2-(4-benzylpiperazin-1-yl)ethanamine

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: To a solution of adamantane-1-carboxylic acid (11.85 g, 0.065 mol) and 2-[4-(phenylmethyl)-1-piperazinyl]ethylamine (12.0 g, 0.054 mol) in dichloromethane (200 mL) at 4° C. was added, with stirring, a solution of diethylcyanophosphonate (11.8 mL, 0.065 mol) in dichloromethane (50 mL), followed by a solution of triethylamine (9.2 mL, 0.065 mol) in dichloromethane (50 mL). The resulting mixture was stirred overnight, during which time it came up to room temperature. The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL), dried over anhydrous sodium sulfate, and concentrated on a rotary evaporator. The desired product (TLC on silica gel using 10% methanol/ethyl acetate, Rf=0.33) was isolated by crystallization from hexane and recrystallized from hexane. It was then converted to its dihydrochloride salt with isopropanolic HCl (12.71 g, 52%), mp=259°-260° C. The resulting mixture was stirred overnight, during which time it came up to room temperature The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL) dried over anhydrous sodium sulfate concentrated on a rotary evaporator

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

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

Procedure: To a solution of adamantane-1-carboxylic acid (11.85 g, 0.065 mol) and 2-[4-(phenylmethyl)-1-piperazinyl]ethylamine (12.0 g, 0.054 mol) in dichloromethane (200 mL) at 4° C. was added, with stirring, a solution of diethylcyanophosphonate (11.8 mL, 0.065 mol) in dichloromethane (50 mL), followed by a solution of triethylamine (9.2 mL, 0.065 mol) in dichloromethane (50 mL). The resulting mixture was stirred overnight, during which time it came up to room temperature. The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL), dried over anhydrous sodium sulfate, and concentrated on a rotary evaporator. The desired product (TLC on silica gel using 10% methanol/ethyl acetate, Rf=0.33) was isolated by crystallization from hexane and recrystallized from hexane. It was then converted to its dihydrochloride salt with isopropanolic HCl (12.71 g, 52%), mp=259°-260° C. The resulting mixture was stirred overnight, during which time it came up to room temperature The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL) dried over anhydrous sodium sulfate concentrated on a rotary evaporator

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

Procedure: To a solution of adamantane-1-carboxylic acid (11.85 g, 0.065 mol) and 2-[4-(phenylmethyl)-1-piperazinyl]ethylamine (12.0 g, 0.054 mol) in dichloromethane (200 mL) at 4° C. was added, with stirring, a solution of diethylcyanophosphonate (11.8 mL, 0.065 mol) in dichloromethane (50 mL), followed by a solution of triethylamine (9.2 mL, 0.065 mol) in dichloromethane (50 mL). The resulting mixture was stirred overnight, during which time it came up to room temperature. The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL), dried over anhydrous sodium sulfate, and concentrated on a rotary evaporator. The desired product (TLC on silica gel using 10% methanol/ethyl acetate, Rf=0.33) was isolated by crystallization from hexane and recrystallized from hexane. It was then converted to its dihydrochloride salt with isopropanolic HCl (12.71 g, 52%), mp=259°-260° C. The resulting mixture was stirred overnight, during which time it came up to room temperature The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL) dried over anhydrous sodium sulfate concentrated on a rotary evaporator

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

Procedure: To a solution of adamantane-1-carboxylic acid (11.85 g, 0.065 mol) and 2-[4-(phenylmethyl)-1-piperazinyl]ethylamine (12.0 g, 0.054 mol) in dichloromethane (200 mL) at 4° C. was added, with stirring, a solution of diethylcyanophosphonate (11.8 mL, 0.065 mol) in dichloromethane (50 mL), followed by a solution of triethylamine (9.2 mL, 0.065 mol) in dichloromethane (50 mL). The resulting mixture was stirred overnight, during which time it came up to room temperature. The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL), dried over anhydrous sodium sulfate, and concentrated on a rotary evaporator. The desired product (TLC on silica gel using 10% methanol/ethyl acetate, Rf=0.33) was isolated by crystallization from hexane and recrystallized from hexane. It was then converted to its dihydrochloride salt with isopropanolic HCl (12.71 g, 52%), mp=259°-260° C. The resulting mixture was stirred overnight, during which time it came up to room temperature The reaction mixture was then washed with 10% aqueous potassium carbonate (200 mL) dried over anhydrous sodium sulfate concentrated on a rotary evaporator

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

Procedure: To a solution of 2,4,6-trimethyl-3-piperazin-1-yl-phenylamine (0.2 g, 0.92 mmol) and Hunig's base (0.7 mL, 4.0 mmol) in anhydrous 1,2-dichloroethane (3 mL) at 0° C. was added triphosgene (0.1 g, 0.35 mmol). The mixture was stirred at 0° C. for 30 minutes before the addition of a solution of 2-(4-benzyl-piperazin-1-yl)-ethylamine (0.2 g, 0.92 mmol) in 1,2-dichloroethane (2 mL). The reaction was stirred overnight and partitioned between water and methylene chloride. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed with florisil, eluting with a mixture of hexanes and ethyl acetate in the ratio of 2:1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1) to give the title compound as a white foam (0.27 g, 64% yield). partitioned between water and methylene chloride The organic layer was washed with brine dried (MgSO4) concentrated The residue was chromatographed with florisil eluting with a mixture of hexanes and ethyl acetate in the ratio of 2 1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1)

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

Procedure: To a solution of 2,4,6-trimethyl-3-piperazin-1-yl-phenylamine (0.2 g, 0.92 mmol) and Hunig's base (0.7 mL, 4.0 mmol) in anhydrous 1,2-dichloroethane (3 mL) at 0° C. was added triphosgene (0.1 g, 0.35 mmol). The mixture was stirred at 0° C. for 30 minutes before the addition of a solution of 2-(4-benzyl-piperazin-1-yl)-ethylamine (0.2 g, 0.92 mmol) in 1,2-dichloroethane (2 mL). The reaction was stirred overnight and partitioned between water and methylene chloride. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed with florisil, eluting with a mixture of hexanes and ethyl acetate in the ratio of 2:1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1) to give the title compound as a white foam (0.27 g, 64% yield). partitioned between water and methylene chloride The organic layer was washed with brine dried (MgSO4) concentrated The residue was chromatographed with florisil eluting with a mixture of hexanes and ethyl acetate in the ratio of 2 1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1)

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

Procedure: To a solution of 2,4,6-trimethyl-3-piperazin-1-yl-phenylamine (0.2 g, 0.92 mmol) and Hunig's base (0.7 mL, 4.0 mmol) in anhydrous 1,2-dichloroethane (3 mL) at 0° C. was added triphosgene (0.1 g, 0.35 mmol). The mixture was stirred at 0° C. for 30 minutes before the addition of a solution of 2-(4-benzyl-piperazin-1-yl)-ethylamine (0.2 g, 0.92 mmol) in 1,2-dichloroethane (2 mL). The reaction was stirred overnight and partitioned between water and methylene chloride. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed with florisil, eluting with a mixture of hexanes and ethyl acetate in the ratio of 2:1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1) to give the title compound as a white foam (0.27 g, 64% yield). partitioned between water and methylene chloride The organic layer was washed with brine dried (MgSO4) concentrated The residue was chromatographed with florisil eluting with a mixture of hexanes and ethyl acetate in the ratio of 2 1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1)

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

Procedure: To a solution of 2,4,6-trimethyl-3-piperazin-1-yl-phenylamine (0.2 g, 0.92 mmol) and Hunig's base (0.7 mL, 4.0 mmol) in anhydrous 1,2-dichloroethane (3 mL) at 0° C. was added triphosgene (0.1 g, 0.35 mmol). The mixture was stirred at 0° C. for 30 minutes before the addition of a solution of 2-(4-benzyl-piperazin-1-yl)-ethylamine (0.2 g, 0.92 mmol) in 1,2-dichloroethane (2 mL). The reaction was stirred overnight and partitioned between water and methylene chloride. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed with florisil, eluting with a mixture of hexanes and ethyl acetate in the ratio of 2:1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1) to give the title compound as a white foam (0.27 g, 64% yield). partitioned between water and methylene chloride The organic layer was washed with brine dried (MgSO4) concentrated The residue was chromatographed with florisil eluting with a mixture of hexanes and ethyl acetate in the ratio of 2 1 to 100% ethyl acetate, and then to a mixture of ethyl acetate and MeOH (30:1)

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

Procedure: The title compound was prepared as outlined in EXAMPLE 1 from 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18) and 4-benzylpiperazin-1 ylethylamine. The product was purified by mass directed purification to give the title compound as an orange solid. m/z (ES+)=398 [M+H]+; RT=2.75 min. The title compound was prepared The product was purified by mass purification