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[ CAS No. 3189-22-8 ] {[proInfo.proName]}

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Chemical Structure| 3189-22-8
Chemical Structure| 3189-22-8
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Product Details of [ 3189-22-8 ]

CAS No. :3189-22-8 MDL No. :MFCD00047203
Formula : C9H9NO Boiling Point : -
Linear Structure Formula :- InChI Key :FSOPPXYMWZOKRM-UHFFFAOYSA-N
M.W : 147.17 Pubchem ID :76660
Synonyms :

Calculated chemistry of [ 3189-22-8 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.11
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 44.79
TPSA : 25.02 Ų

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) : -5.76 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.81
Log Po/w (XLOGP3) : 2.02
Log Po/w (WLOGP) : 2.18
Log Po/w (MLOGP) : 1.23
Log Po/w (SILICOS-IT) : 2.53
Consensus Log Po/w : 1.95

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.56
Solubility : 0.401 mg/ml ; 0.00273 mol/l
Class : Soluble
Log S (Ali) : -2.17
Solubility : 0.989 mg/ml ; 0.00672 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.39
Solubility : 0.06 mg/ml ; 0.000407 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.43

Safety of [ 3189-22-8 ]

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

Application In Synthesis of [ 3189-22-8 ]

* 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.

  • Downstream synthetic route of [ 3189-22-8 ]

[ 3189-22-8 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 50-00-0 ]
  • [ 3189-22-8 ]
  • [ 124-40-3 ]
  • [ 46388-50-5 ]
YieldReaction ConditionsOperation in experiment
97% With acetic acid In water at 0 - 20℃; for 16h; 28.1 8.3 General procedure B General procedure: An indole derivative (1.0 equiv) was dissolved in acetic acid (1.7mL for 3.23mmol of starting material) and water (1.7mL for 3.23mmol of starting material) and chilled to 0°C in an ice bath. Formaldehyde 37% w/w in H2O (1.25 equiv) and dimethylamine 40% w/w in H2O (1.75 equiv) was then added. The reaction was allowed to warm to room temperature and stirred for 16h. The reaction was quenched by adding ice and basified to pH 12-14 with 5N NaOH. The resulting mixture was extracted with dichloromethane 3 times. The combined organic layer was washed with brine, dried over anhydrous sodium sulphate and evaporated under vacuum to obtain the gramine product which was used in the next step without further purification.
With acetic acid
With acetic acid at 20℃;
With acetic acid In water 7e (7-methoxy-1H-indol-3-yl)-acetonitrile Following a similar procedure as the one detailedfor 7d, to a solution ofdimethylamine (40% aqueous, 1.2 mL, 10.9 mmol, 1.6 eq.) and formalin (37%aqueous, 720 μL, 8.9 mmol, 1.3 eq.) inglacial acetic acid (2 mL) and water (1 mL) was added 7-methoxyindole (1.0 g,6.8 mmol, 1.0 eq.). To the 7-methoxygramineobtained after work-up were added CH2Cl2 (20 mL), toluene(40 mL) and methyl iodide (845 mL, 13.6 mmol, 2.0eq.). The reaction mixture was stirred for 12 hours, concentrated to dryness, theresidue solubilized in THF (60 mL), then TMSCN (1.3 mL, 10.2 mmol, 1.5 eq.) andTBAF (20 mL, 1M, 20.4 mmol, 3.0 eq.) were added. The reaction mixture was stirredfor 4 hours and worked-up. Silicagel flash-column chromatography of the residue (elution with heptane/EtOAc,80/20 to 40/60) afforded 0.90 g of 7e (71 %) as an amorphous beige solid. IR νmax (cm-1): 2258 (ν CN),3369 (ν N-H). 1H RMN (d6-DMSO,300 MHz) d (ppm) : 3.91 (3H, s, 7-CH3O), 4.00 (2H, s, CH2),6.71 (1H, d, J6-5 = 7.7 Hz, H6), 6.99 (1H, t, J5-4 =J5-6 = 7.7 Hz, H5), 7.17 (1H, d, J4-5 = 7.7 Hz,H4), 7.23 (1H, s, H2), 11.22 (1H, s, H indolic). 13C RMN (d6-DMSO,75.5 MHz) d (ppm):13.8 (CH2), 55.6 (7-CH3O), 102.6 (C6), 104.6 (C3), 111.2(C4), 119.9 (C nitrile), 120.1 (C5), 124.0 (C2), 126.8 (C3a), 128.0 (C7a),146.7 (C7). ESI-MS: m/z 209.1 ([M+Na]+), 241.1 ([M+Na+MeOH]+). HRESI-MS: m/z 209.0685 (calcdfor C11H10N2ONa+209.0691).
With acetic acid In tetrahydrofuran; 1,4-dioxane; water at 0 - 20℃;
Stage #1: formaldehyd; dimethyl amine With acetic acid In tetrahydrofuran; 1,4-dioxane; water at 0℃; for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: 7-methoxy-1H-indole In tetrahydrofuran; 1,4-dioxane; water at 0 - 20℃; Schlenk technique; Inert atmosphere;

  • 2
  • [ 3189-22-8 ]
  • [ 79-37-8 ]
  • [ 50656-47-8 ]
YieldReaction ConditionsOperation in experiment
In diethyl ether at 0℃; for 1h;
In diethyl ether at 0℃;
In tetrahydrofuran at 0℃; for 1.5h;
In tetrahydrofuran at 0℃; for 2h;
In diethyl ether at 20℃; for 2h;
In diethyl ether at 40℃; for 18h; General procedure: A scintillation vial was charged with the following: 4-Fluoroindole (1b, 0.5 g, 3.7 mmol), diethyl ether (10 mL) and oxalyl chloride (1.0 mL, 11.5 mmol), sealed and heated to 40 C for 18 h on a heater/orbital shaker. The resulting solids were filtered, washed with ether and dried carefully to yield 726 mg (87%) of a yellow solid, which was not isolated. This yellow solid was dissolved into 0.5 M NH3/dioxane (20 mL, 10 mmol), sealed and stirred overnight at room temperature. The mixture was concentrated and the resulting residue was sonicated in water (40 mL). The solids were filtered and air-dried to yield 644 mg (97%) of 3b as a white solid, which was used without further purification.

Reference: [1]Mantus; Clardy [Tetrahedron Letters, 1993, vol. 34, # 7, p. 1085 - 1086]
[2]Collins, Ian; Davey, William B.; Rowley, Michael; Quirk, Kathleen; Bromidge, Frances A.; McKernan, Ruth M.; Thompson, Sally-Anne; Wafford, Keith A. [Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 12, p. 1381 - 1384]
[3]Engler, Thomas A.; Furness, Kelly; Malhotra, Sushant; Sanchez-Martinez, Concha; Shih, Chuan; Xie, Walter; Zhu, Guoxin; Zhou, Xun; Conner, Scott; Faul, Margaret M.; Sullivan, Kevin A.; Kolis, Stanley P.; Brooks, Harold B.; Patel, Bharvin; Schultz, Richard M.; DeHahn, Tammy B.; Kirmani, Kashif; Spencer, Charles D.; Watkins, Scott A.; Considine, Eileen L.; Dempsey, Jack A.; Ogg, Catherine A.; Stamm, Nancy B.; Anderson, Bryan D.; Campbell, Robert M.; Vasudevan, Vasu; Lytle, Michelle L. [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 14, p. 2261 - 2267]
[4]Rege, Pankaj D.; Tian, Yuan; Corey [Organic Letters, 2006, vol. 8, # 14, p. 3117 - 3120]
[5]Kai, Kenji; Horita, Junko; Wakasa, Kyo; Miyagawa, Hisashi [Phytochemistry, 2007, vol. 68, # 12, p. 1651 - 1663]
[6]Location in patent: scheme or table Meanwell, Nicholas A.; Wallace, Owen B.; Fang, Haiquan; Wang, Henry; Deshpande, Milind; Wang, Tao; Yin, Zhiwei; Zhang, Zhongxing; Pearce, Bradley C.; James, Jennifer; Yeung, Kap-Sun; Qiu, Zhilei; Kim Wright; Yang, Zheng; Zadjura, Lisa; Tweedie, Donald L.; Yeola, Suresh; Zhao, Fang; Ranadive, Sunanda; Robinson, Brett A.; Gong, Yi-Fei; Wang, Hwei-Gene Heidi; Blair, Wade S.; Shi, Pei-Yong; Colonno, Richard J.; Lin, Pin-fang [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 7, p. 1977 - 1981]
[7]Location in patent: scheme or table Gitto, Rosaria; De Luca, Laura; Ferro, Stefania; Buemi, Maria Rosa; Russo, Emilio; De Sarro, Giovambattista; Costa, Lara; Ciranna, Lucia; Prezzavento, Orazio; Arena, Emanuela; Ronsisvalle, Simone; Bruno, Giuseppe; Chimirri, Alba [Journal of Medicinal Chemistry, 2011, vol. 54, # 24, p. 8702 - 8706]
[8]Blough, Bruce E.; Landavazo, Antonio; Partilla, John S.; Decker, Ann M.; Page, Kevin M.; Baumann, Michael H.; Rothman, Richard B. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 19, p. 4754 - 4758]
  • 3
  • [ 3189-22-8 ]
  • [ 33513-42-7 ]
  • [ 109021-59-2 ]
YieldReaction ConditionsOperation in experiment
99% With trichlorophosphate at 0 - 20℃; 1-2 I-N-(2-Ethoxyphenethyl)-3-(7-methoxy-1H-indol-3-yl)acrylamide (7; JI051) Phosphoryl chloride (1.15 g, 7.50 mmol) was added dropwise to a stirred mixture of N,N-dimethylformamide (2.8 g, 38.3 mmol) and 3 (1.0 g, 6.79 mmol) at 0°C. The mixture was stirred overnight at RT, then poured into crushed ice and neutralized with 2N NaOH solution. The mixture was extracted with ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to give pure 4 (1.18 g, 6.74 mmol, 99%). [0077] Methyl(triphenylphosphoranylidene)acetate (2.72 g, 8.13 mmol) was added to a stirred mixture of 4 (1.18 g, 6.74 mmol) in benzene (50 ml) at RT. The mixture was refluxed for 3 h. The mixture was then concentrated in vacuo and purified by column chromatography (ethyl acetate/n-hexane) to yield 5 (1.0 g, 4.32 mmol, 64%). Lithium hydroxide monohydrate (0.36 g, 8.58 mmol) was added to a mixture of 5 (1.0 g, 4.32 mmol) in tetrahydrofuran (10 ml), methanol (10 ml), and water (5 ml) at 0°C. The mixture was refluxed for 2 h. The mixture was acidified with 1N HCl solution, and the solid was collected by filtration and dried under reduced pressure to yield 6 (0.68 g, 3.13 mmol, 72%). [0078] To a mixture of 6 (0.3 g, 1.38 mmol) and 1 (0.23 g, 1.39 mmol) in dichloromethane (10 ml) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.32 g, 1.67 mmol), 4-dimethylaminopyridine (0.20 g, 1.64 mmol), and 1-hydroxybenzotriazole monohydrate (0.22 g, 1.63 mmol) at 0°C. The mixture was stirred overnight at RT. The mixture was washed with saturated NaHCO 3 solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/n-hexane) to yield 7 (0.26g, 0.71mmol, 52%). 1H-NMR (CDCl 3) : δ= 1.47 (t, J=6.9 Hz, 3H), 2.92 (t, J=6.6 Hz, 2H), 3.66 (q, J=6.3 Hz, 2H), 3.96 (s, 3H), 4.10 (q, J=7.1 Hz, 2H), 5.80 (brs, 1H), 6.33(d, J= 15.7 Hz, 1H), 6.71 (d, J=7.7 Hz, 1H), 6.86-6.93 (m, 2H), 7.10-7.28 (m, 3H), 7.39-7.45 (m, 2H), 7.82 (d, J=15.4 Hz, 1H), 8.61 (brs, 1H).
95% With trichlorophosphate at 0 - 20℃; for 2h; 9 Intermediate 9: 7-methoxyindole-3-carboxaldehyde Intermediate 9: 7-methoxyindole-3-carboxaldehyde To a solution of phosphorous oxychloride (190 μL, 2.04 mmol) in DMF (2.5 ML) at 0° C. was added 7-methoxy indole (220 μL, 1.70 mmol).The reaction mixture was allowed to warm to room temperature and to stir for 2 hours.The solution was diluted with dichloromethane and made basic with aqueous 1N sodium hydroxide solution.The layers were separated and the organic layer was washed with aqueous 1N sodium hydroxide solution (2*10 ML).The organic layer was dried (MgSO4), concentrated in vacuo, and the crude product was purified by eluding through a pad of silica with dichlormethane, to afford Intermediate 9 as light brown needles (284 mg, 95%).
91.7% With trichlorophosphate for 5h; Ambient temperature;
88% Stage #1: 7-methoxy-1H-indole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 38℃; for 1.25h; Stage #2: With sodium hydroxide In water at 170℃; for 0.0833333h;
78% With trichlorophosphate at 0 - 40℃;
74.1% With trichlorophosphate at 0 - 20℃; for 3h; Inert atmosphere; 144.1 Step 1 : 7-Methoxy-1H-indole-3-carbaldehyde To a solution of POCl3 (1.13 g, 7.37 mmol, 684.85 μ, 1.08 eq) in DMF (12 mL) was added 7- methoxy-lH-indole (1 g, 6.79 mmol, 884.96 μ, 1 eq) at 0 °C. The mixture was stirred at 0-20 °C for 3 h under N2 atmosphere. TLC (PE/EtOAc = 3/1, Rf = 0.25) indicated one major new spot was detected. The mixture was adjusted pH to 10-12 with 2 NNaOH. The mixture was extracted with DCM (30 mL x 3). The combined organic layers were dried over Na2S04, filtered and concentrated to yield a residue which was purified on silica gel column chromatography (from PE/EtOAc = 1/0 to 5/2, TLC: PE/EtOAc = 3/1, Rf = 0.25) to yield 7-methoxy-lH-indole-3-carbaldehyde (900 mg, 5.03 mmol, 74.1% yield, 98.0% purity) as a pink solid. NMR (400 MHz, CDCl3) δ ppm 10.07 (s, 1H), 9.18 (br s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.81 (d, J = 3.1Hz, 1H), 7.24 (t, J = 7.9 Hz, 1H), 6.78 (d, J = 7.7 Hz, 1H), 3.98 (s, 3H); ES-LCMS m/z 176.1 [M+H]+.
With trichlorophosphate
With trichlorophosphate at 0 - 60℃;
With sodium hydroxide; trichlorophosphate
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: 7-methoxy-1H-indole In N,N-dimethyl-formamide at 20℃; for 3h; 4.2.1. Synthesis of compound 3 General procedure: POCl3 (13.09 g, 85.36 mmol) was slowly added dropwise to DMF(10 mL) under ice bath. The mixture was stirred at ice bath for30 min. Then, DMF (6.24 g, 85.36 mmol) solution of indole (5 g,42.68 mmol) was added dropwise to the reaction system. Keepingthe reaction at room temperature for 3 h, ice water and 10% NaOHaq. were added into the reaction system to pH of 7-8 and continue to stir to a lot of white solid precipitation. The solid was recrystallizedfrom ethyl acetate and petroleum ether to obtain compound3 in yields of 97.6%.
Stage #1: 7-methoxy-1H-indole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2h; Stage #2: With sodium hydroxide In water at 90℃; for 1h;
With trichlorophosphate at 0 - 20℃; for 2h; Inert atmosphere;

Reference: [1]Current Patent Assignee: KYOTO UNIVERSITY - WO2019/167973, 2019, A1 Location in patent: Paragraph 0076
[2]Current Patent Assignee: BAYER AG; NIEWOHNER MARIA HF - US2003/236276, 2003, A1 Location in patent: Page 15
[3]Yamada, Fumio; Saida, Yoshihiro; Somei, Masanori [Heterocycles, 1986, vol. 24, # 9, p. 2619 - 2627]
[4]Nelson, Hosea M.; Reisberg, Solomon H.; Shunatona, Hunter P.; Patel, Jigar S.; Toste, F. Dean [Angewandte Chemie - International Edition, 2014, vol. 53, # 22, p. 5600 - 5603][Angew. Chem., 2014, vol. 126, # 22, p. 5706 - 5709,4]
[5]Coowar, Djalil; Bouissac, Julien; Hanbali, Mazen; Paschaki, Marie; Mohier, Eliane; Luu, Bang [Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6270 - 6282]
[6]Current Patent Assignee: IKENA ONCOLOGY INC - WO2018/195397, 2018, A2 Location in patent: Paragraph 00874-00875
[7]Harada, Hiroshi; Hirokawa, Yoshimi; Suzuki, Kenji; Hiyama, Yoichi; Oue, Mayumi; Kawashima, Hitoshi; Yoshida, Naoyuki; Furutani, Yasuji; Kato, Shiro [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 7, p. 1301 - 1305]
[8]Tripathy, Rabindranath; Ghose, Arup; Singh, Jasbir; Bacon, Edward R.; Angeles, Thelma S.; Yang, Shi X.; Albom, Mark S.; Aimone, Lisa D.; Herman, Joseph L.; Mallamo, John P. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798]
[9]Kwon, Tae Hoon; Yoon, Ik Hwan; Shin, Ji-Sun; Lee, Young Hun; Kwon, Bong Jin; Lee, Kyung-Tae; Lee, Yong Sup [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2571 - 2574]
[10]Liu, Hong-Min; Suo, Feng-Zhi; Li, Xiao-Bo; You, Ying-Hua; Lv, Chun-Tao; Zheng, Chen-Xing; Zhang, Guo-Chen; Liu, Yue-Jiao; Kang, Wen-Ting; Zheng, Yi-Chao; Xu, Hai-Wei [European Journal of Medicinal Chemistry, 2019, vol. 175, p. 357 - 372]
[11]Xie, Tao; Sui, Qi-Bang; Qin, Lu-Zhe; Wen, Xiaoan; Sun, Hongbin; Xu, Qing-Long; Zhen, Le [Journal of Organic Chemistry, 2021, vol. 86, # 8, p. 5518 - 5529]
[12]He, Ling; Jiang, Yan; Qiao, Zhen; Qiu, Hanyue; Su, Xiaojiao; Tan, Qiuyuan; Yang, Jiaojiao; Yang, Zhao; Zhang, Min; Zhou, Wenqiang [Angewandte Chemie - International Edition, 2021, vol. 60, # 23, p. 13105 - 13111][Angew. Chem., 2021, vol. 133, # 23, p. 13215 - 13221,7]
  • 4
  • [ 3189-22-8 ]
  • [ 98-09-9 ]
  • [ 146073-32-7 ]
YieldReaction ConditionsOperation in experiment
97.5% Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Inert atmosphere; 1.1 Step 1: Preparation of 7-methoxy-l-(phenylsulfonyl)-lH-indole To a solution of sodium hydride (1.6 g, 40 mmol) in DMF (10 mL) was added a solution of 7-methoxy-lH-indole (1, 3 g, 20 mmol) in DMF at 0 °C, drop wise over 15 min. followed by addition of a solution of benzenesulfonyl chloride (2, 2.86 mL, 22 mmol) in DMF at 0 °C and the reaction mixture was stirred for 2 h at rt under N2atmosphere. To the reaction mixture was added ice cold water (50 mL), then the precipitate was filtered off and washed with ice cold water to obtain brown solid (3) (5.6 g, 97.5 % Yield). MS (ESI) m/z 288.1 (M+H)+.
84% With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane at 5 - 10℃; for 4h;
76% With sodium hydride In N,N-dimethyl-formamide at 40℃; for 0.25h;
73% Stage #1: 7-methoxy-1H-indole With tetrabutylammomium bromide; sodium hydroxide In tetrahydrofuran; water at 20℃; for 0.333333h; Inert atmosphere; Stage #2: benzenesulfonyl chloride In tetrahydrofuran; water Inert atmosphere; 4.2.1 1-Benzenesulfonyl-4-methoxyindole (5a) General procedure: A suspension of 4-methoxyindole (500mg, 3.4mmol), TBAB (10mol%, 109mg, 0.34mmol) and 50% sodium hydroxide (5mL) in THF (10mL) and H2O (3mL) was stirred vigorously for 20minat rt. Benzenesulfonyl chloride (2 eq, 6.8mmol, 1.2g) in THF (15mL) was added dropwise to the reaction mixture. The reaction mixture was stirred overnight then extracted with EtOAc (20mL×3). The combined organic layers were dried with anhydrous Na2SO4 and then concentrated in vacuo to yield a yellow oil. The product was purified using column chromatography (DCM) to yield white solid (910mg, 92%): mp 86-88°C.
67% Stage #1: 7-methoxy-1H-indole With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: benzenesulfonyl chloride In tetrahydrofuran for 1h;
58% Stage #1: 7-methoxy-1H-indole With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.5h; Stage #2: benzenesulfonyl chloride In tetrahydrofuran; mineral oil at 20℃; 28.1 1. To solution of 7-methoxy- 1H- indole (2 g, 13.58 mmol) in 30 mL of THF, was added sodium hydride (60 wt% dispersion, 653 mg, 16.3 mmol) at 0 °C. After 1.5 hr RT,phenylsulfonylchloride (2.6 mL, 20.4 mmol) was added. After overnight at RT, the reaction was quenched with saturated ammonium chloride solution at 0 °C, and extracted with EtOAc (x3). The combined organic extracts were dried (MgS04), filtered, and concentrated. The residue was trituration from MeOH to give 57-methoxy-l-(phenylsulfonyl)-lH-indole (2.26 g, 58%). *H NMR (400 MHz, CDC13) δ ppm: 7.84 (m, 3H), 7.55 (t, J=7.2 Hz, IH), 7.47(t, J=8.0 Hz, 2H), 7.18-7.10 (m, 2H), 6.68 (d, J=8.8 Hz, IH), 6.65 (d, J=3.6 Hz, IH), 3.64(s, 3H).
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; 3 To a solution of 7-methoxyindole (1 eq) in DMF cooled in an ice bath was added NaH (60% dispersion in oil, 1.2 eq). The reaction was stirred for 1 hr at room temperature then recooled in an ice bath. Benzenesulfonyl chloride (1.1 eq) was added then the reaction was stirred for 2 hrs at room temperature. Water/ethyl acetate were added and the ethyl acetate layer was washed repeatedly (3x) with water. The ethyl acetate layer was concentrated and evaporated to dryness.
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 20℃; for 2h; 3 To a solution of 7-methoxyindole (1 eq) in DMF cooled in an ice bath was added NaH (60% dispersion in oil, 1.2 eq). The reaction was stirred for 1 hr at room temperature then recooled in an ice bath. Benzenesulfonyl chloride (1.1 eq) was added then the reaction was stirred for 2 hrs at room temperature. Water/ethyl acetate were added and the ethyl acetate layer was washed repeatedly (3x) with water. The ethyl acetate layer was concentrated and evaporated to dryness.
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; 3.Q Example 3: Synthesis of Compound 188 EPO NaOH/MeOH 1-Benzenesulfonyl- 7-methoxy-lH-indole (Q); To a solution of 7-methoxyindole (1 eq) in DMF cooled in an ice bath was added NaH (60% dispersion in oil, 1.2 eq). The reaction was stirred for 1 hr at room temperature then recooled in an ice bath. Benzenesulfonyl chloride (1.1 eq) was added then the reaction was stirred for 2 hrs at room temperature. Water/ethyl acetate were added and the ethyl acetate layer was washed repeatedly (3x) with water. The ethyl acetate layer was concentrated and evaporated to dryness.
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide for 0.25h; Inert atmosphere; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; 369.a Example 369 l-(l-Methylethyl)-N-[(6-methyl-2-oxo-4-propyl-l,2-dihydro-3-pyridinyl)methyl]-7- (methyloxy)-lH-indole-4-carboxamide a) 7-(Methyloxy)- 1 -(phenylsulfonyl)- lH-indole To a cooled (ice water bath) solution of 7-(methyloxy)-lH-indole (3 g, 20.38 mmol) in DMF (100 mL) was added sodium hydride (0.618 g, 24.46 mmol) portionwise. After 15 minutes a solution of benzenesulfonyl chloride (3.94 mL, 30.6 mmol) in 20 ml of DMF was added dropwise. The reaction mixture was stirred at RT for 24 h, at which time it was concentrated. The residue was dissolved in DCM (100 ml) and washed with water and brine, dried over MgS04, filtered and concentrated. The residue was purified by column chromatography (Biotage; 0% to 100% DCM:Hex; 50g-HP- silica gel column) to give 3.65 of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.65 (s, 3 H), 6.60 - 6.75 (m, 2 H), 7.08 - 7.22 (m, 2 H), 7.40 - 7.62 (m, 3 H), 7.77 - 7.92 (m, 3 H). MS(ES)[M+H]+ 288.0.
3.65 g Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide for 0.25h; Inert atmosphere; Cooling with ice; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; 369.a a) 7-(Methyloxy)-1-(phenylsulfonyl)-1H-indole To a cooled (ice water bath) solution of 7-(methyloxy)-1H-indole (3 g, 20.38 mmol) in DMF (100 mL) was added sodium hydride (0.618 g, 24.46 mmol) portionwise. After 15 minutes a solution of benzenesulfonyl chloride (3.94 mL, 30.6 mmol) in 20 ml of DMF was added dropwise. The reaction mixture was stirred at RT for 24 h, at which time it was concentrated. The residue was dissolved in DCM (100 ml) and washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (Biotage; 0% to 100% DCM:Hex; 50 g-HP-silica gel column) to give 3.65 g of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.65 (s, 3H), 6.60-6.75 (m, 2H), 7.08-7.22 (m, 2H), 7.40-7.62 (m, 3H), 7.77-7.92 (m, 3H). MS(ES) [M+H]+ 288.0.
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Cooling with ice; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; Cooling with ice; 3 1-Benzenesulfonyl-7-methoxy-1H-indole (Q) To a solution of 7-methoxyindole (1 eq) in DMF cooled in an ice bath was added NaH (60% dispersion in oil, 1.2 eq). The reaction was stirred for 1 hr at room temperature then recooled in an ice bath. Benzenesulfonyl chloride (1.1 eq) was added then the reaction was stirred for 2 hrs at room temperature. Water/ethyl acetate were added and the ethyl acetate layer was washed repeatedly (3×) with water. The ethyl acetate layer was concentrated and evaporated to dryness.
Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 20℃; for 2h; 3 To a solution of 7-methoxyindole (1 eq) in DMF cooled in an ice bath was added NaH (60% dispersion in oil, 1.2 eq). The reaction was stirred for 1 hr at room temperature then recooled in an ice bath. Benzenesulfonyl chloride (1.1 eq) was added then the reaction was stirred for 2 hrs at room temperature. Water/ethyl acetate were added and the ethyl acetate layer was washed repeatedly (3x) with water. The ethyl acetate layer was concentrated and evaporated to dryness.

Reference: [1]Current Patent Assignee: JUBILANT PHARMOVA LTD - WO2019/77631, 2019, A1 Location in patent: Paragraph 000133; 000338
[2]Gourdoupis; Stamos [Synthetic Communications, 1994, vol. 24, # 8, p. 1137 - 1144]
[3]Santangelo; Casagrande; Norcini; Gerli [Synthetic Communications, 1993, vol. 23, # 19, p. 2717 - 2725]
[4]Trabbic, Christopher J.; George, Sage M.; Alexander, Evan M.; Du, Shengnan; Offenbacher, Jennifer M.; Crissman, Emily J.; Overmeyer, Jean H.; Maltese, William A.; Erhardt, Paul W. [European Journal of Medicinal Chemistry, 2016, vol. 122, p. 79 - 91]
[5]Mahboobi, Siavosh; Uecker, Andrea; Sellmer, Andreas; Cénac, Christophe; Höcher, Heymo; Pongratz, Herwig; Eichhorn, Emerich; Hufsky, Harald; Trümpler, Antje; Sicker, Marit; Heidel, Florian; Fischer, Thomas; Stocking, Carol; Elz, Sigurd; Böhmer, Frank-D.; Dove, Stefan [Journal of Medicinal Chemistry, 2006, vol. 49, # 11, p. 3101 - 3115]
[6]Current Patent Assignee: SRI INTERNATIONAL INC - WO2016/114816, 2016, A1 Location in patent: Paragraph 0260
[7]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2008/57246, 2008, A2 Location in patent: Page/Page column 232
[8]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2008/51416, 2008, A2 Location in patent: Page/Page column 174
[9]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2006/55760, 2006, A1 Location in patent: Page/Page column 150-151
[10]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/140324, 2011, A1 Location in patent: Page/Page column 134-135
[11]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2014/256739, 2014, A1 Location in patent: Paragraph 0692
[12]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - US9108933, 2015, B2 Location in patent: Page/Page column 307; 309
[13]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2008/112199, 2008, A1 Location in patent: Page/Page column 177
  • 5
  • [ 3189-22-8 ]
  • [ 74-88-4 ]
  • [ 51460-41-4 ]
YieldReaction ConditionsOperation in experiment
90% With potassium-t-butoxide In diethyl ether at 0℃; for 24h;
With sodium hydride 1.) DMF, 0 deg C, 30 min, 2.) DMF, RT, 16 h; Multistep reaction;
Stage #1: 7-methoxy-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h; Stage #2: iodomethane In N,N-dimethyl-formamide; mineral oil at 0 - 20℃;
Stage #1: 7-methoxy-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1.25h; Stage #2: iodomethane In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h;

  • 6
  • [ 3189-22-8 ]
  • [ 334986-99-1 ]
YieldReaction ConditionsOperation in experiment
93% With sodium cyanoborohydride; acetic acid at 0 - 20℃; for 1h; 14.A EXAMPLE 14; Preparation of Methyl [(2l )- l - {(2lS}-2-[5-(4-{2-[(2S)-l - {(2S)-2-[(methoxycarbonyl)amino]-3- methyl butanoyl}pyrrolidin-2-yl]- l H-imidazol-5-yl}-l ,2-dihydropyrrolo[3,2, l -/:/]phenoxazin-9- yl)-l H-imidazol-2-yl]pyrrolidin-l-yl}-3-methyl- l -oxobutan-2-yl] carbamate (Compound 6); To a 0 °C solution of 7-methoxyindole (50 g; 0.34 mol) in AcOH (200 mL) was added NaBH3CN (17.92 g; 0.51 mol) at a rate to keep the reaction temperature below 5 °C. The reaction mixture was then stirred for 1 hour at room temperature, water (0.4 mL) was added, and the resulting solution was concentrated in vacuo. The residue obtained was diluted to 200 mL with EtOAc and the resulting solution was washed with 5% NaHC03, brine, dried over anhydrous Na2S04, filtered and concentrated in vacuo to provide compound Int-14a (47 g, 93%). MS (ESI) m/z (M+H)+: 149.
93% With sodium cyanoborohydride In acetic acid at 0 - 20℃; for 1h; 14.A Synthesis of Com ound Int-14aInt 14aTo a 0 °C solution of 7-methoxyindole (50 g; 0.34 mol) in AcOH (200 mL) was added NaBH3CN (17.92 g; 0.51 mol) at a rate to keep the reaction temperature below 5 °C. The reaction mixture was then stirred for 1 hour at room temperature, water (0.4 mL) was added, and the resulting solution was concentrated in vacuo. The residue obtained was diluted to 200 mL with EtOAc and the resulting solution was washed with 5% NaHC03, brine, dried over anhydrous Na2S04, filtered and concentrated in vacuo to provide compound Int-14a (47 g, 93%) MS (ESI) m/z (M+H)+: 149.
66% With sodium cyanoborohydride; acetic acid at 10℃; for 4h; 6 Syntheses for Substituted Indoline Compounds General procedure: The indole compound (2 mmol) was dissolved in acetic acid (20 mL). NaBH3CN (627 mg, 10 mmol) was added to the solution mixture portionwise at 10° C. The solution mixture was then stirred at 10° C. for 4 h, and then water was added to quench the reaction. Any organic volatile was removed by evaporation under reduced pressure, and the aqueous layer was extracted with dichloromethane. The dichloromethane layer was washed by dilute NaOH solution and then saturated NaCl solution, dried by MgSO4 and filtered. Volatile organic solvent was evaporated under reduced pressure, and the crude product was purified by column chromatography on silica gel using hexane/ethyl acetate (10:1, v/v) as eluent, yielding the indoline compound. Yield=66%. 1H NMR (CDCl3, 400 MHz): δ=6.87-6.91 (1H, m), 6.80 (1H, t, J=8.0 Hz), 6.72-6.76 (1H, m), 3.89-3.91 (1H, br), 3.89 (3H, s), 3.63 (2H, t, J=8.4 Hz), 3.13 (2H, t, J=8.4 Hz). 13C{1H} NMR (CDCl3, 100 MHz) δ=145.3, 140.5, 130.1, 119.0, 117.0, 109.0, 55.1, 47.5, 30.3.
With sodium cyanoborohydride In acetic acid for 0.5h; Ambient temperature;
Stage #1: 7-methoxy-1H-indole With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: With water; sodium hydroxide In N,N-dimethyl-formamide 14 5.1.33. 7-Methoxy-5-(methylsulfanyl)-2,3-dihydro-1H-indole (16i) General procedure: 5.1.24. 7-Fluoro-2,3-dihydro-1H-indole (15f) 7-Fluoro-1H-indole (20.0 g, 148 mmol) was dissolved in acetic acid (60 mL) and sodium cyanoborohydride (18.7 g, 296 mmol) was added in portions. The mixture was stirred for 2 h and then poured into 1500 mL of 2 M aqueous NaOH solution. The mixture was extracted with CH2Cl2. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated under reduced pressure to give the title compound (20.0 g, 98%). 1H NMR (400 MHz, CDCl3) δ 3.08 (2H, t, J = 8.4 Hz), 3.62 (2H, t, J = 8.4 Hz), 6.62-6.66 (1H, m), 6.78-6.83 (1H, m), 6.90 (1H, dd, J = 7.6, 0.4 Hz).
With sodium cyanoborohydride; acetic acid at 0 - 20℃; for 5h; Inert atmosphere;

  • 8
  • [ 124-41-4 ]
  • [ 89976-15-8 ]
  • [ 3189-22-8 ]
YieldReaction ConditionsOperation in experiment
76% With copper(l) iodide In methanol; N,N-dimethyl-formamide at 120℃; for 1h;
With copper(l) iodide In N,N-dimethyl-formamide
  • 9
  • [ 96096-68-3 ]
  • [ 3189-22-8 ]
YieldReaction ConditionsOperation in experiment
50% With hydrazine hydrate In tetrahydrofuran; methanol at 60℃; for 1h;
  • 10
  • [ 3189-22-8 ]
  • [ 4521-61-3 ]
  • (7-methoxy-indol-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% Stage #1: 7-methoxy-1H-indole With sodium t-butanolate In tetrahydrofuran at 20℃; Stage #2: 3,4,5-Trimethoxybenzoyl chloride In tetrahydrofuran
  • 11
  • [ 3189-22-8 ]
  • [ 59337-92-7 ]
  • 3-(7-methoxy-indole-1-sulfonyl)-thiophene-2-carboxylic acid methyl ester [ No CAS ]
  • 12
  • [ 3189-22-8 ]
  • [ 78-94-4 ]
  • 4-(7-methoxy-1H-indol-3-yl)butan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With indium(III) chloride In dichloromethane at 25℃; for 4h; Inert atmosphere;
62% In dichloromethane at 20℃; for 4h;
  • 13
  • [ 41608-64-4 ]
  • [ 3189-22-8 ]
  • 14
  • [ 180624-10-6 ]
  • [ 3189-22-8 ]
  • 15
  • [ 5345-42-6 ]
  • [ 3189-22-8 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In N,N-dimethyl-formamide; A solution of 7-methoxyindole (6.5 g), which is prepared from 3-methyl-2-nitroanisole according to the method disclosed in Heterocycles, 16, 1119-1124 (1981), in DMF (16 ml) is added dropwise to the mixture, and the mixture is stirred at room temperature for two hours. To the mixture is added 30% aqueous sodium hydroxide solution (30 ml) under ice-cooling, and the mixture is heated at about 80 C. for five minutes in a hot bath, and allowed to stand to cool.
  • 16
  • [ 16078-30-1 ]
  • [ 3189-22-8 ]
  • 17
  • [ 611-07-4 ]
  • [ 3189-22-8 ]
  • 18
  • [ 3189-22-8 ]
  • [ 2380-84-9 ]
YieldReaction ConditionsOperation in experiment
74% With sodium thioethylate; In DMF (N,N-dimethyl-formamide); at 155℃; for 15h;Heating / reflux; To a solution of 7-Methoxy-lNo.-indole (2.0 g,13.58 mmol, 1.0 equiv.) in DMF (20 mL) was added NaSEt (2.8 g, 34.0 mmol, 2.5 equiv.). The resulting mixture was heated to 155C under N2 with stirring. After stirred at same temperature for 15 h. the reaction mixture was cooled to room temperature, neutralized with IN HCl (34 mL). The resulting mixture was partitioned 10 with ethyl acetate (300 mL). After separation, the organic layer was washed with water, brine, dried over Na2SO4. After removal of solvent, the crude product was purified by chromatography to afford 1.337 g (74% yield) of intermediate 1-4 as black solid. ]H NMR (400 MHz, CDC13), 5 (ppm): 8.45 (b, 1H), 7.27 (d, 1H), 7.23 (s, 1H), 6.98 (t, 1H), 6.61 (d, ), 6.57 (s, 1H), 3.90 (b, 1H).
  • 19
  • 3-Methoxy-2,β-dinitrostyrene [ No CAS ]
  • [ 3189-22-8 ]
YieldReaction ConditionsOperation in experiment
1.863 g (58%) With acetic acid In diethyl ether; ethyl acetate 8 7-Methoxyindole (3) To a 250-mL Parr hydrogenation bottle, 4.893 g of 2 (21.84 mmol) was added. Compound 2 was dissolved in 90 mL of hot ethyl acetate and 9.0 mL of acetic acid. To this solution 0.260 g of 10% palladium on activated carbon (Aldrich) was added. This mixture was hydrogenated overnight at 4 atm. When the pressure stabilized, the reaction mixture was filtered and the solvent removed by rotary evaporation. The residue was dissolved in 60 mL of diethyl ether. The ether solution was washed with 35 mL of 5% aqueous ammonium hydroxide, 5% aqueous hydrochloric acid, and water, dried with MgSO4, and filtered. The ether was removed by rotary evaporation to yield 2.009 g of a green oil. This oil was chromatographed over 85 g of silica gel with 6:1 hexanes:ethyl acetate to yield 1.863 g (58%) of 3 as a very pale yellow oil: 1 H NMR (CDCl3) δ 3.99 (s, 3H, OCH3), 6.61 (m, 2H), 7.18 (m, 3H), 8.43 (br s, 1H, NH).
  • 20
  • [ 3189-22-8 ]
  • [ 3990-05-4 ]
  • [ 916917-65-2 ]
YieldReaction ConditionsOperation in experiment
With dysprosium(III) trifluoromethanesulfonate In methanol; water at 20 - 50℃;
In acetonitrile at 20℃; for 72h; 6.1 A solution of B (7-Oxo-heptanoic acid ethyl ester, 58 mg, 0.34 mmol), A (7-Methoxy-1 H-indole, 100 mg, 0.68 mmol) and trifluoroacetic acid (0.03 mmol mmol) in CH3CN (1 ml_) was stirred for 72 h at room temperature, then the solvent was evaporated under reduced pressure. Compound C [7,7-Bis-(7- methoxy-1 H-indol-3-yl)-heptanoic acid ethyl ester] was not isolated and was characterised by ES-MS (m/z: 449.6 [M+H]+).
In acetonitrile at 20℃; for 72h; 6.1 A solution of B (7-Oxo-heptanoic acid ethyl ester, 58 mg, 0.34 mmol), A (7-Methoxy-1H-indole, 100 mg, 0.68 mmol) and trifluoroacetic acid (0.03 mmol mmol) in CH3CN (1 mL) was stirred for 72 h at room temperature, then the solvent was evaporated under reduced pressure. Compound C [7,7-Bis-(7-methoxy-1H-indol-3-yl)-heptanoic acid ethyl ester] was not isolated and was characterised by ES-MS (m/z: 449.6 [M+H]+).
  • 21
  • [ 3189-22-8 ]
  • [ 98-59-9 ]
  • [ 139717-63-8 ]
YieldReaction ConditionsOperation in experiment
24% With sodium hydride In tetrahydrofuran at 20℃; 38.1 To a stirred solution of 7-methoxyindole (3 g, 20.4 mmol) in THF (80 ml_) was added toluenesulfonyl chloride (4 g, 21 mmol) and NaH (60%, 1.22 g). The mixture was stirred at RT overnight, quenched with water, and concentrated under reduced pressure. The residue was partitioned between water (100 ml_) and EtOAc (100 ml_). The organic layer was then dried (Na2SO4), filtered and concentrated to provide 38A (1.5 g, 24%).
  • 22
  • [ 3189-22-8 ]
  • [ 79-37-8 ]
  • [ 408354-83-6 ]
YieldReaction ConditionsOperation in experiment
71% With sodium methylate In methanol; diethyl ether 16.a 12-Methoxy-5-methyl-5H,13H-indolo[6,7-a]pyrrolo[3,4-c]carbazole-6,8-dione (a) (7-Methoxy-1H-indol-3-yl)-oxo-acetic acid methyl ester. A solution of 7-methoxy-indole (1.10 g, 7.47 mmol) in Et2O (150 mL) cooled to 0-5° C. was treated with oxalyl chloride (0.75 mL, 8.6 mmol). After 30 min, the mixture was allowed to warm to room temperature and stirred 1h. Additional oxalyl chloride (0.25 mL, 2.87 mmol) was added, the mixture stirred an additional 1 h and then cooled to -78° C. A 25% solution of sodium methoxide in methanol (5.4 mL, 23.8 mmol) was added over 10 min. The suspension was warmed to room temperature, stirred 2 h and then poured into EtOAc/pH 7 buffer. The EtOAc layer was separated and washed with water, brine, dried (MgSO4), filtered and concentrated to ~20 mL. The resulting slurry was diluted with Et2O (75 mL), and filtered. The solid obtained was washed with Et2O and dried under vacuum overnight to afford the title compound as an off-white solid (1.23 g, 71%). Upon standing, the mother liquor afforded a second crop (0.26 g, 15%). 1H NMR (400 MHz, DMSO-d6) 12.63 (br s, 1H), 8.29 (d, J=3.5 Hz, 1H), 7.73 (d, J=8 Hz, 1H), 7.20 (dd, J=8, 8 Hz, 1H), 6.89 (d, J=8 Hz, 1H). 13C NMR (75.5 MHz, DMSO-d6) 178.72, 163.88, 146.37, 137.19, 127.02, 125.54, 123.73, 113.52, 112.92, 104.60, 55.34, 52.42. IR (CHCl3, cm-1) 3452, 1732, 1648. MS (electrospray, m/z) 234.1 (M++1), 232.2 (M--1). Anal. Calcd for C12H11NO4: C, 61.80; H, 4.75; N, 6.01. Found: C, 61.61; H, 4.83; N, 6.01.
  • 23
  • [ 3189-22-8 ]
  • [ 75-36-5 ]
  • [ 944086-13-9 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 7-methoxy-1H-indole With diethylaluminium chloride In hexane; dichloromethane at 0℃; for 0.5h; Stage #2: acetyl chloride In hexane; dichloromethane at 50℃; for 0.166667h; microwave irradiation; Further stages.;
70% Stage #1: 7-methoxy-1H-indole With methylmagnesium bromide In dichloromethane at 20℃; for 1h; Stage #2: acetyl chloride In dichloromethane at 0 - 20℃; for 1h; Stage #3: With hydrogenchloride; water In dichloromethane 8 Typical procedure 8 (See Scheme 6) (TP8): l-(7-Methoxy-lH-indol-3-yDethanone{0229] MeMgBr (3 ml, 3M in ether, 9 mmol) was added to 7-methoxy-lH-indole dissolved in dry Cη2CI2 (6 ml) at 0-5 0C. The resulting red solution was stirred for 1 h at room temperature. Freshly distilled acetyl chloride (353 mg, 4.5 mmol) was then added at 0-5 0C and the resulting brown solution was stirred for 1 h at room temperature. Aqueous HCl (2M) was added to the reaction mixture and the organic phase was separated. The aqueous phase was extracted with CH2Cl2 and the combined organic phases were washed with water, brine and dried with Na2SO^ The filtrate was concentrated at reduced pressure and the crude product was purified by crystallization (heptane/ethyl acetate 3:1), which gave 345 mg (70%) of the title compound as brown crystals.[0230] 1H NMR (400 MHz, CDCl3) δ 8.80 (br s, IH), 7.93 (d, IH, J = 8.0 Hz), 7.81 (d, IH, J= 2.9 Hz)5 7,20 (t, IH5 J= 8 Hz)3 6.73 (d, IH J= 7.9 Hz), 3.96 (s, 3H)5 2.55 (s, 3H).
Stage #1: 7-methoxy-1H-indole With diethylaluminium chloride In hexane; dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: acetyl chloride In hexane; dichloromethane at 0℃; Inert atmosphere;
Stage #1: 7-methoxy-1H-indole With diethylaluminium chloride In hexane; dichloromethane at 0℃; for 0.5h; Stage #2: acetyl chloride In hexane; dichloromethane at 0℃;
Stage #1: 7-methoxy-1H-indole With diethyl aluminiumcholoride In hexane; dichloromethane at 0℃; for 0.5h; Stage #2: acetyl chloride In hexane; dichloromethane at 0 - 20℃;

  • 24
  • [ 67-56-1 ]
  • [ 3189-22-8 ]
  • [ 76-02-8 ]
  • [ 582319-20-8 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: 7-methoxy-1H-indole; trifluoroacetyl chloride With pyridine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: methanol With potassium hydroxide; water Reflux; Inert atmosphere;
  • 25
  • [ 3189-22-8 ]
  • [ 109-70-6 ]
  • [ 944086-42-4 ]
YieldReaction ConditionsOperation in experiment
91% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In dimethyl sulfoxide at 0℃; for 0.5h; Ultrasound irradiation; Stage #2: 1.3-chlorobromopropane In dimethyl sulfoxide 1 -(3 -chloropropyl)-7-methox v- 1 //-indole[0302] A dry round bottomed flask was charged with KOH (574 mg, 10.2 mmol) which was finely ground under Ar. To this powder was added DMSO (15 mL) and 7- methoxy-lH-indoIe (0.90 mL, 6.89 mmol). The suspension was submitted to ultrasound irradiation for 30 min and cooled to 0 0C. To this mixture was added l-bromo-3- chloropropane (2.00 mL, 20.3 mmol) and the mixture was left with stirring overnight. The solution was poured into ice-water (25 mL) and extracted with EtOAc (4x 50 mL). The combined organic layers were washed with H2O5 brine, dried over Na2SO4 and adsorbed onto celite. Purification was by flash chromatography (heptanes - > heptanes:EtOAc 4:1) to give the title compound (1.40 g, 91%). [0303] 1H NMR (400 MHz, CDCl3) δ 7.20 (dd, J = 8.0, 0.9 Hz5 IH), 7.03-6.97 (m, 2H), 6.63-6.61 (m, IH), 6.43 (d, J= 3.1 Hz, IH), 4.54 (t, J= 6.4 Hz, 2H), 3.93 (s, 3H), 3.46-3.43 (m, 2H), 2.30-2.24 (m, 2H).[0304] 13C NMR (IOO MHz, CDCl3) δ 147.4, 131.2, 129.3, 1 19.9, 1 13.8, 1 13.8, 102.2, 101.3, 55.2, 46.1, 42.1, 34.6.
58% Stage #1: 7-methoxy-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.333333h; Stage #2: 1.3-chlorobromopropane In N,N-dimethyl-formamide; mineral oil at 0 - 20℃;
  • 26
  • [ 288-13-1 ]
  • [ 3189-22-8 ]
  • [ 1414867-76-7 ]
YieldReaction ConditionsOperation in experiment
89% With iodine; ammonium formate In 1,4-dioxane at 20℃; for 24h; regioselective reaction;
  • 27
  • [ 109-65-9 ]
  • [ 3189-22-8 ]
  • [ 1438278-46-6 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In N,N-dimethyl-formamide at 21℃; for 0.25h; Stage #2: With iodine In N,N-dimethyl-formamide for 0.5h; Stage #3: 1-bromo-butane With sodium hydride In N,N-dimethyl-formamide; mineral oil
80% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: With iodine In N,N-dimethyl-formamide for 0.5h; Stage #3: 1-bromo-butane Further stages; Preparation of l-butyl-3-iodo-7-methoxy-lH-indole A round bottom flask containing indole (0.22 mL, 1.70 mmol, 1 equiv) in DMF at R.T. was stirred with KOH (0.10 g, 1.78 mmol, 1.05 equiv) for about 15 min and then treated with I2 (0.44g, 1.73 mmol, 1.02 equiv). After 30 min, NaH (0.082 g, 2.04 mmol, 1.2 equiv) was added portion-wise. After additional 15 min had passes 1-bromobutane (0.2 mL, 1.87 mmol, 1.1 equiv) was added and the reaction mixture was stirred until completion. Upon completion (TLC monitoring), H20 was added and allowed to stir for 15 min, upon which the mixture was extracted with DCM and the layers were separated. Aqueous layer was washed with DCM (3x) and the combined organic layers were washed with H20 (2x), dried over anhydrous Na2S04 and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using EtOAc/n-hexanes to afford 0.449g (80% yield) as an clear oil with a yellow tint. TLC system: 10%EtOAc/90%n-hexanes. ]H NMR (400 MHz, CDC13) δ 7.18 (d, 7 = 8.8, 1H), 7.11 (s, 1H), 6.88 (dd, 7 = 2.5, 8.8, 1H), 6.84 (d, 7 = 2.4, 1H), 4.05 (t, 7 = 7.1, 2H), 3.87 (d, 7 = 3.7, 3H), 1.81 - 1.71 (m, 2H), 1.29 (tt, 7 = 5.2, 10.1, 3H), 0.91 (t, 7 = 7.4, 3H).
  • 28
  • [ 109-65-9 ]
  • [ 3189-22-8 ]
  • [ 1438278-43-3 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 1-bromo-butane In N,N-dimethyl-formamide at 50℃; for 12h; (b) 1-Butyl-7-methoxy-1H-indole (2) To a suspension of KOH (16.25 g,290 mmol) in DMF (120 mL) was added 7-methoxyindole (1, 8.54 g, 58 mmol). After stirring at room temperature (RT) for an hour, 1-bromobutane (11.12 g, 81.2 mmol) was added and the reaction mixture was heated to 50 °C for 12 h.The resulting mixture was poured into water (200 mL) and extracted with EtOAc (3 120 mL). Combined organic layers were washed with water two times, dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel using EtOAc/hexanes(1:99) as eluent to afford colorless oily product 2 (10.36 g, 88%). Rf = 0.90 (1:2EtOAc/hexanes). 1H NMR (CDCl3): d 0.91 (t, J = 7.5 Hz, 3H, CH3), 1.27-1.34 (m, 2H, CH2), 1.74-1.80 (m, 2H, CH2), 3.91 (s, 3H, OCH2), 4.35 (t, J = 7.5 Hz, 2H, CH2),6.39 (d, J = 3.0 Hz, 1H, Ar-H), 6.59 (d, J = 8.0 Hz, 1H, Ar-H), 6.94-6.98 (m, 2H, Ar-H), 7.18 (d, J = 8.0 Hz, 1H, Ar-H). MS (ESI): 204 ([M+H]+, 100%).
74% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In N,N-dimethyl-formamide at 21℃; for 1h; Stage #2: 1-bromo-butane In N,N-dimethyl-formamide at 50℃;
74% Stage #1: 7-methoxy-1H-indole With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 1-bromo-butane In N,N-dimethyl-formamide at 50℃; 1.1 1.1. l-butyl-7-methoxy-lH-indole General procedure: To a suspension of KOH (5 equiv) in DMF (13 mL) was added 5- or 7- Methoxyindole (1 equiv). After stirring at R.T. for an hour, 1-bromobutane was added and the reaction mixture was heated to 50 °C and stirred overnight. Upon completion, the resulting mixture was poured into H20 and extracted with DCM. Combined organic extracts were washed with H20, dried over anhydrous Na2S04 and concentrated in vacuo and the resulting residue was purified by flash column chromatography on silica gel using EtOAc/n-hexanes
  • 29
  • [ 89583-07-3 ]
  • [ 3189-22-8 ]
  • [ 133438-31-0 ]
  • 30
  • [ 89583-07-3 ]
  • [ 3189-22-8 ]
  • [ 1438278-45-5 ]
  • 31
  • [ 3189-22-8 ]
  • [ 4545-21-5 ]
  • [ 1440538-05-5 ]
YieldReaction ConditionsOperation in experiment
99% With bis-triphenylphosphine-palladium(II) chloride; oxygen; lithium tert-butoxide In N,N-dimethyl-formamide at 80℃; for 5h;
  • 32
  • [ 3189-22-8 ]
  • [ 1873-88-7 ]
  • [ 1583285-90-8 ]
YieldReaction ConditionsOperation in experiment
88% With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 5,5?-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4?-bi-1,3-benzodioxole; cyclohexene; In tetrahydrofuran; at 65℃; for 24h; From 7-methoxyindole (43.7mg, 0.297 mmol). 1.2 cquiv silane, 65 C, I d. Theresulting mixture was purified by preparative TLC (1 :9 ethyl acetatc:hcxanes) to afford theproduct as a colorless liquid (96.5 mg, 88(Yt) yield). 1H NYlR (400 MHz, CDCh) () 8.46 (:<,H), 7.34 (d, J = 8.0 Hz. lH). 7.09 (t, J = 7.8 Hz, lH), 6.82 (d, J = 2.2 Hz. lH). 6.70 (d, J =7.6 Hz, IH), 4.03 (~. 3H), 0.43 (~. 3H), 0.23 (s, 18H). 13C NMR (101 MHz. CDCh) 6 146.35(s). 135.84 (s), 130.01 (s), 129.01 (s), 120.12 (s), 113.70 (s). 111.84 (s), 102.05 (s), 55.38 (s),1.99 (s), 0.87 (s). The spectra match t11e ones reported.
  • 33
  • [ 3189-22-8 ]
  • [ 1585169-27-2 ]
YieldReaction ConditionsOperation in experiment
70% With 2,2,6,6-tetramethyl-piperidine-N-oxyl; benzoic acid; copper dichloride In acetonitrile at 60℃; for 6h; regioselective reaction;
68% With pyridine; methanesulfonic acid; sodium nitrite at 20℃; General Procedure for the Preparation of 2-(1H-Indol-3-yl)-2,30-biindolin-3-ones General procedure: CH3SO3H (1.0 mmol) was added to a solution of indole (0.5 mmol) and NaNO2(0.5 mmol) in pyridine (0.6mL) in air and the mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure. The residue was purifiedby flash chromatography on silica gel (eluent: EtOAc=PE1:2) to yield the corresponding product.
  • 34
  • [ 3189-22-8 ]
  • [ 100-97-0 ]
  • [ 109021-59-2 ]
YieldReaction ConditionsOperation in experiment
89% With aluminum (III) chloride In N,N-dimethyl-formamide at 120℃; for 1.5h; 9 Example 1 General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 ° C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94%.
77% With silica supported ceric ammonium nitrate In acetonitrile for 12h; Reflux; chemoselective reaction; Typical procedure: General procedure: a mixture of indole (1 mmol), HMTA (2.5 mmol), and 10% CAN-SiO2 was refluxed in CH3CN (5.0 mL). After the reaction was complete, the mixture was evaporated to give a crude residue of CAN-SiO2 and product. The crude residue was washed with EtOAc (10 mL 5) and dried to leave a crude product that was purified by short flash column chromatography (EtOAc/hexane = 1:3).
  • 35
  • [ 3189-22-8 ]
  • [ 79-37-8 ]
  • 2-(7-methoxy-1H-indol-3-yl)-2-oxoacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 7-methoxy-1H-indole; oxalyl dichloride In diethyl ether at 0℃; for 1.5h; Stage #2: With water; sodium hydrogencarbonate for 20.5h; Reflux; 3.2.9. 2-(7-Methoxy-1H-indol-3-yl)-2-oxoacetic Acid (12) The target compound 12 was prepared using a previously published method [26]. To a solution of 7-methoxyindole (0.30 g, 2.04 mmol) in anhydrous diethyl ether (9 mL) was added oxalyl chloride (0.52 mL, 6.11 mmol) dropwise at 0 °C. The reaction mixture was stirred at 0 °C for 1.5 h, followed by dropwise addition of saturated aq. NaHCO3 (10 mL), and then heated at reflux for 20.5 h. After cooling to r.t., 10% HCl was added to the reaction mixture to adjust pH to 1 and the resulting brown precipitate was filtered, washed with cold diethyl ether (20 mL), and dried under vacuum to yield 12 as a brown solid (0.45 g, quant. yield) which was used in the next step without further purification. Mp 206 °C decomp.; Rf = 0.14 (20% MeOH/EtOAc); IR νmax (ATR) 3129, 1712, 1615, 1567, 1450, 1234, 1221, 956, 782 cm-1; 1H NMR (DMSO-d6, 300 MHz) δH 12.51 (1H, br s, NH), 8.23 (1H, d, J = 2.9 Hz, H-2), 7.74 (1H, d, J = 7.9 Hz, H-4), 7.19 (1H, t, J = 7.9 Hz, H-5), 6.87 (1H, d, J = 7.9 Hz, H-6), 3.95 (3H, s, H3-10), OH not observed; 13C NMR (DMSO-d6, 100 MHz) δC 180.8 (C-8), 165.2 (C-9), 146.5 (C-7), 136.8 (C-2), 127.2 (C-3a), 126.6 (C-7a), 123.7 (C-5), 113.6 (C-4), 112.9 (C-3), 104.6 (C-6), 55.4 (C-10); (-)-HRESIMS m/z 220.0603 [M + H]+ (calcd for C11H8NO4, 220.0604).
  • 36
  • [ 3189-22-8 ]
  • C9H8INO [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% Stage #1: 7-methoxy-indole With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333h; Inert atmosphere; Stage #2: With iodine In N,N-dimethyl-formamide for 2.166h; Inert atmosphere;
Stage #1: 7-methoxy-indole With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.666667h; Stage #2: With iodine In N,N-dimethyl-formamide for 0.5h; A solution of 7-methoxyindole (1, 2.95g, 20.0mmol) in DMF (80mL) was stirred with KOH (1.29g, 23.0mmol) at RT for 40min, and then treated with I2 (5.23g, 20.6mmol). After 30min, NaH (60% in mineral oil, 1.04g, 26.0mmol) was added portionwise. After an additional 15min, 1-bromobutane (3.15g, 23.0mmol) was added and the reaction mixture was stirred for overnight. Upon completion (TLC monitoring), water was added, the reaction mixture was extracted with EtOAc (3×80mL). Combined organic layers were washed with water two times, dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel using EtOAc/hexanes (0.5:99.5) as eluent to afford white solid product 7 (4.94g, 75%).
With N-iodo-succinimide In acetonitrile at 20℃; for 2h;
  • 37
  • [ 3189-22-8 ]
  • C18H16N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
98.3% With pyridine; bis-[(trifluoroacetoxy)iodo]benzene; bis(pinacol)diborane In toluene at 55℃; for 12h; 4 To an appropriate amount of an organic solvent (a mixture of pyridine and toluene in a volume ratio of 1: 4) in the reactor was added 100 mg of the compound of the above formula (I), 14 mmol of a two-component catalyst (4 mmol of triphenyl Phosphonium chloride and 10 mmol of silver tetrachlorophthalate), 33 mmol of an oxidizing agent Phi (TFA) 2 and 22 mmol of the accelerator (i.e., the above cyclic borate) were then heated to 55 ° C and at this temperature Followed by stirring for 12 hours. After the reaction was completed, the deionized water was added to the filtrate and the ρ H value of the system was adjusted to 6-7. Then, the mixture was extracted with chloroform to give 2-3, and the organic phase was combined and dried over anhydrous magnesium sulfate. And the residue was separated by 200-300 mesh silica gel column chromatography, and the mixture of petroleum ether and acetone in a volume ratio of 1: 2 was used as the eluent to obtain the compound of the above formula (Π) in a yield of 98.3%
89% With morpholine; copper(I) oxide; tert.-butylhydroperoxide; oxygen In chloroform at 20℃; for 18h; regioselective reaction;
72% With pyridine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; water; oxygen; silver nitrate; benzoic acid at 65℃; for 48h;
  • 38
  • [ 3189-22-8 ]
  • [ 1217-89-6 ]
  • 1-benzyl-3-hydroxy-3-(7-methoxy-1H-indol-3-yl)indolin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate In water; N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere;
  • 39
  • [ 3189-22-8 ]
  • [ 50342-08-0 ]
  • 1-((4,5-dihydro-1H-imidazol-2-yl)methyl)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% Stage #1: 7-methoxy-1H-indole With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.25h; Stage #2: 2-(chloromethyl)-imidazoline In tetrahydrofuran; mineral oil at 20℃; for 6h; 13 General procedure for the preparation of 1-((4,5-dihydro-1H-imidazol-2-yl)methyl)-1H-indoles (3a-n) General procedure: Sodium hydride (0.53 g, 6.6 mmol, 60% oil dispersion) wasadded to the stirred solution of the corresponding indole 1(3.3 mmol) in anhydrous THF (2 mL) at room temperature. After15 min, freshly prepared 2-(chloromethyl)-4,5-dihydro-1H-imidazole2 (0.47 g, 4.0 mmol) was added and the reaction mixture wasstirred at ambient temperature for 6 h. The N-alkylation products 3were isolated upon quenching the reaction mixture with water(5 mL) followed by extraction with dichloromethane (3 5 mL).The combined organic layers were dried over anhydrous sodiumsulfate and evaporated under reduced pressure. The oily residuethus obtained was purified on silica with use of chromatotron(Et3N/MeOH/AcOEt 1:5:100). The products were very polar with Rfvalues close to 0.05.The products 3a-n were then converted into water-soluble hydrochloridesor hydrobromides suitable for biological tests with useof methanolic hydrochloric or hydrobromic acid solutions.
  • 40
  • [ 3189-22-8 ]
  • [ 7677-24-9 ]
  • 7-methoxy-2-(7-methoxy-1H-indol-3-yl)-3-oxoindoline-2-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium acetate; silver carbonate In N,N-dimethyl-formamide at 80℃; for 12h; regioselective reaction; 5. General Procedure for the Preparation of 6. General procedure: To a solution of indole (0.3 mmol), Ag2CO3 (0.105 mmol), TMSCN (0.2 mmol), and NaOAc (0.03 mmol) in DMF (1 mL) was added TEMPO (0.045 mmol) under an air atmosphere and the mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc/PE = 1:2) to yield the corresponding product 6.
  • 41
  • [ 3189-22-8 ]
  • [ 34157-83-0 ]
  • (2R,4aS,6aS,12bR,14aS,14bR)-10,11-dihydroxy-8-(7-methoxy-1H-indol-3-yl)-2,4a,6a,9,12b,14a-hexamethyl-1,2,3,4,4a,5,6,6a,8,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With aluminium(III) chloride hexahydrate In dichloromethane at 20℃; for 3h; Sealed tube; 3.3. General Procedure for the Friedel-Crafts Alkylation General procedure: Celastrol (2a, 0.222 mmol, 100 mg) and indole (3a, 0.266 mmol, 31 mg) were dissolved in dichloromethane (DCM, 2 mL) in a 10 mL closed tube. After intensive stirring at room temperature,the metal catalyst AlCl3.6H2O (5 mol %, 2.7 mg) was added to the solution and the reaction mixturewas stirred for 3 h. When the reaction was finished, pure water (20 mL) was added to stop the reaction and subsequently the aqueous phase was separated and extracted with ethyl acetate (20 mL) three times. The organic layers were combined and dried with anhydrous sodium sulfate. The solvent was removed in vacuo, giving a crude mixture which was purified by flash chromatography on silica column (hexane/ethyl acetate/AcOH = 4:1:0.005) to give the pure products 3a-3q, 1a2b, 1a2c.NMR spectra for all compounds can be found in Supplementary Materials.
With aluminium(III) chloride hexahydrate In dichloromethane at 20℃; for 5h; 31 Example 31. Preparation of Compounds XS0439, XS0442, XS0444-XS0449, XS0478-XS0480, XS0487 and XS0490 The preparation method is exemplified by XS0439: Compound YXY101 (100 mg, 0.22 mmol) was dissolvedin dichloromethane (4 mL) under stirring. 7-Methoxy-substituted indole (65.3 mg, 0.44 mmol) was added, then aluminumtrichloride hexahydrate (5.3 mg, 0.022 mmol). The reaction was carried out under stirring at room temperature for 5hours. The reaction was stopped, the reaction mixture was added with deionized water (15 mL) and extracted threetimes with ethyl acetate. The ethyl acetate layers were combined, washed with saturated NaCL three times, dried overanhydrous Na2SO4, concentrated by a rotary evaporator to obtain a crude product (brown oily matter). The crude productwas separated and purified by rapid column chromatography (ethyl acetate: n-hexane = 1 : 4), dried in vacuo to afforda product as purple red solid. 1H-NMR (DMSO-d6) δ ppm 0.71 (s, 3H), 0.86 (d, J=9.9 Hz, 1H), 0.96 (s, 3H), 1.01 (s, 3H), 1.10 (s, 3H), 1.22-1.29(m, 2H), 1.32 (s, 3H), 1.34-1.40 (m,2H), 1.45 (d, J=8.1 Hz, 1H), 1.50-1.61 (m, 3H), 1.62-1.75 (m, 2H), 1.79 (s, 3H),1.96-2.08 (m, 3H), 2.34 (d, J=15.4 Hz, 1H), 3.88 (s, 3H), 4.79 (d, J=5.9 Hz, 1H), 6.12 (d, J=6.2 Hz, 1H), 6.18 (s, 1H),6.62 (d, J=7.7 Hz, 1H), 6.73 (s, 1H), 6.90 (t, J=7.9 Hz, 1H), 7.22 (d, J=7.9 Hz, 1H), 7.88 (br. s., 1H), 8.99 (br. s., 1H),10.69 (s, 1H), 12.04 (br. s., 1H). 13C-NMR (DMSO-d6) δ ppm 11.9, 18.5, 22.3, 29.1, 29.9, 30.4, 30.5, 30.6, 31.8, 32.9, 34.9, 35.4, 35.5, 35.6, 36.8, 36.9, 37.8, 43.5, 44.3, 55.4, 101.8, 108.8, 112.2, 119.2, 119.8, 121.1, 121.6, 122.6, 126.3, 126.7, 128.5, 140.8,141.4, 144.0, 146.6, 147.0, 180.0.
  • 42
  • [ 3189-22-8 ]
  • [ 1354707-64-4 ]
  • 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% In benzene at 80℃; for 14h; 1.1 4- (2,4-Difluorophenyl) -2- (7-methoxy-1 H-indole-3-y4-oxobutanoic acid (hereinafter sometimes referred to as "present compound 8" for convenience)) 7-methoxyindole (1083 mg, 7.36 mmol) was dissolved in a 50 mL round bottom flask(E) -4- (2,4-difluorophenyl) -4-oxo-2-butenoic acid(1041 mg, 4.90 mmol) was added and dissolved with benzene (20 mL), and at 80 ° C.And heated to reflux for 14 hours. Distilled water (50 mL) was added to the reaction solution, ethyl acetate (50ML). The organic layer was washed with brine (30 mL), then anhydrous sodium sulfateDehydrated, and concentrated under reduced pressure. The product obtained by concentrating was filtered with Kiriyama fun and benzene and aceRecrystallization from tons followed by recrystallization from chloroform gave 4- (2,4-difeRuorophenyl) -2- (7-methoxy-1 H-indol-3-yl) -4-oxobTannic acid (1179 mg, yield 67%) was obtained as colorless crystals.
67% In benzene at 80℃; for 14h; Inert atmosphere; 1 Synthesis of 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic Acid (Compound(5-2)) In a 50-mL round-bottomed flask, 7-methoxyindole (1083 mg, 7.36 mmol) was added and (E)-4-(2,4-difluorophenyl)-4-oxo-2-butenoic acid (1041 mg, 4.90 mmol) was dissolved in benzene (20 mL) and the mixture was heated at 80° C. for 14 hours to reflux. Distilled water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (50 mL). The organic layer was washed with saturated saline (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The product obtained by the concentration was filtrated with a Hirsch funnel, and the residue was recrystallized from benzene and acetone to obtain 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid (1179 mg, yield: 67%) as a colorless crystal.Melting point: 181 to 183° C.;1H-NMR (400 MHz, acetone-d6) δ10.26 (s, 1H), 8.01 (m, 1H), 7.35 (d, J=8.0, 1H), 7.28 (d, J=2.8, 1H), 7.12-7.20 (m, 2H), 6.98 (t, J=7.8, 1H), 6.67 (d, J=7.8, 1H), 4.54 (dd, J=10.8, 3.6, 1H), 4.03 (ddd 18.8, 10.6, 3.3, 1H), 3.92 (s, 3H), 3.36 (td, 18.6, 3.2, 1H);13C-NMR (100 MHz, acetone-d6) δ1195.28, 174.98, 166.54 JC-F (dd, 252, 12 Hz), 163.48 JC-F (dd, 252, 12 Hz), 147.35, 133.44 JC-F (dd, 11, 4 Hz), 128.81, 127.83, 123.22, 123.05 JC-F (dd, 13, 4 Hz), 120.43, 113.76, 112.94 JC-F (dd, 22, 4 Hz), 112.7, 105.59 JC-F (t, 27 Hz), 102.52, 55.52, 46.97 JC-F (d, 8 Hz), 38.59;FAB-MS m/z=360 [M+H]+
In benzene at 80℃; for 14h; Inert atmosphere; 1 Synthesis of 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid (Compound (5-2)) Synthesis of 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid (Compound (5-2)) In a 50-mL round-bottomed flask, 7-methoxyindole (1083 mg, 7.36 mmol) was added and (E)-4-(2,4-difluorophenyl)-4-oxo-2-butenoic acid (1041 mg, 4.90 mmol) was dissolved in benzene (20 mL) and the mixture was heated at 80° C. for 14 hours to reflux. Distilled water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (50 mL). The organic layer was washed with saturated saline (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The product obtained by the concentration was filtrated with a Hirsch funnel, and the residue was recrystallized from benzene and acetone to obtain 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid (1179 mg, yield: 67%) as a colorless crystal. Melting point: 181 to 183° C.; 1H-NMR (400 MHz, acetone-d6) δ 10.26 (s, 1H), 8.01 (m, 1H), 7.35 (d, J=8.0, 1H), 7.28 (d, J=2.8, 1H), 7.12-7.20 (m, 2H), 6.98 (t, J=7.8, 1H), 6.67 (d, J=7.8, 1H), 4.54 (dd, J=10.8, 3.6, 1H), 4.03 (ddd 18.8, 10.6, 3.3, 1H), 3.92 (s, 3H), 3.36 (td, 18.6, 3.2, 1H); 13C-NMR (100 MHz, acetone-d6) δ 1195.28, 174.98, 166.54 JC-F (dd, 252, 12 Hz), 163.48 JC-F (dd, 252, 12 Hz), 147.35, 133.44 JC-F (dd, 11, 4 Hz), 128.81, 127.83, 123.22, 123.05 JC-F (dd, 13, 4 Hz), 120.43, 113.76, 112.94 JC-F (dd, 22, 4 Hz), 112.7, 105.59 JC-F(t, 27 Hz), 102.52, 55.52, 46.97 JC-F(d, 8 Hz), 38.59; FAB-MS m/z=360 [M+H]+
Synthesis of 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic Acid (Compound(5-2)) Synthesis of 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic Acid (Compound(5-2)) In a 50-mL round-bottomed flask, 7-methoxyindole (1083 mg, 7.36 mmol) was added and (E)-4-(2,4-difluorophenyl)-4-oxo-2-butenoic acid (1041 mg, 4.90 mmol) was dissolved in benzene (20 mL) and the mixture was heated at 80° C. for 14 hours to reflux. Distilled water (50 mL) was added to the reaction mixture, and extracted with ethyl acetate (50 mL). The organic layer was washed with saturated saline (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The product obtained by the concentration was filtrated with a Hirsch funnel, and the residue was recrystallized from benzene and acetone to obtain 4-(2,4-difluorophenyl)-2-(7-methoxy-1H-indol-3-yl)-4-oxo-butanoic acid (1179 mg, yield: 67%) as a colorless crystal. Melting point: 181 to 183° C.; 1H-NMR (400 MHz, acetone-d6) δ10.26 (s, 1H), 8.01 (m, 1H), 7.35 (d, J=8.0, 1H), 7.28 (d, J=2.8, 1H), 7.12-7.20 (m, 2H), 6.98 (t, J=7.8, 1H), 6.67 (d, J=7.8, 1H), 4.54 (dd, J=10.8, 3.6, 1H), 4.03 (ddd 18.8, 10.6, 3.3, 1H), 3.92 (s, 3H), 3.36 (td, 18.6, 3.2, 1H); 13C-NMR (100 MHz, acetone-d6) δ1195.28, 174.98, 166.54 JC-F (dd, 252, 12 Hz), 163.48 JC-F (dd, 252, 12 Hz), 147.35, 133.44 JC-F (dd, 11, 4 Hz), 128.81, 127.83, 123.22, 123.05 JC-F (dd, 13, 4 Hz), 120.43, 113.76, 112.94 JC-F (dd, 22, 4 Hz), 112.7, 105.59 JC-F (t, 27 Hz), 102.52, 55.52, 46.97 JC-F (d, 8 Hz), 38.59; FAB-MS m/z=360 [M+H]+

  • 43
  • [ 50-00-0 ]
  • [ 3189-22-8 ]
  • [ 109021-59-2 ]
YieldReaction ConditionsOperation in experiment
88% With iron(III) chloride; ammonia In water; N,N-dimethyl-formamide at 130℃; for 1.5h; Indolecarbaldehydes 2a-2aa; General Procedure General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol,1.0 equiv), 37% aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25% aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g,2 mol%), and DMF (2 mL). The flask was fitted with a reflux condenser,and the mixture was stirred at 130 °C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL),and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane-EtOAc).
  • 44
  • [ 3189-22-8 ]
  • [ 65094-22-6 ]
  • 3-[(difluoromethyl)thio]-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% Stage #1: 7-methoxy-1H-indole With water; iodine; thiourea; potassium iodide In 1,4-dioxane at 20℃; Stage #2: With sodium hydroxide In 1,4-dioxane at 50℃; for 1h; Stage #3: diethyl (bromodifluoromethyl)phosphonate In 1,4-dioxane at 20℃; for 4h;
  • 45
  • [ 3189-22-8 ]
  • sodium 1-(tert-butoxycarbonyl) azetidine-3-sulfinate [ No CAS ]
  • C17H22N2O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With iodine; triphenylphosphine In ethanol at 70℃; for 24h; regioselective reaction; General Procedure A: Coupling of Azetidine Sulfinate Salt 1 to Indoles General procedure: Iodine (1.0 equiv) was added to indole (1.0 equiv), PPh3 (2.0 equiv), and sodium 1-(tert-butoxycarbonyl) azetidine-3-sulfinate (1, 2.0 equiv) in EtOH (0.5 mL) at r.t. The resulting solution was stirred at 70 °C for 1 d. All volatiles were removed in vacuo. Purification by recrystallization or by flash chromatography over silica gel, eluting with PE/EtOAc (0-30%) afforded the desired thioindoles.
  • 46
  • [ 3189-22-8 ]
  • [ 766-77-8 ]
  • 1-(dimethyl(phenyl)silyl)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With dodecacarbonyl-triangulo-triruthenium In toluene at 120℃; for 12h; Schlenk technique; Inert atmosphere; 4.2. General procedure for Ru3(CO)12-Catalyzed dehydrogenative Si-N coupling General procedure: Condition A: A mixture of 33 indole (1) (0.2mmol, 1 equiv), hydrosilane (2) (0.3mmol, 1.5 equiv), 16 Ru3(CO)12 (1.9mg, 0.003mmol, 1.5mol %), were weighted in a Schlenk tube equipped with a stir bar. Dry 11 toluene (2.0mL) was added and the mixture was stirred at 120°C for 12h under Ar atmosphere. Afterwards, it was diluted with CH2Cl2 and transferred to a 50mL round bottom flask. Silica was added to the flask and solvents were evaporated under reduced pressure. Flash column chromatography on silica gel with EtOAc:petroleum ether=1:100 as eluent afforded the 47 N-silylated indole.
  • 47
  • [ 1196-57-2 ]
  • [ 3189-22-8 ]
  • 3-(7-methoxy-1H-indol-3-yl)quinoxalin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With iodine In methanol at 20℃; for 8h; Iodine-Catalyzed Oxidative Cross-Dehydrogenative Coupling of Quinoxalin-2(1H)-ones 1 and Indoles 2; General Procedure General procedure: To a 2 dram vial (8 mL) equipped with a magnetic stir bar were added quinoxalinone 1 (0.50 mmol, 1.0 equiv), indole 2 (0.55 mmol, 1.1 equiv), molecular I2 (7.2 mg, 0.05 mmol, 0.10 equiv), and CH3OH (1.00 mL), respectively. The reaction mixture was stirred at r.t. under atmospheric air for 8 h. Upon completion, distilled deionized H2O (10 mL) and sat. aq Na2S2O3 (5 mL) were added, and the mixture was extracted with EtOAc (2 x 10 mL). The combined organic layers were washed with brine, dried (anhyd Na2SO4), and concentrated in vacuo. The crude product was purified by SiO2 column chromatography to afford the desired indolylquinoxalin-2(1H)-one product 3.
  • 48
  • [ 3189-22-8 ]
  • [ 40996-91-6 ]
  • 3-(2-(7-methoxy-1H-indol-3-yl)ethyl)cyclohex-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With bismuth(lll) trifluoromethanesulfonate In methanol; acetonitrile at 60℃; for 3h; Sealed tube; regioselective reaction; 5.13 5.4 Representative procedure for the 1,6-addition of electron-rich heteroarenes to 3-vinyl-2-cyclohexenone General procedure: To a 1 dram vial was added Bi(OTf)3 (6.7mg, 0.010mmol, 0.025 equiv), indole (47mg, 0.40mmol), 3-vinyl-2-cyclohexenone (97.7mg, 0.80mmol), and acetonitrile/methanol (10:1) solution (0.8mL). The vial was sealed with a PFTE/silicone-lined septum cap. The reaction was heated to 60°C and allowed to stir at this temperature for 3h. The mixture was cooled and concentrated under reduced pressure. The crude reaction mixture was purified by flash column chromatography on silica gel (hexanes/ethyl acetate=80:20 to 70:30) to yield a white solid (82.1mg, 0.343mmol, 86%).
  • 49
  • [ 3189-22-8 ]
  • [ 882-33-7 ]
  • 7-methoxy-3-(phenylthio)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 2h;
63% With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 2h; 8 Example 8 7-methoxyindole (0.2 mmol) was added to a 4 mL reaction flask.1,2-diphenyldisulfide (0.3 mmol),Potassium tert-butoxide (0.4 mmol) and DMF (2.0 mL) were stirred at room temperature. TLC tracks the detection reaction. After 2 hours, the starting material was completely converted.Water and dichloromethane were added to the reaction system, and the organic layer was separated.Wash the water layer twice with dichloromethane, combine all the organic layers, andWash twice with water. The organic layer was dried over anhydrous sodium sulfate, concentrated, and then purified by column chromatography (To the product 32 mg, the yield was 63%, and the reaction process was as follows:
  • 50
  • [ 3189-22-8 ]
  • (1H-indol-4-yl)(phenyl)methanol [ No CAS ]
  • 3-[(1H-indol-4-yl)(phenyl)methyl]-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In acetonitrile at 70℃; for 15h; 4-[(1H-Indol-3-yl)methyl]-1H-indoles 3; General Procedure General procedure: Catalyst 4a (0.01 mmol), 4-indolylmethanol 1 (0.1 mmol) and 1H-in-dole (2; 0.4 mmol) were mixed in 1,2-dichloroethane (0.5 mL) in a dried tube. Then, the mixture was stirred at 70 °C for 15 h. After thecompletion of the reaction which was determined by TLC, the mix-ture was concentrated in vacuo. The residue was purified throughpreparative TLC to afford pure products 3.
  • 51
  • [ 3034-53-5 ]
  • [ 3189-22-8 ]
  • 7-methoxycamalexin [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% Stage #1: 7-methoxy-1H-indole With magnesium; methyl iodide In diethyl ether at 20℃; Stage #2: 2-bromo-1,3-thiazole In benzene for 24h; Reflux; 3 3.2.1 General procedure for preparation of camalexins using Ayer's method General procedure: Methyl iodide (for mono-methoxyindoles: 47µL, 0.78mmol, 2.9eq; for di-methoxyindoles: 40µL, 0.66mmol, 2.9eq) was added to the mixture of Mg (for mono-methoxyindoles: 13.6mg, 0.54mmol, 2.0eq; for di-methoxyindoles: 11.6mg, 0.46mmol, 2eq) in dry Et2O (1.0mL) under argon at room temperature. After all magnesium was dissolved, ether was distilled off and dry benzene (0.50mL) was added to the reaction mixture. A solution of methoxyindole (for mono-methoxyindoles: 40mg, 0.27mmol, 1.0eq; for di-methoxyindoles: 40mg, 0.23mmol, 1.0eq) in dry benzene (1.5mL) was added drop wise to the reaction mixture. The reaction mixture was stirred for an additional 10min, followed by addition of 2-bromothiazole (for mono-methoxyindoles: 57µL, 0.57mmol, 2.1eq; for di-methoxyindoles: 48µL, 0.48mmol, 2.9eq) q) and heating at reflux for 24h. The reaction mixture was quenched with cold water, neutralized with HCl (5%) and extracted with EtOAc. The combined extracts dried and concentrated to dryness. The residue was fractionated by FCC on silica gel (EtOAc-hexane, 3:7) to afford camalexin (1a), methoxycamalexins 1c-1, 1h and 1k.
  • 52
  • [ 3189-22-8 ]
  • [ 59633-90-8 ]
  • C23H31NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With tin(II) trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 3h; 1 Example 1: Synthesis of sesquiterpene fluorene 4 Taking ketene sesquiterpene 3.09 g (2,15.0 mmol) and 7-methoxy oxime 2.2 g (3,15.0 mmol) in 100 ml of 1,2-dichloroethane,Add 0.63 g (1.5 mmol) of tin triflate,The reaction was stirred at room temperature for 3 hours, and the reaction was terminated by TLC.Add 100 ml of water and wash the reaction solution.Aqueous methylene chloride extraction (30 mL x 2),The organic phase is washed with saturated brine,Dry over anhydrous sodium sulfate,Filtered, concentrated, and purified by column chromatography.A white solid of 5.09 g was obtained in a yield of 96%.
  • 53
  • [ 3189-22-8 ]
  • [ 137-26-8 ]
  • 7-methoxy-1H-indol-1-yl dimethylcarbamodithioate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With potassium <i>tert</i>-butylate In 1,2-dichloro-ethane at 20℃; for 1h; General procedure for the synthesis of products 3 General procedure: A mixtureof indole 1 (0.2 mmol), bis(dialkylaminethiocarbonyl)disulfide 2(0.22 mmol), t-BuOK (0.4 mmol), and DCE (2 mL) were added in a5mL glass tube, which was stirred at room temperature for 1e4h.When the reaction was completed, it was mixed with water andethyl acetate. The reaction mixture was extracted three times withethyl acetate. The combined organic layer was dried over anhydrousmagnesium sulfate and filtered. The filtrate was evaporatedunder vacuum and the residue was purified by flash columnchromatography on silica gel (eluted with petroleum ether-ethylacetate) to provide the desired products 3.
81% With potassium <i>tert</i>-butylate In 1,2-dichloro-ethane at 25℃; for 1h; 9 Example 9 7-methoxyindole (0.2 mmol), N,N,N',N'-tetramethylthiuram (0.22 mmol) were added to a 5 mL reaction flask.Potassium tert-butoxide (0.4 mmol) and DCE (2.0 mL) were stirred at room temperature. TLC tracks the detection reaction. After 1 hour, the reaction was stopped.Water and ethyl acetate were added to the reaction mixture, the organic layer was separated, and then aqueous layer was washed three times with ethyl acetate.Combine all the organic layers, dry over anhydrous sodium sulfate, concentrate, and then chromatograph (17% ethyl acetate petroleum ether)The product was obtained in 43.1 mg, yield 81%.
  • 54
  • [ 3189-22-8 ]
  • [ 56-45-1 ]
  • 7-methoxy-D-tryptophan [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: 7-methoxy-1H-indole; L-serin With Salmonella enterica tryptophan synthase In methanol; aq. phosphate buffer at 37℃; Enzymatic reaction; Stage #2: With (2R)-aspartic acid In methanol; aq. phosphate buffer Stage #3: In aq. phosphate buffer; deuteromethanol at 37℃; Enzymatic reaction; stereoselective reaction;
  • 55
  • [ 3189-22-8 ]
  • [ 6904-16-1 ]
  • 2-[2-(7-methoxy-1H-indol-3-yl)but-3-en-1-yl]malononitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With bis(1,5-cyclooctadiene)diiridium(I) dichloride; toluene-4-sulfonic acid In acetonitrile at 50℃; for 12h; Inert atmosphere; Schlenk technique; regioselective reaction; Reaction of Vinylcyclopropanes with Indoles; General Procedure General procedure: Under an argon atmosphere, indole 2 (0.1 mmol) and iridium complex(6.7 mg, 0.01 mmol) were added to a dry Schlenk tube. Then, asolution of vinylcyclopropane 1 (0.2 mmol) and p-toluenesulfonic acid (2 mg, 0.01 mmol) in MeCN (1 mL) was added to the reactionmixture, which was stirred at 50 °C for 12 h. After the completion ofthe reaction (TLC monitoring), the mixture was purified by preparativeTLC (eluent for all products: PE/EtOAc, 3:1) to afford the respectivepure product 3.
  • 56
  • [ 3189-22-8 ]
  • [ 87751-69-7 ]
  • (S,E)-3-(1,3-diphenylallyl)-7-methoxy-1H-indole [ No CAS ]
  • (E)-3-(1,3-diphenylallyl)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
84 % ee With bis(η3-allyl-μ-chloropalladium(II)); (S)-2′-(tert-butyl)-7-(diphenylphosphino)-2,3-dihydro-5′H-spiro[indene-1,4′-oxazole]; caesium carbonate In toluene at 25℃; for 12h; Schlenk technique; Inert atmosphere; Overall yield = 86 %; enantioselective reaction; 3.2. General Procedure for the Pd-Catalyzed Asymmetric Allylic Alkylation of Indoles General procedure: Ligand L1 (5.0 mg, 4 mol%) and [Pd(C3H5)Cl]2 (2.2 mg, 2 mol%) were dissolved in toluene(1.0 mL) in a Schlenk tube under Ar. After 0.5 h of stirring at room temperature, allylic acetate 2(0.36 mmol) dissolved in toluene (0.5 mL) was added, followed by indole 1 (0.3 mmol), and Cs2CO3(195 mg, 0.6 mmol). The mixture was stirred at room temperature for 12 h and then was diluted with CH2Cl2 and washed with saturated NH4Cl (aq). The organic layers were dried over MgSO4 and filtered, and the solvents were evaporated in vacuo. The residue was purified by flash column chromatography, eluting with petroleum ether and ethyl acetate to afford the corresponding product 3.
  • 57
  • [ 3189-22-8 ]
  • [ 50341-24-7 ]
  • C24H19NO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% With potassium dihydrogenphosphate; dipotassium peroxodisulfate; copper(I) bromide In acetonitrile at 80℃; for 12h; 35 In 10 ml reaction tube joining the benzofuran derivative (R1 =4 - methyl, R2 =H) 0.24 mmol and indole derivatives (R4 =5 - methoxy) 0.2 mmol, cuprous bromide 10 μM %, potassium persulphate 0.4 mmol, potassium dihydrogen phosphate 0.4 mmol and acetonitrile 2 ml, reaction in the 80 °C under 12 h. After the reaction is completed, the column chromatography separation to obtain the target compound B (R1 =4 - methyl, R2 =H, R4 =5 - methoxy), to obtain white solid, yield of 39%.
  • 58
  • [ 3189-22-8 ]
  • 7,7′-dimethoxyindigo [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1-Benzyl-1,4-dihydronicotinamide; 1,4-dithio-L-threitol; gordonia polyisoprenivorans NBRC 16320; flavin adenine dinucleotide; catalase In glycerol at 30℃; for 1h; Enzymatic reaction;
With CYP<SUB>BM3</SUB>F87A; dihydrogen peroxide In aq. phosphate buffer; N,N-dimethyl-formamide Green chemistry; Enzymatic reaction; 2.2. Enzymatic synthesis of dyes General procedure: For different substrates were assayed: indole, 4-bromoindole, 5-methoxyindole and 7-methoxyindole. Indole was dissolved in Milli-Qwater, while the other substrates were dissolved in dimethylformamide(DMF). The reaction medium (1 mL) contained 4.5 nmoles ofCYPBM3F87A, 0.5 mM substrate (added in 100 L of DMF) in a 50 mMphosphate buffer, pH 8. The reaction was started adding 10 mMhydrogen peroxide and monitored in a spectrophotometer (PerkingElmer Lambda 25). The dye formation was determined for indigo at 670nm with an extinction coefficient of 3900 M 1cm 1 [36], for 4,4-dibromoindigoat 605 nm with an extinction coefficient of 14,089 M 1cm 1,for 5,5-dimethoxyindigo at 630 nm with a extinction coefficient of 2652M 1cm 1, and for 7,7-dimethoxyindigo at 635 nm with an extinctioncoefficient of 4312 M 1cm 1. The extinction coefficients of bothmethoxyindigos were determined by synthesizing the dye by theBaeyer-Drewson procedure. The chemical nature of synthetized dimethoxyindigos was confirmed by NMR analysis
  • 59
  • [ 3189-22-8 ]
  • [ 39828-35-8 ]
  • (7-methoxy-1H-indol-3-yl)(2,4-dimethoxyphenyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With aluminum (III) chloride; trichlorophosphate In 1,2-dichloro-ethane at 60℃; for 2.5h; 4.1 General procedure for the synthesis of compounds 1-12 General procedure: A mixture of methoxy indole (2mmol) and methoxy benzoylchloride (2mmol) was stirred in the presence of POCl3 (5ml) and AlCl3 (0.5g) in dichloroethane (10ml) at 60°C for 2.5h. The reaction was quenched by 30ml crushed ice and then extracted with dichloromethane (3×30ml). The combined organic layer was washed by saturated sodium carbonate until PH=7, washed with saturated aqueous sodium chloride, dried over with anhydrous Na2SO4, and evaporated to give the crude product. The obtained residue was purified by column chromatography on silica gel using petroleum ether-acetone as the eluent to produce compounds 1-12.
  • 60
  • [ 3189-22-8 ]
  • [ 1071-73-4 ]
  • 3-(tetrahydro-2-methyl-2-furanyl)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With tris(pentafluorophenyl)borate; In 1,2-dichloro-ethane; at 55℃; Take 147 mg (1 mmol) of 7-methoxyindole, 153 mg (1.5 mmol) of 5-hydroxy-2-pentanone and 5.12 mg (0.01 mmol) of tris(pentafluorophenyl)borane, and add 10 mL of reaction tube The reaction was stirred at 55 C, and the mixture was evaporated to dryness. Column chromatography separation (petroleum ether: ethyl acetate = 10:1),The product was obtained as a 3-(tetrahydro-2-methyl-2-furanyl)-7-methoxy-1H-indole 153 mg, yield: 66%.
  • 61
  • [ 3189-22-8 ]
  • [ 930-68-7 ]
  • 3-(7-methoxy-1H-indol-3-yl)cyclohex-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With tert.-butylhydroperoxide; palladium(II) trifluoroacetate; 2,5-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-pyrano[2,3-b]quinoline In tetrahydrofuran; dimethyl sulfoxide at 50℃; for 24h; 3 Example 3: Synthesis of 3-(7-methoxy-1H-indol-3-yl)cyclohex-2-enone (1) 7-Methoxyindole (0.033 mL, 0.25 mmol), cyclohexenone (0.097 mL, 1 mmol), palladium trifluoroacetate (0.0083 g, 0.025 mmol), 2,5-dimethyl -8-trifluoromethyl-3,4-dihydro-2H-pyrano[2,3-b]quinoline (0.0141 g, 0.05 mmol), tert-butyl peroxide (0.075 mL, 0.375 mmol), dimethyl sulfoxide (0.8 mL) and tetrahydrofuran (0.4 mL) were stirred in a dry clean closed reaction tube and heated to 50 ° C for 24 hours. (2) After completion of the reaction, the reaction tube was cooled to room temperature, and 50 ml of ethyl acetate was added to dilute the reaction solution, and transferred to a 100 mL separatory funnel, and 10 mL of saturated saline was added thereto, and the mixture was shaken and allowed to stand to separate the organic phase from the aqueous phase. The aqueous phase was extracted twice with 30 mL of ethyl acetate. EtOAc was evaporated. :1, v / v) separation and purification, rotary distillation to remove the solvent, the oil pump is drained, the product was obtained as a yellow-green oil (39.9 mg, yield 66%). The hydrogen spectrum and carbon spectrum are shown in Figure 5 and Figure 6,
66% With tert.-butylhydroperoxide; palladium(II) trifluoroacetate; 2,5-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-pyrano[2,3-b]quinoline In tetrahydrofuran; dimethyl sulfoxide at 50℃; for 24h; regioselective reaction;
  • 62
  • [ 3189-22-8 ]
  • [ 1859-03-6 ]
  • 7-methoxy-3-(phenylthio)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With ammonium iodide; 1,10-Phenanthroline; acetic acid In 1,4-dioxane at 100℃; for 6h; Sealed tube; 4.2. General procedure for the NH4I/1,10-phenanthroline catalyzed direct sulfenylation of N-heteroarenes with ethyl arylsulfinates General procedure: A Schlenk tube (25 mL) was charged with indole (0.3 mmol), ethyl arylsulfinate (0.4 mmol), NH4I (20 mol%), and 1,10-phenanthroline (10 mol%). 1,4-Dioxane (2 mL) and HOAc (0.5 mL) were added under air atmosphere, the tube was sealed and heated in an oil bath at 100 °C for 6 h. The crude mixture was allowed to cool to room temperature. Then, ethyl acetate and saturated aq. solution of NaCl (5 mL) were added and the layers separated. The aqueous phase was washed three times with ethyl acetate (5 mL x 3). The combined organic layers were dried over anhydrous MgSO4 and concentrated in vacuo. The crude was purified by flash column chromatography with Al2O3 (petroleum ether/EtOAc) giving desired products 3a-z and 4a-t.
  • 63
  • [ 3189-22-8 ]
  • [ 22746-09-4 ]
  • 2-(4-(4,6-dimethylpyrimidin-2-yl)piperazin-1-yl)-1-(7-methoxy-1H-indol-3-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With potassium carbonate; sodium iodide In acetonitrile for 24h; Reflux; General procedure for synthesis of mIPP and its derivatives (3-6). General procedure: Chloroacetylindole (1 equiv.) was added to a stirred mixture of 4,6-dimethyl-2-(piperazin-1-yl)pyrimidine (1 equiv.), potassium carbonate (3 equiv.) and sodium iodide (1 equiv.) in 60 mL of acetonitrile. The reaction mixture was stirred under reflux for 4 h. Upon completion of the reaction determined by TLC analysis, the reaction mixture was cooled to room temperature and acetonitrile was removed in vacuo to give a dry residue. The dry residue was washed with water to remove the salts and the precipitate was dissolved in methanol and dry-loaded onto silica gel. Crude dry-loaded on silica gel were purified by column chromatography (EA: Hexane = 1:100-3:1) to give mIPP and its derivatives.
  • 64
  • [ 3189-22-8 ]
  • [ 79-04-9 ]
  • [ 1018637-79-0 ]
YieldReaction ConditionsOperation in experiment
23% With 1,8-diazabicyclo[5.4.0]undec-7-ene In 1,2-dichloro-ethane at 90℃; Sealed tube; General procedure for direct acylation to obtain 7-methoxy and 7-chloro substituted 3-chloroacetylindole (9-10) General procedure: 7-substituted indoles (1 equiv.) was weighed in a microwave vial and the microwave vial was capped after adding the stir bar before purging with argon. 5 mL of dichloroethane (DCE) was added to the microwave vial to dissolve the 7-substituted indoles. DBU (1 equiv.) was added to the reaction mixture and heated in an oil bath to 90 C. Upon reaching 90 C, chloroacetyl chloride (1.1 equiv.) was added in a single portion into the microwave vial via syringe. The reaction was stirred and monitored with TLC hourly until product spot was observed and qualitative yield was obtained, before heating was stopped. The reaction mixture upon cooling was added to a water-methanol mixture of 6:1 under vigorous stirring to quench the reaction. The quenched reaction was allowed to stir for an additional 1 h and solid crude product was filtered with a sintered glass filter funnel before washing with water.The crude product was allowed to dry in an oven before dissolving in methanol. The dissolved crude product was dry loaded onto silica gel and was purified with column chromatography (EA: Hexane =1:100-1:4) to give the pure 7-substituted 3-chloroacetylindole. 2-Chloro-1-(7-methoxy-1H-indol-3-yl)ethanone (9): Brownish solid, yield: 23%. 1H NMR (400 MHz,DMSO-d6): = 12.27 (s, 1 H), 8.32 (d, J = 3.28 Hz, 1 H), 7.74-7.72 (d, J = 7.92 Hz, 1 H), 7.14 (t, J = 7.92 Hz,1 H), 6.82 (d, J = 7.44 Hz, 1 H), 4.88 (s, 2 H), 3.94 (s, 3H). 13C NMR (DMSO-d6): = 186.20, 146.27,133.96, 126.94, 126.59, 122.95, 114.10, 113.64, 103.86, 55.32, 46.48.
  • 65
  • [ 3189-22-8 ]
  • C8H6Cl2NO4S2(1-)*Na(1+) [ No CAS ]
  • N-(3,4-dichlorophenyl)-2-((7-methoxy-1H-indol-3-yl)thio)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
74.8% With iodine In dimethyl sulfoxide at 60℃; for 2h; General synthesis of compounds 14a-i and 14’a-j General procedure: To a solution of substitued indole (8.33mmol) in DMSO (30mL), compounds 13 or 13’ (12.5mmol) and I2 (0.42g, 1.67mmol) were added. The solution was stirred for 2h at 60 oC. After the completion of the reaction, ethyl acetate (400ml) was added and the mixture was washed with H2O (300mLX3), Na2S2O3 (sat. aq., 100mL) and NaCl (sat. aq., 100mL). The organic layer was dried with Na2SO4, concentrated and purified on a silica gel column to afford the product as a light brown solid.
  • 66
  • [ 3189-22-8 ]
  • C10H12NO5S2(1-)*Na(1+) [ No CAS ]
  • N-(2-ethoxyphenyl)-2-((7-methoxy-1H-indol-3-yl)thio)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68.8% With iodine In dimethyl sulfoxide at 60℃; for 2h; General synthesis of compounds 14a-i and 14’a-j General procedure: To a solution of substitued indole (8.33mmol) in DMSO (30mL), compounds 13 or 13’ (12.5mmol) and I2 (0.42g, 1.67mmol) were added. The solution was stirred for 2h at 60 oC. After the completion of the reaction, ethyl acetate (400ml) was added and the mixture was washed with H2O (300mLX3), Na2S2O3 (sat. aq., 100mL) and NaCl (sat. aq., 100mL). The organic layer was dried with Na2SO4, concentrated and purified on a silica gel column to afford the product as a light brown solid.
  • 67
  • [ 3189-22-8 ]
  • [ 67-64-1 ]
  • 3,3'-(propane-2,2-diyl)bis(7-methoxy-1H-indole) [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With oxygen; Langlois reagent In toluene at 20℃; for 24h; UV-irradiation; Schlenk technique; regioselective reaction;
  • 68
  • [ 3189-22-8 ]
  • [ 948-65-2 ]
  • 2-(7-methoxy-1H-indol-3-yl)-2-phenylindolin-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In tetrahydrofuran at 0℃; for 6h; General procedure for the synthesis of compounds19a-19z General procedure: The starting materials of A-series for the synthesis of 19t-19z were prepared as reported in the literature [17, 18],and others and all of B-series are commercially available.To a solution of A (0.1 mmol) and B (0.15 mmol) in THF was added TEMPO+BF4- (TEMPO oxoammonium tetrafluoroborate,0.1 mmol) at 0 °C. After 6 h, the solvent was removed under reduced pressure and the residue was purified by flash chromatography using acetone-petroleum ether as eluent to afford the desired product (Scheme 1).
  • 69
  • [ 3189-22-8 ]
  • [ 36635-61-7 ]
  • 7-methoxy-3-(tosylmethyl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With ferrous(II) sulfate heptahydrate In water at 110℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; General Procedure for Preparation of Products 3 and 4 General procedure: To a 15 mL two-necked Schlenk tube fitted with glass stopper were added indoles 1 (0.1 mmol),TosMIC derivatives 2 (0.3 mmol), and FeSO4·7H2O (0.015 mmol, 4.2 mg) in a mixed solvent of H2O and PEG400 (v/v = 3/2, 2 mL) under an Ar atmosphere using the standard Schlenk techniques. The Schlenk tube was capped and heated at 110 °C for 24 h. The reaction mixture was then cooled toroom temperature and concentrated directly. After removal of solvent, the residue was purified by preparative thin-layer chromatography (petroleum ether/EtOAc = 1:1) to give the desiredproduct 3 and 4.
  • 70
  • [ 3189-22-8 ]
  • [ 107249-49-0 ]
  • 3-(((4-chlorophenyl)sulfonyl)methyl)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With ferrous(II) sulfate heptahydrate In water at 110℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; General Procedure for Preparation of Products 3 and 4 General procedure: To a 15 mL two-necked Schlenk tube fitted with glass stopper were added indoles 1 (0.1 mmol),TosMIC derivatives 2 (0.3 mmol), and FeSO4·7H2O (0.015 mmol, 4.2 mg) in a mixed solvent of H2O and PEG400 (v/v = 3/2, 2 mL) under an Ar atmosphere using the standard Schlenk techniques. The Schlenk tube was capped and heated at 110 °C for 24 h. The reaction mixture was then cooled toroom temperature and concentrated directly. After removal of solvent, the residue was purified by preparative thin-layer chromatography (petroleum ether/EtOAc = 1:1) to give the desiredproduct 3 and 4.
  • 71
  • [ 3189-22-8 ]
  • [ 36635-63-9 ]
  • 7-methoxy-3-((phenylsulfonyl)methyl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With ferrous(II) sulfate heptahydrate In water at 110℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; General Procedure for Preparation of Products 3 and 4 General procedure: To a 15 mL two-necked Schlenk tube fitted with glass stopper were added indoles 1 (0.1 mmol),TosMIC derivatives 2 (0.3 mmol), and FeSO4·7H2O (0.015 mmol, 4.2 mg) in a mixed solvent of H2O and PEG400 (v/v = 3/2, 2 mL) under an Ar atmosphere using the standard Schlenk techniques. The Schlenk tube was capped and heated at 110 °C for 24 h. The reaction mixture was then cooled toroom temperature and concentrated directly. After removal of solvent, the residue was purified by preparative thin-layer chromatography (petroleum ether/EtOAc = 1:1) to give the desiredproduct 3 and 4.
  • 72
  • [ 3189-22-8 ]
  • [ 63591-85-5 ]
  • [ 57957-24-1 ]
  • C26H26N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With tris(1,10-phenathrolinyl)ruthenium(II) hexafluorophosphate; C50H56O4P(1-)*Li(1+) In dichloromethane at 30℃; for 36h; Irradiation; enantioselective reaction;
  • 73
  • [ 3189-22-8 ]
  • N-(tert-butyl)-2-diazo-N-((6-hydroxynaphthalen-2-yl)methyl)acetamide [ No CAS ]
  • 1'-(tert-butyl)-1-(7-methoxy-1H-indol-3-yl)-6H-spiro[naphthalene-2,3'-pyrrolidine]-5',6-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: 7-methoxy-1H-indole; N-(tert-butyl)-2-diazo-N-((6-hydroxynaphthalen-2-yl)methyl)acetamide With benzoic acid In dichloromethane at 20℃; for 2h; Inert atmosphere; Stage #2: With triethylamine; 2,3-dicyano-5,6-dichloro-p-benzoquinone In methanol; dichloromethane at 0℃; for 0.5h; Inert atmosphere;
  • 74
  • [ 3189-22-8 ]
  • [ 99440-99-0 ]
  • 2-(7-methoxy-1H-indol-3-yl)cyclobutanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With Amberlyst 15 In toluene at 50℃; Cyclobutyl Indoles 4; General Procedure General procedure: In a 5 mL glass vial, a mixture of 2-hydroxycyclobutanone (1a) (100mg, 1.1 mmol), indole 2a-v (1.0 mmol), Amberlyst 15 (10 mol%) and toluene (3.0 mL) was stirred at 50 °C. After completion of the reaction,the crude product was loaded on a silica gel column and purified byflash chromatography using hexanes/diethyl ether (10:1 to 3:1) as the eluent.
  • 75
  • [ 3189-22-8 ]
  • [ 1240045-39-9 ]
YieldReaction ConditionsOperation in experiment
68% With sodium bromide In 2,2,2-trifluoroethanol; dimethyl sulfoxide Electrochemical reaction; 18 Example 18 Assemble the electrochemical microchannel reaction device: first place the anode graphite sheet on the titanium alloy base, then place the 0.1mL PTFE reaction tank on the upper layer of the carbon sheet, then place the graphite sheet on the upper layer of the reaction tank, and finally Fix and connect the adjustable DC power supply with a PTFE screw. Weigh 58 mg of 7-methoxyindole and 82 mg of sodium bromide and dissolve them in 6 mL of dimethyl sulfoxide (DMSO) and 1 mL of trifluoroethanol to make a homogeneous solution. The prepared homogeneous solution was injected into the reaction module using a syringe pump at a flow rate of 0.05 mL/min. Turn on the power supply, adjust the current to 8 mA, and after it stabilizes, collect the product 2-bromo-7-methoxyindole from the outlet of the reaction module with a yield rate of 68%.
  • 76
  • [ 3189-22-8 ]
  • [ 98-83-9 ]
  • 7-methoxy-3-(2-phenylpropan-2-yl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With 1,1,1,3',3',3'-hexafluoro-propanol; tetrabutylammonium acetate at 90℃; for 24h; Inert atmosphere; Schlenk technique; Sealed tube;
88% With sodium carbonate In methanol at 85℃; for 29h; Inert atmosphere; 8 Example 8 Preparation of β-alkylindole derivatives (13): In a nitrogen atmosphere, add 0.5 mmol 7-methoxyindole, 1.0 mmol α-methylstyrene, 2 mL methanol, and 0.5 mmol sodium carbonate to a 10 ml reaction flask, and then pass nitrogen into the double-row tube and magnetically stir. It was heated to 85°C with an oil bath and reacted for 29 hours. Remove the oil bath, add 3 ml of water to the reaction solution, extract three times with 5 ml of ethyl acetate, combine the organic phases, dry with anhydrous MgSO4 for 30 minutes, and filter; The filtrate was concentrated with a rotary evaporator, and after concentration, ethyl acetate and petroleum ether (1:60, v:v) were used as eluents. After column chromatography, the pure product 13 was obtained with a yield of 88%.
  • 77
  • [ 3189-22-8 ]
  • [ 2009-97-4 ]
  • ethyl 2,2-bis(7-methoxy-1H-indol-3-yl)-3-oxobutanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With air In 2,2,2-trifluoroethanol; water at 120℃; for 12h; Sealed tube; General Procedure and Characterization of Products General procedure: A 50 mL tube with a stir bar was charged with H2O, substrates and fluorinated alcohol under air atmosphere. The tube was sealed with a Teflon-lined cap and the reaction mixture was stirred at 120 °C for 12 h. The solvents were revomed under vacuum and the residue was purified by flash chromatography on silica gel to provide the corresponding products.
  • 78
  • [ 3189-22-8 ]
  • [ 108-94-1 ]
  • [ 120329-58-0 ]
  • C75H17NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With iodine In 1,2-dichloro-benzene at 140℃; for 5h; Inert atmosphere; 6 Take a dry 15mL Shrek tube, add [60] fullerene (36.0mg, 0.05mmol), I2 (2.5mg, 0.01mmol), (0.15mmol) and (0.15mmol) as the reaction materials in sequence, and ultrasonic Dissolve the solid in the solvent anhydrous ODCB (4mL)After the medium, the reaction tube was placed in an oil bath at 140° C. and stirred and heated under a nitrogen atmosphere until the reaction was completed for 5 hours. Lift the reaction tube to cool to room temperature, after evaporating the solvent in a vacuum,The residue was separated on a silica gel column, using CS2 as the eluent to recover the unreacted [60] fullerene, and then using CS2/DCM (v/v=10:1) as the eluent to obtain the target product [60] The fullereno 1,2-tetrahydrocarbazole derivative 4ac, the isolated yield of the product 4ac is 33%.
  • 79
  • [ 3189-22-8 ]
  • [ 130-15-4 ]
  • 2-(7-methoxy-1H-indol-3-yl)naphthalene-1,4-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With trifluoroacetic acid In dichloromethane at 20℃; for 0.0708333h; Flow reactor; General procedure for the synthesis of 3-indolyl-1,4-naphthoquinone (3a-j) incontinuous flow General procedure: Indole derivatives (0.5 mmol, 1 equiv.) and 1,4-naphthoquinone (0.75 mmol, 1.5 equiv.)were dissolved in 2mL CH2Cl2 and pumped into inlet A, Trifluoroacetic acid (00.5equiv.) were dissolved in 2mL CH2Cl2. Inlet A and B were injected simultaneouslythrough 336 cm (2.96 cm3) mixing coil at flow rate 0.7-4.6 mL/min. The temperature ofmixing coil was maintained at room temperature throughout the reaction. The mixturecollected at the outlet was concentrated under vacuum was purified by flash columnchromatography on silica gel (EtOAc/Hexane) to provide pure 3-indolyl-1,4-naphthoquinone(3a-j) (Yield 94-99%, Time 4.25 min.). The flow system was cleaned with3mL of CH2Cl2 in both of inlet A and inlet B before the next reaction.
  • 80
  • [ 617-86-7 ]
  • [ 3189-22-8 ]
  • C15H23NOSi [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: 7-methoxy-1H-indole With C30H34ClIrN2 In o-xylene at 120℃; for 6h; Stage #2: triethylsilane With tert-butylethylene for 36h;
  • 81
  • [ 3189-22-8 ]
  • sodium difluoromethanesulfinate-d [ No CAS ]
  • 3-((difluoromethyl-d)thio)-7-methoxy-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With chloro-trimethyl-silane; phosphonic acid diethyl ester In toluene at 85℃; for 3h; Sealed tube;
  • 82
  • [ 90-04-0 ]
  • [ 75-07-0 ]
  • [ 3189-22-8 ]
YieldReaction ConditionsOperation in experiment
96% With C14H22B10Br2FeN2 In toluene at 20℃; for 3.33333h; 5 The ferrous complex prepared in Example 1 was used as a catalyst to catalyze the synthesis of indole derivatives: Toluene (toluene) solution of ferrous complex (0.005mmol) was added to 2-methoxyaniline (1mmol), then acetaldehyde (1mmol) was added, and the reaction was carried out at room temperature for 200 minutes. After completion, the reaction solution was concentrated and passed directly on silica gel Separate by column chromatography and dry until the mass remains unchanged to obtain the corresponding indole derivative C9H9NO (yield 96%)
  • 83
  • [ 3189-22-8 ]
  • [ 353-83-3 ]
  • 7-methoxy-3-((2,2,2-trifluoroethyl)thio)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With sodium dithionite; triphenylphosphine In water; dimethyl sulfoxide at 90℃; for 5h; Schlenk technique; Synthesis of fluoroethylthiolated indoles General procedure: indoles( 5 mmol) 1a , Na2S2O4 1.5 mmol ), additives and 2 ml solvent were added to a Schlenk sealed tube , following iodofluoroethane 2 (1.5 mmol) was added to the mixture solution and then the resulting mixture was string for 10 mins. After addition , the mixture was allowed for string 12h under set temperature. Then, 10ml water was added, and the reaction mixture was extracted by Ethyl acetate 3 times. The organic layer was combined, washed with brine for once and dried over Na2SO4 . The solvent was removed by reduce pressure rotary evaporation and purified by column chromatography on silica gel with Petroleum ether/ Ethyl acetate to give 3/ 4/ 5 .
  • 84
  • [ 3189-22-8 ]
  • [ 1422984-99-3 ]
  • C18H15F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% Stage #1: 7-methoxy-1H-indole With nickel(II) perchlorate hexahydrate; C53H42N2O2 In toluene at 20℃; for 1h; Inert atmosphere; Schlenk technique; Sealed tube; Stage #2: (E)-(3,3,3-trifluoro-1-nitroprop-1-en-2-yl)benzene In toluene at 85℃; for 36h; Inert atmosphere; Schlenk technique; Sealed tube; enantioselective reaction; 3.2 Asymmetric synthesis of indole derivatives containing a trifluoromethylated all-carbon quaternary center though 1,4-addition reactions General procedure: In an argon-filled glovebox, Ni(ClO4)2.6H2O (4.0 mg, 0.011 mmol, 11 mol%), L1 (7.4 mg, 0.01 mmol, 10 mol% ), and indole or substituted indole (0.15 mmol, 1.5 equiv.) were added to a Schlenk tube equipped with a magnetic stir bar. After the reaction tube was sealed with a rubber stopper, it was removed from the glove box and the newly distilled anhydrous toluene (1.0 mL) was added to the tube with a syringe. The reaction was stirred at room temperature for 1 hour and then the disubstituted nitroalkene (0.1 mmol, 1.0 equiv.) was added to the tube carefully with a microinjector. Subsequently, the Schlenk tube was placed into an oil bath which was pre-heated to 85 °C or 100 °C. In order to reduce the volatilization of the toluene, the upper part of the Schlenk tube was cooled by air flow from an electric fan. When the reaction was complete, the solvent was concentrated in vacuo and the residue was subjected to flash silica gel column chromatography (PE/EA = 10:1- 5:1) to afford the product. The enantiomeric excesses were determined by HPLC analysis using chiral stationary phases.
  • 85
  • [ 3189-22-8 ]
  • [ 1422984-99-3 ]
  • C18H15F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With nickel(II) perchlorate hexahydrate; 2,2'-biquinoline In toluene at 100℃; Inert atmosphere; Schlenk technique; Sealed tube; 2.3 Synthesis of the racemic products General procedure: In an argon-filled glovebox, Ni(ClO4)2.6H2O (4.0 mg, 0.011 mmol, 11 mol%), L (2.6 mg, 0.01 mmol, 10 mol% ), and indole (17.6 mg, 0.15 mmol, 1.5 equiv.) were added to a Schlenk tube equipped with a magnetic stir bar. After the reaction tube was sealed with a rubber stopper, it was removed from the glove box and the nitroalkene (0.1 mmol, 1.0 equiv.) and the newly distilled anhydrous toluene (1.0 mL) was added to the tube with a syringe subsequently. Then, the Schlenk tube was placed into an oil bath which was pre-heated to 100 °C and the reaction was stirred overnight. When the reaction was complete, the solvent was concentrated in vacuo and the residue was subjected to flash silica gel column chromatography (n-hexane /EA = 10:1- 5:1) to afford the racemic product.
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