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

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

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

Procedure: Prepared from 4-pyridin-2-yl-benzoic acid hydrochloride and 4-(4-(2-methoxy-phenyl)-piperazin-1-yl)-butylamine according to the general procedure. Yield: 53%. Mp. (oxalate): foam. 1H NMR (CDCl3): δ1.67-1.74 (m, 4H), 2.49 (t, J 6.84, 2H), 2.67 (s, 2H), 3.07 (s, 2H), 3.51 (q, J 6.0, 2H), 3.84 (s, 3H), 6.83 (m, 5H), 7.26 (m, 1H), 7.73-7.79 (m, 2H), 7.89 (d, J 8.2, 2H), 8.06 (d, J 8.6, 2H), 8.71 (dt, J 4.7, 1.3, 1H). 13C NMR (CDCl3): δ 24.8, 27.9, 40.4, 50.8, 53.9, 55.8, 58.5, 111.6, 118.7, 121.3, 121.4, 128.1, 123.4, 127.4, 127.9, 135.6, 137.3, 142.5, 150.3, 152.7, 156.7, 167.8. Anal. (C27H32N4O2.(COOH)2.0.75H2O) C, H, N.|

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

Procedure: 1-N(3-cyanopropyl)-4-N(2-methoxyphenyl)piperazine (5 g) was dissolved in a mixture of MeOH and aqueous ammonia (28%) in 1/1 ratio (20 mL) and the mixture is shook in a Parr apparatus in presence of Raney/Ni (500 mg) at 60 psi for 18 h. The catalyst is removed by filtration and the filtrate concentrated in vacuo. The residue is taken in AcOEt, the organic layer is washed three times with H2O, dried over Na2SO4 and concentrated. The oily residue is dissolved in EtOH and aqueous HCl (37%, 15 mL) is added. The obtained hydrochloride salt is crystallized in Et2O to give the title compound B2 (4.5 g, 81%) as crystals. 1H NMR (200 MHz, CDCl3) δ 1.48-1.64 (m, 4H), 2.16 (s, 2H), 2.36-2.43 (m, 2H), 2.57-2.62 (m, 4H), 2.69-2.76 (m, 2H), 3.18-3.23 (m, 4H), 3.79 (s, 3H), 6.40-6.56 (m, 3H), 7.20 (t, 1H). 13C NMR (50 MHz, CDCl3) δ 24.2, 31.6, 42.0, 49.0, 53.1, 55.1, 58.4, 102.4, 104.3, 108.8, 129.7, 152.6, 160.5. The catalyst is removed by filtration the filtrate concentrated in vacuo the organic layer is washed three times with H2O dried over Na2SO4 concentrated The oily residue is dissolved in EtOH aqueous HCl (37%, 15 mL) is added The obtained hydrochloride salt is crystallized in Et2O

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

Procedure: 1-N(3-cyanopropyl)-4-N(2-methoxyphenyl)piperazine (5 g) was dissolved in a mixture of MeOH and aqueous ammonia (28%) in 1/1 ratio (20 mL) and the mixture is shook in a Parr apparatus in presence of Raney/Ni (500 mg) at 60 psi for 18 h. The catalyst is removed by filtration and the filtrate concentrated in vacuo. The residue is taken in AcOEt, the organic layer is washed three times with H2O, dried over Na2SO4 and concentrated. The oily residue is dissolved in EtOH and aqueous HCl (37%, 15 mL) is added. The obtained hydrochloride salt is crystallized in Et2O to give the title compound B2 (4.5 g, 81%) as crystals. 1H NMR (200 MHz, CDCl3) δ 1.48-1.64 (m, 4H), 2.16 (s, 2H), 2.36-2.43 (m, 2H), 2.57-2.62 (m, 4H), 2.69-2.76 (m, 2H), 3.18-3.23 (m, 4H), 3.79 (s, 3H), 6.40-6.56 (m, 3H), 7.20 (t, 1H). 13C NMR (50 MHz, CDCl3) δ 24.2, 31.6, 42.0, 49.0, 53.1, 55.1, 58.4, 102.4, 104.3, 108.8, 129.7, 152.6, 160.5. The catalyst is removed by filtration the filtrate concentrated in vacuo the organic layer is washed three times with H2O dried over Na2SO4 concentrated The oily residue is dissolved in EtOH aqueous HCl (37%, 15 mL) is added The obtained hydrochloride salt is crystallized in Et2O

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

Procedure: 9.25 g (0.050 mol) of 3,4,6-trichloropyridazine are stirred with 6.90 g (0.050 mol) of powdered anhydrous potassium carbonate and 13.15 g (0.050 mol) of 1-(4-aminobutyl)-4-(2-methoxyphenyl)piperazine in 1350 ml of dry acetonitrile at room temperature for 96 hours. The mixture is subsequently filtered with suction, and the filtrate is concentrated in vacuo. The residue is taken up in ethanol, and the trihydrochloride of 3,6-dichloro-4-((4-(4-(2-methoxyphenyl)-1-piperazinyl)butyl)amino)pyridazine of m.p.: 155°-170° C. is precipitated with ethereal HCl; yield: 54.2% of theory. The mixture is subsequently filtered with suction the filtrate is concentrated in vacuo the trihydrochloride of 3,6-dichloro-4-((4-(4-(2-methoxyphenyl)-1-piperazinyl)butyl)amino)pyridazine of m.p.: 155°-170° C. is precipitated with ethereal HCl

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

Procedure: 4-[4-(2-methyloxyphenyl)piperazinyl]butylamine: according to the method of claim 1, N-(4-bromobutyl)phthalimide and 2-methyloxyphenyl-piperazine was used in reaction to produce N-{4-[4-(2-methyloxyphenyl)piperazinyl]butyl}phthalimide, which was then reacted with hydrazine hydrate. The yield was: 84.3%. Hydrochloride salt had a mp: 173-175° C. was used in reaction

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

Procedure: 4-[4-(2-methyloxyphenyl)piperazinyl]butylamine: according to the method of claim 1, N-(4-bromobutyl)phthalimide and 2-methyloxyphenyl-piperazine was used in reaction to produce N-{4-[4-(2-methyloxyphenyl)piperazinyl]butyl}phthalimide, which was then reacted with hydrazine hydrate. The yield was: 84.3%. Hydrochloride salt had a mp: 173-175° C. was used in reaction

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

Procedure: A mixture of 1,2-benzisothiazole-3-carboxylic acid chloride (2.44 g), 1-(2-methoxyphenyl)-4-(4-aminobutyl)piperazine (3.26 g), and triethylamine (6 ml), in sieve-dried toluene (100 ml) was heated to 80° C., with stirring, overnight. After 24 hr, the reaction mixture was cooled to room temperature and poured into water. The organic phase was separated and the aqueous phase was extracted with ether. The ether extracts and toluene phase were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were collected and concentrated. The residue was taken up in ether and ethereal hydrogen chloride was added. The precipitate was recrystallized from ethanol/ethyl acetate and dried (0.1 mm mercury, refluxing toluene temperature) to provide 2.13 g (34.6%) of product, mp 175°-178° C. After 24 hr The organic phase was separated the aqueous phase was extracted with ether dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The residue was chromatographed on silica The appropriate fractions were collected concentrated ethereal hydrogen chloride was added The precipitate was recrystallized from ethanol/ethyl acetate dried (0.1 mm mercury, refluxing toluene temperature)

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

Procedure: A mixture of 1,2-benzisothiazole-3-carboxylic acid chloride (2.44 g), 1-(2-methoxyphenyl)-4-(4-aminobutyl)piperazine (3.26 g), and triethylamine (6 ml), in sieve-dried toluene (100 ml) was heated to 80° C., with stirring, overnight. After 24 hr, the reaction mixture was cooled to room temperature and poured into water. The organic phase was separated and the aqueous phase was extracted with ether. The ether extracts and toluene phase were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed on silica using ethyl acetate as the eluent. The appropriate fractions were collected and concentrated. The residue was taken up in ether and ethereal hydrogen chloride was added. The precipitate was recrystallized from ethanol/ethyl acetate and dried (0.1 mm mercury, refluxing toluene temperature) to provide 2.13 g (34.6%) of product, mp 175°-178° C. After 24 hr The organic phase was separated the aqueous phase was extracted with ether dried over anhydrous magnesium sulfate filtered the filtrate was concentrated in vacuo The residue was chromatographed on silica The appropriate fractions were collected concentrated ethereal hydrogen chloride was added The precipitate was recrystallized from ethanol/ethyl acetate dried (0.1 mm mercury, refluxing toluene temperature)

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

Procedure: Prepared from 4-pyridin-2-yl-benzoic acid hydrochloride and 4-(4-(2-methoxy-phenyl)-piperazin-1-yl)-butylamine according to the general procedure. Yield: 53%. Mp. (oxalate): foam. 1H NMR (CDCl3): δ1.67-1.74 (m, 4H), 2.49 (t, J 6.84, 2H), 2.67 (s, 2H), 3.07 (s, 2H), 3.51 (q, J 6.0, 2H), 3.84 (s, 3H), 6.83 (m, 5H), 7.26 (m, 1H), 7.73-7.79 (m, 2H), 7.89 (d, J 8.2, 2H), 8.06 (d, J 8.6, 2H), 8.71 (dt, J 4.7, 1.3, 1H). 13C NMR (CDCl3): δ 24.8, 27.9, 40.4, 50.8, 53.9, 55.8, 58.5, 111.6, 118.7, 121.3, 121.4, 128.1, 123.4, 127.4, 127.9, 135.6, 137.3, 142.5, 150.3, 152.7, 156.7, 167.8. Anal. (C27H32N4O2.(COOH)2.0.75H2O) C, H, N.|

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

Procedure: 1-N(3-cyanopropyl)-4-N(2-methoxyphenyl)piperazine (5 g) was dissolved in a mixture of MeOH and aqueous ammonia (28%) in 1/1 ratio (20 mL) and the mixture is shook in a Parr apparatus in presence of Raney/Ni (500 mg) at 60 psi for 18 h. The catalyst is removed by filtration and the filtrate concentrated in vacuo. The residue is taken in AcOEt, the organic layer is washed three times with H2O, dried over Na2SO4 and concentrated. The oily residue is dissolved in EtOH and aqueous HCl (37%, 15 mL) is added. The obtained hydrochloride salt is crystallized in Et2O to give the title compound B2 (4.5 g, 81%) as crystals. 1H NMR (200 MHz, CDCl3) δ 1.48-1.64 (m, 4H), 2.16 (s, 2H), 2.36-2.43 (m, 2H), 2.57-2.62 (m, 4H), 2.69-2.76 (m, 2H), 3.18-3.23 (m, 4H), 3.79 (s, 3H), 6.40-6.56 (m, 3H), 7.20 (t, 1H). 13C NMR (50 MHz, CDCl3) δ 24.2, 31.6, 42.0, 49.0, 53.1, 55.1, 58.4, 102.4, 104.3, 108.8, 129.7, 152.6, 160.5. The catalyst is removed by filtration the filtrate concentrated in vacuo the organic layer is washed three times with H2O dried over Na2SO4 concentrated The oily residue is dissolved in EtOH aqueous HCl (37%, 15 mL) is added The obtained hydrochloride salt is crystallized in Et2O

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