5-Aminoindole

Grey Crystals

1H-indol-5-amine is an indolamine carrying an amino group at position 5.

In Example 1, the m-nitroacetophenone used was replaced with an equimolar 5-nitroindole, and at a hydrogen pressure of4.0 MPa for 24 hours at 80 ° C. The other procedure was the same as in to give 5-aminoindole in a yield of 98percent, _: 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 NaTo reduce a given model compound (5-nitroindol) in accordance with the above reaction scheme (to 5-aminoindol), the reservoir 104 of the hydrogenation apparatus 100 was filled with, as a sample solution, a stock solution of a 1:1 mixture of EtOAc:EtOH containing 5-nitroindol in a concentration of 0.05 mol/dmGeneral procedure: A mixture of nitroarene (1 mmol), SS-Pd (2 molpercent Pd) and sodium borohydride (3 mmol) were taken in a 25 ml round bottomed flask. 3 ml of MeOH:HA mixture of 5-nitro-1H-indole (11 g, 67.9 mmol) and Pd/C (5percent; 1 g), dissolved in ethanol (50 mL), was hydrogenated for 3 h at 40 psi. The reaction mixture was filtered and the excess of ethanol was evaporated under reduced pressure. Solid product was recrystallized from hexane to obtain the pure compound 5-aminoindole (55-1). Yield: 92.5percent. General procedure: A mixture of nitroarene (1 mmol), PdCu/graphene (6 mg) and sodium borohydride (2mmol) were taken in a 25 mL reaction tube. 3 mL of EtOH:H25 mL of hydrazine (98-100percent) are added slowly to a mixture of 25.0 g of 5-nitroindole, 1.2 g of 10percent palladium on carbon and 200 mL of absolute ethanol. After the addition, the resulting reaction mixture is then taken to reflux for 2 hours. The catalyst is eliminated by filtration and the filtrate is evaporated in order to produce a solid yellow residue. The crystals are washed with 200 ml of water and they are dried under vacuum in order to produce 16.5 g (81percent) of 5-aminoindole. Melting point: 131-134° C.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 General procedure: General procedure (9): Nitroindole derivative (1 equiv) was dissolved in ethanol (30 ml_ for 20.40 mmol of starting material) and 10percent palladium on carbon (10 mmolpercent) was added. The reaction flask was shaken under hydrogen at 30 psi using the Parr Shaker Hydrogenation Apparatus for 2.5 h. The reaction was filtered over celite and washed with ethyl acetate. The filtrate was concentrated in vacuo and purified by silica gel flash column chromatography to afford the aminoindole product. Intermediate 16 1/-/-indol-5-amine Intermediate 16 (2.7 g, 20.4 mmol) was prepared as a black solid from 5-nitro-1 /-/-indole (6.3 g, 38.9 mmol, 1 equiv) according to general procedure (9) using 1 :1 hexane/ethyl acetate as the eluent for flash silica gel column chromatography. Yield: 53percent. 5-nitro-1H-indole (6.3 g, 38.9 mmol, 1 equiv) was dissolved in ethanol (30 mL). 10percent palladium on carbon (630 mg, 10 mmolpercent) was added. The reaction flask was shaken under hydrogen at 30 psi using the Parr Shaker Hydrogenation Apparatus for 2.5 h. The reaction was filtered over celite and washed with ethyl acetate. The filtrate was evaporated, concentrated in vacuo and purified by silica gel flash column chromatography (1:1 hexane/ethyl acetate) to afford intermediate 16 as a black solid (2.7 g, 20.4 mmol). Yield: 53percent. General procedure: The nitro compound (1 equiv), HFIP (10 equiv), Fe powder (5 equiv) were mixed in a tube. Then 2 N HCl aqueous solutions was added to the reaction mixture. After stirring at room temperature for 30 min, the reaction mixture was neutralized with sat. NaHCOGeneral procedure: A mixture of nitroarene (1 mmol), PdCu/graphene (6 mg) and sodium borohydride (2 mmol) were taken in a 25 mL reaction tube. 3 mL of EtOH:HGeneral procedure: For the catalytic reactions, typically, 0.5 mmol nitroarene, 2.5 mL solvent, 189 mg ammonium formate (3.0 mmol), and catalyst (20 mg) were added to a 15 mL pressure bottle reactor (maximum pressure 1.0 MPa, the typical reaction pressure wasless than 0.4 MPa) with magnetic stirring. The atmosphere in the reactor was then replaced with Ar gas three times and tightly sealed. The reactor was placed in an oil bath preheated to the desired temperature. After the set reaction time, the reactor was quenched with cold water and the reaction mixture was diluted with 7.5 mL ethanol. The ethanol solution was analyzed by GC and GC‐MS.General procedure: An oven-dried flask was charged with aryl halide (1.0 mmol), aqueous NHFollowing the procedure set forth in (A) above, indole derivatives were deprotected using TFE or HFIP in a microwave reactor at 150° C. as set forth in Table 1 below. (A) A solution of the N-Boc protected amine (1 mmol) in TFE (2, 2, 2-trifluoroethanol) or HFIP (hexafluoroisopropanol) (5 mL) was placed in a sealed microwave vial. The reaction mixture was heated (100°C or 150°C) in a Biotage - Initiator (A) A solution of the N-Boc protected amine (1 mmol) in TFE (2, 2, 2-trifluoroethanol) or HFIP (hexafluoroisopropanol) (5 mL) was placed in a sealed microwave vial. The reaction mixture was heated (100°C or 150°C) in a Biotage - InitiatorB.

Molecular Weight:132.16
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:1
Exact Mass:132.068748264
Monoisotopic Mass:132.068748264
Topological Polar Surface Area:41.8
Heavy Atom Count:10
Complexity:124
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes