1-(4-amino-2-methylphenyl)piperidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 225 μl (2.22 mmol) of 4-methylmorpholine are added to a solution of 600 mg (2.22 mmol) of (3-cyanophenylamino)-2-fluorophenylacetic acid, 453 mg (2.22 mmol) of 1-(4-amino-2-methylphenyl)piperidin-2-one, 426 mg (2.22 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (DAPECI) and 300 mg (2.22 mmol) of hydroxybenzotriazole hydrate (HOBt) in 1 ml of DMF, and the mixture is stirred at room temperature for 24 hours. The reaction mixture is introduced into water, and the precipitate is filtered off, giving 2-(3-cyanophenylamino)-2-(2-fluorophenyl)-N-[3-methyl-4-(2-oxopiperidin-1-yl)phenyl]acetamide as a colourless solid; ESI 456. the precipitate is filtered off

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 800 mg of water-moist palladium on activated carbon are added to a solution of 4.00 g (17.1 mmol) of 1-(4-nitro-2-methylphenyl)piperidin-2-one in 150 ml of methanol, and the mixture is hydrogenated at room temperature and atmospheric pressure for 22 hours. The reaction mixture is filtered, and the filtrate is evaporated, giving 1-(4-amino-2-methylphenyl)piperidin-2-one as a colourless solid; ESI 205. is hydrogenated at room temperature The reaction mixture is filtered the filtrate is evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (48.95 mmol) of 1-(4-amino-2-methylphenyl)piperidin-2-one are heated to the boil in 70 ml of anhydrous toluene together with 9.9 g (24.48 mmol) of 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson's reagent). After 40 minutes, the solvent is removed, and the residue is taken up in dichloromethane (DCM)/1 M aqueous hydrochloric acid. After repeated washing with DCM, a pH of 12 is set using conc. sodium hydroxide solution. Extraction with DCM, drying over Na2SO4 and evaporation of the solvent give 9.25 g (41.98 mmol) of 1-(4-amino-2-methylphenyl)piperidine-2-thione. the solvent is removed After repeated washing with DCM Extraction with DCM drying over Na2SO4 and evaporation of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (48.95 mmol) of 1-(4-amino-2-methylphenyl)piperidin-2-one are heated to the boil in 70 ml of anhydrous toluene together with 9.9 g (24.48 mmol) of 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson's reagent). After 40 minutes, the solvent is removed, and the residue is taken up in dichloromethane (DCM)/1 M aqueous hydrochloric acid. After repeated washing with DCM, a pH of 12 is set using conc. sodium hydroxide solution. Extraction with DCM, drying over Na2SO4 and evaporation of the solvent give 9.25 g (41.98 mmol) of 1-(4-amino-2-methylphenyl)piperidine-2-thione. the solvent is removed After repeated washing with DCM Extraction with DCM drying over Na2SO4 and evaporation of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 225 μl (2.22 mmol) of 4-methylmorpholine are added to a solution of 600 mg (2.22 mmol) of (3-cyanophenylamino)-2-fluorophenylacetic acid, 453 mg (2.22 mmol) of 1-(4-amino-2-methylphenyl)piperidin-2-one, 426 mg (2.22 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (DAPECI) and 300 mg (2.22 mmol) of hydroxybenzotriazole hydrate (HOBt) in 1 ml of DMF, and the mixture is stirred at room temperature for 24 hours. The reaction mixture is introduced into water, and the precipitate is filtered off, giving 2-(3-cyanophenylamino)-2-(2-fluorophenyl)-N-[3-methyl-4-(2-oxopiperidin-1-yl)phenyl]acetamide as a colourless solid; ESI 456. the precipitate is filtered off

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 800 mg of water-moist palladium on activated carbon are added to a solution of 4.00 g (17.1 mmol) of 1-(4-nitro-2-methylphenyl)piperidin-2-one in 150 ml of methanol, and the mixture is hydrogenated at room temperature and atmospheric pressure for 22 hours. The reaction mixture is filtered, and the filtrate is evaporated, giving 1-(4-amino-2-methylphenyl)piperidin-2-one as a colourless solid; ESI 205. is hydrogenated at room temperature The reaction mixture is filtered the filtrate is evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g (48.95 mmol) of 1-(4-amino-2-methylphenyl)piperidin-2-one are heated to the boil in 70 ml of anhydrous toluene together with 9.9 g (24.48 mmol) of 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson's reagent). After 40 minutes, the solvent is removed, and the residue is taken up in dichloromethane (DCM)/1 M aqueous hydrochloric acid. After repeated washing with DCM, a pH of 12 is set using conc. sodium hydroxide solution. Extraction with DCM, drying over Na2SO4 and evaporation of the solvent give 9.25 g (41.98 mmol) of 1-(4-amino-2-methylphenyl)piperidine-2-thione. the solvent is removed After repeated washing with DCM Extraction with DCM drying over Na2SO4 and evaporation of the solvent