(1S,2S)-(+)-2-氨基-3-甲氧基-1-苯基-1-丙醇

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1S,2S)-2-amino-3-methoxy-1-phenyl-1-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 5.3 mmol). The mixture was stirred at reflux for 2.5 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50° C.), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, 1H, J=9.8 Hz), 3.53 (m, 1H), 3.37 (m, 1H). 3.26 (m, 1H), 3.17 (m, 6H), 2.91 (t, 2H, J=7.3 Hz), 2.07 (m, 2H). 13C NMR (D2O, 125 MHz) δ ppm 139.09, 129.33, 129.27, 127.11, 70.85, 66.29, 62.62, 58.76, 48.14, 44.24, 21.47. [α]D=+42.6° (c=0.00091 in water), ES-MS 302 (M−1). at reflux for 2.5 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EG (1.0 g, 63%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 223 mg, 1.13 mmol) and commercially available (1S,2S)-(+)-2-amino-3-methoxy-1-phenyl-1-propanol (200 mg, 1.10 mmol) in DMF (5 mL) was added HOBt (173 mg, 1.13 mmol), DIPEA (0.42 mL, 2.41 mmol) and EDCI (260 mg, 1.36 mmol). After stirring at rt for 12 h the mixture was added to diluted brine (100 mL, water/brine: 1/1). Extraction with ethyl acetate (4×25 mL), washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) followed by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate). The title compound was obtained as colourless solid. δH (CD3OD): 3.37 (3H, s), 3.34 (1H, dd), 3.66 (1H, dd), 4.53 (1H, ddd), 5.03 (1H, d), 7.15 (1H, s), 7.25-7.45 (5H, 3m), 7.68 (1H, s), 8.58 (1H, s); m/z (ES+)=360.22 [M+H]+; RT=3.12 min. Extraction with ethyl acetate (4×25 mL) washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 223 mg, 1.13 mmol) and commercially available (1S,2S)-(+)-2-amino-3-methoxy-1-phenyl-1-propanol (200 mg, 1.10 mmol) in DMF (5 mL) was added HOBt (173 mg, 1.13 mmol), DIPEA (0.42 mL, 2.41 mmol) and EDCI (260 mg, 1.36 mmol). After stirring at rt for 12 h the mixture was added to diluted brine (100 mL, water/brine: 1/1). Extraction with ethyl acetate (4×25 mL), washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) followed by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate). The title compound was obtained as colourless solid. δH (CD3OD): 3.37 (3H, s), 3.34 (1H, dd), 3.66 (1H, dd), 4.53 (1H, ddd), 5.03 (1H, d), 7.15 (1H, s), 7.25-7.45 (5H, 3m), 7.68 (1H, s), 8.58 (1H, s); m/z (ES+)=360.22 [M+H]+; RT=3.12 min. Extraction with ethyl acetate (4×25 mL) washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1S,2S)-2-amino-3-methoxy-1-phenyl-1-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 5.3 mmol). The mixture was stirred at reflux for 2.5 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50° C.), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, 1H, J=9.8 Hz), 3.53 (m, 1H), 3.37 (m, 1H). 3.26 (m, 1H), 3.17 (m, 6H), 2.91 (t, 2H, J=7.3 Hz), 2.07 (m, 2H). 13C NMR (D2O, 125 MHz) δ ppm 139.09, 129.33, 129.27, 127.11, 70.85, 66.29, 62.62, 58.76, 48.14, 44.24, 21.47. [α]D=+42.6° (c=0.00091 in water), ES-MS 302 (M−1). at reflux for 2.5 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EG (1.0 g, 63%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1S,2S)-2-amino-3-methoxy-1-phenyl-1-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 5.3 mmol). The mixture was stirred at reflux for 2.5 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50° C.), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, 1H, J=9.8 Hz), 3.53 (m, 1H), 3.37 (m, 1H) 3.26 (m, 1H), 3.17 (m, 6H), 2.91 (t, 2H, J=7.3 Hz), 2.07 (m, 2H). 13C NMR D2O, 125 MHz) δ ppm 139.09, 129.33, 129.27, 127.11, 70.85, 66.29, 62.62, 58.76, 48.14, 44.24, 21.47. [C]D=+42.6° (c=0.00091 in water), ES-MS 302 (M−1). at reflux for 2.5 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EG (1.0 g, 63%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1S,2S)-2-amino-3-methoxy-1-phenyl-1-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 5.3 mmol). The mixture was stirred at reflux for 2.5 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50° C.), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, 1H, J=9.8 Hz), 3.53 (m, 1H), 3.37 (m, 1H) 3.26 (m, 1H), 3.17 (m, 6H), 2.91 (t, 2H, J=7.3 Hz), 2.07 (m, 2H). 13C NMR D2O, 125 MHz) δ ppm 139.09, 129.33, 129.27, 127.11, 70.85, 66.29, 62.62, 58.76, 48.14, 44.24, 21.47. [C]D=+42.6° (c=0.00091 in water), ES-MS 302 (M−1). at reflux for 2.5 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EG (1.0 g, 63%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 223 mg, 1.13 mmol) and commercially available (1S,2S)-(+)-2-amino-3-methoxy-1-phenyl-1-propanol (200 mg, 1.10 mmol) in DMF (5 mL) was added HOBt (173 mg, 1.13 mmol), DIPEA (0.42 mL, 2.41 mmol) and EDCI (260 mg, 1.36 mmol). After stirring at rt for 12 h the mixture was added to diluted brine (100 mL, water/brine: 1/1). Extraction with ethyl acetate (4×25 mL), washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) followed by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate). The title compound was obtained as colourless solid. δH (CD3OD): 3.37 (3H, s), 3.34 (1H, dd), 3.66 (1H, dd), 4.53 (1H, ddd), 5.03 (1H, d), 7.15 (1H, s), 7.25-7.45 (5H, 3m), 7.68 (1H, s), 8.58 (1H, s); m/z (ES+)=360.22 [M+H]+; RT=3.12 min. Extraction with ethyl acetate (4×25 mL) washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 223 mg, 1.13 mmol) and commercially available (1S,2S)-(+)-2-amino-3-methoxy-1-phenyl-1-propanol (200 mg, 1.10 mmol) in DMF (5 mL) was added HOBt (173 mg, 1.13 mmol), DIPEA (0.42 mL, 2.41 mmol) and EDCI (260 mg, 1.36 mmol). After stirring at rt for 12 h the mixture was added to diluted brine (100 mL, water/brine: 1/1). Extraction with ethyl acetate (4×25 mL), washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) followed by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate). The title compound was obtained as colourless solid. δH (CD3OD): 3.37 (3H, s), 3.34 (1H, dd), 3.66 (1H, dd), 4.53 (1H, ddd), 5.03 (1H, d), 7.15 (1H, s), 7.25-7.45 (5H, 3m), 7.68 (1H, s), 8.58 (1H, s); m/z (ES+)=360.22 [M+H]+; RT=3.12 min. Extraction with ethyl acetate (4×25 mL) washing of the combined extracts with diluted hydrochloric acid (1M, 30 ml), diluted aqueous sodium hydroxide solution (1M, 30 ml) and brine (30 mL) by drying over magnesium sulphate gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (1S,2S)-2-amino-3-methoxy-1-phenyl-1-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 5.3 mmol). The mixture was stirred at reflux for 2.5 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50° C.), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, 1H, J=9.8 Hz), 3.53 (m, 1H), 3.37 (m, 1H). 3.26 (m, 1H), 3.17 (m, 6H), 2.91 (t, 2H, J=7.3 Hz), 2.07 (m, 2H). 13C NMR (D2O, 125 MHz) δ ppm 139.09, 129.33, 129.27, 127.11, 70.85, 66.29, 62.62, 58.76, 48.14, 44.24, 21.47. [α]D=+42.6° (c=0.00091 in water), ES-MS 302 (M−1). at reflux for 2.5 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EG (1.0 g, 63%)