[ CAS No. 771-51-7 ] {[proInfo.proName]}

Name: 771-51-7|2-(1H-Indol-3-yl)acetonitrile|98%
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SKU: A258813
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Quality Control of [ 771-51-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 771-51-7 ]

Product Details of [ 771-51-7 ]

CAS No. :	771-51-7	MDL No. :	MFCD00005628
Formula :	C₁₀H₈N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DMCPFOBLJMLSNX-UHFFFAOYSA-N
M.W :	156.18	Pubchem ID :	351795
Synonyms :		Chemical Name :	2-(1H-Indol-3-yl)acetonitrile

Calculated chemistry of [ 771-51-7 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.1
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	47.82
TPSA :	39.58 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.12 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.33
Log Po/w (XLOGP3) :	1.6
Log Po/w (WLOGP) :	2.23
Log Po/w (MLOGP) :	1.18
Log Po/w (SILICOS-IT) :	2.82
Consensus Log Po/w :	1.83

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.31
Solubility :	0.773 mg/ml ; 0.00495 mol/l
Class :	Soluble
Log S (Ali) :	-2.04
Solubility :	1.42 mg/ml ; 0.00906 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.76
Solubility :	0.0271 mg/ml ; 0.000174 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.36

Safety of [ 771-51-7 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P501-P261-P270-P271-P264-P280-P361+P364-P301+P310+P330-P302+P352+P312-P304+P340+P311-P403+P233-P405	UN#:	3439
Hazard Statements:	H301-H311-H331	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 771-51-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 771-51-7 ]
Downstream synthetic route of [ 771-51-7 ]

[ 771-51-7 ] Synthesis Path-Upstream 1~5

1
[ 771-51-7 ]
[ 61-54-1 ]
[ 13078-91-6 ]

Reference： [1] Chemische Berichte, 1952, vol. 85, p. 324,327

2
[ 771-51-7 ]
[ 879-37-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With cobalt(II) chloride hexahydrate; oxygen; ethylenediamine; zinc In neat (no solvent) at 120℃; for 12 h; Autoclave	General procedure: The reaction was carried out in a 100-mL stainless steel autoclave. Phenylcyanide (0.10 g, 1.00 mmol) was added to a mixture of ethylenediamine (0.12 g, 2.00 mmol), CoCl26H2O (0.24 g, 1.00 mmol) and Zn (0.07 g, 1.00 mmol) and the vessel was placed in an autoclave. For some of the reactions that were carried out in solvent, 5 mL of solvent was also added. The autoclave was pressurized to 5.00 atm with O2. The mixture was stirred in a preheated oil bath at 120 C for 12 h. Then, the reaction mixture was cooled to room temperature and the product was purified by column chromatography on silica gel using n-hexane:CH2Cl2 (1:1) to give the benzamide(88 percent yield).

Reference： [1] Tetrahedron, 1989, vol. 45, # 5, p. 1347 - 1354
[2] Research on Chemical Intermediates, 2015, vol. 41, # 8, p. 5071 - 5078
[3] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 5, p. 501 - 506[4] Khimiya Geterotsiklicheskikh Soedinenii, 1980, # 5, p. 645 - 650

3
[ 771-51-7 ]
[ 778-82-5 ]

Reference： [1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 5, p. 501 - 506[2] Khimiya Geterotsiklicheskikh Soedinenii, 1980, # 5, p. 645 - 650

4
[ 771-51-7 ]
[ 58665-00-2 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2101 - 2112

5
[ 771-51-7 ]
[ 93-17-4 ]
[ 53629-44-0 ]
[ 120-20-7 ]
[ 168209-33-4 ]

Reference： [1] Tetrahedron Letters, 1995, vol. 36, # 14, p. 2497 - 2500

[ 771-51-7 ] Synthesis Path-Downstream 1~56

1
[ 120-72-9 ]
[ 3010-02-4 ]
[ 771-51-7 ]
[ 74-90-8 ]
[ 1968-05-4 ]
[ 109-89-7 ]

Reference： [1]Chemische Berichte,1954,vol. 87,p. 940,944

2
[ 700-06-1 ]
[ 143-33-9 ]
[ 771-51-7 ]

Reference： [1]Annali di Chimica,1953,vol. 43,p. 308,312

3
[ 700-06-1 ]
[ 151-50-8 ]
[ 771-51-7 ]

Reference： [1]Annali di Chimica,1953,vol. 43,p. 308,312

4
[ 771-51-7 ]
[ 61-54-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	With lithium aluminium tetrahydride; In diethyl ether; at 0℃; for 12h;Inert atmosphere;	(1) Dissolved in lithium hydride (LiAlH4, 123 mg, 3.24 mmol) in diethyl ether (Et2O, 2 mL) at 0 C under nitrogen.A solution of <strong>[771-51-7]indole-3-acetonitrile</strong> (126 mg, 0.81 mmol) in diethyl ether (2 mL) was added dropwise, and the mixture was gradually evaporated.Reaction for 12 h.(2) At 0 C, a saturated sodium tartrate potassium salt solution (5 mL) was added to the reaction mixture, stirred at room temperature for 30 min, and then extracted with ethyl acetate (5 mL×5). 30 mL of petroleum ether was poured into it, and the mixture was frozen at -50 C for 30 min, and then filtered to give white solid color amine, 97 mg, yield 75%.

Reference： [1]Patent: CN108264474,2018,A .Location in patent: Paragraph 0043; 0044; 0065; 0066; 0067; 0068
[2]Organic Letters,2014,vol. 16,p. 1092 - 1095
[3]Monatshefte fur Chemie,1957,vol. 88,p. 768,776
[4]Chemische Berichte,1952,vol. 85,p. 324,327
[5]Khimicheskaya Nauka i Promyshlennost,1959,vol. 4,p. 281
Chem.Abstr.,1959,p. 21879
[6]Synthetic Communications,1988,vol. 18,p. 2331 - 2336
[7]ChemPlusChem,2019,vol. 84,p. 1508 - 1511

5
[ 771-51-7 ]
[ 61-54-1 ]
[ 13078-91-6 ]

Reference： [1]Chemische Berichte,1952,vol. 85,p. 324,327

6
[ 771-51-7 ]
[ 15992-12-8 ]

Yield	Reaction Conditions	Operation in experiment
78%		General procedure: B(C6F5)3 (67.3 mg, 0.13 mmol, 5 mol %) was added to a stirred solution of 3,4-dichlorobenzaldehyde (172 mg, 1 mmol) and NaN3 (97.5 mg, 1.5 mmol) in DMF (5 mL) and was heated at 120 C. After completion of reaction (as monitored by TLC), the reaction mixture was cooled to room temperature and was added 5 mL of cold water followed by 10 mL of 2 N HCl and 10 mL of ethyl acetate. The resulting mixture was stirred vigorously for 15 min. The organic layer was separated and aqueous layer was again extracted with ethyl acetate (3 × 15 mL). The combined organic layer was washed with water and dried over anhydrous sodium sulfate and was evaporated under reduced pressure. The crude product was purified by column chromatography (silica gel, EtOAc/hexane 9:1) to obtain pure 5-(3,4-dichlorophenyl)-1H-tetrazole. The known compounds were characterized and confirmed by comparison of their spectral data and physical properties with reported literature.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 3507 - 3510
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 5320 - 5334
[3]Journal of Organic Chemistry,1959,vol. 24,p. 1464,1466
[4]Recueil des Travaux Chimiques des Pays-Bas,1958,vol. 77,p. 1107,1113
[5]ACS Chemical Biology,2018,vol. 13,p. 2585 - 2594

7
[ 74-90-8 ]
[ 5355-42-0 ]
[ 771-51-7 ]

Yield	Reaction Conditions	Operation in experiment
	With benzene at 150℃;
	With benzene at 150℃;

Reference： [1]Current Patent Assignee: WINTHROP CHEM - US2315661, 1940, A
[2]Current Patent Assignee: I.G. FARBENINDUSTRIE AG (historic) - DE722809, 1939, C [DRP/DRBP Org.Chem.][DRP/DRBP Org.Chem.]

8
[ 68997-45-5 ]
[ 771-51-7 ]
[ 88137-39-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In ethanol for 0.25h; Ambient temperature;

Reference： [1]Naruto; Mizuta; Yoshida; Uno; Kawashima; Kadokawa; Nishimura [Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 6, p. 2023 - 2032]

9
[ 771-51-7 ]
[ 81068-25-9 ]
[ 81813-86-7 ]

Yield	Reaction Conditions	Operation in experiment
24%	With sodium ethanolate In ethanol for 96h; Ambient temperature;

Reference： [1]Naruto; Mizuta; Yoshida; Uno; Kawashima; Kadokawa; Nishimura [Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 6, p. 2023 - 2032]

10
[ 771-51-7 ]
[ 81068-25-9 ]
[ 88137-00-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate In ethanol for 96h; Ambient temperature;

Reference： [1]Naruto; Mizuta; Yoshida; Uno; Kawashima; Kadokawa; Nishimura [Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 6, p. 2023 - 2032]

11
[ 771-51-7 ]
[ 26934-35-0 ]
[ 88136-99-6 ]

Yield	Reaction Conditions	Operation in experiment
23%	With sodium ethanolate In ethanol for 96h; Ambient temperature;

Reference： [1]Naruto; Mizuta; Yoshida; Uno; Kawashima; Kadokawa; Nishimura [Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 6, p. 2023 - 2032]

12
[ 771-51-7 ]
[ 2591-98-2 ]

Reference： [1]Helvetica Chimica Acta,1984,vol. 67,p. 1040 - 1052
[2]Angewandte Chemie - International Edition,2015,vol. 54,p. 4344 - 4348
Angew. Chem.,2015,vol. 54-127,p. 4418 - 4422,5
[3]Chemische Berichte,1955,vol. 88,p. 1956,1960
[4]Phytochemistry,2010,vol. 71,p. 1952 - 1962

13
[ 771-51-7 ]
[ 879-37-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With cobalt(II) chloride hexahydrate; oxygen; ethylenediamine; zinc; In neat (no solvent); at 120℃; under 3800.26 Torr; for 12h;Autoclave;	General procedure: The reaction was carried out in a 100-mL stainless steel autoclave. Phenylcyanide (0.10 g, 1.00 mmol) was added to a mixture of ethylenediamine (0.12 g, 2.00 mmol), CoCl26H2O (0.24 g, 1.00 mmol) and Zn (0.07 g, 1.00 mmol) and the vessel was placed in an autoclave. For some of the reactions that were carried out in solvent, 5 mL of solvent was also added. The autoclave was pressurized to 5.00 atm with O2. The mixture was stirred in a preheated oil bath at 120 C for 12 h. Then, the reaction mixture was cooled to room temperature and the product was purified by column chromatography on silica gel using n-hexane:CH2Cl2 (1:1) to give the benzamide(88 % yield).

Reference： [1]Tetrahedron,1989,vol. 45,p. 1347 - 1354
[2]Research on Chemical Intermediates,2015,vol. 41,p. 5071 - 5078
[3]Chemistry of Heterocyclic Compounds,1980,vol. 16,p. 501 - 506
Khimiya Geterotsiklicheskikh Soedinenii,1980,p. 645 - 650

14
[ 771-51-7 ]
[ 106050-92-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; silica gel; In dichloromethane; at 20℃; for 0.416667h;	To a solution of (1H-indol-3-yl)-acetonitrile2 (700 mg, 4.5 mmol, 1.0 equiv) in CH2Cl2 (60 mL) were added silica(400 mg, 6.7 mmol, 1.5 equiv) and N-bromosuccinimide(800 mg, 4.5 mmol, 1.0 equiv) in portions. The reaction mixturewas stirred at room temperature for 25 min and filtered. The filtratewas evaporated under vacuum. To a solution the resulting2-bromoindole derivative 10 in toluene (40 mL) were added ethanol(20 mL), PhB(OH)2 (1.1 g, 9.0 mmol), Na2CO3 (1.4 g, 13.4 mmol)and LiCl (570 mg, 13.4 mmol). The mixture was degassed beforethe addition of PdCl2(PPh3)2 (380 mg, 0.54 mmol.). The reactionmixture was heated at 80 C for 16 h. The reaction was allowedto cool to room temperature then water was added. The aqueouslayer was extracted with EtOAc. The combined organic layers werewashed with saturated aqueous Na2CO3 solution, dried overMgSO4, filtered over silica and evaporated under vacuum. Theresulting residue 13a was dissolved in NMP (100 mL) and NaH(188 mg, 80%, 6.3 mmol) then pyridine-3-carbaldehyde 8 (760 lL,8.1 mmol) were successively added. The mixture was stirred atroom temperature for 2 h then quenched with saturated ammoniumchloride aqueous solution and extracted with EtOAc. Thecombined organic layers were washed with water, brine, driedover MgSO4 and evaporated under vacuo. The residue was purified by silica gel flash-column chromatography (eluent: heptane/EtOAc,50/50) to afford 14a as a yellow powder (440 mg, 31%).

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 1051 - 1054
[2]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 865 - 869
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 4752 - 4772
[4]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 721 - 734

15
[ 771-51-7 ]
[ 4404-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; at 65℃; for 4h;	To a solution of compound 11 (64.1 mmol, 1.0 equiv) in EtOH (60 mL) was added hydroxylaminehydrochloride (96.2 mmol, 1.5 equiv) and NaHCO3 (192.3 mmol, 3.0 equiv). The mixture was stirredfor 4 h at 65 C. The reaction mixture was diluted with EtOAc, filtered and concentrated in vacuo. Water was added to the residue and extracted with ethyl acetate (3 x 100 mL), washed with brine(1 x 100 mL), dried over anhydrous MgSO4, and concentrated. The residue was subjected to silica gel chromatography with EtOAc /MeOH (9:1) to make carboxamidine 12.
	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; at 65℃;	(a) Dissolve 3.0 g of compound 1 indole acetonitrile in 60 mL of ethanol, add 1.60 g of hydroxylamine hydrochloride and 4.85 g of sodium bicarbonate,The reaction was stirred at 65 C for 3-4 hours. The solid sodium bicarbonate was removed by filtration, and the filtrate was evaporated to dryness under reduced pressure. The mixture was extracted and washed 3 times with ethyl acetate and water.The organic phase was dried over anhydrous sodium sulfate, concentrated by filtration, and the residue was separated and purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 7: 3) to obtain compound 2.

Reference： [1]Chemistry of Heterocyclic Compounds,1984,vol. 20,p. 1324 - 1330
Khimiya Geterotsiklicheskikh Soedinenii,1984,p. 1609 - 1615
[2]Archiv der Pharmazie,1998,vol. 331,p. 375 - 379
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 1176 - 1183
[4]Marine Drugs,2018,vol. 16
[5]Journal of Medicinal Chemistry,2018,vol. 61,p. 11298 - 11308
[6]Patent: CN110627778,2019,A .Location in patent: Paragraph 0104-0106

16
glucobrassicin [ No CAS ]
[ 700-06-1 ]
[ 771-51-7 ]
[ 1968-05-4 ]

Reference： [1]Phytochemistry,1990,vol. 29,p. 769 - 771
[2]Phytochemistry,1990,vol. 29,p. 769 - 771

17
glucobrassicin [ No CAS ]
[ 700-06-1 ]
[ 771-51-7 ]
[ 1968-05-4 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1990,p. 2273 - 2276

18
[ 771-51-7 ]
[ 74-88-4 ]
[ 51584-17-9 ]

Yield	Reaction Conditions	Operation in experiment
100%		To a suspension of NaH (60% dispersion in mineral oil) (3.33 g, 83.3 mmol) in anhydrous DMF (25 mL) was added dropwise a solution of 3-indolylacetonitrile 18 (10.0 g, 64 mmol) in DMF (50 mL). After stirring for 30 min, at room temperature, the flask was then cooled to 0 C. Iodomethane (6 mL, 95.8 mmol) was added dropwise in solution with DMF (30 mL). The reaction was then allowed to warm and was stirred at ambient temperature for 3 h. The reaction was then quenched by pouring it into a mixture of ethyl acetate (300 mL) and 5% aqueous HCl (400 mL). Following product extraction, the organic layer was washed with water (2×250 mL), brine (300 mL), dried over magnesium sulfate and filtered. The resultant solution was then evaporated thoroughly, under reduced pressure, at a water bath temperature of 90 C, to yield the N-methyl acetonitrile 19 in quantitative yield (11.1 g, 100%) as an off-white crystalline material: mp 57-59 C (lit.37 59-60 C); Rf (30% ethyl acetate/hexane) 0.40; numax/cm-1 (KBr) 2954, 2247, 1657, 1553, 1464; deltaH (300 MHz, CDCl3) 3.73 [3H, s, NCH3], 3.78 [2H, s, C-H2], 7.04 [1H, s, C-H2], 7.14-7.19 [1H, td, J 8.0, 1.5, C-H5], 7.23-7.38 [2H, m, C-H6,7], 7.54-7.57 [1H, d, J 7.9, C-H4]; deltaC (75 MHz, CDCl3) 14.3 (CH2, CH2CN), 32.9 (CH3, NCH3), 103.0 (C, aromatic C), 109.6 (CH, aromatic CH), 118.2 (CH, aromatic CH), 119.7 (CH, aromatic CH), 122.4 (CH, aromatic CH), 126.2 (C, CH2CN), 126.5 (C, aromatic C), 127.3 (CH, aromatic CH), 137.1 (C, aromatic C); m/z (ES+) 171.1 [M+H]+, (100%).

Reference： [1]Journal of Organic Chemistry,1998,vol. 63,p. 6053 - 6058
[2]Tetrahedron,2011,vol. 67,p. 4601 - 4611
[3]Heterocycles,2004,vol. 63,p. 1131 - 1142
[4]Journal of the American Chemical Society,2015,vol. 137,p. 14861 - 14864
[5]European Journal of Medicinal Chemistry,1996,vol. 31,p. 123 - 132
[6]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 47 - 50
[7]Journal of Medicinal Chemistry,2006,vol. 49,p. 3509 - 3519
[8]Journal of Medicinal Chemistry,2008,vol. 51,p. 5271 - 5284
[9]Chemistry - A European Journal,2011,vol. 17,p. 2916 - 2922

19
[ 771-51-7 ]
[ 24424-99-5 ]
[ 218772-62-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine;dmap; In dichloromethane; at 0 - 20℃; for 2 - 3h;	To a cooled (ice-water bath), stirred solution of 3-indolylacetonitrile (64) (53.4 g, 0.342 mol) in dichloromethane (800 mL) was added triethylamine (84 mL, 0.603 mol) and dimethylaminopyridine (2.64 g, 0.0216 mol). BOC anhydride (88.4 g, 0.405 mol) was melted by slightly heating in warm water bath, and then added slowly to the reaction mixture as a liquid. After the addition was complete, ice bath was removed and stirring continued at room temperature for 2 -3 hours, or until no more starting indole was present by TLC (eluted with 25% EtOAc in hcxancs). The reaction was washed with IN HCl (2 x 400 mL) and brine, then, dried with Na2SO4, filtered, and concentrated in vacuo to yield 3-cyanomethyl-indole-l- carboxylic acid tert-butyl ester (65) as a pale yellow solid (87.2 g, 100%). 1H-NMR (400MHz, CDCl3): 8.18-8.16 (d, IH), 7.64 (s, IH), 7.53-7.51 (dd, IH), 7.40-7.36 (m, IH), 7.32-7.26 (m, IH), 3.78 (s, 2H), 1.68 (s, 9H).
93%	With dmap; In dichloromethane;	Example 41A tert-butyl 3-(cyanomethyl)-1H-indole-1-carboxylate A solution of 3-cyanomethylindole (7.50 g, 48 mmol), di-tert-butyl dicarbonate (11.5 g, 52.8 mmol), and DMAP (300 mg) in dichloromethane (200 mL) was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by flash column chromatography on silica gel with dichloromethane to provide the desired product (11.44 g, 93%). MS (DCI/NH3) m/e 257 (M+H)+.
93%	With dmap; In dichloromethane; at 20℃;	tert-butyl 3-(cyanomethyl)-1H-indole-1-carboxylate A solution of 3-cyanomethylindole (7.50 g, 48 mmol), di-tert-butyl dicarbonate (11.5 g, 52.8 mmol), and DMAP (300 mg) in dichloromethane (200 mL) was stirred at room temperature overnight. The mixture was concentrated and the residue was purified by flash column chromatography on silica gel with dichloromethane to provide the desired product (11.44 g, 93%). MS (DCI/NH3) m/e 257 (M+H)+.

85%	With dmap; triethylamine; In dichloromethane; for 4h;Inert atmosphere;	To a stirred solution of 2-(1H-indol-3-yl)acetonitrile 1 (5.0 g, 32.0 mmol) in CH2Cl2 (100 mL) were added Et3N (5.8 g, 57.6 mmol), DMAP (234 mg, 1.92 mmol) and Boc-anhydride (8.3 g, 38.4 mmol) at RT under inert atmosphere. The reaction was stirred for 4 h and monitored by TLC. The reaction mixture was diluted with water (100 mL) and extracted with CH2Cl2 (3 x 75 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude product was triturated with n-pentane (2 x 20 mL) and dried under reduced pressure to afford compound 2 (7.0 g, 85%) as an off-white solid. 1H NMR (500 MHz, DMSO-d6): delta 8.08 (d, J= 8.0 Hz, 1H), 7.70-7.67 (m, 2H), 7.40 (t, J= 8.0 Hz, 1H), 7.32 (t, J= 8.0 Hz, 1H), 4.12 (s, 2H), 1.63 (s, 9H).
84%	With dmap; triethanolamine; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; ethyl acetate;	A. To a stirred solution of 3-indolylacetonitrile (3.9 g, 25 mmol) in DCM (100 mL, anhyd) was added BOC anhydride (6.5 g, 30 mmol), DMAP (3.6 g, 30 mmol) and TEA (4.2 mL, 30 mmol). After 2 hours, the reaction mixture was diluted with DCM (100 mL), washed with 1N HCl (2*50 mL) and brine, then dried (Na2SO4), concentrated and chromatographed (silica gel, 6% EtOAc/Hex) to yield (1-tert-butoxycarbonylindol-3-yl)acetonitrile (5.4 g, 84%) as a pale yellow solid; 1H-NMR (CDCl3): delta 8.17 (1H, br d), 7.64 (1H, br s), 7.52 (1H, br d), 7.38 (1H, app t), 7.30 (1H, app t), 3.78 (2H, s), 1.68 (9H, s).
84%	With dmap; triethylamine; In dichloromethane; for 2h;	A. To a stirred solution of 3-indolylacetonitrile (3.9 g, 25 mmol) in DCM (100 mL, anhyd) was added BOC anhydride (6.5 g, 30 mmol), DMAP (3.6 g, 30 mmol) and TEA (4.2 mL, 30 mmol). After 2 hours, the reaction mixture was diluted with DCM (100 mL), washed with 1 N HCI (2 x 50 mL) and brine, then dried (NaPS04), concentrated and chromatographed (silica gel, 6% EtOAc/Hex) to yield (1-tert- butoxycarbonylindol-3-yl) acetonitrile (5.4 g, 84%) as a pale yellow solid ;'H-NMR (CDCI3) : 8 8.17 (1 H, br d), 7.64 (1 H, br s), 7.52 (1H, br d), 7.38 (1 H, app t), 7.30 (1 H, app t), 3.78 (2H, s), 1.68 (9H, s).
44%	With dmap; In dichloromethane; at 25℃; for 8h;	At 25C the 2- (1H- indol-3-yl) acetonitrile (10.0g, 64.1mmol) and DMAP (500mg, 4.1mmol) was added to a dichloromethane (50 mL), and then slowly added Boc2O (21.0g , 96.2mmol). Reaction was continued for 8 hours, then washed with a saturated sodium chloride solution (40 mL) with, liquid-separation the organic phase was dried over anhydrous sodium sulfate. Filtered, the filtrate was spin dry, purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 10/1) to give the title compound as a pale yellow solid (7.2g, 44.0%).
44%	With dmap; In dichloromethane; at 25℃; for 8h;	2- (1H-indol-3-yl) acetonitrile (10.0 g, 64.1 mmol) and DMAP (500 mg, 4.1 mmol) were added to dichloromethane (50 mL) at 25 C followed by slow addition of Boc20 , 96.2 mmol).The reaction was continued for 8 hours, then washed with saturated sodium chloride solution (40 mL) and the organic phase separated on drying with anhydrous sodium sulfate.Filtration and the filtrate was evaporated to dryness and purified by column chromatography (petroleum ether / ethyl acetate = 10/1) to give the title compound as a pale yellow solid (7.2 g, 44.0%).
	In acetonitrile; at 20℃;	A solution of 1H-indol-3-ylacetonitrile (8.0g) in acetonitrile (150mL) was added by di-tert-butyl dicarbonate (13.5g) and dimethylaminopyridine (938mg) successively and stirred at the room temperature. The reaction mixture was concentrated and the obtained residue was purified by column chromatography on silica gel (hexane: ethyl acetate = from 10: 1 to 5: 1) to give the title compounds (10.5mg) having the following physical data. TLC: Rf 0.36 (hexane: ethyl acetate =5:1); NMR(CDCl3):delta 1.68 (s, 9H), 3.78 (d, J=1.28 Hz, 2H), 7.26-7.33 (m, 1H), 7.34-7.44 (m, 1H), 7.49-7.57 (m, 1H), 7.64 (s, 1H), 8.17 (d, J=8.06 Hz, 1H).
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	INTERMEDIATE 46 : 3-cyanomethyl-indole-l-carboxylic acid tert-butyl ester [00183] A solution of <strong>[771-51-7]3-indoleacetonitrile</strong> (10 g, 64 mmol) in DMF (160 ml) was stirred at RT. K2CO3 (13.3 g, 96 mmol) and di-tert-butyl dicarbonate (15.35 g, 70 mmol) were added thereto and the reaction mixture was stirred at RT for 12 hr. H20 (100 ml) was added to the reaction mixture and the resulting precipitate was captured by filtration. The solids were dissolved in hot methanol (20 ml) and the solution was allowed to cool slowly, producing light orange solids that were isolated by filtration to give 3- cyanomethyl-indole-1-carboxylic acid tert-butyl ester (9.2 g). 1H-NMR (300 MHz, DMSO-d6) : No. 8.08 (d, 1); 7.70 - 7.66 (m, 2); 7.42-7. 29 (m, 2); 4.12 (s, 2); 1.63 (3,9). NH40Ac standard conditions. DAD Rf = 3.31 min. M+H = 257.
	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	Intermediate 46: 3-cyanomethyl-indole-1-carboxylic acid tert-butyl ester A solution of <strong>[771-51-7]3-indoleacetonitrile</strong> (10 g, 64 mmol) in DMF (160 ml) was stirred at RT. K2CO3 (13.3 g, 96 mmol) and di-tert-butyl dicarbonate (15.35 g, 70 mmol) were added thereto and the reaction mixture was stirred at RT for 12 hr. H2O (100 ml) was added to the reaction mixture and the resulting precipitate was captured by filtration. The solids were dissolved in hot methanol (20 ml) and the solution was allowed to cool slowly, producing light orange solids that were isolated by filtration to give 3-cyanomethyl-indole-1-carboxylic acid tert-butyl ester (9.2 g). 1H-NMR (300 MHz, DMSO-d6): delta 8.08 (d, 1); 7.70-7.66 (m, 2); 7.42-7.29 (m, 2); 4.12 (s, 2); 1.63 (3, 9). NH4OAc standard conditions. DAD Rf=3.31 min. M+H=257.
68 g	With dmap; In dichloromethane; at 20℃;	(f) . tert-butyl 3-(cyanomethyl)-1 H-indole-1 -carboxylate <strong>[771-51-7]3-indoleacetonitrile</strong> (50 g), di-ie f-butyl dicarbonate (76.8 g) and 4-dimethylaminopyridine (1 .96 g) were added to DCM (200 ml). The mixture was stirred at room temperature overnight. The solution was washed with brine and water and then dried (Na2S04). The organic layer was concentrated and the residue was purified by chromatography on silica gel eluting with heptane and increasing amounts of ethyl acetate. Yield: 68 g

Reference： [1]Patent: WO2007/70796,2007,A1 .Location in patent: Page/Page column 110; 111; 117
[2]Tetrahedron,2009,vol. 65,p. 9015 - 9020
[3]New Journal of Chemistry,2015,vol. 39,p. 1968 - 1973
[4]Patent: US2003/187026,2003,A1
[5]Patent: US2003/199511,2003,A1 .Location in patent: Page/Page column 28
[6]Patent: WO2015/77502,2015,A1 .Location in patent: Paragraph 00395
[7]Patent: US2005/54634,2005,A1
[8]Patent: WO2003/99821,2003,A1 .Location in patent: Page 131-132
[9]Journal of Medicinal Chemistry,2009,vol. 52,p. 904 - 907
[10]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5039 - 5044
[11]Patent: CN104496987,2016,B .Location in patent: Paragraph 0205; 0206; 0207; 0208
[12]Patent: CN104529865,2017,B .Location in patent: Paragraph 0164; 0166; 0167
[13]Tetrahedron Letters,1998,vol. 39,p. 8729 - 8732
[14]Patent: EP1637521,2006,A1 .Location in patent: Page/Page column 58
[15]Patent: WO2004/92167,2004,A1 .Location in patent: Page 112
[16]Patent: US2005/239781,2005,A1 .Location in patent: Page/Page column 99
[17]Patent: WO2013/41458,2013,A1 .Location in patent: Page/Page column 31

20
[ 700-06-1 ]
[ 64-17-5 ]
[ 151-50-8 ]
water [ No CAS ]
[ 771-51-7 ]

Reference： [1]Annali di Chimica,1953,vol. 43,p. 308,312

21
[ 771-51-7 ]
[ 4455-09-8 ]
[ 416860-86-1 ]

Reference： [1]Chemical and pharmaceutical bulletin,2002,vol. 50,p. 31 - 39

22
[ 771-51-7 ]
[ 592-33-6 ]
[ 203719-68-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2261 - 2267

23
[ 771-51-7 ]
[ 99275-51-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	With Iodine monochloride; In dichloromethane; at 20℃; for 4h;Inert atmosphere;	General procedure: A solution of indole, azaindole or pyrrole (0.1 mmol) in dichloromethane (5 mL) was added to a suspension of 1:1 (W/W) ICl (concentration indicated in the Table; 0.1 mmol = 162 mg) and Celite (162 mg) ratio in dichloromethane (10 mL). The mixture was stirred at room temperature for the time indicated in Tables 1-4. The reaction mixture was then poured into saturated thiosulfate solution (20 mL) extracted with dichloromethane (2 x 15 mL). The organic layer was washed in brine and, dried over sodium sulfate and the solvent was removed at reduced pressure. The desired compound was purified by chromatography column using hexane and ethyl acetate mixtures as eluting solvent. Yields of iodinated compounds are summarized in Tables 1-4. All the compounds were characterized by IR, NMR and were compared with authentic samples.

Reference： [1]Tetrahedron,2012,vol. 68,p. 6269 - 6275
[2]Journal of Organic Chemistry,2003,vol. 68,p. 5132 - 5138

24
[ 771-51-7 ]
[ 54744-66-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; dimethyl sulfoxide; In water; at 0 - 20℃; for 1h;Inert atmosphere;	To a stirred solution of <strong>[771-51-7]indole-3-acetonitrile</strong> (3.12 g, 20 mmol) in DMSO (30 mL) was addedhydrogen chloride (37% HCl, VDMSO:VHCl = 1:5) dropwise at 0 C. The resulting mixture was allowedto warm to room temperature. Then the mixture was stirred for 1 h. The solvents were removed toobtain the white solid. The solid was crystallized from acetone to provide the desired product 2 (3.20 g,93% yield).
93%		3.12 g (20 mmol)Of <strong>[771-51-7]indole-3-acetonitrile</strong> was placed in a 100 mL dry round bottom flask followed by 30 mL of DMSO,Stirred at room temperature for 15 min to completely dissolve,The reaction solution was placed in an ice bath at 0 C,And then with a constant pressure funnel to slowly add 150mL concentrated hydrochloric acid,The mass fraction of HCl in concentrated hydrochloric acid was 37 wt%Where VDMSO: VHCl = 1: 5;After completion of the dropwise addition, the reaction solution was stirred at room temperature,TLC point plate (petroleum ether: ethyl acetate volume ratio of 4: 1) to detect the raw material reaction isWhether it is completeTo be completed,The reaction solution was placed under an ice bath at 0 C,Add 20 mL of water to dilute,With anhydrous K2CO3 or anhydrous Na2CO3 adjusted pH between 7 to 8;The whole system was moved to room temperature,Extracted with ethyl acetate (3 x 200 mL,That is extracted twice with 200 mL of ethyl acetate, extracted three times)Combine organic phase,The organic phases were washed with saturated NaCl solution (3 x 200 mL each, washed twice with 200 mL of saturated NaCl solution, washed three times)Anhydrous Na2SO4 dried,Concentrated under reduced pressure,To obtain 3.20 g of compound IAN1,The yield was 93%.
93%		Weigh 3.12g (20mmol) of <strong>[771-51-7]indole-3-acetonitrile</strong> In a 250mL dry round bottom flask, 30mL of DMSO was added and stirred at room temperature for 15min to completely dissolve the reaction solution was placed in an ice bath at 0 C, and then with A constant pressure funnel slowly added dropwise 150 mL of concentrated hydrochloric acid (37% HCl, VDMSO: VHCl= 1: 5). After the dropwise addition was completed, the reaction mixture was allowed to move to room temperature and stirred for 30 min. The reaction mixture was checked for completeness by TLC (PE: EA = 4: 1).The reaction solution was placed in an ice bath at 0 , diluted with 50mL of water, with anhydrous K2CO3Or anhydrous Na2CO3Adjust the pH value of the solid, while stirring, while detecting the pH of the solution, the pH of the solution is modulated at 7 to 8.The whole system was moved to room temperature and extracted with ethyl acetate (3 × 100 mL). The organic phases were combined and the organic phases were washed with saturated sodium chloride (3 × 50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 3.20 g of <strong>[771-51-7]indole-3-acetonitrile</strong> (18.6 mmol, 93%).

93%	With hydrogenchloride; water; In dimethyl sulfoxide; at 0 - 20℃; for 0.5h;	Weigh 3.12 g (20 mmol) of <strong>[771-51-7]indole-3-acetonitrile</strong> in a 250 mL dry round bottom flask, add 30 mL of DMSO,The mixture was stirred for 15 min at room temperature to completely dissolve the mixture. The reaction mixture was placed in an ice bath at 0 C, and then slowly filled with a constant pressure funnel150mL of concentrated hydrochloric acid (37% HCl, VDMSO: VHCl = 1: 5) was added dropwise and the reaction mixture was allowed to move to room temperature and stirred for 30 min.The reaction of TLC (PE: EA = 4: 1) was complete. The reaction solution was placed in an ice bath at 0 , diluted with 50mL of water, with anhydrousK2CO3 or anhydrous Na2CO3 solid pH value, while stirring, while detecting the pH of the solution, the pH of the solution is modulated at 7 ~ 8between. The whole system was moved to room temperature, extracted with ethyl acetate (3 x 100 mL) and the organic phases were combined and the organic phase was washed with saturatedSodium chloride (3 x 50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 3.20 g of compound a, indoxyl-3-acetonitrile(18.6 mmol, 93%); the reaction equation is as follows:
91%	With tetrabutyl-ammonium chloride; bis-[(trifluoroacetoxy)iodo]benzene; In dichloromethane; at -10℃;Green chemistry;	Add the starting material 10 (58 mg, 0.2 mmol), tetrabutylammonium chloride hydrate (67 mg,0.24 mmol) to the same reactor, then add 1.5 mL of the solvent dichloromethane, and control the reaction temperature to -10 C. A 0.5 mL solution of[bis(trifluoroacetoxy)iodo]benzene (103 mg, 0.24 mmol) in dichloromethane was added dropwise, and the reaction was quickly confirmed by TLC. The reaction was quenched by the addition of 10 mL EtOAc EtOAc. Chromatographic separation (petroleum ether / ethyl acetate, 3:1) gave 3- acetonitrile-1-hydro-oxindole 31.2 mg, 91%.

Reference： [1]Molecules,2016,vol. 21
[2]Patent: CN106279183,2017,A .Location in patent: Paragraph 0037; 0038; 0039
[3]Patent: CN106588936,2017,A .Location in patent: Paragraph 0037; 0038; 0039
[4]Patent: CN107522702,2017,A .Location in patent: Paragraph 0034; 0035; 0036; 0037
[5]Natural Product Research,2019
[6]Bioorganic and Medicinal Chemistry,2019,vol. 27
[7]Journal of Asian Natural Products Research,2020,p. 1 - 7
[8]Patent: CN108101830,2018,A .Location in patent: Paragraph 0120; 0121; 0122; 0123
[9]Advanced Synthesis and Catalysis,2018,vol. 360,p. 4710 - 4714
[10]Heterocycles,2004,vol. 63,p. 1131 - 1142
[11]Tetrahedron,2006,vol. 62,p. 3040 - 3051
[12]Journal of Medicinal Chemistry,2008,vol. 51,p. 5271 - 5284

25
[ 771-51-7 ]
[ 100-39-0 ]
[ 59414-85-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; N-benzyl-trimethylammonium hydroxide; In methanol; water; at 20℃; for 2h;	A. A mixture of 3-indolylacetonitrile (5 g, 32 mmol), triton B (40% in MeOH, 0.5 g), benzyl bromide (7.8 mL, 2 eq. ) and aqueous NaOH (50%, 12.6 mL) was stirred for 2 hours at 20 C. Water was added. Solid was collected by filtration and washed with water and hexane and dried under high vacuum to give [1-benzyl-1 H- indol-3-yl] acetonitrile (6.97 g). MS (ES): 247 (MH+).

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5271 - 5284
[2]Synthetic Communications,2004,vol. 34,p. 3121 - 3127
[3]Patent: WO2003/99821,2003,A1 .Location in patent: Page 178
[4]Synlett,2008,p. 1479 - 1482

26
[ 87-52-5 ]
[ 143-33-9 ]
[ 771-51-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With ethyl acetate; In dimethyl sulfoxide; at 80℃; for 3h;	Dissolve a mixture of the (lH-Indol-3-ylmethyl)-dimethylamine (3.54 mmol), sodium cyanide (0.500g, 10.62 mmol), and ethyl acetate (1.7 mL, 17.7 mmol) in dry dimethyl sulfoxide (12 mL) and heat to 80C under nitrogen for 3h. Cool the reaction mixture to room temperature, dilute with ethyl acetate (150 mL), and wash with water (50 mL). Dry the organic layer over anhydrous magnesium sulfate, and remove the solvent in vacuo to yield (lH-indol-3-yl)-acetonitrile 0.850 g (96%).

