Name: 10601-19-1|5-Methoxy-1H-indole-3-carbaldehyde|97%
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[ 1006-94-6 ]
[ 33513-42-7 ]
[ 10601-19-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With trichlorophosphate at 0 - 20℃;
98%	With sodium hydroxide; trichlorophosphate
98%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.333333h; Stage #2: 5-methoxylindole at 0 - 20℃; for 1.5h;

95%	With trichlorophosphate
94%	Stage #1: N,N-dimethyl-formamide With oxalyl dichloride at 0℃; for 1h; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 20℃; for 5h; Stage #3: With sodium hydroxide In N,N-dimethyl-formamide at 100℃; for 0.166667h;	5.2.1. General procedure for syntheses of compounds (4a-k) General procedure: Oxalyl chloride (0.3 mL) was added in a drop-wise manner to cooled (ice-bath) DMF (3 mL) under stirring. The mixture was then stirred at 0 °C for 1 h. A solution of the substituted indole (4 mmol) in DMF (1.5 mL) was then added to the reaction mixture in a dropwise manner. The resulting mixture was stirred at room temperature for 5 h. A 2 N solution of sodium hydroxide (2 mL) was then added, and the mixture was heated at 100 °C for 10 min. The mixture was then cooled and extracted with ethyl acetate (3 X 50 mL). The organic layers were combined and washed with sequentially water and brine. The organics were dried (Na2SO4) and distilled to dryness to give the crude residue, which was purified by flash column chromatography using ethyl acetate/petroleum ether (3:1, v/v) as the eluent to give pure indole-3-carbaldehyde (4a-k).
93%	With trichlorophosphate at 35℃; for 1h;
93%	With trichlorophosphate at 20℃; for 5h; Inert atmosphere;
92%	With trichlorophosphate at 0 - 55℃; for 2h;	Synthesis of indole-3-carbaldehyde derivatives (18a, 18b) General procedure: To a solution of compounds 17a, 17b (10 mmol) in 20 mL of DMF, phosphorus oxychloride (1.4 mL, 15 mmol) was added dropwise at 0°C. In 2 h of the reaction at 55°C, the mixture was poured into 150 mL of ice water. 20 % NaOH solution was added to adjust pH at 8.0. The crude product was filtered off and recrystallized from anhydrous ethanol to give the corresponding product.
90%	With trichlorophosphate at 0 - 40℃;
90%	With 1,2-Diiodoethane; water; triphenylphosphine at 80℃; for 2h;	3.1 General Procedure for the Formylation of electron-rich and -neutralindoles General procedure: Into a 25 mL tube, Ph3P (0.75 mmol, 1.5 equiv.), ICH2CH2I (0.75 mmol, 1.5 equiv.),1 (0.5 mmol, 1 equiv.), DMF (2 mL) and H2O (5 mL) were added under an airatmosphere. The mixture was stirred at 80 oC for 2 hours. Then the mixture was cooledto room temperature. A saturated aqueous brine solution was added, and the crudeorganic product was extracted by CH2Cl2. The combined organic phase was dried withanhydrous Na2SO4. After filtration, the solution was concentrated under reducedpressure to remove the solvent. The residue was subjected to flash columnchromatography on silica gel (pentane/ethyl acetate) to give the pure products 4a-4i.
89.4%	With trichlorophosphate at 35℃;	4.1.12 1H-Indole-3-carbaldehyde (4a) General procedure: To a stirring solution of POCl3 (18.36 g, 0.120 mol) in DMF (25 mL), indole (11.7 g, 0.100 mol) in DMF (15 mL) was added dropwise. The mixture was stirred at 35°C for 1 h, and then be poured into ice water and neutralized with 20 % NaOH aq. The solution was filtered and the residue was washed with water and dried under IR to give the compound 4a as yellow needle (13.86 g, 95.48 %). Mp = 192-194°C, lit.31 Mp = 196-197°C.
85%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #3: With sodium hydroxide In water Cooling with ice; Reflux;	Synthesis of 5-methoxy-indole-3-carbaldehydes; Preparation of S-methoxy-indole-3-carbaldehyde, 5-methoxy-2-methyl-indole-3- carbaldehyde, and 3-formyl-5-methoxy-indole-2-carboxylic acid POCI3 (1.6 ml_, 17 mmol, 1.1 eq.) was added to DMF (6 mL) at 00C and the solution was stirred for 30 minutes. This mixture was added to a stirring solution of the selected 5-methoxy- indole (15.5 mmol, 1 eq.) in DMF (11.5 mL) at 00C. The resulting mixture was stirred at 00C for 30 minutes, then allowed to warm to room temperature. The reaction was poured into ice, basified to pH 10 with 5 N NaOH, warmed to room temperature, refluxed for 5 minutes and allowed to cool to rt. Finally, it was acidified to pH 4 with 2 N HCI and the resulting precipitate was filtered and washed with water until pH 7. The solid product was dried under vacuum.5-Methoxy-indole-3-carbaldehydeYield: 85%. MS (m/z): 176.2 (MH+).
83%	With trichlorophosphate at 0 - 40℃; for 1.5h;	3.1.1. General Procedure for Synthesizing the Indoles-3-Carboxaldehydes (4b and 4e-4g) General procedure: Phosphorus oxychloride (0.42 g, 2.74 mmol) was added dropwise to a solution of the indole 5b, 5e-5g (0.30 g, 2.29 mmol) in DMF (0.84 g, 11.4 mmol) at 0 °C for 30 min. The solution was then heated at 40 °C for 1 h. Ice was added to the reaction vessel, followed by a solution of sodium hydroxide (2 M). The solution was refluxed for 40 min. The mixture was cooled and extracted using ethyl acetate, and the organic phase was washed with brine. The organic extracts were combined, dried over Na2SO4, and concentrated. The crude residue was purified by chromatography on a silica gel column using hexane-ethyl acetate as an eluent to obtain the desired product [19].
80%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 20℃; for 2h; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 20 - 60℃; for 1h;
79%	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 38℃; for 1.25h; Stage #2: With sodium hydroxide In water at 170℃; for 0.0833333h;
79%	With phosphorus pentachloride at 20℃; for 1h;	6 example 6 A 5-methoxy-1H-indole (14.7 g, 0.1 mol) was dissolved in N, N -dimethylformamide (73.5 g, 1 mol) in a 500ml of reaction flask at 0 ° C with mechanical agitation, then phosphorus pentachloride / N, N -dimethylformamide mixed formylation reagent (15 g, 0.12 mol) was added in portions. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, 100 mL of water was added and stirred at room temperature for 1 hour. The reaction was neutralized with 2N sodium hydroxide solution and the resulting suspension was filtered. The filter cake was dissolved in methanol / tetrahydrofuran and the pH was adjusted to 1 with concentrated hydrochloric acid. The solution was stirred at room temperature for 45 minutes and neutralized with 4N sodium hydroxide solution to neutral. The solvent was partially evaporated to give the product, filtered and washed with water. Finally, 5-methoxy-1-hydrogen-indole-3- carboxaldehyde was obtained (14 g, 79%). This product can be used in the production of Tegaserod Hydrogen Maleate.
69%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 20℃; for 0.75h; Cooling with ice; Stage #2: 5-methoxylindole at 40℃; for 1.25h;	General procedure 2 for the synthesis of substituted indole-3-carbaldehydes The Vilsmeier-Haack reagent was generated by the addition of 2 ml of POCI3 over the course of15 minutes to 8 ml of DMF cooled in an ice-salt bath. After the addition was complete, the icebath was removed and the contents of the flask allowed to warm to room temperature overapprox. 30 minutes. The substituted indole (21.9 mmol) was dissolved in 10 ml of DMF andadded over a period of 15 minutes to the formylating mixture. The stirring was continued for an10 hour during which the flask contents were heated to 40°C in a hot water bath. A total of 50 mlice cold H20 and 20 ml of 5 M NaOH were added, the mixture quickly brought to a boil and leftto cool slowly. The crystals were removed by filtration, washed with cold water and vacuumdried. The products thus obtained were in most cases sufficiently pure for the subsequentreactions, and the impure aldehydes were recrystallized from ethanol-water mixtures. Yields15 varied from 48 to 90%.; The compound was synthesized from 5-methoxy-1H-indole (170 mmol) according to the25 general procedure 2, with the exception that it was scaled up proportionally to the 5-methoxyindole (69% yield).LC-MS: m/z = 176.11; tR = 2.20 min.
63%	With Vilsmeier reagent at 20℃; for 1h;	26.a (a) 5-methoxyindole (200 mg, 1.36 mmol) dissolved in anhydrous DMF,Drip the newly prepared Vilsmeier reagent,Allow to react at room temperature for one hour, then pour into ice water and filter by suction.Dryed to a yellow solid 150 mg, yield 63%.
59%	With trichlorophosphate
54%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.166667h; Stage #2: 5-methoxylindole at 45℃; for 2h;
	With trichlorophosphate und anschliessenden Hydrolysieren mit wss.Natronlauge;
	With trichlorophosphate at 35℃; for 1h;
	With hydrogenchloride; trichlorophosphate 1.) 0 deg C, 1 h, 2.) MeOH, THF, RT, 45 min; Yield given. Multistep reaction;
	With trichlorophosphate at 0℃;
	With trichlorophosphate at 0 - 60℃;
	With sodium hydroxide; trichlorophosphate
	With trichlorophosphate at 0 - 23℃;
	With trichlorophosphate
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate for 0.5h; Cooling with ice; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0 - 100℃; for 3.08333h;	General procedure for the formylation of indoles 4a-4h or azaindole 5 General procedure: Phosphorous oxychloride (2 mmol) was added dropwise to dimethylformamide (3 mL) cooled under ice-bath and allowed to stir for 30 min. A solution of indoles 4a-4h or azaindole 5 (1 mmol) in DMF (5 mL) was added dropwise for 5 min at 0 oC. The mixture was further allowed to stir for 3 h at 90-100 oC. Reaction mixture was cooled to room temperature and poured into crushed ice. Excess POCl3 was quenched with 1 N NaOH and left overnight at room temperature. Ice-cold reaction mixture was then extracted (50 mL × 3) with EtOAc. Combined organic layer was concentrated on rotary evaporator and crude products were purified by silica gel (No.100-200) column chromatography to get indole-3-carboxaldehydes 1a-1h or 6 in 60-80% yield.
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.666667h; Inert atmosphere; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0 - 35℃; for 1.33333h; Stage #3: With sodium hydroxide In water; N,N-dimethyl-formamide at 100℃; for 0.5h; Cooling with ice;	5.1.9. General procedure for the synthesis of 5-methyl-1H-indole-3-carbaldehyde General procedure: To a 100 mL three-necked round flask was introduced anhydrous N,N-dimethylformamide (4.2 mL, 34.35 mmol) at 0 °C under argon followed by slow addition of phosphorus oxychloride (1.3 mL, 13.62 mmol). Solution was mixed at 0 °C for 40 min. A solution of 5-methyl-1H-indole (1.627 g, 12.41 mmol) in 2.5 mL of DMF was slowly added maintaining the temperature below 10 °C. The solution was stirred for 40 min at 0 °C and then 35 °C for additional 40 min. Then ice was added to the flask and a solution of sodium hydroxide (5.5 g, 137.25 mmol dissolved in 14.6 mL of water) was introduced using a dropping funnel. Solution was vigorously stirred during the addition, then heated to 100 °C for 30 min and left to reach room temperature. The brown precipitate was filtered off and washed with large volumes of water. The powder was dried in vacuum. Yield 71.5%.
	With trichlorophosphate
	With trichlorophosphate
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2h; Stage #2: With sodium hydroxide In water at 90℃; for 1h;
	With trichlorophosphate Cooling with ice;
	With sodium hydroxide; trichlorophosphate
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 20℃; Inert atmosphere; Stage #2: With water; sodium hydrogencarbonate for 0.5h;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 15℃; for 0.25h; Stage #2: 5-methoxylindole at 0 - 70℃; for 3h;	General synthetic method General procedure: Compound 2b was obtained by four steps ofreactions. Step 1: POCl3 (10.0mmol) wasadded into DMF (N,N-dimethylformamide;10.0mmol) and stirred at 158C for 15 min 5-Fluoroindole (1.0mmol) was dissolved inDMF, which was added in dropwise to themixture at 08C. The mixture was stirred at708C for 3 h. The reaction solution waspoured into icy water (50ml) and continuedstirring until precipitation appeared. Thesolid was filtered and washed with water.Step 2: 5-fluoro-indole-3-carboxaldehyde(1.2 mmol), 4b-amino-podophyllotoxin(413 mg, 1.0 mmol), and two drops ofglacial acetic acid in 95% C2H5OH(10.0ml) were stirred at r.t. for 12 h untilprecipitation appeared. The solid wasfiltered and washed with glacial aceticacid. Step 3: the compound b (1.0mmol)was reducted in anhydrous methanol byNaBH4 (4.0mmol) at 08C for 3h, 5% HClwas added to themixture to end the reaction.The saturated NaHCO3 was add to adjustpH.7. The solvent was evaporated undervacuum. Finally, the residue was dissolvedin anhydrous CH2Cl2 and chromatographedon silica gel plate using petroleum ether andethyl acetate (v/v 1:1) to give the correspondingsecondary amine 2b (0.31 g, 56%)as white solid. For 1H NMR spectral data(CDCl3) (see Table 2). HR-ESI-MSm/z: 561.2033 [M H] (calcd forC31H30FN2O7, 561.2037)
	With sodium hydroxide; trichlorophosphate In water at 0℃; for 6h; Reflux;
	With trichlorophosphate at 20℃; for 2h;	General procedure for preparation of 1H-indole-3-carboxaldehyde (4-6) General procedure: A solution of substituted indole 1-3 (82.6 mmol) in DMF (20 mL) was added dropwise to a stirring suspension of phosphorus oxychloride (7.0 mL, 75.0 mmol) in DMF (35 mL). After stirring at room temperature for 2 h, the reaction mixture was poured onto ice. The mixture was made basic with a solution of NaOH (330 mmol, 13.2 g) in H2O (44 mL), then was extracted with Et2O (2 * 50 mL). The combined organic layers were washed with brine, dried (MgSO4), and concentrated under vacuum. Flash chromatography on silica gel (10% ethyl acetate/hexanes) gave the title compounds 4-6 as an off-white solid, respectively.
	With trichlorophosphate at 20℃;
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2.5h; Stage #2: With sodium hydroxide In water at 90℃; for 1h;
	With trichlorophosphate at 20℃;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: 5-methoxylindole at 20℃;	General Procedure for Synthesis of Bis(indolyl)-hydrazide-Hydazones (NMK-BH1-6). General procedure: The intermediatesindole-2(3)-carbohydrazide (2) and indole-3-carboxaldehyde(4) were prepared starting from commercially available indole,as described previously. Indole-3-carboxylic acids 1were prepared from the reaction of indole with trifluoroaceticanhydride followed by hydrolysis with sodium hydroxide. Toobtain the corresponding ester, a solution of indole-3-carboxylicacid 1 (1 mmol) in absolute ethanol (20 mL) was refluxed witha catalytic amount of concentrated sulfuric acid for 20 h and theresidue was extracted with ethyl acetate (30 mL), washed with asaturated sodium bicarbonate solution (20 mL), dried, andevaporated. As shown in Scheme 1, a solution of theappropriate ester (1 mmol) and hydrazine hydrate (2 mmol)in ethanol (15 mL) was refluxed for 24 h and cooled, and thesolid that was obtained was filtered and recrystallized fromethanol to give pure indole-2(3)-carbohydrazide (2) in 85-90% yield.For preparation of indole-3-carboxaldehydes 4, withcontinuous stirring, phosphorous oxychloride (8.41 mL, 90mmol) was added to 0 °C dimethylformamide (28 mL, 370mmol) for 30 min followed by addition of a solution of indole 3(85.47 mmol) in DMF (10 mL, 130 mmol) at roomtemperature until it became a yellow paste. At the end of thereaction, 30 g of crushed ice was added to the paste followed bydropwise addition of a sodium hydroxide solution (1 N solution, 100 mL) while the mixture was being stirred. Theresulting suspension was heated rapidly to 90 °C, cooled atroom temperature, and refrigerated overnight. The product wasfiltered, washed with water (2 × 100 mL), and air-dried toafford the pure indole-3-carboxaldehydes 4 in 80-90% yields(Scheme 1).Finally, to the mixture of indole-2(3)-carboxylic acidhydrazide 2 (1 mmol) and indole-3-carboxaldehyde 4 (1mmol) in absolute ethanol (20 mL) was added a catalyticamount of glacial acetic acid, and the mixture was refluxed at 80°C for 5 h and cooled and the solid that separated out wasfiltered and recrystallized from ethanol to afford bis(indolyl)-hydrazide-hydrazones in 75-90% yields (Scheme 1).
	With trichlorophosphate at 0℃; for 2h;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate Cooling with ice; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 20℃; for 1h; Stage #3: With sodium hydroxide In water at 100℃; for 0.25h;	General procedure for the preparation of indolylnitroalkenes General procedure: Phosphorus oxychloride (0.86 mL) was added dropwise to dimethylformamide (1.0 mL) with ice-bath cooling. The chosen indoles (1.0 g) were added as a dimethylformamide solution for preparation of corresponding indolecarbaldehydes. The resulting mixture was stirred at room temperature for one hour. The reaction mixture was quenched with chilled water, followed by the addition of aq Sodium hydroxide solution and refluxed at 100 °C for 15 min. The reaction mixture was cooled to room temperature and maintained at 0 °C overnight. The precipitates formed were collected and washed with water. After this, the -NH groups of different indolecarbaldehydes were protected with methyl, tosyl, benzyl, or methylsulfonyl by using corresponding halogenides (1.5 equiv) under different basic conditions, such as sodium hydride (1.5 equiv) using acetonitrile as a solvent. Then, the reaction of resulting N-protected indolecarbaldehydes (1.0 g) with nitromethane (5 mL) in the presence of 30 mol % of ammonium acetate as the catalyst to furnish the desired indolylnitroalkenes.9
	Stage #1: N,N-dimethyl-formamide With thionyl chloride at 20℃; for 0.5h; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0 - 20℃; for 0.833333h; Stage #3: With sodium hydroxide In water; N,N-dimethyl-formamide Reflux;	tert-Butyl 5-Bromo-3-[(E)-2-nitrovinyl]-1H-indole-1-carboxylate (9b); Typical Procedure General procedure: 5-Bromoindole (1.35 g, 6.9 mmol) was formylated as described for1H-indole-3-carbaldehyde to produce 6-bromo-1H-indole-3-carbaldehyde(1.50 g, 97%) with the exception that the obtained productwas not purified by refluxing in EtOH.5-Bromo-1H-indole-3-carbaldehyde (1.50 g, 6.7 mmol) and NH4OAc(0.52 g, 6.7 mmol) were heated at reflux in CH3NO2 (18 mL, 335mmol) for 45 min, cooled to r.t., and treated with H2O (70 mL). Theproduct was extracted with EtOAc (70 mL), washed with H2O (5 × 50mL) and NaCl solution (20 mL), and dried over anhydrous Na2SO4. Thesolvent was removed in vacuo to afford 6-bromo-3-[(E)-2-nitrovinyl]-1H-indole (1.72 g, 96%, brownish crystals), which was dried in vacuoand used without further purification.A suspension of 5-bromo-3-[(E)-2-nitrovinyl]-1H-indole (1.72 g, 6.4mmol) and DMAP (0.08 g, 0.64 mmol) in anhydrous THF (7 mL) wastreated with a solution of Boc2O (2.1 g, 9.7 mmol) in anhydrous THF(7 mL) dropwise at 0-5 °C over a period of 15 min, stirred at r.t. for 3h, and concentrated in vacuo. The residue was dissolved in CH2Cl2 (50mL), washed with citric acid solution (10%, 20 mL), H2O (20 mL), andconcd NaCl solution (15 mL), and dried over anhydrous Na2SO4. TheCH2Cl2 was evaporated in vacuo and the residue was purified by chromatographyon a column of silica gel (EtOAc-hexane, 6:1) to provide tert-butyl 5-bromo-3-[(E)-2-nitrovinyl]-1H-indole-1-carboxylate. Yield: 2.11 g (83% from 5-bromoindole); pale-yellow solid; mp 156-157 °C (MeOH); Rf = 0.55 (EtOAc-hexane, 1:8).
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate for 0.333333h; Stage #2: 5-methoxylindole at 0℃; for 0.5h;	5-Methoxy-1H-indole-3-carbaldehyde (22) DMF (3.0 mL, 38.9 mmol) and POCl3 (0.85 mL, 9.28 mmol) were stirred in an ice bath for 20 min until the yellow Vilsmeier compound formed. This Vilsmeier compound was then added to a solution of 21 (1.04 g, 6.45 mmol) in DMF (5 mL) and the reaction was stirred for 30 min in 0 °C. NaOH (2 M, 50 mL) was added and the solution was stirred for 10 min. Then the solution was extracted with DCM (2×100 mL), dried with Na2SO4 and evaporated. The obtained yellow solid 1.20 g (90%) was used without purification. 1H NMR (300 MHz, CDCl3): δ (ppm) 9.93 (s, 1H), 8.54 (d, J = 2.4 Hz, 1H), 7.93 (d, J = 9.0 Hz, 1H), 7.46 (s, 1H), 6.97 (dd, J = 9.0, 2.5 Hz, 1H), 3.72 (s, 3H), 1.24 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ (ppm) 197.18, 184.79, 147.90, 142.01, 138.27, 121.04, 113.21, 113.10, 102.50, 70.28; MS (ESI) m/z: 176.1 [M+H]+.
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate for 0.5h; Stage #2: 5-methoxylindole at 20℃; for 1h;	4.1.3 General procedure for the synthesis of indole-3-carboxaldehydes (20) General procedure: A round-bottomed flask containing (28mL, 370mmol) freshly distilled dimethylformamide (DMF) was cooled to 0°C for about 30min and freshly distilled phosphorus oxychloride (8.41mL, 90mmol) was subsequently added with stirring to the DMF over a period of 30min. A solution of indole 19 (85.47mmol) in DMF (10mL, 130mmol) was added to the yellow solution over a period of 1h. The solution was stirred at room temperature till it become a yellow paste. At the end of the reaction, 30g of crushed ice was added to the paste with stirring to make a clear cherry-red aqueous solution. Sodium hydroxide solution (1N, 100mL) was added dropwise with stirring to this cherry-red solution. The resulting suspension was heated rapidly to 90°C and allowed to cool at room temperature, after which it was refrigerated for overnight. The product was filtered, washed with water (2×100mL) and air-dried to afford pure indole-3-carboxaldehydes 20 in 80-90% yields. Indole-3-carboxaldehyde, pale yellow solid; mp 194-196°C (Lit. [37]196-197°C).
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.25h; Inert atmosphere; Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0 - 20℃; for 3.25h; Inert atmosphere; Stage #3: With sodium hydroxide In water; N,N-dimethyl-formamide for 0.0833333h; Reflux;
	With trichlorophosphate at 20℃; for 8h;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate Stage #2: 5-methoxylindole In N,N-dimethyl-formamide at 0℃; for 2h;
	With trichlorophosphate at 0℃; for 2h;	4.1.2. General procedure for synthesis of 1H-indole-3-carboxaldehyde (2a-c) General procedure: The relevant indole derivate (1a-c, 40 mmol) and phosphorusoxychloride (10 mL) were dissolved into DMF (20 mL), respectively.The solution of indole was added dropwise to POCl3 at 0 °C andstirred for 2 h. Then the reaction mixturewas diluted with icewater(300 mL), neutralized with NaOH to pH 9.0, and extracted withethyl acetate (50 mL x 3). The organic layer was washed with brine,dried over anhydrous sodium sulfate, filtered and concentrated invacuum. Recrystallization afforded compound 2a-c with yields of95.3-98.1%.
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 20℃; Stage #2: With water; sodium hydroxide at 0 - 90℃; for 2h;
	With trichlorophosphate at 0℃; for 0.166667h;
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate Sealed tube; Stage #2: With potassium hydroxide In water Sealed tube;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: 5-methoxylindole 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%.
	With trichlorophosphate at 0 - 60℃; for 6.5h;	General synthetic procedure for the synthesis of indol-3-aldehydes (E) General procedure: A solution of indole (1.71 mmol) in dimethyl formamide (1 ml) was added to a cooled solutionof trichlorophosphate (1.88 mmol) in dimethyl formamide (1 ml) and stirred at room temperature for30 min and allowed to stir for 6 h at 60 °C. The reaction mixture was allowed for cooling and pouredinto ice-cold water and added dropwise to an ice-cold solution of 2M NaOH. The suspension wasextracted with ethylacetate, the combined organic extract was concentrated to dryness to yield desiredindole-3-carboxaldehyde.
	With trichlorophosphate
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2.5h; Stage #2: With sodium hydroxide In water at 90℃; for 1h;
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: 5-methoxylindole for 1h; Heating;
	With trichlorophosphate at 5 - 20℃; for 12h;
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2h; Stage #2: With sodium hydroxide In water at 90℃; for 1h;
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate at 0 - 40℃; for 2.5h; Inert atmosphere; Stage #2: With water; sodium hydroxide at 90℃; for 1h; Inert atmosphere;
	With trichlorophosphate at 0 - 20℃; for 2h; Inert atmosphere;
	With trichlorophosphate
	Stage #1: 5-methoxylindole; N,N-dimethyl-formamide With trichlorophosphate Inert atmosphere; Stage #2: With potassium hydroxide In water Inert atmosphere;

