CN110396059A - A kind of synthetic method of 5- cyanoindole - Google Patents
A kind of synthetic method of 5- cyanoindole Download PDFInfo
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- CN110396059A CN110396059A CN201910707385.8A CN201910707385A CN110396059A CN 110396059 A CN110396059 A CN 110396059A CN 201910707385 A CN201910707385 A CN 201910707385A CN 110396059 A CN110396059 A CN 110396059A
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- indoles
- sodium
- cyanoindole
- toluenesulfonyl
- bromo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Abstract
The present invention relates to a kind of synthetic methods of 5- cyanoindole, by the way that using indoles as starting material, by reacting with sodium hydrogensulfite, then successively, progress acetylation, bromination, protection, cyanalation and deprotection obtain 5- cyanoindole.Cost of material used in synthetic method provided by the invention is low in cost and is easy to get, to reduce production cost.The product chemistry purity is high that synthetic route of the present invention is short, yield is high simultaneously, obtains, all reactions are not required to special producing equipment, and gained intermediate and final product are all not required to column chromatography and crystallization purifying.So the present invention not only reduces production cost, is convenient for industry's enlarging production；And high purity product can be provided for market, obtain good economic benefit.
Description
Technical field
The present invention relates to pharmaceutical intermediate field more particularly to a kind of synthetic methods of 5- cyanoindole.
Background technique
5- cyanoindole treats a variety of diseases because it is widely used in synthesis as a kind of important chemical industry or medicine intermediate
Disease active drug molecule and be widely noticed.Such as synthesizing treatment malignant tumour, cardiovascular disease, leukaemia, op parkinson's
The drugs such as disease.And the synthesis of 5- cyanoindole is usually by 5- halogeno indole and cyanide (Cymag, zinc cyanide or cuprous cyanide
Deng) synthesis.This usual toxicity of method is big, pollution is big, is unfavorable for amplification on a large scale, production.Another kind synthesis 5- cyano Yin
The method of diindyl is the compound cyclization synthesis of indole by cyano.However the cost of the raw material of this method is relatively high, is also not easy
It is produced in amplifying.
Summary of the invention
The present invention overcomes the deficiencies in the prior art, provide a kind of synthetic method of 5- cyanoindole.Such as Fig. 1, the present invention
React with sodium hydrogensulfite to obtain the intermediate of aniline derivatives using indoles, and anil can have in bromination process it is good
5- bromo indole can be obtained in good para-selectivity, then passes sequentially through protection, cyanalation, and deprotection obtains 5- cyanoindole.
In order to achieve the above objectives, the technical solution adopted by the present invention are as follows: a kind of synthetic method of 5- cyanoindole is provided,
It is characterized by comprising following steps:
(1) sodium group is introduced on the heterocycle in Indole Molecular structure；
(2) amino for generating product to the step (1) carries out acetylation protection；
(3) step (2) are generated with No. 5 position brominations of the phenyl ring of product；Deacetylated protection simultaneously sloughs sodium sulfonate group
Group obtains 5- bromo indole；
(4) amino for generating product to the step (3) carries out tosylation protection；
(5) step (4) is replaced to generate the bromine on product phenyl ring using cyano；
(6) the de- tosylation of product is generated to the step (5) to protect to obtain 5- cyanoindole.
As a preferred embodiment, comprising the following steps:
(1) it is reacted by indoles and sodium hydrogensulfite, generates indoline -2- sulfonate sodium；
(2) by -2 sulfonate sodium of indoline and acetic anhydride, N- acetyl group-indoline -2- sulfonate sodium is generated；
(3) it is reacted by N- acetyl group-indoline -2- sulfonate sodium with bromine, generates 5- bromo indole；
(4) it is reacted by 5- bromo indole with paratoluensulfonyl chloride, generates the bromo- 1- p-toluenesulfonyl-indoles of 5-；
(5) by the bromo- 1- p-toluenesulfonyl-indoles of 5- and ferrocyanide nak response, 5- cyano -1- is generated to toluene sulphur
Acyl group-indoles；
(6) it is reacted by 5- cyano -1- p-toluenesulfonyl-indoles with sodium hydroxide, generates 5- cyanoindole.
As a kind of more preferable scheme, comprising the following steps:
(1) it is reacted by indoles ethanol solution and aqueous solution of sodium bisulfite, generates indoline -2- sulfonate sodium；
(2) -2 sulfonate sodium of indoline is added in acetic anhydride and is reacted, generate N- acetyl group-indoline -2- sodium sulfonate
Salt；
(3) it is dissolved in water by N- acetyl group-indoline -2- sulfonate sodium, bromine is added dropwise, generate 5- bromo indole；
(4) existing for the sodium hydrogen under the conditions of, through 5- bromo indole and paratoluensulfonyl chloride in n,N-Dimethylformamide
Reaction generates the bromo- 1- p-toluenesulfonyl-indoles of 5-；
(5) it is reacted in n,N-Dimethylformamide by the bromo- 1- p-toluenesulfonyl-indoles of 5- with potassium ferrocyanide,
Generate 5- cyano -1- p-toluenesulfonyl-indoles；
(6) it is reacted in the mixed liquor of second alcohol and water by 5- cyano -1- p-toluenesulfonyl-indoles with sodium hydroxide,
Generate 5- cyanoindole；
As a kind of more preferable scheme, in the step (1), by the ethanol solution of the aqueous solution of sodium hydrogensulfite and indoles
It is reacted 24 hours at 25-28 DEG C；It is filtered, washed, is dried to obtain indoline -2- sulfonate sodium；The indoles and bisulfite
The molar ratio of sodium is 1:2.
As a kind of more preferable scheme, in the step (2), indoline -2- sulfonate sodium is added to 10 times of volumes
In acetic anhydride, it is heated to 65-75 DEG C under nitrogen protection and reacts 2 hours, is warming up to 85-95 DEG C later, reacts 0.5 hour；It is cold
But, it is filtered, washed, is dried in vacuo and obtains N- acetyl group-indoline -2- sulfonate sodium.
As a kind of more preferable scheme, in the step (3), N- acetyl group-indoline -2- sulfonate sodium is dissolved in water
In, bromine is added dropwise under the conditions of being not higher than 5 DEG C；It stirs 30 minutes under the conditions of 0-5 DEG C after being added dropwise to complete, is warming up to later
Then 20-30 DEG C of dropwise addition solution of sodium bisulfite is added solid sodium hydroxide and reacts 12 hours under the conditions of 50-60 DEG C；Cooling,
It is filtered, washed, is dried in vacuo and obtains 5- bromo indole；The molar ratio of the N- acetyl group-indoline -2- sulfonate sodium and bromine is
1:2.
As a kind of more preferable scheme, in the step (4), 5- bromo indole is dissolved in n,N-Dimethylformamide, In
Sodium hydrogen is added portionwise under the conditions of 0-5 DEG C into system, paratoluensulfonyl chloride is added dropwise to system after stirring 30 minutes；It is added dropwise to complete
The reaction was continued afterwards 30 minutes, is poured into water later；It is filtered, washed, is dried in vacuo and obtains the bromo- 1- p-toluenesulfonyl-indoles of 5-；
The molar ratio of the 5- bromo indole and paratoluensulfonyl chloride is 1:1.1.
As a kind of more preferable scheme, in the step (5), the bromo- 1- p-toluenesulfonyl-indoles of 5-, palladium acetate,
Alkali, three hydration potassium ferrocyanides are dispersed in N,N-dimethylformamide；It is heated to 130-150 DEG C of reaction 12 under nitrogen protection
Hour；It is cooled to room temperature, reaction solution is poured into the mixed liquor of water and ethyl acetate, be filtered, washed, separate organic phase；To have
Machine mutually washs, is concentrated, with obtaining 5- cyano -1- p-toluenesulfonyl-indoles after alcohol crystal；The palladium acetate is relative to 5-
The equivalents of bromo- 1- p-toluenesulfonyl-indoles is 0.5-1mol%；The bromo- 1- p-toluenesulfonyl-indoles of 5- and ferrous iron
The molar ratio of potassium cyanide is 1:0.3-1:1.
