1-[3-(4-chlorophenyl)propyl]piperazine

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

Procedure: A mixture of 1-(3-chloropropyl)-3-(4-cyanophenyl)urea (3.57 g; 15 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (3.58 g; 15 mmole), triethylamine (1.52 g; 15 mmole), and ethanol (100 ml) was refluxed for 35 hours. The solvent was removed in vacuo and water added to the residue. The product was extracted with ether, dried, and concentrated in vacuo. The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield). The product was dissolved in ether and precipitated with ethereal hydrochloric acid to provide, after recrystallization from water, the title compound as colorless crystals, m.p. 219°-221° C. was refluxed for 35 hours The solvent was removed in vacuo and water added to the residue The product was extracted with ether dried concentrated in vacuo The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield) precipitated with ethereal hydrochloric acid to provide after recrystallization from water

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

Procedure: A mixture of 1-(3-chloropropyl)-3-n-hexylurea (2.21 g; 10 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (2.39 g; 10 mmole), triethylamine (1.01 g; 10 mmole) and alcohol (25 ml) was refluxed for 18 hours. The cooled reaction mixture was diluted with ether and washed with water, dried (sodium sulfate) and concentrated in vacuo. The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) and precipitated with ethereal hydrochloric acid to provide the title compound (1.6 g; 38% yield) as colorless crystals, m.p. 213°-216° C. was refluxed for 18 hours The cooled reaction mixture washed with water dried (sodium sulfate) concentrated in vacuo The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) precipitated with ethereal hydrochloric acid

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

Procedure: A mixture of 1-(3-chloropropyl)-3-n-hexylurea (2.21 g; 10 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (2.39 g; 10 mmole), triethylamine (1.01 g; 10 mmole) and alcohol (25 ml) was refluxed for 18 hours. The cooled reaction mixture was diluted with ether and washed with water, dried (sodium sulfate) and concentrated in vacuo. The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) and precipitated with ethereal hydrochloric acid to provide the title compound (1.6 g; 38% yield) as colorless crystals, m.p. 213°-216° C. was refluxed for 18 hours The cooled reaction mixture washed with water dried (sodium sulfate) concentrated in vacuo The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) precipitated with ethereal hydrochloric acid

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

Procedure: The procedure described in Example 17(a) was followed, using 27.0 g of 3-(4-chlorophenyl)propyl piperazine, 22.0 g of potassium hydroxide, 250 ml of dimethyl sulfoxide and 17.7 g of 1-bromo-3-chloropropane to give 22.9 g (54% of theory) of 1-[3-(4-chlorophenyl)propyl]-4-(3-chloropropyl)piperazine dihydrochloride.

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

Procedure: The procedure described in Example 17(a) was followed, using 27.0 g of 3-(4-chlorophenyl)propyl piperazine, 22.0 g of potassium hydroxide, 250 ml of dimethyl sulfoxide and 17.7 g of 1-bromo-3-chloropropane to give 22.9 g (54% of theory) of 1-[3-(4-chlorophenyl)propyl]-4-(3-chloropropyl)piperazine dihydrochloride.

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

Procedure: The procedure described in Example 12 is followed using 1[3-(4-chlorophenyl)propyl]-piperazine (4.8 g), bis(2-chloroethyl) disulfide (1.9 g), potassium hydroxide (5.0 g), and dimethylsulfoxide (50 ml). Workup as described in Example 12 provides an oil which is purified on a silica gel column (methylene chloride:methanol, 9:1). The resulting oil (1.5 g) is precipitated with ethereal hydrochloric acid and recrystallized from water/ethanol to give 1,1'-(dithiodi-2, 1-ethanediyl)bis{4-[3-(4-chlorophenyl)propyl]piperazine} tetrahydrochloride as a white crystalline solid, m.p. 284°-286° C. provides an oil which is purified on a silica gel column (methylene chloride:methanol, 9:1) The resulting oil (1.5 g) is precipitated with ethereal hydrochloric acid recrystallized from water/ethanol

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

Procedure: The procedure described in Example 17(a) was followed, using 27.0 g of 3-(4-chlorophenyl)propyl piperazine, 22.0 g of potassium hydroxide, 250 ml of dimethyl sulfoxide and 17.7 g of 1-bromo-3-chloropropane to give 22.9 g (54% of theory) of 1-[3-(4-chlorophenyl)propyl]-4-(3-chloropropyl)piperazine dihydrochloride.

