3-[(2-hydroxyethylamino)methyl]benzonitrile

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of ethanolamine (2.32 g, 0.0381 mol) in toluene (100 mL), was added 3-cyanobenzaldehyde (5 g, 0.0381 mol) under N2 and refluxed at 140° C. After complete distilling out of toluene, the reaction mass was cooled to RT and dissolved in dry methanol (100 mL). To this solution was added in portions sodium borohydride (2.17 g, 0.0571 mol) at 0° C. The reaction mass was evaporated under pressure, washed with water (100 mL), extracted in DCM (100 mL), dried using sodium sulphate and concentrated under reduced pressure. The obtained crude was purified using column chromatography on silica and chloroform/methanol as eluent to afford the title compound as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 7.76 (s, 1H), 7.65-7.69 (m, 2H), 7.49-7.52 (m, 1H), 4.45-4.48 (m, 1H), 3.74 (s, 2H), 3.42-3.46 (m, 2H), 2.51-2.54 (m, 2H). After complete distilling out of toluene the reaction mass was cooled to RT dissolved in dry methanol (100 mL) The reaction mass was evaporated under pressure washed with water (100 mL) extracted in DCM (100 mL) dried concentrated under reduced pressure The obtained crude was purified

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of ethanolamine (2.32 g, 0.0381 mol) in toluene (100 mL), was added 3-cyanobenzaldehyde (5 g, 0.0381 mol) under N2 and refluxed at 140° C. After complete distilling out of toluene, the reaction mass was cooled to RT and dissolved in dry methanol (100 mL). To this solution was added in portions sodium borohydride (2.17 g, 0.0571 mol) at 0° C. The reaction mass was evaporated under pressure, washed with water (100 mL), extracted in DCM (100 mL), dried using sodium sulphate and concentrated under reduced pressure. The obtained crude was purified using column chromatography on silica and chloroform/methanol as eluent to afford the title compound as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 7.76 (s, 1H), 7.65-7.69 (m, 2H), 7.49-7.52 (m, 1H), 4.45-4.48 (m, 1H), 3.74 (s, 2H), 3.42-3.46 (m, 2H), 2.51-2.54 (m, 2H). After complete distilling out of toluene the reaction mass was cooled to RT dissolved in dry methanol (100 mL) The reaction mass was evaporated under pressure washed with water (100 mL) extracted in DCM (100 mL) dried concentrated under reduced pressure The obtained crude was purified

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

実験手順: Tert-butyl acrylate (3.56 ml, 29 mmol) was added into a solution of 3-{[(2-hydroxyethyl)amino]methyl}benzonitrile (4.9 g, 28 mmol) in anhydrous DMF (5 mL) under nitrogen atmosphere. The resulting mixture was heated at 80° C. for 12 hours. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.75 (s, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.50 (m, 1H), 4.36 (t, 1H), 3.62 (s, 2H), 3.43 (m, 2H), 2.69 (t, 2H), 2.47 (m, 2H), 2.34 (t, 2H), 1.38 (s, 9H). extracted with ethyl acetate (100 mL) The organic layer was dried over sodium sulfate concentrated under reduced pressure

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

実験手順: Tert-butyl acrylate (3.56 ml, 29 mmol) was added into a solution of 3-{[(2-hydroxyethyl)amino]methyl}benzonitrile (4.9 g, 28 mmol) in anhydrous DMF (5 mL) under nitrogen atmosphere. The resulting mixture was heated at 80° C. for 12 hours. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.75 (s, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.50 (m, 1H), 4.36 (t, 1H), 3.62 (s, 2H), 3.43 (m, 2H), 2.69 (t, 2H), 2.47 (m, 2H), 2.34 (t, 2H), 1.38 (s, 9H). extracted with ethyl acetate (100 mL) The organic layer was 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: 3-(Bromomethyl)benzonitrile (20.0 g, 0.125 mol) was added portion wise into a mixture of ethanolamine (11.4 g, 0.19 mol) and sodium bicarbonate (21.0 g, 0.25 mol) in ACN (200 mL) at 0° C. The resulting mixture was stirred for 4 hours. The reaction mixture was concentrated under vacuum. The residue was taken up with water and extracted with DCM (200 mL). The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by chromatography to afford the title compound as white solid (9.8 g, 54%). 1H NMR (DMSO-d6, 400 MHz) δ 7.76 (s, 1H), 7.67 (m, 2H), 7.51 (m, 1H), 4.47 (brs, 1H), 3.74 (s, 2H), 3.44 (m, 2H), 2.51 (m, 2H), 2.12 (brs, 1H). The reaction mixture was concentrated under vacuum extracted with DCM (200 mL) The organic layer was dried over sodium sulfate evaporated under reduced pressure The residue was purified by chromatography

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

実験手順: Tert-butyl acrylate (3.56 ml, 29 mmol) was added into a solution of 3-{[(2-hydroxyethyl)amino]methyl}benzonitrile (4.9 g, 28 mmol) in anhydrous DMF (5 mL) under nitrogen atmosphere. The resulting mixture was heated at 80° C. for 12 hours. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.75 (s, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.50 (m, 1H), 4.36 (t, 1H), 3.62 (s, 2H), 3.43 (m, 2H), 2.69 (t, 2H), 2.47 (m, 2H), 2.34 (t, 2H), 1.38 (s, 9H). extracted with ethyl acetate (100 mL) The organic layer was 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: 3-(Bromomethyl)benzonitrile (20.0 g, 0.125 mol) was added portion wise into a mixture of ethanolamine (11.4 g, 0.19 mol) and sodium bicarbonate (21.0 g, 0.25 mol) in ACN (200 mL) at 0° C. The resulting mixture was stirred for 4 hours. The reaction mixture was concentrated under vacuum. The residue was taken up with water and extracted with DCM (200 mL). The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by chromatography to afford the title compound as white solid (9.8 g, 54%). 1H NMR (DMSO-d6, 400 MHz) δ 7.76 (s, 1H), 7.67 (m, 2H), 7.51 (m, 1H), 4.47 (brs, 1H), 3.74 (s, 2H), 3.44 (m, 2H), 2.51 (m, 2H), 2.12 (brs, 1H). The reaction mixture was concentrated under vacuum extracted with DCM (200 mL) The organic layer was dried over sodium sulfate evaporated under reduced pressure The residue was purified by chromatography

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of ethanolamine (2.32 g, 0.0381 mol) in toluene (100 mL), was added 3-cyanobenzaldehyde (5 g, 0.0381 mol) under N2 and refluxed at 140° C. After complete distilling out of toluene, the reaction mass was cooled to RT and dissolved in dry methanol (100 mL). To this solution was added in portions sodium borohydride (2.17 g, 0.0571 mol) at 0° C. The reaction mass was evaporated under pressure, washed with water (100 mL), extracted in DCM (100 mL), dried using sodium sulphate and concentrated under reduced pressure. The obtained crude was purified using column chromatography on silica and chloroform/methanol as eluent to afford the title compound as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 7.76 (s, 1H), 7.65-7.69 (m, 2H), 7.49-7.52 (m, 1H), 4.45-4.48 (m, 1H), 3.74 (s, 2H), 3.42-3.46 (m, 2H), 2.51-2.54 (m, 2H). After complete distilling out of toluene the reaction mass was cooled to RT dissolved in dry methanol (100 mL) The reaction mass was evaporated under pressure washed with water (100 mL) extracted in DCM (100 mL) dried concentrated under reduced pressure The obtained crude was purified