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Chemical Structure| 15861-24-2 Chemical Structure| 15861-24-2
Chemical Structure| 15861-24-2

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5-Cyanoindole is an indole derivative that, as a bioactive molecule, may influence tryptophan metabolism or be associated with neurotransmitters, holding potential for anti-inflammatory and anticancer research.

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Product Citations

Product Citations

Shriver, James A. ; Kaller, Kaylie S. ; Kinsey, Ally L. ; Wang, Katelyn R. ; Sterrenberg, Summer R. ; Van Vors, Madison K. , et al.

Abstract: The spontaneous conversion of 3-indoxyl to indigo was a well-established process used to produce indigo dyes. It was recently shown that some indoles, when reacted with molybdenum hexacarbonyl and cumyl peroxide, proceed through an indoxyl intermediate to produce significant amounts of indirubin through a competing mechanism. Modulation of this system to lower temperatures allows for careful tuning, leading to selective production of indirubins in a general process. A systematic assay of indoles show that electron deficient indoles work well when substituted at the 5 and 7 positions. In contrast, 6-substituted electron rich indoles give the best results whereas halogeno indoles work well in all cases. This process shows broad functional group tolerance for generally reactive carbonyl-containing compounds such as aldehydes and carboxylic acids.

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Product Details of 5-Cyanoindole

CAS No. :15861-24-2
Formula : C9H6N2
M.W : 142.16
SMILES Code : C1=C(C#N)C=CC2=C1C=C[NH]2
MDL No. :MFCD00005669
InChI Key :YHYLDEVWYOFIJK-UHFFFAOYSA-N
Pubchem ID :27513

Safety of 5-Cyanoindole

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 5-Cyanoindole

* 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 [ 15861-24-2 ]
  • Downstream synthetic route of [ 15861-24-2 ]

[ 15861-24-2 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 15861-24-2 ]
  • [ 24424-99-5 ]
  • [ 475102-10-4 ]
YieldReaction ConditionsOperation in experiment
96%
Stage #1: With dmap In tetrahydrofuran at 20℃; for 0.5 h;
Stage #2: for 2 h;
In a 100 mL round-bottom flask was placed 1H-INDOLE-5-CARBONITRILE (2.0 g, 14.07 MMOL) in 20 mL of anhydrous THF. To this solution was added DMAP (0.86 g, 7.03 MMOL) and the mixture was allowed to stir for 0.5 h at rt. At this point, BOC20 (3.07 g, 14.07 MMOL) was added and the reaction stirred for an additional 2 h. The reaction was then quenched with water and extracted twice with ethyl ether. The combined organic layers were washed successively with 1 N HCI, water, and brine, then dried over MGS04 and concentrated to provide 3.26 g (96percent) of the desired product as a white SOLID.APOS;H- NMR (DMSO-d6) 8 8.20-8. 14 (m, 2H), 7.83 (d, 1H), 7.70 (d, 1H), 6.80 (d, 1H), 1.63 (s, 9H).
96%
Stage #1: With dmap In tetrahydrofuran at 20℃; for 0.5 h;
Stage #2: for 2 h;
In a 100 ml round-bottom flask was placed 1W-indole-5-carbonitrile (2.0 g, 14.07mmol) in 20 ml of anhydrous THF. To this solution was added DMAP (0.86 g, 7.03mmol) and the mixture was allowed to stir for 0.5 h at rt. At this point, BocaO (3.07 g,14.07 mmol) was added and the reaction stirred for an additional 2 h. The reaction wasthen quenched with water and extracted twice with ethyl ether. The combined organiclayers were washed successively with 1N HCI, water, and brine, then dried over MgSO4and concentrated to provide 3.26 g (96percent) of the desired product as a white solid. 1H-NMR (DMSO-c/e) 5 8.20-8.14 (m, 2H), 7.83 (d, 1H), 7.70 (d, 1H), 6.80 (d, 1H), 1.63 (s,9H).
90% With dmap In acetonitrile at 20℃; for 0.5 h; [0486] tert-butyl 5-cyano-l H-indole-1 -carboxylate (INT-65) [0487] To a flask containing 5-cyanoindole (500 mg, 3.52 mmol) in CH3CN (5 mL) was added Boc20 (920 mg, 4.22 mmol) and DMAP (42 mg, 0.35 mmol) and the mixture was stirred at room temperature for 0.5 h. The mixture was concentrated, redissolved in DCM and chromatographed (EtOAc / hexanes) to provide 766 mg (90percent) of tert-butyl 5-cyano-lH- indole-l-carboxylate INT -65 as a white solid. LCMS-ESI (m/z) calculated for C14H14N20 :242.27; found 243.1 [M+H]+, tR = 3.93 min.
References: [1] Synthesis, 2009, # 21, p. 3617 - 3632.
[2] Journal of Organic Chemistry, 2002, vol. 67, # 21, p. 7551 - 7552.
[3] Patent: WO2004/43950, 2004, A1, . Location in patent: Page 134.
[4] Patent: WO2005/51957, 2005, A1, . Location in patent: Page/Page column 54-55.
[5] Patent: WO2011/60389, 2011, A1, . Location in patent: Page/Page column 98-99.
[6] Synthesis, 2008, # 5, p. 707 - 710.
[7] Synlett, 2008, # 2, p. 294 - 296.
[8] Journal of Organic Chemistry, 2005, vol. 70, # 1, p. 175 - 178.
[9] Journal of Organic Chemistry, 2007, vol. 72, # 14, p. 5046 - 5055.
[10] Patent: US2004/242559, 2004, A1, . Location in patent: Page 18.
[11] European Journal of Medicinal Chemistry, 2017, vol. 128, p. 70 - 78.
  • 2
  • [ 15861-24-2 ]
  • [ 1092114-59-4 ]
YieldReaction ConditionsOperation in experiment
95% With iodine; potassium hydroxide In N,N-dimethyl-formamide at 10℃; for 0.5 h; Inert atmosphere; Darkness Example 1
Synthesis of 3-iodo-1H-indole-5-carbonitrile (V)
1H-indole-5-carbonitrile (5 g, 35.2 mmol), KOH (7.90 g, 141 mmol) and I2 (8.90 g, 35.2 mmol) are suspended in 25 mL of DMF under inert atmosphere.
The reaction is maintained under stiffing in the dark for 30 min at 10° C., and then treated with an 0.1M solution of Na2S2O3 (150 mL) The resulting suspension is maintained under stirring for 30 min, then filtered, and the resulting solid is washed with water and dried at 50° C. under vacuum to constant weight.
Product (V) (9.0 g) is obtained as a white solid with a yield of 95percent.
1H-NMR (400 MHz, CDCl3), δ: 8.78 (1H, bs); 7.80 (1H, s); 7.46-7.40 (3H, m).
94.5% With iodine; potassium hydroxide In N,N-dimethyl-formamide at 20℃; Preparation of compound 69a: 3-iodo-l/7-indole-5-carbonitrileTo a solution of l//-indole-5-carbonitrile (lg, 7.048 mmol) in DMF (10 mL) was added KOH pellets (1.15 g, 21.14 mmol), followed by I2 (3.57 g, 14.08 mmol) portionwise. The reaction was stirred for 1 h at RT. 10percent aq sodium bisulphite solution (10 mL) was added to the mixture and an off-white solid precipitate was formed. The suspension was filtered and the solid was washed with H20 (10 mL) and dried under vacuum to give 3-iodo-lH- indole-5-carbonitrile (1.7 g, 94.5percent) as an off white solid. .H NMR (400MHz, DMSO-d6): δ 12.18 (brs, 1H), 7.78 (s, 1H), 7.75 (d, J=1.2Hz, 1H), 7.59 (dd, J=8.4, 0.4Hz, 1H), 7.52 (dd, J=8.4, 1.6Hz, 1H).
93% With N-iodo-succinimide In dimethyl sulfoxide at 30℃; for 1 h; General procedure: To a 5 mL round-bottom flask containing 0.1 g of indole dissolved in 2.0 mL of DMSO, NIS (1.05 equiv) was added, and the reaction mixture was stirred for 0.5-24 h (cf. Table 3). After completion of the reaction as monitored by TLC, the reaction mixture was diluted with 20 mL of ethyl acetate, and it was washed with saturated solution of Na2S2O3. The organic phase was subsequently dried over anhyd. sodium sulfate and the solvent was removed in vacuo. The resultant crude product compound was subjected silica gel column chromatography to isolate the product; in the case of 5-methoxy-3-iodoindole, neutral alumina was employed.
88% With iodine; potassium iodide; sodium hydroxide In methanol; water at 25℃; for 6 h; Compound 13 (15 g) was taken in methanol (300 ml) and water (30 ml) mixture and NaOH (4.6 g) and KI (20.89 g) were added. Iodine (30.51 g) was added portion wise at RT. Reaction mix- ture was stirred at RT for 6 hr. Reaction was monitored using LCMS & TLC. Reaction mixture was diluted with water (1000 ml) and the precipitated solid was filtered-off and dried under vac- uum. Yellow solid obtained was dissolved in DCM and dried over sodium sulphate and concen- trated under vacuum.25 g of pure solid compound 14 was obtained. 1H NMR (300 MHz, DMSO-d6) δ 12.09 (s, 1H), 7.82– 7.73 (m, 2H), 7.64– 7.47 (m, 2H).
75% With iodine; sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.416667 h; 5-Cyanoindole (0.500 g, 3.52 mmol) was dissolved in DMF (25 mL), and sodium hydroxide (0.493 g, 8.79 mmol) and iodine (0.902 g, 3.55 mmol) were added thereto, then the mixture was stirred at room temperature for 25 minutes. A saturated aqueous sodium thiosulfate solution was added to the mixture, and the precipitated solid was filtered off to give 5-cyano-3-iodoindole(0.707 g, 75percent). ESI-MS: m/z 269 [M + H]+.

References: [1] Patent: US2014/275542, 2014, A1, . Location in patent: Paragraph 0060; 0061.
[2] Patent: WO2012/129338, 2012, A1, . Location in patent: Page/Page column 192-193.
[3] Tetrahedron, 2019, vol. 75, # 14, p. 2169 - 2174.
[4] Patent: WO2018/210659, 2018, A1, . Location in patent: Page/Page column 160.
[5] Patent: EP2163554, 2010, A1, . Location in patent: Page/Page column 107.
[6] Organic Letters, 2013, vol. 15, # 12, p. 2982 - 2985.
[7] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 15, p. 4031 - 4033.
[8] Patent: US2004/63768, 2004, A1, . Location in patent: Page/Page column 9.
[9] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 1, p. 22 - 26.
 

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