1-(2-phenylethyl)piperidin-4-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.0 g of 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 80 ml of tetrahydrofuran is cooled to below 0° C. and 3.17 g of N-methylmorpholine is added under stirring thereto. Further, 2.35 g of isobutyl chlorocarbonate is added and the mixture is stirred at the same temperature for 45 minutes. To the resultant mixture is added 3.52 g of 4-amino-1-(2-phenylethyl)piperidine and the mixture stirred for 2 hours. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, and diluted hydrochloric acid is added thereto. The precipitated crystals are collected by filtration and recrystallized from ethanol to give 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide hydrochloride monohydrate, melting at 257°-259° C. with decomposition. the mixture is stirred at the same temperature for 45 minutes the mixture stirred for 2 hours are added The organic layer is separated diluted hydrochloric acid is added The precipitated crystals are collected by filtration recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.56 g of 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 100 ml of tetrahydrofuran and 10 ml of dimethylformamide is cooled to below 0° C. and 2.2 ml of triethylamine is added under stirring thereto. Further, 2.3 g of ethyl chlorocarbonate is added and the mixture is stirred at a temperature below 5° C. for an hour. To the resultant mixture is added 4.2 g of 4-amino-1-(2-phenylethyl)piperidine and the mixture stirred for 4 hours. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off and the residue is recrystallized from ethyl acetate-ethanol to give 6-chloro-3,4-dihydro-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide, melting at 233°-235° C. the mixture is stirred at a temperature below 5° C. for an hour the mixture stirred for 4 hours are added The organic layer is separated washed with water dried over magnesium sulfate The solvent is distilled off the residue is recrystallized from ethyl acetate-ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.66 Grams of 4-nitrophthalic anhydride and 10.11 grams of 4-amino-1-(2-phenylethyl)piperidine were reacted in a similar manner to that described in Example 12 to give 10.51 grams of the title compound as the monohydrochloride.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.0 g of 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 80 ml of tetrahydrofuran is cooled to below 0° C. and 3.17 g of N-methylmorpholine is added under stirring thereto. Further, 2.35 g of isobutyl chlorocarbonate is added and the mixture is stirred at the same temperature for 45 minutes. To the resultant mixture is added 3.52 g of 4-amino-1-(2-phenylethyl)piperidine and the mixture stirred for 2 hours. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, and diluted hydrochloric acid is added thereto. The precipitated crystals are collected by filtration and recrystallized from ethanol to give 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide hydrochloride monohydrate, melting at 257°-259° C. with decomposition. the mixture is stirred at the same temperature for 45 minutes the mixture stirred for 2 hours are added The organic layer is separated diluted hydrochloric acid is added The precipitated crystals are collected by filtration recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.56 g of 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 100 ml of tetrahydrofuran and 10 ml of dimethylformamide is cooled to below 0° C. and 2.2 ml of triethylamine is added under stirring thereto. Further, 2.3 g of ethyl chlorocarbonate is added and the mixture is stirred at a temperature below 5° C. for an hour. To the resultant mixture is added 4.2 g of 4-amino-1-(2-phenylethyl)piperidine and the mixture stirred for 4 hours. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off and the residue is recrystallized from ethyl acetate-ethanol to give 6-chloro-3,4-dihydro-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide, melting at 233°-235° C. the mixture is stirred at a temperature below 5° C. for an hour the mixture stirred for 4 hours are added The organic layer is separated washed with water dried over magnesium sulfate The solvent is distilled off the residue is recrystallized from ethyl acetate-ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedure of Lobbezoo, J. Med. Chem. 24:777 (1981). N-(β-phenylethyl)-4-piperidinone (15.0 g, 74.0 mmol) dissolved in 200 ml of methanol containing 1 ml of a 4% thiophene in methanol solution is treated with benzyl amine (10.0 g, 93.0 mmol) and 2 g of 10% palladium-on-carbon in a Parr flask and hydrogenated for 18 hours (initial pressure, 26.5 psi, final pressure 22.0 psi). The catalyst is filtered and replaced with 2.0 g of fresh 10% palladium-on-carbon. The catalyst is filtered and replaced again with 4.8 g of fresh 10% palladium-on-carbon. The hydrogenation is followed over 3 days, at which point, hydrogen uptake ceases (initial pressure, 35 psi, final pressure, 29 psi). The catalyst is filtered through Celite and is washed with methanol. GLC analysis (2 ft SE-30, 100 C, 1 minute, programmed 20 C/minute rise to 250 C) indicated that 7% unreacted benzyl amine remained). This material nevertheless was used for subsequent experiments. The catalyst is filtered The catalyst is filtered The catalyst is filtered through Celite is washed with methanol GLC analysis (2 ft SE-30, 100 C, 1 minute, programmed 20 C/minute rise to 250 C)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(2-phenylethyl)-4-piperidinamine (8.17 g) and 2-chloro-N,N-dimethyl-4-pyrimidinamine (6.3 g) was stirred for 20 hours at 120° C. The reaction mixture was diluted with water and extracted with CH2Cl2. The organic layer was washed with water, dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH(NH3) 96/4). The pure fractions were collected and the solvent evaporated. The residue was crystallized from CH3CN. The precipitate was filtered off and dried, yielding 3.69 g (28.4%) of N4,N4-dimethyl-N2-[1-(2-phenylethyl)-4-piperidinyl]-2,4-pyrimidinediamine (comp. 11). extracted with CH2Cl2 The organic layer was washed with water dried filtered the solvent evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH(NH3) 96/4) The pure fractions were collected the solvent evaporated The residue was crystallized from CH3CN The precipitate was filtered off dried