As a kind of more preferable scheme, the alkali is sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, phosphorus
One of sour potassium.
As a kind of more preferable scheme, in the step (6), by 5- cyano -1- p-toluenesulfonyl-indoles and hydroxide
Sodium is added in the mixed liquor of 6 times of volumes methanols and 2 times of volume of water, is heated to 55-65 DEG C and reacts 2 hours；It is concentrated under reduced pressure and falls to remove
Residue is dispersed in water by methanol；Extraction, dry, concentration；It is washed with 0-5 DEG C of isopropanol, crystallization obtains 5- cyano Yin
Diindyl.
Advantageous effects are the present invention compared with prior art: original used in synthetic method provided by the invention
Material Costco Wholesale is cheap and is easy to get, to reduce production cost.Synthetic route of the present invention is short, yield is high, obtains simultaneously
Product chemistry purity is high, all reactions are not required to special producing equipment, and gained intermediate and final product are all not required to column chromatography
And crystallization purifying.So the present invention not only reduces production cost, is convenient for industry's enlarging production；And high-purity can be provided for market
Product obtains good economic benefit.
Detailed description of the invention
Present invention will be further explained below with reference to the attached drawings and examples.
Fig. 1 is synthetic route chart of the invention.
Specific embodiment
The invention will be further described combined with specific embodiments below.Following embodiment is only used for clearly illustrating
Technical solution of the present invention, and not intended to limit the protection scope of the present invention.
The synthesis of 1 indoline -2- sulfonate sodium of embodiment:
46.8g sodium hydrogensulfite, 160ml water are added in 500ml reaction flask；Then 23.4g indoles is dissolved in 50mL second
In alcohol, room temperature is instilled in 500ml reaction flask；Pico- heat release is reacted, temperature is controlled at 25-28 DEG C, and has solid generation, and at any time
Between increase it is more and more thicker；After being stirred at room temperature for 24 hours, filter solid is crossed, is washed again with 50mL ethyl acetate after solid 20mL ethanol washing
It washs；Room temperature with oil pump be dried under reduced pressure white solid indoline -2- sulfonate sodium 47g；Yield: 98%, purity: 97%.
The synthesis of 2 N- acetyl group of embodiment-indoline -2- sulfonate sodium:
47g indoline -2- sulfonate sodium is added in 450mL aceticanhydride, mechanical stirring；70 DEG C are heated under nitrogen protection
After reacting 2h, it is warming up to 90 DEG C of stirring 0.5h；It is cooled to 25 DEG C later, filtering, 80mL ethyl acetate washing is dried in vacuo to be in
The N- acetyl group of white solid-indoline -2- sulfonate sodium 51g, yield: 90%, purity: 95%.
The synthesis of 3 5- bromo indole of embodiment:
N- acetyl group-indoline -2- sulfonate sodium of 51g is dissolved in 400ml water, is cooled to 0 DEG C, 5 DEG C or less dropwise additions
35g bromine；After being added dropwise to complete under the conditions of 5 DEG C stir 30min after rise to 25 DEG C of dropwise addition solution of sodium bisulfite be quenched it is extra
Bromine；12h is stirred under the conditions of being added 55 DEG C of 31g solid sodium hydroxide, a large amount of solids are precipitated；20 DEG C are cooled to, filtering, clear water is washed
Wash 2 times, be dried in vacuo 30g 5- bromo indole solid；Yield: 88%, purity: 98%.
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 8.05 (s, 1H), 7.81 (s, 1H), 7.42 (dd, 1H), 7.29 (d, 1H), 7.07 (d, 1H), 6.56 (dd, 1H).
