ethyl piperazine-2-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-(10,11 -dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil. at 0° C. the phases were separated The aqueous layer was extracted with toluene (50 ml) the combined organic phases were washed with brine (2×100 ml) dried (MgSO4) concentrated in vacuo The residue was dissolved in acetonitrile (10 ml) The resulting mixture was heated at reflux temperature for 18 h the mixture was extracted with ethyl acetate (3×20 ml) The combined organic extracts were washed with brine (2×20 ml) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel (27 g)

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

実験手順: To a stirred solution of 2-ethoxycarbonylpiperazine (4.6 g, 29.1 mmol) in dry methylene chloride (200 mL), was added benzoyl chloride (3.55 ml, 29.1 mmol) and triethylamine (2 ml) sequentially. After stirring for 8 hours at room temperature, a saturated NaHCO3 solution was added and the aqueous phase was extracted with ethyl acetate (3×200 ml). The organic layers were combined, dried over MgSO4 and concentrated to give a crude mixture, which included the desired product XXXIX. The crude was then used for the further reaction without purification. the aqueous phase was extracted with ethyl acetate (3×200 ml) dried over MgSO4 concentrated

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

実験手順: To a solution of 4-Benzhydryl-piperazine-2-carboxylic acid ethyl ester (0.5 g, 1.54 mmol) in dry CH2Cl2 (25 ml) was added 3,3-diphenylpropanoic acid (0.35 g, 1.54 mmol) under nitrogen. To the reaction was added EDC (0.59 g, 3.08 mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temperature overnight. The reaction was then concentrated under reduced pressure. The residue dissolved in ethyl acetate: water (10:1) (100 ml). The organic was washed with water (20 ml, 2×) and 10% NaOH (20 ml) and dried over MgSO4 and evaporated to dryness. The resulting residue was purified by column chromatography using hexane: ethyl acetate (3:1) to give title compound in 73% yield. The reaction was then concentrated under reduced pressure The residue dissolved in ethyl acetate: water (10:1) (100 ml) The organic was washed with water (20 ml, 2×) and 10% NaOH (20 ml) dried over MgSO4 evaporated to dryness The resulting residue was purified by column chromatography

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

実験手順: Piperazine 2-carboxylic acid ethyl ester (2.25 g, 14.25 mmol) was dissolved in dry benzene (30 ml) followed by addition of triehylamine (2.2 ml, 15.67 mmol). Trimethoxybenzyl bromide (3.72 g, 14.25 mmol) in dry benzene (30 ml) was added dropwise. The resulting mixture was stirred under nitrogen at room temperature overnight. The resulting salt was removed through filtration and solvent was evaporated. The crude product was purified by column chromatography using CH2Cl2:MeOH (15:1) to give the desired product in 44% yield. The resulting salt was removed through filtration and solvent was evaporated The crude product was purified by column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-(10,11 -dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil. at 0° C. the phases were separated The aqueous layer was extracted with toluene (50 ml) the combined organic phases were washed with brine (2×100 ml) dried (MgSO4) concentrated in vacuo The residue was dissolved in acetonitrile (10 ml) The resulting mixture was heated at reflux temperature for 18 h the mixture was extracted with ethyl acetate (3×20 ml) The combined organic extracts were washed with brine (2×20 ml) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel (27 g)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-(10,11 -dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil. at 0° C. the phases were separated The aqueous layer was extracted with toluene (50 ml) the combined organic phases were washed with brine (2×100 ml) dried (MgSO4) concentrated in vacuo The residue was dissolved in acetonitrile (10 ml) The resulting mixture was heated at reflux temperature for 18 h the mixture was extracted with ethyl acetate (3×20 ml) The combined organic extracts were washed with brine (2×20 ml) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel (27 g)

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: To a solution of ethyl 2-piperazinecarboxylate (0.9 g, 5.7 mmol) in chloroform (11 mL) was added 3,5-dichlorophenyl isocyanate (1.05 g, 5.7 mmol). The reaction was stirred overnight after which time a precipitate had formed. The reaction was concentrated and the solid was chromatographed on silica gel using ethyl acetate as eluant to provide 0.53 g (27%) of ethyl 4-[(3,5-dichloroanilino)carbonyl]-2-piperazinecarboxylate as an off white powder. Electrospray Mass Spec 346.1 (M+H)+. had formed The reaction was concentrated the solid was chromatographed on silica gel

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

実験手順: To a solution of ethyl 2-piperazinecarboxylate (0.9 g, 5.7 mmol) in chloroform (11 mL) was added 3,5-dichlorophenyl isocyanate (1.05 g, 5.7 mmol). The reaction was stirred overnight after which time a precipitate had formed. The reaction was concentrated and the solid was chromatographed on silica gel using ethyl acetate as eluant to provide 0.53 g (27%) of ethyl 4-[(3,5-dichloroanilino)carbonyl]-2-piperazinecarboxylate as an off white powder. Electrospray Mass Spec 346.1 (M+H)+. had formed The reaction was concentrated the solid was chromatographed on silica gel

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

実験手順: Reacting 2-ethoxycarbonylpiperazine with 2,2 aquivalents of isopropyl bromide in the same conditions as for example 21, and treating the obtained product in the same conditions as for example 1, step d, the desired product is obtained. treating the obtained product in the same conditions as for example 1, step d

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

実験手順: To a solution of ethyl 2-piperazinecarboxylate (0.9 g, 5.7 mmol) in chloroform (11 mL) was added 3,5-dichlorophenyl isocyanate (1.05 g, 5.7 mmol). The reaction was stirred overnight after which time a precipitate had formed. The reaction was concentrated and the solid was chromatographed on silica gel using ethyl acetate as eluant to provide 0.53 g (27%) of ethyl 4-[(3,5-dichloroanilino)carbonyl]-2-piperazinecarboxylate as an off white powder. Electrospray Mass Spec 346.1 (N+H)+. had formed The reaction was concentrated the solid was chromatographed on silica gel