1-(4-bromophenyl)-N,N-dimethylmethanamine

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

Procedure: A solution of 1-bromo-4-(bromomethyl)benzene (20 g, 80.65 mmol, 1.00 equiv), dimethylamine (13.20 g, 96.80 mmol, 1.20 equiv, 33%) and potassium carbonate (13.36 g, 96.81 mmol, 1.20 equiv) in ethanol (200 mL) was stirred overnight at 50° C. The solid material was removed by filtration and the filtrate was concentrated under vacuum. The residue was dissolved in 200 mL of water and extracted with 3×200 mL of dichloromethane. The combined organic layer was washed with 3×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1) to give 10 g (58%) of (4-bromophenyl)-N,N-dimethylmethanamine as a yellow oil. LC-MS: (ES, m/z): 255 [M+CH3CN+H]+, 214 [M+H]+, 169. The solid material was removed by filtration the filtrate was concentrated under vacuum The residue was dissolved in 200 mL of water extracted with 3×200 mL of dichloromethane The combined organic layer was washed with 3×200 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1)

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

Procedure: A solution of 1-bromo-4-(bromomethyl)benzene (20 g, 80.65 mmol, 1.00 equiv), dimethylamine (13.20 g, 96.80 mmol, 1.20 equiv, 33%) and potassium carbonate (13.36 g, 96.81 mmol, 1.20 equiv) in ethanol (200 mL) was stirred overnight at 50° C. The solid material was removed by filtration and the filtrate was concentrated under vacuum. The residue was dissolved in 200 mL of water and extracted with 3×200 mL of dichloromethane. The combined organic layer was washed with 3×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1) to give 10 g (58%) of (4-bromophenyl)-N,N-dimethylmethanamine as a yellow oil. LC-MS: (ES, m/z): 255 [M+CH3CN+H]+, 214 [M+H]+, 169. The solid material was removed by filtration the filtrate was concentrated under vacuum The residue was dissolved in 200 mL of water extracted with 3×200 mL of dichloromethane The combined organic layer was washed with 3×200 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1)

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

Procedure: Reaction of dimethylamine with 4-bromobenzyl bromide in cold benzene gave 4-bromo-N,N-dimethylbenzylamine which was successively reacted with magnesium, formaldehyde, and cysteamine (in a similar procedure to Example 7) to give 2-[4-(dimethylaminomethyl)benzylthio]ethylamine as an oil.

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

Procedure: A solution of the Grignard reagent prepared from 344 mg of magnesium and 2.27 g of 1,4-dibromobenzene in 15 ml of THF (tetrahydrofuran) is added dropwise to a suspension of 2 g of 4-bromo-N,N-dimethylbenzylamine and 158 mg of tetrakistriphenylphosphinepalladium in 10 ml of THF. The addition is carried out at room temperature and under an argon atmosphere. After completion of the addition, the mixture is heated to boiling for an additional 5 hours and then evaporated under reduced pressure. The residue is then treated with ether and saturated ammonium chloride solution and the aqueous phase is separated. This is extracted with ether. The organic extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1. 4'-Bromo-N,N-dimethylbiphenylmethanamine, m.p. 60°-62° C., is obtained. The addition is carried out at room temperature and under an argon atmosphere After completion of the addition the mixture is heated evaporated under reduced pressure The residue is then treated with ether and saturated ammonium chloride solution the aqueous phase is separated This is extracted with ether The organic extracts are washed with saturated sodium chloride solution dried over magnesium sulfate evaporated The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1

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

Procedure: 2M Ethanolic dimethylamine solution (30 ml) was added to a solution of 4-bromobenzyl bromide (5 g) in DMF (20 ml). The mixture was stirred at ambient temperature for 18 h and was then partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The organic phase was dried, evaporated and purified by column chromatography, eluting with a gradient of 0 to 5% methanol in DCM to yield the product as a clear oil. MS (M+H)+ 214. 1H NMR (CDCl3) 2.21 (s, 6H), 3.35 (s, 2H), 7.18 (d, 2H), 7.43 (d, 2H). was then partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution The organic phase was dried evaporated purified by column chromatography eluting with a gradient of 0 to 5% methanol in DCM

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

Procedure: A solution of the Grignard reagent prepared from 344 mg of magnesium and 2.27 g of 1,4-dibromobenzene in 15 ml of THF (tetrahydrofuran) is added dropwise to a suspension of 2 g of 4-bromo-N,N-dimethylbenzylamine and 158 mg of tetrakistriphenylphosphinepalladium in 10 ml of THF. The addition is carried out at room temperature and under an argon atmosphere. After completion of the addition, the mixture is heated to boiling for an additional 5 hours and then evaporated under reduced pressure. The residue is then treated with ether and saturated ammonium chloride solution and the aqueous phase is separated. This is extracted with ether. The organic extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1. 4'-Bromo-N,N-dimethylbiphenylmethanamine, m.p. 60°-62°C., is obtained. The addition is carried out at room temperature and under an argon atmosphere After completion of the addition the mixture is heated evaporated under reduced pressure The residue is then treated with ether and saturated ammonium chloride solution the aqueous phase is separated This is extracted with ether The organic extracts are washed with saturated sodium chloride solution dried over magnesium sulfate evaporated The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1

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

Procedure: At 5° C. 4-bromobenzylbromide (100 g, 402 mmol) in 100 mL DMF is added to a mixture of dimethylamine (40% in water, 150 mL, 1.33 mol). After 0.5 h stirring at RT, 6 M aqueous HCl is added and the reaction mixture is extracted with diethyl ether. The combined organic phases are washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue is purified by vacuum distillation (bp 58° C. at 2 mbar). Yield: 77.6 g. At 5° C the reaction mixture is extracted with diethyl ether The combined organic phases are washed with brine dried over Na2SO4 concentrated in vacuo The residue is purified by vacuum distillation (bp 58° C. at 2 mbar)

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

Procedure: A solution of the Grignard reagent prepared from 344 mg of magnesium and 2.27 g of 1,4-dibromobenzene in 15 ml of THF (tetrahydrofuran) is added dropwise to a suspension of 2 g of 4-bromo-N,N-dimethylbenzylamine and 158 mg of tetrakistriphenylphosphinepalladium in 10 ml of THF. The addition is carried out at room temperature and under an argon atmosphere. After completion of the addition, the mixture is heated to boiling for an additional 5 hours and then evaporated under reduced pressure. The residue is then treated with ether and saturated ammonium chloride solution and the aqueous phase is separated. This is extracted with ether. The organic extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1. 4'-Bromo-N,N-dimethylbiphenylmethanamine, m.p. 60°-62° C., is obtained. The addition is carried out at room temperature and under an argon atmosphere After completion of the addition the mixture is heated evaporated under reduced pressure The residue is then treated with ether and saturated ammonium chloride solution the aqueous phase is separated This is extracted with ether The organic extracts are washed with saturated sodium chloride solution dried over magnesium sulfate evaporated The residue is purified by chromatography on silica gel while eluting with methylene chloride/methanol 9:1

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

Procedure: A solution of 1-bromo-4-(bromomethyl)benzene (20 g, 80.65 mmol, 1.00 equiv), dimethylamine (13.20 g, 96.80 mmol, 1.20 equiv, 33%) and potassium carbonate (13.36 g, 96.81 mmol, 1.20 equiv) in ethanol (200 mL) was stirred overnight at 50° C. The solid material was removed by filtration and the filtrate was concentrated under vacuum. The residue was dissolved in 200 mL of water and extracted with 3×200 mL of dichloromethane. The combined organic layer was washed with 3×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1) to give 10 g (58%) of (4-bromophenyl)-N,N-dimethylmethanamine as a yellow oil. LC-MS: (ES, m/z): 255 [M+CH3CN+H]+, 214 [M+H]+, 169. The solid material was removed by filtration the filtrate was concentrated under vacuum The residue was dissolved in 200 mL of water extracted with 3×200 mL of dichloromethane The combined organic layer was washed with 3×200 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1)

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

Procedure: A 20-mL eggplant flask equipped with a three-way cock and a magnetic stirrer was heat dried while pumping to a vacuum of 5 Pa before its interior was purged with argon atmosphere. Into the flask, iron complex A (1.0 mg, 0.002 mmol) was admitted as catalyst and dissolved in toluene (0.5 mL). To the solution, 1,2-bis(dimethylsilyl)benzene (475 μL) was added through a syringe, and N,N-dimethyl-4-bromobenzamide (228 mg, 1.0 mmol) was added. The solution was stirred at 100° C. for 30 minutes. Toluene was distilled off in vacuum. The crude product was purified by silica gel-packed column chromatography using hexane/ethyl acetate (20/1) as developing solvent, obtaining N,N-dimethyl-4-bromobenzylamine (184 mg, 0.86 mmol, 86%). The results are shown as Entry 2 in Table 5. The resulting amine was identified for geometry by 1H and 13C-NMR spectroscopy and IR spectroscopy. A 20-mL eggplant flask equipped with a three-way cock and a magnetic stirrer was heat dried was purged with argon atmosphere Toluene was distilled off in vacuum The crude product was purified by silica gel-

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

Procedure: A solution of 1-bromo-4-(bromomethyl)benzene (20 g, 80.65 mmol, 1.00 equiv), dimethylamine (13.20 g, 96.80 mmol, 1.20 equiv, 33%) and potassium carbonate (13.36 g, 96.81 mmol, 1.20 equiv) in ethanol (200 mL) was stirred overnight at 50° C. The solid material was removed by filtration and the filtrate was concentrated under vacuum. The residue was dissolved in 200 mL of water and extracted with 3×200 mL of dichloromethane. The combined organic layer was washed with 3×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1) to give 10 g (58%) of (4-bromophenyl)-N,N-dimethylmethanamine as a yellow oil. LC-MS: (ES, m/z): 255 [M+CH3CN+H]+, 214 [M+H]+, 169. The solid material was removed by filtration the filtrate was concentrated under vacuum The residue was dissolved in 200 mL of water extracted with 3×200 mL of dichloromethane The combined organic layer was washed with 3×200 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum The residue was purified on a silica gel column eluted with dichloromethane/methanol (20:1)