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Structure of 128798-39-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 128798-39-0 |
| Formula : | C13H13N |
| M.W : | 183.25 |
| SMILES Code : | [C-]#[N+]C1=CCC(C2=CC=CC=C2)CC1 |
| MDL No. : | MFCD06658504 |
| GHS Pictogram: |
|
| Signal Word: | Danger |
| Hazard Statements: | H301-H311-H315-H319-H331-H335 |
| Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P332+P313-P337+P313-P361-P403+P233-P405-P501 |
| Class: | 6.1 |
| UN#: | 2811 |
| Packing Group: | Ⅲ |
* 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.

[ 33225-72-8 ]

[ 128798-39-0 ]
[ 100-52-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 0.09 g | Example 13 2-Amino-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension. | |
| 0.09 g | Triethylamine (0.046g) and benzaldehyde (0.048g) in addition to methanol (3mL) solution of (R) -6- chloro-4-fluoro-indan-1-ylamine hydrochloride(0.1g), at 65 It was stirred for 0.5 hours. The reaction mixture was allowed to cool to room temperature, <strong>[33225-72-8]2-nitro-nicotinic acid</strong> (0.083 g) and4-phenyl-cyclohexen-1-yl isocyanide a (0.083 g) was added and stirred overnight at 65 ° C.. After the reaction mixture was allowed to cool to roomtemperature, and then concentrated under reduced pressure. The obtained residue in tetrahydrofuran (4 mL), water (40 muL) and 4 mol / Lhydrogen chloride in 1,4-dioxane solution (340muL) was added, and stirred for 1 hour at room temperature. Water and saturated sodium bicarbonatesolution was added to the reaction mixture, the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine,dried over anhydrous magnesium sulfate. The solvent was obtained by vacuum distillation residue was purified by silica gel column chromatography(eluting solvent methanol / ethyl acetate / n-hexane = 0/60 / 40-0 / 100 / 0-20 / 80/0), 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - was obtained[(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide (0.090 g). A suspension of Raney catalysts were prepared as follows. Raney (TM) 2800 nickel, slurryin water, stirring the mixture of ethanol and a suspension (200 muL) of active catalyst (Sigma-Aldrich), and the solvent was removed by decantation.The catalyst was washed 3 times with ethanol, ethanol (1 mL) was added and the suspension. The Raney catalyst suspension, under an argonatmosphere, 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - [(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide It added at room temperature in ethanol(1mL) solution of (0.090g), and the mixture was stirred under a hydrogen atmosphere for 5 hours. The catalyst was removed by filtration, and thefiltrate was concentrated under reduced pressure. The residue aminopropyl silica gel column chromatography (eluting solvent ethyl acetate /n-hexane = 90 / 10-100 / 0) to give the title compound (0.071 g). |
[ 33225-72-8 ]
[ 128798-39-0 ]
[ 100-52-7 ]
[ 20485-41-0 ]

[ 128798-39-0 ]
[ 100-52-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 0.35 g | N-[(R)-Carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]-4-methylthiazole-5-carboxamide To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.45 g) in methanol (10 mL) were added benzaldehyde (0.22 g) and triethylamine (0.21 g), and the mixture was stirred for 2.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature. To the mixture were added <strong>[20485-41-0]4-methylthiazole-5-carboxylic acid</strong> (0.31 g) and 4-phenylcyclohexen-1-ylisocyanide (0.37 g). The mixture was stirred for 20 hours at 65° C. The reaction mixture was concentrated under reduced pressure, and the obtained residue was suspended in tetrahydrofuran (5 mL), and water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (1.5 mL) were added. The mixture was stirred for 1 hour at room temperature. To the reaction mixture were added a saturated aqueous solution of sodium bicarbonate and dichloromethane, and the formed two-layer mixture was stirred vigorously. The organic layer was separated by ISOLUTE (registered trademark) Phase Separator, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=71/29 to 92/8) to afford the title compound (0.35 g). The structural formula is shown in Table 35. RT (min.): 3.241 MS (ESI, m/z): 442.0800 (M-H)- 1H-NMR (CDCl3) delta: 1.65-2.30 (2H, m), 2.45-3.05 (5H, m), 4.40-6.00 (4H, m), 6.85-7.10 (1H, m), 7.30-7.60 (5H, m), 7.72 (1H, br s), 8.77 (1H, s). | |
| 0.35 g | (R) -6- chloro-4-fluoro-indan-1-ylamine hydrochloride (0.45g) Was added methanol (10mL) solution to benzaldehyde (0.22g) and triethylamine(0.21g). The mixture was stirred for 2.5 hours at 65 , and cooled to room temperature. 4-methyl-5-carboxylic acid and (0.31g) 4- phenyl cyclohexen-1-yl isocyanide the (0.37g) was added to the mixture, and the mixture was stirred for 20 hours at 65 . The reaction mixture was concentrated underreduced pressure and resulting residue is suspended in tetrahydrofuran (5 mL), water (40 muL) and 4 mol / L hydrogen chloride in 1,4-dioxanesolution (1.5 mL) was added. The mixture was stirred for 1 hour at room temperature. The reaction mixture of methylene chloride and a saturatedaqueous solution of sodium hydrogen carbonate was added to the vigorously stirring the mixture of the resulting two-layer. The organic layer wasseparated using an ISOLUTE (registered trademark) Phase Separator, and concentrated under reduced pressure. The residue was purified by silicagel column chromatography (eluting solvent ethyl acetate / n- hexane = 71 / 29-92 / 8), to give the title compound (0.35g). |
[ 730980-51-5 ]
[ 128798-39-0 ]
[ 100-52-7 ]
[ 65-85-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Example 2-4LP N-[(R)-Carbamoylphenylmethyl]-N-[(R)-6-methoxyindan-1-yl]benzamide (0395) RT (min.): 3.332 (0396) MS (ESI, m/z): 399.1711 (M-H)- (0397) 1H-NMR (CDCl3) delta: 1.65-1.82 (1H, m), 1.96-2.11 (1H, m), 2.46-2.75 (2H, m), 3.90 (3H, s), 4.69 (1H, br s), 5.20-5.90 (3H, m), 6.78-6.87 (1H, m), 7.06 (1H, d, J=8.3 Hz), 7.24-7.67 (11H, m). N-[(S)-Carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide To a solution of (R)-5-chloroindan-1-ylamine hydrochloride (0.05 g) in methanol (1 mL) were added triethylamine (35 muL) and benzaldehyde (0.026 g), and the mixture was stirred for 1.5 hours at 50 C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added benzoic acid (0.03 g) and 4-phenylcyclohexen-1-ylisocyanide (0.045 g). The mixture was stirred for 3 days at 50 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (2 mL), water (5 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (185 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=55/45 to 75/25 to 100/0) to afford N-[(R)-carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide (Example 2-1LP, 0.040 g) as low polarity product and N-[(S)-carbamoylphenylmethyl]-N-[(R)-5-chloroindan-1-yl]benzamide (Example 2-1HP, 0.023 g) as high polarity product. The structural formulae are shown in Table 4. |
[ 33225-72-8 ]

[ 128798-39-0 ]
[ 100-52-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension. To a solution of 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g) in ethanol (1 mL) was added the suspension of Raney catalyst at room temperature, and the mixture was stirred for 5 hours under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent:ethyl acetate/n-hexane=90/10 to 100/0) to afford the title compound (0.071 g). |
[ 20485-41-0 ]

[ 128798-39-0 ]
[ 100-52-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.45 g) in methanol (10 mL) were added benzaldehyde (0.22 g) and triethylamine (0.21 g), and the mixture was stirred for 2.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature. To the mixture were added <strong>[20485-41-0]4-methylthiazole-5-carboxylic acid</strong> (0.31 g) and 4-phenylcyclohexen-1-ylisocyanide (0.37 g). The mixture was stirred for 20 hours at 65° C. The reaction mixture was concentrated under reduced pressure, and the obtained residue was suspended in tetrahydrofuran (5 mL), and water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (1.5 mL) were added. The mixture was stirred for 1 hour at room temperature. To the reaction mixture were added a saturated aqueous solution of sodium bicarbonate and dichloromethane, and the formed two-layer mixture was stirred vigorously. The organic layer was separated by ISOLUTE (registered trademark) Phase Separator, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=71/29 to 92/8) to afford the title compound (0.35 g). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| General procedure: To a solution of (R)-5-chloroindan-1-ylamine hydrochloride (0.05 g) in methanol (1 mL) were added triethylamine (35 muL) and benzaldehyde (0.026 g), and the mixture was stirred for 1.5 hours at 50 C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added benzoic acid (0.03 g) and 4-phenylcyclohexen-1-ylisocyanide (0.045 g). The mixture was stirred for 3 days at 50 C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (2 mL), water (5 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (185 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=55/45 to 75/25 to 100/0) to afford N--[(R)-carbamoylphenylmethyl]-N--[(R)-5-chloroindan-1-yl]benzamide (Example 2-1LP, 0.040 g) as low polarity product and N--[(S)-carbamoylphenylmethyl]-N--[(R)-5-chloroindan-1-yl]benzamide (Example 2-1HP, 0.023 g) as high polarity product. Examples 2-2 to 2-260 were synthesized in a manner similar to that of Example 2-1 by using the corresponding starting materials. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| General procedure: A mixture of amine (2.00 mmol) and aldehyde (2.00 mmol) in MeOH (4 ml) was stirred for 2 h at 50 C. After being cooled to room temperature, carboxylic acid (2.00 mmol) and 4-phenylcyclohenen-1-yl isocyanide (367 mg, 2.00 mmol) were added to the solution. The mixture was stirred 5 h at 50 C, and then concentrated in vacuo. The residue was suspended in 1,4-dioxane (6 mL) and water (1.5 mL). To the mixture was added HCl in 1,4-dioxane(4 mol/L, 1.5 mL), and the mixture was stirred for 1 h at room temperature. A saturated aqueous solution of NaHCO3 and EtOAc were added to the reaction mixture. The organic layer was washed with water and brine, and dried over anhydrous MgSO4. The solution was concentrated in vacuo, and the residue was purified using silica gel column chromatography. |