CN1970556B - 1-furfuryl-3-substituted Indolinyl-2-one derivative, its preparation method and uses - Google Patents

1-furfuryl-3-substituted Indolinyl-2-one derivative, its preparation method and uses Download PDF

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CN1970556B
CN1970556B CN2006101191834A CN200610119183A CN1970556B CN 1970556 B CN1970556 B CN 1970556B CN 2006101191834 A CN2006101191834 A CN 2006101191834A CN 200610119183 A CN200610119183 A CN 200610119183A CN 1970556 B CN1970556 B CN 1970556B
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ketone
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indole
furfuryl group
quinoline
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CN1970556A (en
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闻韧
周福生
董肖椿
郑剑斌
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Fudan University
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Abstract

The invention belongs to the drug synthesis field, and relates to a novel indoline-2-ketones compound of formula (1), in particular to a 1-(5-substituted furfuryl) indoline-2-ketones compound with aromatic methylene, C=N or C=O substitute at 3 position and analogues thereof, and preparation method and application in the medicine. The result of rice blast mould activity test experiment for the novel indoline-2-ketones compound of the invention shows that the compound has excellent anti rice blast mould activity. The compound of the invention can be further used for developing antifungal drugs. The formula (1) is shown as follow, wherein R<1> is CHR<4>, NR<5>, and O; R<2> is H, halogen, and hydrocarbon radical; R<3> is O, indoline ring, and five-membered ring; R<4> is aromatic radical, alkylene, and substituted phenyl; R<5> is -NHC (S) NH2.

Description

1-furfuryl group-3-substituted Indolinyl-2-ketone derivatives, preparation method and purposes
Technical field
The invention belongs to the synthetic field of medicine, relate to 1-furfuryl group-3-substituted Indolinyl-2-ketone derivatives, preparation method and application.Be specifically related to a kind of 3 derivatives that 1-(5-replaces furfuryl group) the indole-2-ketone compounds that the two keys of fragrant methylene radical, carbon-to-nitrogen double bon or carbon oxygen replace is arranged, and preparation method thereof and in medically application.
Background technology
The antibiotic New Times that medical revolution occurs opening up, however along with microbiotic the popularizing and abuse of the whole world, no matter the resistance trend has all appearred in gram-positive microorganism or negative bacterium, the resistance problem of gram positive bacterium is even more serious.Some non-pathogenic bacterias become conditioned pathogen, as Bacillus proteus, Pseudomonas aeruginosa etc.; And infection such as virus and deep fungal still lack good control medicine.And along with the widespread use of antitumour drug, immunosuppressor etc., the carrying out in a large number and acquired immune deficiency syndrome (AIDS) popular of organ transplantation, the sickness rate of acute invasive infections with fungi (IFI) but is trend of rising gradually.The appearance of these situations, an urgent demand constantly provide the novel antibacterial medicine, and existing antibacterials development strategy has been proposed challenge.The newtype drug that can do with resistant organism is all actively being sought by the many drugmakers in the world.Continue to seek the lead compound of antifungal drug, have practical significance for exploitation wide spectrum, antifungal drug efficient, low toxicity.
The compound structure with anti-mycotic activity that present investigator is paid close attention to is different.People notice the anti-microbial activity of indole-2-ketone compounds very early.It is the inhibitor of a class 2 type shikimate kinases that research report indole-2-ketone compounds is arranged.The indole-2-ketone compounds can be used for treating or preventing the infection of organism by the biosynthesizing that shikimic acid pathway influences aromatic amino acid.Other has the investigator that the anti-mycotic activity that extracts the derivative of the furans-2-methyl acrylate that obtains from Vicia faba is estimated, and has proved conclusively this compounds and has had anti-mycotic activity.
Summary of the invention:
The purpose of this invention is to provide new indole compounds 1-furfuryl group-3-substituted Indolinyl-2-ketone derivatives, be specifically related to a kind of 3 1-(5-replaces furfuryl group) indole-2-ketone compounds and analogues thereof that have the two keys of fragrant methylene radical, carbon-to-nitrogen double bon or carbon oxygen to replace with good anti-mycotic activity.
Another object of the present invention provides the preparation method of above-mentioned 1-furfuryl group-3-substituted Indolinyl-2-ketone derivatives.
Indole-2-ketone compounds of the present invention has the structure of following general formula (I):
Figure S061B9183420061222D000021
Wherein:
R 1=CHR 4, NR 5, O, wherein, R 4=phenyl, 4-p-methoxy-phenyl, 4-nitrophenyl, 3-nitrophenyl, 4-bromophenyl, 3-bromophenyl, cinnamyl, indol-3-yl; R 5=-NHC (S) NH 2
R 2＝H，CH 3，Br；
R 3=O, indole-2-ketone ring, rhodanine ring.
The preliminary pharmacodynamic study of novel cpd of the present invention, by external antipiriculin experiment, part of compounds has shown good activity, can further prepare the novel anti fungi-medicine.
Preferred compound of the present invention has the structure of following compound 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48 or 49:
Figure S061B9183420061222D000022
Figure S061B9183420061222D000061
The present invention prepares compound 1 or 2 by following method and process:
Figure S061B9183420061222D000062
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenyl aldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone (compound 1 or 2) through condensation, cyclization, reduction.
The present invention prepares compound 3 or 4 by following method and process:
Figure S061B9183420061222D000071
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the aubepine condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone (compound 3 or 4) through condensation, cyclization, reduction.
The present invention prepares compound 5 or 6 by following method and process:
Figure S061B9183420061222D000072
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the paranitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone (compound 5 and 6) through condensation, cyclization, reduction.
The present invention prepares compound 7 or 8 by following method and process:
Figure S061B9183420061222D000081
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the m-nitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone (compound 7 or 8) through condensation, cyclization, reduction.
The present invention prepares compound 9 or 10 by following method and process:
Figure S061B9183420061222D000082
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the p-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone (compound 9 or 10) through condensation, cyclization, reduction.
The present invention prepares compound 11 or 12 by following method and process:
Figure S061B9183420061222D000091
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the 3-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone (compound 11 or 12) through condensation, cyclization, reduction.
The present invention prepares compound 13 or 14 by following method and process:
Figure S061B9183420061222D000092
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenylacrolein condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone (compound 13 or 14) through condensation, cyclization, reduction.
The present invention prepares compound 15 by following method and process:
Figure S061B9183420061222D000101
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain indole-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the indole-3-formaldehyde condensation and obtain 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical) indole-2-ketone (compound 15) through condensation, cyclization, reduction.
The present invention prepares compound 16 or 17 by following method and process:
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenyl aldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone (compound 16 or 17) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 18 or 19 by following method and process:
Figure S061B9183420061222D000111
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the aubepine condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone (compound 18 or 19) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 20 or 21 by following method and process:
Figure S061B9183420061222D000112
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the paranitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone (compound 20 or 21) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 22 or 23 by following method and process:
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the m-nitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone (compound 22 or 23) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 24 or 25 by following method and process:
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the p-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone (compound 24 or 25) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 26 or 27 by following method and process:
Figure S061B9183420061222D000131
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the 3-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone (compound 26 or 27) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 28 or 29 by following method and process:
Figure S061B9183420061222D000132
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenylacrolein condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone (compound 28 or 29) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 30 by following method and process:
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the indole-3-formaldehyde condensation and obtain 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone (compound 30) through condensation, cyclization, reduction, bromo.
The present invention prepares compound 31 or 32 by following method and process:
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenyl aldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone (compound 31 or 32) through condensation, cyclization, reduction.
The present invention prepares compound 33 or 34 by following method and process:
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the aubepine condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone (compound 33 or 34) through condensation, cyclization, reduction.
The present invention prepares compound 35 or 36 by following method and process:
Figure S061B9183420061222D000152
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the paranitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone (compound 35 or 36) through condensation, cyclization, reduction.
The present invention prepares compound 37 or 38 by following method and process:
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the m-nitrobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone (compound 37 or 38) through condensation, cyclization, reduction.
The present invention prepares compound 39 or 40 by following method and process:
Figure S061B9183420061222D000162
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the p-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone (compound 39 or 40) through condensation, cyclization, reduction.
The present invention prepares compound 41 and 42 by following method and process:
Figure S061B9183420061222D000171
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the 3-bromobenzaldehyde condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone (compound 41 or 42) through condensation, cyclization, reduction.
The present invention prepares compound 43 or 44 by following method and process:
Figure S061B9183420061222D000172
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the phenylacrolein condensation and obtain (Z)-and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone (compound 43 or 44) through condensation, cyclization, reduction.
The present invention prepares compound 45 by following method and process:
Adopt para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with the indole-3-formaldehyde condensation and obtain 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone (compound 45) through condensation, cyclization, reduction.
The present invention prepares compound 46 by following method and process:
Figure S061B9183420061222D000182
Adopt aniline and Chloral Hydrate, oxammonium hydrochloride to obtain istain, and then carry out alkylation reaction with the chloromethyl furtural and obtain 1-(5-formyl radical furfuryl group) istain (compound 46) through condensation, cyclization.
The present invention prepares compound 47 by following method and process:
Figure S061B9183420061222D000183
Compound 46 obtains 1-(rhodanine-5-thiazolinyl furfuryl group) istain (compound 47) with the rhodanine condensation in ethanolic soln.
The present invention prepares compound 48 by following method and process:
Compound 46 obtains compound 48 with the indole-2-ketone condensation in ethanolic soln.
The present invention prepares compound 49 by following method and process:
Figure S061B9183420061222D000192
Compound 48 obtains compound 49 with the thiosemicarbazide condensation in benzole soln.
Above-mentioned 3 preliminary pharmacodynamic studies (Rice Blast Fungus active testing) of 1-(4-replaces furfuryl group) indole-2-ketone derivative warp that have the two keys of fragrant methylene radical, carbon-to-nitrogen double bon or carbon oxygen to replace involved in the present invention, the result shows that described compound has antipiriculin activity preferably, and then can be developed as antifungal drug.Wherein the minimum inhibition concentration of the Rice Blast Fungus of compound 1 (MIC) is 1.56 μ g/ml; The MIC value of compound 2 is 12.5 μ g/ml; The MIC value of compound 3 is 5.6 μ g/ml; The MIC value of compound 4 is 15.6 μ g/ml; The MIC value of compound 5 is 100 μ g/ml; The MIC value of compound 6 is 6.25 μ g/ml; The MIC value of compound 7 is 12.5 μ g/ml; The MIC value of compound 8 is 6.25 μ g/ml; The MIC value of compound 9 is 3.12 μ g/ml; The MIC value of compound 10 is 6.25 μ g/ml; The MIC value of compound 11 is 0.78 μ g/ml; The MIC value of compound 12 is 1.56 μ g/ml; The MIC value of compound 13 is 6.25 μ g/ml; The MIC value of compound 14 is 6.25 μ g/ml; The MIC value of compound 15 is 3.12 μ g/ml; The MIC value of compound 16 is 1.56 μ g/ml; The MIC value of compound 17 is 3.12 μ g/ml; The MIC value of compound 18 is 12.5 μ g/ml; The MIC value of compound 19 is 25 μ g/ml; The MIC value of compound 20 is 25 μ g/ml; The MIC value of compound 21 is 12.5 μ g/ml; The MIC value of compound 22 is 6.25 μ g/ml; The MIC value of compound 23 is 6.25 μ g/ml; The MIC value of compound 24 is 6.25 μ g/ml; The MIC value of compound 25 is 6.25 μ g/ml; The MIC value of compound 26 is 3.12 μ g/ml; The MIC value of compound 27 is 3.12 μ g/ml; The MIC value of compound 28 is 100 μ g/ml; The MIC value of compound 29 is 25 μ g/ml; The MIC value of compound 30 is 100 μ g/ml; The MIC value of compound 31 is 1.56 μ g/ml; The MIC value of compound 32 is 1.56 μ g/ml; The MIC value of compound 33 is 3.12 μ g/ml; The MIC value of compound 34 is 3.12 μ g/ml; The MIC value of compound 35 is 25 μ g/ml; The MIC value of compound 36 is 6.25 μ g/ml; The MIC value of compound 37 is 6.25 μ g/ml; The MIC value of compound 38 is 6.25 μ g/ml, and the MIC value of compound 39 is 3.12 μ g/ml; The MIC value of compound 40 is 3.12 μ g/ml; The MIC value of compound 41 is 1.56 μ g/ml; The MIC value of compound 42 is 3.12 μ g/ml; The MIC value of compound 43 is 12.5 μ g/ml; The MIC value of compound 44 is 6.25 μ g/ml; The MIC value of compound 45 is 25 μ g/ml; The MIC value of compound 46-49 is greater than 100 μ g/ml.The MIC value of positive control grisovin (Griseofulvin) is 50.0 μ g/ml.
Embodiment:
Embodiment 1: synthetic compound 1 or 2, (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone
1) synthetic 3-Ben Yajiaji indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 150mg (1.13mmol), phenyl aldehyde 143mg (1.35mmol), 2.5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow needle to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 170mg (68%), m.p.178-179 ℃ (document 175-176 ℃).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone
In the 25ml round-bottomed flask, add 3-Ben Yajiaji indole-2-ketone 150mg (0.68mmol), salt of wormwood 140mg (1.02mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 147mg (1.02mmol) and potassiumiodide 10mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 400mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone 65mg, yield 29%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.28(2H，dd，J＝7.82，7.04Hz，Ar-H)，7.61(1H，s，CH)，7.57(1H，d，J＝7.43Hz，Ar-H)，7.49-7.42(3H，m，Ar-H)，7.28(1H，ddd，J＝7.83，7.82，1.17Hz，Ar-H)，7.17(1H，d，J＝3.53Hz，furan-H)，7.10(1H，ddd，J＝7.43，7.82，1.17Hz，Ar-H)，6.91(1H，d，J＝7.82Hz，Ar-H)，6.46(1H，d，J＝3.52Hz，furan-H)，5.06(2H，s，CH 2)。ESI-MS?m/z?[M+H] +330。Product (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji indole-2-ketone 65mg, yield 29%.
1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.91(1H，s，CH)，7.68-7.65(3H，m，Ar-H)，7.50-7.44(3H，m，Ar-H)，7.26(1H，t，J＝7.43，7.83Hz，Ar-H)，7.18(1H，d，J＝3.52Hz，furan-H)，6.93-6.90(2H，m，Ar-H)，6.48(1H，d，J＝3.52Hz，furan-H)，5.07(2H，s，CH 2)。ESI-MS?m/z?[M+H] +330。
Embodiment 2: synthetic compound 2, (Z) 1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone and compound 3, (E) 1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone.
1) synthetic 3-(4-anisole methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 150mg (1.13mmol), aubepine 194mg (1.35mmol), 2.5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow needle to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 160mg (56%), m.p.162-163 ℃ (163 ℃ in document).
2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone.
In the 25ml round-bottomed flask, add 3-(4-anisole methylene radical) indole-2-ketone 130mg (0.52mmol), salt of wormwood 86mg (0.62mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 89mg (0.62mmol) and potassiumiodide 10mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 200mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone 40mg, yield 21%. 1H?NMR(CDCl 3)δ(ppm)：9.57(1H，s，CHO)，8.39(2H，d，J＝8.60Hz，Ar-H)，7.55(1H，s，CH)，7.54(1H，d，J＝7.44Hz，Ar-H)，7.24(1H，t，J＝6.65，7.82Hz，Ar-H)，7.16(1H，d，J＝3.52Hz，furan-H)，7.08(1H，t，J＝7.43，7.82Hz，Ar-H)，6.97(2H，d，J＝8.61Hz，Ar-H)，6.89(1H，d，J＝7.83Hz，Ar-H)，6.44(1H，d，J＝3.52Hz，furan-H)，5.06(2H，s，CH 2)，3.88(3H，s，OCH 3)。ESI-MS?m/z[M+H] +360。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical) indole-2-ketone 60mg, yield 32%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.86(1H，s，CH)，7.79(1H，d，J＝7.83Hz，Ar-H)，7.67(2H，d，J＝8.60Hz，Ar-H)，7.25(1H，t，J＝7.43，7.83Hz，Ar-H)，7.18(1H，d，J＝3.52Hz，furan-H)，7.00(2H，d，J＝8.61Hz，Ar-H)，6.94(1H，t，J＝7.44，7.82Hz，Ar-H)，6.90(1H，d，J＝7.82Hz，Ar-H)，6.47(1H，d，J＝3.13Hz，furan-H)，5.07(2H，s，CH 2)，3.89(3H，s，OCH 3)。ESI-MS?m/z[M+H] +360。
Embodiment 3: synthetic compound 5; (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone and 6, (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone 1) synthetic 3-(4-oil of mirbane methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 200mg (1.5mmol), paranitrobenzaldehyde 227mg (1.5mmol), 2.5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has orange red crystal to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets the orange red solid 290mg of product (72%), m.p.243-244 ℃ (document 240-243 ℃).
2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone
In the 25ml round-bottomed flask, add 3-(4-oil of mirbane methylene radical) indole-2-ketone 200mg (0.75mmol), salt of wormwood 156mg (1.13mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 162mg (1.13mmol) and potassiumiodide 20mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 400mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone 30mg, yield 11%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，8.35(2H，d，J＝8.61Hz，Ar-H)，8.67(2H，d，J＝8.61Hz，Ar-H)，7.59(1H，s，CH)，7.58(1H，d，J＝7.05Hz，Ar-H)，7.24(1H，t，J＝7.82，7.44Hz，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.12(1H，t，J＝7.43，7.44Hz，Ar-H)，6.95(1H，d，J＝7.82Hz，Ar-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M+H] +375，[M+Na] +397。Obtain product (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical) indole-2-ketone 40mg, yield 14%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，8.34(2H，d，J＝8.61Hz，Ar-H)，7.85(1H，s，CH)，7.80(2H，d，J＝8.61Hz，Ar-H)，7.46(1H，d，J＝7.82Hz，Ar-H)，7.31(1H，t，J＝7.83，7.82Hz，Ar-H)，7.18(1H，d，J＝3.52Hz，furan-H)，6.94(1H，d，J＝7.82Hz，Ar-H)，6.92(1H，t，J＝7.82，7.43Hz，Ar-H)，6.51(1H，d，J＝3.52Hz，furan-H)，5.06(2H，s，CH 2)。ESI-MS?m/z[M+H 2O] +392，[M+Na] +397。
Embodiment 4: synthetic compound 7; (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone and 8, (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone 1) synthetic 3-(3-oil of mirbane methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 300mg (2.26mmol), m-nitrobenzaldehyde 341mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has orange red crystal to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets the orange red solid 500mg of product (83%), m.p.239-240 ℃ (document 255-257 ℃, 227 ℃).
2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone
In the 25ml round-bottomed flask, add 3-(3-oil of mirbane methylene radical) indole-2-ketone 400mg (1.5mmol), salt of wormwood 312mg (2.26mmol) and N, dinethylformamide (DMF) 6ml, add chloromethyl furtural 325mg (2.26mmol) and potassiumiodide 40mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 700mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone 85mg, yield 15%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，9.12(1H，t，J＝1.96Hz，Ar-H)，8.57(1H，dd，J＝7.83，7.05，0.78Hz，Ar-H)，8.26(1H，dt，J＝8.22，1.58，0.79Hz，Ar-H)，7.63(1H，t，J＝7.83，8.21Hz，Ar-H)，7.59(1H，s，CH)，7.58(1H，d，J＝7.05Hz，Ar-H)，7.33(1H，t，J＝7.83Hz，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.12(1H，t，J＝7.43，7.82Hz，Ar-H)，6.94(1H，d，J＝7.83Hz，Ar-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)。ESI-MS?m/z[M+H] +375，[M+Na] +397。Obtain product (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical) indole-2-ketone 70mg, yield 13%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，8.52(1H，s，Ar-H)，8.30(1H，dd，J＝8.21，1.96Hz，Ar-H)，7.94(1H，d，J＝7.83Hz，Ar-H)，7.85(1H，s，CH)，7.68(1H，t，J＝7.83，8.21Hz，Ar-H)，7.46(1H，d，J＝7.83Hz，Ar-H)，7.31(1H，t，J＝7.83Hz，Ar-H)，7.19(1H，d，J＝3.52Hz，furan-H)，6.94(1H，d，J＝8.21Hz，Ar-H)，6.93(1H，t，J＝7.44，7.82Hz，Ar-H)，6.50(1H，d，J＝3.52Hz，furan-H)，5.07(2H，s，CH 2)。ESI-MS?m/z[M+H] +375，[M+Na] +397。
Embodiment 5: synthetic compound 9, (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone and compound 10, (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone
1) synthetic 3-(4-bromobenzene methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 200mg (1.5mmol), p-bromobenzaldehyde 278mg (1.5mmol), 2.5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 280mg (62%), m.p.201-202 ℃ (document 195-196 ℃).2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone
In the 25ml round-bottomed flask, add 3-(4-bromobenzene methylene radical) indole-2-ketone 200mg (0.67mmol), salt of wormwood 138mg (1.00mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 144mg (1.00mmol) and potassiumiodide 20mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 260mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone 45mg, yield 17%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.16(2H，d，J＝8.70Hz，Ar-H)，7.57(2H，d，J＝8.64Hz，Ar-H)，7.55(1H，d，J＝7.58Hz，Ar-H)，7.50(1H，s，CH)，7.29(1H，ddd，J＝7.78，7.70，1.08Hz，Ar-H)，7.16(1H，d，J＝3.57Hz，furan-H)，7.09(1H，ddd，J＝7.63，7.58，0.88Hz，Ar-H)，6.91(1H，d，J＝7.87Hz，Ar-H)，6.46(1H，d，J＝3.57Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M] +408。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical) indole-2-ketone, 30mg, yield 11%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.79(1H，s，CH)，7.63-7.58(1H，m，Ar-H)，7.61(2H，d，J＝8.22Hz，Ar-H)，7.52(2H，d，J＝8.21Hz，Ar-H)，7.27(1H，m，Ar-H)，7.18(1H，d，J＝3.13Hz，furan-H)，6.92(2H，m，Ar-H)，6.48(1H，d，J＝3.52Hz，furan-H)，5.06(2H，s，CH 2)。ESI-MS?m/z[M] +408。
Embodiment 6: synthetic compound 11, (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone and compound 12, (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone
1) synthetic 3-(3-bromobenzene methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 350mg (2.63mmol), 3-bromobenzaldehyde 487mg (2.63mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 650mg (82%), m.p.140-141 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone
In the 25ml round-bottomed flask, add 3-(3-bromobenzene methylene radical) indole-2-ketone 400mg (1.34mmol), salt of wormwood 368mg (2.66mmol) and N, dinethylformamide (DMF) 6ml, add chloromethyl furtural 386mg (2.66mmol) and potassiumiodide 40mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 800mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone 25mg, yield 4.5%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.48(1H，s，Ar-H)，8.18(1H，d，J＝7.82Hz，Ar-H)，7.55(2H，d，J＝7.44Hz，Ar-H)，7.49(1H，s，CH)，7.35-7.27(2H，m，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.10(1H，t，J＝7.43，7.83Hz，Ar-H)，6.91(1H，d，J＝7.82Hz，Ar-H)，6.47(1H，d，J＝3.13Hz，furan-H)，5.06(2H，s，CH 2)。ESI-MS?m/z[M] +408。Product (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical) indole-2-ketone 140mg, yield 26%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，7.81(1H，s，CH)，7.78(1H，s，Ar-H)，7.58-7.56(3H，m，Ar-H)，7.36(1H，t，J＝8.22，7.82Hz，Ar-H)，7.28(1H，t，J＝7.83，7.82，1.18Hz，Ar-H)，7.18(1H，d，J＝3.91Hz，furan-H)，6.94(1H，t，J＝7.83Hz，Ar-H)，6.92(1H，d，J＝7.83Hz，Ar-H)，6.48(1H，d，J＝3.53Hz，furan-H)，5.06(2H，s，CH 2)。ESI-MS?m/z[M] +408。
Embodiment 7: synthetic compound 13, (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone and compound 14, (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone
1) synthetic 3-Chinese cassia tree methylene radical indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 300mg (2.26mmol), phenylacrolein 298mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has orange red crystal to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product red solid 350mg (63%) (Z formula and E formula mixture).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone
In the 25ml round-bottomed flask, add 3-Chinese cassia tree methylene radical indole-2-ketone 200mg (0.81mmol), salt of wormwood 224mg (1.62mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 234mg (1.62mmol) and potassiumiodide 20mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 20 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone 50mg, yield 17.4%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.60(1H，dd，J＝15.65，11.74Hz，CH)，7.61(2H，d，J＝8.22Hz，Ar-H)，7.48(1H，d，J＝7.43Hz，Ar-H)，7.40-7.31(3H，m，Ar-H)，7.34(1H，d，J＝11.73Hz，CH)，7.23(1H，d，J＝7.82Hz，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.06(1H，d，J＝15.65Hz，CH)，7.06(1H，d，J＝7.82Hz，Ar-H)，6.88(1H，d，J＝7.83Hz，Ar-H)，6.45(1H，d，J＝3.92Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M+H] +356。Product (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical indole-2-ketone 30mg, yield 10.5%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.76(1H，d，J＝7.44Hz，indole-H)，7.67(1H，dd，J＝15.26，12.52Hz，CH)，7.60(2H，d，J＝8.60Hz，indole-H)，7.56(1H，d，J＝12.52Hz，CH)，7.45-7.37(3H，m，Ar-H)，7.28(1H，ddd，J＝7.83，7.43，1.18Hz，indole-H)，7.20(1H，d，14.87Hz，CH)，7.17(1H，d，J＝3.52Hz，furan-H)，7.12(1H，ddd，J＝7.43，7.83，1.18Hz，indole-H)，6.92(1H，d，J＝7.82Hz，Ar-H)，6.44(1H，d，J＝3.92Hz，furan-H)，5.05(2H，s，CH 2)。ESI-MS?m/z[M+H] +356。
Embodiment 8: synthetic compound 15,1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical) indole-2-ketone
1) synthetic 3-(3-indoles methylene radical) indole-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add indole-2-ketone 300mg (2.26mmol), indole-3-formaldehyde 328mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=1: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 420mg (72%), m.p.229-230 ℃ (225 ℃ in document).
2) 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical) indole-2-ketone
In the 25ml round-bottomed flask, add 3-(3-indoles methylene radical) indole-2-ketone 350mg (1.35mmol), salt of wormwood 371mg (2.69mmol) and N, dinethylformamide (DMF) 6ml, add chloromethyl furtural 389mg (2.69mmol) and potassiumiodide 40mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=1: 1), show that reaction finishes of TLC check after 10 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 600mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (2: 1) obtains product 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical) indole-2-ketone 240mg, yield 48%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，9.52(1H，s，NH)，7.95(1H，s，CH)，7.95-7.92(1H，m，Ar-H)，7.82(1H，s，Ar-H)，7.63(1H，d，J＝7.83Hz，Ar-H)，7.44-7.40(1H，m，Ar-H)，7.36-7.32(2H，m，Ar-H)，7.19(1H，d，J＝7.83Hz，Ar＝H)，7.15(1H，d，J＝3.52Hz，furan-H)，7.08(1H，t，J＝7.82，7.44Hz，Ar-H)，6.89(1H，d，J＝7.43Hz，Ar-H)，6.33(1H，d，J＝3.52Hz，furan-H)，5.50(2H，s，CH 2)。ESI-MS?m/z[M+H] +369。
Embodiment 9: synthetic compound 16; (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone and compound 17, (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone 1) synthetic 3-Ben Yajiaji-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 300mg (1.42mmol), phenyl aldehyde 180mg (1.70mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 340mg (80%), m.p.212-213 ℃ (214 ℃ in document).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-Ben Yajiaji-5-bromo indole quinoline-2-ketone 300mg (1.0mmol), salt of wormwood 276mg (2.0mmol) and N, dinethylformamide (DMF) 4ml, add chloromethyl furtural 289mg (2.0mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 10 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone 30mg, yield 7%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.30-8.27(2H，m，Ar-H)，7.68(1H，s，Ar-H)，7.59(1H，s，CH)，7.49-7.46(3H，m，Ar-H)，7.39(1H，d，J＝8.22Hz，indole-H)，7.17(1H，d，J＝2.74Hz，furan-H)，6.81(1H，d，J＝8.22Hz，indole-H)，6.46(1H，d，J＝2.74Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MSm/z[M] +408。Product (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-bromo indole quinoline-2-ketone 30mg, yield 7%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，7.96(1H，s，CH)，7.78(1H，d，J＝1.96Hz，indole-H)，7.65-7.62(2H，m，Ar-H)，7.54-7.47(3H，m，Ar-H)，7.38(1H，dd，J＝8.61，8.21Hz，indole-H)，7.19(1H，d，J＝3.52Hz，furan-H)，6.81(1H，d，J＝8.21Hz，indole-H)，6.48(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)。ESI-MS?m/z[M] +408。
Embodiment 10: synthetic compound 18, (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone and compound 19, (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), aubepine 324mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 560mg (90%), m.p.229-230 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone 500mg (1.52mmol), salt of wormwood 313mg (2.27mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 328mg (2.27mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 600mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone 130mg, yield 20%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.39(2H，d，J＝9.00Hz，Ar-H)，7.65(1H，d，J＝1.95Hz，indole-H)，7.52(1H，s，CH)，7.35(1H，dd，J＝8.61，8.22，1.95Hz，indole-H)，7.16(1H，d，J＝3.52Hz，furan-H)，6.98(2H，d，J＝9.00Hz，Ar-H)，6.78(1H，d，J＝8.60Hz，indole-H)，6.44(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)，3.89(3H，s，OCH 3)。ESI-MS?m/z[M] +438，[M+2] +440。Product (AE)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-bromo indole quinoline-2-ketone 80mg, yield 12%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.91(1H，d，J＝1.95Hz，indole-H)，7.89(1H，s，CH)，7.65(2H，d，J＝8.61Hz，Ar-H)，7.37(1H，dd，J＝8.61，8.21，1.96Hz，indole-H)，7.18(1H，d，J＝3.52Hz，furan-H)，7.03(2H，d，J＝9.00Hz，Ar-H)，6.81(1H，d，J＝8.22Hz，indole-H)，6.46(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)，3.91(3H，s，OCH 3)。ESI-MS?m/z[M] +438，[M+2] +440。
Embodiment 11: synthetic compound 20, (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone and compound 21, (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), paranitrobenzaldehyde 313mg (2.08mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product orange solids 630mg (97%), m.p.274-275 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 400mg (1.56mmol), salt of wormwood 240mg (1.74mmol) and N, dinethylformamide (DMF) 8ml adds chloromethyl furtural 251mg (1 after at room temperature stirring half an hour.74mmol) with potassiumiodide 30mg, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show to react and finish of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 40mg, yield 5.7%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.35(2H，d，J＝9.00Hz，Ar-H)，8.28(2H，d，J＝9.00Hz，Ar-H)，7.69(1H，d，J＝1.95Hz，indole-H)，7.57(1H，s，CH)，7.45(1H，dd，J＝8.61，8.60，1.95Hz，indole-H)，7.18(1H，d，J＝3.52Hz，furan-H)，6.85(1H，d，J＝8.22Hz，indole-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.01(2H，s，CH 2)。ESI-MS?m/z[M] +453。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 40mg, yield 5.7%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，8.37(2H，d，J＝8.61Hz，Ar-H)，7.89(1H，s，CH)，7.78(2H，d，J＝8.61Hz，Ar-H)，7.57(1H，d，J＝1.57Hz，indole-H)，7.43(1H，dd，J＝8.61，8.60，1.95Hz，indole-H)，7.19(1H，d，J＝3.52Hz，furan-H)，6.85(1H，d，J＝8.22Hz，indole-H)，6.51(1H，d，J＝3.53Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MSm/z[M+Na+H] +477。
Embodiment 12: synthetic compound 22, (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone and compound 23, (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), m-nitrobenzaldehyde 313mg (2.08mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets the orange solid 640mg (98%) of product, m.p.275-276 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 400mg (1.56mmol), salt of wormwood 240mg (1.74mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 251mg (1.74mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 30mg, yield 4%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，9.17(1H，t，J＝1.96Hz，Ar-H)，8.53(1H，dd，J＝7.82，0.78Hz，Ar-H)，8.29(1H，dq，J＝8.22，2.35Hz，Ar-H)，7.70(1H，d，J＝1.96Hz，indole-H)，7.64(1H，t，J＝8.22Hz，Ar-H)，7.58(1H，s，CH)，7.44(1H，dd，J＝8.22，8.21，1.96Hz，indole-H)，7.18(1H，d，J＝3.91Hz，furan-H)，6.85(1H，d，J＝8.21Hz，indole-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M+Na+H] +477。Product (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-bromo indole quinoline-2-ketone 10mg, yield 1.4%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，8.48(1H，s，Ar-H)，8.33(1H，d，J＝8.21Hz，Ar-H)，7.94(1H，d，J＝7.83Hz，Ar-H)，7.90(1H，s，CH)，7.72(1H，t，J＝8.21，7.83Hz，Ar-H)，7.57(1H，d，J＝1.57Hz，indole-H)，7.43(1H，dd，J＝8.61，8.22，1.57Hz，indole-H)，7.19(1H，d，J＝3.52Hz，furan-H)，6.85(1H，d，J＝8.21Hz，indole-H)，6.51(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)。ESI-MS?m/z[M+H 2O+H] +472。
Embodiment 13: synthetic compound 24, (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone and compound 25, (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), p-bromobenzaldehyde 384mg (2.08mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 630mg (87%), m.p.241 ℃ (no reported in literature).
