2-(methylamino)acetonitrile;hydrochloride

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

実験手順: In DMF (3ml) was dissolved (E)-N-[4-(chloromethyl)-phenyl]-3-(4-methylphenyl)cinnamamide (200mg), and to the solution were added methylaminoacetonitrile hydrochloride (77mg) and potassium carbonate (382mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)-cinnamamide (Compound 64) (129mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate-diisopropylether

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

実験手順: In DMF (3ml) was dissolved (E)-N-[4-(chloromethyl)-phenyl]-3-(4-methylphenyl)cinnamamide (200mg), and to the solution were added methylaminoacetonitrile hydrochloride (77mg) and potassium carbonate (382mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)-cinnamamide (Compound 64) (129mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate-diisopropylether

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

実験手順: In DMF (3 ml) was dissolved (E)-N-[4—(chloromethyl)phenyl]-3—(4-methylphenyl)cinnamamide (200 mg). and to the solution were added methylaminoacetonitrile hydrochloride (77 mg) and potassium carbonate (382 mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3—(4-methylphenyl)cinnamamide (Compound 64) (129 mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate-diisopropylether

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10.3 ml (0.74 mole) of triethylamine, 7.2 g (0.74 mole) of 3-cyanobutan-2-one and 0.5 g of p-toluenesulfonic acid are successively added to a suspension of 7.8 g (0.74 mole) of N-methylaminoacetonitrile hydrochloride in 70 ml of chloroform, and the mixture is boiled for 5 hours, using a water separator. After it has been boiled, the mixture is washed twice with 10 ml of water each time and dried over sodium sulfate; the solvent is then stripped off in vacuo. In order to remove all of the chloroform, the residue is twice taken up in 100 ml (each time) of dry ethanol, and the mixture concentrated each time in vacuo. The resulting oil is warmed (bath temperature of 50° C.) in 100 ml of 1 N sodium ethylate/ethanol for 2 hours; some of the ethanol is removed. The mixture is then taken up in 100 ml of water and extracted several times with methylene chloride. After being dried over sodium sulfate and concentrated on a rotary evaporator, the extracts yield a solid residue, which is recrystallized from diisopropyl ether. the mixture is washed twice with 10 ml of water each time dried over sodium sulfate In order to remove all of the chloroform the mixture concentrated each time in vacuo some of the ethanol is removed extracted several times with methylene chloride After being dried over sodium sulfate concentrated on a rotary evaporator the extracts yield a solid residue, which is recrystallized from diisopropyl ether

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

実験手順: 3.29 g (30.8 mmoles) of methylamino-acetonitrile hydrochloride is placed in the presence of 19.6 g (154 mmoles) of oxalyl chloride in 30 ml of 1,2-dichlorobenzene. The mixture is heated for 8 hours at 80° C. After concentrating the reaction medium to dryness, the residue obtained is purified by flash chromatography (Petroleum ether-CH2Cl2 gradient 100-0 to 0-100). 3.35 g of intermediate 4c is obtained in beige powder form (yield: 60%). After concentrating the reaction medium to dryness the residue obtained is purified by flash chromatography (Petroleum ether-CH2Cl2 gradient 100-0 to 0-100)

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

実験手順: 2.7 parts of methylaminoacetonitrile hydrochloride was added to a solution of 2 parts of sodium hydroxide in 25 parts of water at ~15°. When the addition was complete a solution of 5.8 parts of 2-phenoxybenzoyl chloride in 50 parts of methylene chloride was added dropwise. The mixture was stirred vigorously for 5 hrs. at ~20°. The methylene chloride layer was then separated, washed with water and dried over magnesium sulfate. Removal of the magnesium sulfate by filtration and concentration of the filtrate gave 4.6 parts of N-cyanomethyl-N-methyl-2-phenoxybenzamide as a viscous oil. NMR (CDCl3) 3δ(S,3H,CH3), 4.1δ,4.3δ (2S,2H,CH2), 7.05δ, (m,9H,Aromatic H). When the addition was added dropwise at ~20° The methylene chloride layer was then separated washed with water dried over magnesium sulfate Removal of the magnesium sulfate by filtration and concentration of the filtrate

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

実験手順: In DMF (3 ml) was dissolved (E)-N-[4-(chloromethyl)-phenyl]-3-(4-methylphenyl)cinnamamide (200 mg), and to the solution were added methylaminoacetonitrile hydrochloride (77 mg) and potassium carbonate (382 mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)-cinnamamide (Compound 64) (129 mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate-diisopropylether

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

実験手順: In DMF (3 ml) was dissolved (E)-N-[4-(chloromethyl)phenyl]-3- (4-methylphenyl)cinnamamide (200 mg), and to the solution were added methylaminoacetonitrile hydrochloride (77 mg) and potassium carbonate (382 mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetatediisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)cinnamamide (Compound 64) (129 mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetatediisopropylether

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

実験手順: In DMF (3ml) was dissolved (E)-N-[4-(chloromethyl)-phenyl]-3-(4-methylphenyl)cinnamamide (200mg), and to the solution were added methylaminoacetonitrile hydrochloride (77mg) and potassium carbonate (382mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)-cinnamamide (Compound 64) (129mg) as colorless crystals. The mixture was extracted with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate-diisopropylether