Reference： [1]Sharma, Kavita; Iyer, Aishwarya; Sengupta, Kundan; Chakrapani, Harinath [Organic Letters, 2013, vol. 15, # 11, p. 2636 - 2639]
[2]Location in patent: scheme or table Zhang, Pu Yong; Wan, Sheng Biao; Ren, Su Mei; Jiang, Tao [Chinese Chemical Letters, 2010, vol. 21, # 11, p. 1307 - 1309]
[3]Ghashghaei, Ouldouz; Pedrola, Marina; Seghetti, Francesca; Martin, Victor V.; Zavarce, Ricardo; Babiak, Michal; Novacek, Jiri; Hartung, Frederick; Rolfes, Katharina M.; Haarmann-Stemmann, Thomas; Lavilla, Rodolfo [Angewandte Chemie - International Edition, 2021, vol. 60, # 5, p. 2603 - 2608][Angew. Chem., 2021, vol. 133, # 5, p. 2635 - 2640,6]
[4]Klohr, Steven E.; Cassady, John M. [Synthetic Communications, 1988, vol. 18, # 7, p. 671 - 674]
[5]Zheng, Jing; Deng, Lijuan; Chen, Minfeng; Xiao, Xuzhi; Xiao, Shengwei; Guo, Cuiping; Xiao, Gaokeng; Bai, Liangliang; Ye, Wencai; Zhang, Dongmei; Chen, Heru [European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167]
[6]Moody, Christopher J.; Swann, Elizabeth [Journal of the Chemical Society. Perkin transactions I, 1993, # 21, p. 2561 - 2566]
[7]Naik, Prajakta N.; Khan, Ayesha; Kusurkar, Radhika S. [Tetrahedron, 2013, vol. 69, # 50, p. 10733 - 10738]
[8]Zhang; Xu; Wang; Kang [Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 3006 - 3016]
[9]Coowar, Djalil; Bouissac, Julien; Hanbali, Mazen; Paschaki, Marie; Mohier, Eliane; Luu, Bang [Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6270 - 6282]
[10]Zhu, Yu-Rong; Lin, Jin-Hong; Xiao, Ji-Chang [Synlett, 2022, vol. 33, # 3, p. 259 - 263]
[11]Guo, Xiaoke; Yang, Qian; Xu, Jing; Zhang, Li; Chu, Hongxi; Yu, Peng; Zhu, Yingying; Wei, Jinglian; Chen, Weilin; Zhang, Yaozhong; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6466 - 6476]
[12]Current Patent Assignee: PFIZER INC - WO2010/30727, 2010, A1 Location in patent: Page/Page column 99
[13]Canche Chay, Cristina I.; Cansino, Rocio Gomez; Espitia Pinzon, Clara I.; Torres-Ochoa, Ruben O.; Martinez, Roberto [Marine Drugs, 2014, vol. 12, # 4, p. 1757 - 1772]
[14]Li, Dong-Dong; Qin, Ya-Juan; Zhang, Xin; Yin, Yong; Zhu, Hai-Liang; Zhao, Lin-Guo [Chemical Biology and Drug Design, 2015, vol. 86, # 4, p. 731 - 745]
[15]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]
[16]Current Patent Assignee: HANGZHOU DOEASY PHARMA - CN106554345, 2017, A Location in patent: Paragraph 0036-0037
[17]Current Patent Assignee: POLISH ACADEMY OF SCIENCES - WO2018/15558, 2018, A1 Location in patent: Page/Page column 15; 29
[18]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN108191719, 2018, A Location in patent: Paragraph 0252
[19]Adams, David; Bénardeau, Agnès; Bickerdike, Mike J.; Bentley, Jon M.; Bissantz, Caterina; Bourson, Anne; Cliffe, Ian A.; Hebeisen, Paul; Kennett, Guy A.; Knight, Antony R.; Malcolm, Craig S.; Mizrahi, Jacques; Plancher, Jean-Marc; Richter, Hans; Röver, Stephan; Taylor, Sven; Vickers, Steven P. [Chimia, 2004, vol. 58, # 9, p. 613 - 620]
[20]Chen, Chou-Hsiung; Genapathy, Sivaneswary; Fischer, Peter M.; Chan, Weng C. [Organic and Biomolecular Chemistry, 2014, vol. 12, # 48, p. 9764 - 9768]
[21]Young [Journal of the Chemical Society, 1958, p. 3493,3494]
[22]Courant, Jacqueline; Leblois, Danielle; Tandon, Manju; Robert-Piessard, Sylvie; le Baut, Guillaume; et al. [European Journal of Medicinal Chemistry, 1989, vol. 24, p. 145 - 154]
[23]Buchheit; Gamse; Giger; Hoyer; Klein; Kloeppner; Pfannkuche; Mattes [Journal of medicinal chemistry, 1995, vol. 38, # 13, p. 2331 - 2338]
[24]Gurkan, A. Selen; Karabay, Arzu; Buyukbingol, Zeliha; Adejare, Adeboye; Buyukbingol, Erdem [Archiv der Pharmazie, 2005, vol. 338, # 2-3, p. 67 - 73]
[25]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]
[26]Diana, Patrizia; Carbone, Anna; Barraja, Paola; Montalbano, Alessandra; Martorana, Annamaria; Dattolo, Gaetano; Gia, Ornella; Via, Lisa Dalla; Cirrincione, Girolamo [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 8, p. 2342 - 2346]
[27]Location in patent: scheme or table Bursavich, Matthew G.; Brooijmans, Natasja; Feldberg, Lawrence; Hollander, Irwin; Kim, Stephen; Lombardi, Sabrina; Park, Kaapjoo; Mallon, Robert; Gilbert, Adam M. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 8, p. 2586 - 2590]
[28]Location in patent: scheme or table Kumar, Dalip; Maruthi Kumar; Ghosh, Soumitra; Shah, Kavita [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 212 - 215]
[29]Location in patent: experimental part Yadav, Rammohan R.; Battini, Narsaiah; Mudududdla, Ramesh; Bharate, Jaideep B.; Muparappu, Nagaraju; Bharate, Sandip B.; Vishwakarma, Ram A. [Tetrahedron Letters, 2012, vol. 53, # 17, p. 2222 - 2225]
[30]Location in patent: experimental part Xu, Qinyuan; Huang, Li; Liu, Juan; Ma, Liang; Chen, Tao; Chen, Jinying; Peng, Fei; Cao, Dong; Yang, Zhuang; Qiu, Neng; Qiu, Jingxiang; Wang, Guangcheng; Liang, Xiaolin; Peng, Aihua; Xiang, Mingli; Wei, Yuquan; Chen, Lijuan [European Journal of Medicinal Chemistry, 2012, vol. 52, p. 70 - 81]
[31]Kumar, Dalip; Arun; MaruthiKumar; Acosta, Glen; Noel, Brett; Shah, Kavita [ChemMedChem, 2012, vol. 7, # 11, p. 1915 - 1920]
[32]Selen Gurkan-Alp; Mumcuoglu, Mine; Andac, Cenk A.; Dayanc, Emre; Cetin-Atalay, Rengul; Buyukbingol, Erdem [European Journal of Medicinal Chemistry, 2012, vol. 58, p. 346 - 354]
[33]Cheng, Hong-Gang; Lu, Liang-Qiu; Wang, Tao; Yang, Qing-Qing; Liu, Xiao-Peng; Li, Yang; Deng, Qiao-Hui; Chen, Jia-Rong; Xiao, Wen-Jing [Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3250 - 3254][Angew. Chem., 2013, vol. 125, # 11, p. 3332 - 3336,5]
[34]Chen, Jian; Geng, Zhi-Cong; Li, Ning; Huang, Xiao-Fei; Pan, Feng-Feng; Wang, Xing-Wang [Journal of Organic Chemistry, 2013, vol. 78, # 6, p. 2362 - 2372]
[35]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]
[36]Lanke, Veeranjaneyulu; Ramaiah Prabhu, Kandikere [Organic Letters, 2013, vol. 15, # 24, p. 6262 - 6265]
[37]Liu, Jing; Cao, Bo; Gao, Ying; Bai, Mei; Mei, Xin; Chen, Hong; Jiang, Yun-Gen; Huang, Da-Jiang [Journal of Asian Natural Products Research, 2013, vol. 15, # 9, p. 985 - 992]
[38]Sashidhara, Koneni V.; Dodda, Ranga Prasad; Sonkar, Ravi; Palnati, Gopala Reddy; Bhatia, Gitika [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 499 - 509]
[39]Wang, Yan-Ting; Qin, Ya-Juan; Yang, Na; Zhang, Ya-Liang; Liu, Chang-Hong; Zhu, Hai-Liang [European Journal of Medicinal Chemistry, 2015, vol. 99, p. 125 - 137]
[40]Chen, Jie; Yan, Jun; Hu, Jinhui; Pang, Yanqing; Huang, Ling; Li, Xingshu [RSC Advances, 2015, vol. 5, # 83, p. 68128 - 68135]
[41]Chen, Weiliang; Xia, Yong; Lin, Lili; Yuan, Xiao; Guo, Songsong; Liu, Xiaohua; Feng, Xiaoming [Chemistry - A European Journal, 2015, vol. 21, # 43, p. 15104 - 15107]
[42]Yan, Jun; Chen, Jie; Zhang, Shun; Hu, Jinhui; Huang, Ling; Li, Xingshu [Journal of Medicinal Chemistry, 2016, vol. 59, # 11, p. 5264 - 5283]
[43]Das Mukherjee, Dipanwita; Kumar, N. Maruthi; Tantak, Mukund P.; Das, Amlan; Ganguli, Arnab; Datta, Satabdi; Kumar, Dalip; Chakrabarti, Gopal [Biochemistry, 2016, vol. 55, # 21, p. 3020 - 3035]
[44]Zhang, Ya-Liang; Qin, Ya-Juan; Tang, Dan-Jie; Yang, Meng-Ru; Li, Bo-Yan; Wang, Yan-Ting; Cai, Hong-Yu; Wang, Bao-Zhong; Zhu, Hai-Liang [ChemMedChem, 2016, vol. 11, # 13, p. 1446 - 1458]
[45]Kaur, Jasneet; Islam, Nasarul; Kumar, Akshay; Bhardwaj, Vimal K.; Chimni, Swapandeep Singh [Tetrahedron, 2016, vol. 72, # 49, p. 8042 - 8049]
[46]Golantsov, Nikita E.; Festa, Alexey A.; Varlamov, Alexey V.; Voskressensky, Leonid G. [Synthesis, 2017, vol. 49, # 11, p. 2562 - 2562]
[47]Xu, Shengtao; Yao, Hong; Pei, Lingling; Hu, Mei; Li, Dahong; Qiu, Yangyi; Wang, Guangyu; Wu, Liang; Yao, Hequan; Zhu, Zheying; Xu, Jinyi [European Journal of Medicinal Chemistry, 2017, vol. 132, p. 310 - 321]
[48]Tantak, Mukund P.; Klingler, Linus; Arun; Kumar, Anil; Sadana, Rachna; Kumar, Dalip [European Journal of Medicinal Chemistry, 2017, vol. 136, p. 184 - 194]
[49]Xu, Jun; Tong, Rongbiao [Green Chemistry, 2017, vol. 19, # 13, p. 2952 - 2956]
[50]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]
[51]Yang, Meng-Ru; Qin, Ya-Juan; Chen, Chen; Zhang, Ya-Liang; Li, Bo-Yan; Liu, Tian-Bao; Gong, Hai-Bin; Wang, Bao-Zhong; Zhu, Hai-Liang [RSC Advances, 2016, vol. 6, # 36, p. 30412 - 30424]
[52]Chen, Kun; Zhang, Ya-Liang; Fan, Jing; Ma, Xiang; Qin, Ya-Juan; Zhu, Hai-Liang [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 722 - 737]
[53]Jiang, Yan; Yu, Shuo-Wen; Yang, Yi; Liu, Ying-Le; Xu, Xiao-Ying; Zhang, Xiao-Mei; Yuan, Wei-Cheng [Organic and Biomolecular Chemistry, 2018, vol. 16, # 36, p. 6647 - 6651]
[54]Xu, Feijie; Li, Wenlong; Shuai, Wen; Yang, Limei; Bi, Yi; Ma, Cong; Yao, Hequan; Xu, Shengtao; Zhu, Zheying; Xu, Jinyi [European Journal of Medicinal Chemistry, 2019, vol. 173, p. 1 - 14]
[55]Lu, Lin; Luo, Chenguang; Peng, Hui; Jiang, Huanfeng; Lei, Ming; Yin, Biaolin [Organic Letters, 2019, vol. 21, # 8, p. 2602 - 2605]
[56]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]
[57]Sigalapalli, Dilep Kumar; Pooladanda, Venkatesh; Singh, Priti; Kadagathur, Manasa; Guggilapu, Sravanthi Devi; Uppu, Jaya Lakshmi; Tangellamudi, Neelima D.; Gangireddy, Pavan Kumar; Godugu, Chandraiah; Bathini, Nagendra Babu [Bioorganic Chemistry, 2019, vol. 92]
[58]Survase, Dattatray N.; Karhale, Shrikrishna S.; Khedkar, Vijay M.; Helavi, Vasant B. [Synthetic Communications, 2019, vol. 49, # 24, p. 3486 - 3497] Karadayi, Fikriye Zengin; Yaman, Murat; Kisla, Mehmet Murat; Konu, Ozlen; Ates-Alagoz, Zeynep [New Journal of Chemistry, 2021, vol. 45, # 20, p. 9010 - 9019]
[59]Wang, Shuai; Shen, Yao-Bin; Li, Long-Fei; Qiu, Bin; Yu, Liping; Liu, Qing; Xiao, Jian [Organic Letters, 2019, p. 8904 - 8908]
[60]Ding, Yangyang; Kang, Congmin; Liu, Kai [Pharmaceutical Chemistry Journal, 2020, vol. 54, # 4, p. 345 - 352]
[61]Monakhova, Natalia; Korduláková, Jana; Vocat, Anthony; Egorova, Anna; Lepioshkin, Alexander; Salina, Elena G.; Nosek, Jozef; Repková, Eva; Zemanová, Júlia; Jurdáková, Helena; Górová, Renáta; Roh, Jaroslav; Degiacomi, Giulia; Sammartino, José Camilla; Pasca, Maria Rosalia; Cole, Stewart T.; Mikušová, Katarína; Makarov, Vadim [ACS Infectious Diseases, 2021, vol. 7, # 1, p. 88 - 100]
[62]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]
[63]Devi, Manju; Jadhav, Amol P.; Singh, Ravi P. [New Journal of Chemistry, 2021, vol. 45, # 19, p. 8445 - 8448]
[64]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]
[65]Ates-Alagoz, Zeynep; Kisla, Mehmet Murat; Karadayi, Fikriye Zengin; Baran, Sercan; Doğan, Tuğba Somay; Mutlu, Pelin [New Journal of Chemistry, 2021, vol. 45, # 38, p. 18025 - 18038]
[66]Ma, Jinhui; Luo, Jiajun; Jiang, Kai; Zhang, Guangwen; Liu, Shubin; Yin, Biaolin [Organic Letters, 2021, vol. 23, # 20, p. 8033 - 8038]

