N,N-dibenzyl-2-chloroethanamine;hydrochloride

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

実験手順: To a cold suspension of 33 g (0.82 mol) 50% sodium hydride in 500 mL dimethylformamide, add 50.4 g (0.315 mol) 4-(1H-imidazol-1-yl)phenol portionwise, maintaining the temp below 10° C. After addition, stir at room temp for 1 hr. Add 93.2 (0.315 mol) 2-chloro-N,N-dibenzylethanamine hydrochloride portionwise followed by 2.35 g (0.16 mol) sodium iodide. Heat the reaction to 50° C. for 24 hr. After this time, quench with 15 mL H2O, filter, and remove the solvents. Dissolve the residue in methanolic HCl and remove the solvents to provide the title compound which can be recrystallized from isopropanol. maintaining the temp below 10° C After addition Heat the reaction to 50° C. for 24 hr After this time, quench with 15 mL H2O filter remove the solvents Dissolve the residue in methanolic HCl remove the solvents

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

実験手順: To a cold suspension of 33 g (0.82 mol) 50% sodium hydride in 500 mL dimethylformamide, add 50.4 g (0.315 mol) 4-(1H-imidazol-1-yl)phenol portionwise, maintaining the temp below 10° C. After addition, stir at room temp for 1 hr. Add 93.2 (0.315 mol) 2-chloro-N,N-dibenzylethanamine hydrochloride portionwise followed by 2.35 g (0.16 mol) sodium iodide. Heat the reaction to 50° C. for 24 hr. After this time, quench with 15 mL H2O, filter, and remove the solvents. Dissolve the residue in methanolic HCl and remove the solvents to provide the title compound which can be recrystallized from isopropanol. maintaining the temp below 10° C After addition Heat the reaction to 50° C. for 24 hr After this time, quench with 15 mL H2O filter remove the solvents Dissolve the residue in methanolic HCl remove the solvents

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-Hydroxy-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid (GB1417129) (0.905 g, 3.69 mmol) was suspended in dry DMF (50 mL). To this was added potassium carbonate (3.06 g, 22 mmol) and dibenzyl-(2-chloroethyl)amine hydrochloride (2.37 g, 8 mmol). The mixture was heated at 60° C. for 16 h, then more potassium carbonate (0.55 g) and dibenzyl-(2-chloroethyl)amine hydrochloride (1.18 g, 4 mmol) were added. After a further 25 h at 75° C. the mixture was evaporated. The residue was diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine, dried and evaporated under reduced pressure. The crude product (4.0 g) was purified by chromatography on silica gel (100 g), eluting with 0-4% methanol in dichloromethane, to give the title compound (2.25 g, 89%); ESMS m/z 692 [M+H]+ (100%). After a further 25 h at 75° C. the mixture was evaporated The residue was diluted with water extracted with ethyl acetate (×3) The combined organic extracts were washed with brine dried evaporated under reduced pressure The crude product (4.0 g) was purified by chromatography on silica gel (100 g) eluting with 0-4% methanol in dichloromethane

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Ethyl-6-hydroxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (GB 1433774) (1.4 g, 6 mmol) was dissolved in dry DMF (80 mL). To this was added potassium carbonate (5 g, 36 mmol) and dibenzyl-(2-chloroethyl)amine hydrochloride (4.37 g, 14.8 mmol). The mixture was heated at 65° C. with stirring for 72 h, then allowed to cool overnight. The mixture was evaporated to a small volume, diluted with water and extracted with ethyl acetate (×2). The combined organic extracts were washed with brine, dried and evaporated under reduced pressure to give a dark viscous oil (4.9 g). This residue was purified by chromatography on silica gel (100 g), eluting with 0.2-3.8% methanol in dichloromethane, to give the title compound as a brown solid (2.46 g, 60%); ESMS m/z 680 [M+H]+ (100%). to cool overnight The mixture was evaporated to a small volume diluted with water extracted with ethyl acetate (×2) The combined organic extracts were washed with brine dried evaporated under reduced pressure

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

実験手順: The material given in Example 1 was prepared in accordance with the following. 20.0 g. of N,N-dibenzyl-2-chloroethylamine hydrochloride and 27.6 g of potassium carbonate were mixed in 250 ml of acetonitrile. The mixture was refluxed for 15 min. and 13.8 g of 4-benzyloxyphenol were added, whereupon the mixture was refluxed for 5 hours while stirred. After filtration and evaporation the residue was recrystallized from petroleum ether. 18.4 g of 1-(N,N-dibenzylamino)-2-(4-benzyloxyphenoxy)-ethane was obtained. The structure was determined using NMR. was prepared in accordance with the following The mixture was refluxed for 15 min. was refluxed for 5 hours After filtration and evaporation the residue was recrystallized from petroleum ether

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

実験手順: Benzyl cyanide (0.97 mL, 8.4 mmole) was reacted with lithium bis(trimethylsilyl)amide (LHMDSA) (8.4 mL, 8.4 mmole) in 5 mL of THF at -78° C. for 1 hour. After an additional aliquot of LHMDSA (4.2 mL, 4.2 mmole) was added, N-(2-chloroethyl)dibenzylamine hydrochloride (1.0 g, 3.4 mmole) was then added. The reaction was allowed to stand at room temperature and was then warmed to 50° C. for 3.5 hours. The mixture was poured into ice/water, and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford alpha-(N,N-dibenzylaminoethyl) benzyl cyanide (1.05 g), isolated in 94% yield (MS: (M+H)+ =341). After an additional aliquot of LHMDSA (4.2 mL, 4.2 mmole) was added to stand at room temperature the product was extracted with ethyl acetate The ethyl acetate layer was washed with brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: To a cold suspension of 33 g (0.82 mol) 50% sodium hydride in 500 mL dimethylformamide, add 50.4 g (0.315 mol) 4-(1H-imidazol-1-yl)phenol portionwise, maintaining the temp below 10° C. After addition, stir at room temp for 1 hr. Add 93.2 (0.315 mol) 2-chloro-N,N-dibenzylethanamine hydrochloride portionwise followed by 2.35 g (0.16 mol) sodium iodide. Heat the reaction to 50° C. for 24 hr. After this time, quench with 15 mL H2O, filter, and remove the solvents. Dissolve the residue in methanolic HCl and remove the solvents to provide the title compound which can be recrystallized from isopropanol. maintaining the temp below 10° C After addition Heat the reaction to 50° C. for 24 hr After this time, quench with 15 mL H2O filter remove the solvents Dissolve the residue in methanolic HCl remove the solvents