Reference： [1]Patent: WO2003/76398,2003,A2 .Location in patent: Page/Page column 33

27
[ 31731-23-4 ]
[ 771-51-7 ]
[ 2776-06-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride

Reference： [1]Pedras, M. Soledade C.; Okinyo, Denis P. O. [Organic and Biomolecular Chemistry, 2008, vol. 6, # 1, p. 51 - 54]

28
[ 500-22-1 ]
[ 771-51-7 ]
[ 57046-73-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium methylate; sodium; In methanol;	Example 1 (Z)-2-(1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile; To a solution of sodium methanolate [prepared from sodium (530 mg, 9.8 mmol, 1.5 eq.) in anhydrous methanol (10 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (1 g, 6.4 mmol, 1.0 eq.) and pyridine-3-carbaldehyde (1000 mul, 10.7 mmol, 1.7 eq.). The reaction apparatus was protected from light and the mixture heated at reflux for 3 hours. The reaction was allowed to cool to room temperature and again cooled to -78C in a dry ice/ethanol bath. The resulting precipitate was filtered and washed with methanol and diethyl ether to afford the compound (1) as a yellow powder (1.07 g, 68%). TLC: Rf = 0.12 (heptane 60/EtOAc 40); Mp 201C; IR max (cm-1): 2219 (nu CN); 1H NMR (DMSO, 500 MHz): delta (ppm): 7.19 (1H, t, J5'-6' = J5'-4' = 7.9 Hz, H5'), 7.25 (1H, t, J6'-5' = J6'-7' = 7.9 Hz, H6'), 7.52 (1H, d, J7'-6'= 7.9 Hz, H7'), 7.54 (1H, dd, J5'-4' = 8.2 Hz, J5'-6' = 4.9 Hz, H5'), 7.82 (1H, s, H3), 7.85 (1H, s, H2'), 8.10 (1H, d, J4'-5' = 7.9 Hz, H4'), 8.32 (1H, d, J4'-5' = 8.2 Hz, H4'), 8.59 (1H, dd, J6'-5' = 4.9 Hz, J6'-4' = 1.5 Hz, H6'), 9.00 (1H, d, J2'-4' = 2.4 Hz, H2'); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 108.2 (C2), 110.6 (C3'), 112.7 (C7'), 118.2 (C1), 119.7 (C4), 120.8 (C5'), 122.8 (C6'), 123.7 (C3a'), 123.8 (C5'), 127.4 (C2'), 130.9 (C3'), 132.6 (C3), 134.7 (C4'), 137.4 (C7a'), 149.7 (C6'), 150.0 (C2'); ESI-MS m/z: 246.1 [M+H]+, 268.1 [M+Na]+, 300.1 [M+Na+MeOH]+; HRES-MS m/z 246.0999 (calcd for C16H12N3, 246.1031).
68%	With sodium methylate; for 3h;Inert atmosphere; Darkness; Reflux;	EXAMPLE 1 (Z)-2-(1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile To a solution of sodium methanolate [prepared from sodium (530 mg, 9.8 mmol, 1.5 eq.) in anhydrous methanol (10 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (1 g, 6.4 mmol, 1.0 eq.) and pyridine-3-carbaldehyde (1000 mul, 10.7 mmol, 1.7 eq.). The reaction apparatus was protected from light and the mixture heated at reflux for 3 hours. The reaction was allowed to cool to room temperature and again cooled to -78 C. in a dry ice/ethanol bath. The resulting precipitate was filtered and washed with methanol and diethyl ether to afford the compound (1) as a yellow powder (1.07 g, 68%). TLC: Rf=0.12 (heptane 60/EtOAc 40); Mp 201 C.; IR ?max (cm-1): 2219 (nuCN); 1H NMR (DMSO, 500 MHz): delta (ppm): 7.19 (1H, t, J5'-6'=J5'-4'=7.9 Hz, H5'), 7.25 (1H, t, J6'-5'=J6'-7'=7.9 Hz, H6'), 7.52 (1H, d, J7'-6'=7.9 Hz, H7'), 7.54 (1H, dd, J5"-4"=8.2 Hz, J5"-6"=4.9 Hz, H5"), 7.82 (1H, s, H3), 7.85 (1H, s, H2'), 8.10 (1H, d, J4'-5'=7.9 Hz, H4'), 8.32 (1H, d, J4"-5"=8.2 Hz, H4"), 8.59 (1H, dd, J6"-5"=4.9 Hz, J6"-4"=1.5 Hz, H6"), 9.00 (1H, d, J2"-4"=2.4 Hz, H2"); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 108.2 (C2), 110.6 (C3'), 112.7 (C7'), 118.2 (C1), 119.7 (C4), 120.8 (C5'), 122.8 (C6'), 123.7 (C3a'), 123.8 (C5"), 127.4 (C2'), 130.9 (C3"), 132.6 (C3), 134.7 (C4"), 137.4 (C7a'), 149.7 (C6"), 150.0 (C2"); ESI-MS m/z: 246.1 [M+H]+, 268.1 [M+Na]+, 300.1 [M+Na+ MeOH]+; HRES-MS m/z 246.0999 (calcd for C16H12N3, 246.1031).
58%		General procedure: To an <strong>[771-51-7]indole-3-acetonitrile</strong> derivative (1.0 equiv) dissolved in anhydrous methanol (4mL for 2.31mmol of starting material) in a dried microwave vial, sodium methoxide (1.7 equiv) was added and stirred at room temperature for 15min protected from light. Quinoline/isoquinoline-carboxaldehyde derivative (1.2 equiv) was added and the mixture was subjected to microwave irradiation at 95C for 8.5min. The reaction was cooled to room temperature and then chilled in an ice/salt bath. The resulting precipitate was filtered, washed with methanol, and dried under vacuum to afford a solid as the product.

Reference： [1]Patent: EP2266562,2010,A1
[2]Angewandte Chemie - International Edition,2010,vol. 49,p. 8228 - 8231
[3]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 31
[4]European Journal of Medicinal Chemistry,2018,vol. 156,p. 344 - 367

29
[ 771-51-7 ]
[ 100-52-7 ]
[ 1257531-63-7 ]

Yield	Reaction Conditions	Operation in experiment
64%		EXAMPLE 9 (Z)-2-(1H-indol-3-yl)-3-phenyl-acrylonitrile To a solution of sodium ethanolate [prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (200 mg, 1.3 mmol, 1.0 eq.) and, after 30 minutes stirring, benzaldehyde (157 mul, 1.5 mmol, 1.2 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 90:10 to 80:20) to afford the compound (9) as a yellow powder (200 mg, 64%). 1H NMR (DMSO, 300 MHz): delta (ppm): 7.18 (1H, td, J5'-4'=J5'-6'=7.4 Hz, J5'-7'=1.1 Hz, H5'), 7.24 (1H, t, J6'-5'=J6'-7'=7.4 Hz, J6'-4'=1.1 Hz, H6'), 7.42 (1H, m, H4"), 7.50 (3H, m, H7', H3" and H5"), 7.77 (1H, s, H3), 7.80 (1H, d, J=2.6 Hz, H2'), 7.91 (2H, d, J2"-3"=J6"-5"=7.3 Hz, H2" and H6"), 8.05 (1H, d, J4'-5'=7.4 Hz, H4'), 11.72 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 105.8 (C2), 110.7 (C3'), 112.4 (C7'), 118.4 (C1), 119.4 (C4'), 120.5 (C5'), 122.5 (C6'), 123.7 (C3a'), 126.6 (C2'), 128.5 (C2" and C6"), 128.8 (C3" and C5"), 129.3 (C4"), 134.6 (C1"), 136.6 (C3), 137.2 (C7a'); TLC: Rf=0.58 (heptane 50/EtOAc 50); MS: ESI: m/z: 267.1 ([M+Na]+), 511.2 ([2M+Na]+) HRMS (ESI): calcd for C17H2N2Na: m/z=267.0898. found: 267.0905. Microanalysis: Calcd for C17H12N2%: C, 83.58; H, 4.95; N, 11.47. Found %: C, 83.32; H, 4.91; N, 11.36. IR numax (cm-1): 2220 (nuCN); 3320 (nuN-H); Mp 112 C.

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 8228 - 8231
[2]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 37; 38

30
[ 2776-06-9 ]
[ 771-51-7 ]

Yield	Reaction Conditions	Operation in experiment
	With Sclerotinia sclerotiorum indolyl-3-acetaldoxime dehydratase at 23℃; for 1h; aq. buffer; Darkness; Enzymatic reaction;

Reference： [1]Location in patent: experimental part Pedras, M. Soledade C.; Minic, Zoran; Thongbam, Premila D.; Bhaskar, Vangala; Montaut, Sabine [Phytochemistry, 2010, vol. 71, # 17-18, p. 1952 - 1962]

31
potassium cyanide [ No CAS ]
[ 46397-90-4 ]
[ 771-51-7 ]

Yield	Reaction Conditions	Operation in experiment
67%	With methyl iodide; In methanol; water; at 20℃; for 16h;	To a solution of N,N-diethyl-3-aminomethyl indole 17 (0.370 g, 1.83 mmol) in methanol (10 mL) was added a solution of potassium cyanide (0.245 g, 3.77 mmol) in water (2 mL). Iodomethane (0.3 mL, 4.79 mmol) was added dropwise and the reaction mixture was then stirred vigorously at room temperature for 16 h. Following evaporation of the solvent, the crude residue was dissolved in ethyl acetate (100 mL) and successively washed with saturated aqueous sodium bicarbonate solution (100 mL), water (3×100 mL) and brine (2×100 mL). Following chromatography employing ethyl acetate/hexane, the title compound 18 was dried, and isolated as a beige amorphous solid (0.191 g, 67%): mp 32-34 C (lit.36 34-36 C); Rf (30% ethyl acetate/hexane) 0.35; numax/cm-1 (KBr) 3412, 2252, 1621, 1458, 1420; deltaH (300 MHz, CDCl3) 3.82 [2H, s, C-H2], 7.15-7.21 [2H, m, C-H2,5], 7.22-7.28 [1H, td, J 7.1, 1.1, C-H6], 7.37-7.40 [1H, d, J 8.0, C-H7], 7.57-7.60 [1H, d, J 7.8, C-H4], 8.19 [1H, br s, NH]; deltaC (75 MHz, CDCl3) 14.4 (CH2, CH2CN), 104.7 (C, aromatic C), 111.6 (CH, aromatic CH), 118.1 (CH, aromatic CH), 118.2 (C, aromatic C), 120.3 (CH, aromatic CH), 122.8 (CH, aromatic CH), 122.9 (CH, aromatic CH), 126.0 (C, CH2CN), 136.3 (C, aromatic C); m/z (ES+) 130.0 [M+H-HCN]+, (100%).

Reference： [1]Tetrahedron,2011,vol. 67,p. 4601 - 4611

32
[ 771-51-7 ]
[ 89031-84-5 ]
[ 1312995-87-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 3h;	Step 1. Synthesis of 2-(1-(3-(tert-butyldimethylsilyloxy)propyl)-1H-indol-3-yl)acetonitrile (25). To a suspension of sodium hydride (0.65 g, 16.36 mmol, 60% in mineral oil) in DMF (30 mL) was added a solution of (1H-indol-3-yl)-acetonitrile (2.128 g, 13.64 mmol) in DMF (10 mL) in a dropwise manner. Once the evolution of gas had stopped the reaction was stirred for another 30 minutes at room temperature, followed by the dropwise addition of (3-bromopropoxy)(tert-butyl)dimethylsilane (3.17 mL, 13.64 mmol). The reaction mixture was stirred at room temperature for 2.5 hours. The reaction mixture was then poured into EtOAc (50 mL) and 1 N HCl (40 mL). The EtOAc layer was separated, washed with aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using flash column chromatography (SiO2, 5% EtOAc in hexanes) to give 2-(1-(3-(tert-butyldimethylsilyloxy)propyl)-1H-indol-3-yl)acetonitrile (3.85 g, 86%) as a yellow oil.

Reference： [1]Patent: US2011/160237,2011,A1 .Location in patent: Page/Page column 40-41

33
[ 771-51-7 ]
[ 58665-00-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2101 - 2112

34
[ 771-51-7 ]
[ 616-38-6 ]
[ 51584-17-9 ]

Yield	Reaction Conditions	Operation in experiment
91,5%	With tetrabutylammomium bromide; In water; N,N-dimethyl-formamide;	Example 3 Preparation of 1-methyl<strong>[771-51-7]indole-3-acetonitrile</strong>. A 1 L, three-necked flask equipped with a thermocouple, condenser, and addition funnel was charged with <strong>[771-51-7]indole-3-acetonitrile</strong> (58.0 g, 90% pure=0.334 mol), tetrabutylammonium bromide (11.6 g, 36 mmol), N,N-dimethylformamide (348 mL) and dimethyl carbonate (92.8 mL, 1.10 mol) and the resulting mixture was heated to 126+-1 C. The progress of the reaction was monitored by HPLC and after 3 h at this temperature, the presence of remaining starting indole could not be detected. After the reaction mixture was then cooled to zero to -5 C., water (696 mL) was added which resulted in the formation of a precipitate. The mixture was stirred at -5 C. for 1 hour, then the solid was collected by filtration, washed with water (150 mL) and dried under high vacuum at 45 C. for 24 h to give 1-methyl<strong>[771-51-7]indole-3-acetonitrile</strong> (52.0 g, 91.5%) as a brown solid.
	With potassium carbonate; In water; N,N-dimethyl-formamide;	Example 1 Preparation of 1-methyl<strong>[771-51-7]indole-3-acetonitrile</strong> A 500 mL, three-necked flask equipped with a thermocouple, condenser, and addition funnel was charged with <strong>[771-51-7]indole-3-acetonitrile</strong> (10.0 g, 0.064 mol), potassium carbonate (5.0 g, 36 mmol), N,N-dimethylformamide (60 mL) and dimethyl carbonate (11.0 mL, 0.13 mol). The resulting mixture was heated to 124+-1 C. The progress of the reaction was monitored by HPLC. After 10 h at this temperature, the presence of the starting indole could not be detected. The reaction mixture was then cooled to zero to -5 C. Water (140 mL) was added which resulted in the formation of a precipitate. The mixture was stirred at -5 C. for 1 hour, then the solid was collected by filtration, washed with water (150 mL), and dried under high vacuum at 45 C. for 24 h to give 1-methyl<strong>[771-51-7]indole-3-acetonitrile</strong> (I and II, 9.69 g, 89%) as a brown solid.

Reference： [1]Organic Process Research and Development,2001,vol. 5,p. 604 - 608
[2]Patent: US6326501,2001,B1
[3]Patent: US6326501,2001,B1

35
[ 5162-44-7 ]
[ 771-51-7 ]
2-(1-(but-3-enyl)-1H-indol-3-yl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		General procedure: Indole-3-carboxaldehyde(1.45 g,10 mmol) was added into the mixture of K2CO3 (2.78 g, 20 mmol) and CH3CN(20 mL), and was stirred at room temperature for 1h. Then 4-bromo-1-butene (1.3mL, 10 mmol) was added dropwise. After the reaction was finished, remove solventCH3CN, then the residue was extracted with ethyl acetate (3 × 30mL), and the combined organic extracts were dried over anhydrous sodiumsulfate. Subsequently the crude products were purified by column chromatographyeluting with ethyl acetate/petroleum (1/5, V/V) to afford the target compound 1aas oil (1.86 g).Yield: 94 %; 1H NMR (400 MHz, CDCl3): delta 9.99 (s, 1H),8.04 (d, 1H, J = 3.6 Hz), 7.69 (s,1H), 7.39-7.26 (m, 3H), 5.82-5.72 (m, 1H), 5.11-5.05 (m, 2H), 4.23 (t, 2H, J = 7 Hz), 2.66-2.61 (m, 2H).

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 1703 - 1705

36
[ 108-86-1 ]
[ 771-51-7 ]
2-(1-phenyl-1H-indol-3-yl)acetonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With copper; potassium carbonate; In dimethyl sulfoxide; at 130℃; for 7h;	General procedure: Cu-clay nanohybrid (N1, 5 wt.%) was added to a mixture of bromobenzene (1.2 mmol), imidazole (1 mmol) and K2CO3 (2 mmol) in DMSO and stirred at 130 C. The reaction was monitored by thin layer chromatography. After the reaction, the catalyst was separated from the reaction mixture by centrifugation and washed with distilled ethyl acetate. The recovered catalyst was used for further reaction. The product was extracted with ethyl acetate and purified using column chromatography on silica gel (ethyl acetate/hexane: 30/70). The purified products were characterized by NMR and IR spectroscopies and ESI-MS technique.

Reference： [1]Catalysis Communications,2015,vol. 59,p. 238 - 243

37
[ 771-51-7 ]
[ 120-57-0 ]
[ 1258850-09-7 ]

Yield	Reaction Conditions	Operation in experiment
35%		EXAMPLE 11 (Z)-3-benzo[1,3]dioxol-5-yl-2-(1H-indol-3-yl)-acrylonitrile To a solution of sodium ethanolate [prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (200 mg, 1.3 mmol, 1.0 eq.) and, after 30 minutes stirring, benzo[1,3]dioxole-5-carbaldehyde (230 mg, 1.5 mmol, 1.2 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the residue was triturated with diethyl and washed with ethanol to afford the compound (11) as a yellow powder (130 mg, 35%); 1H NMR (DMSO, 500 MHz): delta (ppm): 6.12 (2H, s, 2H2"), 7.06 (1H, d, J7"-6"=7.9 Hz, H7"), 7.16 (1H, t, J5'-4'=J5'-6'=7.6 Hz, H5'), 7.22 (1H, t, J6'-5'=J6'-7'=7.6 Hz, H6'), 7.43 (1H, d, J6"-7"=7.9 Hz, H6"), 7.49 (1H, s, H7'), 7.56 (1H, s, H4"), 7.66 (1H, s, H3), 7.74 (1H, s, H2'), 8.01 (1H, d, J4'-5'=7.6 Hz, H4'); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 101.6 (C2"), 103.4 (C2), 107.4 (C4"), 108.7 (C7"), 110.6 (C3'), 112.5 (C7'), 118.8 (C1), 119.4 (C4'), 120.3 (C5'), 122.3 (C6'), 123.7 (C3a'), 124.2 (C6"), 126.1 (C2'), 128.8 (C5"), 136.5 (C3), 137.1 (C7a'), 147.7 (C3a"), 148.3 (C7a"); TLC: Rf=0.60 (heptane 40/EtOAc 60); SM: ESI: m/z: 287.1 ([M-H]-); HRMS (ESI): calcd for C18H11N2O2: m/z=287.0821. found: 287.0831. IR nuMAX (cm-1): 2212 (nuCN), 3348 (nuN-H); Mp 168 C.
35%		General procedure: Following a similar procedure as the one detailedfor 4a, to a solution of sodiumethanolate [prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrousethanol (4 mL)] were added (1H-indol-3-yl)-acetonitrile2 (200 mg, 1.3 mmol, 1.0 eq.) and benzo[1,3]dioxole-5-carbaldehyde3k (230 mg, 1.5 mmol, 1.2 eq.). The reaction apparatus wasprotected from light and the mixture stirred at roomtemperature for 48 hours, filtered and the crude triturated with diethyl ether andethanol to afford 4k as a yellowpowder (130 mg, 35 %). TLC: Rf = 0.60 (heptane/EtOAc, 40/60). Mp 168C. IR numax(cm-1): 2212 (nu CN), 3348 (nu N-H). 1H NMR (d6-DMSO, 500 MHz) delta (ppm): 6.12 (2H, s, 2H2??), 7.06 (1H, d, J7??-6?? =7.9 Hz, H7??), 7.16 (1H, t, J5?-4? = J5?-6? = 7.6 Hz,H5?), 7.22 (1H, t, J6?-5? = J6?-7? = 7.6 Hz, H6?), 7.43(1H, d, J6??-7?? = 7.9 Hz, H6??), 7.49 (1H, s, H7?), 7.56 (1H,s, H4??), 7.66 (1H, s, H3), 7.74 (1H, s, H2?), 8.01 (1H, d, J4?-5? =7.6 Hz, H4?). 13C NMR (d6-DMSO, 75.5 MHz) delta (ppm): 101.6(C2??), 103.4 (C2), 107.4 (C4??), 108.7 (C7??), 110.6 (C3?), 112.5 (C7?), 118.8(C1), 119.4 (C4?), 120.3 (C5?), 122.3 (C6?), 123.7 (C3a?), 124.2 (C6??), 126.1(C2?), 128.8 (C5??), 136.5 (C3), 137.1 (C7a?), 147.7 (C3a??), 148.3 (C7a??).ESI-MS: m/z 287.1 ([M-H]-).HRESI-MS: m/z 287.0831 (calcd for C18H11N2O2,287.0821).

