ethyl N-(2-bromoethyl)carbamate

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 mixture of 12.94 parts of ethyl (2-bromoethyl)carbamate, 15.68 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.08 parts of sodium hydrogen carbonate and 160 parts of ethanol is stirred and refluxed overnight. The formed precipitate is filtered off and washed with trichloromethane. The layers from the filtrate are separated. The organic phase is dried, filtered and evaporated. The residue is stirred in 2-propanone. The unreacted starting material is filtered off and the filtrate is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from ethanol 70%. The product is filtered off and dried, yielding 6.5 parts of ethyl {2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}carbamate; mp. 187.7° C. refluxed overnight The formed precipitate is filtered off washed with trichloromethane The layers from the filtrate are separated The organic phase is dried filtered evaporated The residue is stirred in 2-propanone is filtered off the filtrate is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent The pure fractions are collected the eluent is evaporated The residue is crystallized from ethanol 70% The product is filtered off dried

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

実験手順: A mixture of 12.94 parts of ethyl (2-bromoethyl)carbamate, 13.51 parts of 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.1 parts of sodium hydrogen carbonate and 160 parts of ethanol is stirred and refluxed overnight. The reaction mixture is cooled, filtered over hyflo and the filtrate is evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide, as eluent. The pure fractions are collected and the eluent is evaporated, yielding 4.4 parts of ethyl 2-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethylcarbamate as a residue. refluxed overnight The reaction mixture is cooled filtered over hyflo the filtrate is evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide The pure fractions are collected the eluent is evaporated

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

実験手順: A mixture of 12.94 parts of ethyl (2-bromoethyl)carbamate, 13.51 parts of 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.1 parts of sodium hydrogen carbonate and 160 parts of ethanol is stirred and refluxed overnight. The reaction mixture is cooled, filtered over hyflo and the filtrate is evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide, as eluent. The pure fractions are collected and the eluent is evaporated, yielding 4.4 parts of ethyl 2-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethylcarbamate as a residue. refluxed overnight The reaction mixture is cooled filtered over hyflo the filtrate is evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide The pure fractions are collected the eluent is evaporated

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 3-(2-(4-(6-hydroxybenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one, prepared as described in the previous step, (6.6 g, 0.015 mmol) in DMF (50 mL) and acetone (50 mL) was treated with potassium carbonate (3.0 g, 0.03 mmol) and ethyl (2-bromoethyl)carbamate (2.4 g, 0.015 mmol). After stirring overnight at 60° C., the reaction mixture was poured in water (150 mL), extracted with chloroform (3×100 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (elution with dichloromethane/methanol (90/10). The combined fractions were treated with HBr (150 mL, 48%) and heated to reflux for 30 min. The mixture was allowed to cool down to room temperature and made basic with ammonium hydroxide (28% NH3 in H2O) and extracted with chloroform (3×100 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (gradient elution with dichloromethane/methanol (90/10 to 50/50) resulting in a solid which was dissolved in isopropanol (50 mL) and treated with isopropanol/HCl. The precipitate was removed by filtration and washed with iPrOH/diisopropyl ether (50/50, 3×20 mL). The precipitate was dried under vacuum to yield the title compound ESI-MS (M+1) 452. 1H NMR (360 MHz, DMSO-d6) δ ppm 1.76-1.85 (m, 1H) 1.87-1.96 (m, 1H) 2.19 (d, J=12.81 Hz, 1H) 2.37-2.48 (m, 4H) 2.98-3.10 (m, 3H) 3.10-3.28 (m, 5H) 3.37-3.46 (m, 3H) 3.72 (d, J=11.34Hz, 3H) 3.79-3.85 (m, 2H) 4.31 (t, J=4.94Hz, 1H) 7.05 (dd, J=8.78, 1.83 Hz, 1H) 7.35-7.39 (m, 1H) 8.08 (d, J=8.78 Hz, 1H). extracted with chloroform (3×100 mL) The combined organic layers were dried over Na2SO4 filtered concentrated purified by silica gel chromatography ( elution with dichloromethane/methanol (90/10) The combined fractions were treated with HBr (150 mL, 48%) heated to reflux for 30 min to cool down to room temperature extracted with chloroform (3×100 mL) The combined organic layers were dried over Na2SO4 filtered concentrated purified by silica gel chromatography ( gradient elution with dichloromethane/methanol (90/10 to 50/50) resulting in a solid which The precipitate was removed by filtration washed with iPrOH/diisopropyl ether (50/50, 3×20 mL) The precipitate was dried under vacuum

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

実験手順: A mixture of 12.94 parts of ethyl (2-bromoethyl)carbamate, 15.68 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.08 parts of sodium hydrogen carbonate and 160 parts of ethanol is stirred and refluxed overnight. The formed precipitate is filtered off and washed with trichloromethane. The layers from the filtrate are separated. The organic phase is dried, filtered and evaporated. The residue is stirred in 2-propanone. The unreacted starting material is filtered off and the filtrate is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from ethanol 70%. The product is filtered off and dried, yielding 6.5 parts of ethyl {2-[4-(5-chloro-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-ethyl}carbamate; mp. 187.7° C. refluxed overnight The formed precipitate is filtered off washed with trichloromethane The layers from the filtrate are separated The organic phase is dried filtered evaporated The residue is stirred in 2-propanone is filtered off the filtrate is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent The pure fractions are collected the eluent is evaporated The residue is crystallized from ethanol 70% The product is filtered off dried

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

実験手順: A mixture of 12.94 parts of ethyl (2-bromoethyl)carbamate, 13.51 parts of 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.1 parts of sodium hydrogen carbonate and 160 parts of ethanol is stirred and refluxed overnight. The reaction mixture is cooled, filtered over hyflo and the filtrate is evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide, as eluent. The pure fractions are collected and the eluent is evaporated, yielding 4.4 parts of ethyl 2-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]ethylcarbamate as a residue. refluxed overnight The reaction mixture is cooled filtered over hyflo the filtrate is evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, 10% of methanol and one drop of ammonium hydroxide The pure fractions are collected the eluent is evaporated

反応条件: temp:0.00; pressure:0.00; stir: