3-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylpropan-1-amine

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

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

Procedure: N-isopropyl-3-trifluoromethylbenzenesulfonamide (5.362 g, 0.02 mol) in dimethylformamide (30 mL) was treated with sodium hydride (60% in mineral oil), (0.802 g) and stirred for 2 hours. Then N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine (5.436 g, 0.02 mol) was added and the reaction heated overnight. Filtration and removal of solvent provided the crude product (6.95 g). Column chromatography and high pressure liquid chromatography provided the pure product (4.35 g) as a gum. 1H NMR (CDCl3) 1.15 (d, 6, J=3.5H, Me2) 2.25 (s, 3, N-Me) 3.84 (d, 6, (OMe)2) 6.76 (m, 3, Ar) 7.25 (m, 3, Ar). the reaction heated overnight Filtration and removal of solvent provided the crude product (6.95 g)

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

Procedure: N-isopropyl-3-trifluoromethylbenzenesulfonamide (5.362 g, 0.02 mol) in dimethylformamide (30 mL) was treated with sodium hydride (60% in mineral oil), (0.802 g) and stirred for 2 hours. Then N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine (5.436 g, 0.02 mol) was added and the reaction heated overnight. Filtration and removal of solvent provided the crude product (6.95 g). Column chromatography and high pressure liquid chromatography provided the pure product (4.35 g) as a gum. 1H NMR (CDCl3) 1.15 (d, 6, J=3.5H, Me2) 2.25 (s, 3, N-Me) 3.84 (d, 6, (OMe)2) 6.76 (m, 3, Ar) 7.25 (m, 3, Ar). the reaction heated overnight Filtration and removal of solvent provided the crude product (6.95 g)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.5 g of 3-hydroxy-5-phenyl-isoxazole were dissolved in 100 ml of dimethylformamide. The solution was reacted with 3 g of finely powdered potassium carbonate and the reaction mixture was heated for 15 minutes at 100° C. in a nitrogen atmosphere. Then 5.8 g of 3-[N-(2-(3,4-dimethoxyphenyl)-ethyl)-N-methylamino]-propyl chloride were added batchwise. The reaction mixture was stirred for 4 hours at 100° C., after which the salts that formed were filtered off, the filtrate was concentrated to dryness, and the residue dissolved in methyl-tert-butyl ether. The solution was then washed with aqueous sodium carbonate solution, dried with magnesium sulfate, and concentrated to dryness. The remaining crude oily title compound that was left as a residue was purified by flash chromatography using ethyl acetate as the eluent. 4.75 g of the title compound were obtained. after which the salts that formed were filtered off the filtrate was concentrated to dryness the residue dissolved in methyl-tert-butyl ether The solution was then washed with aqueous sodium carbonate solution dried with magnesium sulfate concentrated to dryness The remaining crude oily title compound that was left as a residue was purified by flash chromatography

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

Procedure: 29 ml of 1-bromo-3-chloropropane were dissolved in 300 ml of dimethylformamide and 24 g of potassium carbonate were added to the solution. A solution of 18 g N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-methylamine in 50 ml of dimethylformamide were added to the reaction mixture with stirring, dropwise within 2 hours. Then the reaction mixture was stirred for another hour. Then the salts formed were filtered off. The filtrate was concentrated at a maximum bath temperature of 50° C. The residue was dissolved in 200 ml of 0.5 m citric acid solution and the solution was extracted to remove unreacted bromochloropropane with methyl-tert-butyl ether. The aqueous phase was then made slightly alkaline by adding sodium hydrogen carbonate and extracted several times with ethyl acetate. Then the combined ethyl acetate extracts were dried with magnesium sulfate and concentrated. 21 g of 3-[N-(2-(3,4-dimethoxyphenyl)-ethyl)-N-methylamino]-propyl chloride were obtained as the residue. Then the reaction mixture was stirred for another hour Then the salts formed were filtered off The filtrate was concentrated at a maximum bath temperature of 50° C The residue was dissolved in 200 ml of 0.5 m citric acid solution the solution was extracted to remove unreacted bromochloropropane with methyl-tert-butyl ether by adding sodium hydrogen carbonate extracted several times with ethyl acetate Then the combined ethyl acetate extracts were dried with magnesium sulfate concentrated

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

Procedure: 29 ml of 1-bromo-3-chloropropane were dissolved in 300 ml of dimethylformamide and 24 g of potassium carbonate were added to the solution. A solution of 18 g N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-methylamine in 50 ml of dimethylformamide were added to the reaction mixture with stirring, dropwise within 2 hours. Then the reaction mixture was stirred for another hour. Then the salts formed were filtered off. The filtrate was concentrated at a maximum bath temperature of 50° C. The residue was dissolved in 200 ml of 0.5 m citric acid solution and the solution was extracted to remove unreacted bromochloropropane with methyl-tert-butyl ether. The aqueous phase was then made slightly alkaline by adding sodium hydrogen carbonate and extracted several times with ethyl acetate. Then the combined ethyl acetate extracts were dried with magnesium sulfate and concentrated. 21 g of 3-[N-(2-(3,4-dimethoxyphenyl)-ethyl)-N-methylamino]-propyl chloride were obtained as the residue. Then the reaction mixture was stirred for another hour Then the salts formed were filtered off The filtrate was concentrated at a maximum bath temperature of 50° C The residue was dissolved in 200 ml of 0.5 m citric acid solution the solution was extracted to remove unreacted bromochloropropane with methyl-tert-butyl ether by adding sodium hydrogen carbonate extracted several times with ethyl acetate Then the combined ethyl acetate extracts were dried with magnesium sulfate concentrated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 17 g of 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one were dissolved in 200 ml of dimethylformamide. 11 g of potassium carbonate were added to the solution and the reaction mixture was heated at 100° C. under a nitrogen atmosphere for 0.5 hours. A solution of 21 g of 3-[N-(2-(3,4-di-methoxyphenyl)-ethyl)-N-methylamino]-propylchloride in 150 ml of dimethylformamide was then added dropwise. After 2 hours the salts which formed were filtered out, the filtrate was evaporated to dryness, and the residue was dissolved in ethyl acetate. The solution was subsequently washed with 7% strength aqueous sodium hydroxide solution in order to remove unreacted 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one, dried with sodium sulfate and evaporated to dryness. The residue which remained was 35 g of oily crude product. This product was purified by chromatography over finely particulate silica gel under slightly elevated pressure (flash chromatography) using tert-butyl methyl ether/methanol 10:1 as eluent. 22.3 g of the title compound were obtained as an oil. IR spectrum of the base (as film): 1513 cm-1, 1260 cm-1, 1236 cm-1. After 2 hours the salts which formed were filtered out the filtrate was evaporated to dryness the residue was dissolved in ethyl acetate The solution was subsequently washed with 7% strength aqueous sodium hydroxide solution in order to remove unreacted 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one dried with sodium sulfate evaporated to dryness This product was purified by chromatography over finely particulate silica gel under slightly elevated pressure (flash chromatography)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 17 g of 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one were dissolved in 200 ml of dimethylformamide. 11 g of potassium carbonate were added to the solution and the reaction mixture was heated at 100° C. under a nitrogen atmosphere for 0.5 hours. A solution of 21 g of 3-[N-(2-(3,4-di-methoxyphenyl)-ethyl)-N-methylamino]-propylchloride in 150 ml of dimethylformamide was then added dropwise. After 2 hours the salts which formed were filtered out, the filtrate was evaporated to dryness, and the residue was dissolved in ethyl acetate. The solution was subsequently washed with 7% strength aqueous sodium hydroxide solution in order to remove unreacted 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one, dried with sodium sulfate and evaporated to dryness. The residue which remained was 35 g of oily crude product. This product was purified by chromatography over finely particulate silica gel under slightly elevated pressure (flash chromatography) using tert-butyl methyl ether/methanol 10:1 as eluent. 22.3 g of the title compound were obtained as an oil. IR spectrum of the base (as film): 1513 cm-1, 1260 cm-1, 1236 cm-1. After 2 hours the salts which formed were filtered out the filtrate was evaporated to dryness the residue was dissolved in ethyl acetate The solution was subsequently washed with 7% strength aqueous sodium hydroxide solution in order to remove unreacted 5-(3,4-dimethoxyphenyl)-pyrazolin-3-one dried with sodium sulfate evaporated to dryness This product was purified by chromatography over finely particulate silica gel under slightly elevated pressure (flash chromatography)

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

Procedure: N-isopropyl-3-trifluoromethylbenzenesulfonamide (5.362 g, 0.02 mol) in dimethylformamide (30 mL) was treated with sodium hydride (60% in mineral oil), (0.802 g) and stirred for 2 hours. Then N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine (5.436 g, 0.02 mol) was added and the reaction heated overnight. Filtration and removal of solvent provided the crude product (6.95 g). Column chromatography and high pressure liquid chromatography provided the pure product (4.35 g) as a gum. 1H NMR (CDCl3) 1.15 (d, 6, J=3.5H, Me2) 2.25 (s, 3, N-Me) 3.84 (d, 6, (OMe)2) 6.76 (m, 3, Ar) 7.25 (m, 3, Ar). the reaction heated overnight Filtration and removal of solvent provided the crude product (6.95 g)

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

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

Procedure: 39 g of 5-acetyl-6-hydroxy-4,7-dimethoxybenzofuran are refluxed with 40 g of 3-chloropropyl-(2-(3,4-dimethoxyphenyl)-ethyl)-methylamine in 250 ml of methyl ethyl ketone for 14 hours. The mixture is filtered, the solvent is stripped off and the oily residue is dissolved in dilute HCl. The aqueous phase is washed with ether, rendered alkaline with dilute sodium hydroxide solution and extracted with ether. Stripping off the solvent gives 45 g of crude oily product which is further reacted without purification. The mixture is filtered the oily residue is dissolved in dilute HCl The aqueous phase is washed with ether extracted with ether gives 45 g of crude oily product which is further reacted without purification

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

Procedure: N-isopropyl-3-trifluoromethylbenzenesulfonamide (5.362 g, 0.02 mol) in dimethylformamide (30 mL) was treated with sodium hydride (60% in mineral oil), (0.802 g) and stirred for 2 hours. Then N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine (5.436 g, 0.02 mol) was added and the reaction heated overnight. Filtration and removal of solvent provided the crude product (6.95 g). Column chromatography and high pressure liquid chromatography provided the pure product (4.35 g) as a gum. 1H NMR (CDCl3) 1.15 (d, 6, J=3.5H, Me2) 2.25 (s, 3, N--Me) 3.84 (d, 6, (OMe)2) 6.76 (m, 3, Ar) 7.25 (m, 3, Ar). the reaction heated overnight Filtration and removal of solvent provided the crude product (6.95 g)