[ CAS No. 5457-28-3 ] {[proInfo.proName]}

Name: 5457-28-3|1H-Indole-3-carbonitrile|97%
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Quality Control of [ 5457-28-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5457-28-3 ]

Product Details of [ 5457-28-3 ]

CAS No. :	5457-28-3	MDL No. :	MFCD00022717
Formula :	C₉H₆N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CHIFTAQVXHNVRW-UHFFFAOYSA-N
M.W :	142.16	Pubchem ID :	230282
Synonyms :

Calculated chemistry of [ 5457-28-3 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.01
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) :	-5.62 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.46
Log Po/w (XLOGP3) :	2.18
Log Po/w (WLOGP) :	2.04
Log Po/w (MLOGP) :	0.88
Log Po/w (SILICOS-IT) :	2.51
Consensus Log Po/w :	1.81

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.7
Solubility :	0.283 mg/ml ; 0.00199 mol/l
Class :	Soluble
Log S (Ali) :	-2.64
Solubility :	0.322 mg/ml ; 0.00227 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.34
Solubility :	0.0644 mg/ml ; 0.000453 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.37

Safety of [ 5457-28-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 5457-28-3 ]

* 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 [ 5457-28-3 ]
Downstream synthetic route of [ 5457-28-3 ]

[ 5457-28-3 ] Synthesis Path-Upstream 1~7

1
[ 5457-28-3 ]
[ 1670-85-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With dihydrogen peroxide; sodium hydroxide In ethanol at 20℃;	General procedure: To a stirred solution of 19a, 19b (15 mmol) in anhydrous ethanol was added 40 percent NaOH (5 mL), then 10.5mL of 30 percent H2O2(104.7 mmol) was slowly added to the mixture upon monitoring by TLC. The precipitated solid was filtered off, washed with water, recrystallized from anhydrous ethanol, and dried in vacuum to give the respective product. 1H-Indole-3-carboxamide (20a). White solid, yield 75 percent, mp 195–197°C (197–199°C [31]). 1H NMR spectrum, δ, ppm: 6.84 s (1H, NH), 7.13~7.21 m (2H, ArH), 7.47 d (J = 8.0 Hz, 2H, ArH), 8.08 s (1H, NH), 8.20 d (J = 7.5 Hz, 1H, ArH), 11.60 s (1H, NH).

Reference： [1] Applied Organometallic Chemistry, 2014, vol. 28, # 12, p. 900 - 907
[2] Catalysis Science and Technology, 2015, vol. 5, # 3, p. 1606 - 1622
[3] Synthetic Communications, 2013, vol. 43, # 21, p. 2867 - 2875
[4] Dalton Transactions, 2016, vol. 45, # 34, p. 13590 - 13603
[5] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 3006 - 3016
[6] Heterocycles, 2009, vol. 78, # 4, p. 947 - 959
[7] Archiv der Pharmazie (Weinheim, Germany), 1937, vol. 275, p. 506,511
[8] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 9, p. 2535 - 2538
[9] RSC Advances, 2013, vol. 3, # 3, p. 895 - 899

2
[ 5457-28-3 ]
[ 90271-86-6 ]
[ 224434-83-7 ]

Reference： [1] Organic letters, 2000, vol. 2, # 14, p. 2121 - 2123

3
[ 5457-28-3 ]
[ 60524-00-7 ]

Reference： [1] Patent: WO2017/120429, 2017, A1,

4
[ 5457-28-3 ]
[ 122135-84-6 ]
[ 4341-76-8 ]

Reference： [1] Journal of Organic Chemistry, 2005, vol. 70, # 21, p. 8638 - 8641

5
[ 5457-28-3 ]
[ 118959-44-7 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 9, p. 2535 - 2538

6
[ 5457-28-3 ]
[ 224434-83-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With N-Bromosuccinimide In dichloromethane	EXAMPLE 8 This example describes the synthesis of 6-bromocyanoindole 14.Direct bromination of 3-cyanoindole 13 with NBS over silica in CH2Cl2 (Mistry et al, Tetrahedron Lett., 1986, 27, 1051, incorporated herein by reference) gave a 50percent yield of bromoindole 14 as the major product.Small amounts (10percent) of the 5-substituted regioisomer were also observed. Although the yield was modest, the preparation of 14 requires only one step from commercially available 3-cyanoindole and is easily separated from the minor regioisomer by flash chromatography. HMQC correlations confirmed the position of substitution.

Reference： [1] Patent: US2003/232988, 2003, A1, . Location in patent: Page column 0106

7
[ 5457-28-3 ]
[ 90271-86-6 ]
[ 224434-83-7 ]

Reference： [1] Organic letters, 2000, vol. 2, # 14, p. 2121 - 2123

[ 5457-28-3 ] Synthesis Path-Downstream 1~88

1
[ 5457-28-3 ]
[ 1670-85-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With dihydrogen peroxide; sodium hydroxide; In ethanol; at 20℃;	General procedure: To a stirred solution of 19a, 19b (15 mmol) in anhydrous ethanol was added 40 % NaOH (5 mL), then 10.5mL of 30 % H2O2(104.7 mmol) was slowly added to the mixture upon monitoring by TLC. The precipitated solid was filtered off, washed with water, recrystallized from anhydrous ethanol, and dried in vacuum to give the respective product. 1H-Indole-3-carboxamide (20a). White solid, yield 75 %, mp 195-197C (197-199C [31]). 1H NMR spectrum, delta, ppm: 6.84 s (1H, NH), 7.13~7.21 m (2H, ArH), 7.47 d (J = 8.0 Hz, 2H, ArH), 8.08 s (1H, NH), 8.20 d (J = 7.5 Hz, 1H, ArH), 11.60 s (1H, NH).

Reference： [1]Applied Organometallic Chemistry,2014,vol. 28,p. 900 - 907
[2]Catalysis science and technology,2015,vol. 5,p. 1606 - 1622
[3]Synthetic Communications,2013,vol. 43,p. 2867 - 2875
[4]Dalton Transactions,2016,vol. 45,p. 13590 - 13603
[5]Russian Journal of General Chemistry,2017,vol. 87,p. 3006 - 3016
[6]Heterocycles,2009,vol. 78,p. 947 - 959
[7]Archiv der Pharmazie,1937,vol. 275,p. 506,511
[8]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2535 - 2538
[9]RSC Advances,2013,vol. 3,p. 895 - 899

2
[ 1670-85-5 ]
[ 5457-28-3 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2003,vol. 42,p. 3148 - 3151
[2]Journal of the Chemical Society,1956,p. 2853,2856
[3]Tetrahedron,1992,vol. 48,p. 2919 - 2924

3
[ 1477-49-2 ]
[ 5457-28-3 ]

Reference： [1]Journal of Organic Chemistry,1958,vol. 23,p. 1171,1176

4
[ 110-45-2 ]
[ 2973-50-4 ]
[ 5457-28-3 ]

Reference： [1]Chemische Berichte,1910,vol. 43,p. 2550

5
[ 120-72-9 ]
[ 33513-42-7 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
81%		General procedure: To a flask containing 1,3,5-trimethoxybenzene (1009.1 mg, 6 mmol) were added POCl3 (1011.9 mg, 6.6 mmol) and DMF (1754.1 mg, 24 mmol) at 0 C. After being stirred for 3 h at 40 C, I2 (3045.7 mg, 12 mmol) and aq NH3 (12 mL, 28-30%) were added to the reaction mixture. The obtained mixture was stirred for 3 h at rt. After the reaction, the mixture was poured into aq satd Na2SO3 solution and extracted with CHCl3 (3×20 mL). The organic layer was dried over Na2SO4, filtered, and evaporated to provide almost pure 2,4,6-trimethoxybenzonitrile (1156.1 mg) in 99% yield. If necessary, it was recrystallized from a mixture of hexane and EtOAc (1:1).

Reference： [1]Tetrahedron,2012,vol. 68,p. 4588 - 4595
[2]Organic and Biomolecular Chemistry,2015,vol. 13,p. 8322 - 8329
[3]Organic Letters,2012,vol. 14,p. 3924 - 3927
[4]Zeitschrift fur Chemie,1983,vol. 23,p. 214 - 215
[5]Organic Letters,2015,vol. 17,p. 4396 - 4399

6
[ 67-56-1 ]
[ 5457-28-3 ]
[ 74862-25-2 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1980,vol. 16,p. 501 - 506
Khimiya Geterotsiklicheskikh Soedinenii,1980,p. 645 - 650
[2]Tetrahedron Letters,1990,vol. 31,p. 2445 - 2448
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 1019 - 1031
[4]Synthesis,1994,p. 832 - 836
[5]Journal of Pharmaceutical Sciences,1995,vol. 84,p. 101 - 106

7
[ 5457-28-3 ]
[ 22259-53-6 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride; In tetrahydrofuran; 1,4-dioxane; at 0℃; for 1h;Reflux;	To a 1 L four-neck flask were added dioxane (200 mL), THF (100 mL) and 3- cyanoindole (30 g, 211 mmol). The solution was cooled to 0 oC and LiAlH4 (30 g, 780 mmol) was added portion-wise. After stirring at 0 oC for 10 minutes, the mixture was heated to reflux for 0.5 h until TLC showed completion. The mixture was carefully quenched with water (300 mL) at 0 oC, filtered, and the filtrate was separated. The aqueous layer was extracted with EA (500 mL x 2). The combined organic layers were dried over sodium sulfate, concentrated and washed with PE/EA to give 3-aminomethylindole (21 g, 70percent) as a brick red solid. (2137) 1H NMR (300 MHz, DMSO-d6) 10.80 (br, 1 H), 7.59 (d, J = 7.5 Hz, 1 H), 7.34 (d, J = 8.1 Hz, 1 H), 7.20 (s, 1 H), 7.09- 7.04 (m, 1 H), 6.99- 6.94 (m, 1 H), 3.87 (s, 2 H).

Reference： [1]Heterocycles,1992,vol. 33,p. 77 - 80
[2]Synthetic Communications,1988,vol. 18,p. 671 - 674
[3]Patent: WO2017/120429,2017,A1 .Location in patent: Page/Page column 256

8
[ 5457-28-3 ]
[ 95649-37-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydroxylamine hydrochloride; triethylamine; In ethanol; at 80℃; for 12h;	Amidoxime Formation Cyano indole la-d ( 1 equiv.) and hydroxylamine hydrochloride (3 equiv.), and TEA (3 equiv.) were added to a round bottom flask containing ethanol. The reaction mixture was heated to 80 C for 12 hours or until the reaction appeared to have gone to completion via monitoring by TLC. The solution was cooled to room temperature and the solvent was removed under reduced pressure. The resulting solid was loaded onto celite and purified on a silica gel column with 0-10% methanol in ethyl acetate.
99%	With hydroxylamine hydrochloride; triethylamine; In ethanol; at 80℃; for 12h;	General procedure: Cyanoindole la-d ( 1 equiv.) and hydroxylamine hydrochloride (3 equiv.), and TEA (3 equiv.) were added to a round bottom flask containing ethanol. The reaction mixture was heated to 80 C for 12 hours or until the reaction appeared to have gone to completion via monitoring by TLC. The solution was cooled to room temperature and the solvent was removed under reduced pressure. The resulting solid was loaded onto celite and purified on a silica gel column with 0-10% methanol in ethyl acetate.
99%	With hydroxylamine hydrochloride; triethylamine; In ethanol; at 80℃;	General procedure: Cyanoindole (1equiv) and HONH2HCl (3 equiv), and TEA (3 equiv) were added to around bottom flask containing EtOH (10 mL EtOH/1 mmol cyanoindole).The reaction mixture was heated to 80 C for 12 h oruntil the reaction appeared to have gone to completion via monitoringby TLC. The solutionwas cooled to room temperature and the solvent was removed under reduced pressure. The resulting solidwas loaded onto Celite and purified on a silica gel column with0e10% MeOH in EtOAc to afford the corresponding amidoximeproduct.

67%

With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; for 6h;Reflux;

General procedure: To a stirred suspension of corresponding nitrile and hydroxylamine hydrochloride (1.5 equiv.) in EtOH (10 mL per gram of nitrile) a NaHCO3 (1.5 equiv.) was added. The reaction mixture was stirred under reflux for a 6 h. After the reaction had completed, the reaction mixture was concentrated under reduced pressure, and the residue was diluted with cold water (200 mL). The resulting precipitate was filtered off and washed with cold water (50 mL).

Reference： [1]Patent: WO2016/54261,2016,A1 .Location in patent: Page/Page column 63; 64; 66
[2]Patent: WO2017/172989,2017,A1 .Location in patent: Page/Page column 90-91
[3]European Journal of Medicinal Chemistry,2021,vol. 212
[4]Tetrahedron Letters,2017,vol. 58,p. 3672 - 3677
[5]Journal of medicinal chemistry,1991,vol. 34,p. 140 - 151

9
[ 942-24-5 ]
[ 5457-28-3 ]

Reference： [1]Synthesis,1998,p. 329 - 332

10
[ 22259-53-6 ]
[ 5457-28-3 ]

Reference： [1]Journal of Chemical Research - Part S,1999,p. 726 - 727

11
[ 5457-28-3 ]
[ 90271-86-6 ]
[ 224434-83-7 ]

Reference： [1]Organic letters,2000,vol. 2,p. 2121 - 2123

12
[ 700-06-1 ]
[ 5457-28-3 ]

Reference： [1]Synlett,2002,p. 1291 - 1292
[2]Chemical Communications,2012,vol. 48,p. 5506 - 5508
[3]Green Chemistry,2019,vol. 21,p. 4334 - 4340

13
[ 5457-28-3 ]
[ 79-22-1 ]
3-cyano-1-methoxycarbonylindole [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 8146 - 8147

14
[ 5457-28-3 ]
[ 118959-44-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2535 - 2538

15
silica [ No CAS ]
[ 5457-28-3 ]
[ 224434-83-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With N-Bromosuccinimide; In dichloromethane;	EXAMPLE 8 This example describes the synthesis of 6-bromocyanoindole 14.Direct bromination of 3-cyanoindole 13 with NBS over silica in CH2Cl2 (Mistry et al, Tetrahedron Lett., 1986, 27, 1051, incorporated herein by reference) gave a 50% yield of bromoindole 14 as the major product.Small amounts (10%) of the 5-substituted regioisomer were also observed. Although the yield was modest, the preparation of 14 requires only one step from commercially available 3-cyanoindole and is easily separated from the minor regioisomer by flash chromatography. HMQC correlations confirmed the position of substitution.

Reference： [1]Patent: US2003/232988,2003,A1 .Location in patent: Page column 0106

16
[ 5457-28-3 ]
[ 4892-02-8 ]
[ 501376-47-2 ]

Yield	Reaction Conditions	Operation in experiment
20%	With triethylamine; In toluene; for 24h;Heating / reflux;	Example 172 2-(1H-Indol-3-yl)-4H-1,3-benzothiazine-4-one 3-Cyanoindole (1.00g, 7.0mmol) and methyl thiosalicylate (1.20 g, 7.0 mmol) were dissolved in toluene (10 ml), and triethylamine (1.5 ml, 10.4 mmol) was added thereto.. The reaction mixture was refluxed for 24 hrs.. The solvent was evaporated.. The residue was recrystallized from ethanol to give the titled compound (0.38 g, 20 %) as pale yellow crystals. mp. 276.5-277.0 C IR(KBr): 1626, 1591, 1516, 1493, 1454, 1439, 1356, 1329, 1300, 1261, 1242, 1143, 1107, 1086, 1068, 908, 817, 729 cm-1.1H-NMR (CDCl3) δ: 7.28-7.31 (2H, m), 7.53-7.56 (1H, m), 7.61-7.66 (1H, m), 7.71-7.75 (2H, m), 8.31 (1H, d, J = 7.6 Hz), 8.49-8.51 (1H, m), 8.55 (1H, d, J = 3.0 Hz), 12.41 (1H, br s).

Reference： [1]Patent: EP1424336,2004,A1 .Location in patent: Page 127

17
[ 5457-28-3 ]
[ 917494-89-4 ]
1-[3,3,3-trifluoro-2-hydroxy-2-(1-phenyl-1H-indazol-5-yl)propyl]-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%		Example 6: l-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propyl]-li3r-indoIe-3-carbonitrileTo a solution of l-phenyl-5-(2-trifluoromethyloxiranyl)-lH-indazole (50.0 mg, 0.1 mmol) in 0.5 mL of TΗF was added <strong>[5457-28-3]indole-3-carbonitrile</strong> (45.0 mg, 0.3 mmol) and sodium ethoxide (21% wt. in ethanol, 0.13 mL, 0.30 mmol). The resulting solution was allowed to stir in a sealed reaction tube at 9O0C for 12 hours. The reaction mixture was cooled to room temperature and 2.0 mL water of water was added. The aqueous layer was extracted with two 5 mL portions of ethyl ether. The organic layers were combined and washed with water and brine, then dried over sodium sulfate, and filtered. The solvents were removed by rotary evaporation in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 95%-90% hexanes/EtOAc). The desired product 1 -[3,3,3 -trifluoro-2- EPO <DP n="128"/>hydiOxy-2-(l-phenyl-lH-indazol-5-yl)propyl]-lH-<strong>[5457-28-3]indole-3-carbonitrile</strong> was obtained as a white solid (20 mg, 27% yield; M+Η+: 447).

Reference： [1]Patent: WO2006/135826,2006,A1 .Location in patent: Page/Page column 125-126

18
[ 5457-28-3 ]
[ 122-51-0 ]
[ 894852-19-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 160℃; for 72h;High pressure; Large scale;	[00111] A suspension of <strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> (1000 mg, 7.03 mmol) in triethyl orthoformate (11.7 mL, 70.34 mmol) was heated to 160C in a high-pressure tube and stirred for 3 days. The reaction mixture was evaporated to dryness and the residue was purified by column chromatography on silica gel (0-20% ethyl acetate in Ao-hexane) to afford 1-(diethoxymethyl)-<strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> as a colourless oil. [00112] Yield 1806 mg (quant.). 1H NMR (400 MHz, DMSO) d 8.41 (s, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.38 (dd, J=7.5, 7.5 Hz, 1H), 7.33 (dd, J=7.5, 7.5 Hz, 1H),6.59 (s, 1H),3.62 (q, J=7.0 Hz,4H), 1.17 (t, J=7.0 Hz,6H).
86%	at 160℃; for 72h;	a) 1 -diethoxymethyl- 1 H-indole-3 -carbonitrile; <n="143"/>lH-Indole-3-carbonitrile (5.07 g, 35.7 mmol) was heated with triethylorthoformate (60 mL) in a pressure vessel at 1600C for 3 d. Upon cooling, the solvent was evaporated and the residue was submitted to chromatography (20% ether in hexanes) to afford the title compound (7.46 g, 86%). NMR (300 MHz, CDCl3, δ): 7.92 (s, IH), 7.76 (m, IH), 7.62 (m, IH), 7.32 (m, 2H), 6.23 (s, IH), 3.63 (m, 4H), 1.23 (t, J =7.2 Hz, 6H).

Reference： [1]Patent: WO2021/216665,2021,A1 .Location in patent: Paragraph 00111-00112
[2]Patent: WO2007/53131,2007,A2 .Location in patent: Page/Page column 141-142

19
[ 700-06-1 ]
[ 487-89-8 ]
[ 5457-28-3 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 6286 - 6288
Angewandte Chemie,2009,vol. 121,p. 6404 - 6406

20
[ 1899-24-7 ]
[ 5457-28-3 ]
[ 1071973-90-4 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 50℃; for 5h;	A suspension of <strong>[5457-28-3]3-cyanoindole</strong> (0.14 g), 5-bromo-2-furaldehyde (0.18 g), and cesium carbonate (0.39 g) in N,N-dimethylformamide (3 mL) was stirred at room temperature or 3 hours. This reaction mixture was heated at 50C, stirred for 2 hours. After cooling to ambient, water was added to this reaction mixture. This mixture was extracted with ethyl acetate, and this organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1) to give the title compound (0.086 g).

Reference： [1]Patent: EP2133332,2009,A1 .Location in patent: Page/Page column 25

21
[ 5457-28-3 ]
[ 696-62-8 ]
1-(4-methoxyphenyl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In toluene; at 110℃;Inert atmosphere;	1 eq 3-Cyanoindole, 2 eq 4-Iodoanisole, 2.1 eq Potassium phosphate, 4.5 eq N,N'- dimethylethylenediamine and 0.2 eq Copper(I) iodide were mixed in oven-dried vial and Toluene added. The mixture was stirred under N2-atmosphere at 110 0C over night. The reaction mixture was cooled to rt, filtered and evaporated in vacuo. The crude product was purified on silica column using 4:1 n- heptane:EtOAc as mobile phase.
	With phosphate potassium salt; N,N`-dimethylethylenediamine;copper(l) iodide; In toluene; at 110℃;Inert atmosphere;	Step (a): 1 eq 3-Cyanoindole, 2 eq 4-iodoanisole, 2.1 eq potassium phosphate, 4.5 eq N,N'-dimethylethylenediamine and 0.2 eq copper(I) iodide were mixed in an oven-dried vial and toluene was added. The mixture was stirred under N2-atmosphere at 110 0C over night. The reaction mixture was cooled to rt, filtered and evaporated in vacuo. The crude product was purified on silica using n-heptane: EtOAc (4:1) as mobile phase.

Reference： [1]Patent: WO2010/31852,2010,A1 .Location in patent: Page/Page column 23
[2]Patent: WO2009/127686,2009,A1 .Location in patent: Page/Page column 24

22
[ 5457-28-3 ]
[ 89978-52-9 ]
[ 1071970-57-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; In toluene; at 110℃; for 38h;	A mixture of 1H-indole-3-carbonitrile (0.1 g), <strong>[89978-52-9]2-bromoisonicotinic acid ethyl ester</strong> (0.16 g), potassium phosphate (0.27 g), (1R,2R)-(-)-N,N'-dimethylcyclohexane-1,2-diamine (0.017 g), copper iodide (0.006 g) and toluene (0.7 mL) was stirred at 110C for 38 hours. The insoluble material was removed by filtration, and this filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane = 10/90 to 66/34) to give the title compound (0.061 g).

Reference： [1]Patent: EP2133332,2009,A1 .Location in patent: Page/Page column 36

23
[ 5457-28-3 ]
[ 58313-23-8 ]
[ 1071970-55-2 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; dimethylaminoacetic acid; caesium carbonate; In dimethyl sulfoxide; at 75℃; for 72h;	To a solution of <strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> (0.28 g) in dimethyl sulfoxide (3 mL) were added 3-iodobenzoic acid ethyl ester (0.61 g), cesium carbonate (0.65 g), copper iodide (0.038 g) and N, N-dimethyl grycine (0.041 g), this mixture was stirred at 75C for 3 days. To this reaction mixture was added ethyl acetate, the insoluble material was removed by filtration and this filtrate was concentrated under reduced pressure. To this residue was added water, the precipitated solid was collected by filtration, and washed with water and n-hexane, and dried under reduced pressure at 40C to give the title compound (0.38 g).

