N-benzyl-3-chloro-N-methylpropan-1-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.3 g of 2-methyl-5-(2-fluorophenyl)-pyrazolin-3-one were dissolved in 50 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone. 0.55 g of sodium hydride (as an 80% strength solution in paraffin) was added to this solution and the reaction mixture was stirred at 80° C. for 30 minutes. 3.3 g of 3-(N-benzyl-N-methylamino)-propyl chloride were added to the reaction mixture which was stirred at 80° C. for a further 2 hours. After the reaction mixture had cooled, 10 ml of a 2N solution of hydrochloric acid in isopropanol were added to it, and the mixture was then added dropwise to 2 liters of a 1:3 mixture of acetone and tert-butyl methyl ether. The resulting precipitate was filtered out and dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate. The organic phase was separated and the aqueous phase was subsequently extracted repeatedly with ethyl acetate. The combined ethyl acetate extracts were dried with sodium sulfate and evaporated. The crude base obtained was purified by chromatography on silica gel. 4.4 g of 3-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazole were obtained. was stirred at 80° C. for a further 2 hours After the reaction mixture had cooled The resulting precipitate was filtered out dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate The organic phase was separated the aqueous phase was subsequently extracted repeatedly with ethyl acetate The combined ethyl acetate extracts were dried with sodium sulfate evaporated The crude base obtained was purified by chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 260 ml of 1-bromo-3-chloropropane were dissolved in 400 ml of acetone. 230 g of potassium carbonate were added to the solution. A solution of 115 ml of N-methyl-N-benzylamine in 115 ml of acetone was added dropwise to the reaction mixture with stirring at a bath temperature of 40° C., the addition being distributed over a period of 30 minutes. The reaction mixture was subsequently stirred at a temperature of 40° C. for 4 hours. The precipitated salts were then filtered out. The filtrate was concentrated under reduced pressure at a temperature of 40° C. The residue was acidified to a pH of 1 using 16% strength aqueous hydrochloric acid solution and was washed 3 times with tert-butyl methyl ether in order to remove unreacted 1-bromo-3-chloropropane. The aqueous phase was subsequently brought to a pH of 8 by addition of 16% strength sodium hydroxide solution and was extracted repeatedly with ethyl acetate. The combined ethyl acetate phases were dried with magnesium sulfate and concentrated. 71 g of 3-(N-benzyl-N-methyl-amino)-propyl chloride were obtained. the addition The reaction mixture was subsequently stirred at a temperature of 40° C. for 4 hours The precipitated salts were then filtered out The filtrate was concentrated under reduced pressure at a temperature of 40° C was washed 3 times with tert-butyl methyl ether in order to remove unreacted 1-bromo-3-chloropropane The aqueous phase was subsequently brought to a pH of 8 by addition of 16% strength sodium hydroxide solution was extracted repeatedly with ethyl acetate The combined ethyl acetate phases were dried with magnesium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, 1-methyethyl ester (2.0 g, 6.0 mmol) in dimethylformamide (7.0 ml) was treated with finely ground potassium carbonate (1.7 g, 12.0 mmoles), N-benzyl-3-chloro-N-methylpropylamine (2.37 g, 12.0 mmol) and a catalytic amount of 18-crown-6. The reaction was heated at 70°-75° C. under argon overnight. The reaction was allowed to cool down to room temperature and was diluted with ether. It was filtered, and the filtrate was washed with water, brine and was dried over anhydrous magnesium sulfate. Evaporation of solvent provided a brown oil which was purified by flash chromatography (20% acetone in hexanes) to yield the title compound (1.51 g) as a yellow oil. The reaction was heated at 70°-75° C. under argon overnight It was filtered the filtrate was washed with water, brine was dried over anhydrous magnesium sulfate Evaporation of solvent provided a brown oil which was purified by flash chromatography (20% acetone in hexanes)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.3 g of 2-methyl-5-(2-fluorophenyl)-pyrazolin-3-one were dissolved in 50 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone. 0.55 g of sodium hydride (as an 80 % strength solution in paraffin) was added to this solution and the reaction mixture was stirred at 80° C. for 30 minutes. 3.3 g of 3-(N-benzyl-N-methylamino)-propyl chloride were added to the reaction mixture which was stirred at 80° C. for a further 2 hours. After the reaction mixture had cooled, 10 ml of a 2N solution of hydrochloric acid in isopropanol were added to it, and the mixture was then added dropwise to 2 liters of a 1:3 mixture of acetone and tert-butyl methyl ether. The resulting precipitate was filtered out and dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate. The organic phase was separated and the aqueous phase was subsequently extracted repeatedly with ethyl acetate. The combined ethyl acetate extracts were dried with sodium sulfate and evaporated. The crude base obtained was purified by chromatography on silica gel. 4.4 g of 3-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazole were obtained. was stirred at 80° C. for a further 2 hours After the reaction mixture had cooled The resulting precipitate was filtered out dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate The organic phase was separated the aqueous phase was subsequently extracted repeatedly with ethyl acetate The combined ethyl acetate extracts were dried with sodium sulfate evaporated The crude base obtained was purified by chromatography on silica gel

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 260 ml of 1-bromo-3-chloropropane were dissolved in 400 ml of acetone. 230 g of potassium carbonate were added to the solution. A solution of 115 ml of N-methyl-N-benzylamine in 115 ml of acetone was added dropwise to the reaction mixture with stirring at a bath temperature of 40° C., the addition being distributed over a period of 30 minutes. The reaction mixture was subsequently stirred at a temperature of 40° C. for 4 hours. The precipitated salts were then filtered out. The filtrate was concentrated under reduced pressure at a temperature of 40° C. The residue was acidified to a pH of 1 using 16% strength aqueous hydrochloric acid solution and was washed 3 times with tert-butyl methyl ether in order to remove unreacted 1-bromo-3-chloropropane. The aqueous phase was subsequently brought to a pH of 8 by addition of 16% strength sodium hydroxide solution and was extracted repeatedly with ethyl acetate. The combined ethyl acetate phases were dried with magnesium sulfate and concentrated. 71 g of 3-(N-benzyl-N-methylamino)-propyl chloride were obtained. the addition The reaction mixture was subsequently stirred at a temperature of 40° C. for 4 hours The precipitated salts were then filtered out The filtrate was concentrated under reduced pressure at a temperature of 40° C was washed 3 times with tert-butyl methyl ether in order to remove unreacted 1-bromo-3-chloropropane The aqueous phase was subsequently brought to a pH of 8 by addition of 16% strength sodium hydroxide solution was extracted repeatedly with ethyl acetate The combined ethyl acetate phases were dried with magnesium sulfate concentrated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.3 g of 2-methyl-5-(2-fluorophenyl)-pyrazolin-3-one were dissolved in 50 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone. 0.55 g of sodium hydride (as an 80% strength solution in paraffin) was added to this solution and the reaction mixture was stirred at 80° C. for 30 minutes. 3.3 g of 3-(N-benzyl-N-methylamino)-propyl chloride were added to the reaction mixture which was stirred at 80° C. for a further 2 hours. After the reaction mixture had cooled, 10 ml of a 2N solution of hydrochloric acid in isopropanol were added to it, and the mixture was then added dropwise to 2 liters of a 1:3 mixture of acetone and tert-butyl methyl ether. The resulting precipitate was filtered out and dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate. The organic phase was separated and the aqueous phase was subsequently extracted repeatedly with ethyl acetate. The combined ethyl acetate extracts were dried with sodium sulfate and evaporated. The crude base obtained was purified by chromatography on silica gel. 4.4 g of 3-[3-(N-benzyl-N-methylamino)-propyloxy]-2-methyl-5-(2-fluorophenyl)-pyrazole were obtained. was stirred at 80° C. for a further 2 hours After the reaction mixture had cooled The resulting precipitate was filtered out dissolved in a mixture of saturated aqueous sodium carbonate solution and ethyl acetate The organic phase was separated the aqueous phase was subsequently extracted repeatedly with ethyl acetate The combined ethyl acetate extracts were dried with sodium sulfate evaporated The crude base obtained was purified by chromatography on silica gel