2
[ 10601-19-1 ]
[ 77-78-1 ]
[ 39974-94-2 ]

Reference： [1]Archiv der Pharmazie,1988,vol. 321,p. 823 - 826
[2]Heteroatom Chemistry,2012,vol. 23,p. 41 - 48
[3]Synthetic Communications,2012,vol. 42,p. 1746 - 1759
[4]Journal of Chemical Sciences,2011,vol. 123,p. 609 - 614

3
[ 10601-19-1 ]
[ 23084-36-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 1,3-dimethyl-2-imidazolidinone; sodium hexamethyldisilazane In tetrahydrofuran at 185℃; for 12h;
85%	With hydroxylamine hydrochloride In N,N-dimethyl-formamide at 110℃;	Synthesis of indole-3-carbonitrile derivatives (19a, 19b) General procedure: To a solution of 18a, 18b (30 mmol) in DMF (13 mL) was added NH2OH·HCl (45 mmol) upon stirring. The reaction mixture was stirred at 110°C and its progress was monitored by TLC. Upon cooling down the reaction mixture, it was poured into ice cold water. The precipitated solid was filtered off and washed with water and recrystallized from anhydrous ethanol to give the respective product.
77%	With Nitroethane; sodium acetate In acetic acid for 10h; Heating;

52%	With tert.-butylhydroperoxide; copper(II) nitrate trihydrate; acetic acid; N,N-dimethyl-formamide at 130℃; for 48h;
	With formic acid; hydroxylamine hydrochloride; sodium formate at 130℃;
	With tert.-butylhydroperoxide; copper(II) nitrate trihydrate; acetic acid; N,N-dimethyl-formamide

Reference： [1]Jih, Ru Hwu; Fung, Fuh Wong [European Journal of Organic Chemistry, 2006, # 11, p. 2513 - 2516]
[2]Zhang; Xu; Wang; Kang [Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 3006 - 3016]
[3]Klohr, Steven E.; Cassady, John M. [Synthetic Communications, 1988, vol. 18, # 7, p. 671 - 674]
[4]Zhang, Lianpeng; Lu, Ping; Wang, Yanguang [Organic and Biomolecular Chemistry, 2016, vol. 14, # 5, p. 1840 - 1840]
[5]Location in patent: scheme or table Kumar, Dalip; Kumar, N. Maruthi; Chang, Kuei-Hua; Gupta, Ritika; Shah, Kavita [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 19, p. 5897 - 5900]
[6]Zhang, Lianpeng; Lu, Ping; Wang, Yanguang [Organic and Biomolecular Chemistry, 2015, vol. 13, # 30, p. 8322 - 8329]

4
[ 10601-19-1 ]
[ 74-88-4 ]
[ 39974-94-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; mineral oil;	a. 5-Methoxy-1-methylindole-3-carboxaldehyde (43) 5-Methoxyindole-3-carboxaldehyde (300 mg, 1.71 mmol) was added in portions over 5 min to a suspension of sodium hydride (82 mg, 2.05 mmol, 60% dispersion in mineral oil) in DMF (8 mL) stirring under argon. The mixture was stirred for 30 min, methyl iodide (0.13 mL, 2.05 mmol) was added and the mixture was stirred for 1 h. Sodium bicarbonate (10%, 40 mL) was added and the mixture was extracted with EtOAc (4). The combined organic layers were washed with sodium bicarbonate (10%, 2) and saturated NaCl, dried (MgSO4), filtered and evaporated. Column chromatography of the crude product (50:50 EtOAc:hexanes) afforded 43 (320 mg, 99%) as a light yellow solid; Rf=0.35 (50:50 EtOAc:hexanes); mp=130-132 C.; lit mp=132-133 C.53; 1H NMR (CDCl3): delta 9.95 (s, 1H), 7.79 (d, 1H, J=2.4 Hz), 7.62 (s, 1H), 7.25 (d, J=8.8 Hz), 6.96 (dd, 1H, J=2.4 and 8.9 Hz), 3.90 (s, 3H), 3.85 (s, 3H).
		A solution of 5-methoxyindole-3-carboxaldehyde (80 g) in dimethylformamide (1 L) under nitrogen was treated portion-wise with sodium hydride (20.1 g, 60% dispersion in mineral oil) over 15 minutes. After stirring at ambient temperature for 30 minutes the mixture was treated dropwise with methyl iodide (31.3 mL) over 10 minutes and stirring was then continued for a further 2 hours. The reaction mixture was poured cautiously into water then extracted with ethyl acetate. The organic phase was washed with water, then dried over sodium sulfate and then evaporated. The residue was triturated with pentane to give the title compound (76 g) as a pale brown solid, m.p. 133-134 C. 1H NMR [(CD3)2SO]: delta 9.86 (1H, s); 8.20 (1H, s); 7.60 (1H, d, J=2.6 Hz); 7.50 (1H, d, J=8.9 Hz); 6.96 (1H, dd, J=8.9 and 2.6 Hz); 3.86 and 3.80 (6H, s).
		General procedure: Compounds 7-9 were synthesized from the corresponding compounds 4-6. A solution of compounds 4-6 (60 mmol) in THF (30 mL) were added dropwise to a suspension of NaH (3.60 g, 60% dispersion in mineral oil, 150 mmol) in THF (30 mL) at 0 C. After stirring for 15 min, the heterogeneous mixture was treated with iodomethane (5.04 mL, 79.2 mmol) at room temperature for 1 h. Then the reaction mixture was cooled to 0 C, quenched with saturated NH4Cl (60 mL), and extracted with ether (3 * 50 mL). The organic layers were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give 1-Methyl-1H-indole-3-carboxaldehyde (7-9), a light brown solid. The crude 7-9 were used in the next step without any further purification.

1.03 g		5-methoxy-indole 22 (1.78 g, 9.40 mmol) was added gradually and under dry argon to a suspension of NaH (0.564 g of a 60% dispersion, 14.11 mmol) in dry DMF (4 mL). The suspension was stirred at room temperature for 10 min and cooled to 0 C, and MeI (0.81 g, 5.71 mmol) was added over 5 min. The solution was then heated at 40 C for 30 min, cooled, poured into cold water. The mixture was extracted with EtOAc (2× 150 mL), dried and evaporated. The residue was used without purification (1.03 g, 95%). 1H NMR (300 MHz, DMSO-d6): delta (ppm) 9.72 (s, 1H), 8.45 (s, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.37 (d, J = 9.1 Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H); MS (ESI) m/z: 190.1 [M+H]+.
		To a suspension of NaH (8.9 g, 0.223 mol) in DMF (300 mL) was cooled in an ice-bath. To this, a solution of the starting amine (30 g, 0.171 mol) in DMF (150 mL) was added dropwise. The reaction mixture was stirred at rt for 60 minutes. Then iodomethane (31.5 g, 0.223 mol) was added. The reaction mixture was stirred at rt for 1 hour. Then the mixture was poured onto 10% aqueous solution of NaHCO3, extracted with EA. The combined organicphases were washed with 10% aqueous solution of NaHCO3, brine and dried. The solution was concentrated to get crude product, which was triturated from EAHex to afford product as a light-yellow solid (29.5 g, 91.2%)
	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 24h;	General procedure: The relevant indole-3-carboxaldehyde (2a-c, 10 mmol) in THF(25 mL) was added dropwise to a stirred solution of NaH (25 mmol)in THF (25 mL) at 0 C and CH3I (13.2 mmol) was added after 15 minstirring. The reaction mixturewas moved to room temperature andstirred for further 24 h. Then the solvent was removed in vacuumand the residue was extracted by ethyl acetate. The organic layerwas washed with brine, dried over anhydrous sodium sulfate,filtered and concentrated in vacuum. Recrystallization affordedcompound 3a-c with yields of 93.4-97.5%.