Reference： [1]Patent: EP2133332,2009,A1 .Location in patent: Page/Page column 36

24
[ 5457-28-3 ]
[ 124517-47-1 ]
C₁₈H₁₄N₂ [ No CAS ]
[ 1198150-95-6 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 7841 - 7844

25
[ 1198795-24-2 ]
[ 5457-28-3 ]
rac-(9S*,9aR*,10R*)-9-hydroxy-9-methyl-6-oxo-7,8,9,9a,10-hexahydropyrido[1,2-a]indole-10-carbonitrile [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 4475 - 4480

26
[ 5457-28-3 ]
[ 1332627-57-2 ]

Yield	Reaction Conditions	Operation in experiment
55%		A solution of 3-indolecarbonitrile (50 mg, 0.35 mmol) in THF (0.5 mL) was added to a suspension of lithium aluminum deuteride (30 mg, 0.70 mmol) in dry THF (0.5 mL) and stirred at 55-60 C for 4 h. The reaction mixture was cooled to room temperature, diluted with NaOH (1 M, 0.5 mL) and filtered. The filtrate was diluted with water (10 mL) and extracted with EtOAc (3 × 20 mL). The combined organic extract was dried over Na2SO4 and concentrated. The residue was separated (SiO2, CH2Cl2/MeOH/NH4OH) to afford [1',1'-2H2]indolyl-3-methanamine as a white solid (27 mg, 55% yield). Carbon disulfide (12 mg, 0.152 mmol) was added to a solution of [1',1'-2H2]indolyl-3-methanamine (15 mg, 0.10 mmol) and Et3N (21 mg, 0.202 mmol) in pyridine (1 mL) and stirred at rt for 15 min. Next, MeI (180 mg, 1.27 mmol) was added and stirring was continued for another 20 min. The reaction mixture was diluted with toluene (2 mL) and concentrated under reduced pressure. The crude product was separated (SiO2, EtOAC/hexanes) to yield [1',1'-2H2]brassinin (14 mg, 58%). 1H NMR (500.3 MHz, CD3CN): δ 9.26 (br s, NH), 8.24 (br s, NH), 7.63 (d, J = 8 Hz, 1H), 7.42 (d, J = 8 Hz, 1H), 7.31 (s, 1H), 7.16 (dd, J = 8, 8 Hz, 1H), 7.07 (dd, J = 8, 8 Hz, 1H), 2.55 (s, 3H). Minor peaks of a rotamer were observed at δ 2.67 and 8.55 (only dideuterated brassinin was detected). 13C NMR (125.8 MHz, CD3CN): δ 199.1 (s), 137.7 (s), 128.1 (s), 126.1 (s), 123.2 (d), 120.7 (d), 120.0 (d), 112.8 (d), 111.8 (s), 42.9 (quintet, JC-D = 21.5 Hz), 18.5 (q). HRMS: m/z measured 238.0560 (238.0567 calcd for C11H102H2N2S2).

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1390 - 1399

27
[ 5457-28-3 ]
[ 557-93-7 ]
[ 1301751-04-1 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 2062 - 2064
[2]Journal of Organic Chemistry,2011,vol. 76,p. 9488 - 9496

28
[ 5457-28-3 ]
[ 23078-34-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium azide; In methanol; N,N-dimethyl-formamide; at 20 - 100℃; for 8h;	General procedure: A mixture of benzonitrile (1 mmol), sodium azide (2 mmol), Ln(OTf)3-SiO2 (2008 mg) and DMF/MeOH (4:1, 5 mL) in a pressure vial was initially stirred at room temperature. After 30 min, the temperature of the reaction mixture was raised to 100 C and stirred for another 7 h. After consumption of 1a (as indicated by TLC), the catalyst was separated by filtration and the filtrate was treated with ethyl acetate (15 mL). The organic layer was washed with 4 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layer was washed with water (2 × 10 mL), dried over anhydrous sodium sulfate and concentrated to afford white crystalline solid.5-Phenyl-1H-tetrazole(3a)IR (KBr, cm-1): 3331, 2907, 2850, 2611, 1607, 1485, 1433, 1050, 828, 742. 1H NMR (300 MHz, CDCl3): 8.04-8.007 (m, 1H), 7.611-7.574 (m, 2H). 13C NMR (75 MHz, CDCl3): 156.03, 131.19, 129.08, 126.805, 123.924. MS: m/z = 146 [M]+.
80%	With sodium azide; acetic acid; urea; In water; N,N-dimethyl-formamide; at 60 - 110℃; for 9h;	General procedure: The procedure for the synthesis of the tetrazole 2a is representative. A mixture of sodium azide (0.39 g 0.0060 mol), urea (0.36 g, 0.0060 mol) and water (2.5 mL) was taken in a round-bottom flask and stirred at 60 C for 1 h. Charged benzonitrile 1a (0.5 g 0.0048 mol), acetic acid(0.5 mL) and DMF (2.5mL) at 60 C and heat to 110C stirred for 8 h. After completion of the reaction (as indicated by TLC), the reaction mixture was cooled to room temperature and diluted the reaction mass with water (2.5 mL)and ethyl acetate (5.0 mL) at 25-35 C. Add 5N aqueous hydrochloric acid (2.5 mL) at 25-35 C. Stirred for 20- 30 min, the resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (2.5 mL). The combined organic layer was washed with 40 % aq.NaCl solution (2.5 mL) and dried over anhydrous Na2SO4 and concentrated to give a crude product, which was isolated using chilled water after 3-4 h maintenance, and eventually filtered off to give 0.67 g (95%) of an off-white solid.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 3557 - 3560
[2]Tetrahedron Letters,2018,vol. 59,p. 445 - 449
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 5320 - 5334

29
[ 59108-90-6 ]
[ 5457-28-3 ]
[ 1273565-86-8 ]

Yield	Reaction Conditions	Operation in experiment
20%; 45%	With 2-iodoxybenzoic acid; In acetonitrile; at 20℃;	3-Indolethiocarboxamide (9) was prepared from 3-indolecarboxynitrile (10) by modification of a previously published procedure (Gu et al., 1999), as follows. A mixture of 3-indolecarboxynitrile (100 mg, 0.700 mmol) and thioacetamide (105 mg, 1.40 mmol) in 10% HCl-DMF solution (1.5 ml) was stirred at 95 C for 12 h. The reaction mixture was then neutralized with NaHCO3 (sat. solution), extracted with EtOAc, the organic layer was dried and separated by FCC (silica gel, CH2Cl2-MeOH, 99:1) to afford indole-3-thiocarboxamide (9) (71.5 mg, 59%). The 13C NMR spectroscopic data of 9 is reported here for the first time, other spectroscopic data being similar to that previously reported (Jiang and Gu, 2000).

Reference： [1]Phytochemistry,2011,vol. 72,p. 199 - 206

30
[ 32112-94-0 ]
[ 578-68-7 ]
[ 36193-65-4 ]
[ 5457-28-3 ]

Reference： [1]Journal of Physical Organic Chemistry,2011,vol. 24,p. 999 - 1008

31
[ 13390-30-2 ]
[ 36193-65-4 ]
[ 5457-28-3 ]

Reference： [1]Journal of Physical Organic Chemistry,2011,vol. 24,p. 999 - 1008

32
[ 101772-15-0 ]
[ 36193-65-4 ]
[ 5457-28-3 ]

Reference： [1]Journal of Physical Organic Chemistry,2011,vol. 24,p. 999 - 1008

33
[ 7483-33-2 ]
[ 36193-65-4 ]
[ 5457-28-3 ]

Reference： [1]Journal of Physical Organic Chemistry,2011,vol. 24,p. 999 - 1008

34
[ 120-72-9 ]
potassium ferrocyanide [ No CAS ]
[ 5457-28-3 ]

Reference： [1]Chinese Chemical Letters,2012,vol. 23,p. 903 - 906

35
[ 5457-28-3 ]
[ 360575-28-6 ]
[ 1413064-90-0 ]

Yield	Reaction Conditions	Operation in experiment
16%		Step 1: To a cooled (ice bath) solution of <strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> (1 g, 7.03 mmol) in dry dimethylformamide (10 mL) under nitrogen atmosphere was added sodium hydride (383 mg, 8.44 mmol, 60% in oil) in 2 portions over about 4 minutes. The material was stirred for 5 minutes and then the ice bath was removed and the mixture warmed to ambient. 2-Bromo-6-fluorobenzaldehyde (1.43 g, 7.03 mmol) was added as a powder in one portion. The material was stirred vigorously for 2 hours. The mixture was placed on a rotary evaporator attached to a mechanical pump and the solvent was stripped. The remainder was taken up in a 5% solution of aqueous ammonium chloride (40 ml) and ethyl acetate (40 ml) and transferred to a separatory funnel. The organic phase was collected and washed with 50% diluted brine solution (40 ml). The ethyl acetate phase was collected and the aqueous phase was back extracted with ethyl acetate (2×35 mL). The organic phases were combined, dried (magnesium sulfate), filtered and stripped. The crude product was adsorbed onto silica (10 g, from dichloromethane) and purified by HPLC (dry loading; silica gel; 40 g) eluting with 100% methylene chloride to provide semi-pure product (990 mg). This material was purified via trituration from hot dichloromethane/hexane to provide 1-(3-bromo-2-formylphenyl)-<strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> as an orange solid (354 mg, 16% yield). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.02-7.11 (m, 1H) 7.27-7.38 (m, 2H) 7.45 (d, J=7.93 Hz, 1H) 7.61 (t, J=8.12 Hz, 1H) 7.68 (s, 1H) 7.80-7.86 (m, 1H) 7.90 (dd, J=7.93, 1.13 Hz, 1H) 10.05 (s, 1H).

Reference： [1]Patent: US2012/295885,2012,A1 .Location in patent: Page/Page column 48

36
[ 120-72-9 ]
[ 140-29-4 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240
[2]Journal of Organic Chemistry,2013,vol. 78,p. 3374 - 3378

37
[ 120-72-9 ]
[ 104-47-2 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
71%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240

38
[ 120-72-9 ]
[ 555-21-5 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
43%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240

39
[ 120-72-9 ]
[ 459-22-3 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
22%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240

40
[ 120-72-9 ]
[ 1823-91-2 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240

41
[ 120-72-9 ]
[ 613-88-7 ]
[ 5457-28-3 ]

Yield	Reaction Conditions	Operation in experiment
15%	With copper(l) iodide; In N,N-dimethyl-formamide; at 100℃; for 34h;	General procedure: A mixture of CuI (0.6 mmol), indoles (0.5 mmol) and benzyl cyanide (0.6 mmol) in DMF (3.0 mL) was stirred under air at 100 C for 34 h and then cooled to room temperature. After the reaction mixture was quenched with 10 mL of water, it was extracted with DCM (3×10 mL). The combined organic layers were washed with the saturated aqueous solution of sodium chloride and dried over MgSO4. The solution was concentrated under reduced pressure and purified by column chromatography to afford 3-cyanoindoles.

Reference： [1]Tetrahedron,2013,vol. 69,p. 4236 - 4240

42
[ 120-72-9 ]
[ 110-18-9 ]
[ 5457-28-3 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 2315 - 2317

43
[ 5457-28-3 ]
[ 92489-89-9 ]
[ 1440976-24-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 3808 - 3816

44
[ 120-72-9 ]
[ 5457-28-3 ]
[ 65610-73-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With trifluorormethanesulfonic acid; palladium diacetate; acetic acid; 2-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine; In 1,4-dioxane; water; at 100℃; for 24h;	General procedure: To a mixture of indole (1 mmol), nitrile (1.2 mmol), Pd(OAc)2 (5 mol%), L1 (5mol%), dioxane (1 mL), acetic acid (0.6 mL) and H2O (0.4 mL) were added and stirred at100 C for 24 h. The reaction mixture was neutralized with saturated NaHCO3 solution andthen extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, andconcentrated under reduced pressure. The residue was purified by flash columnchromatography on a silica gel using petroleum ether/EtOAc as the eluent to give the desiredproduct.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 7198 - 7202

