and 1- adamantanecarboxylic acid, the by-product of generation is utmostly inhibited.Add
The additional proportion of agent is added to be no more than 3 equivalents of 2- arylindazoles class compound 1.
Further, in the above-mentioned technical solutions, reaction temperature is selected from 60-140 DEG C, and preferable reaction temperature is 120 DEG C.
Further, in the above-mentioned technical solutions, reaction is without completing under inert gas protection, air, nitrogen or
It can be gone on smoothly in oxygen.
In the course of the research, with 1a (2- phenyl indazole) and 2a (N- methylmaleimido) in [RhCp*Cl2]2For catalysis
For agent, cupric acetate generate 3a for reaction in the presence of oxidant and additive 1- adamantanecarboxylic acid, mechanism speculate in reaction process
It is as follows: [the RhCp* (OAc) that 1a first and in situ ion-exchange are formed2] coordination, intermediate compound I is formed, then C-H metal metaplasia
At rhodium ring II, insertion is then coordinated and migrated with 2a and forms rhodium ring III, it is intermediate that following III overturns generation in acid condition
Body IV, subsequent IV reduction, which is eliminated, obtains intermediate V and Rh (I).Next, V oxidative dehydrogenation aromatisation obtains product 3a, while Rh
(I) Rh (III) is regenerated under Cu (II) oxidation, reaction is expressed as follows:
The invention has the following advantages that 1) synthesis process is simple, efficient, pass through transition metal-catalyzed lower 2- arylindazoles class
The dehydrocyclization tandem reaction that compound and maleimide occur, efficiently synthesizes indazole and maleimide fused polycycle
Object is closed, combined coefficient is high；2) reaction can carry out in air atmosphere, and mild condition is easy to operate；(3) the applicable model of substrate
It encloses wide.Therefore, the present invention provides a kind of efficient for the synthesis of 2- arylindazoles and maleimide fused-polycyclic compounds
Practical new method.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
Crude product detection only have product 3a, cross silica gel post separation (using methylene chloride as eluent) red solid product 3a (81mg,
90%).The characterize data of the compound is as follows:1H NMR(600MHz,CF3CO2D): δ 3.57 (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):δ
23.6,110.6,116.0,119.2,121.9,125.0,127.1,127.9,130.9,131.3,132.6,133.2,136.2,
136.5,140.8,165.9,167.5.HRMS calcd for C18H12N3O2:302.0924[M+H]+,found:
302.0918.
Embodiment 2
Sequentially added in 15mL reaction tube 1a (0.3mmol, 58.3mg), toluene (3mL), 2a (0.45mmol, 50mg),
Dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg) and copper acetate
(0.6mmol, 109mg) will react the seal of tube under air conditions, be subsequently placed in 120 DEG C of oil baths and be stirred to react 16h.Reaction
After, it is cooled to room temperature to reaction tube, 10mL water is added, (10mL × 3) are then extracted with ethyl acetate, organic phase is used later
Water and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (methylene chloride: acetic acid second
Ester=50:1) obtain red solid product 3a (44mg, 49%).In addition, also obtaining white solid 4a (34.5mg, 38%), characterize
It is as follows:1H NMR(400MHz,CDCl3): δ 3.24 (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.
Embodiment 3
Sequentially added in 15mL reaction tube 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), will under air conditions
The seal of tube is reacted, is subsequently placed in 60 DEG C of oil baths and is stirred to react 16h.After reaction, it is cooled to room temperature, is added to reaction tube
Then (10mL × 3) are extracted with ethyl acetate in 10mL water, organic phase water and saturated salt solution successively wash later, anhydrous sulphur
Sour sodium is dry.Filtering, be spin-dried for, cross silica gel post separation (using methylene chloride as eluant, eluent) red solid product 3a (27mg,
30%).In addition, also obtaining white solid 4a (24mg, 26%).
Embodiment 4
Sequentially added in 15mL reaction tube 1a (0.3mmol, 58mg), tetrahydrofuran (3mL), 2a (0.45mmol,
50mg), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg) and He Yishui
It closes copper acetate (0.6mmol, 120mg), the seal of tube will be reacted under air conditions, is subsequently placed in 140 DEG C of oil baths and is stirred to react
16h.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, (10mL × 3) are then extracted with ethyl acetate, later
Organic phase water and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (with dichloromethane
Alkane is eluant, eluent) obtain red solid product 3a (26mg, 29%).In addition, also obtaining white solid 4a (15mg, 16%).
Embodiment 5
Sequentially added in 15mL reaction tube 1a (0.3mmol, 58mg), 1,2- dichloroethanes (3mL), 2a (0.33mmol,
37mg), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), acetic acid
Zinc (0.6mmol, 110mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will then be set
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then uses acetic acid
Ethyl ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, rotation
Dry, TLC only detects product 3a, cross silica gel post separation (using methylene chloride as eluant, eluent) red solid product 3a (77mg,
85%).
Embodiment 6
Sequentially added in 15mL reaction tube 1a (0.3mmol, 58mg), methylene chloride (3mL), 2a (0.9mmol,
100mg), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([[RhCp*Cl2]2, 0.015mmol, 9.3mg), vinegar
Sour caesium (0.6mmol, 115mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), will react the seal of tube, then under air conditions
It is placed in 120 DEG C of oil baths and is stirred to react 16h.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then uses second
Acetoacetic ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, rotation
It is dry, it crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3a (54mg, 60%).
Embodiment 7
1a (0.3mmol, 58mg), acetonitrile (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.0015mmol, 1mg), copper acetate
(0.6mmol, 109mg) and trifluoroacetic acid (0.3mmol, 22 μ L), the seal of tube will be reacted under air conditions, is subsequently placed in 120
16h is stirred to react in DEG C oil bath.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, is then extracted with ethyl acetate
(10mL × 3) are taken, organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicon
Rubber column gel column separates (using methylene chloride as eluant, eluent) and obtains red solid product 3a (18mg, 20%).In addition, also obtaining white solid 4a
(14mg, 15%).
Embodiment 8
Sequentially added in 15mL reaction tube 1a (0.3mmol, 58mg), hexafluoroisopropanol (3mL), 2a (0.45mmol,
50mg), dichloro (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.018mmol, 11mg), copper acetate
(0.6mmol, 109mg) and acetic acid (0.3mmol, 17 μ L), the seal of tube will be reacted under air conditions, is subsequently placed in 120 DEG C of oil
16h is stirred to react in bath.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, is then extracted with ethyl acetate
(10mL × 3), organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel
Post separation (using methylene chloride as eluant, eluent) obtains red solid product 3a (37mg, 40%).In addition, also obtaining white solid 4a
(23mg, 26%).
Embodiment 9
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and p-methyl benzenesulfonic acid monohydrate (0.3mmol, 57mg), will react the seal of tube, so under Oxygen Condition
It is placed in 120 DEG C of oil baths and is stirred to react 16h.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then uses
Ethyl acetate extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering,
It is spin-dried for, crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtain red solid product 3a (72mg, 80%).
Embodiment 10
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.15mmol, 27mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), will react the seal of tube under a nitrogen atmosphere, be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3a (41mg, 45%).In addition, it is solid also to obtain white
Body 4a (9mg, 10%).
Embodiment 11
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.9mmol, 164mg) and 1- adamantanecarboxylic acid (0.15mmol, 27mg), the seal of tube will be reacted under Oxygen Condition, will then be set
16h is stirred to react in 100 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then uses acetic acid
Ethyl ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, rotation
It is dry, it crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3a (56mg, 60%).In addition, also obtaining white
Color solid 4a (10mg, 11%).
Embodiment 12
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.9mmol, 162mg), the seal of tube will be reacted under air conditions, will then be set
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then uses acetic acid
Ethyl ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, rotation
It is dry, it crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3a (81mg, 90%).
Embodiment 13
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg), zinc acetate (0.3mmol, 55mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), under air conditions
The seal of tube will be reacted, is subsequently placed in 120 DEG C of oil baths and is stirred to react 16h.After reaction, it is cooled to room temperature, adds to reaction tube
Enter 10mL water, (10mL × 3) are then extracted with ethyl acetate, organic phase water and saturated salt solution successively wash later, anhydrous
Sodium sulphate is dry.Filtering, be spin-dried for, cross silica gel post separation (using methylene chloride as eluant, eluent) red solid product 3a (79mg,
87%).
Embodiment 14
1a (0.3mmol, 58mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg), acetic acid (0.3mmol, 17 μ L) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), will under air conditions
The seal of tube is reacted, is subsequently placed in 120 DEG C of oil baths and is stirred to react 16h.After reaction, it is cooled to room temperature, is added to reaction tube
Then (10mL × 3) are extracted with ethyl acetate in 10mL water, organic phase water and saturated salt solution successively wash later, anhydrous sulphur
Sour sodium is dry.Filtering, be spin-dried for, cross silica gel post separation (using methylene chloride as eluant, eluent) red solid product 3a (74mg,
82%).
Embodiment 15
1b (0.3mmol, 62mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3b (85.5mg, 90%).The characterization of the compound
Data are as follows:1H NMR(400MHz,CDCl3): δ 2.58 (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 calcd
for C19H14N3O2:316.1081[M+H]+,found:316.1096.
Embodiment 16
1c (0.3mmol, 67mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3c (92mg, 93%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.47 (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.HRMS
calcd for C19H14N3O3:332.1030[M+H]+,found:332.1042.
Embodiment 17
1d (0.3mmol, 64mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3d (72mg, 75%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.44 (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 for
C18H10FNaN3O2:342.0649[M+Na]+,found:342.0652.
Embodiment 18
1e (0.3mmol, 69mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3e (78mg, 78%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.64 (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)13C
NMR(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 for
C18H11ClN3O2:336.0534[M+H]+,found:336.0553.
Embodiment 19
1f (0.3mmol, 79mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3f (80mg, 72%).The characterization number of the compound
According to as follows:1H NMR(400MHz,CF3CO2D): δ 3.57 (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,1), J=270.7Hz 123.6,125.0,125.3 (q,3), J=3.8Hz 127.5,131.4,132.1 (q,3J=
3.1Hz),132.5,133.90,133.92(q,2), J=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.
Embodiment 20
1g (0.3mmol, 62mg), toluene (3mL), 2g (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3g (80mg, 85%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 2.67 (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.
Embodiment 21
1h (0.3mmol, 67mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3h (89mg, 90%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.56 (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.
Embodiment 22
1i (0.3mmol, 69mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3i (77mg, 77%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.54 (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.HRMS
calcd for C18H11ClN3O2:336.0534[M+H]+,found:336.0528.
Embodiment 23
1j (0.3mmol, 63mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3j (84mg, 89%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.62 (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 for
C19H13N3NaO2:338.0900[M+Na]+,found:338.0883.
Embodiment 24
1k (0.3mmol, 67mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3k (81mg, 82%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.49 (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.
Embodiment 25
1l (0.3mmol, 67mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3l (72mg, 75%).The characterization number of the compound
According to 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.
Embodiment 26
1m (0.3mmol, 69mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3m (80mg, 80%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.46 (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.
Embodiment 27
1n (0.3mmol, 67mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3n (85mg, 86%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 3.51 (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
Embodiment 28
1o (0.3mmol, 72mg), toluene (3mL), 2a (0.45mmol, 50mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3o (91mg, 88%).The characterization number of the compound
According to 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 for
C19H12N3O4:346.0822[M+H]+,found:346.0835.
Embodiment 29
1a (0.3mmol, 58mg), toluene (3mL), 2b (0.45mmol, 56mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3p (86mg, 91%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 1.47 (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):δ
11.9,34.1,110.5,115.2,116.0,119.2,121.9,125.1,127.0,127.8,130.9,131.2,132.6,
133.1,136.1,136.4,140.8,165.6,167.2.HRMS calcd for C19H14N3O2:316.1081[M+H]+,
found:316.1080.
Embodiment 30
1a (0.3mmol, 58mg), toluene (3mL), 2c (0.45mmol, 84mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3q (104mg, 92%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 5.14 (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.
Embodiment 31
1a (0.3mmol, 58mg), toluene (3mL), 2d (0.45mmol, 81mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3r (101mg, 91%).The characterization number of the compound
According to 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.
Embodiment 32
1a (0.3mmol, 58mg), toluene (3mL), 2e (0.45mmol, 69mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3s (91mg, 88%).The characterization number of the compound
According to as follows:1H NMR(400MHz,CF3CO2D): δ 1.90 (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 for
C21H18N3O2:344.1394[M+H]+,found:344.1382.
Embodiment 33
1a (0.3mmol, 58mg), toluene (3mL), 2f (0.45mmol, 78mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3t (93mg, 85%).The characterization number of the compound
According to as follows:1H NMR(600MHz,CF3CO2D): δ 7.56-7.59 (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)13C
NMR(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.HRMS
calcd for C23H14N3O2:364.1081[M+H]+,found:364.1098.
Embodiment 34
1b (0.3mmol, 63mg), toluene (3mL), 2f (0.45mmol, 78mg), two are sequentially added in 15mL reaction tube
Chlorine (pentamethylcyclopentadiene base) closes rhodium (III) dimer ([RhCp*Cl2]2, 0.015mmol, 9.3mg), copper acetate
(0.6mmol, 109mg) and 1- adamantanecarboxylic acid (0.3mmol, 54mg), the seal of tube will be reacted under air conditions, will be subsequently placed in
16h is stirred to react in 120 DEG C of oil baths.After reaction, it is cooled to room temperature to reaction tube, 10mL water is added, then use acetic acid second
Ester extracts (10mL × 3), and organic phase water and saturated salt solution successively wash later, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for,
It crosses silica gel post separation (using methylene chloride as eluant, eluent) and obtains red solid product 3u (99mg, 87%).The characterization number of the compound
According to 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):δ
19.8,110.5,115.0,115.9,119.4,121.6,124.8,126.9,127.0,129.1,129.7,130.2,131.1,
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.
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (10)
- The synthetic method of 1.2- arylindazoles and maleimide fused-polycyclic compounds, which is characterized in that including following step Rapid: 2- arylindazoles class compound 1 and maleimide 2, in the presence of rhodium catalyst and oxidant, temperature reaction obtains 2- virtue Base indazole and maleimide fused-polycyclic compounds 3, the reaction equation in the synthetic method are as follows:Wherein, R1Selected from hydrogen, halogen, two oxygroup of alkyl, alkoxy or methene；R2Selected from hydrogen, halogen, alkyl or alkoxy；R3Choosing From aryl, alkyl or benzyl.
- 2. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: R1For hydrogen, fluorine, chlorine, C1-4Alkyl, C1-4Two oxygroup of alkoxy or methene, R2For hydrogen, trifluoromethyl, fluorine, chlorine, C1-4Alkane Base or C1-4Alkoxy, R3For phenyl, C1-4Alkyl, benzyl or cyclohexyl.
- 3. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: the rhodium catalyst is [RhCp*Cl2]2Or [RhCp* (MeCN)3](SbF6)2；Oxidant is acetate.
- 4. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 3, special Sign is: the oxidant is the mixing of one or both of copper acetate, copper acetate monohydrate, zinc acetate, cesium acetate.
- 5. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: reaction carries out in organic solvent, and organic solvent is toluene, chlorobenzene, tetrahydrofuran, 1,2- dichloroethanes, dichloromethane Alkane, acetonitrile, dioxane or hexafluoroisopropanol.
- 6. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: heating reaction temperature is 60-140 DEG C.
- 7. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: the 2- arylindazoles class compound 1, maleimide 2, rhodium catalyst and oxidant molar ratio are 1:1-3: 0.005-0.06:0.5-3。
- 8. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 1, special Sign is: additive being added when reaction, additive is organic acid or organic base.
- 9. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 8, special Sign is: organic acid is in acetic acid, trifluoroacetic acid, p-methyl benzenesulfonic acid, p-methyl benzenesulfonic acid monohydrate, 1- adamantanecarboxylic acid One or more, organic base is selected from n,N-diisopropylethylamine, N, one of N- dicyclohexylmethylamine, triethylamine or a variety of.
- 10. the synthetic method of 2- arylindazoles and maleimide fused-polycyclic compounds according to claim 8, special Sign is: additive is p-methyl benzenesulfonic acid, p-methyl benzenesulfonic acid monohydrate or 1- adamantanecarboxylic acid, and the additional proportion of additive is not More than 3 equivalents of 2- arylindazoles class compound 1.
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| CN110698431B (en) * | 2019-11-20 | 2022-07-01 | 陕西师范大学 | Synthetic method of 1, 2-benzothiazine compound |
| CN112174962A (en) * | 2020-10-27 | 2021-01-05 | 河南师范大学 | Synthesis method of benzo [ e ] pyridylimidazo [4,5-g ] isoindole-1, 3(2H) -diketone compound |
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