Reference： [1]Tetrahedron,2005,vol. 61,p. 1793 - 1801
[2]Organic Letters,2013,vol. 15,p. 2636 - 2639
[3]Patent: US2003/8850,2003,A1
[4]Journal of Medicinal Chemistry,2018,vol. 61,p. 6261 - 6276
[5]Chemical Biology and Drug Design,2015,vol. 86,p. 731 - 745
[6]Heterocyclic Communications,2010,vol. 16,p. 195 - 199
[7]Journal of Medicinal Chemistry,1997,vol. 40,p. 2335 - 2346
[8]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3111 - 3114
[9]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798
[10]Patent: US2004/9983,2004,A1 .Location in patent: Page/Page column 105
[11]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2586 - 2590
[12]European Journal of Medicinal Chemistry,2015,vol. 99,p. 125 - 137
[13]RSC Advances,2015,vol. 5,p. 68128 - 68135
[14]Journal of Medicinal Chemistry,2016,vol. 59,p. 5264 - 5283
[15]ChemMedChem,2016,vol. 11,p. 1446 - 1458
[16]European Journal of Medicinal Chemistry,2017,vol. 132,p. 310 - 321
[17]Organic and Biomolecular Chemistry,2017,vol. 15,p. 7404 - 7410
[18]Patent: WO2018/31662,2018,A1 .Location in patent: Page/Page column 176
[19]European Journal of Medicinal Chemistry,2018,vol. 156,p. 722 - 737
[20]Organic Letters,2019,vol. 21,p. 2602 - 2605
[21]Organic Letters,2019,vol. 21,p. 2048 - 2051

5
[ 10601-19-1 ]
[ 4455-09-8 ]
[ 416860-89-4 ]

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

6
[ 10601-19-1 ]
[ 98-68-0 ]
[ 651331-50-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 5-methoxyindole-3-carboxaldehyde With sodium hydroxide In dichloromethane at 20℃; Stage #2: 4-methoxy-phenyl-sulphonyl chloride In dichloromethane at 20℃;
94%	With potassium hydroxide In water; toluene at 20℃; for 4 - 5h;	80.1 Step 1: Preparation of 1-(4-Methoxy benzenesulfonyl)-5-methoxy-1H- indole-3- carboxyaldehyde) (117) [0455] To a dry round bottom flask, 5-methoxy indole-3-aldehyde 2 (1.0 g, 5.7 mmol) was dissolved with toluene (4 mL). Tetrabutylammonium iodide (10 mg) and 50% KOH solution (2 mL) were added next. After about 5 minutes of stirring, 4-methoxybenzene sulfonyl chloride (1.7 grams, 8. 2 mmol) was added. Within 2-3 hours, solid began to precipitate out of the solution. This reaction was allowed to stir at ambient temperature for 2 hours, after which water (50 mL) and ethyl acetate (150 ml) was added to the reaction. The layers were separated ; the organic layer was washed with saturated bicarbonate (3 X 75 mL) and water (4X 75 mL) to ensure removal of the hydroxide and sulfonate salt, and washed with brine (1 X 75 ml) and dried over anhydrous sodium sulfate. Evaporation under reduced pressure afforded 117 as a light brown solid. (1.86g, 94%) H NMR (CDC13) 8 10.0 (s, 1H), 8.20 (s, 1H), 7.92 (d, J = 9.2 Hz, 2H), 7.85 (d, J= 8.8, 1H), 7.74 (d, J= 2. 4, 1H), 7.04 (dd, J= 2.8 Hz, 9.2 Hz, 1H), 6.97 (d, J= 9.2 Hz, 2H), 3.85 (s, 3H).

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: DAIICHI SANKYO COMPANY, LIMITED - WO2005/9958, 2005, A1 Location in patent: Page 140-141

7
[ 1006-94-6 ]
[ 50-00-0 ]
[ 10601-19-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With iron(III) chloride; ammonia In water; N,N-dimethyl-formamide at 130℃; for 1h;	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).
89.5%	With iron(III) chloride; trichlorophosphate In water; N,N-dimethyl-formamide at 35℃; for 1h; Cooling with ice; Inert atmosphere;	2 Synthesis of Intermediate 3 0.68 mmol (147 mg) of 5-methoxyindole was dissolved in 200 μL of DMF for later use. Cool 340 μL of DMF with an ice water bath to 0°C and fill it with nitrogen protection, and then pour 100 μLPOCl3 into it. After it is fully dissolved, slowly add it to the DMF solution of 5-methoxyindole, and heat it to 35 under nitrogen protection. , the reaction was stirred for 1 h. After the reaction, it was quenched with ice water, NaOH solution and water were added successively, and then extracted with ethyl acetate. The solvent was recovered by distillation under reduced pressure and separated by column chromatography (PE: EtOAc = 97:3) to obtain the intermediate 3-aldehyde. The isolated yield of 5-methoxyindole was 89.5%.
	With acetic acid; diethylamine In water at 20℃; for 3h;

Reference： [1]Wang, Qing-Dong; Zhou, Bin; Yang, Jin-Ming; Fang, Dong; Ren, Jiangmeng; Zeng, Bu-Bing [Synlett, 2017, vol. 28, # 19, p. 2670 - 2674]
[2]Current Patent Assignee: TAIYUAN UNIVERSITY OF TECHNOLOGY - CN113620857, 2021, A Location in patent: Paragraph 0023; 0025; 0029
[3]Tsotinis, Andrew; Vlachou, Margarita; Papahatjis, Demetris P.; Calogeropoulou, Theodora; Nikas, Spyros P.; Garratt, Peter J.; Piccio, Vincent; Vonhoff, Stefan; Davidson, Kathryn; Teh, Muy-Teck; Sugden, David [Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3509 - 3519]

8
[ 10601-19-1 ]
[ 151-50-8 ]
[ 2436-17-1 ]

Yield	Reaction Conditions	Operation in experiment
1.08 g	With methyl iodide In methanol; water at 20℃; for 10h;

Reference： [1]Tsotinis, Andrew; Vlachou, Margarita; Papahatjis, Demetris P.; Calogeropoulou, Theodora; Nikas, Spyros P.; Garratt, Peter J.; Piccio, Vincent; Vonhoff, Stefan; Davidson, Kathryn; Teh, Muy-Teck; Sugden, David [Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3509 - 3519]

9
[ 5367-32-8 ]
[ 10601-19-1 ]

Reference： [1]Journal of medicinal chemistry,1995,vol. 38,p. 2331 - 2338

10
[ 10601-19-1 ]
[ 135531-92-9 ]

Reference： [1]Heterocycles,1991,vol. 32,p. 443 - 448

11
[ 7720-39-0 ]
[ 10601-19-1 ]
C₁₃H₁₃N₅O [ No CAS ]

Reference： [1]Medicinal Chemistry,2010,vol. 6,p. 344 - 354

12
[ 1006-94-6 ]
[ 100-97-0 ]
[ 10601-19-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	With iodine; oxygen; pyrographite In N,N-dimethyl-formamide at 120℃; for 0.8h;	2. General Procedure for the C3-Formylation of Indoles General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I2 (0.2 mmol, 0.0507g, 20 mol%) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO3 solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product.
71%	With water; iodine In N,N-dimethyl-formamide at 150℃; for 0.133333h; Flow reactor;	3. C3-formylation of indoles in the continuous flow reactor General procedure: The continuous flow reactor system consisted of the dual pump (KP-22-13, SS), PTFE tubing (length: 16 m, ID: 1 mm), T-junction (1.25 mm thru-hole), back pressure regulator (40, 75, 100, 250 psi), oil bath and hot plate. In this experiment, we used BOLA PTFE tubing to experiment at high temperature. In order to react stably at the temperature above the boiling point of water, looked for the maximum temperature conditions according to the pressure of the back pressure regulator in which the bubble does not occur. The reaction started in the concentration of indole (1.0 mmol), HMTA (2.0 mmol) and I 2 (1.0 mmol) in solvent (10 mL). Since this reaction proceeds in a single phase of liquid, the reaction time was set by the inner volume of tubing and the flow rate in the continuous flow reactor. After the reaction is over, the product was quantified using 1 H NMR and the NMR yield was obtained.
60%	With silica supported ceric ammonium nitrate In acetonitrile for 15h; 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).

With acetic acid for 2.5h; Reflux;

Reference： [1]Wang, Qing-Dong; Yang, Jin-Ming; Fang, Dong; Ren, Jiangmeng; Zeng, Bu-Bing [Tetrahedron Letters, 2017, vol. 58, # 30, p. 2877 - 2880]
[2]Sung, Ha Kyoung; Kim, Dong Hyun; Kim, Joon Seok; Park, Chan Pil [Bulletin of the Korean Chemical Society, 2021, vol. 42, # 3, p. 388 - 392]
[3]Tongkhan, Sukanya; Radchatawedchakoon, Widchaya; Kruanetr, Senee; Sakee, Uthai [Tetrahedron Letters, 2014, vol. 55, # 29, p. 3909 - 3912]
[4]Valeur, Eric; Christmann-Franck, Serge; Lepifre, Franck; Carniato, Denis; Cravo, Daniel; Charon, Christine; Bozec, Sophie; Musil, Djordje; Hillertz, Per; Doare, Liliane; Schmidlin, Fabien; Lecomte, Marc; Schultz, Melanie; Roche, Didier [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 18, p. 5909 - 5914]

13
[ 10601-19-1 ]
[ 15317-58-5 ]
[ 1431138-16-7 ]

Reference： [1]ChemMedChem,2012,vol. 7,p. 1915 - 1920

14
[ 10601-19-1 ]
[ 15317-58-5 ]
[ 1431138-04-3 ]

Reference： [1]ChemMedChem,2012,vol. 7,p. 1915 - 1920

15
[ 10601-19-1 ]
[ 21987-25-7 ]

Yield	Reaction Conditions	Operation in experiment
98.5%	With N,N,N,N,N,N-hexamethylphosphoric triamide; hydrazine hydrate monohydrate; potassium hydroxide at 120℃; Green chemistry;	7-9 Example 7 16.16 g (99%, 0.1 mol) of 5-methoxyindole-3-carbaldehyde and 9.15 g (92%, 0.15 mol) of potassium hydroxide, 7.65 g (98%, 0.15 mol) of hydrazine hydrate and 100 mL of hexamethylphosphoramide was placed in a round bottom flask. Stirring and refluxing reaction for 1 h, Continue heating to distill off the water and the pre-fraction. Continue to heat up to 120 ° C, Keep warm for 2~3h, Then the solvent was distilled off under reduced pressure. Processed 5-methoxy-3-methylindole 15.84g, Product purity is 99.5%, 5-methoxyindole-3-formaldehyde conversion rate 100.0%, The yield of 5-methoxy-3-methylindole was 98.5%.
40%	With lithium aluminium hydride In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; Schlenk technique;

