Name: 19012-03-4|1-Methyl-1H-indole-3-carbaldehyde|98%
Brand: Ambeed
SKU: A117213
Price: 5.0 USD
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1
[ 603-76-9 ]
[ 68-12-2 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
96%		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).
		General procedure: POCl3 (5.87 ml, 63.0 mmol) was added dropwise to DMF (45 ml) at 0 C, and the mixture was stirred for 20 min at same temperature. A solution of 6-fluoro-1-methylindole (6.71 g, 45.0 mmol) in DMF (45 ml) was added slowly to the mixture at 0 C. After being stirred at room temperature for 1.5 h, the reaction mixture was poured into ice, and the resulting mixture was neutralized with 1 N NaOH and extracted with EtOAc. The extract was washed with brine, dried over MgSO4, and concentrated to dryness. The residue was purified by column chromatography on silica gel with EtOAc as eluent to give the title compound (4.18 g, 52%) as a colorless solid.
		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.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 158 - 167
[2]Organometallics,2010,vol. 29,p. 1032 - 1040
[3]Journal of Organic Chemistry,2010,vol. 75,p. 1047 - 1060
[4]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 904 - 910
[5]Collection of Czechoslovak Chemical Communications,1981,vol. 46,p. 3278 - 3284
[6]Tetrahedron,1993,vol. 49,p. 4015 - 4034
[7]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1301 - 1305
[8]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 1201 - 1212
[9]Tetrahedron Letters,2012,vol. 53,p. 2222 - 2225
[10]MedChemComm,2013,vol. 4,p. 228 - 232
[11]Medicinal Chemistry Research,2016,vol. 25,p. 941 - 950

2
[ 487-89-8 ]
[ 74-88-4 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
98%		(1014) A 100 mL round bottom flask with stir bar was charged with 47 (Combi-Blocks, 0.500 g, 3.4 mmol, 1 eq). The flask was evacuated and back-filled with Ar (×3). Anh. DMF (10 mL) was added. The resulting solution was cooled to 0 C. with stirring. NaH (60% in oil, 0.179 g, 4.5 mmol, 1.3 eq) was added. After 45 min MeI (0.43 mL, 0.98 g, 6.9 mmol, 2 eq) was added, and the reaction was stirred at 0 C. to room temperature overnight. The reaction was diluted with water and extracted with EtOAc (×1). The layers were separated. The organic layer was washed with water (×2), brine (×1), and dried over Na2SO4. The solids were filtered off, and the volatiles were removed via rotary evaporation. The crude was plug filtered through silica gel eluting with 20% EtOAc/hexanes yielding 0.53 g (3.3 mmol, 98% yield) of 48 as a red oil which gradually solidified.
97%		To a stirred solution of indole-3-carboxaldehdye 29 (4.02 g, 27.7 mmol) in dry THF (100 mL) at 0 C was slowly added NaH (60% dispersion in mineral oil) (1.85 g, 46.3 mmol) portionwise under nitrogen. The reaction mixture was stirred at room temperature for 1 h and then CH3I (3.40 mL, 54.6 mmol) was added. The reaction mixture was stirred for a further 4 h and then quenched with the addition of H2O (50 mL). The aqueous solution was extracted with EtOAc (3 × 100 mL). The combined organic layer was washed with H2O (3 × 100 mL), brine (2 × 100 mL), dried over anhydrous MgSO4, filtered and evaporated to dryness. The crude residue was purified by flash column chromatography (SiO2, 1% MeOH/CH2Cl2) to afford aldehyde 30 (4.26 g, 97%) as a pale yellow-white powdery solid.
96%	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 4h;	To a solution of 1Hindole-indole-3-carbaldehyde (4) (20 mmol) and CH3I (20 mmol)in THF (50 mL), NaH (20 mmol) were added at 0 C. The mixturewas stirred well for 4 h at room temperature (the progress of thereaction was monitored by TLC). Then it was poured over crushedice and light yellow precipitate appeared. After filtered and precipitatecrystallization process by absolute ethanol gave the desiredproduct in 96% yield.

80%	With tetrabutylammomium bromide; sodium hydroxide; In toluene; for 12h;	General procedure: A total of 10 mmol of an appropriate indole-carbaldehyde, 50 ml of toluene, 36 ml of 30%NaOH solution, 1 mmol (322 mg) of tetrabutylammonium bromide (TBAB) and 10.5 mmol ofalkyl iodide (0.66 ml of methyl iodide, for instance) were placed in a stoppered flask. The20 mixture was stirred until the substrate disappeared on TLC (on average 12 h). After completionof the reaction, the phases were separated, next the organic extract was washed with 30 ml ofH20 followed by 30 ml brine, and was dried over MgS04, and toluene was rotary evaporated.Sodium metabisulfite (40 mmol) dissolved in 13 ml water and 15 ml ethanol were added to theobtained oil. The formed adduct was vacuum filtered, washed sparingly with cold ethanol and25 transferred to a vigorously stirred 10% NaOH solution (50 ml). The precipitated product wasextracted with three 25 ml portions of ethyl acetate, the extracts were washed with 25 mlwater, followed with 25 ml brine, dried over MgS04, and the solvent was rotary evaporated.The crude product was triturated twice with 5 ml of hexane:isopropanol 2:1 mixture, vacuumfiltered, and dried.; The compound was synthesized from 1H-indole-3-carbaldehyde (10 g, 68.9 mmol) according tothe general procedure 3 (80% yield)LC-MS: m/z = 159.83 tR = 2.09
75%		General procedure: To a solution of indole-aldehyde (435mg 3mmol) in CH3CN (30mL) was added Cs2CO3 (829mg, 6mmol), and the mixture was refluxed for 2h. To this solution, alkyl halide (3.3mmol) was added, and the mixture was heated under reflux for 1h. After the completion of the reaction, the solvent was evaporated under reduced pressure and water was added to the reaction mixture and extracted 3 times for ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography.
66%		General procedure 8: Under dry conditions is prepared a solution of KOH (4 eq. , 2-3 N) in DMSO. After stirring at room temperature for 5 minutes is added the starting indole (1 eq. ) under argon atmosphere and the mixture is stirred an additional 45 minutes. The alkylating agent (1.1 eq. ) is then added dropwise at 0C and the mixture is allowed to come to room temperature. The reaction is followed by TLC. H2O is added and the aqueous phase is extracted with Et2O (3x). The combined organic phases are washed once with H2O, once with brine, dried over MgS04. Removal of solvent under vacuum affords the expected compound which can be used without further purification. Preparation 33: 1-Methyl-1-H-indole-3-carbaldehyde General procedure 8 was followed usind KOH (15.46 g, 0.28 mole) in DMSO (100 mL), lH-indole-3-carbaldehyde (10 g, 69 mmoles) and iodomethane (4.73 mL, 76 mmoles). The title compound was obtained as a yellow/brown solid (7.2 g, 66% yield). 1H-NMR (DMSO-d6) 8 9.90 (s, lH), 8.26 (s, lH), 8.11 (d, lH), 7.58 (d, lH), 7.30 (m, 2H), 3.90 (s, 3H).
61%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 5h;Inert atmosphere;	3.40 mmol of indole-3-carbaldehyde was dissolved in 5 mL of distilled DMF. Then, 3.4 mmol of K2CO3 and 1 mL CH3I were added over it and stirred throughly. The mixture was boiled under nitrogen at 100 C for 5 h under reflux. The solution obtained after 5 h was cooled, precipitated with ice-water, and filtered. White solid, yield: 61% (0.33 g), m.p: 62 C, 1H NMR (DMSO-d6, 300 MHz): 9.9 (s, 1H), 8.29 (s, 1H), 8.1 (d, 1H, J = 7.24), 7.57 (d, 1H, J = 8.014), 7.3 (dd, J = 7.09, 1.15), 7.4 (dd, J = 5.82, 4.61).
		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.
		Under ice-cooling, to the reaction vessel sequentially added POCl3(20 mL) and DMF (40mL), 1a (35mmol), the reaction 2h, poured into ice water, PH adjusted to 9.0 with NaOH, extracted with ethyl acetate and dried to give 2a.In an ice bath was added to the reaction vessel 2a (25mmol), THF (15mL), NaH (62.5mmol), stirred for 15min, then add CH3I (33mmol) room temperature for 24h.TLC tracking, after sufficient reaction extracted with ethyl acetate and dried to give 3a.Was added to the reaction vessel 3a (2mmol) and acetophenone (2mmol), absolute ethanol (20 mL) and KOH (6mmol, 336mg), room temperature for 24h, filtered and recrystallized from ethanol and methylene chloride 4a.Successively added to the reaction vessel in absolute ethanol (5mL), 4a (1mmol) ,hydrazine monohydrate (2mmol), refluxed for 2h, cooled to -20 transferred overnight, the solid was washed with petroleum ether and filtered 5a.To the reaction vessel was added acetic acid (2mmol), EDC · HCl ( 3mmol), HOBt (1.2mmol)and methylene chloride (5mL), under nitrogen was added 5a (1mmol), the reaction for 24h, filtered and washed with ethanol and water net crude product in ethanol and recrystallized from methylene chloride 6a.Yield:. ~ 172 .mp171 deg.] C 30.2%
		Under ice-cooling, to the reaction vessel sequentially added POCl3(20 mL) and DMF (40mL), a1 (35mmol), the reaction 2h, poured into ice water, PH adjusted to 9.0 with NaOH, extracted with ethyl acetate and dried to give b1.Was added to the reaction vessel b1 (25mmol) under ice-cooling, THF (15mL), NaH (62.5mmol), stirred for 15min, then add CH3I (33mmol) room temperature for 24h.TLC tracking, after sufficient reaction was extracted with ethyl acetate and dried to give c1.Was added to the reaction vessel c1 (2mmol) and acetophenone (2mmol), absolute ethanol (20 mL) and KOH (6mmol, 336mg), room temperature for 24h, filtered and recrystallized from ethanol and methylene chloride d1.Was added to the reaction vessel d1 (1mmol), semicarbazide hydrochloride (3mmol) and ethanol (10 mL), after stirring and dissolving NaOH solution was added, the reaction was thoroughly filtered, recrystallized from ethanol and methylene chloride e1.% Yield56.5
		General procedure: The preparation method comprises the following steps: adding POCl3 (20mL) and DMF (40mL) to the reaction vessel under ice bath condition, compound 1 (35 mmol) was reacted for 2h, poured into ice water, adjust pH to 9.0 with NaOH, and extracted with ethyl acetate to give compound 2. Under the ice bath, compound 2 (25 mmol), THF (15 mL), NaH (62.5 mmol), were added to the reaction vessel under ice cooling, stirred for 15min, and then CH3I (33mmol) was added at room temperature reaction 24h TLC tracking. After completion of the reaction, extracted and dried with ethyl acetate to give compound 3. To the reaction vessel was added compound 3 (2 mmol) and acetophenone (2 mmol), absolute ethanol (20 mL) and KOH (6 mmol). After 24h reaction at room temperature, it was filtered and recrystallized with ethanol and methylene chloride to give compound 4. An anhydrous ethanol(5 mL), compound 4 (1mmol), hydrazine hydrate (2 mmol) was added to the reaction vessel, refluxed for 2h, cooled to -20 C overnight, solid filtration and washing was carried out with petroleum ether to give compound 5. To the reaction vessel was added a mixture of niacin (2 mmol), EDC*HCl (3 mmol), HOBt (1.2 mmol) and dichloromethane (5 mL), compound 5 (1 mmol) was added under an inert gas atmosphere, After 24 hours of reaction, filtered and washed with ethanol and water. The crude product was recrystallized from ethanol and methylene chloride to give a series of the niacin dihydropyrazole compounds of the present invention (Compound 6), the compounds are shown in Table 1.
		General procedure: The preparation method comprises the following steps: adding POCl3 (20mL) and DMF (40mL) to the reaction vessel under ice bath condition, compound 1 (35 mmol) was reacted for 2 h and poured into ice water to adjust the pH to 9.0 with NaOH and extracted with ethyl acetate to give compound 2. Compound 2 (25 mmol), THF (15 mL), NaH (62.5 mmol) were added to the reaction vessel under ice-cooling and stirred for 15 min, And then CH3I (33mmol) was added at room temperature for 24h. TLC tracking. After completion the reaction, extraction and drying with ethyl acetate gave compound 3. To the reaction vessel was added compound 3 (2 mmol) and acetophenone (2 mmol), absolute ethanol (20 mL) and KOH (6 mmol). After 24 hours of reaction at room temperature,it was filtered and recrystallized with ethanol and dichloromethane to give compound 4. To the reaction vessel was added compound 4 (1mmol), thiosemicarbazide (3 mmol) and absolute ethanol (10 mL). After stirring, NaOH solution was added and heated to reflux for 24 h. After filtration, it was recrystallized with ethanol and methylene chloride to give a series of 1-methyl-1H-indole-pyrazoline thiourea compounds of the present invention (Compound 5), the compounds are shown in Table 1.
	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%.
		Indole-3-carbaldehyde (1.45 g, 10 mmol) and 50 mL of dry tetrahydrofuran were added to a 100 mL round bottom flask. Then, sodium hydride (0.36 g, 15 mmol) was added in portions at 0C, and the reaction was carried out at this temperature for half an hour. Thereafter, methyl iodide (2.84 g, 20 mmol) was added to the system, and the reaction was carried out at room temperature for 3 hours. After completion of the reaction, saturated ammonium chloride solution was added for quenching and extraction with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. After that, the organic phase was de-solventized under reduced pressure to obtain a yellow solid III-1, 1.59 g, with a crude yield of 100%. To N-methylindole-3-carbaldehyde (1.59 g, 10 mmol) was added isopropylamine (1.18 g, 20 mmol) and 30 mL of absolute ethanol. After the addition, the reaction was refluxed for 6 hours. Subsequently, sodium borohydride (0.46 g, 12 mmol) was added to it in batches at 0C and stirred at room temperature for 1 hour. The reaction mixture was desolvated under reduced pressure, dissolved in dichloromethane and washed successively with water and saturated brine. The organic phase was dried with anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain a yellow oily substance IV-12.0 g with a yield of 99%.A solution of 12 mmol of bromodifluoroacetyl chloride in 10 mL of dichloromethane was dropped into 50 mL of dichloromethane solution of 10 mmol of IV-1 and 24 mmol of triethylamine at 0C. After reacting at room temperature overnight, the system was washed successively with water and saturated brine. The organic phase was dried with anhydrous magnesium sulfate, and dissolved under reduced pressure. Finally, it was separated by column chromatography with petroleum ether (60-90C)/ethyl acetate system to obtain 2.5 g of white solid V-1 with a yield of 70%. Add compound V-1 (71.6 mg, 0.2 mmol), Ir(ppy) 3 (1.3 mg, 0.002 mmol), K2HPO4 (52.2 mg, 0.3 mmol), 1.8 mL of methyl tert-butyl ether and water to the dry reaction tube 0.2mL. Then the gas was replaced 3 times at -78C under the protection of Ar. Then, the reaction was stirred for 10 hours under the irradiation of a 3-watt LED blue light. After completion, the reaction system was directly desolvated under reduced pressure to obtain crude product VI-1. To the crude VI-1 product, PCC (51.7 mg, 0.24 mmol) and dichloromethane 1 mL were added, and the reaction was stirred at room temperature for 1 hour. After completion, 10 mL of dichloromethane was added, and washed sequentially with water and saturated brine. The organic phase was dried with anhydrous sodium sulfate, dissolved under reduced pressure, and separated by column chromatography with petroleum ether (60-90C)/ethyl acetate system to obtain a yellow solid Ia-1 with a yield of 80%