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

Procedure: The procedure described in Example 17(a) was followed, using 27.0 g of 3-(4-chlorophenyl)propyl piperazine, 22.0 g of potassium hydroxide, 250 ml of dimethyl sulfoxide and 17.7 g of 1-bromo-3-chloropropane to give 22.9 g (54% of theory) of 1-[3-(4-chlorophenyl)propyl]-4-(3-chloropropyl)piperazine dihydrochloride.

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

Procedure: A mixture of 1-(3-chloropropyl)-3-(4-cyanophenyl)urea (3.57 g; 15 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (3.58 g; 15 mmole), triethylamine (1.52 g; 15 mmole), and ethanol (100 ml) was refluxed for 35 hours. The solvent was removed in vacuo and water added to the residue. The product was extracted with ether, dried, and concentrated in vacuo. The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield). The product was dissolved in ether and precipitated with ethereal hydrochloric acid to provide, after recrystallization from water, the title compound as colorless crystals, m.p. 219°-221° C. was refluxed for 35 hours The solvent was removed in vacuo and water added to the residue The product was extracted with ether dried concentrated in vacuo The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield) precipitated with ethereal hydrochloric acid to provide after recrystallization from water

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

Procedure: A mixture of 1-(3-chloropropyl)-3-n-hexylurea (2.21 g; 10 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (2.39 g; 10 mmole), triethylamine (1.01 g; 10 mmole) and alcohol (25 ml) was refluxed for 18 hours. The cooled reaction mixture was diluted with ether and washed with water, dried (sodium sulfate) and concentrated in vacuo. The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) and precipitated with ethereal hydrochloric acid to provide the title compound (1.6 g; 38% yield) as colorless crystals, m.p. 213°-216° C. was refluxed for 18 hours The cooled reaction mixture washed with water dried (sodium sulfate) concentrated in vacuo The resulting yellow viscous oil was purified on a silica gel column (methylene chloride/methanol; 93:7) precipitated with ethereal hydrochloric acid

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

Procedure: A mixture of 1-(3-chloropropyl)-3-(4-cyanophenyl)urea (3.57 g; 15 mmole), 1-[3-(4-chlorophenyl)propyl]piperazine (3.58 g; 15 mmole), triethylamine (1.52 g; 15 mmole), and ethanol (100 ml) was refluxed for 35 hours. The solvent was removed in vacuo and water added to the residue. The product was extracted with ether, dried, and concentrated in vacuo. The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield). The product was dissolved in ether and precipitated with ethereal hydrochloric acid to provide, after recrystallization from water, the title compound as colorless crystals, m.p. 219°-221° C. was refluxed for 35 hours The solvent was removed in vacuo and water added to the residue The product was extracted with ether dried concentrated in vacuo The resulting reddish-yellow oil was purified on a silica gel column (methylene chloride/methanol 9:1) to give the product as a free base (2.8 g; 42% yield) precipitated with ethereal hydrochloric acid to provide after recrystallization from water

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

Procedure: The procedure described in Example 17(a) was followed, using 27.0 g of 3-(4-chlorophenyl)propyl piperazine, 22.0 g of potassium hydroxide, 250 ml of dimethyl sulfoxide and 17.7 g of 1-bromo-3-chloropropane to give 22.9 g (54% of theory) of 1-[3-(4-chlorophenyl)propyl]-4-(3-chloropropyl)piperazine dihydrochloride.