Reference： [1]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 39
[2]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 721 - 734

38
[ 771-51-7 ]
[ 459-57-4 ]
[ 310411-38-2 ]

Yield	Reaction Conditions	Operation in experiment
48%		EXAMPLE 12 (Z)-3-(4-fluoro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile To a solution of sodium ethanolate [prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (200 mg, 1.3 mmol, 1.0 eq.) and, after 30 minutes stirring, 4-fluoro-benzaldehyde (163 mul, 1.5 mmol, 1.2 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the residue purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 95:5 to 80:20). The product was further purified by aluminium oxide pad filtration (eluent: CH2Cl2/MeOH) to afford the compound (12) as a yellow powder (160 mg, 48%). 1H NMR (DMSO, 300 MHz): delta (ppm): 7.17 (1H, t, J5'-4'=J5'-6'=7.7 Hz, H5'), 7.23 (1H, t, J6'-5'=J6'-7'=7.7 Hz, H6'), 7.35 (2H, t, J3"-2"=J5"-6"=J3"-F=J5"-F=8.9 Hz, H3" and H5"), 7.50 (1H, d, J7'-6'=7.7 Hz, H7'), 7.77 (1H, s, H3), 7.79 (1H, m, H2'), 7.96 (2H, dd, J2"-3"=J6"-5"=8.9 Hz and J2"-F=J6"-F=5.6 Hz, H2" and H6"), 8.05 (1H, d, J4'-5'=7.7 Hz, H4'), 11.71 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 105.6 (C2), 110.5 (C3), 112.4 (C7'), 115.8 (2C, d, 2JC-F=21 Hz, C3" and C5"), 118.3 (C1), 119.5 (C4'), 120.5 (C5'), 122.5 (C6'), 123.6 (C3a'), 126.5 (C2'), 130.7 (2C, d, 3JC-F=8 Hz, C2" and C6"), 131.2 (1C, d, 4JC-F=3 Hz, C1"), 135.3 (C3), 137.1 (C7a'), 162.3 (1C, 1JC-F=248 Hz, C4"); TLC: Rf=0.58 (heptane 50/EtOAc 50); MS: ESI: m/z: 285.1 ([M+Na]+), 317.2 ([M+Na+ MeOH]+), 547.3 ([2M+Na]+); HRMS (ESI): calcd for C17H11N2FNa: m/z=285.0804. found: 285.0807. Microanalysis: Calcd for C17H11N2F %: C, 77.85; H, 4.23; F, 7.24; N, 10.68. Found %: C, 77.57; H, 4.15; N, 10.53. IR numax (cm-1): 2212 (nuCN), 3320 (nuN-H); Mp 132 C.
48%		General procedure: Followinga similar procedure as the one detailed for 4a, to a solution of sodium ethanolate [prepared from sodium (50mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)] were added (1H-indol-3-yl)-acetonitrile 2 (200 mg, 1.3 mmol, 1.0 eq.) and 4-fluoro-benzaldehyde3d (163 ml, 1.5 mmol, 1.2 eq.). The reaction apparatus wasprotected from light and the mixture stirred at room temperature for 48 hours, concentrated todryness, and the residue purified by both silica gel flash-column chromatography(eluent: heptane/EtOAc, 95/5 to 80/20) and aluminium oxide pad filtration(eluent: CH2Cl2/MeOH) to afford 4d as a yellow powder (160 mg, 48 %). TLC: Rf = 0.58 (heptane/EtOAc,50/50). Mp 132C. IR numax (cm-1): 2212 (nu CN),3320 (nu N-H). 1H NMR (d6-DMSO, 300 MHz) delta (ppm): 7.17 (1H, t, J5?-4? =J5?-6? = 7.7 Hz, H5?), 7.23 (1H, t, J6?-5? = J6?-7? =7.7 Hz, H6?), 7.35 (2H, t, J3??-2?? = J5??-6?? = J3??-F= J5??-F = 8.9 Hz, H3?? and H5??), 7.50 (1H, d, J7?-6? = 7.7Hz, H7?), 7.77 (1H, s, H3), 7.79 (1H, m, H2?), 7.96 (2H, dd, J2??-3?? =J6??-5?? = 8.9 Hz and J2??-F = J6??-F = 5.6Hz, H2?? and H6??), 8.05 (1H, d, J4?-5? = 7.7 Hz, H4?), 11.71 (1H,s, indolic H). 13C NMR (d6-DMSO, 75.5 MHz) delta (ppm): 105.6 (C2), 110.5 (C3), 112.4(C7?), 115.8 (2C, d, 2JC-F = 21 Hz, C3?? and C5??), 118.3(C1), 119.5 (C4?), 120.5 (C5?), 122.5 (C6?), 123.6 (C3a?), 126.5 (C2?), 130.7(2C, d, 3JC-F = 8 Hz, C2?? and C6??), 131.2 (1C, d, 4JC-F= 3 Hz, C1??), 135.3 (C3), 137.1 (C7a?), 162.3 (1C, 1JC-F= 248 Hz, C4??). ESI-MS: m/z285.1 ([M+Na]+), 317.2 ([M+Na+MeOH]+), 547.3 ([2M+Na]+). HRESI-MS: m/z 285.0807(calcd for C17H11N2FNa, 285.0804). Anal. calcdfor C17H11N2F: C 77.85, H 4.23, F 7.24, N10.68, Found: C 77.57, H 4.15, N 10.53.

Reference： [1]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 39; 40
[2]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 721 - 734

39
[ 771-51-7 ]
[ 104-88-1 ]
[ 1258850-10-0 ]

Yield	Reaction Conditions	Operation in experiment
56%		EXAMPLE 13 (Z)-3-(4-chloro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile To a solution of sodium ethanolate [prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (200 mg, 1.3 mmol, 1.0 eq.) and, after 30 minutes stirring, 4-chloro-benzaldehyde (216 mg, 1.5 mmol, 1.2 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the crude purified by silica gel flash-column chromatography (eluent: heptane/EtOAc, 95:5 to 80:20). The residue was triturated with diisopropyl ether and heptane to afford the compound (13) as a yellow powder (200 mg, 56%). 1H NMR (DMSO, 300 MHz): delta (ppm): 7.17 (1H, t, J5'-4'=J5'-6'=7.5 Hz, H5'), 7.24 (1H, t, J6'-5'=J6'-7'=7.5 Hz, H6'), 7.49 (1H, d, J7'-6'=7.5 Hz, H7'), 7.57 (2H, d, J3"-2"=J5"-6"=8.6 Hz, H3" and H5"), 7.76 (1H, s, H3), 7.81 (1H, s, H2'), 7.92 (2H, d, J2"-3"=J6"-5"=8.6 Hz, H2" and H6"), 8.06 (1H, d, J4'-5'=7.5 Hz, H4'), 11.74 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 106.5 (C2), 110.6 (C3'), 112.4 (C7'), 118.2 (C1), 119.5 (C4'), 120.5 (C5'), 122.1 (C6'), 123.6 (C3a'), 126.9 (C2'), 128.8 (C3" and C5"), 130.1 (C2" and C6"), 133.6 (C1" and C4"), 134.8 (C3), 137.2 (C7a'); TLC: Rf=0.64 (heptane 50/EtOAc 50); MS: ESI: m/z: 277.1 ([M-H]-); HRMS (ESI): calcd for C7H10ClN2: m/z=277.0533. found: 277.0534. Microanalysis: Calcd for C17H11ClN2, 0.1H2O %: C, 72.78; H, 4.02; Cl, 12.64; N, 9.99. Found %: C, 72.54; H, 4.05; N, 9.39. IR numax (cm-1): 2224 (nuCN), 3296 (nuN-H); Mp 140 C.
56%		General procedure: Following a similar procedure as the one detailed for 4a, to a solution of sodium ethanolate[prepared from sodium (50 mg, 2.3 mmol, 1.7 eq.) in anhydrous ethanol (4 mL)]were added (1H-indol-3-yl)-acetonitrile2 (200 mg, 1.3 mmol, 1.0 eq.) and 4-chloro-benzaldehyde 3f (216 mg, 1.5 mmol, 1.2 eq.). The reaction apparatus was protected from light and themixture stirred at roomtemperature for 48 h, concentrated to dryness, the crude purified by silica gelflash-column chromatography (eluent: heptane/EtOAc, 95/5 to 80/20) and the residuetriturated with diisopropyl ether and heptane to afford 4f as a yellow powder (200 mg, 56 %). TLC: Rf = 0.64 (heptane/EtOAc,50/50). Mp 140C. IR numax (cm-1): 2224 (nu CN),3296 (nu N-H). 1H NMR (d6-DMSO, 300 MHz) delta (ppm): 7.17 (1H, t, J5?-4? = J5?-6? =7.5 Hz, H5?), 7.24 (1H, t, J6?-5? = J6?-7? = 7.5 Hz,H6?), 7.49 (1H, d, J7?-6? = 7.5 Hz, H7?), 7.57 (2H, d, J3??-2??= J5??-6?? = 8.6 Hz, H3?? and H5??), 7.76 (1H, s, H3), 7.81(1H, s, H2?), 7.92 (2H, d, J2??-3?? = J6??-5?? = 8.6 Hz,H2?? and H6??), 8.06 (1H, d, J4?-5? = 7.5 Hz, H4?), 11.74 (1H, s,indolic H). 13C NMR (d6-DMSO, 75.5 MHz) delta (ppm): 106.5 (C2), 110.6 (C3?), 112.4 (C7?), 118.2 (C1),119.5 (C4?), 120.5 (C5?), 122.1 (C6?), 123.6 (C3a?), 126.9 (C2?), 128.8 (C3??and C5??), 130.1 (C2?? and C6??), 133.6 (C1?? and C4??), 134.8 (C3), 137.2(C7a?). ESI-MS: m/z 277.1 ([M-H]-). HRESI-MS: m/z 277.0534 (calcd for C17H10ClN2,277.0533). Anal. calcd for C17H11ClN2, 0.1 H2O: C 72.78, H 4.02, Cl 12.64, N 9.99, Found : C 72.54, H 4.05, N, 9.39.