The synthesis of the bromo- 1- p-toluenesulfonyl-indoles of 4 5- of embodiment:
The 5- bromo indole of 45g is dissolved in the DMF (N,N-dimethylformamide) of 300mL；Under nitrogen protection, in 0 DEG C of item
Lower 11g sodium hydrogen of part is added step-wise in system, stirs 30min under the conditions of 0 DEG C later；TsCl (toluene sulphur is slowly added dropwise later
Acyl chlorides) DMF solution (55gTsCl is dissolved in 100mLDMF) arrive system；Continue stirring 30min after being added dropwise to complete to fall back
In；Filtering, solid are washed 2 times with clear water, are dried in vacuo to obtain the bromo- 1- p-toluenesulfonyl of 5--indoles solid 80g；Yield:
95%, purity: 98%.
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 8.28 (d, 1H), 8.01 (t, 1H), 7.75 (d, 2H), 7.61 (dd, 1H), 7.44 (d, 2H), 7.39 (s, 1H),
6.44 (dd, 1H), 2.43 (s, 3H).
The synthesis of 5 5- cyano -1- p-toluenesulfonyl of embodiment-indoles:
By the bromo- 1- p-toluenesulfonyl-indoles of the 5- of 25g, 0.1g palladium acetate, 7.6g sodium carbonate, 6.5g tri- is hydrated ferrous iron
Potassium cyanide, 300mLDMF are added in 500mL reaction flask；130 DEG C of reaction 12h are heated under nitrogen protection；It is cooled to room temperature down
Enter into the mixed liquor of 200mL water and 150mL ethyl acetate；Diatomite filtering, 50mL ethyl acetate wash diatomite, filtrate into
Organic phase is isolated in row liquid separation；Organic phase is washed with brine once, and 30g liquid is done to obtain in concentration；The stirring of 25mL ethyl alcohol is added, by
Solid is gradually crystallized out, is filtered after 4h；Solid 10mL ethanol washing obtains 5- cyano -1- p-toluenesulfonyl-indoles after dry
Solid 15.5g, yield: 74%, purity: 98%.
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 8.31 (d, 1H), 8.08 (t, 1H), 7.75 (d, 2H), 7.70 (d, 1H), 7.62 (dd, 1H), 7.44 (d, 2H),
6.44 (dd, 1H), 2.43 (s, 3H).
The synthesis of 6 5- cyano -1- p-toluenesulfonyl of embodiment-indoles:
By the bromo- 1- p-toluenesulfonyl-indoles of the 5- of 25g, 0.2g palladium acetate, 7.6g sodium carbonate, 13g tri- is hydrated ferrous cyanogen
Change potassium, 300mLDMF is added in 500mL reaction flask；150 DEG C of reaction 12h are heated under nitrogen protection；It is cooled to room temperature and pours into
To in the mixed liquor of 200mL water and 150mL ethyl acetate；Diatomite filtering, 50mL ethyl acetate wash diatomite, and filtrate carries out
Organic phase is isolated in liquid separation；Organic phase is washed with brine once, and 35g liquid is done to obtain in concentration；The stirring of 25mL ethyl alcohol is added, gradually
Solid is crystallized out, is filtered after 4h；It is solid to obtain 5- cyano -1- p-toluenesulfonyl-indoles after dry for solid 10mL ethanol washing
Body 16.8g, yield: 80%, purity: 95%.
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 8.31 (d, 1H), 8.08 (t, 1H), 7.75 (d, 2H), 7.70 (d, 1H), 7.62 (dd, 1H), 7.44 (d, 2H),
6.44 (dd, 1H), 2.43 (s, 3H).
The synthesis of 7 5- cyano -1- p-toluenesulfonyl of embodiment-indoles:
By the bromo- 1- p-toluenesulfonyl-indoles of the 5- of 10g, 0.04g palladium acetate, 3.9g potassium carbonate, 2.6g tri- is hydrated ferrous iron
Potassium cyanide, 100mLDMF are added in 250mL reaction flask；150 DEG C of reaction 12h. are heated under nitrogen protection；It is cooled to room temperature down
Enter into the mixed liquor in 100mL water and 100mL ethyl acetate；Diatomite filtering, 50mL ethyl acetate wash diatomite, filtrate
It carries out liquid separation and isolates organic phase；Organic phase is washed with brine once, concentration；The stirring of 10mL ethyl alcohol is added, is gradually crystallized out
Solid filters after 4h；Solid 4mL ethanol washing obtains 5- cyano -1- p-toluenesulfonyl-indoles solid after dry
14.2g, yield: 68%, purity: 99%.
