(S)-1-氨基-3-吗啡啉丙烷-2-醇

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-(1H-imidazol-1-ylcarbonyl)-3,5-dimethyl-1H-pyrrole-2-carbaldehyde (6.8 g, 31.3 mmol), (2S)-1-amino-3-morpholin-4-ylpropan-2-ol (10.0 g, 62.5 mmol), 5-chlorooxindole (5.3 g, 31.6 mmol), and THF (100 ml) were mixed and heated to 60° C. After stirring for 68 h at 60° C., triethylamine (14 ml) was added and stirred for 5 h at 60° C. Added 4.6 g of (2S)-1-amino-3-morpholin-4-ylpropan-2-ol, and stirred for 20 h at 60° C. The yellow slurry was cooled to room temperature and filtered. The cake was washed with 2×50 ml THF and dried overnight at 50° C. under house vacuum. 5-[(Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (5.48 g) was obtained with 38% yield. stirred for 5 h at 60° C stirred for 20 h at 60° C The yellow slurry was cooled to room temperature filtered The cake was washed with 2×50 ml THF dried overnight at 50° C. under house vacuum

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m) 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile: 0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ10.86 (1H,bs); 7.75 (1H,d); 7.70 (1H,s); 7.50 (1H,m); 6.88 (2H,m); 4.72 (1H,bs); 3.78 (1H,bs); 3.56 (4H,m); 3.32 (6H,m); 3.15 (1H,m); 2.43 (8H,bm)

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet was charged with 4.92 g 5-Fluorooxindole, 7.0 g Imidazole amide, 15.5 g (R)-1-Amino-3-(4-morpholinyl)-2-propanol, 9.78 g Triethylamine and 88 ml Tetrahydrofuran. The mixture was heated to 60° C. for 16.5 hours. The reaction is cooled to ambient temperature and filtered. The solids obtained are slurried (3) three successive times in acetonitrile at 11 ml/g, dried in vacuo for 3.6 g (25.25%). [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm). A 0.25 L flask fitted with a thermometer, condenser, magnetic stirring, and nitrogen inlet The reaction is cooled to ambient temperature filtered The solids obtained dried in vacuo for 3.6 g (25.25%) [HPLC, Hypersil BDS, C-18, 5μ, (6:4), Acetonitrile:0.1M Ammonium Chloride, PHA-571437=4.05 min.] H1NMR (DMSO): δ 10.86 (1H, bs); 7.75 (1H, d); 7.70 (1H, s); 7.50 (1H, m); 6.88 (2H, m); 4.72 (1H, bs); 3.78 (1H, bs); 3.56 (4H, m); 3.32 (6H, m); 3.15 (1H, m); 2.43 (8H, bm)