3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-amine

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

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazinyl]propylamine (1.0 g, 0.04 mol) in 50 mL of methylene dichloride, benzofurane-2-carboxylic acid chloride (1.01 g, 0.0056 mol) and triethylamine (1 g, 0.01 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC using silica gel column and ethyl acetate as the eluent. The title compound was separated and converted to the dihydrochloride salt with ethanolic HCl (0.9 g), m.p. 228°-232° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure The title compound was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazinyl]propylamine (2.5 g, 0.01 mol) in 50 mL of methylene chloride, adamantane-1-carboxylic acid chloride (2.02 g, 0.010 mol) and triethylamine (2 g, 0.02 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC. In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) and subjected to flash chromatography using a 9 inch column of silica gel and ethyl acetate as the eluent. The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated and converted to the hydrochloride hemihydrate salt with ethanolic HCl (2.3 g), m.p. 186°-190° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated

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

Procedure: The product of Example 27 (3.9 g, 16 mmol) and 2-chloropyridine (1.82 g, 16 mmol) were heated at 160° C. in a sealed vessel for 6 h. After cooling, the residue was taken up into CH2Cl2 (50 ml) washed with aqueous NaOH (3×50 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by chromatography [alumina; ethyl acetate-toluene (1:4)] to give the product (0.7 g) as a brown oil. After cooling washed with aqueous NaOH (3×50 ml) dried (MgSO4) evaporated in vacuo The residue was purified by chromatography [alumina; ethyl acetate-toluene (1:4)]

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

Procedure: A solution of the product of Example 26 (4.4 g, 18 mmol) in concentrated ethanolic ammonia solution (150 ml) was hydrogenated over 5% rhodium on alumina powder (0.6 g) at 50 p.s.i. (about 3.4×105Pa) for 50 h to give the product (3.9 g) as a brown oil.

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

Procedure: The title compound was prepared by stirring [4-(2-methoxyphenyl)piperazino]propylamine (1.4 g, 0.005 mol), indole-2-carboxylic acid chloride (1.0 g, 0.005 mol) and triethylamine (1 g, 0.01 mol) in 50 mL of CH2Cl2 for 24 hours. The methylene chloride solution was washed with water, dried (anhydrous Na2SO4) and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC over silica gel column and using ethyl acetate as the eluent and the desired product (TLC Rf =0.65 in 30% methanol/ethyl acetate system) was separated and converted to the dihydrochloride dihydrate salt with ethanolic HCl, m.p. 173°-178° C. The methylene chloride solution was washed with water dried (anhydrous Na2SO4) evaporated under reduced pressure the desired product (TLC Rf =0.65 in 30% methanol/ethyl acetate system) was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazino]propylamine (1.0 g, 0.04 mol) in 50 mL of methylene dichloride, benzofurane-2-carboxylic acid chloride (1.01 g, 0.0056 mol) and triethylamine (1 g, 0.01 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC using silica gel column and ethyl acetate as the eluent. The title compound was separated and converted to the dihydrochloride salt with ethanolic HCl (0.9 g), m.p. 228°-232° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure The title compound was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazino]propylamine (1.0 g, 0.04 mol) in 50 mL of methylene dichloride, benzofurane-2-carboxylic acid chloride (1.01 g, 0.0056 mol) and triethylamine (1 g, 0.01 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC using silica gel column and ethyl acetate as the eluent. The title compound was separated and converted to the dihydrochloride salt with ethanolic HCl (0.9 g), m.p. 228°-232° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure The title compound was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazino]propylamine (2.5 g, 0.01 mol) in 50 mL of methylene chloride, adamantane-1-carboxylic acid chloride (2.02 g, 0.010 mol) and triethylamine (2 g, 0.02 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC. In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) and subjected to flash chromatography using a 9 inch column of silica gel and ethyl acetate as the eluent. The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated and converted to the hydrochloride hemihydrate salt with ethanolic HCl (2.3 g), m.p. 186°-190° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated

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

Procedure: The title compound was prepared by stirring [4-(2-methoxyphenyl)piperazinyl]propylamine (1.4 g, 0.005 mol), indole-2-carboxylic acid chloride (1.0 g, 0.005 mol) and triethylamine (1 g, 0.01 mol) in 50 mL of CH2Cl2 for 24 hours. The methylene chloride solution was washed with water, dried (anhydrous Na2SO4) and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC over silica gel column and using ethyl acetate as the eluent and the desired product (TLC Rf =0.65 in 30% methanol/ethyl acetate system) was separated and converted to the dihydrochloride dihydrate salt with ethanolic HCl, m.p. 173°-178° C. The methylene chloride solution was washed with water dried (anhydrous Na2SO4) evaporated under reduced pressure the desired product (TLC Rf =0.65 in 30% methanol/ethyl acetate system) was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazinyl]propylamine (1.0 g, 0.04 mol) in 50 mL of methylene dichloride, benzofurane-2-carboxylic acid chloride (1.01 g, 0.0056 mol) and triethylamine (1 g, 0.01 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC using silica gel column and ethyl acetate as the eluent. The title compound was separated and converted to the dihydrochloride salt with ethanolic HCl (0.9 g), m.p. 228°-232° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure The title compound was separated

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

Procedure: To a stirred solution of [4-(2-methoxyphenyl)piperazinyl]propylamine (2.5 g, 0.01 mol) in 50 mL of methylene chloride, adamantane-1-carboxylic acid chloride (2.02 g, 0.010 mol) and triethylamine (2 g, 0.02 mol) were added. Stirring was continued at room temperature overnight. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining residue was subjected to preparative HPLC. In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) and subjected to flash chromatography using a 9 inch column of silica gel and ethyl acetate as the eluent. The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated and converted to the hydrochloride hemihydrate salt with ethanolic HCl (2.3 g), m.p. 186°-190° C. The methylene chloride solution was washed with water dried over anhydrous sodium sulfate evaporated under reduced pressure In repeated preparations, the residue was dissolved in ethyl acetate (10 mL) The title compound (TLC Rf =0.53 in 30% methanol/ethyl acetate system) was separated