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 8.31 (d, 1H), 8.08 (t, 1H), 7.75 (d, 2H), 7.70 (d, 1H), 7.62 (dd, 1H), 7.44 (d, 2H),
6.44 (dd, 1H), 2.43 (s, 3H).
The synthesis of 8 5- cyanoindole of embodiment:
5- cyano -1- p-toluenesulfonyl-indoles of 5g, 2g sodium hydroxide, 30mL first are added in 100mL reaction flask
Alcohol, 10mL water；It is heated to 60 DEG C of reaction 2h；It is concentrated under reduced pressure methanol later；Residue is added to 30mL water and 30mL acetic acid
In the mixed liquor of ethyl ester；Liquid separation is extracted, dry organic phase is concentrated to give 3.0g solid；It is washed with 3mL5 DEG C of isopropanol, crystallization is dry
It is dry to obtain 5- cyanoindole solid 2.0g, yield: 84%, purity: 97%；
It is detected using nuclear magnetic resonance:
1H NMR(400MHz,CDCl3)
δ 7.90 (s, 1H), 7.81 (s, 1H), 7.58 (d, 1H), 7.43 (d, 1H), 7.07 (d, 1H), 6.56 (d, 1H).
Through magnetic resonance detection, 5- cyanoindole is synthesized out.
Based on the above description of the preferred embodiments of the present invention, through the above description, related personnel completely can be with
Without departing from the scope of the technological thought of the present invention', various changes and amendments are carried out.The technical scope of this invention
It is not limited to the contents of the specification, it is necessary to determine the technical scope according to the scope of the claims.
Claims (10)
1. a kind of synthetic method of 5- cyanoindole, it is characterised in that: the following steps are included:
(1) sodium group is introduced on the heterocycle in Indole Molecular structure；
(2) amino for generating product to the step (1) carries out acetylation protection；
(3) step (2) are generated with No. 5 position brominations of the phenyl ring of product；Deacetylated protection is simultaneously sloughed sodium group and is obtained
To 5- bromo indole；
(4) amino for generating product to the step (3) carries out tosylation protection；
(5) step (4) is replaced to generate the bromine on product phenyl ring using cyano；
(6) the de- tosylation of product is generated to the step (5) to protect to obtain 5- cyanoindole.
2. the synthetic method of 5- cyanoindole according to claim 1, it is characterised in that: the following steps are included:
(1) it is reacted by indoles and sodium hydrogensulfite, generates indoline -2- sulfonate sodium；
(2) by -2 sulfonate sodium of indoline and acetic anhydride, N- acetyl group-indoline -2- sulfonate sodium is generated；
(3) it is reacted by N- acetyl group-indoline -2- sulfonate sodium with bromine, generates 5- bromo indole；
(4) it is reacted by 5- bromo indole with paratoluensulfonyl chloride, generates the bromo- 1- p-toluenesulfonyl-indoles of 5-；
(5) by the bromo- 1- p-toluenesulfonyl-indoles of 5- and ferrocyanide nak response, 5- cyano -1- tolysulfonyl is generated
Base-indoles；
(6) it is reacted by 5- cyano -1- p-toluenesulfonyl-indoles with sodium hydroxide, generates 5- cyanoindole.