Reference： [1]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 40; 41
[2]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 721 - 734

40
[ 771-51-7 ]
[ 10070-92-5 ]
[ 1258850-12-2 ]

Yield	Reaction Conditions	Operation in experiment
21%		2) Preparation of (Z)-2-(1H-indol-3-yl)-3-pyrimidin-5-yl-acrylonitrile To a solution of sodium ethanolate [prepared from sodium (53 mg, 2.3 mmol, 1.8 eq.) and anhydrous ethanol (10 mL)] were added, under an argon atmosphere, (1H-indol-3-yl)-acetonitrile (200 mg, 1.3 mmol, 1.0 eq.) and, after 10 minutes stirring, <strong>[10070-92-5]pyrimidine-5-carbaldehyde</strong> (207 mg, 1.9 mmol, 1.5 eq.). The reaction apparatus was protected from light and the mixture stirred at room temperature for 40 hours. The solvent was removed under reduced pressure, and the crude purified by silica gel flash-column chromatography (eluent: CH2Cl2/MeOH, 1:99 to 2:98). The residue was triturated with diethyl ether to afford the compound (15) as a yellow powder (65 mg, 21%). 1H NMR (DMSO, 500 MHz): delta (ppm): 7.22 (1H, t, J5'-6'=J5'-4'=7.9 Hz, H5'), 7.27 (1H, t, J6'-5'=J6'-7'=7.9 Hz, H6'), 7.53 (1H, d, J7'-6'=7.9 Hz, H7'), 7.81 (1H, s, H3), 7.88 (1H, s, H2'), 8.13 (1H, d, J4'-5'=7.9 Hz, H4'), 9.19 (1H, s, H2"), 9.25 (1H, s, H4" and H6"), 11.87 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz): delta (ppm): 113.9 and 114.3 (C2 and C3'), 116.5 (C7'), 121.6 (C1), 123.6 (C4'), 124.8 (C5'), 126.7 (C6'), 127.3 (C3a'), 131.9 (C2'), 132.3 (C3), 133.3 (C5"), 141.2 (C7a'), 159.8 (C4" and C6"), 161.4 (C2"); TLC: Rf=0.47 (CH2Cl2 96/MeOH, 4); MS: ESI: m/z: 245.0 ([M-H]-); HRMS (ESI): calcd for C15H9N4: m/z=245.0827. found: 245.0818. IR numax (cm-1): 2219 (nuCN); Mp 231 C.

Reference： [1]Patent: US9212138,2015,B2 .Location in patent: Page/Page column 42; 43

41
[ 771-51-7 ]
[ 591-31-1 ]
(Z)-2-(1H-indol-3-yl)-3-(3-methoxy-phenyl)-acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%		General procedure: To a solution of sodium methanolate (260 mg,4.80 mmol, 1.5 equiv) in anhydrous ethanol (15 mL) were added,under an argon atmosphere, (1H-indol-3-yl)-acetonitrile 2(500 mg, 3.20 mmol, 1.0 equiv) and, after 30 min stirring, 3-methoxy-benzaldehyde 3a (700 lL, 5.76 mmol, 1.08 equiv). The reactionapparatus was protected from light and the mixture stirredat 40 C for 11 h. The reaction was allowed to cool to room temperatureand then, the solvent was removed under reduced pressure.The crude product was purified by silica gel flash-column chromatography(eluent: CH2Cl2, 100) to afford 4a as a yellow powder(580 mg, 66%). TLC: Rf = 0.45 (CH2Cl2 100). Mp 103 C. IR mmax(cm1): 2219 (mCN), 3315 (mN-H). 1H NMR (d6-DMSO, 300 MHz) d(ppm): 3.82 (3H, s), 6.99 (1H, dm, J = 7.8 Hz,), 7.18 (1H, t,J = 7.8 Hz), 7.24 (1H, t, J = 7.8 Hz), 7.41 (1H, t, J = 7.8 Hz), 7.49(2H, m), 7.51 (1H, s), 7.74 (1H, s), 7.79 (1H, s), 8.05 (1H, d,J = 7.8 Hz), 11.72 (1H, s). 13C NMR (d6-DMSO, 75.5 MHz) d (ppm):55.2, 102.0, 106.0, 110.6, 112.4, 113.7, 115.2, 118.4, 119.5, 120.5,120.8, 122.5, 123.6, 126.7, 129.8, 135.9, 136.3, 137.2, 159.3;ESI-MS: m/z 297.1 ([M+Na]+). HRESI-MS: m/z 297.0997 (calcd forC18H14N2ONa, 297.1004). Anal. Calcd for C18H14N2O, 0.2 H2O:C, 77.79; H, 5.22, N, 10.08; O, 6.91. Found: C, 77.77; H, 5.13;N, 10.23.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 721 - 734

42
[ 74-96-4 ]
[ 771-51-7 ]
[ 851041-59-3 ]

Yield	Reaction Conditions	Operation in experiment
47%		To a solution of NaH (1.8 g, 75 mmol) in THF (20 mL) was added <strong>[771-51-7]indole-3-acetonitrile</strong> (3.12 g,20 mmol) in DMSO (30 mL) dropwise at 0 C. The resulting mixture was allowed to reach roomtemperature for a further 30 min. Then, the resulting mixture was added the compound RBr inTHF (5 mL) dropwise at 0 C. The reaction mixture was quenched with ammonium chloride (1 mL),and extracted three times with ethyl acetate. The organic extracts were combined, washed with brine,dried over Na2SO4, and concentrated. Purification by flash chromatography (petroleum ether-ethylacetate = 4:1) on silica gel afforded the compound 5 (1.47 g, 47% yield).

Reference： [1]Molecules,2016,vol. 21

43
[ 80278-67-7 ]
[ 771-51-7 ]
(Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		General procedure: General procedure (1): Microwave method: To an indole-3-acetonitrile derivative (1.0 equiv) dissolved in anhydrous methanol (4 ml_ for 2.31 mmol of starting material) in a dried microwave vial, sodium methoxide (1.7 equiv) was added and stirred at room temperature for 15 min protected from light. Quinoline/isoquinoline-carboxaldehyde derivative (1.2 equiv) was added and the mixture was subjected to microwave irradiation at 95 °C for 8.5 min. The reaction was cooled to room temperature and then chilled in an ice/salt bath. The resulting precipitate was filtered, washed with methanol, and dried under vacuum to afford a solid as the product. Compound 1 [a131] (114 mg, 0.386 mmol) was prepared as a yellow solid from indole-3- acetonitrile (120 mg, 0.769 mmol), <strong>[80278-67-7]isoquinoline-5-carboxaldehyde</strong> (147 mg, 0.938 mmol) and sodium methoxide (71 mg, 1.307 mmol) according to general procedure (1) microwave method. Yield: 47percent. Yellow crystals were obtained by recrystallization using acetone and methanol. 1H NMR (400 MHz, DMSO) delta: 9.41 (s, 1 H), 8.60 (d, J = 6.0 Hz, 1 H), 8.34 (s, 1 H), 8.26 (d, J = 7.3 Hz, 1 H), 8.22 (d, J = 8.1 Hz, 1 H), 8.12 (d, J = 7.6 Hz, 1 H), 8.05 (d, J = 6.0 Hz, 1 H), 7.95 (s, 1 H), 7.82 (t, J = 7.8 Hz, 1 H), 7.54 (d, J = 7.9 Hz, 1 H), 7.28 - 7.19 (m, 2H). 13C NMR (100 MHz, DMSO) delta: 152.93, 143.69, 137.26, 133.54, 132.54, 131.29, 130.25, 128.91 , 128.23, 127.44, 127.11 , 123.83, 122.56, 120.69, 119.50, 117.96, 117.12, 112.56, 110.43, 110.41. LC-MS (ESI): m/z 296.1 [M + H]+. HRMS (ESI): m/z calculated [M + H]+ C2oH14N3+ 296.1182, found 296.1190.
47%		General procedure: To an indole-3-acetonitrile derivative (1.0 equiv) dissolved in anhydrous methanol (4mL for 2.31mmol of starting material) in a dried microwave vial, sodium methoxide (1.7 equiv) was added and stirred at room temperature for 15min protected from light. Quinoline/isoquinoline-carboxaldehyde derivative (1.2 equiv) was added and the mixture was subjected to microwave irradiation at 95°C for 8.5min. The reaction was cooled to room temperature and then chilled in an ice/salt bath. The resulting precipitate was filtered, washed with methanol, and dried under vacuum to afford a solid as the product.

Reference： [1]Patent: WO2016/200339,2016,A1 .Location in patent: Page/Page column 76-77
[2]European Journal of Medicinal Chemistry,2018,vol. 156,p. 344 - 367

44
[ 80278-67-7 ]
[ 771-51-7 ]
(Z)-3-(isoquinolin-5-yl)-2-(1-(2-(4-methylpiperazin-1-yl)acetyl)-1H-indol-3-yl)acrylonitrile [ No CAS ]

Reference： [1]Patent: WO2016/200339,2016,A1

45
[ 771-51-7 ]
[ 1593-60-8 ]
2-(2-(p-tolylthio)-1H-indol-3-yl)acetonitrile [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 5284 - 5288

46
[ 50-00-0 ]
[ 771-51-7 ]
[ 1509-35-9 ]
(2R,3S)-2-(((1-(2-(1H-indol-3-yl)ethyl)-1H-tetrazol-5-yl)methyl)amino)-3-methylpentanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	Stage #1: formaldehyd; D-alloisoleucine In methanol at 20℃; for 0.166667h; Stage #2: indole-3-acetonitrile With sodium azide In methanol at 20℃; for 12h;

Reference： [1]Madhavachary, Rudrakshula; Wang, Qian; Dömling, Alexander [Chemical Communications, 2017, vol. 53, # 61, p. 8549 - 8552]

47
[ 879-37-8 ]
[ 771-51-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	at 335℃; for 1h;	General procedure: Following the amide intermediate Preparation Example A. The reaction vessel is closed (when the amide intermediate has a boiling point at normal pressure equal to or lower than the reaction temperature TB described below) or the reaction vessel is kept open (when the amide intermediate has a boiling point higher than the normal pressure When the reaction temperature is TB), stirring is continued (600 r/min), the reaction temperature is changed to TB, and after the reaction temperature TB is maintained for TD hours, the reaction is substantially completed. Then, the reaction vessel was sealed and connected to a vacuum pump so that the degree of vacuum in the reaction vessel reached 20-50 mbar (according to the type of nitrile product) and the distillate was used as the nitrile product. The yield of the nitrile product was calculated and sampled for nuclear magnetic resonance and elemental analysis to characterize the nitrile product obtained. Specific reaction conditions and characterization results are shown in Tables A-7, A-8, A-9, A-10, A-11 and A-12 below. These characterization results show that the nitrile product obtained has an extremely high purity (above 99%).In these nitrile product preparation examples, 10 g of phosphorus pentaoxide is preferably added to the reaction vessel as a catalyst at one stage, optionally at the beginning of the reaction.

Reference： [1]Patent: CN104557610,2018,B .Location in patent: Paragraph 0153; 0154; 0155; 0158; 0159

48
[ 771-51-7 ]
[ 787615-01-4 ]
(Z)-2-(1H-indol-3-yl)-3-(isoquinolin-8-yl)acrylonitrile [ No CAS ]