* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With silver tetrafluoroborate; 4,4'-Dimethoxy-2,2'-bipyridin; potassium <i>tert</i>-butylate; hydrogen In 1,4-dioxane at 80℃; for 48 h; Autoclave
In Example 1, the m-nitroacetophenone used was replaced with an equimolar 6-nitroindole at a hydrogen pressure of4.0 MPa at 80 ° C for 48 hours. The other procedure was the same as in Example 1 to give 6-aminoindole in a yield of 94percent, _: A solution of 16.44 mg (0.04 mmol) 4,4'-dimethoxy-2,2'-bipyridine silver 11.22 mg (0.1 mmol) of potassuim t-butoxide and 1 mL of 1,4-dioxane were charged into an autoclave. After stirring, 165.15 mg (1 mmol) of m-nitroacetophenone was added and the mixture was stirred at 80 °C. The reaction was carried out for 8 hours. After the reaction has finishedm the reaction solution was extracted with water and dichloromethane to collect the organic phase. Then, the organic phase was dried over anhydrous Na2SO4, suction filtered, rotary evaporated and chromatographed to give a yellow solid 3-acetanilide. Yield 96 percent.
90%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃;
General procedure: A mixture of compounds 1–4 (6.13 mmol) in ethanol (30 mL) was treated with 10percent Pd/C (20 wt. percentof 1–4) and subjected overnight to 50 psi H2 (g) in a Parr hydrogenation apparatus. The reaction mixture was filtered and concentrated in vacuo. Pure products 1M–4M were obtained via flash chromatography by eluting with a gradient of 30percent–40percent EtOAc/hexanes.
85%
With hydrazine hydrate In ethanol at 80℃; for 1 h; Inert atmosphere
General procedure: Hydrazine hydrate was chosen as the hydrogen donor for the low emission of pollutants. In a typical procedure, hydrazine hydrate (4 equiv) was added into the reactor which containing fresh prepared catalyst as described above. Then the reactor was put into a preheated oil bath with a stirring speed of 500 rpm, and the substrate (1 mmol)dissolved in 1 mL ethanol was added drop-wisely under argon. The reactions were monitored by TLC. After the reaction, the reaction mixture was vacuum filtered through a pad of silica on a glass-fritted funnel and an additional 15 mL of ethyl acetate (5 mL portions) was used to rinse the product from the silica, the filtrate was concentrated in vacuum and analyzed by GC. Products were purified by column chromatography and identified by 1H NMR and 13C NMR.
Reference：
[1] Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2437 - 2451
[2] Patent: US2005/70534, 2005, A1, . Location in patent: Page/Page column 14
[3] Patent: CN106748834, 2017, A, . Location in patent: Paragraph 0016; 0033; 0036
[4] Molecules, 2014, vol. 19, # 1, p. 925 - 939
[5] Catalysis Communications, 2016, vol. 84, p. 25 - 29
[6] Chemistry - A European Journal, 2018, vol. 24, # 31, p. 7926 - 7938
[7] Journal of the American Chemical Society, 1954, vol. 76, p. 5149
[8] Patent: US4997844, 1991, A,
[9] Patent: US6228877, 2001, B1,
[10] ACS Catalysis, 2014, vol. 4, # 5, p. 1441 - 1450
[11] Patent: WO2016/57834, 2016, A1, . Location in patent: Paragraph 000420
[12] Journal of the American Chemical Society, 2018, vol. 140, # 48, p. 16460 - 16463
2
[ 61293-29-6 ]
[ 5318-27-4 ]
Reference：
[1] Patent: US3976639, 1976, A,
3
[ 61293-29-6 ]
[ 5318-27-4 ]
Reference：
[1] Organic Preparations and Procedures International, 1995, vol. 27, # 5, p. 576 - 579
4
[ 16732-65-3 ]
[ 5318-27-4 ]
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 370,373
5
[ 19727-83-4 ]
[ 5318-27-4 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 31, p. 7926 - 7938
6
[ 496-15-1 ]
[ 5318-27-4 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 31, p. 7926 - 7938
7
[ 121-14-2 ]
[ 5318-27-4 ]
Reference：
[1] Patent: US3976639, 1976, A,
8
[ 99365-39-6 ]
[ 5318-27-4 ]
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 370,373
9
[ 5318-27-4 ]
[ 52415-29-9 ]
Reference：
[1] Organic Preparations and Procedures International, 1995, vol. 27, # 5, p. 576 - 579
10
[ 5318-27-4 ]
[ 73183-34-3 ]
[ 642494-36-8 ]
Reference：
[1] Journal of Organic Chemistry, 2013, vol. 78, # 5, p. 1923 - 1933
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 18h;
31 Synthesis of tert-Butyl 1H-indol-6-ylcarbamate (compound 64-2)
Synthesis of tert-Butyl 1H-indol-6-ylcarbamate (compound 64-2)[0000222] To a stirred solution of 1H-indol-6-amine (1.12 g, 8.5 mmol, 1 equiv) was added di-tert-butyl dicarbonate (1.95 g, 8.9 mmol, 1.05 equiv) in tetrahydrofuran (6 mL) . Saturated aqueous sodium bicarbonate (6 mL) was added and the reaction was stirred at room temperature for 18 hours. The layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 5 mL) . The organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure to give compound 64-2 as a white solid (2.2 g, 97% yield)
92%
With sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;
82%
With sodium hydroxide In diethyl ether at 20℃;
77%
With sodium hydrogencarbonate In tetrahydrofuran; water at 30℃; for 18h;
126.a (S)-N-(1H-lndol-6-yl)-N-methyl-3-(6-methyl-4-(trifluoromethyl)pyridin-2-yl)-2- oxooxazolidine-4-carboxamide
Step a. To a stirred solution of 1H-indol-6-amine (1.12 g, 8.47 mmol) in THF (6 ml_) was added (Boc)20 (1.94 g, 8.90 mmol) followed by sat. aq. NaHCC>3 (6 ml_) and the reaction was stirred at 30°C for 18 h. Upon completion, the mixture was quenched with water (30 ml_) and extracted with EtOAc (30 ml_ x 2). The combined organic layers were washed with brine (30 ml_), dried over Na2SC>4 and evaporated. The residue was purified by column chromatography (20% EtOAc in PE) to give tert-butyl 1 H-indol-6-yl-carbamate (1.6 g, 77% yield) as a white solid. m/z ES+ [M+Na]+255.0;1H NMR (400 MHz, DMSO-d6) d ppm 10.93 (s, 1H), 9.20 (s, 1H), 7.74 (s, 1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.29 - 7.22 (m, 1 H), 7.04 (dd, = 1.6, 8.4 Hz, 1 H), 6.36(t, J = 2.0 Hz, 1 H), 1.54 (s, 9H).
With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane;Inert atmosphere;
Example 25; 4-(3-(6-Chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(tetrahydrofuran-3-ylamino)- 9H-pyrido[3,4-b]indole- 1 -carboxamide; 1.; To a yellow, homogeneous solution of 1H-indol-6-amine (1.3007 g, 9.84 mmol) and DIPEA (2.58 mL, 14.76 mmol) in 1,4-dioxane (19.68 mL) under nitrogen was added 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (2.81 g, 10.83 mmol) The reaction was stirred overnight, diluted with EtOAc (1500 mL), washed with water (3 x 50 mL) and brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to give the desired product (2.666 g, 9.65 mmol, 98% yield) as a light tan solid.
N-(1H-6-indolyl)-1H-indolyl-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
33%
In acetonitrile; for 6h;Reflux;
General procedure: Aniline (3 equiv) was added to a stirringsolution of 2 (100 mg, 0.59 mmol, 1 equiv) in MeCN (4 ml). The mixture washeated to reflux and allowed to stir for 6 h, after which time the reaction wascooled and concentrated in vacuo to yield a brown amorphous solid. Flashchromatography (hexane/EtOAc, 1:1) afforded 3 (118 mg, 0.5 mmol, 85%) as awhite amorphous solid. This representative method was applied to varyingamounts of 2, 17 and 18 using the same equivalents and solvent ratios above toafford products 4-16. N-Phenyl-1H-indolyl-3-carboxamide (3).
6-chloro-N-(1H-indol-5-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at -60 - 20℃;
General procedure: Five mmol 2,4-dichloro-5-substitued-pyrimidines (8a-8g) or 4,6-dichloro-1H-pyrazolo [3,4-d]pyrimidine (8h) and DIPEA (1.2mL, 7.5mmol) were dissolved in DMF (4mL) and cooled to -60°C. Indol-5-amine or amines 9a-9i (5mmol) dissolved in DMF (2mL) were added dropwise. The reaction mixture was stirred at -60°C for about 1h. Next, the cooling bath was removed, the reaction mixture was stirred at room temperature for 2h, and was poured to 10mL cooled water after the reaction was complete as monitored by TLC. The formed precipitate was collected by filtration, washed with ethanol yielding compounds 10a-10h, 11a-11j, which were dried and used in the next step without further purification.