Reference： [1]Patent: US2016/168140,2016,A1 .Location in patent: Paragraph 1014
[2]Tetrahedron,2018,vol. 74,p. 5089 - 5101
[3]European Journal of Medicinal Chemistry,2020,vol. 200
[4]Tetrahedron,1998,vol. 54,p. 3549 - 3566
[5]Phytochemistry,2009,vol. 70,p. 1129 - 1138
[6]Journal of Medicinal Chemistry,2018,vol. 61,p. 6261 - 6276
[7]Journal of Materials Chemistry B,2016,vol. 4,p. 4895 - 4900
[8]Journal of the American Chemical Society,2006,vol. 128,p. 8146 - 8147
[9]Heterocycles,1986,vol. 24,p. 3115 - 3128
[10]Patent: WO2018/15558,2018,A1 .Location in patent: Page/Page column 15; 29
[11]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 2060 - 2079
[12]Organic Letters,2009,vol. 11,p. 5214 - 5217
[13]ChemMedChem,2011,vol. 6,p. 904 - 921
[14]Patent: WO2005/58309,2005,A1 .Location in patent: Page/Page column 68
[15]Journal of the Chinese Chemical Society,2014,vol. 61,p. 507 - 516
[16]Journal of the Chemical Society. Perkin transactions I,1984,p. 2903 - 2909
[17]Journal of Molecular Structure,2017,vol. 1147,p. 364 - 379
[18]Journal of Organic Chemistry USSR (English Translation),1983,vol. 19,p. 1367 - 1376
Zhurnal Organicheskoi Khimii,1983,vol. 19,p. 1518 - 1529
[19]Synthesis,1987,p. 396 - 397
[20]European Journal of Medicinal Chemistry,1989,vol. 24,p. 39 - 42
[21]European Journal of Medicinal Chemistry,1989,vol. 24,p. 145 - 154
[22]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3111 - 3114
[23]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798
[24]Synlett,2006,p. 3324 - 3328
[25]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2586 - 2590
[26]Combinatorial Chemistry and High Throughput Screening,2011,vol. 14,p. 570 - 582
[27]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2009,vol. 74,p. 1031 - 1045
[28]Chemistry - An Asian Journal,2014,vol. 9,p. 1242 - 1246
[29]European Journal of Medicinal Chemistry,2015,vol. 99,p. 125 - 137
[30]Chemistry - An Asian Journal,2016,vol. 11,p. 221 - 225
[31]ChemMedChem,2016,vol. 11,p. 1446 - 1458
[32]Patent: CN105541805,2016,A .Location in patent: Paragraph 0019
[33]Patent: CN105541804,2016,A .Location in patent: Paragraph 0019
[34]Synthetic Communications,2016,vol. 46,p. 1902 - 1908
[35]Patent: CN106749192,2017,A .Location in patent: Paragraph 0022; 0012
[36]Patent: CN106831724,2017,A .Location in patent: Paragraph 0022; 0023
[37]Organic and Biomolecular Chemistry,2017,vol. 15,p. 7404 - 7410
[38]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 3071 - 3076
[39]European Journal of Medicinal Chemistry,2018,vol. 156,p. 722 - 737
[40]New Journal of Chemistry,2018,vol. 42,p. 13549 - 13557
[41]Organic Letters,2019,vol. 21,p. 2602 - 2605
[42]Organic Letters,2019,vol. 21,p. 2048 - 2051
[43]Patent: CN111264542,2020,A .Location in patent: Paragraph 0035-0037

3
[ 19012-03-4 ]
[ 530-40-5 ]
[ 73540-72-4 ]

Yield	Reaction Conditions	Operation in experiment
76%	With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether 1.) -78 deg C, 1 h, 2.) -78 deg C -> RT, 12 h;

Reference： [1]Watanabe; Snieckus [Journal of the American Chemical Society, 1980, vol. 102, # 4, p. 1457 - 1460]

4
[ 19012-03-4 ]
[ 69097-20-7 ]
2,3-Bis(trimethylsiloxy)-3-(1-methyl-3-indolyl)propansaeure-trimethylsilylester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With trimethylsilyl trifluoromethanesulfonate In dichloromethane for 3h; Ambient temperature;

Reference： [1]Oesterle, Thomas; Simchen, Gerhard [Liebigs Annalen der Chemie, 1987, p. 693 - 700]

5
[ 19012-03-4 ]
[ 872-73-1 ]
[ 76384-54-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With piperidine In ethanol for 0.583333h; Heating;

Reference： [1]Stupnikova, T. V.; Kalafat, V. N.; Klyuev, N. A.; Marshtupa, V. P.; Sagitullin, R. S. [Chemistry of Heterocyclic Compounds, 1980, p. 1031 - 1034][Khimiya Geterotsiklicheskikh Soedinenii, 1980, vol. 16, # 10, p. 1360 - 1364]

6
[ 19012-03-4 ]
[ 24662-37-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tert.-butylhydroperoxide; copper(II) nitrate trihydrate; acetic acid; N,N-dimethyl-formamide at 130℃; for 48h;
82%	With tert.-butylhydroperoxide; copper(II) nitrate trihydrate; acetic acid; N,N-dimethyl-formamide at 130℃; for 48h;
79%	With oxygen; acetonitrile; copper(l) chloride In N,N-dimethyl acetamide at 130℃; for 24h; Schlenk technique;

75%	With ammonium dihydrogen phosphate; acetic acid In various solvent(s) for 12h; Heating;
50%	With oxygen; copper(ll) bromide; potassium hexacyanoferrate(III) In N,N-dimethyl-formamide at 150℃; for 12h; Sealed tube;
	With diammonium phosphate; 1-Nitropropane In acetic acid
	With hydrazinium dihydrogen phosphate; acetic acid; 1-Nitropropane
	With hydroxylamine hydrochloride; acetic anhydride 1.) pyridine, 85 deg C, 2.) reflux, 2 h; Yield given. Multistep reaction;
	Multi-step reaction with 2 steps 1: 65 percent / NH₂OH / ethanol / 24 h / 60 °C 2: 58 percent / CH₃COONa; (CH₃CO)2O / 4 h / 100 °C
	With formic acid; hydroxylamine hydrochloride; sodium formate at 130℃;
	With formic acid; hydroxylamine hydrochloride; sodium formate at 130℃; for 3h;
100 %Spectr.	With 1-methyl-3-(4-sulfonylbutyl)-1H-imidazol-3-ium trifluoromethanesulfonate; trimethylsilylazide; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 20 - 50℃; for 3h; Sonication;
	With formic acid; hydroxylamine hydrochloride; sodium formate at 130℃; for 3h;