45
[ 110-52-1 ]
[ 5457-28-3 ]
1-(4-bromobutyl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tripotassium phosphate tribasic; at 65℃; for 0.5h;	General procedure: 4-(1H-indol-3-yl)butanoic acid 1a (101 mg, 0.5 mmol), 1,4-dibromobutane 2a (431 mg, 2 mmol) and K3PO4 (424 mg,2 mmol) were dissolved in 3ml ionic liquid [C6min]Br and stirred at65 C for 0.5 h, and then 1-(2-methoxyphenyl)- piperazine 3a(384 mg, 2 mmol) and K3PO4 (424 mg, 2 mmol) were added andstirred at 65 C for another 1.5 h. Extracted with ethyl acetate(10ml 5),washed with distilledwater (10 ml) and saturated brine(10 ml), then dried with anhydrous Na2SO4, and the solvent evaporatedunder reduced pressure. 4aaa was obtained by columnchromatography in 75.1% (169 mg) yields.
		General procedure: To a solution of the appropriate indole carbonitrile 2ad(1.35 mmol) in dry DMF (2 mL), sodium hydride 60% dispersion inmineral oil (NaH) (0.05 g, 2.03 mmol) was slowly added at 0-5 C and the reaction mixture was stirred at room temperature for 30 min. After that, a solution of 4-(2-chloroethyl)morpholine or 1-(2-chloroethyl)piperidine (5.40 mmol), or 1,3-dibromopropane or1,4-dibromobutane (6.75 mmol) in dry DMF (2 mL) was added dropwise and the reaction mixture was stirred at 50 C for 1-2 h orat room temperature for 1-24 h. After cooling, the mixture was poured into water and ice and the obtained precipitate was filteredoff, dried, and recrystallized from ethanol to give the desired products 3c,d, and 4a. For derivatives 4b-d, 5a,c,d, 6a,c, d, and 7a-d the mixture was extracted with ethyl acetate (3 20 mL), dried(Na2SO4), filtered and the solvent evaporated under reduced pressure.The residue was purified by column chromatography using petroleum ether:ethyl acetate (6:4 for 4a-d, 7:3 for 6a-d, 8:2 for 7a-d)or dichloromethane:ethyl acetate (9:1 for 5c,d) as eluent.
		General procedure: To a solution of the appropriate indole carbonitrile 2ad(1.35 mmol) in dry DMF (2 mL), sodium hydride 60% dispersion inmineral oil (NaH) (0.05 g, 2.03 mmol) was slowly added at 0-5 C and the reaction mixture was stirred at room temperature for 30 min. After that, a solution of 4-(2-chloroethyl)morpholine or 1-(2-chloroethyl)piperidine (5.40 mmol), or 1,3-dibromopropane or1,4-dibromobutane (6.75 mmol) in dry DMF (2 mL) was added dropwise and the reaction mixture was stirred at 50 C for 1-2 h orat room temperature for 1-24 h. After cooling, the mixture was poured into water and ice and the obtained precipitate was filteredoff, dried, and recrystallized from ethanol to give the desired products 3c,d, and 4a. For derivatives 4b-d, 5a,c,d, 6a,c, d, and 7a-d the mixture was extracted with ethyl acetate (3 20 mL), dried(Na2SO4), filtered and the solvent evaporated under reduced pressure.The residue was purified by column chromatography using petroleum ether:ethyl acetate (6:4 for 4a-d, 7:3 for 6a-d, 8:2 for 7a-d)or dichloromethane:ethyl acetate (9:1 for 5c,d) as eluent.

Reference： [1]Organic Letters,2015,vol. 17,p. 2864 - 2866
[2]European Journal of Medicinal Chemistry,2020,vol. 205
[3]European Journal of Medicinal Chemistry,2022,vol. 234
[4]European Journal of Medicinal Chemistry,2022,vol. 234

46
[ 5457-28-3 ]
[ 219963-60-7 ]
1-((4-methoxy-3-(4-(2,2,2-trichloroacetyl)piperazin-1-yl)phenyl)sulfonyl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%		To 10 mL of tetrahydrofuran was added 3-carbonitrile indole (284 mg, 2.0 mmol) and sodium hydride (96 mg, 2.4 mmol, 60%) at 0 C, then the mixture was reacted for 1 hour at 25 C. The mixture was cooled to 5 C, and a solution of 4-methoxy-3 -(4-(2,2,2-trichloroacetyl)piperazin- 1 -yl)benzene- 1 -sulfonyl chloride (1.05 g, 2.4 mmol) in tetrahydrofuran (4 mL) was added slowly. The mixture was reacted for 2 hours, then 100 mL of dichloromethane was added and the resulting mixture was washed with saturated aqueous sodium bicarbonate (60 mL). The organic layer was separated and dried over anhydrous magnesium sulfate, then filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(V/V)=5/1 to give the title compound as a white solid (965 mg, 89%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 541.0 [M+Hfb; and ‘H NMR (400 MHz, CDC13): 6 8.08 (s, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.65 (t, J = 6.3 Hz, 1H), 7.45 (t, J= 6.2 Hz, 1H), 7.33-7.26 (m, 2H), 6.92 (d,J= 8.7 Hz, 1H), 3.96 (brs, 4H), 3.91 (s, 3H), 3.11 (t,J 5.0 Hz, 4H).

Reference： [1]Patent: WO2015/90233,2015,A1 .Location in patent: Paragraph 00216

47
[ 5457-28-3 ]
[ 61-54-1 ]
[ 172615-59-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With palladium 10% on activated carbon; hydrogen; acetic acid; at 20℃;	General procedure: To a solution of tryptamine (1 mmol) in 10 mL of glacial acetic acid was added appropriatenitrile (1.5 mmol) and 10% Pd/C (0.2 mmol) in one portion. The mixture washydrogenated at room temperature under balloon pressure for 24-40 h. Thereaction was monitored by TLC. The catalyst was removed by filtration throughcelite and washed with dichloromethane. The resulting solution was madebasic with aqueous NH3 and then extracted with dichloromethane. Thecombined organic layers were dried on Na2SO4 and solvent was evaporated.The residue was purified by chromatography on activated neutral aluminiumoxide using dichloromethane: methanol as an eluent to give tetrahydro-bcarboline.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 6012 - 6015

48
[ 5457-28-3 ]
[ 4559-70-0 ]
2-(diphenylphosphoryl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With manganese triacetate; In ethanol; at 50℃; for 1h;	<strong>[5457-28-3]3-cyanoindole</strong>,Diphenylphosphine oxide as a raw material,The reaction steps are as follows:To the reaction flask was added 0.074 g (0.5 mmol) of <strong>[5457-28-3]3-cyanoindole</strong>,Diphenylphosphine oxide (0.152 g, 0.75 mmol)Manganese acetate 0.201 g (0.75 mmol)And 30 ml of ethanol, reacted at 50 C for 1 hour;The crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4: 1) to give the title product (yield 91%).
84%	With magnesium(II) nitrate; silver carbonate; In methanol; at 60℃;Molecular sieve;	dd 3-74 cyanohydrazine 0.074 g (0.5 mmol) and diphenylphosphine oxide 0.152 g (0.75) to the reaction flask. Mmmol), silver carbonate 0.013 g (0.05 mmol), 4 Å molecular sieve 0.2 g, magnesium nitrate 0.111 g (0.75 mmol) and 30 m Methanol is raised, reacted at 60 C; TLC tracks the reaction until it is completely finished; the crude product obtained after the end of the reaction is separated by column chromatography (stone Oleic ether: ethyl acetate = 4:1) gave the desired product (yield: 84%).

Reference： [1]Patent: CN105037422,2017,B .Location in patent: Paragraph 0098; 0099; 0100
[2]Patent: CN104926868,2018,B .Location in patent: Paragraph 0098; 0099; 0100
[3]Advanced Synthesis and Catalysis,2016,vol. 358,p. 1753 - 1758

49
[ 5457-28-3 ]
[ 452972-15-5 ]
1-(4-chloropyridin-3-yl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; copper diacetate; In N,N-dimethyl-formamide; at 20℃; for 20h;Inert atmosphere;	In 100mL three-necked flask, N2 protection, the <strong>[5457-28-3]1H-<strong>[5457-28-3]indole-3-carbonitrile</strong></strong> (700mg, 4.9mmol) and 4-chloro-3-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine(1300mg, 5.4mmol) was dissolved in dimethylformamide (50 mL), washed added copper acetate (1800mg, 9.9mmol), pyridine (1200mg, 15.1mmol ), then stir to room temperature. Every four hours, additional 4-chloro-3-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (700mg, 3.0mmol), total additional 5 times. The reaction mixture was quenched into 100mL ice water and the reaction extracted with ethyl acetate (150mL, 3 times), saturated brine (150mL, 3 times). The organic phase was dried over anhydrous sodium sulfate spin dry, high-pressure preparation as a white solid.

Reference： [1]Patent: CN105439946,2016,A .Location in patent: Paragraph 0310; 0311; 0312

50
[ 5457-28-3 ]
ethyl (S)-2-[(prop-2-yn-1-ylthio)carbonothioyl]oxy}propanoate [ No CAS ]
ethyl (R)-2-(3-cyano-1H-indol-1-yl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In chlorobenzene;Inert atmosphere; Reflux;	General procedure: Propargyl xanthate (S)-18 (1 equiv) and the acidic substrate HA (2 equiv) were dissolved in toluene, unless stated otherwise (10mL/mmol of propargyl xanthate). The mixture was refluxed under an argon atmosphere and followed by TLC until total conversion of the starting material (2-6 h). Then, the solvent was removed under reduced pressure and the crude was purified by flash column chromatography. Due to the low solubility of compounds 13d, 13e, 19d, and 19f in toluene, chlorobenzene was used as a solvent in the reactions. In the experiment involving 13h, benzonitrile was used as a solvent and the reaction was carried out at 130 C. Finally, a few of the experiments were also carried out using the acid partner HA as the limiting reagent. No significant changes in yields were observed.

Reference： [1]Synthesis,2016,vol. 48,p. 3393 - 3399

51
[ 5457-28-3 ]
[ 3336-41-2 ]
1-(3,5-dichloro-4-hydroxybenzoyl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With HATU; In N,N-dimethyl-formamide; at 20℃; for 24h;	3,5-Dichloro-4-hydroxybenzoic acid (414 mg, 2.0 mmol), 3-cyanoindole (370 mg, 2.6 mmol), HATU(775 mg, 2.1 mmol) and dry N, N-dimethylformamide (10 mL) were added to a 50 mL two-necked flask, and N, N-diisopropylethylamine After this time, the reaction mixture was stirred at room temperature for 24 h. A saturated aqueous ammonium chloride solution (80 mL) was added to the reaction mixture, and the aqueous phase was extracted with ethyl acetate (60 mL x 2), and the organic phases were combined. The organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / dichloromethane (v / v) = 1/100) to give the title compound as a white solid (93 mg, 14percent).

Reference： [1]Patent: CN106045898,2016,A .Location in patent: Paragraph 0060; 0061; 0062; 0063; 0064

52
[ 5457-28-3 ]
[ 583029-16-7 ]
N-(1-(3-Cyano-1H-indol-2-yl)-2,2,2-trifluoroethyl)acetamide [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 4090 - 4093

53
[ 5457-28-3 ]
4'-methoxy-4-methylchalcone [ No CAS ]
1-(3-(4-methoxyphenyl)-3-oxo-1-(p-tolyl)propyl)-1H-indole-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With potassium hydroxide; In dichloromethane; at 25℃; for 9h;	General procedure: Enone 1a (62.5 mg, 0.3 mmol), <strong>[5457-28-3]3-cyanoindole</strong> (51.2 mg, 0.36mmol, 1.2 equiv), KOH (0.8 mg, 0.015 mmol, 5.0 mol%), and CH2Cl2 (3.0 mL) were sequentially charged into a dry round-bottomedflask (25 mL). The reaction mixture was stirred at 25 Cuntil the reaction complete (monitored by TLC). The reactionmixture was diluted with CH2Cl2 (3.0 mL), and washed withbrine (3 × 4.0 mL). The aqueous phase was extracted withCH2Cl2 (4.0 mL). The organic phase was combined, dried withanhydrous Na2SO4, and concentrated under reduced pressure.The residue was purified by flash column chromatography onsilica gel (PE-EtOAc, 6:1) to afford the pure product 2a.