N-(1H-indol-6-yl)-3-(trifluoromethyl) benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;
4.2.3. General synthesis of substituted N-(1H-indole-6-yl)benzamide derivatives
General procedure: A flask was charged with 6-amino Indole (1eq.) in the presenceof dichloromethane (DCM, 0.5 M) and E3N (1.2 eq.) under nitrogenat 0 °C. This was followed by addition of substituted benzoylchlorides (1 eq.) to stir at room temperature overnight. The reactionmixture was quenched by water to be extracted with ethyl acetateand dried over anhydrous Na2SO4. The ethyl acetate layer wasevaporated in vacuo. The crude product was purified using silica gelcolumn chromatography using ethyl acetate/hexane solventmixture (50:50) to obtain substituted N-(1H-indole-6-yl) benzamidederivatives
N-(1H-indol-6-yl)-4-methyl-3-nitrobenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48.3%
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;
4.1.1. General procedure for synthesis of compounds 1-30
General procedure: To a stirred solution of the appropriate indolamine (1.50 mmol),and Et3N (4.50 mmol) in dry CH2Cl2 (3 mL/mmol) at 0 C was addeddropwise a solution of benzylsulfonamide (2.25 mmol) under nitrogen.The mixture was reacted at 0 C for 2 h, and for 18e22 h atroom temperature. The residue was poured into water (20 mL) andextracted with CH2Cl2 (3 x 20 mL). The combined organic layerswere dried (Na2SO4), filtered and concentrated under reducedpressure. Purification by column chromatography on silica gel (CH2Cl2/MeOH, 98:2) gave compounds 1e30.
With methanesulfonato(2-dicyclohexylphosphine-3,6-dimethoxyl-2’,4’,6’-triisopropyl-1,1’-biphenyl)(2’-amino-1,1’-biphenyl-2-yl)palladium(II); caesium carbonate In tert-Amyl alcohol at 100℃; for 2h; Inert atmosphere;
249 Example 249: Synthesis of 6-((1H-indol-6-yl)amino)-2-methylnicotinonitrile(Compound 598)
1H-indol-6-amine (53.2 mg, 0.4 mmol, 1.0 equiv.) and 2-chloro-4-(2,2,2- trifluoroethoxy) pyrimidine (79.0 mg, 0.4 mmol, 1.0 equiv.) were dissolved in t-AmOH (3.0 mL), then Cs2CO3 (260 mg, 0.8 mmol, 2.0 equiv.) and Brettphos Pd G3 (16.92 mg, 0.02 mmol, 0.05 equiv.) were added under N2atmosphere. The mixture was stirred at 100 °C for 2 hours.3.0 mL water was added to the reaction mixture and extracted with EtOAc. The organic layer was collected and concentrated solvent by Speedvac. The residue was purified by prep HPLC to give 6-((1H-indol-6-yl)amino)-2-methylnicotinonitrile (49.02 mg, 0.198 mmol) as solid. MS-ESI, 249.2 [M+H+].1H NMR (400 MHz, DMSO-d6) d ppm 11.01 (br s, 1 H) 9.56 (s, 1 H) 7.92 (s, 1 H) 7.74 (d, 1 H) 7.46 (d, 1 H) 7.26 (t, 1 H) 7.07 (dd, 1 H) 6.68 (d, 1 H) 6.36 (br s, 1 H) 2.52-2.56 (m, 3 H)
2.1.2. Synthesis of organic PT CT Complex
The synthesis of organic PT CT complex by using a mixture of 1 mmol saturated methanol solution of 6 AMI (0.132g), and CLA (0.208g). This donor and acceptor upon mixing a violet color so- lution have appeared. The solution was stirred at 25 °C for 120 min and allowed to evaporate for 8-10 days, forming a solid crys- talline PT CT complex. The solid substance was filtered through Whatmann:41 filter paper and washed away with methanol sev- eral times before being dried over anhydrous CaCl 2 . The chemi- cal formula of the produced PT CT complex (Molecular formula: C 14 H 10 Cl 2 O 4 N 2 + , m. wt: 341.14), and its elemental analysis (using SEM EDX) are experimentally and theoretically estimated.
4- ((1H-indol-6-yl)amino)-2H-chromen-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78.1%
With triethylamine In ethanol at 25℃; for 8h;
5.4. Synthesis of compounds 12a-12f
General procedure: Compounds 11a-11f (1.0 mmol, 1.0 eq), intermediate 8 (1.5 mmol,1.5 eq) and TEA (triethyl amine, 1.0 mmol, 1.0 eq) were added into 10mL of EtOH and then stirred at 25 C for 8 h. Then, the mixtures wereconcentrated under reduced pressure to give crude products, whichwere then purified by silica gel column chromatography using PE/EA(2/1, v/v) as eluents to get compounds 12a-12f.
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