2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 400mg (1.04mmol), salt of wormwood 215mg (1.56mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 225mg (1.56mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 40mg, yield 8%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.17(2H，d，J＝8.61Hz，Ar-H)，7.66(1H，d，J＝1.95Hz，indole-H)，7.59(2H，d，J＝8.21Hz，Ar-H)，7.48(1H，s，CH)，7.40(1H，dd，J＝8.22，1.96Hz，indole-H)，7.17(1H，d，J＝3.52Hz，furan-H)，6.82(1H，d，J＝8.22Hz，indole-H)，6.46(1H，d，J＝3.52Hz，furan-H)，5.02(2H，s，CH 2)。ESI-MS?m/z[M+H] +488。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 20mg, yield 4%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.83(1H，s，CH)，7.73(1H，d，J＝1.95Hz，indole-H)，7.65(2H，d，J＝8.60Hz，Ar-H)，7.50(2H，d，J＝7.82Hz，Ar-H)，7.40(1H，dd，J＝8.21，1.95Hz，indole-H)，7.18(1H，d，J＝3.52Hz，furan-H)，6.82(1H，d，J＝8.61Hz，indole-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M+H] +488。
Embodiment 14: synthetic compound 18, (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone and compound 19, (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 340mg (1.60mmol), 3-bromobenzaldehyde 326mg (1.76mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product orange solid 560mg (91%), m.p.234-236 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 400mg (1.04mmol), salt of wormwood 215mg (1.56mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 225mg (1.56mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 40mg, yield 8%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.51(1H，d，J＝1.17Hz，Ar-H)，8.16(1H，d，J＝7.82Hz，Ar-H)，7.65(1H，d，J＝1.57Hz，indole-H)，7.57(1H，dd，J＝7.82，1.96Hz，Ar-H)，7.45(1H，s，CH)，7.40(1H，dd，J＝8.22，1.57Hz，indole-H)，7.33(1H，t，J＝7.82Hz，Ar-H)，7.17(1H，d，J＝3.91Hz，furan-H)，6.81(1H，d，J＝8.22Hz，indole-H)，6.47(1H，d，J＝3.52Hz，furan-H)，5.02(2H，s，CH 2)。ESI-MS?m/z[M+H] +488。Product (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-bromo indole quinoline-2-ketone 20mg, yield 4%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，7.85(1H，s，CH)，7.76(1H，s，Ar-H)，7.70(1H，d，J＝1.96Hz，indole-H)，7.61(1H，dd，J＝8.21，0.78Hz，Ar-H)，7.55(1H，dt，J＝7.82，0.78Hz，Ar-H)，7.40(1H，d，J＝8.61Hz，indole-H)，7.39(1H，t，J＝8.21Hz，Ar-H)，7.18(1H，d，J＝3.52Hz，furan-H)，6.82(1H，d，J＝8.61Hz，indole-H)，6.48(1H，d，J＝3.52Hz，furan-H)，5.04(2H，s，CH 2)。ESI-MS?m/z[M+H] +488。
Embodiment 15: synthetic compound 28, (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone and compound 29, (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone
1) synthetic 3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), phenylacrolein 299mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product red solid 150mg (25%) (Z formula and E formula mixture).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-Chinese cassia tree Ben Yajiaji-5-bromo indole quinoline-2-ketone 150mg (0.46mmol), salt of wormwood 96mg (0.69mmol) and N, dinethylformamide (DMF) 4ml, add chloromethyl furtural 100mg (0.69mmol) and potassiumiodide 7mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 200mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone 50mg, yield 25%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，8.56(1H，dd，J＝15.65，1.74Hz，CH)，7.62(2H，dd，J＝8.22，7.43Hz，Ar-H)，7.58(1H，d，J＝1.95Hz，indole-H)，7.42-7.34(3H，m，Ar-H)，7.36(1H，d，J＝16.43Hz，CH)，7.35(1H，d，J＝8.61Hz，indole-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.09(1H，d，J＝15.65Hz，CH)，6.78(1H，d，J＝8.61Hz，indole-H)，6.45(1H，d，J＝3.52Hz，furan-H)，5.02(2H，s，CH 2)。ESI-MS?m/z[M] +434。Product (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-bromo indole quinoline-2-ketone 30mg, yield 15%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，7.80(1H，s，indole-H)，7.60(2H，d，J＝7.04Hz，Ar-H)，7.57(1H，d，J＝15.65Hz，CH)，7.53(1H，d，J＝14.87Hz，CH)，7.46-7.34(4H，m，Ar-H)，7.22(1H，d，J＝13.30Hz，CH)，7.16(1H，d，J＝3.53Hz，furan-H)，6.80(1H，d，J＝8.61Hz，indole-H)，6.43(1H，d，J＝3.52Hz，furan-H)，5.02(2H，s，CH 2)。ESI-MS?m/z[M] +434。
Embodiment 16: synthetic compound 30,1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone
1) synthetic 3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-bromo indole quinoline-2-ketone 400mg (1.89mmol), indole-3-formaldehyde 328mg (2.26mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product orange solids 500mg (83%), m.p.286-287 ℃ (no reported in literature).
2) 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone 400mg (1.18mmol), salt of wormwood 244mg (1.77mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 256mg (1.77mmol) and potassiumiodide 20mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (2: 1) obtains product 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-bromo indole quinoline-2-ketone 20mg, yield 4%. 1H?NMR(DMSO-d 6)δ(ppm)：10.67(1H，s，NH)，9.52(1H，s，CHO)，9.50(1H，s，indole-H-2’)，8.31(1H，d，J＝8.22Hz，Ar-H)，8.24(1H，s，CH)，8.20(1H，s，Ar-H)，7.59(1H，d，J＝7.44Hz，Ar-H)，7.49(1H，d，J＝1.17Hz，Ar-H)，7.32-7.27(3H，m，Ar-H)，6.80(1H，d，J＝3.91Hz，furan-H)，6.79(1H，d，J＝8.21Hz，Ar-H)，5.77(2H，s，CH 2)。ESI-MS?m/z[M] +447。
Embodiment 17: synthetic compound 31, (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone and compound 32, (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone
1) synthetic 3-Ben Yajiaji-5-bromo indole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 300mg (2.04mmol), phenyl aldehyde 260mg (2.45mmol), 4ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 370mg (77%), m.p.193-194 ℃ (182 ℃ in document).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-Ben Yajiaji-5-skatole quinoline-2-ketone 300mg (1.28mmol), salt of wormwood 264mg (1.91mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 277mg (1.91mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 400mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone 50mg, yield 11%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.28(2H，dd，J＝7.63，1.95Hz，Ar-H)，7.58(1H，s，CH)，7.48-7.43(3H，m，Ar-H)，7.39(1H，s，Ar-H)，7.16(1H，d，J＝3.53Hz，furan-H)，7.09(1H，dd，J＝8.02，7.83Hz，Ar-H)，6.79(1H，d，J＝7.83Hz，Ar-H)，6.44(1H，d，J＝3.52Hz，furan-H)，5.03(2H，s，CH 2)，2.38(3H，s，CH 3)。ESI-MS?m/z[M+H] +344。Product (E)-1-(5-formyl radical furfuryl group)-3-Ben Yajiaji-5-skatole quinoline-2-ketone 160mg, 36%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.88(1H，s，CH)，7.66(2H，dd，J＝7.24，0.79Hz，Ar-H)，7.51-7.45(4H，m，Ar-H)，7.17(1H，d，J＝3.72，furan-H)，7.06(1H，dd，J＝8.02Hz，Ar-H)，6.79(1H，d，J＝8.02Hz，Ar-H)，6.46(1H，d，J＝3.72Hz，furan-H)，5.05(2H，s，CH 2)，2.22(3H，s，CH 3)。ESI-MS?m/z[M+H] +344。
Embodiment 18: synthetic compound 33, (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone and compound 34, (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 400mg (2.72mmol), aubepine 444mg (3.27mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product orange solids 560mg (90%), m.p.178-180 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone 300mg (1.13mmol), salt of wormwood 234mg (1.70mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 245mg (1.70mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone 200mg, yield 47%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.38(2H，d，J＝8.80Hz，Ar-H)，7.53(1H，s，CH)，7.37(1H，s，Ar-H)，7.15(1H，d，J＝3.52Hz，furan-H)，7.06(1H，d，J＝7.83Hz，Ar-H)，6.98(2H，d，J＝9.00Hz，Ar-H)，6.78(1H，d，J＝7.82Hz，Ar-H)，6.43(1H，d，J＝3.53Hz，furan-H)，5.05(2H，s，CH 2)，3.88(3H，s，OCH 3)，2.38(3H，s，CH 3)。ESI-MS?m/z[M+H] +374。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-anisole methylene radical)-5-skatole quinoline-2-ketone 100mg, 24%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.83(1H，s，CH)，7.67(2H，d，J＝8.80Hz，Ar-H)，7.62(1H，d，J＝0.98Hz，Ar-H)，7.17(1H，d，J＝3.53Hz，furan-H)，7.06(1H，dd，J＝8.02，7.83，0.98Hz，Ar-H)，7.01(2H，d，J＝8.61Hz，Ar-H)，6.79(1H，d，J＝8.02Hz，Ar-H)，6.45(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)，3.90(3H，s，OCH 3)，2.26(3H，s，CH 3)。ESI-MS?m/z[M+H] +374。
Embodiment 19: synthetic compound 35, (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone and compound 36, (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 300mg (2.04mmol), paranitrobenzaldehyde 370mg (2.45mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product red solid 540mg (95%), m.p.282-284 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone adds 3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 300mg (1.07mmol) in the 25ml round-bottomed flask; salt of wormwood 222mg (1.61mmol) and N; dinethylformamide (DMF) 8ml; add chloromethyl furtural 232mg (1.61mmol) and potassiumiodide 30mg after at room temperature stirring half an hour; continue reaction; (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 80mg, yield 19%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.34(2H，d，J＝8.80Hz，Ar-H)，8.26(2H，d，J＝9.00Hz，Ar-H)，7.55(1H，s，CH)，7.39(1H，s，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.14(1H，d，J＝8.02Hz，Ar-H)，6.82(1H，d，J＝7.82Hz，Ar-H)，6.47(1H，d，J＝3.52Hz，furan-H)，5.01(2H，s，CH 2)，2.38(3H，s，CH 3)。ESI-MS?m/z[M+H] +389。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 20mg, yield 5%. 1H?NMR(DMSO-d 6)δ(ppm)：9.49(1H，s，CHO)，8.37(2H，d，J＝8.61Hz，Ar-H)，7.98(2H，d，J＝8.61Hz，Ar-H)，7.79(1H，s，CH)，7.48(1H，d，J＝3.52Hz，furan-H)，7.28(1H，s，Ar-H)，7.15(1H，d，J＝8.22Hz，Ar-H)，7.04(1H，d，J＝7.83Hz，Ar-H)，6.75(1H，d，J＝3.53Hz，furan-H)，5.10(2H，s，CH 2)，2.15(3H，s，CH 3)。ESI-MS?m/z[M+H] +389411。
Embodiment 20: synthetic compound 37, (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone and compound 38, (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 300mg (2.04mmol), m-nitrobenzaldehyde 370mg (2.45mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets the orange red solid 490mg of product (86%), m.p.215-217 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone adds 3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 400mg (1.13mmol) in the 25ml round-bottomed flask; salt of wormwood 295mg (2.14mmol) and N; dinethylformamide (DMF) 8ml; add chloromethyl furtural 310mg (2.14mmol) and potassiumiodide 30mg after at room temperature stirring half an hour; continue reaction; (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 600mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 30mg, yield 5%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，9.11(1H，s，Ar-H)，8.59(1H，d，J＝7.82Hz，Ar-H)，8.27(1H，d，J＝8.21Hz，Ar-H)，7.62(1H，t，J＝8.22，7.82Hz，Ar-H)，7.56(1H，s，CH)，7.41(1H，s，Ar-H)，7.17(1H，d，J＝3.91Hz，furan-H)，7.13(1H，d，J＝8.21Hz，Ar-H)，6.82(1H，d，J＝7.83Hz，Ar-H)，6.47(1H，d，J＝3.52Hz，furan-H)，5.03(2H，s，CH 2)，2.39(3H，s，CH 3)。ESI-MS?m/z[M+H] +389。Product (E)-1-(5-formyl radical furfuryl group)-3-(3-oil of mirbane methylene radical)-5-skatole quinoline-2-ketone 35mg, 5%. 1H?NMR(DMSO-d 6)δ(ppm)：9.60(1H，s，CHO)，8.57(1H，s，Ar-H)，8.30(1H，d，J＝7.82Hz，Ar-H)，7.94(1H，d，J＝7.43，Ar-H)，7.82(1H，s，CH)，7.68(1H，t，J＝7.83，7.82Hz，Ar-H)，7.34(1H，s，Ar-H)，7.19(1H，d，J＝3.52Hz，furan-H)，7.11(1H，d，J＝8.22Hz，Ar-H)，6.82(1H，d，J＝8.22Hz，Ar-H)，6.49(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)，2.21(3H，s，CH 3).ESI-MS?m/z[M+H] +389。
Embodiment 21: synthetic compound 39, (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone and compound 40, (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 400mg (2.72mmol), p-bromobenzaldehyde 604mg (3.27mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 720mg (84%), m.p.234-235 ℃ (no reported in literature).
2) (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 300mg (0.96mmol), salt of wormwood 198mg (1.43mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 207mg (1.43mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 400mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 50mg, yield 12%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，8.16(2H，d，J＝8.61Hz，Ar-H)，7.57(2H，d，J＝8.61Hz，Ar-H)，7.48(1H，s，CH)，7.37(1H，s，Ar-H)，716(1H，d，J＝3.52Hz，furan-H)，7.09(1H，d，J＝7.83Hz，Ar-H)，6.79(1H，d，J＝7.83，Ar-H)，6.45(1H，d，J＝3.53Hz，furan-H)，5.02(2H，s，CH 2)，2.37(3H，s，CH 3)。ESI-MS?m/z[M] +422。Product (E)-1-(5-formyl radical furfuryl group)-3-(4-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 110mg, yield 27%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.77(1H，s，CH)，7.62(2H，d，J＝8.60Hz，Ar-H)，7.53(2H，d，J＝8.21Hz，Ar-H)，7.43(1H，s，Ar-H)，7.17(1H，d，J＝3.52Hz，furan-H)，7.08(1H，d，J＝7.43，Ar-H)，6.79(1H，d，J＝7.82Hz，Ar-H)，6.46(1H，d，J＝3.92Hz，furan-H)，5.04(2H，s，CH 2)，2.24(3H，s，CH 3)。ESI-MS?m/z[M] +422。
Embodiment 22: synthetic compound 41, (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone and compound 42, (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 300mg (2.04mol), 3-bromobenzaldehyde 453mg (2.45mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 520mg (81%), m.p.212-213 ℃ (no reported in literature).2) (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 450mg (1.43mmol), salt of wormwood 297mg (2.15mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 311mg (2.15mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 600mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 60mg, yield 10%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.48(1H，t，J＝1.95，1.57Hz，Ar-H)，8.18(1H，d，J＝7.83Hz，Ar-H)，7.55(1H，dt，J＝8.22，1.95，0.78Hz，Ar-H)，7.46(1H，s，CH)，7.37(1H，s，Ar-H)，7.32(1H，t，J＝8.22，7.82Hz，Ar-H)，7.16(1H，d，J＝3.52，furan-H)，7.10(1H，d，J＝7.83Hz，Ar-H)，6.79(1H，d，J＝8.22Hz，Ar-H)，6.45(1H，d，J＝3.52Hz，furan-H)，5.03(2H，s，CH 2)，2.37(3H，s，CH 3)。ESI-MS?m/z[M] +422。Product (E)-1-(5-formyl radical furfuryl group)-3-(3-bromobenzene methylene radical)-5-skatole quinoline-2-ketone 110mg, yield 18%. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.82(1H，s，Ar-H)，7.77(1H，s，CH)，7.57(1H，t，J＝7.83，7.43Hz，Ar-H)，7.41(1H，s，Ar-H)，7.36(1H，t，J＝8.21，7.83Hz，Ar-H)，7.18(1H，d，J＝3.52Hz，furan-H)，7.08(1H，d，J＝7.83，Ar-H)，6.79(1H，d，J＝7.82Hz，Ar-H)，6.46(1H，d，J＝3.52Hz，furan-H)，5.04(2H，s，CH 2)，2.23(3H，s，CH 3)。ESI-MS?m/z[M] +422。
Embodiment 23: synthetic compound 43, (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone and compound 44, (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone
1) synthetic 3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 400mg (2.72mmol), phenylacrolein 432mg (3.27mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product dark red solid 400mg (56%) (Z formula and E formula mixture).
2) (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone and (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-Chinese cassia tree Ben Yajiaji-5-skatole quinoline-2-ketone 400mg (1.53mmol), salt of wormwood 415mg (2.87mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 396mg (2.87mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 600mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product (Z)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone 30mg, yield 5%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，8.59(1H，dd，J＝15.65，1.74Hz，CH)，7.62(2H，d，J＝8.21Hz，Ar-H)，7.40-7.32(4H，m，Ar-H)，7.33(1H，d，J＝16.04Hz，CH)，7.17(1H，d，J＝3.52Hz，furan-H)，7.05(1H，d，J＝7.82Hz，Ar-H)，7.04(1H，d，J＝15.65Hz，CH)，6.77(1H，d，J＝7.83，Ar-H)，6.44(1H，d，J＝3.52Hz，furan-H)，5.02(2H，s，CH 2)，2.36(3H，s，CH 3)。ESI-MS?m/z[M+H] +370。Product (E)-1-(5-formyl radical furfuryl group)-3-Chinese cassia tree methylene radical-5-skatole quinoline-2-ketone 40mg, yield 7%. 1H?NMR(CDCl 3)δ(ppm)：9.58(1H，s，CHO)，7.65(1H，dd，J＝14.87，12.13Hz，CH)，7.61(2H，d，J＝6.65Hz，Ar-H)，7.54(1H，s，indole-H)，7.53(1H，d，J＝12.13Hz，CH)，7.46-7.38(3H，m，Ar-H)，7.19(1H，d，J＝14.87Hz，CH)，7.16(1H，d，J＝3.52Hz，furan-H)，7.08(1H，d，J＝8.22Hz，indole-H)，6.79(1H，d，J＝8.21，indole-H)，6.42(1H，d，J＝3.52Hz，furan-H)，5.03(2H，s，CH 2)，2.42(3H，s，CH 3)。ESI-MS?m/z[M+H] +370。
Embodiment 24: synthetic compound 45,1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone
1) synthetic 3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask that is connected to prolong, add 5-skatole quinoline-2-ketone 300mg (2.04mmol), indole-3-formaldehyde 355mg (2.45mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 2h.Back TLC check (developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product yellow solid 420mg (75%), m.p.252-254 ℃ (no reported in literature).2) 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone
In the 25ml round-bottomed flask, add 3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone 350mg (1.23mmol), salt of wormwood 264mg (1.92mmol) and N, dinethylformamide (DMF) 8ml, add chloromethyl furtural 277mg (1.92mmol) and potassiumiodide 30mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 4 hours.Reaction solution is transferred in the separating funnel, and adds 30ml water, extract with ethyl acetate (15ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 500mg crude product.Crude product separates with silica gel column chromatography, and eluent is a sherwood oil: ethyl acetate (4: 1) obtains product 1-(5-formyl radical furfuryl group)-3-(3-indoles methylene radical)-5-skatole quinoline-2-ketone 130mg, yield 27%. 1H?NMR(CDCl 3)δ(ppm)：9.60(1H，s，CHO)，9.51(1H，s，NH)，7.97(1H，dd，J＝7.04Hz，Ar-H)，7.93(1H，s，CH)，7.78(1H，d，J＝7.82Hz，Ar-H)，7.49(1H，s，Ar-H)，7.45(1H，s，Ar-H)，7.42(1H，dd，J＝8.22Hz，Ar-H)，7.36-7.32(2H，m，Ar-H)，7.15(1H，d，J＝3.52Hz，furan-H)，7.01(1H，d，J＝8.22Hz，Ar-H)，6.78(1H，dd，J＝7.83，2.74Hz，Ar-H)，6.33(1H，d，J＝3.52Hz，furan-H)，5.51(2H，s，CH 2)，2.41(3H，s，CH 3)。ESI-MS?m/z[M+H] +383。
Embodiment 25: synthetic compound 46,1-(5-formyl radical furfuryl group) istain
In the 25ml round-bottomed flask, add istain 500mg (3.4mmol), salt of wormwood 680mg (4.9mmol) and N, dinethylformamide (DMF) 3ml, add chloromethyl furtural 540mg (3.74mmol) and potassiumiodide 110mg after at room temperature stirring half an hour, continue reaction, (the developping agent: sherwood oil: ethyl acetate=3: 1), show that reaction finishes of TLC check after 12 hours.Reaction solution is transferred in the separating funnel, and adds 40ml water, extract with ethyl acetate (25ml * 3 time).Merge organic layer, wash with water (15ml * 5 time) and saturated aqueous common salt (20ml * 2 time).The back is with anhydrous magnesium sulfate drying, and the 2h after-filtration steams the solvent decompression fall, and gets the 800mg crude product.Crude product obtains product 1-(4-formyl radical furfuryl group) istain 450mg, yield 52% with re-crystallizing in ethyl acetate. 1H?NMR(CDCl 3)δ(ppm)：9.59(1H，s，CHO)，7.64-7.59(2H，m，Ar-H)，7.20(1H，d，J＝3.52Hz，furan-H)，7.16(1H，t，J＝7.82，7.44Hz，Ar-H)，7.03(1H，d，J＝7.82Hz，Ar-H)，6.57(1H，d，J＝3.52Hz，furan-H)，4.99(2H，s，CH 2)。
Embodiment 26: synthetic compound 47,1-(rhodanine-5-thiazolinyl-furfuryl group) istain
In the 25ml round-bottomed flask that is connected to prolong, add compound 46 330mg (1.29mmol), rhodanine 150mg (1.13mmol), 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 1h.Back TLC check (developping agent: chloroform: methyl alcohol=100: 3), show that reaction finishes.Reaction solution is cooled to room temperature, has the red-brown crystal to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets product red-brown solid 320mg (77%). 1H?NMR(DMSO-d 6)δ(ppm)：13.6(1H，br?s，NH)，7.63(1H，dt，J＝7.83，7.43，1.57Hz，Ar-H)，7.57(1H，d，J＝7.43Hz，Ar-H)，7.37(1H，s，CH)，7.29(1H，d，J＝7.82Hz，Ar-H)，7.14(1H，t，J＝7.44，7.04Hz，Ar-H)，7.09(1H，d，J＝3.52Hz，furan-H)，6.81(1H，d，J＝3.52Hz，furan-H)，5.05(2H，s，CH 2)。
Embodiment 27: synthetic compound 48; 1-(5-(indoline-2 ketone-3-thiazolinyl)-furfuryl group) istain adds compound 46 330mg (1.29mmol) in the 25ml round-bottomed flask that is connected to prolong; indoline-2 ketone 150mg (1.13mmol); 5ml dehydrated alcohol and catalytic amount piperidines are heated with stirring to backflow under nitrogen protection.Reaction 1h.Back TLC check (developping agent: chloroform: methyl alcohol=100: 3), show that reaction finishes.Reaction solution is cooled to room temperature, has orange red crystal to separate out, suction filtration is used twice of washing with alcohol.Final vacuum black out drying gets the orange red solid 400mg of product (96%). 1H?NMR(DMSO-d 6)δ(ppm)：10.50(1H，brs，NH)，8.12(1H，d，J＝7.63Hz，Ar-H)，7.65(1H，ddd，J＝7.64，7.94Hz，Ar-H)，7.58(1H，dd，J＝7.33，6.72Hz，Ar-H)，7.28(1H，d，J＝7.94Hz，Ar-H)，7.22(1H，s，CH)，7.20(1H，d，J＝3.66Hz，furan＝H)，7.19(1H，d，J＝7.63Hz，Ar-H)，7.13(1H，t，J＝7.33Hz，Ar-H)，6.94(1H，d，J＝3.66Hz，furan-H)，6.82-6.78(2H，m，Ar-H)，5.17(2H，s，CH 2)。
Embodiment 28: synthetic compound 49,1-(5-(indoline-2 ketone-3-thiazolinyl)-furfuryl group)-istain-3-thiosemicarbazone
In being housed, the 100mL round-bottomed flask of agitator and water trap adds 0.1g (0.27mmol) compound 48,0.027g (0.30mmol) thiosemicarbazide, the tosic acid of catalytic amount and 60mL benzene, backflow 5h, back TLC check (developping agent: chloroform: methyl alcohol=100: 3), show that reaction finishes.Reaction solution is cooled to room temperature, has yellow crystals to separate out, suction filtration is used the benzene washed twice.Final vacuum black out drying gets product yellowish red color solid 90mg (76%). 1H?NMR(DMSO-d 6)δ(ppm)：12.49(1H，br?s，NH)，10.50(1H，s，NH)，8.96(2H，d，NH 2)，8.08(1H，d，J＝7.80Hz，Ar-H)，7.70(1H，d，J＝7.33Hz，Ar-H)，7.40(1H，t，J＝7.80Hz，Ar-H)，7.28(1H，d，J＝7.80Hz，Ar-H)，7.21(1H，s，CH)，7.21(1H，d，J＝2.93Hz，furan＝H)，7.15(2H，t，J＝7.80.?7.31Hz，Ar-H)，6.97(1H，d，J＝3.41Hz，furan-H)，6.86(1H，t，J＝7.80，7.31Hz，Ar-H)，6.70(1H，d，J＝7.80Hz，Ar-H)，5.25(2H，s，CH 2)。
Embodiment 29: the experiment of Rice Blast Fungus active testing
What foundation such as rugged professor Cheng Fu was delayed in employing is the biological activity assay method of index with the distortion of rice blast mould (Pyricularia oryzae) conidium, mycelial growth morphologic variation or inhibition sprouting, is used to seek antimycotic activeconstituents.Concrete activity index is calibrated standard really and is divided into: suppress active and (suppress the sprouting of spore, spore keeps original form substantially), it is strong active that (spore is not sprouted, or sprout, or mycelial growth, but serious variation all takes place in form), distortion active (spore germination or mycelial growth, but the variation of form generation medium tenacity), weak distortion active (mycelial growth, but growth conditions is unusual) and non-activity (mycelial growth is normal).
Experiment reagent and instrument: the mould P-2b bacterial strain of rice blast, molecular cytobiology institute in Tokyo University's provides.Substratum is 50% seawater potato glucose substratum (1/2PD).Inverted microscope is Shanghai opticinstrument six factory's products.
The mould P-2b inoculation of rice blast (is contained yeast extract 0.2% in slant medium, Zulkovsky starch 1%, agar 2%), cultivate 12～14d at 27 ℃, scrape with an amount of sterilized water and to get spore, remove by filter mycelia, obtain spore suspension, add 2% yeast extract then, and make that with the sterilized water adjusting final spore concentration is 4 * 10 4Individual/mL, the concentration of yeast extract is 0.02% in the spore suspension.The active detection utilizes 96 porocyte culture plates to carry out.Detect and use grisovin (Griseofulvin) as positive control, sample of each row test of 96 orifice plates, eight concentration of each sample test, add excellent 96 orifice plates and cultivate 16h at 27 ℃, observe the situation of spore growth and mycelia distortion then with inverted microscope, no longer suppress the mould growth of rice blast as judging terminal point with target compound, obtain minimum inhibition concentration (MIC).
Table 1 is the active testing result of The compounds of this invention 1～45.
Table 1
Figure S061B9183420061222D000471
Figure S061B9183420061222D000481
Figure S061B9183420061222D000501
Figure S061B9183420061222D000511
The result shows that compound all demonstrates the activity of antipiriculin preferably among the present invention.Wherein compound 1 (1.56), 2 (12.5), 3 (5.6), 4 (15.6), 6 (6.25), 7 (12.5), 8 (6.25), 9 (3.12), 10 (6.25), 11 (0.78), 12 (1.56), 13 (6.25), 14 (6.25), 15 (3.12), 16 (1.56), 17 (3.12), 18 (12.5), 19 (25), 20 (25), 21 (12.5), 22 (6.25), 23 (6.25), 24 (6.25), 25 (6.25), 26 (3.12), 27 (3.12), 29 (25), 31 (1.56), 32 (1.56), 33 (3.12), 34 (3.12), 35 (25), 36 (6.25), 37 (6.25), 38 (6.25), 39 (3.12), 40 (3.12), 41 (1.56), 42 (3.12), 43 (12.5), 44 (6.25), 45 (25) activity is better than positive control grisovin (50.0 μ g/mL).Wherein, compound 11 is active optimum, reaches 0.78 μ g/mL.

Claims (13)

1.1-furfuryl group-3-substituted Indolinyl-2-ketone, it is characterized in that the having general formula structure of (I),
Figure FSB00000410916800011
Wherein
R 1=CHR 4R 4=phenyl, 4-p-methoxy-phenyl, 4-nitrophenyl, 3-nitrophenyl, 4-bromophenyl, 3-bromophenyl, indol-3-yl;
R 2＝H，CH 3，Br；
R 3＝O。
2. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 1 that it is characterized in that having following structure,
Figure FSB00000410916800012
3. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 11 that it is characterized in that having following structure,
4. the compound 13 that has following structure,
Figure FSB00000410916800021
5. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 15 that it is characterized in that having following structure,
6. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 22 that it is characterized in that having following structure,
Figure FSB00000410916800023
7. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 24 that it is characterized in that having following structure,
Figure FSB00000410916800031
8. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 33 that it is characterized in that having following structure,
9. 1-furfuryl group according to claim 1-3-substituted Indolinyl-2-ketone compound, the compound 36 that it is characterized in that having following structure,
10. according to the preparation method of claim 2,3,4 or 5 described compounds, it is characterized in that aniline and Chloral Hydrate, oxammonium hydrochloride obtain indole-2-ketone through condensation, cyclization, reduction, and then respectively with phenyl aldehyde, 3-bromobenzaldehyde, phenylacrolein or indole-3-formaldehyde condensation, carry out hydrocarbonylation with the chloromethyl furtural again and obtain compound 1, compound 11, compound 13 or compound 15.
11. preparation method according to claim 6 or 7 described compounds, it is characterized in that adopting aniline and Chloral Hydrate, oxammonium hydrochloride to obtain 5-bromo indole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with m-nitrobenzaldehyde or p-bromobenzaldehyde condensation respectively and obtain compound 22 or compound 24 through condensation, cyclization, reduction, bromo.
12. according to Claim 8 or the preparation method of 9 described compounds, it is characterized in that adopting para-totuidine and Chloral Hydrate, oxammonium hydrochloride to obtain 5-skatole quinoline-2-ketone, and then carry out hydrocarbonylation with the chloromethyl furtural again with aubepine or paranitrobenzaldehyde condensation respectively and obtain compound 33 or compound 36 through condensation, cyclization, reduction.
13. the purposes of the 1-of claim 1 furfuryl group-3-substituted Indolinyl-2-ketone in preparation antipiriculin medicine.
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