Structure of 494799-16-5
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CAS No. : | 494799-16-5 |
Formula : | C15H15NO2 |
M.W : | 241.29 |
SMILES Code : | OC(=O)C1=CC=C2C(NC=C2C2=CCCCC2)=C1 |
MDL No. : | MFCD20526522 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogen;palladium hydroxide on carbon; In tetrahydrofuran; methanol; under 3102.97 Torr; for 14h; | Step 2; methy\\ 3-cvclohexyl-1H-indole-6-carboxylate; A solution (0.5 M) of 3-cyclohexenyl-1H-indole-6-carboxylic acid (from Step 1) in THF/M eOH (0.5 M, 1:1, v/v) was hydrogenated for 14 h over Pd(OH)2/C (0.1 eq., 20percent) at 60 psi. The catalyst was removed by filtration on a pad of celite.(TM). and the filtrate evaporated to dryness to afford 3-cyclohexyl-1 H-indoIe-6-carboxylic acid (90percent) as a white solid 1H NMR (300 MHz, DMSO-d6, 300 K) 6 1.20 -1.53 (m, SH), L70-L87 (m, 3H), 1.90-2.02 (m, 2H), 2.69-2.86 (m, 1H), 7.40 (s, 1H), 7.55-7.65 (rn, 2H), 8.0 (s, 1H), 11.40 (s, 1H); MS (ES+ m/z 244 (M+H)+. A solution of the foregoing compound in MeOH {0.4 M) was treated at 0 °C with thionylchloride (0.5 eq.) and refluxed for 24 h. Volatiles were removed under vacuum to afford the title compound (100percent) as a solid. |
90% | With ammonium formate;palladium 10% on activated carbon; In ethanol; at 50℃; for 4h; | To a solution of 3-(1-cyclohexen-1-yl)-1 H-indole-6-carboxylic acid (Intermediate 60) (1 g, 4.1 mmol) in ethanol was added Pd/C 10percent (catalytic quantity) and ammonium formiate (2.6 g, 41 mmol). The mixture was stirred at 500C for 4 hours. A precipitate was formed, HCI 1 N was added until the precipitate was dissolved. The mixture was filtered on celite, the filtrate was evaporated. The residue was diluted with diethyl ether, washed with water. The organic phase was dried over Na2SO4, filtered and evaporated to give the title compound as beige solid (900 mg, 90percent). NMR1H NMR (300 MHz), , delta : 7.96 (s, 1 H), 7.57 (q, 2H), 7.28 (s, 1 H), 2.77 (m, 1 H), 1.96 (m, 1 H), 1.77 (m, 3H), 1.43 (m, 4H), 1.26 (m, 1 H). |
87% | With hydrogen;palladium hydroxide on carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 3h; | Step B.A mixture of 1-2 (14.0 g, 58 mmol) and 20percent Pd(OH)2/C (600 mg) in methanol (50 mL) and THF (50 mL) was shaken in a hydrogenation apparatus under 55 psi pressure at room temperature for 3 h. The catalyst was removed by filtration and washed with methanol. The filtrate was concentrated to dryness. The residue was triturated in hexane, then the beige solid was collected by filtration, washed with hexane and dried under vacuum to give 12.3 g (87percent) of the target product 1-3: m/z : 244 (M+H)+. |
83% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; dichloromethane; under 2585.81 - 3102.97 Torr; for 15h; | Step 4. 3-Cyclohexyl-1H-indole-6-carboxylic acid (164)[0310] Compound 163 from Step 3 (75.5g) was split into two batches. Each batches were suspended in 600 mL solvent (1:1 MeOH:THF). Pd catalyst (10percent on carbon, Ig / batch) was added as a slurry in CH2Cl2 (5 mL) and the mixture was hydrogenated for 15hr at 50-60 psi. The catalyst was filtered off by means of Celite and the solvents were removed via vacuum distillation to a give compound 164 as a yellow solid. Yield 63g (83percent). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | 3-Cyclohexyl-1H-indole-6-carboxylic acid; 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | 3-Cyclohexyl-1H-indole-6-carboxylic acid.; 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | 3-Cyclohexyl-1H-indole-6-carboxylic acid. 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; under 2844.39 Torr; for 18h;Parr bottle; | 3-cyclohexyl-1H-indole-6-carboxylic acid. Intermediate 3A (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The mixture was shaken under 55 psi of H2 for 18 hours. The catalyst was removed by filtration. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | 3-Cyclohexyl-1H-indole-6-carboxylic acid.; 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | Intermediate 17 3-Cyclohexyl-1H-indole-6-carboxylic acid. 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
79% | With hydrogen;palladium 10% on activated carbon; In tetrahydrofuran; methanol; at 20℃; under 2844.39 Torr; for 18h; | 3-Cyclohexenyl-1H-indole-6-carboxylic acid (38 g) was added to a Parr bottle, followed by methanol (100 mL) and THF (100 mL). The bottle was flushed with argon and 10percent palladium on carbon (1.2 g) was added. The flask was then evacuated and subsequently refilled with H2 to a pressure of 55 psi, and the resultant mixture was shaken for 18 hours at RT. The catalyst was then removed by filtration through celite. Concentration of the filtrate provided the desired product as a pale purple solid (30.6 g, 79percent). ESI-MS m/z 244 (MH+). |
78% | With hydrogen;palladium(II) hydroxide/carbon; In tetrahydrofuran; methanol; under 2844.39 Torr; for 20h; | The unsaturated derivative from above was hydrogenated for 20 h under 55 psi hydrogen gas pressure over 20percent Pd (OH) 2/C (10.25 g) using 1: 1 THF-MEOH (2.5 L) as solvent. After filtration of the catalyst, volatiles were removed under reduced pressure and the residue was triturated with hexane. The beige solid was collected by filtration, washed with hexane and dried under vacuum (356.4 g, 78percent yield). |
50% | With palladium 10% on activated carbon; ammonium formate; In ethanol; at 50℃; for 4h; | To a stirred solution of compound 34 (2 g, 8.29 mmol) in EtOH (20 mL) under argon atmosphere, 10percent Pd/C (200 mg) and ammonium formate (5.2 g, 82.9 mmol) was added. The reaction mass was stirred at 50 °C for 4 h. The progress of the reaction was monitored by TLC. After completion, the reaction mass cooled to RT, quenched with iN HC1 and ethyl acetate andfiltered through a pad of celite. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated in vacuo to afford the crude. The crude compound was triturated with DCM to afford compound C19 (1 g, 50percent) as a light-brown solid. ?H-NMR (400 MHz, DMSOd 6): oe 12.42 (s, 1H), 11.13 (s, 1H), 7.98 (s, 1H), 7.62?7.57 (m, 2H), 7.30 (s, 1H), 2.80?2.76 (m, 1H), 1.99 ? 1.97 (m, 2H), 1.88 - 1.71 (m, 4H), 1.50 ? 1.38 (m, 4H), LCMS Observed (m/z):244.05 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Example 1; Preparation of (2E)-3-{4-[({1-[({3-CycIohexyl -1-[2- (dimethylamino) - 2-oxoethyl -2-phenyl-1H-indol-6-yl}carbonyl)amino]cyclopenthyl}carbonyl) amino]phenyl }acrylic acid; Step 1; 3-Cyclohex-1-en-1-yl-1H-indole-6-carboxylic acid; To a solution of methyl-indole-6-carboχylate in MeOH (1,7 M) was added cyclohexanone (3.0eq.) followed by 30% NaOMe in MeOH (6,0 eq.) in 100 ml portions over 20 min. The resulting mixture was stirred at RT for 45 min and relaxed for 8 h. Water was added, and the mixture stirred at RT until all solids had dissolved. The organic solvent was removed under vacuum and the pH of the aqueous phase adjusted to 1, by slow addition of concentrated HCl at 0 C. The precipitate was isolated by filtration, and then washed with water, until the pH of the water reached 6- 7, Drying under high vacuum gave the title compound as a beige solid (100%), | |
97.5% | 3-Cyclohexenyl-1H-indole-6-carboxylic acid.; Cyclohexanone (96 mL, 0.926 mol) was added to a stirred solution of methyl indole-6-carboxylic acid (50.0 g, 0.335 mol) in methanol (920 mL) at 22 C. Methanolic sodium methoxide (416 mL of 25% w/w, 1.82 mol) was added in portions over 10 minutes. The mixture was stirred at reflux for 18 hours, cooled to room temperature, concentrated, diluted with cold water, and acidified with 36% HCl solution. The resulting precipitate was collected by filtration, washed with cold water, and dried over phosphorous pentoxide (0.1 mm) to provide the title compound as a tan colored solid (80.9 g, 97.5% yield). | |
58% | With water; potassium hydroxide; In methanol; at 75℃; for 18h; | To a stirred solution of compound 26 (2 g, 11.4 mmol) and cyclohexanone (3.36 g,34.2 mmol) in MeOH (15 mL), aqueous KOH (1.92 g, 34.2 mmol, dissolved in 13 mL water) was added. The resulting reaction mixture was stirred at 75 C for 18 h. The progress of the reaction was monitored by LCMS. After completion, the reaction mixture was concentrated in vacuo. The residue was diluted with water, acidified with acetic acid pH-6; the obtained solidwas filtered; washed with water and dried in vacuo to afford the crude. The crude compound was triturated with IPA to afford compound 34 (1.6 g, 58%) as light brown solid. ‘H-NMR (400 MHz, DMSO-d6): ö 11.33 (s, 1H), 7.97 (s, 1H), 7.75 (d, J= 8.0 Hz, 1H), 7.61 (d, J= 8.4 Hz, 1H), 7.47 (s, 1H), 6.19 (s, 1H), 2.42 -2.39 (m, 2H), 2.22 - 2.20 (m, 2H), 1.76 - 1.72 (m, 4H). LCMS observed (m/z): 242 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | KOH (6.4 g, 0.11 mol) was dissolved in water (10 ml) and methanol (10 ml) was added. Methyl indole-6-carboxylate (2 g, 11.4 mmol) was added and the reaction mixture was stirred at 75C for 18 hours. Methanol was evaporated and the residue was diluted with water (100 ml), pH was neutralized to pH=6 with acetic acid. The precipitate was filtered, washed with water and dried. The solid was triturated in isopropyl ether, filtered and washed with isopropyl ether to give the title compound (2.2 g, 80%).NMR1H NMR (300 MHz), , δ : 8.16 (sd, 1 H), 8.00 (d, 1 H), 7.78 (dd, 1 H), 7.72 (d, 1 H), 6.36 (m, 1 H), 2.58 (m, 2H), 2.39 (m, 2H), 1.90 (m, 2H), 1.81 'm, 2H). |