Reference： [1]Zhang, Lianpeng; Lu, Ping; Wang, Yanguang [Organic and Biomolecular Chemistry, 2015, vol. 13, # 30, p. 8322 - 8329]
[2]Zhang, Lianpeng; Lu, Ping; Wang, Yanguang [Organic and Biomolecular Chemistry, 2016, vol. 14, # 5, p. 1840 - 1840]
[3]Liu, Lixin; Dong, Jianyu; Zhang, Yaxing; Zhou, Yongbo; Yin, Shuang-Feng [Organic and Biomolecular Chemistry, 2015, vol. 13, # 39, p. 9948 - 9952]
[4]Swain; Baker; Kneen; Herbert; Moseley; Saunders; Seward; Stevenson; Beer; Stanton; Watling; Ball [Journal of Medicinal Chemistry, 1992, vol. 35, # 6, p. 1019 - 1031]
[5]Wu, Qian; Luo, Yi; Lei, Aiwen; You, Jingsong [Journal of the American Chemical Society, 2016, vol. 138, # 9, p. 2885 - 2888]
[6]Swain, Christopher J.; Kueen, Clare; Baker, Raymond [Tetrahedron Letters, 1990, vol. 31, # 17, p. 2445 - 2448]
[7]Swain, Christopher J.; Kneen, Clare; Herbert, Richard; Baker, Raymond [Journal of the Chemical Society. Perkin transactions I, 1990, # 11, p. 3183 - 3186]
[8]Gevorkyan, K. A.; Papayan, G. L.; Chshmarityan, S. G.; Paronikyan, R. G.; Akopyan, N. E. [Pharmaceutical Chemistry Journal, 1988, vol. 22, # 10, p. 765 - 769][Khimiko-Farmatsevticheskii Zhurnal, 1988, vol. 22, # 10, p. 1203 - 1207]
[9]Everett, Steven A.; Naylor, Matthew A.; Stratford, Michael R.L.; Patel, Kantilal B.; Ford, Eleonora; Mortensen, Alan; Ferguson, Amanda C.; Vojnovic, Borivoj; Wardman, Peter [Journal of the Chemical Society. Perkin Transactions 2 (2001), 2001, # 10, p. 1989 - 1997]
[10]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]
[11]Location in patent: experimental part Kumar, Dalip; Narayanam, Maruthi Kumar; Chang, Kuei-Hua; Shah, Kavita [Chemical Biology and Drug Design, 2011, vol. 77, # 3, p. 182 - 188]
[12]Nandi, Ganesh C.; Laali, Kenneth K. [Tetrahedron Letters, 2013, vol. 54, # 17, p. 2177 - 2179]
[13]Kumar Mehra, Manish; Malik, Monika; Kumar, Bintu; Kumar, Dalip [Organic and Biomolecular Chemistry, 2021, vol. 19, # 5, p. 1109 - 1114]

7
[ 19012-03-4 ]
[ 5028-20-6 ]
[ 113311-88-9 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 529 - 535
Khimiya Geterotsiklicheskikh Soedinenii,1987,vol. 23,p. 639 - 645
[2]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 529 - 535
Khimiya Geterotsiklicheskikh Soedinenii,1987,vol. 23,p. 639 - 645

8
[ 19012-03-4 ]
[ 10102-94-0 ]
[ 25055-65-6 ]
[ 25055-66-7 ]
N-methyl-2,6-dibromoindole-3-carbaldehyde [ No CAS ]

Reference： [1]Environmental Toxicology and Chemistry,2001,vol. 20,p. 589 - 596

9
[ 19012-03-4 ]
[ 79-19-6 ]
2-((1-methyl-1H-indol-3-yl)methylene)hydrazinecarbothioamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With acetic acid; In ethanol; for 10h;Reflux;	General procedure: The appropriate aldehyde (1.1 mmol) was dissolved in anhydrous ethanol (10 mL), thiosemicarbazide (1.0 mmol) and acetic acid (0.2 mL) were added to the above solution. The reaction mixture was refluxed for 10 h and then was cooled to room temperature. The appearing precipitate was filtered, washed by ether and recrystallized from ethanol to obtain the corresponding 1-(1-arylethylidene)thiosemicarbazone compounds 1a-s.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4330 - 4335
[2]European Journal of Medicinal Chemistry,2016,vol. 123,p. 161 - 170
[3]Journal of Medicinal Chemistry,2002,vol. 45,p. 2695 - 2707
[4]Dyes and Pigments,2019,vol. 169,p. 105 - 110

10
[ 5654-97-7 ]
[ 19012-03-4 ]
3-(1-methyl-1H-indol-3-ylmethylene)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate; In ethanol; at 20℃;	General procedure: Various aldehydes (1.0 equiv) were added to stirred solutions of indolin-2-one, 5-chloroindolin-2-one or <strong>[5654-97-7]7-azaoxindole</strong> (1.0equiv) in absolute ethanol. After stirring at room temperature for 5 min NaOEt/EtOH (0.5 mL) was added and the mixture was then stirred at room temperature overnight. The solvent was then removed under vacuum. The residue was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum. The solid part was purified by chromatography over silica gel using ethyl acetate/petroleum ether as the eluent to afford desired compounds 1a-1g, 2a, 3a.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 953 - 957
[2]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6953 - 6960

11
[ 19012-03-4 ]
[ 32501-05-6 ]
1,3-Dihydro-3-[(1-methyl-1H-indol-3-yl)methylene]-2H-pyrrolo[3,2-b]pyridin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 953 - 957

12
[ 19012-03-4 ]
[ 1078-28-0 ]
[ 141-43-5 ]
1-(2-amino-ethyl)-6-methoxy-2-[2-(1-methyl-1H-indol-3-yl)-vinyl]-quinolinium [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 6331 - 6335

13
[ 19012-03-4 ]
[ 1530-33-2 ]
[ 62747-55-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With n-butyllithium In tetrahydrofuran

Reference： [1]Kawasaki, Ikuo; Terano, Masami; Kurume, Ai; Hara, Satoko; Yamashita, Masayuki; Ohta, Shunsaku [Tetrahedron Letters, 2005, vol. 46, # 38, p. 6549 - 6553]

14
[ 19012-03-4 ]
[ 2521-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 65 percent / t-BuOK / tetrahydrofuran 2: 80 percent / n-BuLi / tetrahydrofuran; hexane 3: 85 percent / NH₂OH*HCl; AcONa / methanol 4: 1,2-dichloro-benzene / Heating

Reference： [1]Kusurkar, Radhika S.; Goswami, Shailesh K.; Vyas, Sandhya M. [Tetrahedron Letters, 2003, vol. 44, # 25, p. 4761 - 4763]

15
[ 19012-03-4 ]
[ 118959-44-7 ]

Reference： [1]Pharmaceutical Chemistry Journal,1988,vol. 22,p. 765 - 769
Khimiko-Farmatsevticheskii Zhurnal,1988,vol. 22,p. 1203 - 1207

16
[ 19012-03-4 ]
[ 19293-60-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) NH₂OH*HCl, 2.) acetic anhydride / 1.) pyridine, 85 deg C, 2.) reflux, 2 h 2: 81.2 percent / LiAlH₄ / diethyl ether; tetrahydrofuran / 12 h / Heating
	Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium carbonate / water; ethanol / 3 h / 20 °C 2: hydrogen; 5%-palladium/activated carbon; hydrogenchloride / methanol / 20 °C / 7500.75 Torr

Reference： [1]Gevorkyan, K. A.; Papayan, G. L.; Chshmarityan, S. G.; Paronikyan, R. G.; Akopyan, N. E. [Pharmaceutical Chemistry Journal, 1988, vol. 22, # 10, p. 765 - 769][Khimiko-Farmatsevticheskii Zhurnal, 1988, vol. 22, # 10, p. 1203 - 1207]
[2]Zhong, Xin; Chen, Ning; Xu, Jiaxi [New Journal of Chemistry, 2018, vol. 42, # 16, p. 13549 - 13557]

17
[ 19012-03-4 ]
[ 31896-75-0 ]

Yield	Reaction Conditions	Operation in experiment
57%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 12h;	To the ice-cold solution of N-Me-indole-3-aldehyde 1a (40 mg, 0.253 mmol) in THF (5 mL) was added, lithium aluminum hydride (LAH) (40 mg, 1.01 mmol). The reaction was stirred at 0 C for 12 h. Quenched with ethyl acetate (2 mL) and filtered over a celite bed using ethyl acetate. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding BIM 3ai (20 mg, 0.072 mmol 57%) as a pale brown oil; Rf = 0.5 (9:1; hexane:EtOAc); IR (neat): 3059, 2975, 2926, 1726, 1646, 1607, 1468, 1416, 1372, 1330, 1262, 1120, 1044, 740, 703, 671, 599, 553 and 425 cm-1; 1H NMR (400 MHz, CDCl3): d = 7.61 (2 H, d, J = 7.1 Hz), 7.28 (2 H, d, J = 7.5 Hz), 7.20 (2 H, d, J = 6.9 Hz), 7.08 (2 H, s), 6.77 (2 H, s), 4.21 (2 H, s), 3.68 (6 H, s); 13C NMR (100 MHz, CDCl3): d = 137.2, 128.0, 127.0, 121.5, 119.4, 118.6, 114.4, 109.2, 32.7 and 21.0; HRESI-MS: [C19H19N2]+ = [M+H]+ requires 275.1548; found 275.1545.