3. the synthetic method of 5- cyanoindole according to claim 2, it is characterised in that: the following steps are included:
(1) it is reacted by indoles ethanol solution and aqueous solution of sodium bisulfite, generates indoline -2- sulfonate sodium；
(2) -2 sulfonate sodium of indoline is added in acetic anhydride and is reacted, generate N- acetyl group-indoline -2- sulfonate sodium；
(3) it is dissolved in water by N- acetyl group-indoline -2- sulfonate sodium, bromine is added dropwise, generate 5- bromo indole；
(4) existing for the sodium hydrogen it under the conditions of, is reacted in n,N-Dimethylformamide by 5- bromo indole with paratoluensulfonyl chloride,
Generate the bromo- 1- p-toluenesulfonyl-indoles of 5-；
(5) it is reacted, is generated in n,N-Dimethylformamide with potassium ferrocyanide by the bromo- 1- p-toluenesulfonyl-indoles of 5-
5- cyano -1- p-toluenesulfonyl-indoles；
(6) it is reacted, is generated in the mixed liquor of second alcohol and water with sodium hydroxide by 5- cyano -1- p-toluenesulfonyl-indoles
5- cyanoindole；
4. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (1), by sulfurous
The aqueous solution of sour hydrogen sodium and the ethanol solution of indoles react 24 hours at 25-28 DEG C；It is filtered, washed, is dried to obtain indoline-
2- sulfonate sodium；The molar ratio of the indoles and sodium hydrogensulfite is 1:2.
5. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (2), indoles
Quinoline -2- sulfonate sodium is added in the acetic anhydride of 10 times of volumes, is heated to 65-75 DEG C of reaction 2 hours under nitrogen protection, later
It is warming up to 85-95 DEG C, is reacted 0.5 hour；It cools down, be filtered, washed, being dried in vacuo and obtain N- acetyl group-indoline -2- sodium sulfonate
Salt.
6. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (3), by N- second
Acyl group-indoline -2- sulfonate sodium is molten in water, and bromine is added dropwise under the conditions of being not higher than 5 DEG C；At 0-5 DEG C after being added dropwise to complete
Under the conditions of stir 30 minutes, be warming up to 20-30 DEG C of dropwise addition solution of sodium bisulfite later, then be added solid sodium hydroxide exist
It is reacted 12 hours under the conditions of 50-60 DEG C；Cool down, be filtered, washed, being dried in vacuo and obtain 5- bromo indole；N- acetyl group-the indoles
The molar ratio of quinoline -2- sulfonate sodium and bromine is 1:2.
7. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (4), by 5- bromine
Indoles is dissolved in n,N-Dimethylformamide, and sodium hydrogen is added portionwise under the conditions of 0-5 DEG C into system, will be right after stirring 30 minutes
Toluene sulfochloride is added dropwise to system；The reaction was continued 30 minutes after being added dropwise to complete, and is poured into water later；It is filtered, washed, is dried in vacuo
Obtain the bromo- 1- p-toluenesulfonyl-indoles of 5-；The molar ratio of the 5- bromo indole and paratoluensulfonyl chloride is 1:1.1.
8. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (5), 5-
Bromo- 1- p-toluenesulfonyl-indoles, palladium acetate, alkali, three hydration potassium ferrocyanides are dispersed in N,N-dimethylformamide；In
130-150 DEG C is heated under nitrogen protection to react 12 hours；It is cooled to room temperature, reaction solution is poured into the mixing of water and ethyl acetate
It in liquid, is filtered, washed, separates organic phase；By organic phase washing, concentration, with obtaining 5- cyano -1- after alcohol crystal to toluene sulphur
Acyl group-indoles；The palladium acetate is 0.5-1mol% relative to the equivalents of the bromo- 1- p-toluenesulfonyl-indoles of 5-；The 5-
The molar ratio of bromo- 1- p-toluenesulfonyl-indoles and potassium ferrocyanide is 1:0.3-1:1.
9. the synthetic method of 5- cyanoindole according to claim 8, it is characterised in that: the alkali is sodium hydroxide, hydrogen
Potassium oxide, potassium carbonate, sodium carbonate, cesium carbonate, one of potassium phosphate.
10. the synthetic method of 5- cyanoindole according to claim 3, it is characterised in that: in the step (6), by 5-
Cyano -1- p-toluenesulfonyl-indoles and sodium hydroxide are added in the mixed liquor of 6 times of volumes methanols and 2 times of volume of water, are heated to
55-65 DEG C is reacted 2 hours；Reduced pressure is fallen to remove methanol, and residue is dispersed in water；Extraction, dry, concentration；With 0-5 DEG C
Isopropanol washing, crystallization obtain 5- cyanoindole.
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