	Multi-step reaction with 2 steps 1: lithium aluminium hydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere 2: sodium hydroxide; magnesium(II) sulfate / lithium hydroxide monohydrate; diethyl ether / 0.5 h / 0 °C
400 mg	With lithium aluminium hydride In tetrahydrofuran for 3h; Inert atmosphere; Reflux;	1C.76.A Preparation of 5-methoxy-3-methyl-1H-indole To a solution of 5-methoxy-1H-indole-3-carbaldehyde (500 mg, 2.854 mmol) in THF (10 mL) at room temperature was added a 2M solution of LiAlH4in THF (2.846 mL, 5.691 mmol) drop wise under nitrogen. The reaction mixture was stirred for 3 h at reflux. After cooled down in an ice-water bath, the reaction was quenched carefully with water (216 μL), aqueous 15% NaOH solution (216 μL) and water (3 x 216 μL). The mixture was filtered, the filtrate was concentrated. The residue was purified by silica gel column chromatography to give the title compound (400 mg) as an oil. LCMS m/z = 162.2 [M+H]+; NMR (400 MHz, CDC13) δ ppm 2.31 (d, J = 1.1 Hz, 3H), 3.88 (s, 3H), 6.86 (dd, J = 8.7 and 2.4 Hz, 1H), 6.94-6.97 (m, 1H), 7.02 (d, J = 2.4 Hz, 1H), 7.24 (dd, J = 8.8 and 0.4 Hz, 1H), 7.76 (bs, 1H).
225 mg	With lithium aluminium hydride In tetrahydrofuran at 20℃;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; Schlenk technique;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; for 12h;
	With lithium aluminium hydride In tetrahydrofuran at 20℃;
	With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN109678780, 2019, A Location in patent: Paragraph 0031-0033
[2]Chang, Rong; Gao, Xuebo; Guo, Zhen; Hao, Danyang; Rao, Junxin; Zhang, Zhuxia; Zhou, Cong-Ying [Journal of Organic Chemistry, 2022]
[3]Cheng, Hong-Gang; Lu, Liang-Qiu; Wang, Tao; Yang, Qing-Qing; Liu, Xiao-Peng; Li, Yang; Deng, Qiao-Hui; Chen, Jia-Rong; Xiao, Wen-Jing [Angewandte Chemie - International Edition, 2013, vol. 52, # 11, p. 3250 - 3254][Angew. Chem., 2013, vol. 125, # 11, p. 3332 - 3336,5]
[4]Beaud, Rodolphe; Guillot, Regis; Kouklovsky, Cyrille; Vincent, Guillaume [Chemistry - A European Journal, 2014, vol. 20, # 24, p. 7492 - 7500]
[5]Current Patent Assignee: PFIZER INC - WO2015/66344, 2015, A1 Location in patent: Page/Page column 233
[6]Shao, Changdong; Shi, Guangfa; Zhang, Yanghui; Pan, Shulei; Guan, Xiaohong [Organic Letters, 2015, vol. 17, # 11, p. 2652 - 2655]
[7]Chen, Weiliang; Xia, Yong; Lin, Lili; Yuan, Xiao; Guo, Songsong; Liu, Xiaohua; Feng, Xiaoming [Chemistry - A European Journal, 2015, vol. 21, # 43, p. 15104 - 15107]
[8]Zhou, Zijun; Li, Yanjun; Gong, Lei; Meggers, Eric [Organic Letters, 2017, vol. 19, # 1, p. 222 - 225]
[9]Wang, Shuai; Shen, Yao-Bin; Li, Long-Fei; Qiu, Bin; Yu, Liping; Liu, Qing; Xiao, Jian [Organic Letters, 2019, p. 8904 - 8908]
[10]Bai, Jian-Fei; Zhao, Lulu; Wang, Fang; Yan, Fachao; Kano, Taichi; Maruoka, Keiji; Li, Yuehui [Organic Letters, 2020, vol. 22, # 14, p. 5439 - 5445]
[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]Devi, Manju; Jadhav, Amol P.; Singh, Ravi P. [New Journal of Chemistry, 2021, vol. 45, # 19, p. 8445 - 8448]

16
[ 1640-39-7 ]
[ 10601-19-1 ]
[ 1448422-50-1 ]

Yield	Reaction Conditions	Operation in experiment
80.2%	Stage #1: 2,3,3-trimethylindoleniune With hydrogenchloride In water at 20℃; for 0.5h; Stage #2: 5-methoxyindole-3-carboxaldehyde In ethanol for 4h; Reflux; Inert atmosphere;	5.2.2. Synthesis of simplified vinca alkaloids (5a-k) General procedure: General procedure: Concentrated hydrochloric acid (1.5 mL) was added dropwise into 2,3,3-trimethylindolenine (159.2 mg, 1.0 mmol). The mixture was stirred at room temperature for 30 min. Then excess reagent was removed by rotary evaporation under reduced pressure to give 2,3,3-trimethylindolenine hydrochloride (2) 195.7 mg (1.0 mmol). The HCl saltwas then dissolved in anhydrous ethanol (10 mL) followed the addition of substituted indole-3-carbaldehyde 4a-k (1.1 mmol). The mixture was allowed to reflux for 4 h in an atmosphere of pure nitrogen. The reaction was monitored by TLC until the disappearance of starting materials. Then the reaction mixture was cooled to room temperature and extracted with dichloromethane (3 x 50 mL). The combined organic layer was washed with water and brine, and dried over anhydrous MgSO4. Removal of excess solvent was carried on by rotary evaporation under reduced pressure to get the crude product. The residue was further purified by flash column chromatography using ethyl acetate/petroleum ether (3:2, v/v) as the eluent to give pure products (5a-k).

Reference： [1]Zheng, Jing; Deng, Lijuan; Chen, Minfeng; Xiao, Xuzhi; Xiao, Shengwei; Guo, Cuiping; Xiao, Gaokeng; Bai, Liangliang; Ye, Wencai; Zhang, Dongmei; Chen, Heru [European Journal of Medicinal Chemistry, 2013, vol. 65, p. 158 - 167]

17
[ 10601-19-1 ]
[ 198821-79-3 ]
C₂₀H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	General procedure: The mixture of the compound 15 (190.2 mg, 1.0 mmol) and 2-thiophenecarboxaldehyde (123.4 mg, 1.1 mol) in anhydrous ethanol (3.0 mL) was stirred over night at room temperature or reflux temperature. The corresponding imine was reduced with solid sodium borohydride (75.7 mg, 2.0 mmol) which was added slowly, the mixture was further stirred over night at room temperature. An additional ethanol (2.0 mL) was added to the reaction vessel after which 10% hydrochloric acid aqueous solution was added to quench excess sodium borohydride. The acidic mixture was basified with 25% aqueous ammonia solution. The desired product was extracted with dichloromethane (3 20 mL) and the solution was dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel, eluting with a gradient of 40-60% ethyl acetate in petroleum ether to give the title compound 17a1 [164.9 mg, 57.6% (from 15)] as a white solid, mp 100-101 C.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 69,p. 32 - 43

18
[ 10601-19-1 ]
[ 198821-79-3 ]
N-[(5-methoxy-1H-3-indolyl)methyl][3-methoxy-4-(5-oxazolyl)phenyl]amine [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 69,p. 32 - 43

19
[ 10601-19-1 ]
[ 3619-17-8 ]
C₁₄H₁₇N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63.81%	In methanol at 60℃; for 12h;

Reference： [1]Meng, Xia; Wang, Xingjian; Duan, Hongdong; Bu, Juan; Qin, Dawei; Zhang, Yi [Research on Chemical Intermediates, 2013, vol. 39, # 8, p. 3829 - 3833]

20
[ 10601-19-1 ]
[ 15362-40-0 ]
[ 1574402-13-3 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium hydroxide; In ethanol; water;	General procedure: A finely ground mixture of 5-substituted indole-3-carboxaldehyde (1 mmol) and active methylene compound (indolinone/oxindole/barbituric acid/1-(3-chlorophenyl)-3-methyl-2-pyrazolin-5-one)/2-trifluoromethylbenzaldehyde (1.2 mmol) was irradiated in microwave oven for 1-5 min. The solid product was washed with diethyl ether and purified by column chromatography to get pure products 2-5 and 11-28 except compound 3. Compound 3 was prepared by treatment of 5-substituted indole-3-carboxaldehyde with indolinone in ethanol-water in presence of NaOH (1.5 mmol).

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 74,p. 440 - 450

21
[ 10601-19-1 ]
DMS [ No CAS ]
[ 39974-94-2 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 1569 - 1580

22
[ 10601-19-1 ]
[ 10297-73-1 ]
3-(5-methoxy-1H-indol-3-yl)-1-(4-(methylsulfonyl)phenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydroxide In ethanol; water at 20℃; for 10h;	3.2.1. 3-(5-Substituted-1H-indol-3-yl)/(1-methyl-1H-indol-3-yl)-1-(4-(substituted)phenyl)prop-2-en-1-ones (1-9) General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completation, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol.

Reference： [1]Özdemir, Ahmet; Altintop, Mehlika Dilek; Turan-Zitouni, Gülhan; Çiftҫi, Gülşen Akalin; Ertorun, Öipek; Alataş, Özkan; Kaplancikli, Zafer Asim [European Journal of Medicinal Chemistry, 2014, vol. 89, p. 304 - 309]

23
[ 1006-94-6 ]
[ 110-18-9 ]
[ 10601-19-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With water; iodine; oxygen; sodium carbonate In 1,4-dioxane at 100℃; for 36h; Schlenk technique; Sealed tube;	Experimental Procedures for the C3-Formylation of Indoles General procedure: Under air, a 20 mL of Schlenk tube equipped with a stir bar was charged with indole 1 (0.2 mmol, 1 equiv),TMEDA (75 µL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 µL). Then I2 (101.5 mg, 0.4 mmol, 2.0 equiv) was added and the tube was sealed with a rubber plug and charged with O2. The reaction mixture was stirred at 100 °C for 36 h in oil bath. After cooling to room temperature, the resultant mixture was evaporated with EtOAc (20 mL) under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the products.

Reference： [1]Zhang, Bo; Liu, Bin; Chen, Jianbin; Wang, Jiehui; Liu, Miaochang [Tetrahedron Letters, 2014, vol. 55, # 41, p. 5618 - 5621]

24
[ 10601-19-1 ]
[ 16718-42-6 ]
(E)-4,5,6-trimethoxy-2-((5-methoxy-1H-indol-3-yl)methylene)-2,3-dihydro-1H-inden-1-one [ No CAS ]

Reference： [1]RSC Advances,2015,vol. 5,p. 68128 - 68135

25
[ 10601-19-1 ]
[ 5055-39-0 ]
N'-((5-methoxy-1H-indol-3-yl)methylene)-1H-indole-3-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In ethanol at 80℃; for 5h;	General Procedure for Synthesis of Bis(indolyl)-hydrazide-Hydazones (NMK-BH1-6). General procedure: The intermediatesindole-2(3)-carbohydrazide (2) and indole-3-carboxaldehyde(4) were prepared starting from commercially available indole,as described previously. Indole-3-carboxylic acids 1were prepared from the reaction of indole with trifluoroaceticanhydride followed by hydrolysis with sodium hydroxide. Toobtain the corresponding ester, a solution of indole-3-carboxylicacid 1 (1 mmol) in absolute ethanol (20 mL) was refluxed witha catalytic amount of concentrated sulfuric acid for 20 h and theresidue was extracted with ethyl acetate (30 mL), washed with asaturated sodium bicarbonate solution (20 mL), dried, andevaporated. As shown in Scheme 1, a solution of theappropriate ester (1 mmol) and hydrazine hydrate (2 mmol)in ethanol (15 mL) was refluxed for 24 h and cooled, and thesolid that was obtained was filtered and recrystallized fromethanol to give pure indole-2(3)-carbohydrazide (2) in 85-90% yield.For preparation of indole-3-carboxaldehydes 4, withcontinuous stirring, phosphorous oxychloride (8.41 mL, 90mmol) was added to 0 °C dimethylformamide (28 mL, 370mmol) for 30 min followed by addition of a solution of indole 3(85.47 mmol) in DMF (10 mL, 130 mmol) at roomtemperature until it became a yellow paste. At the end of thereaction, 30 g of crushed ice was added to the paste followed bydropwise addition of a sodium hydroxide solution (1 N solution, 100 mL) while the mixture was being stirred. Theresulting suspension was heated rapidly to 90 °C, cooled atroom temperature, and refrigerated overnight. The product wasfiltered, washed with water (2 × 100 mL), and air-dried toafford the pure indole-3-carboxaldehydes 4 in 80-90% yields(Scheme 1).Finally, to the mixture of indole-2(3)-carboxylic acidhydrazide 2 (1 mmol) and indole-3-carboxaldehyde 4 (1mmol) in absolute ethanol (20 mL) was added a catalyticamount of glacial acetic acid, and the mixture was refluxed at 80°C for 5 h and cooled and the solid that separated out wasfiltered and recrystallized from ethanol to afford bis(indolyl)-hydrazide-hydrazones in 75-90% yields (Scheme 1).

Reference： [1]Das Mukherjee, Dipanwita; Kumar, N. Maruthi; Tantak, Mukund P.; Das, Amlan; Ganguli, Arnab; Datta, Satabdi; Kumar, Dalip; Chakrabarti, Gopal [Biochemistry, 2016, vol. 55, # 21, p. 3020 - 3035]

26
[ 10601-19-1 ]
[ 70291-62-2 ]
2-[(5-methoxy-1H-indol-3-ylmethylene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With acetic acid In ethanol at 20℃; for 24h;	General procedure for synthesis of 2-[(indolyl)methylene)amino]cycloalka[b]thiophene-3-carbonitrile (TN5, TN5 1-7, TN6,TN6 1-7, TN7, TN7 1-7, TN8, TN8 1-7). General procedure: An equimolar mixture of Gewald adducts (5CN, 6CN, 7CN and 8CN) and substituted indole-carboxaldehydes in absolute ethanol with 0.5 mL of acetic acid was stirred under room temperature for 24 hs. Water was addedand the solid that precipitated out was filtered under vacuum, washed with water, dried and recrystallized from absolute ethanol (Scheme 1) according previously methodology [20].

Reference： [1]Félix, Mayara B.; de Souza, Edson R.; de Lima, Maria do C.A.; Frade, Daiana Karla G.; Serafim, Vanessa de L.; Rodrigues, Klinger Antonio da F.; Néris, Patrícia Lima do N.; Ribeiro, Frederico F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; Mendonça Junior, Francisco Jaime B.; de Oliveira, Márcia R. [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 18, p. 3972 - 3977]

27
[ 23917-22-8 ]
[ 10601-19-1 ]
2-[(5-methoxy-1H-indol-3-ylmethylene)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With acetic acid In ethanol at 20℃; for 24h;	General procedure for synthesis of 2-[(indolyl)methylene)amino]cycloalka[b]thiophene-3-carbonitrile (TN5, TN5 1-7, TN6,TN6 1-7, TN7, TN7 1-7, TN8, TN8 1-7). General procedure: An equimolar mixture of Gewald adducts (5CN, 6CN, 7CN and 8CN) and substituted indole-carboxaldehydes in absolute ethanol with 0.5 mL of acetic acid was stirred under room temperature for 24 hs. Water was addedand the solid that precipitated out was filtered under vacuum, washed with water, dried and recrystallized from absolute ethanol (Scheme 1) according previously methodology [20].

Reference： [1]Félix, Mayara B.; de Souza, Edson R.; de Lima, Maria do C.A.; Frade, Daiana Karla G.; Serafim, Vanessa de L.; Rodrigues, Klinger Antonio da F.; Néris, Patrícia Lima do N.; Ribeiro, Frederico F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; Mendonça Junior, Francisco Jaime B.; de Oliveira, Márcia R. [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 18, p. 3972 - 3977]

28
[ 10601-19-1 ]
[ 73-31-4 ]

Reference： [1]Green Chemistry,2017,vol. 19,p. 2952 - 2956

29
[ 10601-19-1 ]
[ 118427-29-5 ]
(E)-3-(2(4-isopropylphenyl)hydrazonomethyl)-5-methoxy-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	In methanol at 20℃;	3.1.4. Synthesis of Compound 19 4-isopropylphenylhydrazine hydrochloride (1.8 mmol) was added to a solution of5-methoxy-indole-3-carbaldehyde (1 mmol) in methanol (5 mL). After stirring overnight at roomtemperature, the resulting precipitate was filtered and crystallized.

Reference： [1]Purgatorio, Rosa; De Candia, Modesto; De Palma, Annalisa; De Santis, Francesco; Pisani, Leonardo; Campagna, Francesco; Cellamare, Saverio; Altomare, Cosimo Damiano; Catto, Marco [Molecules, 2018, vol. 23, # 7]

30
[ 10601-19-1 ]
[ 140-87-4 ]
2-cyano-N'-((5-methoxy-1H-indol-3-yl)methylene)acetohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.8%	With acetic acid In ethanol at 20℃; for 12h;	5 2-Cyano-N'-((4-nitro-1H-indol-3-yl)methylene)acetohydrazide (3d) 4.1.1.5 2-Cyano-N'-((5-methoxy-1H-indol-3-yl)methylene)acetohydrazide (3e) Compound 3e was obtained as yellow powder (81.8%). M.p. (°C): 212-214. Rf (6:4 AcOEt/n-hexane): 0.42. IR (KBr): 1254.6 (NH, Ar), 1620.2 (C=N), 1672.9 (HN-C=O), 2269.3 (CN), 3332.5 (NH) cm-1. NMR 1H (300 MHz, DMSO-d6): δ (s, 3H, CH3), 4.21 (s, 2H, CH2), 6.83 (d, 1H, J 8.7 Hz, ArH), 7.33 (d, 1H, J 8.7 Hz, ArH), 7.61 (s, 1H, ArH), 7.75 (s, 1H, ArNCH), 8.17 (s, 1H, N=CH), 11.46 (s, 2H, ArNH e NH). NMR 13C (75 MHz, DMSO-d6): δ 24.78 (CH2), 55.53 (CH3), 103.81 (CH, Ar), 111.33 (C, Ar), 113.11 (CH, Ar), 116.76 (CN), 124.91 (C, Ar), 131.63 (HC-N, Ar), 132.31 (C-N, Ar), 142.46 (HC=N), 154.92 (C-OCH3, Ar), 164.07 (C=O). HRMS m/z [M+H]+ calcd for C13H12N4O2: 256.0960; found: 256.0876.

Reference： [1]Moraes, Ana Daura Travassos de Oliveira; Miranda, Mirelly Dianne Santos de; Jacob, Íris Trindade Tenório; Amorim, Cézar Augusto da Cruz; Moura, Ricardo Olímpio de; Silva, Simone Ângela Soares da; Soares, Milena Botelho Pereira; Almeida, Sinara Mônica Vitalino de; Souza, Túlio Ricardo Couto de Lima; Oliveira, Jamerson Ferreira de; Silva, Teresinha Gonçalves da; Melo, Cristiane Moutinho Lagos de; Moreira, Diogo Rodrigo Magalhães; Lima, Maria do Carmo Alves de [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 20, p. 5388 - 5396]

31
[ 10601-19-1 ]
[ 236406-39-6 ]
C₂₃H₃₃N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium cyanoborohydride; acetic acid; In methanol; at 20 - 50℃;pH 6-7;	General procedure: To a stirring solution of 8 (0.3 mmol) in MeOH (5 mL) was added the corresponding aldehyde (0.4 mmol) and NaCNBH3 (0.5 mmol)at room temperature. The mixture was adjusted to pH 6-7 by acetic acid, stirred overnight at room temperature, and quenched by 1M NaOH solution (5 mL). The mixture was diluted by H2O (15 mL), and extracted by DCM (10mL x 3). The combined organic layer waswashed by brine, dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified over silica gel column(DCM: MeOH = 20 : 1) to yield oils 9b-s (70-93%).

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 179,p. 208 - 217

32
[ 10601-19-1 ]
[ 13221-86-8 ]
2,4-dihydroxy-N'-[(E)-(5-methoxy-1H-indol-3-yl)methylidene]benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	In ethanol Reflux;	4.2. General procedure for the synthesis of compounds 3a-i General procedure: To an ethanol solution of an appropriate hydrazides 2a-i (2.0 mmol) a stirred solution of 5-methoxyindole-3-carboxaldehyde 1 (2.0 mmol) in abs. ethanol was added. The solution was refluxed for 2-3 h. The solid product formed 3a-i was collected by filtration and recrystallized with ethanol.

Reference： [1]Angelova, Violina T.; Rangelov, Miroslav; Todorova, Nadezhda; Dangalov, Miroslav; Andreeva-Gateva, Pavlina; Kondeva-Burdina, Magdalena; Karabeliov, Valentin; Shivachev, Boris; Tchekalarova, Jana [Bioorganic Chemistry, 2019, vol. 90]

33
[ 10601-19-1 ]
[ 15317-58-5 ]
N'-[(E)-(5-methoxy-1H-indol-3-yl)methylidene]-1H-indole-3-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	In ethanol;Reflux;	General procedure: To an ethanol solution of an appropriate hydrazides 2a-i (2.0 mmol) a stirred solution of 5-methoxyindole-3-carboxaldehyde 1 (2.0 mmol) in abs. ethanol was added. The solution was refluxed for 2-3 h. The solid product formed 3a-i was collected by filtration and recrystallized with ethanol.

Reference： [1]Bioorganic Chemistry,2019,vol. 90

34
[ 10601-19-1 ]
[ 2301-80-6 ]
4-((E)-2-(5-methoxy-1H-indol-3-yl)vinyl)-1-methylpyridinium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With piperidine In methanol for 2h; Reflux;	General procedure for the synthesis of mono-styryl dyes by Knoevenagel condensation General procedure: A mixture of the heterocyclic salt I17-I18 (1 mmol), aldehyde (1.5 mmol), and piperidine (0.10 mL, 1 mmol) in MeOH (5 mL) was heated under reflux for 2 h. After cooling toroom temperature, the precipitated solid was collected by filtration, washed with MeOH (2 × 5mL), Et2O (2 × 5 mL), dried and recrystallized from a suitable solvent (as indicated below), togive the analytically pure dye as an iodide salt.

Reference： [1]Xie, Xiao; Zuffo, Michela; Teulade-Fichou, Marie-Paule; Granzhan, Anton [Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 1872 - 1889]

35
[ 10601-19-1 ]
[ 5448-47-5 ]
2-(1H-indol-3-yl)-N'-[(Z)-(5-methoxy-1H-indol-3yl)methylidene]acetohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol Reflux;	Synthetic procedure for obtaining hydrazone derivatives 5a-5g General procedure: Stirred solution of substitutedcarbaldehydes (2.0 mmol) 4 in abs. ethanol was added to a solution of an appropriate hydrazide 1 (2.0 mmol) in abs. ethanol. The solution obtained was refluxed for 2-3 h. The solid product formed was collected by filtration.

Reference： [1]Angelova, Violina T.; K.-Yovkova, Elena; Karabeliov, Valentin R.; Kondeva-Burdina, Magdalena S.; Vassilev, Nikolay G. [Bioorganic and Medicinal Chemistry Letters, 2022, vol. 59]

36
[ 17831-88-8 ]
[ 10601-19-1 ]
4-(5-methoxy-1H-indole-3-carbonyl)-2H-chromen-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.4%	With sodium hydride; 1,3-dimethyl-1H-imidazol-3-ium iodide In N,N-dimethyl-formamide at 25℃; for 8h;	5.9. Synthesis of compounds 17a-17c General procedure: 5-Chloro-2H-chromen-2-one (8) (1.2 mmol, 1.2 eq), commerciallyavailable indole aldehydes (1.0 mmol, 1.0 eq), 1,3-dimethylimidazoliumiodide (0.1 mmol, 0.1 eq) (0.1 mmol, 0.1 eq) and NaH (0.1mmol, 0.1 eq) were added into 10 mL of DMF and then stirred at 25 Cfor 8 h. Then, the mixture was added 20 mL H2O and extracted with 20mL EtOAc for three times. The combined organic layer was then washedwith brine, dried over anhydrous Na2SO4, and concentrated underreduced pressure to provide the crude products. Finally, the crudeproducts were then purified by silica gel column chromatography usingPE/EA (3/1, v/v) as eluents to get compounds 17a-17c.