Reference： [1]Tetrahedron,2016,vol. 72,p. 8106 - 8116
[2]Journal of the American Chemical Society,1959,vol. 81,p. 6023,6025

18
[ 19012-03-4 ]
[ 708-76-9 ]
[ 4397-53-9 ]
[ 487-68-3 ]
[ 699016-40-5 ]
[ 2233-18-3 ]
[ 5736-94-7 ]
[ 26260-02-6 ]
[ 3934-87-0 ]
[ 492-88-6 ]
[ 6280-80-4 ]
[ 4659-47-6 ]
[ 89-98-5 ]
[ 71653-64-0 ]
[ 123-08-0 ]
[ 120-14-9 ]
[ 446-52-6 ]
[ 66-99-9 ]
[ 10040-98-9 ]
[ 85070-48-0 ]
[ 93777-26-5 ]
[ 134-96-3 ]
[ 79124-75-7 ]
2-chloro-6-fluoro-3-methylbenzaldehyde [ No CAS ]
[ 544431-10-9 ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2-fluoro-phenyl)-acrylamide [ No CAS ]
3-(2-chloro-phenyl)-2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(4-hydroxy-phenyl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2-iodo-phenyl)-acrylamide [ No CAS ]
3-(3-chloro-2-fluoro-phenyl)-2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-naphthalen-2-yl-acrylamide [ No CAS ]
3-(5-bromo-2-fluoro-phenyl)-2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-3-(3,4-dimethoxy-phenyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(1-methyl-1H-indol-3-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(4-imidazol-1-yl-phenyl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2-fluoro-4-iodo-phenyl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2,4,6-trimethyl-phenyl)-acrylamide [ No CAS ]
2-cyano-3-(2-difluoromethoxy-phenyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-acrylamide [ No CAS ]
3-(2-chloro-6-fluoro-3-methyl-phenyl)-2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2,3,6-trichloro-phenyl)-acrylamide [ No CAS ]
2-cyano-3-(3-ethoxy-2-hydroxy-phenyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
{2-[2-cyano-2-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-vinyl]-phenoxy}-acetic acid [ No CAS ]
2-cyano-3-(3,4-dihydroxy-5-methoxy-phenyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(4-hydroxy-3,5-dimethoxy-phenyl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(2-hydroxy-4,6-dimethoxy-phenyl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(3-p-tolyloxy-phenyl)-acrylamide [ No CAS ]
3-(4-benzyloxy-phenyl)-2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acrylamide [ No CAS ]
2-cyano-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-3-(4-hexyloxy-phenyl)-acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A 0.25 M stock solution of 2-cyano-N- (5-ethyl- [1, 3, 4] thiadiazol-2- yl)-acetamide was prepared in 1.0 M diisopropylethylamine in DMF. Benzaldehyde and other heterocyclic aldehydes were individually weighed and were dissolved to 0.25 M using a Tecan Genesis workstation. The Tecan was used to dispense 200 muL of template 1 to each reaction vessel then was used to dispense 400 L of aldehyde stock solutions to individual reaction vessels. The reaction vessels were sealed and were heated at 45-50 C, with agitation, for 18 hours. The reaction vessels were then cooled, unsealed, and 50 L of aminopropyl-functionalized silica gel (Aldrich) was dispensed to each reaction vessel. Activated 4 angstrom molecular sieves (powdered, 50 L) were then dispensed to each reaction. Reaction vessels were then sealed and were heated at 45-50 C with agitation for 3 h. Reactions were then unsealed and were filtered to remove solids. B. Sample solutions were dried in vacuo using a Genevac. Samples were dissolved in 500 pL of DMSO and 500 pL of methanol and purity was determined by LC-MS with using a combination of UV254, UV220, and ELSD detection [purity = (UV254+UV220/2)]. The HPLC conditions were: 4.6 mm x 50 mm C18 column, 10-90% acetonitrile gradient over 5 minutes (mobile phases were H20 with 0.05 % TFA and acetonitrile with 0.035 % TFA), with a flow rate of 3.5 ml/min. Samples which were <80% pure were purified using a mass directed LC-MS purification. Purified samples were concentrated in vacuo then were dissolved in DMSO and were reformatted into 96 well microtiter plates. Samples were tested for purity using LC-MS and quantity was estimated by correlating ELSD response to a standard concentration-ELSD response curve. Samples were then concentrated to dryness and were dissolved in DMSO to a final concentration of 10 uM based on ELSD quantitation. C. The following compounds were prepared in the manner described above in Steps A and B using the appropriate aldehyde in place of benzaldehyde: 2-Cyano-3- (3, 4-dimethoxy-phenyl)-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 345 (MH+) ; 3- (4-Benzyloxy-phenyl)-2-cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES) : 391 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3- (4-hydroxy-phenyl)- acrylamide ; MS (ES): 301 (MH+) ; Acetic acid 4- [2-cyano-2- (5-ethyl- [1, 3,4] thiadiazol-2-ylcarbamoyl)-vinyl]- phenyl ester; MS (ES): 343 (MH+); 2-Cyano-3- (2, 4-dichloro-phenyl)-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 353 (MH+) ; 3- (2-Bromo-phenyl)-2-cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 363 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3- (2-fluoro-phenyl)- acrylamide ; MS (ES): 303 (MH+) ; 3- (4-tert-Butyl-phenyl)-2-cyano-N- (5-ethyl- [1, 3, 4] thiadiazol-2-yl)- acrylamide ; MS (ES): 341 (MH+) ; 3- (2-Chloro-4-fluoro-phenyl)-2-cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 337 (MH+) ; 2-Cyano-3- (2, 5-dimethyl-phenyl)-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 313 (MH+) ; 2-Cyano-5- (4-methoxy-phenyl)-penta-2, 4-dienoic acid (5-ethyl- [1,3, 4] thiadiazol-2-yl)-amide ; MS (ES): 341 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3-(4-hydroxy-3, 5-dimethoxy- phenyl)-acrylamide ; MS (ES): 361 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3- (4-hydroxy-3-iodo-5- methoxy-phenyl)-acrylamide ; MS (ES): 457 (MH+) ; 2-Cyano-3- (3, 4-dihydroxy-phenyl)-N- (5-ethyl- [1, 3, 4] thiadiazol-2-yl)- acrylamide ; MS (ES): 317 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3- (4-hydroxy-3-methoxy-5- nitro-phenyl)-acrylamide ; MS (ES): 376 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yi)-3- (4-hydroxy-3-methoxy-5- nitro-phenyl)-acrylamide ; MS (ES): 376 (MH+) ; 3-(4-Benzyloxy-3,5-dimethyl-phenyl)-2-cyano-N-(5-ethyl- [1,3, 4] thiadiazol-2-yl)-acrylamide ; MS (ES): 419 (MH+) ; 2-Cyano-3- (3, 5-dibromo-2-methoxy-phenyl)-N- (5-ethyl- [1, 3,4] thiadiazol- 2-yl)-acrylamide ; MS (ES) : 471 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3, 4] thiadiazol-2-yl)-3- (4-hexyloxy-phenyl)- acrylamide ; MS (ES): 385 (MH+) ; Acetic acid 4- [2-cyano-2- (5-ethyl- [1, 3,4] thiadiazol-2-ylcarbamoyl)-vinyl]- 2, 6-dimethoxy-phenyl ester; MS (ES): 403 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yi)-3- (4-imidazol-1-yi-phenyl)- acrylamide ; MS (ES): 351 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)-3-(2-trifluoromethyl-phenyl)- acrylamide ; MS (ES): 353 (MH+) ; 3- (2-Chloro-3, 4-dimethoxy-phenyl)-2-cyano-N- (5-ethyl- [1, 3,4] thiadiazol- 2-yl)-acrylamide ; MS (ES): 379 (MH+) ; 2-Cyano-N- (5-ethyl- [1, 3, 4] thiadiazol-2-yl)-3- ( 1-methyl-1 H-indol-3-yl)- acrylamide ; MS (ES): 338 (MH+) ; 2-Cyano-3- (2, 6-dichloro-phenyl)-N- (5-ethyl- [1, 3,4] thiadiazol-2-yl)- acrylamide ; MS (ES): 353 (MH+) ; 2-Cyano-3-(4-dimethylamino-2-nitro-phenyl)-N-(5-ethyl-[1, 3,4] thiadiazol- 2-yl)-acrylamide ; MS (ES): 373 (MH+) ; 2-Cyano-N-(5-ethyl-[1, 3,4] thiadiazol-2-yl)-3- (2-iodo-phe...

Reference： [1]Patent: WO2005/72731,2005,A1 .Location in patent: Page/Page column 95-103

19
[ 19012-03-4 ]
[ 603954-49-0 ]
[ 875318-39-1 ]

Yield	Reaction Conditions	Operation in experiment
90%		A mixture of 2-[4-(aminomethyl)-l-piperidinyl]- 5-pyrimidinecarboxylic acid, ethylester (0.0114 mol), l-methyl-l//-indole-3-carboxaldehyde (0.017 mol) and MgSO4(0.5g) in MeOH (80ml) was stirred and refluxed for 15 hours, then cooled to roomtemperature. Sodium tetrahydroborate (0.018 mol) was added portionwise. The mixturewas stirred at room temperature 5 hours, poured out into water and extracted withEtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent wasevaporated. The residue (6.6g) was purified by column chromatography over silica gel(15-40um) (eluent: DCM/MeOH/NH4OH 94/6/0.5). The pure fractions were collectedand the solvent was evaporated, yielding 4.3g (90%) of intermediate 1.
53%		a) Preparation of intermediate 7 A mixture of 2-[4-(aminomethyl)-1-piperidinyl]-5-pyrimidinecarboxylic acid ethyl ester (0.0076 mol) and 1-methyl-1H-indole-3-carboxaldehyde (0.0114 mol) in CH3OH (80ml) was stirred and refluxed for 15 hours, then cooled to room temperature. NaBH4 (0.012 mol) was added portionwise. The mixture was stirred at room temperature overnight, poured into H2O and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (3.2g) was purified by column chromatography over silica gel (eluent:CH2C12/CH3OH/NH4OH 95/6/0.5; 15-40mum). The pure fractions were collected and the solvent was evaporated, yielding 1.6g (53%) of intermediate 7.

Reference： [1]Patent: WO2006/10750,2006,A1 .Location in patent: Page/Page column 28
[2]Patent: WO2007/82878,2007,A1 .Location in patent: Page/Page column 27

20
[ 137-45-1 ]
[ 19012-03-4 ]
[ 338756-99-3 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	(b) Preparation of Compound 190 A mixture of the pyrazolone (VIi) (0.035 g, 0. 166mmol), 1-methyl indole-3-carboxaldehyde (0.032 g, 0.2 mmol) and ethanol (1 mL) was heated to 65 C. and stirred overnight. The orange precipitate that formed was filtered to obtain compound 190 (0.024 g, 0.068 mmol).

Reference： [1]Patent: US6455525,2002,B1

21
[ 19012-03-4 ]
[ 645-35-2 ]
[ 1206607-11-5 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1219 - 1223

22
[ 19012-03-4 ]
[ 867-13-0 ]
[ 113660-41-6 ]

Yield	Reaction Conditions	Operation in experiment
90.27%		To a suspension of sodium hydride (60% in mineral oil, 0.380 g, 9.42 mmol, 1.5 eq) inTHF (20 mL) was added ethyl 2-(diethoxyphosphoryl)acetate (1.86 g, 9.42 mmol, 1.5 eq)dropwise at 0C and the mixture was allowed to stir at the same temperature for 30 minutes. Tothis mixture was added a solution of 1-methyl-1H-indole-3-carbaldehyde (1.0 g, 6.28 mmol, 1.0eq) in THF (5 mL) and the resulting mixture was allowed to stir at room temperature for 2 h.Progress of reaction was monitored by TLC. After completion, reaction mixture was diluted with saturated aq. NH4C1 (100 mL) and extracted with ethyl acetate (3 x 50 mL). Combined organic layer was washed with brine, dried over anhydrous Na2SO4 and evaporated to dryness under vacuum to afford crude which was purified by Combi-Flash on silica gel (100-200 mesh) usingethyl acetate-hexane system as eluent to afford ethyl (2E)-3-(1-methyl-1H-indol-3-yl)prop-2- enoate (1.3 g, 90.27 %).LCMS: 230 [M+1]

Reference： [1]Patent: WO2019/103897,2019,A1 .Location in patent: Page/Page column 155; 156
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6217 - 6223
[3]Biomedicine and Pharmacotherapy,2018,vol. 107,p. 475 - 483

23
[ 19012-03-4 ]
[ 52509-14-5 ]
(E)-3-(1-methyl-1H-indol-3-yl)acrylaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6217 - 6223

24
[ 19012-03-4 ]
[ 658-27-5 ]
[ 1219443-82-9 ]

Reference： [1]Molecules,2010,vol. 15,p. 2187 - 2202

25
[ 19012-03-4 ]
[ 16732-66-4 ]
[ 1219443-93-2 ]

Reference： [1]Molecules,2010,vol. 15,p. 2187 - 2202

26
[ 19012-03-4 ]
[ 269726-49-0 ]
[ 1314582-27-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With chloro-trimethyl-silane In N,N-dimethyl-formamide at 100℃; for 6h; Inert atmosphere;	3.2. Procedure A: general procedure of heteroannelated pyridines synthesis in DMF/TMSCl General procedure: Appropriate indole of 1.0 equiv, 1.1 equiv of the corresponding aminoheterocycle, and 4 equiv of TMSCl in 15 mL of anhydrous DMF was heated at 100 °C under dry argon atmosphere in a pressure tube. After 6 h the solvent was removed under reduced pressure and the residue was purified by silica gel flash chromatography.

Reference： [1]Location in patent: experimental part Knepper, Ingo; Iaroshenko, Viktor O.; Vilches-Herrera, Marcelo; Domke, Lutz; Mkrtchyan, Satenik; Zahid, Muhammad; Villinger, Alexander; Langer, Peter [Tetrahedron, 2011, vol. 67, # 29, p. 5293 - 5303]

27
[ 19012-03-4 ]
[ 2434-53-9 ]
[ 1314582-32-5 ]

Yield	Reaction Conditions	Operation in experiment
58%	With chloro-trimethyl-silane; In N,N-dimethyl-formamide; at 100℃; for 6h;Inert atmosphere;	General procedure: Appropriate indole of 1.0 equiv, 1.1 equiv of the corresponding aminoheterocycle, and 4 equiv of TMSCl in 15 mL of anhydrous DMF was heated at 100 C under dry argon atmosphere in a pressure tube. After 6 h the solvent was removed under reduced pressure and the residue was purified by silica gel flash chromatography.

Reference： [1]Tetrahedron,2011,vol. 67,p. 5293 - 5303

28
[ 19012-03-4 ]
[ 1131-18-6 ]
[ 1314582-30-3 ]

Yield	Reaction Conditions	Operation in experiment
87%	With chloro-trimethyl-silane; In N,N-dimethyl-formamide; at 100℃; for 6h;Inert atmosphere;	General procedure: Appropriate indole of 1.0 equiv, 1.1 equiv of the corresponding aminoheterocycle, and 4 equiv of TMSCl in 15 mL of anhydrous DMF was heated at 100 C under dry argon atmosphere in a pressure tube. After 6 h the solvent was removed under reduced pressure and the residue was purified by silica gel flash chromatography.

Reference： [1]Tetrahedron,2011,vol. 67,p. 5293 - 5303

29
[ 16312-21-3 ]
[ 19012-03-4 ]
[ 365990-30-3 ]

Reference： [1]Synthetic Communications,2011,vol. 41,p. 2756 - 2762

30
[ 19012-03-4 ]
[ 19012-02-3 ]
[ 27664-08-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In water; at 60℃; for 12h;	General procedure: To a solution of N-methyl-3-acetylindol (1 mmol) and the benzaldehyde derivative (1 mmol) in methanol (10 ml) was added KOH (1 ml from a 50% solution in H2O). The mixture was heated at 60 C for 12 h then evaporated to dryness. The crude was dissolved in ethyl acetate (30 ml) then washed with HCl (1N, 10 ml) and H2O (10 ml), respectively. The organic layer was separated, dried over Na2SO4 and evaporated. The product was purified by chromatography column eluted with hexane:ethyl acetate (8:2) to yield the title compound as a yellow powder.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 6143 - 6148
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 3193 - 3200

31
[ 875-30-9 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,4-diaza-bicyclo[2.2.2]octane; dimethylsulfane; oxygen In dimethyl sulfoxide at 100℃; for 29h; chemoselective reaction;
73%	With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; oxygen; tetra-n-butylammonium azide In acetonitrile at 25℃; for 24h; Irradiation;

Reference： [1]Location in patent: experimental part Wang, Yi-Feng; Zhang, Feng-Lian; Chiba, Shunsuke [Synthesis, 2012, vol. 44, # 10, p. 1526 - 1534]
[2]Shee, Maniklal; Singh, N. D. Pradeep [Advanced Synthesis and Catalysis, 2022, vol. 364, # 12, p. 2032 - 2039]

32
[ 19293-60-8 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 1,4-diaza-bicyclo[2.2.2]octane; dimethylsulfide; oxygen In dimethyl sulfoxide at 100℃; for 24h; chemoselective reaction;

Reference： [1]Location in patent: experimental part Wang, Yi-Feng; Zhang, Feng-Lian; Chiba, Shunsuke [Synthesis, 2012, vol. 44, # 10, p. 1526 - 1534]

33
[ 19012-03-4 ]
[ 5782-85-4 ]
[ 1352562-83-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With acetic acid In ethanol for 6h;

Reference： [1]Location in patent: experimental part Khaledi, Hamid; Alhadi, Abeer A.; Yehye, Wagee A.; Ali, Hapipah Mohd; Abdulla, Mahmood A.; Hassandarvish, Pouya [Archiv der Pharmazie, 2011, vol. 344, # 11, p. 703 - 709]

34
[ 603-76-9 ]
[ 110-18-9 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With water; iodine; oxygen; sodium carbonate; In 1,4-dioxane; at 100℃; under 760.051 Torr; for 36h;Schlenk technique; Sealed tube;	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 muL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 muL). 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.
90%	With C48H39N3; oxygen; potassium iodide; In water; acetonitrile; for 48h;Irradiation;	Compound 1 (1 mmol) was weighed and dissolved in 5 mL of acetonitrile to dissolve KI (664 mg, 4 mmol) in 1 mL of water and 20 mg. CMP-CSU1, Add to a 25 mL reaction flask and add 300 mul of 2 with a pipette. The LED lamp was continuously illuminated for 48 hours under continuous oxygen supply. The solvent was evaporated to dryness and purified to give the corresponding product 3a (yield: 90%), 3b (yield: 66%), 3c (yield: 72%).

Reference： [1]Chemical Communications,2012,vol. 48,p. 5928 - 5930
[2]Tetrahedron Letters,2014,vol. 55,p. 5618 - 5621
[3]Patent: CN108250124,2018,A .Location in patent: Paragraph 0035-0040
[4]ACS Catalysis,2018,vol. 8,p. 8084 - 8091
[5]Advanced Synthesis and Catalysis,2012,vol. 354,p. 2438 - 2442
[6]ACS Catalysis,2014,vol. 4,p. 1897 - 1900
[7]Journal of Materials Chemistry A,2020,vol. 8,p. 8706 - 8715

35
[ 19012-03-4 ]
[ 105-53-3 ]
[ 72010-38-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	With piperidine; acetic acid In ethanol Reflux;
	With piperidine; acetic acid In toluene for 4h; Inert atmosphere; Reflux; Dean-Stark;

Reference： [1]Wang, Jinfang; Zhou, Yu; Zhang, Lei; Li, Zeng; Chen, Xianjie; Liu, Hong [Organic Letters, 2013, vol. 15, # 7, p. 1508 - 1511]
[2]Mei, Guangjian; Yuan, Hao; Gu, Yueqing; Chen, Wei; Chung, Lung Wa; Li, Chuang-Chuang [Angewandte Chemie - International Edition, 2014, vol. 53, # 41, p. 11051 - 11055][Angew. Chem., 2014, vol. 126, # 41, p. 11231 - 11235,5]

36
[ 19012-03-4 ]
[ 37466-90-3 ]
[ 1467028-67-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium metabisulfite; In ethanol; water; for 4h;	General procedure: To a mixture of 2-pyridine aldehyde (5a, 107 mg, 1mmol) and 1,2-diaminobenzene (6a, 108 mg, 1 mmol) in ethanol (25 mL)was added an aqueous solution of sodium pyrosulfite (1.52g, 8 mmol, 5 mL) and refluxed for 4 to 6 h, until the TLC indicated that reaction was completed. The reaction mixture was concentrated under vacuum and the residue was dissolved in CHCl3 (2 x15 mL) and washed with water. The combined organic phases were dried over anhydrousNa2SO4, filtered and the solvent was removed under vacuumand purified by column chromatography (70% EtOAc-hexane) to afford compound 7a as a brown solid.

Reference： [1]Medicinal Chemistry,2013,vol. 9,p. 651 - 659

37
[ 19012-03-4 ]
[ 197376-41-3 ]
[ 1449006-63-6 ]

Yield	Reaction Conditions	Operation in experiment
52%		General procedure: Titanium tetrachloride (1.90 g, 10 mmol) was slowly added to100 mL of anhydrous THF at 0 C, followed by addition of 5 mmol of the aldehyde (1) and stirred for 10 min, then <strong>[197376-41-3]ethyl 2-(3-bromopyridin-2-yl)acetate</strong> (2) (1.47 g, 6 mmol) was added. Subsequently, a solution of pyridine (3.16 g, 40 mmol) in 25 mL of anhydrous THF was added dropwise during a period of 30-60 min at 0 C. The reaction mixture was then stirred for 1 h at room temperature and refluxed for 24 h. After that the mixture was poured on to crashed ice and extracted with ethyl acetate (4 30 mL). The combined extracts were successively washed with brine, saturated sodium hydrogen carbonate and brine, and then dried over anhydrous MgSO4. The organic phase was filtrated and the solvent was removed in vacuo, the residue was purified by column chromatography (silica gel) using PE/EA (5:1) / DCM/MeOH (50:1) to provide 3.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 66,p. 531 - 539

38
[ 1640-39-7 ]
[ 19012-03-4 ]
[ 1426231-20-0 ]

Yield	Reaction Conditions	Operation in experiment
92.9%		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]European Journal of Medicinal Chemistry,2013,vol. 65,p. 158 - 167

39
[ 19012-03-4 ]
[ 1439-36-7 ]
[ 169057-08-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	In toluene at 120℃; for 12h; Inert atmosphere;	General procedure forsynthesis of 1 General procedure: 1-methyl-1H-indole-2-carbaldehyde (6.3 mmol) wasdissolved in 20 mL of toluene. (Triphenylphosphoranylidene)-2-propanone (9.4mmol) was added and the mixture was heated at 120 °C for 12 h. After cooling,the solvent was removed in vacuo. Then the residue was poured into ether andfiltered to remove Ph3P=O. The filtrate was concentrated and theresidue was purified by column chromatography (petroleum ether : ethyl acetate= 10:1 to 8:1) to give the product 1

Reference： [1]Su, Tao; Han, Xiuling; Lu, Xiyan [Tetrahedron Letters, 2014, vol. 55, # 1, p. 27 - 30]

40
[ 19012-03-4 ]
[ 562-46-9 ]
[ 1578269-88-1 ]

Yield	Reaction Conditions	Operation in experiment
73%	With ammonium acetate; In methanol; at 120℃; for 0.166667h;Microwave irradiation;	General procedure: One-pot three component mixture of 2 mmol appropriate 1,3-cyclic dicarbonyl compound (1,3-cyclohexanedione/<strong>[562-46-9]4,4-dimethyl-1,3-cyclohexanedione</strong> or 5,5-dimethyl-1,3-cyclohexanedione),1 mmol substituted indole carboxaldehyde (1-methyl-1H-indole-2-carbaldehyde/1-methyl-1H-indole-3-carbaldehyde/5-bromo-1H-indole-3-carbaldehyde or 6-bromo-1H-indole-3-carbaldehyde)and 5 mmol ammonium acetate was filled into 10 mL-microwavepressure vial and heated under microwave irradiation (power50W, maximum temperature 120 C) for 10 min in 5 mL methanol.After the reactionwas completed, the reaction mixture was pouredinto ice-water, the obtained precipitatewas filtered and crystallizedfrom ethanolewater.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 75,p. 258 - 266

41
[ 603-76-9 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
76%	With palladium(II) trifluoroacetate; oxygen; copper diacetate; trifluoroacetic acid; In N,N-dimethyl-formamide; at 120℃;Schlenk technique;	Add to a 25 mL Schlenk reactor1-methylindole (0.3 mmol), Pd(TFA) 2 (2 mol%),Cu (OAc) 2 (1.5 eq), trifluoroacetic acid (TFA) (0.5 eq) and DMF (2 mL).The reaction was stirred under an oxygen atmosphere at 120 C.The reaction was monitored by TLC plate and GC-MS.After the reaction, the solvent was dried by rotary evaporator and separated by column chromatography (elution)The liquid was ethyl acetate / n-hexane to give the pure title product (white solid,Yield 76%),

Reference： [1]Patent: CN108117504,2018,A .Location in patent: Paragraph 0030; 0031
[2]Tetrahedron,2013,vol. 69,p. 10858 - 10868
[3]European Journal of Organic Chemistry,2018,vol. 2018,p. 6624 - 6628
[4]Organic Letters,2019,vol. 21,p. 7702 - 7707
[5]Organic Letters,2019,vol. 21,p. 7702 - 7707

42
[ 19012-03-4 ]
[ 10297-73-1 ]
3-(1-methyl-1H-indol-3-yl)-1-(4-(methylsulfonyl)phenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium hydroxide; In ethanol; water; at 20℃; for 10h;	General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/<strong>[19012-03-4]1-methylindole-3-carboxaldehyde</strong> (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]European Journal of Medicinal Chemistry,2014,vol. 89,p. 304 - 309

43
[ 19012-03-4 ]
[ 1443-80-7 ]
3-(1-methyl-1H-indol-3-yl)-1-(4-cyanophenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydroxide; In ethanol; water; at 20℃; for 10h;	General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/<strong>[19012-03-4]1-methylindole-3-carboxaldehyde</strong> (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]European Journal of Medicinal Chemistry,2014,vol. 89,p. 304 - 309

44
[ 19012-03-4 ]
[ 2719-21-3 ]
3-(1-methyl-1H-indol-3-yl)-1-(4-(acetamido)phenyl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydroxide; In ethanol; water; at 20℃; for 10h;	General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/<strong>[19012-03-4]1-methylindole-3-carboxaldehyde</strong> (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]European Journal of Medicinal Chemistry,2014,vol. 89,p. 304 - 309

45
[ 19012-03-4 ]
[ 74-89-5 ]
[ 24662-37-1 ]

Yield	Reaction Conditions	Operation in experiment
41 %Chromat.	With copper(l) iodide; oxygen; trifluoroacetic acid at 130℃; for 2h; Schlenk technique; Sealed tube;	1.General procedure,substrates scope and spectral data for the products General procedure: A 100 mL sealed Schlenk tube equipped with a magnetic stir bar and charged with CuI (1 equiv,0.2 mmol) was evacuated and back filled with oxygen (this process was repeated 3 times). And then indole (0.2 mmol), CF3COOH (1.2 equiv, 0.24 mmol) DMF(1 mL) were added. The reaction mixture was stirred at 130 oC, after completion as monitored by TLC and GC, the reaction was cooled to room temperature. After addition of aqueous NH3 solution, the reaction mixture was extracted with EtOAc (3×5ml). The combined organic layers were dried over NaSO4, filtered and concentrated. The residue was purified by flash columnchromatography on silica gel to give the analitycally pure product.

Reference： [1]Xiao, Jing; Li, Qiang; Chen, Tieqiao; Han, Li-Biao [Tetrahedron Letters, 2015, vol. 56, # 43, p. 5937 - 5940]

46
[ 603-76-9 ]
[ 33513-42-7 ]
[ 19012-03-4 ]
[ 85092-84-8 ]
[ 24662-37-1 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; oxygen; trifluoroacetic acid at 130℃; for 36h; Schlenk technique; Sealed tube;	1.General procedure,substrates scope and spectral data for the products General procedure: A 100 mL sealed Schlenk tube equipped with a magnetic stir bar and charged with CuI (1 equiv,0.2 mmol) was evacuated and back filled with oxygen (this process was repeated 3 times). And then indole (0.2 mmol), CF3COOH (1.2 equiv, 0.24 mmol) DMF(1 mL) were added. The reaction mixture was stirred at 130 oC, after completion as monitored by TLC and GC, the reaction was cooled to room temperature. After addition of aqueous NH3 solution, the reaction mixture was extracted with EtOAc (3×5ml). The combined organic layers were dried over NaSO4, filtered and concentrated. The residue was purified by flash columnchromatography on silica gel to give the analitycally pure product.

Reference： [1]Xiao, Jing; Li, Qiang; Chen, Tieqiao; Han, Li-Biao [Tetrahedron Letters, 2015, vol. 56, # 43, p. 5937 - 5940]

47
[ 19012-03-4 ]
[ 1291076-24-8 ]
[ 1291078-07-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 2h;	General procedure: A suspension of spirocycle 20 (440 mg, 1.36 mmol) in aqueous 10% NaHCO3 solution was extracted with CH2Cl2. The organic phase was dried over Na2SO4 and evaporated. The resulting oil was dissolved in CH2Cl2 (15 mL), treated with benzaldehyde (0.166 mL, 1.63 mmol) and NaBH(OAc)3 (433 mg, 2.04 mmol), and the resulting clear solution was stirred at RT for 2 h. Water was added to the mixture and the pH was brought to basic conditions with NH3. The mixture was extracted with CH2Cl2. The organic layer was dried, evaporated, and the crude residue was purified by column chromatography (eluent: petroleum ether/EtOAc 7:3) to give compound 24d (482 mg, 94%) as a light yellow solid.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 108,p. 53 - 67

48
[ 19012-03-4 ]
[ 1538-08-5 ]
2,2,2-trifluoro-N'-((1-methyl-1H-indol-3-yl)methylene)acetohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With acetic acid; In ethanol; for 4h;Reflux;	General procedure: Indole-3-aldehyde 16 (1 mmol) and the correspondingalkyl/aryl acid hydrazide 17 (1.05 mmol) were refluxed in ethanol (5 mL) in the presence of glacial acetic acid(0.3 mL) for 4 h. On cooling the reaction mixture to roomtemperature, the crude product was precipitated, filteredand dried. Further recrystallization of the crude products inethanol allowed to obtain pure products in 85-95 % yields.

Reference： [1]Medicinal Chemistry Research,2016,vol. 25,p. 941 - 950

49
[ 19012-03-4 ]
[ 6622-91-9 ]
[ 53645-40-2 ]

Reference： [1]Chemistry - An Asian Journal,2016,vol. 11,p. 221 - 225

50
[ 19012-03-4 ]
[ 1885-32-1 ]
C₁₈H₁₅N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With iron(III) chloride; In water; at 110℃;Sealed tube;	(1016) A 20 mL vial with stir bar was charged with 49 (0.0822 g, 0.55 mmol, 1 eq), 48 (0.0915 g, 0.57 mmol, 1.05 eq), and FeCl3 (0.0444 g, 0.27 mmol, 0.5 eq). Water (1 mL) was added. The vial was closed (screw cap), and the mixture was heated to 110 C. overnight. After cooling to room temperature the mixture was diluted with water. The solids were collected via vacuum filtration. The filter cake was triturated with water followed by MeOH and air dried. 0.06 g (0.21 mmol, 38% yield) of crude 50 was isolated as a solid. Mass spectrum (ESI+): m/z=290 [M+1].

Reference： [1]Patent: US2016/168140,2016,A1 .Location in patent: Paragraph 1016

51
[ 19012-03-4 ]
[ 13214-64-7 ]
(4Z)-4-[(1-methyl-1H-indol-3-yl)methylene]-2-(4-methoxyphenyl)-1,3-oxazol-5(4H)-one [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2016,vol. 53,p. 1200 - 1206

52
[ 19012-03-4 ]
[ 10075-51-1 ]
[ 100-58-3 ]
1-benzyl-5-bromo-3-[(1-methyl-1H-indol-3-yl)(phenyl)methyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	In tetrahydrofuran; at 60℃; for 20h;Cooling with ice;	To an ice-cold solution of aromatic aldehyde (1 equiv.) and nucleophile (2 equiv.) in THF (4 mL) was added the solution of arylmagnesium bromide in THF (4 mL, 1.3 equiv.). After 10 minutes the reaction was refluxed at 80 C for 14 h. Reaction mixture was diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was further extracted with ethyl acetate (2 x 10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by flash column chromatography (9:1, hexane: EtOAc) gave the corresponding triarylmethane derivatives up to 98 % yields.

Reference： [1]Tetrahedron Letters,2016,vol. 57,p. 5381 - 5384

53
[ 19012-03-4 ]
[ 66003-76-7 ]
[ 1757-72-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: N-methyl-3-formylindole With C₉H₁₈NZn⁽¹⁺⁾Cl^(1-) In tetrahydrofuran at 50℃; for 1h; Schlenk technique; Inert atmosphere; Stage #2: Diphenyliodonium triflate With copper(I) trifluoromethanesulfonate * 1/2 toluene In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;

Reference： [1]Liu, Chuan; Wang, Qiu [Organic Letters, 2016, vol. 18, # 19, p. 5118 - 5121]

54
[ 603-76-9 ]
[ 100-97-0 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With aluminum (III) chloride; In N,N-dimethyl-formamide; at 120℃; for 4.5h;	General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94%.
86%	With iodine; oxygen; pyrographite; In N,N-dimethyl-formamide; at 120℃; for 4h;	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.

Reference： [1]Patent: CN108329249,2018,A .Location in patent: Paragraph 0041-0044; 0141-0144
[2]Tetrahedron Letters,2017,vol. 58,p. 2877 - 2880

55
[ 19012-03-4 ]
[ 930-68-7 ]
(E)-6-((1-methyl-1H-indol-3-yl)methylene)cyclohex-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		The starting material cyclohexene-2-one (0.95 g, 10.0 mmol) was dissolved in 15 ml of anhydrous dichloromethane at a temperature of -50 CFollowed by addition of 200 mg of TiCl4 and PPh3 (2.62 g, 10.0 mmol) over 15 min followed by the addition of 1-methyl-1H-indole-3-carbaldehyde(3.18 g, 20.0 mmol) and reacted overnight at room temperature. After the reaction was complete, 10% K2CO3 solution was added for 10 min to collect organicLayer, spin steam, column chromatography purification. To give 2.03 g of a solid, yield: 86%

Reference： [1]Patent: CN106673988,2017,A .Location in patent: Paragraph 0120; 0121
[2]European Journal of Medicinal Chemistry,2020,vol. 204

56
[ 603-76-9 ]
[ 50-00-0 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	With iron(III) chloride; ammonia; In water; N,N-dimethyl-formamide; at 130℃; for 4h;	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).

Reference： [1]Organic Letters,2019,vol. 21,p. 7702 - 7707
[2]Synlett,2017,vol. 28,p. 2670 - 2674

57
[ 19012-03-4 ]
[ 30011-36-0 ]
4-benzyl-5-methyl-5H-pyrido[4,3-b]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20 - 80℃; for 9h; Molecular sieve; Inert atmosphere;

Reference： [1]Uredi, Dilipkumar; Motati, Damoder Reddy; Blake Watkins [Organic Letters, 2018, vol. 20, # 20, p. 6336 - 6339]

58
[ 3760-54-1 ]
[ 603-76-9 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With trifluoromethylsulfonic anhydride; caesium carbonate; cesium fluoride In toluene at -78 - 70℃; for 14.3333h; Inert atmosphere;

Reference： [1]Li, Lian-Hua; Niu, Zhi-Jie; Liang, Yong-Min [Organic and Biomolecular Chemistry, 2018, vol. 16, # 42, p. 7792 - 7796]

59
[ 19012-03-4 ]
[ 32387-21-6 ]

Yield	Reaction Conditions	Operation in experiment
66%	With 2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; 1,4-diaza-bicyclo[2.2.2]octane; oxygen; In tetrahydrofuran; at 20℃; for 16h;	General procedure: To a dry, two-neck 25 mL round-bottom flask equipped with a magnetic stir bar was added NHC catalyst F (0.025 mmol) and aldehyde 1 (0.5 mmol). The reaction vessel was charged with anhydrous THF (3 mL), followed by flushing with O2 gas. DABCO (0.25 mmol) was added and the flask was again flushed with O2 gas. The reaction mixture was stirred for 16 h at r.t. under an O2 atmosphere (1 atm, O2 balloon). After completion of the reaction, as monitored by TLC, the mixture was diluted with EtOAc (10 mL) and aqueous 1.0 M NaOH solution was added. The aqueous layer was separated, washed with EtOAc (10 mL) and acidified using 3.0 M aqueous HCl solution (10 ml). This aqueous layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the pure desired product.

Reference： [1]Synthesis,2018,vol. 50,p. 4290 - 4294
[2]Organic Letters,2019,vol. 21,p. 2048 - 2051

60
[ 19012-03-4 ]
[ 19433-17-1 ]
[ 5562-56-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	With pyridine; iodine; In 1,4-dioxane; at 110℃; for 12h;Sealed tube;	Compound 1b (1.0 mmol, 177 mg) was added to a 25 mL sealed tube.Compound 2m (0.5 mmol, 79.6 mg), iodine simple substance (0.5 mmol, 127 mg),Pyridine (0.5 mmol, 39.6 mg) and 1,4-dioxane (2 mL),The reaction was then stirred in an oil bath at 110 C for 12 h. The reaction was quenched by the addition of 50 mL EtOAc (EtOAc)The organic phase was washed successively with a Na2S2O3 solution having a mass concentration of 10% and saturated brine, and dried over anhydrous sodium sulfate. Filter, spin dry,Separated by silica gel column(petroleum ether/ethyl acetate = 10/1, v/v)Obtained a white solid product 3x(124.2 mg, 69%).

Reference： [1]Organic and Biomolecular Chemistry,2018,vol. 16,p. 9030 - 9037
[2]Patent: CN108976198,2018,A .Location in patent: Paragraph 0112; 0113; 0114

61
[ 19012-03-4 ]
[ 61542-10-7 ]
2-(3-methoxypropyl)-1-methyl-indole-3-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: N-methyl-3-formylindole With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate for 0.0833333h; Inert atmosphere; Stage #2: 1-iodo-3-methoxypropane With 2,2,6,6-tetramethyl-piperidine In methanol at 20℃; for 16h; Irradiation; regioselective reaction;

Reference： [1]Bissonnette, Noah B.; Boyd, Michael J.; May, Gregory D.; Giroux, Simon; Nuhant, Philippe [Journal of Organic Chemistry, 2018, vol. 83, # 18, p. 10933 - 10940]

62
[ 101691-94-5 ]
[ 19012-03-4 ]
1-methyl-2-(tetrahydropyran-4-ylmethyl)indole-3-carbaldehyde [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 10933 - 10940

63
[ 19012-03-4 ]
[ 1363381-15-0 ]
[ 2242624-69-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: N-methyl-3-formylindole With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate for 0.0833333h; Inert atmosphere; Stage #2: 6-iodo-2-oxaspiro[3.3]heptane With 2,2,6,6-tetramethyl-piperidine In methanol at 20℃; for 16h; Irradiation; regioselective reaction;

Reference： [1]Bissonnette, Noah B.; Boyd, Michael J.; May, Gregory D.; Giroux, Simon; Nuhant, Philippe [Journal of Organic Chemistry, 2018, vol. 83, # 18, p. 10933 - 10940]

64
[ 25637-18-7 ]
[ 19012-03-4 ]
1-methyl-2-tetrahydropyran-4-yl-indole-3-carbaldehyde [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 10933 - 10940

65
[ 19012-03-4 ]
[ 590-93-2 ]
[ 10124-78-4 ]
[ 95-55-6 ]
N-(2-hydroxyphenyl)-N-(1-(1-methyl-1H-indol-3-yl)-2-(naphthalen-2-ylamino)-2-oxoethyl)but-2-ynamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium sulfate In methanol at 20℃;

Reference： [1]He, Yi; Liu, Zhen; Wu, Danjun; Li, Zhenghua; Robeyns, Koen; Van Meervelt, Luc; Van Der Eycken, Erik V. [Organic Letters, 2019, vol. 21, # 12, p. 4469 - 4474]

66
[ 19012-03-4 ]
[ 5963-77-9 ]
[ 119072-55-8 ]
[ 95-55-6 ]
N-(2-(tert-butylamino)-1-(1-methyl-1H-indol-3-yl)-2-oxoethyl)-N-(2-hydroxyphenyl)pent-2-ynamide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 4469 - 4474

67
[ 19012-03-4 ]
[ 590-93-2 ]
[ 7188-38-7 ]
[ 1134-36-7 ]
N-(2-(tert-butylamino)-1-(1-methyl-1H-indol-3-yl)-2-oxoethyl)-N-(4-hydroxy-[1,1'-biphenyl]-3-yl)but-2-ynamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium sulfate In methanol at 20℃;

Reference： [1]He, Yi; Liu, Zhen; Wu, Danjun; Li, Zhenghua; Robeyns, Koen; Van Meervelt, Luc; Van Der Eycken, Erik V. [Organic Letters, 2019, vol. 21, # 12, p. 4469 - 4474]

68
[ 19012-03-4 ]
[ 5963-77-9 ]
[ 119072-55-8 ]
N-(tert-butyl)-9-ethyl-5-methyl-11,14-dioxo-5,5a,6,8a,11,13-hexahydro-6,8b-methanopyrrolizino[1,2-d]carbazole-13-carboxamide [ No CAS ]
N-(tert-butyl)-9-ethyl-5-methyl-11,14-dioxo-5,5a,6,8a,11,13-hexahydro-6,8b-methanopyrrolizino[1,2-d]carbazole-13-carboxamide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 4469 - 4474

69
[ 19012-03-4 ]
C₁₀H₉FN₂OS [ No CAS ]
2-((4-fluorobenzyl)imino)-5-((1-methyl-1H-indol-3-yl)methylene)thiazolidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With piperidine; In ethanol; at 60℃; for 8h;	General procedure: To a stirred solution ofthiazolidin-4-one (C) (0.5 mmol) in 5 ml of absolute ethanol, substituted indole-3-aldehyde (F) (0.6mmol) was added. Next, 50 muL of piperidine (0.5 mmol) was added to the mixture, and the mixture wasstirred for 8 h at 60 C until a precipitate formed. The mixture was cooled to room temperature, and theprecipitate was filtered and washed with petroleum ether and absolute ethanol to give respectivecompound G1-G44 at good to very good yield. Reaction mixtures that did not form precipitates wereextracted with ethylacetate. The ethyl acetate layer was washed with brine solution, and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography andeluted with 60% ethyl acetate in petroleum ether/ hexane.

Reference： [1]Bioorganic Chemistry,2019,vol. 92

70
[ 19012-03-4 ]
C₁₀H₈Cl₂N₂OS [ No CAS ]
2-((3,4-dichlorobenzyl)imino)-5-((1-methyl-1H-indol-3-yl)methylene)thiazolidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With piperidine; In ethanol; at 60℃; for 8h;	General procedure: To a stirred solution ofthiazolidin-4-one (C) (0.5 mmol) in 5 ml of absolute ethanol, substituted indole-3-aldehyde (F) (0.6mmol) was added. Next, 50 muL of piperidine (0.5 mmol) was added to the mixture, and the mixture wasstirred for 8 h at 60 C until a precipitate formed. The mixture was cooled to room temperature, and theprecipitate was filtered and washed with petroleum ether and absolute ethanol to give respectivecompound G1-G44 at good to very good yield. Reaction mixtures that did not form precipitates wereextracted with ethylacetate. The ethyl acetate layer was washed with brine solution, and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography andeluted with 60% ethyl acetate in petroleum ether/ hexane.

Reference： [1]Bioorganic Chemistry,2019,vol. 92

71
[ 19012-03-4 ]
[ 140-29-4 ]
C₁₈H₁₄N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: The schematic diagram of the synthesis of AIE-1 and AIE-2 is given inScheme 1and followed the earlier reported procedure [37]. In brief, phenylacetonitrile (5 mmol, 1 eq.) and sodium ethoxide (5 mmol, 1 eq.) were dissolved in anhydrous ethanol (15 mL). After 10-15 min stirring at room temperature, 1-methylindole-3-carboxyaldehyde (5 mmol, 1eq.) was added to the reaction mixture and refluxed overnight at 70 C. Upon cooling the reaction mixture, a yellow precipitate was obtained and the precipitate was filtered followed by several washes with fresh ethanol. The obtained precipitate was dried under vacuum for 2 h to afford yellow crystalline probe AIE-1. Whereas for the synthesis of AIE-2, we followed the same procedure as for AIE-1 but, instead of phenylacetonitrile, we used 0.5 eq. of 1,4-phenylenediacetonitrile to get yellowish-orange probe AIE-2. AIE-1.Yellow crystalline solid, yield 80%.1H-NMR (500 MHz, DMSO-d6): 8.36 (s, 1H), 8.23 (s, 1H), 8.11 (d, J = 10, 1H), 7.80 (d, J = 10, 2H), 7.58 (d, J = 10, 1H), 7.48 (t, J = 10, 2H), 7.36 (t, J = 10, 1H), 7.31 (t, J = 10, 1H), 7.24 (t, J = 10, 1H), 3.95 (s, 3H).13C-NMR (125 MHz, DMSO-d6): 135.8, 133.8, 133.3, 130.1, 128.4, 127.2, 127.1, 124.3, 122.3, 120.3, 119.2, 118.3, 110.0, 109.3, 101.8, 32.7. ESI-MS (positive mode) calculated for C18H14N2[M + H+]: 259.12; Found: 259.12.

Reference： [1]Molecules,2020,vol. 25

72
[ 19012-03-4 ]
[ 622-75-3 ]
C₃₀H₂₂N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: The schematic diagram of the synthesis of AIE-1 and AIE-2 is given inScheme 1and followed the earlier reported procedure [37]. In brief, phenylacetonitrile (5 mmol, 1 eq.) and sodium ethoxide (5 mmol, 1 eq.) were dissolved in anhydrous ethanol (15 mL). After 10-15 min stirring at room temperature, 1-methylindole-3-carboxyaldehyde (5 mmol, 1eq.) was added to the reaction mixture and refluxed overnight at 70 C. Upon cooling the reaction mixture, a yellow precipitate was obtained and the precipitate was filtered followed by several washes with fresh ethanol. The obtained precipitate was dried under vacuum for 2 h to afford yellow crystalline probe AIE-1. Whereas for the synthesis of AIE-2, we followed the same procedure as for AIE-1 but, instead of phenylacetonitrile, we used 0.5 eq. of <strong>[622-75-3]1,4-phenylenediacetonitrile</strong> to get yellowish-orange probe AIE-2.

Reference： [1]Molecules,2020,vol. 25

73
[ 19012-03-4 ]
[ 109-73-9 ]
[ 108-56-5 ]
ethyl 1-butyl-4-hydroxy-2-(1-methyl-1H-indol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 7528 - 7535
Angew. Chem.,2020,vol. 132,p. 7598 - 7605,8

74
[ 24662-37-1 ]
[ 19012-03-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium hydride; zinc(II) chloride; In tetrahydrofuran; mineral oil; at 40℃; for 2h;Inert atmosphere; Sealed tube;	General procedure: To a mixture of NaH (60% dispersion in mineral oil; 60.0 mg, 1.50 mmol) and ZnCl2 (102 mg, 0.750 mmol) in a 25-mL sealed tube was added a solution of nitrile 1 or 3 (0.500 mmol) in THF (2.5 mL). The mixture was sealed and stirred at 40 C. The reaction was quenchedby following one of the two protocols. Workup protocol 1: Upon full consumption of the nitrile (TLC or GC monitoring), silica gel (2.0 g) was added to the mixture and it was diluted with hexane (10 mL) at 0 C. The resulting mixture was stirred for 1 h at 24 C. The mixture was then filtered through layers of cottonand sand and washed with EtOAc. The volatile materials were removedin vacuo from the resulting filtrate. The crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4. Workup protocol 2: Upon full consumption of amide (TLC or GC monitoring), the reaction was quenched with pH 10 ammonium buffer at 0C and the organic materials were extracted with CH2Cl2 (3 × 20 mL). The combined organic extracts were dried (MgSO4). The volatile materials were removed in vacuo and the resulting crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4.

Reference： [1]Synthesis,2020,vol. 52,p. 1369 - 1378

75
[ 19012-03-4 ]
[ 3112-88-7 ]
3-[(Z)-2-phenyl-2-(phenylsulfonyl)ethenyl]-N-methylindole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With diethyl chlorophosphate; lithium hexamethyldisilazane In tetrahydrofuran at -78 - 0℃; for 2h; Inert atmosphere;	One-Shot Synthesis of Ethenyl Sulfone 1a from Benzyl Sulfone (representative). General procedure: To a 50 mL of two-neck round-bottomed flask charged with a magnetic stirrer bar were addedbenzyl sulfone (279 mg, 1.2 mmol) in dehydrated THF (12 mL), benzaldehyde (106 mg, 1.0 mmol)and diethyl chlorophosphate (207 mg, 1.2 mmol). A solution of lithium bis(trimethylsilyl)amide (1.3M in THF, 1.7 mL, 2.2 mmol) was added dropwise at -78 °C, and the mixture was stirred at -78 °C for 1 h and at 0 °C for additional 1 h. The reaction mixture was quenched with 5 mL of saturatedNH4Cl aq., and the organic and aqueous layers were separated. The organic layer was extracted withEtOAc, and combined organic layer was washed with water and brine. The organic layer was driedover MgSO4, and the solvents were removed under reduced pressure. The crude product wassubjected to a flash chromatography (EtOAc/CH2Cl2/hexane, 1:1:8) and recrystallization (MeOH) toafford the desired ethenyl sulfone 1a (181 mg) in 56% yield.

Reference： [1]Adachi, Kazumasa; Dakegata, Aki; Fukuyama, Takahide; Okuda, Yasuhiro; Orita, Akihiro; Ryu, Ilhyong; Takemoto, Mai; Wakamatsu, Kan; Watanabe, Hikaru [Chemistry Letters, 2020, vol. 49, # 4, p. 409 - 412]

76
[ 19012-03-4 ]
[ 4943-83-3 ]
C₂₀H₁₅N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: N-methyl-3-formylindole; 2-amino-N-(prop-2-yn-1-yl)benzamide With magnesium sulfate; toluene-4-sulfonic acid In tetrahydrofuran at 20℃; for 12h; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran for 0.5h; Cooling with ice;	21 Under electromagnetic stirring, compound 3u (500mg, 2.87mmol), p-toluenesulfonic acid (148mg, 0.86mmol), tetrahydrofuran (40.0mL), anhydrous magnesium sulfate (1033mg, 8.61mmol), Compound Y N-methyl-indole-3-carbaldehyde (457mg, 2.87mmol), the mixture was reacted at room temperature for 12h, DDQ (782mg, 3.44mmol) was added in an ice-water bath, and the reaction was carried out for 30 minutes. The reaction was completed and removed under reduced pressure The solvent and the crude product were purified by column chromatography (eluent: VEA:VPE=1:10, 1:4, 1:2) to obtain 300 mg of light yellow solid compound 4u (yield 33%).

Reference： [1]Current Patent Assignee: GUANGXI NORMAL UNIVERSITY - CN113480537, 2021, A Location in patent: Paragraph 0141; 0143; 0145

77
[ 19012-03-4 ]
[ 134610-32-5 ]
(E)-1-(3,4-dimethoxy-5-nitrophenyl)-3-(1-methyl-1H-indol-3-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.6%	With piperidine In ethanol at 95℃;	4.1.6. General synthesis method for 13a-13l, 14a-14d General procedure: The general procedure for the preparation of 13 was totallyundertaken according to our previously reported method [21]. To asolution of intermediate 10, 11 or 12 (1equiv) in EtOH (5 mL),piperidine (1.2 equiv) was added. Commercially availablesubstituted benzaldehydes 13 (0.8 equiv) were subsequently added.After the mixture was stirred at 95 °C for 12-24 h, the reaction was quenched with diluted hydrochloric acid to pH 6 and then extracted with EtOAc. The organic layer was orderly washed with aqueous NaHCO3, water, saturated NaCl, and dried over anhydrousNa2SO4. After concentrated under reduced pressure, the crudeproduct was purified by silica gel (ethyl acetate: petroleum 1:10)to afford the target compounds.

Reference： [1]Yan, Jun; Xu, Yuzhu; Jin, Xing; Zhang, Qiaoxuan; Ouyang, Feng; Han, Liqiao; Zhan, Min; Li, Xingshu; Liang, Baoxia; Huang, Xianzhang [European Journal of Medicinal Chemistry, 2022, vol. 227]

78
[ 19012-03-4 ]
[ 14134-81-7 ]
2-(2-(1-methyl-indol-3-yl)vinyl)-1-ethyl-3,3-dimethyl-3H-indolium iodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With piperidine In acetonitrile at 90℃;	General procedure: (Knoevenagel condensation) General procedure: Both the aldehyde(1 eq.) and 1-ethyl-3,3-dimethyl-3H-indolium iodide 4 (1 eq.) were solubilized in dry MeCN (final concentration of 1 M). Piperidine (10 mol%) was added and the solution was heated to 80 °C for 6 h-16 h. The solvent was removed under reduced pressure and the crude mixture was purified by recrystallization in diethyl ether.

Reference： [1]Bénard, Magalie; Boujut, Margot; Chevalier, Arnaud; Franck, Xavier; Galas, Ludovic; Gallavardin, Thibault; Schapman, Damien [Dyes and Pigments, 2022, vol. 198]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	19012-03-4	MDL No. :	MFCD00014570
Formula :	C₁₀H₉NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KXYBYRKRRGSZCX-UHFFFAOYSA-N
M.W :	159.19	Pubchem ID :	87894
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.1
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.59
TPSA :	22.0 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) :	-6.04 cm/s

Log Po/w (iLOGP) :	1.71
Log Po/w (XLOGP3) :	1.73
Log Po/w (WLOGP) :	1.99
Log Po/w (MLOGP) :	1.18
Log Po/w (SILICOS-IT) :	2.09
Consensus Log Po/w :	1.74

[ CAS No. 19012-03-4 ] {[proInfo.proName]}

Quality Control of [ 19012-03-4 ]

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Calculated chemistry of [ 19012-03-4 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 19012-03-4 ]

Application In Synthesis of [ 19012-03-4 ]

[ 19012-03-4 ] Synthesis Path-Upstream 1~2

[ 19012-03-4 ] Synthesis Path-Downstream 1~78

Related Functional Groups of
[ 19012-03-4 ]

Aldehydes

Related Parent Nucleus of
[ 19012-03-4 ]

Indoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-2.41
Solubility :	0.625 mg/ml ; 0.00393 mol/l
Class :	Soluble
Log S (Ali) :	-1.81
Solubility :	2.47 mg/ml ; 0.0155 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.78
Solubility :	0.264 mg/ml ; 0.00166 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.11

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

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
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

[ CAS No. 19012-03-4 ] {[proInfo.proName]}

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[ 19012-03-4 ] Synthesis Path-Upstream 1~2

[ 19012-03-4 ] Synthesis Path-Downstream 1~78

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