CN108997197A - A kind of cyano carbazole analog derivative and its synthetic method - Google Patents

A kind of cyano carbazole analog derivative and its synthetic method Download PDF

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CN108997197A
CN108997197A CN201810940607.6A CN201810940607A CN108997197A CN 108997197 A CN108997197 A CN 108997197A CN 201810940607 A CN201810940607 A CN 201810940607A CN 108997197 A CN108997197 A CN 108997197A
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alkoxy
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李艳忠
杨亚婕
袁洋
王孟丹
宋博
郑重
徐穆榕
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East China Normal University
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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    • A—HUMAN NECESSITIES
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Abstract

The invention discloses a kind of synthetic methods of cyano carbazole analog derivative, and using indoles acetylenic ketone compounds and alpha-cyano ketone compounds as raw material, " one kettle way " synthesizes the cyano carbazole analog derivative as shown in formula (I).The synthetic method is specifically, the first step realizes C-C σ-bond activation of alpha-cyano ketone by promotor；C-H and/or C-C bond activation selectively occurs under the catalysis of the catalyst for second step.Preparation method of the present invention has many advantages, such as that raw material is simple and easy to get, universality is good, post-processing is easy, yield is good, environmentally friendly.The present invention also provides application of formula (I) the cyano carbazole analog derivative in drug.

Description

A kind of cyano carbazole analog derivative and its synthetic method
Technical field
The invention belongs to organic compound and the technical field of synthesis, it is related to a kind of cyano carbazole analog derivative and its synthesis Method.
Background technique
Cyano carbazole analog derivative is a kind of important organic compound, is primary structure in many natural products and drug Unit, and there is stronger bioactivity mostly.It can be used for organic synthesis intermediate, there is great valence in terms of pharmaceutical synthesis Value.Carbazole compound is a kind of important nitrogen heterocyclic, has special rigid condensed cyclic structure.Carbazole compound knot Structure, which has the following characteristics that, is easily formed metastable cation；Intramolecular has biggish conjugated system and strong intramolecular Electronics transfer；Universal thermal stability and photochemical stability with higher；It is easy to carry out a variety of functional groups of structural modification introducing； Carbazole compound itself is one of coai-tar product, and raw material is easy to get.This special construction of carbazole makes it as a kind of important conjunction At intermediate, it is widely used in organic synthesis field.Carbazole compound is widely present in natural products, such most chemical combination Object has significant bioactivity, plays an important role in field of medicaments, can be used for protein kinase and topoisomerase inhibits The research such as agent, bariatrician, anti-inflammatory, antiviral and anti-tumor drug.
Therefore, people have been attracted widely to pay close attention to the study on the synthesis of carbazole compound.Currently, there are many related carbazoles The report of synthetic method.Such as: document (1) Kong, W.；Fu,C.；Ma,S.Chem.Commun.2009,4572-4574；(2) Yuan,Z.-G.；Wang,Q.；Zheng,A.；Zhang,K.；Lu,L-Q.；Tang,Z.；Xiao,W.- J.Chem.Commun.2016,52,5128-5131.But the prior art also has shortcoming, such as reaction raw materials are not easy to obtain , catalyst is expensive and functional group compatibility is relatively narrow etc..Therefore, it is still necessary to develop more economical, easy and reaction item The mild synthetic method of part.
Summary of the invention
Promote to select under lower generation C-C cleavage reaction and catalyst the object of the present invention is to provide a kind of promotor The tandem reaction of C-H and/or C-C bond activation reaction, preparation method of the present invention simple and easy to get, universality with raw material occur for selecting property Well, the advantages that post-processing is easy, yield is good, environmentally friendly.
The invention also provides a kind of preparation method of cyano carbazole analog derivative shown in formula (I), with indoles acetylenic ketone and Alpha-cyano ketone compounds are raw material, and under the effect of catalyst, promotor and oxidant, synthesis obtains the cyanogen as shown in formula (I) Base carbazole analog derivative.
The invention proposes a kind of cyano carbazole analog derivatives, shown in structure such as formula (I):
Wherein,
R1For electrophilic or electron substituent group, it is selected from aryl, aryl, the halogen that alkyl-substituted aryl, alkoxy replace The aryl or alkyl of aryl, cyano substitution that element replaces；
R2For aryl, hydrogen, halogen, alkyl or alkoxy；
R3The aryl or alkyl that aryl, the halogen replaced for aryl, alkyl-substituted aryl, alkoxy replaces.
Preferably,
R1For electrophilic or electron substituent group, it is selected from phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy take The aryl or C1-C10 alkyl that aryl, the cyano that aryl, the halogen in generation replace replace；
R2For phenyl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3For phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replace aryl, halogen replace aryl or C1-C10 alkyl.
It is further preferred that
R1For phenyl, p-methoxyphenyl；
R2For methyl, chlorine, bromine；
R3For p-methylphenyl, p-fluorophenyl, rubigan.
The invention proposes a kind of preparation method of cyano carbazole analog derivative shown in formula (I), the first steps, in solvent In, using indoles acetylenic ketone compounds and alpha-cyano ketone compounds as raw material, C-C σ-bond activation occurs under promotor effect and obtains To scission of link reaction intermediate；Second step, is added oxidant and catalyst, and selectivity occurs C-H and/or C-C bond activation, synthesizes To the cyano carbazole analog derivative as shown in formula (I):
Its reaction process is as shown in reaction formula (II):
Wherein,
R1For electrophilic or electron substituent group, aryl, the halogen replaced selected from aryl, alkyl-substituted aryl, alkoxy The aryl or alkyl of aryl, cyano substitution that element replaces；
R2For aryl, hydrogen, halogen, alkyl or alkoxy；
R3The aryl or alkyl that aryl, the halogen replaced for aryl, alkyl-substituted aryl, alkoxy replaces.
Preferably,
R1For electrophilic or electron substituent group, it is selected from phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy take The aryl or C1-C10 alkyl that aryl, the cyano that aryl, the halogen in generation replace replace；
R2For phenyl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3For phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replace aryl, halogen replace aryl or C1-C10 alkyl.
It is further preferred that
R1For phenyl, p-methoxyphenyl；
R2For methyl, chlorine, bromine；
R3For p-methylphenyl, p-fluorophenyl, rubigan.
In the present invention, the indoles acetylenic ketone compounds include the acetylenic ketone for being connected with electron-withdrawing group on phenyl ring, are connected on phenyl ring The acetylenic ketone of electron-donating group；The alpha-cyano ketone compounds include cyano ketone compounds, the benzene that electron-withdrawing group is had on phenyl ring The cyano ketone compounds and alkyl-substituted alpha-cyano ketone compounds of electron-donating group are connected on ring.
In the present invention, the promotor is alkali, is selected from DBACO, K2CO3、Cs2CO3Deng one of or it is a variety of；Preferably, The promotor is Cs2CO3。
In the present invention, the catalyst is one of copper catalyst, iron catalyst etc. or a variety of, is selected from FeBr2、 FeCl3、CuBr2Deng one of or it is a variety of；It preferably, is FeBr2。
In the present invention, the oxidant is peroxide, is selected from K2S2O8、(NH4)2S2O8, one of TBHP etc. or more Kind；It preferably, is (NH4)2S2O8。
In the present invention, the indoles acetylenic ketone compounds: alpha-cyano ketone compounds: promotor: catalyst: oxidant Molar ratio is 1.0:1.1:(1.5-3.0): (0.03-0.1): (2.0-4.0)；Preferably, the indoles acetylenic ketone compounds: α- Cyano ketone compounds: promotor: catalyst: the molar ratio of oxidant is 1.0:1.1:1.5:0.05:3.0；1.0:1.1: 2.0:0.05:3.0；1.0:1.1:3.0:0.05:3.0；1.0:1.1:2.0:0.03:3.0；1.0:1.1:2.0:0.1:3.0； 1.0:1.1:2.0:0.05:2.0；1.0:1.1:2.0:0.05:4.0；It is further preferred that the indoles acetylenic ketone compounds: Alpha-cyano ketone compounds: promotor: catalyst: the molar ratio of oxidant is 1.0:1.1:2.0:0.05:3.0.
In the present invention, the solvent is n,N-Dimethylformamide, in n,N-dimethylacetamide, dimethyl sulfoxide, toluene It is one or more；It preferably, is n,N-Dimethylformamide.
In the present invention, the temperature reacted in the first step is 80 DEG C -100 DEG C；It preferably, is 100 DEG C.
In the present invention, the time reacted in the first step is 2.5 hours；Preferably, it is reacted 2.5 hours for 100 DEG C.
In the present invention, the temperature reacted in the second step is 40-80 DEG C；It preferably, is 40 DEG C, 60 DEG C, 80 DEG C；Into one Step is 60 DEG C preferably.
In the present invention, in the second step, the time of the reaction is 3 hours；Preferably, it is reacted 3 hours for 60 DEG C.
In the present invention, the yield of the preparation method is 25-77%.
In the present invention, the reaction preferably carries out under a nitrogen.
It is preferably carried out in scheme at one, shown in synthetic method following reaction formula of the present invention:
Wherein,
R1For electrophilic or electron substituent group, aryl, the halogen replaced selected from aryl, alkyl-substituted aryl, alkoxy The aryl or alkyl of aryl, cyano substitution that element replaces；
R2For aryl, hydrogen, halogen, alkyl or alkoxy；
R3The aryl or alkyl that aryl, the halogen replaced for aryl, alkyl-substituted aryl, alkoxy replaces.
Preferably,
R1For electrophilic or electron substituent group, taken selected from phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy The aryl or C1-C10 alkyl that aryl, the cyano that aryl, the halogen in generation replace replace；
R2For phenyl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3For phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replace aryl, halogen replace aryl or C1-C10 alkyl.
It is further preferred that
R1For phenyl, p-methoxyphenyl；
R2For methyl, chlorine, bromine；
R3For p-methylphenyl, p-fluorophenyl, rubigan.
In a specific embodiment, in preparation method of the present invention, with Cs2CO3For promotor, FeBr2For catalyst, As shown in following formulas (II-2):
Wherein,
R1For electrophilic or electron substituent group, aryl, the halogen replaced selected from aryl, alkyl-substituted aryl, alkoxy The aryl or alkyl of aryl, cyano substitution that element replaces；
R2For aryl, hydrogen, halogen, alkyl or alkoxy；
R3The aryl or alkyl that aryl, the halogen replaced for aryl, alkyl-substituted aryl, alkoxy replaces.
Preferably,
R1For electrophilic or electron substituent group, taken selected from phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy The aryl or C1-C10 alkyl that aryl, the cyano that aryl, the halogen in generation replace replace；
R2For phenyl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3For phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replace aryl, halogen replace aryl or C1-C10 alkyl.
It is further preferred that
R1For phenyl, p-methoxyphenyl；
R2For methyl, chlorine, bromine；
R3For p-methylphenyl, p-fluorophenyl, rubigan.
Reaction principle of the invention are as follows: the first step realizes C-C σ-bond activation of alpha-cyano ketone by promotor；Second step exists C-H and/or C-C bond activation occurs for the lower selectivity of catalyst effect.
The invention also provides cyano carbazole analog derivatives to prepare anti-tumor activity and antibacterial and antiviral activity drug In application.
Cyano carbazole analog derivative be present invention firstly provides noval chemical compound, until so far, there are no relevant report. Cyano carbazole analog derivative proposed by the present invention is essential building blocks in many natural products and drug, is had mostly stronger Bioactivity.It can be used for organic synthesis intermediate, there is substantial worth in terms of pharmaceutical synthesis.Therefore, people are to cyano carbazole The study on the synthesis of analog derivative gives many concerns.
The present invention includes the following advantages: Material synthesis is easy, and promotor and catalyst used are environmentally friendly.This hair Bright synthetic reaction universality is good, raw material is simple and easy to get, post-processing is easy, yield is good, environmentally friendly.
Specific embodiment
In conjunction with following specific embodiments, the present invention is described in further detail, and of the invention protects content not limit to In following embodiment.Without departing from the spirit and scope of the invention, those skilled in the art it is conceivable that variation and excellent Point is all included in the present invention, and using appended claims as protection scope.Implement process of the invention, condition, Reagent, experimental method etc. are among the general principles and common general knowledge in the art, this hair in addition to what is specifically mentioned below It is bright that there are no special restrictions to content.
Embodiment 1, the synthesis of IA
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene indol-2-one, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material is respectively Phenylacetylene indol-2-one 0.3mmol, 2- cyano-acetophenone 0.33mmol, Cs2CO30.6mmol, solvent dimethyl sulfoxide 3ml, 100 DEG C are reacted 2.5 hours, are then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate 0.9mmol is added, is placed in 60 It is reacted 3 hours at DEG C, obtains target product formula (IA), yellow solid, separation yield 73%.Mp 273-275℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ4.27(s,3H),7.03-7.11(m,5H),7.17-7.26(m, 5H), 7.39-7.43 (m, 1H), 7.48-7.50 (m, 1H), 7.55-7.60 (m, 1H), 8.44 (d, J=7.6Hz, 1H), 11.57 (s,1H)；13C NMR(100MHz,CDCl3)δ30.81,87.30,109.26,111.32,115.07,118.00,121.77, 122.06,123.55,126.72,127.76,128.13,128.91,129.04,131.54,131.77,137.83,140.40, 141.46,143.50,149.18,160.74,202.08.
High resolution mass spec data: HRMS (ESI) calcd for C27H19N2O2(M+H)+:403.1441,found 403.1443.
Embodiment 2, the synthesis of IB
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant are selected pair respectively Methoxy-phenylacetylene indol-2-one, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the use of raw material Amount is respectively to Methoxy-phenylacetylene indol-2-one 0.3mmol, 2- cyano-acetophenone 0.33mmol, Cs2CO30.6mmol, solvent Dimethyl sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate is added 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (IB), yellow solid, separation yield 70%.Mp 192-194 ℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 3.69 (s, 3H), 4.26 (s, 3H), 6.62 (d, J=8.4Hz, 2H),7.05-7.10(m,2H),7.15-7.26(m,5H),7.38-7.43(m,1H),7.47-7.49(m,1H),7.54-7.58 (m, 1H), 8.43 (d, J=8.0Hz, 1H), 11.60 (s, 1H)；13C NMR(100MHz,CDCl3)δ30.80,55.10, 87.11,109.22,111.06,113.62,115.11,118.26,121.82,122.01,123.47,126.60,127.75, 128.97,130.29,131.68,132.93,140.44,141.41,143.65,149.06,160.18,160.78,202.11.
High resolution mass spec data: HRMS (ESI) calcd for C28H21N2O3(M+H)+:433.1547,found 433.1557.
Embodiment 3, the synthesis of IC
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene -6- Methvl-indole -2- ketone, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the use of raw material Amount is respectively phenylacetylene -6- Methvl-indole -2- ketone 0.3mmol, 2- cyano-acetophenone 0.33mmol, Cs2CO30.6mmol, solvent Dimethyl sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate is added 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (IC), yellow solid, separation yield 63%.Mp 202-204 ℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ2.48(s,3H),4.05(s,3H),6.91-7.01(m,5H), 7.05-7.16 (m, 7H), 8.13 (d, J=7.6Hz, 1H), 11.42 (s, 1H)；13C NMR(100MHz,CDCl3)δ21.97, 30.56,87.14,109.35,111.22,114.92,118.01,119.26,122.97,123.45,127.66,128.02, 128.75,128.99,131.51,131.63,137.04,137.82,140.35,141.73,143.32,148.49,160.21, 201.99.
High resolution mass spec data: HRMS (ESI) calcd for C28H21N2O2(M+H)+:417.1598,found 417.1607.
Embodiment 4, the synthesis of ID
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene -4- Methoxv-indole -2- ketone, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, raw material Dosage is respectively phenylacetylene -4- Methoxv-indole -2- ketone 0.3mmol, 2- cyano-acetophenone 0.33mmol, Cs2CO30.6mmol、 Solvent dimethyl sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, over cure is added Sour ammonium 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (ID), brown solid, separation yield 72%.Mp 280-281℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 3.98 (s, 3H), 4.13 (s, 3H), 6.70 (d, J=8.4Hz, 1H), 7.05 (d, J=8.4Hz, 1H), 7.14-7.23 (m, 7H), 7.32-7.41 (m, 2H), 7.59 (d, J=8.0Hz, 2H), 10.24(s,1H)；13C NMR(100MHz,CDCl3)δ31.03,56.39,85.76,102.11,103.87,110.08, 110.20,118.17,120.11,127.88,128.13,128.40,128.64,129.49,130.09,133.20,136.68, 138.30,141.96,143.02,145.96,151.90,152.59,196.27.
High resolution mass spec data: HRMS (ESI) calcd for C28H21N2O3(M+H)+:433.1547,found 433.1540.
Embodiment 5, the synthesis of IE
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively The chloro- indol-2-one of acetylene -5-, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material Chloro- indol-2-one 0.3mmol, 2- cyano-acetophenone 0.33mmol, the Cs of respectively phenylacetylene -5-2CO30.6mmol, solvent diformazan Sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate is added 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (IE), yellow solid, separation yield 64%.Mp 271-272 ℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ4.25(s,3H),7.04-7.11(m,5H),7.18-7.26(m, 5H), 7.38-7.41 (m, 1H), 7.49-7.52 (m, 1H), 8.38 (d, J=1.2Hz, 1H), 11.60 (s, 1H)；13C NMR (100MHz,CDCl3)δ31.00,87.50,110.27,110.60,115.14,117.69,122.77,123.08,126.86, 127.64,127.80,128.20,129.04,131.48,131.91,137.61,139.79,140.16,143.79,149.78, 160.86,201.92.
High resolution mass spec data: HRMS (ESI) calcd for C27H18N2O2Cl(M+H)+:437.1051, found437.1051.
Embodiment 6, the synthesis of IF
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively The bromo- indol-2-one of acetylene -4-, 2- cyano-acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material Bromo- indol-2-one 0.3mmol, 2- cyano-acetophenone 0.33mmol, the Cs of respectively phenylacetylene -4-2CO30.6mmol, solvent diformazan Sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate is added 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (IF), crocus solid, separation yield 77%.Mp 248- 250℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ4.16(s,3H),7.08-7.13(m,5H),7.16-7.19(m, 2H),7.22-7.28(m,2H),7.33-7.39(m,3H),7.42-7.45(m,1H),10.29(s,1H)；13C NMR (100MHz,CDCl3)δ31.43,86.74,108.89,109.33,114.32,117.90,118.76,121.63,126.99, 127.55,128.14,128.17,128.94,129.24,130.53,132.68,136.74,139.12,143.29,143.53, 148.28,156.29,198.73.
High resolution mass spec data: HRMS (ESI) calcd for C27H18N2O2Br(M+H)+:481.0546, found481.0561.
Embodiment 7, the synthesis of IG
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene indol-2-one, 2- cyano melilotal, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material Respectively phenylacetylene indol-2-one 0.3mmol, 2- cyano melilotal 0.33mmol, Cs2CO30.6mmol, solvent diformazan Sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate is added 0.9mmol is placed at 60 DEG C and reacts 3 hours, obtains target product formula (IG), yellow solid, separation yield 55%.Mp 283-285 ℃。
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 2.21 (s, 3H), 4.26 (s, 3H), 6.5 (d, J=7.6Hz, 2H),7.09-7.16(m,5H),7.25-7.27(m,2H),7.37-7.42(m,1H),7.46-7.49(m,1H),7.54-7.58 (m, 1H), 8.42 (d, J=7.6Hz, 1H), 11.44 (s, 1H)；13C NMR(100MHz,CDCl3)δ21.16,30.78, 87.09,109.19,111.29,115.25,118.11,121.74,121.96,123.52,126.65,128.03,128.42, 128.78,129.36,131.50,137.51,137.87,141.43,142.64,143.44,148.93,160.45,201.57.
High resolution mass spec data: HRMS (ESI) calcd for C28H20N2O2Na(M+Na)+:439.1417, found439.1420.
Embodiment 8, the synthesis of IH
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene indol-2-one, 2- cyano are to fluoro acetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material point Not Wei phenylacetylene indol-2-one 0.3mmol, 2- cyano to fluoro acetophenone 0.33mmol, Cs2CO30.6mmol, solvent dimethyl sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate 0.9mmol is added, It is placed at 60 DEG C and reacts 3 hours, obtain target product formula (IH), yellow solid, separation yield 60%.Mp 221-222℃.
Nuclear magnetic data:1HNMR(400MHz,CDCl3)δ4.26(s,3H),6.71-6.76(m,2H),7.13(brs,3H), 7.25 (brs, 4H), 7.38-7.43 (m, 1H), 7.47-7.50 (m, 1H), 7.55-7.59 (m, 1H), 8.42 (d, J=7.6Hz, 1H),11.44(s,1H)；13C NMR(100MHz,CDCl3)δ30.80,87.32,109.27,111.34,114.85(JC-F= 22.1Hz),114.85,117.92,121.68,122.10,123.53,126.78,128.26,129.11,131.48,131.64 (JC-F=9.2Hz), 136.51,137.74,141.44,143.48,148.84,160.61,164.76 (JC-F=253.7Hz), 200.33.
High resolution mass spec data: HRMS (ESI) calcd for C27H17N2O2FNa(M+Na)+:443.1166, found443.1168.
Embodiment 9, the synthesis of II
Indoles acetylenic ketone compounds, alpha-cyano ketone compounds, promotor, solvent, catalyst, oxidant select benzene respectively Acetylene indol-2-one, 2- cyano parachloroacetophenone, Cs2CO3, dimethyl sulfoxide, ferrous bromide, ammonium persulfate, the dosage of raw material point It Wei not phenylacetylene indol-2-one 0.3mmol, 2- cyano parachloroacetophenone 0.33mmol, Cs2CO30.6mmol, solvent dimethyl sulfoxide 3ml is reacted 2.5 hours at 100 DEG C, is then cooled to room temperature, and ferrous bromide 0.015mmol, ammonium persulfate 0.9mmol is added, It is placed at 60 DEG C and reacts 3 hours, obtain target product formula (II), yellow solid, separation yield 74%.Mp 267-269℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ4.22(s,3H),6.99-7.02(m,2H),7.12-7.15(m, 5H), 7.23-7.25 (m, 2H), 7.37-7.46 (m, 2H), 7.53-7.57 (m, 1H), 8.39 (d, J=7.6Hz, 1H), 11.51 (s,1H)；13C NMR(100MHz,CDCl3)δ30.74,87.36,109.25,111.28,114.70,117.83,121.61, 122.09,123.46,126.75,127.96,128.25,129.14,130.35,131.51,137.65,137.89,138.60, 141.36,143.43,148.88,160.71,200.59.
High resolution mass spec data: HRMS (ESI) calcd for C27H18N2O2Cl(M+H)+:437.1051, found437.1065.
Protection content of the invention is not limited to above embodiments.Without departing from the spirit and scope of the invention, originally Field technical staff it is conceivable that variation and advantage be all included in the present invention, and with appended claims be protect Protect range.

Claims (10)

1. cyano carbazole analog derivative, which is characterized in that shown in its structure such as formula (I):
Wherein, R1For electrophilic or electron substituent group, taken selected from phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy The aryl or C1-C10 alkyl that aryl, the cyano that aryl, the halogen in generation replace replace；
R2For phenyl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3The aryl or C1- that aryl, the halogen replaced for phenyl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replaces C10 alkyl.
2. the synthetic method of (I) cyano carbazole analog derivative shown in a kind of formula, which is characterized in that with indoles acetylenic ketone compounds It is raw material with alpha-cyano ketone compounds, under the action of catalyst, promotor and oxidant, synthesis is obtained as shown in formula (I) Cyano carbazole analog derivative, shown in reaction process such as formula (II):
Wherein,
R1For electrophilic or electron substituent group, the aryl replaced selected from the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy, The aryl or C1-C10 alkyl of aryl, cyano substitution that halogen replaces；
R2For aryl, hydrogen, halogen, C1-C10 alkyl or C1-C10 alkoxy；
R3The aryl or C1- that aryl, the halogen replaced for aryl, the alkyl-substituted aryl of C1-C10, C1-C10 alkoxy replaces C10 alkyl.
3. synthetic method as claimed in claim 2, which is characterized in that the specific steps are that: the first step, in a solvent, with Yin Diindyl acetylenic ketone compounds and alpha-cyano ketone compounds are raw material, and C-C σ-bond activation occurs under promotor effect and obtains scission of link Reaction intermediate；Oxidant, catalyst is added in second step, C-H and/or C-C bond activation occurs for selectivity, and synthesis obtains described Cyano carbazole analog derivative.
4. synthetic method as claimed in claim 2 or claim 3, which is characterized in that the promotor be alkali, the alkali include DBACO, K2CO3、Cs2CO3One of or it is a variety of.
5. synthetic method as claimed in claim 2 or claim 3, which is characterized in that the catalyst includes FeBr2、FeCl3、CuBr2 One of or it is a variety of.
6. synthetic method as claimed in claim 2 or claim 3, which is characterized in that the oxidant is peroxide, the peroxidating Object includes K2S2O8、(NH4)2S2O8, one of TBHP or a variety of.
7. synthetic method as claimed in claim 3, which is characterized in that the solvent is n,N-Dimethylformamide, N, N- bis- One of methylacetamide, dimethyl sulfoxide, toluene are a variety of.
8. synthetic method as claimed in claim 3, which is characterized in that the temperature reacted in the first step is 80-100 DEG C； In the second step, the temperature of the reaction is 40-80 DEG C.
9. synthetic method as claimed in claim 3, which is characterized in that the time reacted in the first step is 2.5h； In the second step, the time of the reaction is 3h.
10. synthetic method as claimed in claim 2, which is characterized in that the indoles acetylenic ketone compounds: alpha-cyano ketone Close object: promotor: catalyst: the molar ratio of oxidant is 1:1.1:(1.5-3.0): (0.03-0.1): (2.0-4.0).
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