Reference： [1]Song, Jian; Guan, Yong-Feng; Liu, Wen-Bo; Song, Chun-Hong; Tian, Xin-Yi; Zhu, Ting; Fu, Xiang-Jing; Qi, Ying-Qiu; Zhang, Sai-Yang [European Journal of Medicinal Chemistry, 2022, vol. 238]

37
[ 6272-26-0 ]
[ 10601-19-1 ]
[ 1200534-45-7 ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium hydroxide In methanol; lithium hydroxide monohydrate at 25℃;	General procedure for the synthesis of compounds 1-18 (method A). General procedure: To a suspension of 1 mmol of 6-hydroxybenzofuran-3(2H)-one in 5 mL of a 1 : 1 mixture of water and methanol was added 1 mL of 50% aqueous KOH. To this clear solution, obtained after stirring for 10 min, was added 1.2 mmol of the appropriate carboxaldehyde. The mixture was stirred for 6-8 h at 25°C then diluted with 20 mL of hot water and acidified with glacial acetic acid to pH 5. The resulting precipitate was collected by filtration, washed with water, dried and recrystallized from methanol to give the corresponding target compounds.

Reference： [1]Li, Yi; Zhao, Haiqing; Niu, Chao; Aisa, Haji Akber; Hou, Xueling [Russian Journal of General Chemistry, 2022, vol. 92, # 8, p. 1562 - 1573][Zh. Obshch. Khim., 2022, vol. 92, # 8, p. 1562 - 1573]

38
[ 10601-19-1 ]
[ 18699-02-0 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
85%	With piperidine; triethylamine In 1,4-dioxane at 90℃; Inert atmosphere; Sealed tube;

Reference： [1]Kelly, Brendan J.; Diez-Cecilia, Elena; Pan, Luzhe; Sweeting, Braden; Villar, Laura; Kreft, Alexander; Gupta, Mayuri; Johnson, Shea L.; Weaver, Donald F. [Canadian Journal of Chemistry, 2022, vol. 100, # 9, p. 660 - 675]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	10601-19-1	MDL No. :	MFCD00005623
Formula :	C₁₀H₉NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	TUWARWGEOHQXCO-UHFFFAOYSA-N
M.W :	175.18	Pubchem ID :	82758
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.1
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	50.18
TPSA :	42.09 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.32 cm/s

Log Po/w (iLOGP) :	1.48
Log Po/w (XLOGP3) :	1.48
Log Po/w (WLOGP) :	1.99
Log Po/w (MLOGP) :	0.57
Log Po/w (SILICOS-IT) :	2.65
Consensus Log Po/w :	1.63

[ CAS No. 10601-19-1 ] {[proInfo.proName]}

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[ 10601-19-1 ] Synthesis Path-Upstream 1~21

[ 10601-19-1 ] Synthesis Path-Downstream 1~38

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[ 10601-19-1 ]

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[ 10601-19-1 ]

Indoles

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

Log S (ESOL) :	-2.24
Solubility :	1.01 mg/ml ; 0.00577 mol/l
Class :	Soluble
Log S (Ali) :	-1.97
Solubility :	1.87 mg/ml ; 0.0107 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.36
Solubility :	0.0772 mg/ml ; 0.000441 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.28

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:

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: at 0℃; for 1 h; Stage #2: at 20℃; for 5 h; Stage #3: With sodium hydroxide In N,N-dimethyl-formamide at 100℃; for 0.166667 h;	General procedure: Oxalyl chloride (0.3 mL) was added in a drop-wise manner to cooled (ice-bath) DMF (3 mL) under stirring. The mixture was then stirred at 0 °C for 1 h. A solution of the substituted indole (4 mmol) in DMF (1.5 mL) was then added to the reaction mixture in a dropwise manner. The resulting mixture was stirred at room temperature for 5 h. A 2 N solution of sodium hydroxide (2 mL) was then added, and the mixture was heated at 100 °C for 10 min. The mixture was then cooled and extracted with ethyl acetate (3 X 50 mL). The organic layers were combined and washed with sequentially water and brine. The organics were dried (Na₂SO₄) and distilled to dryness to give the crude residue, which was purified by flash column chromatography using ethyl acetate/petroleum ether (3:1, v/v) as the eluent to give pure indole-3-carbaldehyde (4a-k).
92%	at 0 - 55℃; for 2 h;	General procedure: To a solution of compounds 17a, 17b (10 mmol) in 20 mL of DMF, phosphorus oxychloride (1.4 mL, 15 mmol) was added dropwise at 0°C. In 2 h of the reaction at 55°C, the mixture was poured into 150 mL of ice water. 20 percent NaOH solution was added to adjust pH at 8.0. The crude product was filtered off and recrystallized from anhydrous ethanol to give the corresponding product.
89.4%	at 35℃;	General procedure: To a stirring solution of POCl₃ (18.36 g, 0.120 mol) in DMF (25 mL), indole (11.7 g, 0.100 mol) in DMF (15 mL) was added dropwise. The mixture was stirred at 35°C for 1 h, and then be poured into ice water and neutralized with 20 percent NaOH aq. The solution was filtered and the residue was washed with water and dried under IR to give the compound 4a as yellow needle (13.86 g, 95.48 percent). Mp = 192–194°C, lit.³¹ Mp = 196–197°C.

85%	Stage #1: at 0℃; Stage #2: at 0℃; for 0.5 h; Stage #3: With sodium hydroxide In waterCooling with ice; Reflux	Synthesis of 5-methoxy-indole-3-carbaldehydes; Preparation of S-methoxy-indole-3-carbaldehyde, 5-methoxy-2-methyl-indole-3- carbaldehyde, and 3-formyl-5-methoxy-indole-2-carboxylic acid POCI₃ (1.6 ml_, 17 mmol, 1.1 eq.) was added to DMF (6 mL) at 0⁰C and the solution was stirred for 30 minutes. This mixture was added to a stirring solution of the selected 5-methoxy- indole (15.5 mmol, 1 eq.) in DMF (11.5 mL) at 0⁰C. The resulting mixture was stirred at 0⁰C for 30 minutes, then allowed to warm to room temperature. The reaction was poured into ice, basified to pH 10 with 5 N NaOH, warmed to room temperature, refluxed for 5 minutes and allowed to cool to rt. Finally, it was acidified to pH 4 with 2 N HCI and the resulting precipitate was filtered and washed with water until pH 7. The solid product was dried under vacuum.5-Methoxy-indole-3-carbaldehydeYield: 85percent. MS (m/z): 176.2 (MH⁺).
83%	at 0 - 40℃; for 1.5 h;	General procedure: Phosphorus oxychloride (0.42 g, 2.74 mmol) was added dropwise to a solution of the indole 5b, 5e–5g (0.30 g, 2.29 mmol) in DMF (0.84 g, 11.4 mmol) at 0 °C for 30 min. The solution was then heated at 40 °C for 1 h. Ice was added to the reaction vessel, followed by a solution of sodium hydroxide (2 M). The solution was refluxed for 40 min. The mixture was cooled and extracted using ethyl acetate, and the organic phase was washed with brine. The organic extracts were combined, dried over Na₂SO₄, and concentrated. The crude residue was purified by chromatography on a silica gel column using hexane-ethyl acetate as an eluent to obtain the desired product [19].
79%	at 20℃; for 1 h;	A 5-methoxy-1H-indole (14.7 g, 0.1 mol) was dissolved in N, N -dimethylformamide (73.5 g, 1 mol) in a 500ml of reaction flask at 0 ° C with mechanical agitation, then phosphorus pentachloride / N, N -dimethylformamide mixed formylation reagent (15 g, 0.12 mol) was added in portions. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, 100 mL of water was added and stirred at room temperature for 1 hour. The reaction was neutralized with 2N sodium hydroxide solution and the resulting suspension was filtered. The filter cake was dissolved in methanol / tetrahydrofuran and the pH was adjusted to 1 with concentrated hydrochloric acid. The solution was stirred at room temperature for 45 minutes and neutralized with 4N sodium hydroxide solution to neutral. The solvent was partially evaporated to give the product, filtered and washed with water. Finally, 5-methoxy-1-hydrogen-indole-3- carboxaldehyde was obtained (14 g, 79percent). This product can be used in the production of Tegaserod Hydrogen Maleate.
69%	Stage #1: at 20℃; for 0.75 h; Cooling with ice Stage #2: at 40℃; for 1.25 h;	The Vilsmeier-Haack reagent was generated by the addition of 2 ml of POCI3 over the course of15 minutes to 8 ml of DMF cooled in an ice-salt bath. After the addition was complete, the icebath was removed and the contents of the flask allowed to warm to room temperature overapprox. 30 minutes. The substituted indole (21.9 mmol) was dissolved in 10 ml of DMF andadded over a period of 15 minutes to the formylating mixture. The stirring was continued for an10 hour during which the flask contents were heated to 40°C in a hot water bath. A total of 50 mlice cold H20 and 20 ml of 5 M NaOH were added, the mixture quickly brought to a boil and leftto cool slowly. The crystals were removed by filtration, washed with cold water and vacuumdried. The products thus obtained were in most cases sufficiently pure for the subsequentreactions, and the impure aldehydes were recrystallized from ethanol-water mixtures. Yields15 varied from 48 to 90percent.; The compound was synthesized from 5-methoxy-1H-indole (170 mmol) according to the25 general procedure 2, with the exception that it was scaled up proportionally to the 5-methoxyindole (69percent yield).LC-MS: m/z = 176.11; tR = 2.20 min.
63%	at 20℃; for 1 h;	(a) 5-methoxyindole (200 mg, 1.36 mmol) dissolved in anhydrous DMF,Drip the newly prepared Vilsmeier reagent,Allow to react at room temperature for one hour, then pour into ice water and filter by suction.Dryed to a yellow solid 150 mg, yield 63percent.

Yield	Reaction Conditions	Operation in experiment
91%	With iodine; oxygen; pyrographite In N,N-dimethyl-formamide at 120℃; for 0.8 h;	General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I₂(0.2 mmol, 0.0507g, 20 molpercent) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 ^oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO₃ solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na₂SO₄and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product.
60%	With silica supported ceric ammonium nitrate In acetonitrile for 15 h; Reflux	General procedure: a mixture of indole (1 mmol), HMTA (2.5 mmol), and 10percent 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).

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydrogencarbonate In N,N-dimethyl-formamide; mineral oil	a. 5-Methoxy-1-methylindole-3-carboxaldehyde (43) 5-Methoxyindole-3-carboxaldehyde (300 mg, 1.71 mmol) was added in portions over 5 min to a suspension of sodium hydride (82 mg, 2.05 mmol, 60percent dispersion in mineral oil) in DMF (8 mL) stirring under argon. The mixture was stirred for 30 min, methyl iodide (0.13 mL, 2.05 mmol) was added and the mixture was stirred for 1 h. Sodium bicarbonate (10percent, 40 mL) was added and the mixture was extracted with EtOAc (4). The combined organic layers were washed with sodium bicarbonate (10percent, 2) and saturated NaCl, dried (MgSO₄), filtered and evaporated. Column chromatography of the crude product (50:50 EtOAc:hexanes) afforded 43 (320 mg, 99percent) as a light yellow solid; R_f=0.35 (50:50 EtOAc:hexanes); mp=130-132° C.; lit mp=132-133° C.⁵³; ¹H NMR (CDCl₃): δ 9.95 (s, 1H), 7.79 (d, 1H, J=2.4 Hz), 7.62 (s, 1H), 7.25 (d, J=8.8 Hz), 6.96 (dd, 1H, J=2.4 and 8.9 Hz), 3.90 (s, 3H), 3.85 (s, 3H).
1.03 g	Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667 h; Inert atmosphere Stage #2: at 0 - 40℃; for 0.5 h; Inert atmosphere	5-methoxy-indole 22 (1.78 g, 9.40 mmol) was added gradually and under dry argon to a suspension of NaH (0.564 g of a 60percent dispersion, 14.11 mmol) in dry DMF (4 mL). The suspension was stirred at room temperature for 10 min and cooled to 0 °C, and MeI (0.81 g, 5.71 mmol) was added over 5 min. The solution was then heated at 40 °C for 30 min, cooled, poured into cold water. The mixture was extracted with EtOAc (2× 150 mL), dried and evaporated. The residue was used without purification (1.03 g, 95percent). ¹H NMR (300 MHz, DMSO-d₆): δ (ppm) 9.72 (s, 1H), 8.45 (s, 1H), 7.82 (d, J = 9.1 Hz, 1H), 7.37 (d, J = 9.1 Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H); MS (ESI) m/z: 190.1 [M+H]⁺.

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P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling