Name: 90734-97-7|4-Methoxy-1H-indole-3-carbaldehyde|98%
Brand: Ambeed
SKU: A212127
Rating: 97 (28 reviews)

1
[ 487-89-8 ]
[ 124-41-4 ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: Indole-3-carboxaldehyde With thallium(III) trifluoroacetate In trifluoroacetic acid at 30℃; for 3h; Stage #2: With copper(l) iodide; iodine In N,N-dimethyl-formamide at 20℃; for 1h; Stage #3: sodium methylate In N,N-dimethyl-formamide at 100 - 110℃; for 3h;	4.2.1. 4-Methoxyindole-3-carboxylic acid (33) Indole-3-carboxaldehyde (100.2 mg; 0.69 mmol, 36) was added to a solution of thallium trifluoroacetate (562.1 mg, 1.03 mmol) in TFA (1.2 ml), and the mixture was stirred at 30 °C for 3 h. After evaporation of the solvent under reduced pressure, I2 (525.8 mg, 2.07 mmol), CuI (525.8 mg, 2.76 mmol), and DMF (5.0 ml) were added to the residue. After stirring the reaction mixture at r.t. for 1 h, NaOCH3 (15% w/v, 5 ml) was added and the stirring continued at 100-110 °C for 3 h. The reaction was cooled to room temperature, diluted with CH2Cl2-MeOH (95:5) and filtered through Celite. The filtrate was washed with water and brine, dried and concentrated under reduced pressure. Purification of the product by FCC over silica using EtOAc:hexane (3:1) as the eluent yielded pure 4-methoxyindole-3-carboxaldehyde (62.1 mg, 75%).
	Yield given. Multistep reaction;
	Stage #1: Indole-3-carboxaldehyde With trifluoroacetic acid; thallium(III) trifluoroacetate at 30℃; for 3h; Stage #2: With copper(l) iodide; iodine In N,N-dimethyl-formamide at 25℃; for 1h; Stage #3: sodium methylate In methanol; N,N-dimethyl-formamide at 110℃; for 1h;

Reference： [1]Location in patent: experimental part Pedras, M. Soledade C.; Hossain, Sajjad [Phytochemistry, 2011, vol. 72, # 18, p. 2308 - 2316]
[2]Somei, Masanori; Yamada, Fumio; Kunimoto, Masako; Kaneko, Chikara [Heterocycles, 1984, vol. 22, # 4, p. 797 - 801]
[3]Pedras, M. Soledade C.; Yaya, Estifanos E. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 7, p. 1149 - 1166]

2
[ 4837-90-5 ]
[ 68-12-2 ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
100%		4-Methoxy-1H-indole-3-carbaldehyde (17). N-Chlorosuccinimide (2.72 g, 20.41 mmol) was added portionwise to a solution of triphenylphosphine (5.35 g, 20.41 mmol) in tetrahydrofuran (100.0 mL) and stirred at room temperature for 30 min. DMF (1.54 mL, 40.8 mmol) was added to the suspension, and the mixture was heated to reflux for 1 h. Then <strong>[4837-90-5]4-<strong>[4837-90-5]methoxy-1H-indole</strong></strong> 16 (1.0 g, 6.80 mmol) was added and the mixture was heated to reflux for 1 h. After cooling, tetrahydrofuran was evaporated, water (80.0 mL) added, and the mixture heated to reflux for 1 h and then alkalinized with 10% NaOH. After the aqueous phase was extracted with EtOAc (3×50 mL) and the collected organic layers were dried and evaporated. The crude product was purified by means of flash chromatography (50% n-hexane in EtOAc) to give 17 as orange solid in quantitative yield: mp (EtOAc) 154-156 C.; 1H NMR (CDCl3) delta 4.00 (s, 3H), 6.72 (m, 1H), 7.07 (d, 1H, J=8.1 Hz), 7.19 (d, 1H, J=8.1 Hz), 7.92 (d, 1H, J=2.9 Hz), 9.05 (br s, 1H), 10.50 (s, 1H); FAB-MS m/z 175 (100) [M]+, 160, 144, 129, 116, 104, 89, 77. Anal. (C10H9NO2) C, H, N.
95%	With trichlorophosphate; at 0 - 45℃; for 1h;	Phosphoryl chloride (9.61 mL, 105 mmol) was added slowly over 3 min to anhydrous DMF (60 mL) at 0 C. A solution of 4-methoxyindole (10.30 g, 70.00 mmol) , in anhydrous DMF (40 mL) was then added slowly over 5 min. The resulting bright yellow suspension was heated to 45 C and stirred for 1 h. The reaction was then quenched with ice water (800 mL) , and the resulting purplish-brown solution was washed with Et20 (2 x 100 mL) (Note: If insufficient water is used, a voluminous precipitate may form during the Et20 washes.) . The washed aqueous layer was basified with concentrated aqueous NaOH (effervescence) , resulting in a color change to pale-yellow and slow formation of a crystalline precipitate (Note: This precipitate is an adduct of the product and should not be collected) . The basic mixture was then extracted with Et?0 (3 x 600 mL) (Note: Lesser quantities of Et20 can be used if the aqu^eous/organic mixture is left to stir overnight.), and the combined organics were washed with brine (200 mL) , dried over a2SO<j, and concentrated to provide the product 1 as a tan crystalline solid (11.69 g, 95%) . H NMR (400 MHz, CDC13) delta 10.51 (s, 1H), 8.96 (br s, 1H) , 7.93 (d, J = 3.1 Hz, 1H) , 7.22 (t, J = 8.0 Hz, 1H) , 7.08 (d, J = 8.2 Hz, 1H) , 6.73 (d, J = 7.9 Hz, 1H), 4.01 (s, 3H) ; 13C NMR (101 MHz, CDCI3) delta 188.6, 154.7, 137.9, 128.8, 124.5, 119.6, 116.3, 105.4, 102.8, 55.5.
85%		(5-1) Production of <strong>[4837-90-5]4-<strong>[4837-90-5]methoxy-1H-indole</strong></strong>-3-carbaldehyde (6a) A mixture of the indole (5a) (1.7 g, 11.55mmol, 1 eq) obtained in (4-1) and N,N-dimethylformamide (4.5 mL, 57.76 mmol, 5 eq) was stirred at 0C, and sodium pyrophosphate (1.9 mL, 13.86 mmol, 1.2 eq) was added dropwise to thismixture. The resulting solution was stirred at 0C for 0. 5 hour, and then, at 40C for 1 hour. Ice, and then, aqueous solution of sodium hydroxide (2M) was added, and the mixture was heated under reflux. The solution was extracted three times with ethyl acetate (50 mL). The extracts were combined, washed with aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated. The concentrate was subjected to silica gel flush chromatography using hexane-ethyl acetate (60-40) to give white solid of the title compound (6a) (1.72 g, yield 85%).

5.44 g		Example 50 3-Formyl-<strong>[4837-90-5]4-<strong>[4837-90-5]methoxy-1H-indole</strong></strong> Add phosphorus oxychloride (1.1 eq.) with vigorous stirring to DMF (cooled in an ice bath). After the addition is complete, allow to stir in the ice bath for ~10 minutes, then add a solution of <strong>[4837-90-5]4-<strong>[4837-90-5]methoxy-1H-indole</strong></strong> (5 g) in anhydrous DMF with vigorous stirring. Allow to stir at 0C. After 1 hour, warm to room temperature. After 16 hours, carefully add 4 eq. of 2N NaOH with vigorous stirring. Heat to about 80C and then cool. Pour the reaction mixture into cold water with vigorous stirring to give a solid. Collect the solid by filtration and dry in a vacuum oven at room temperature to give the title compound. Acidify the filtrate and extract with EtOAc. Combine the organic layers and wash with 50% brine. Collect the organic layer, dry (MgSO4) filter, and remove the solvent to give the title compound as a light purple solid. Total yield of the title compound is 5.44 g: MS (ES+): m/z 175 (M+H)+, 160 (M-CH3)+; (ES-): m/z 174 (M-H)-.
		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%.

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 151 - 169
[2]Patent: US2009/238761,2009,A1 .Location in patent: Page/Page column 27-28; 21
[3]Journal of the American Chemical Society,2016,vol. 138,p. 6754 - 6764
[4]Patent: WO2017/165738,2017,A1 .Location in patent: Page/Page column 67; 68
[5]Journal of Medicinal Chemistry,2004,vol. 47,p. 6270 - 6282
[6]Patent: EP1533299,2005,A1 .Location in patent: Page/Page column 10
[7]European Journal of Organic Chemistry,2002,p. 3995 - 4004
[8]Monatshefte fur Chemie,1990,vol. 121,p. 77 - 80
[9]Archiv der Pharmazie,1990,vol. 323,p. 427 - 432
[10]Chemical Communications,2012,vol. 48,p. 12243 - 12245
[11]Journal of Medicinal Chemistry,2015,vol. 58,p. 9179 - 9195
[12]Heterocycles,1984,vol. 22,p. 797 - 801
[13]Organic and Biomolecular Chemistry,2014,vol. 12,p. 9764 - 9768
[14]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 8453 - 8459
[15]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798
[16]RSC Advances,2015,vol. 5,p. 68128 - 68135
[17]Patent: EP1859798,2015,B1 .Location in patent: Paragraph 0203
[18]Chemistry - An Asian Journal,2015,vol. 10,p. 2738 - 2743
[19]Journal of Medicinal Chemistry,2016,vol. 59,p. 5264 - 5283
[20]Organic and Biomolecular Chemistry,2017,vol. 15,p. 7404 - 7410
[21]Organic and Biomolecular Chemistry,2018,vol. 16,p. 6647 - 6651
[22]European Journal of Medicinal Chemistry,2019,vol. 175,p. 357 - 372

3
[ 4837-90-5 ]
[ 122-51-0 ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
36%	With trichloroacetic acid In dichloromethane for 0.333333h; Ambient temperature;
36%	With trichloroacetic acid In dichloromethane for 0.333333h;

Reference： [1]Pindur, Ulf; Witzel, Helmut [Monatshefte fur Chemie, 1990, vol. 121, # 1, p. 77 - 80]
[2]Pindur; Witzel [Archiv der Pharmazie, 1990, vol. 323, # 7, p. 427 - 432]

4
[ 72527-73-2 ]
[ 124-41-4 ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
83.2%	With copper(l) iodide In methanol; N,N-dimethyl-formamide at 110 - 120℃; for 0.5h;

Reference： [1]Somei, Masanori; Yamada, Fumio; Kunimoto, Masako; Kaneko, Chikara [Heterocycles, 1984, vol. 22, # 4, p. 797 - 801]

5
[ 90734-97-7 ]
[ 52335-75-8 ]
[ 96888-16-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 57% 2: 19%	With sodium tetrahydroborate; dimethyl amine In water for 2h; Ambient temperature;

Reference： [1]Yamada, Fumio; Kobayashi, Kensuke; Shimizu, Aya; Aoki, Naokatsu; Somei, Masanori [Heterocycles, 1993, vol. 36, # 12, p. 2783 - 2804]

6
[ 90734-97-7 ]
[ 124-40-3 ]
[ 52335-75-8 ]
[ 96888-16-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 19% 2: 57%	With sodium tetrahydroborate In water for 2h; Ambient temperature;

Reference： [1]Yamada, Fumio; Kobayashi, Kensuke; Shimizu, Aya; Aoki, Naokatsu; Somei, Masanori [Heterocycles, 1993, vol. 36, # 12, p. 2783 - 2804]

7
[ 90734-97-7 ]
[ 98-59-9 ]
[ 217488-99-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine at 90 - 95℃; for 1h;

Reference： [1]Vangveravong, Suwanna; Kanthasamy, Arthi; Lucaites, Virginia L.; Nelson, David L.; Nichols, David E. [Journal of Medicinal Chemistry, 1998, vol. 41, # 25, p. 4995 - 5001]

8
[ 90734-97-7 ]
[ 143-33-9 ]
[ 4837-74-5 ]
N-(4-methoxyindol-3-yl)methylformamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 86% 2: 11%	With sodium tetrahydroborate In methanol; formamide at 100℃; for 5h;

Reference： [1]Yamada, Fumio; Hashizume, Tomoko; Somei, Masanori [Heterocycles, 1998, vol. 47, # 1, p. 509 - 516]

9
[ 335451-35-9 ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 0.166667h;

Reference： [1]Amat; Seffar; Llor; Bosch [Synthesis, 2001, # 2, p. 267 - 275]

10
[ 90734-97-7 ]
[ 98-09-9 ]
1-benzenesulfonyl-4-methoxy-1H-indole-3-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydride In tetrahydrofuran at 20℃;

Reference： [1]Ley, Steven V.; Priour, Alain [European Journal of Organic Chemistry, 2002, # 23, p. 3995 - 4004]

11
1-(2,2-dimethyl-propionyl)-4-methoxy-1H-indole-3-carbaldehyde [ No CAS ]
[ 90734-97-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With polymer-supported potassium thiophenolate In tetrahydrofuran; methanol at 40℃;

Reference： [1]MacCoss, Rachel N.; Henry, Dara J.; Brain, Christopher T.; Ley, Steven V. [Synlett, 2004, # 4, p. 675 - 678]

12
[ 90734-97-7 ]
[ 98-68-0 ]
[ 651331-49-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 4-methoxyindole-3-carboxaldehyde With sodium hydroxide In dichloromethane at 20℃; for 0.5h; Stage #2: 4-methoxy-phenyl-sulphonyl chloride In dichloromethane at 20℃; for 12h;
97%	Stage #1: 4-methoxyindole-3-carboxaldehyde In dichloromethane at 20℃; for 0.5h; Stage #2: 4-methoxy-phenyl-sulphonyl chloride at 20℃; for 12h;	1.1 (6-1) (6-1) Production of 4-methoxy-1-(4-methoxybenzsulfonyl)-1H-indole-3-carbaldehyde (7a) To the solution of the compound (6a) (1.68 g, 9.59 mmol, 1 eq) obtainedin (5-1) indichloromethane (20mL) wasaddedpellets of sodium hydroxide (574 mg, 14.34 mmol, 1.5 eq), and the mixture was stirred at room temperature for 30 minutes. 4-methoxybenzsulfonyl chloride (2.96 g, 14.34 mmol, 1.5 eq) was then added, and the mixture was stirred at room temperature for 12 hours. Ammonium chloride (100 mL) was then added, and the solution was extracted three times with ethyl acetate (100 mL). The extracts were combined, washed with aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated. The resulting concentrate was subjected to silica gel flush chromatography using hexane-ethyl acetate (70-30) to give white solid of the title compound (7a) (3.15 g, yield 97%).

Reference： [1]Coowar, Djalil; Bouissac, Julien; Hanbali, Mazen; Paschaki, Marie; Mohier, Eliane; Luu, Bang [Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6270 - 6282]
[2]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; UNIVERSITY OF STRASBOURG; MEIJI HOLDINGS CO., LTD - EP1533299, 2005, A1 Location in patent: Page/Page column 11

13
[ 90734-97-7 ]
[ 74-88-4 ]
[ 620175-74-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃;
	With sodium hydride In tetrahydrofuran at 20℃;
	With sodium hydride In tetrahydrofuran

	With sodium hydride In tetrahydrofuran at 20℃; for 12h;
	Stage #1: 4-methoxyindole-3-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 2h;

Reference： [1]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]
[2]Chen, Jie; Yan, Jun; Hu, Jinhui; Pang, Yanqing; Huang, Ling; Li, Xingshu [RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135]
[3]Yan, Jun; Chen, Jie; Zhang, Shun; Hu, Jinhui; Huang, Ling; Li, Xingshu [Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283]
[4]Zhang, Shun; An, Baijiao; Li, Jiayan; Hu, Jinhui; Huang, Ling; Li, Xingshu; Chan, Albert S. C. [Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410]
[5]He, Lingchen; Hu, Xin-Gen; Jiang, Jun; Li, Juan; Li, Xinhua; Liu, Hongxin; Song, Chao; Wan, Junlin; Wu, Chaofei; Xiao, Hong-Ping [Organic and Biomolecular Chemistry, 2022, vol. 20, # 1, p. 122 - 126]

14
[ 90734-97-7 ]
4-(4-methoxy-1-methyl-1H-indol-3-ylmethylene)-5-[1,2,3]thiadiazol-5-yl-2,4-dihydro-pyrazol-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: NaH / dimethylformamide / 0 - 20 °C 2: piperidine / ethanol / Heating

Reference： [1]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]

15
[ 90734-97-7 ]
4-(4-methoxy-1-methyl-1H-indol-3-ylmethylene)-5-(4-methyl-[1,2,3]thiadiazol-5-yl)-2,4-dihydro-pyrazol-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: NaH / dimethylformamide / 0 - 20 °C 2: piperidine / ethanol / Heating

Reference： [1]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]

16
[ 103260-65-7 ]
[ 90734-97-7 ]