N-methyl-2-morpholin-4-ylethanamine

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:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a sealed tube was added 3-chloro-1,2-benzisoxazole (3.0 g) and N-methyl-N-[2-(4-morpholinyl)ethyl]-amine (12.7 g). The reaction was heated to 140° C. over 72 hours and then cooled to room temperature. The residue was partitioned between EtOAc and water, extracted again with EtOAc, and the organic phase was dried over MgSO4 and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM provided the product (1.2 g), as an oil. cooled to room temperature The residue was partitioned between EtOAc and water extracted again with EtOAc the organic phase was dried over MgSO4 concentrated in vacuo Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM

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

実験手順: To a sealed tube was added 3-chloro-1,2-benzisoxazole (3.0 g) and N-methyl-N-[2-(4-morpholinyl)ethyl]-amine (12.7 g). The reaction was heated to 140° C. over 72 hours and then cooled to room temperature. The residue was partitioned between EtOAc and water, extracted again with EtOAc, and the organic phase was dried over MgSO4 and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM provided the product (1.2 g), as an oil. cooled to room temperature The residue was partitioned between EtOAc and water extracted again with EtOAc the organic phase was dried over MgSO4 concentrated in vacuo Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM

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

実験手順: To a sealed tube was added 3-chloro-6-methoxy-1,2-benzisoxazole (6.0 g) and N-methyl-N-[2-(4-morpholinyl)ethyl]-amine (13.8 g). The reaction was heated to 140° C. over 48 hours and then cooled to room temperature. The residue was partitioned between ethyl acetate (EtOAc) and water, extracted again with EtOAc, and the organic phase was dried over magnesium sulfate (MgSO4) and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 1% methanol/dichloromethane (MeOH/DCM) provided the product (4.7 g), m.p. 43°-44° C. cooled to room temperature The residue was partitioned between ethyl acetate (EtOAc) and water extracted again with EtOAc the organic phase was dried over magnesium sulfate (MgSO4) concentrated in vacuo Flash column chromatography (silica gel) eluting with 1% methanol/dichloromethane (MeOH/DCM)

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

実験手順: Similar reaction of crude 5-chloro-2,4-dinitrobenzoyl chloride in Et2O with 4-[2-(methylamino)ethyl]morpholine (2 equiv) in water, followed by chromatography of the product on alumina-90, eluting with EtOAc, gave 5-chloro-N-methyl-N-[2-(4-morpholino)ethyl]-2,4-dinitrobenzamide (48%), mp (EtOAc/iPr2O) 123-123.5° C. 1H NMR [(CD3)2SO] [rotamer mixture] δ8.94 & 8.94 (2xs, 1H, H-3), 8.13 & 8.09 (2xs, 1H, H-6), [3.63-3.54 (m), 3.51, t (J=4.6 Hz) & 3.28-3.18(m), 6H, O(CH2)CH2, N(CH3)CH2], 3.05 & 2.89 (2xs, 3H, CH3), [2.57 (t, J=6.6 Hz), 2.50-2.38 (m) & 2.25 (t, J=4 3 Hz), 6H, CH2N(CH2)CH2]. Anal. Calcd. for C14H17ClN4O6: C, 45.11,H, 4.60; N, 15.03. Found: C, 45.01;H, 4,43, N, 15.02%. eluting with EtOAc

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

実験手順: Similar reaction of crude 5-chloro-2,4-dinitrobenzoyl chloride in Et2O with 4-[2-(methylamino)ethyl]morpholine (2 equiv) in water, followed by chromatography of the product on alumina-90, eluting with EtOAc, gave 5-chloro-N-methyl-N-[2-(4-morpholino)ethyl]-2,4-dinitrobenzamide (48%), mp (EtOAc/iPr2O) 123-123.5° C. 1H NMR [(CD3)2SO] [rotamer mixture] δ8.94 & 8.94 (2xs, 1H, H-3), 8.13 & 8.09 (2xs, 1H, H-6), [3.63-3.54 (m), 3.51, t (J=4.6 Hz) & 3.28-3.18(m), 6H, O(CH2)CH2, N(CH3)CH2], 3.05 & 2.89 (2xs, 3H, CH3), [2.57 (t, J=6.6 Hz), 2.50-2.38 (m) & 2.25 (t, J=4 3 Hz), 6H, CH2N(CH2)CH2]. Anal. Calcd. for C14H17ClN4O6: C, 45.11,H, 4.60; N, 15.03. Found: C, 45.01;H, 4,43, N, 15.02%. eluting with EtOAc

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

実験手順: To a sealed tube was added 3-chloro-1,2-benzisoxazole (3.0 g) and N-methyl-N-[2-(4-morpholinyl)ethyl]-amine (12.7 g). The reaction was heated to 140° C. over 72 hours and then cooled to room temperature. The residue was partitioned between EtOAc and water, extracted again with EtOAc, and the organic phase was dried over MgSO4 and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM provided the product (1.2 g), as an oil. cooled to room temperature The residue was partitioned between EtOAc and water extracted again with EtOAc the organic phase was dried over MgSO4 concentrated in vacuo Flash column chromatography (silica gel) eluting with 1-3% MeOH/DCM

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

実験手順: To a solution of N-methyl-2-morpholinoethanamine (2.1 g, 13.12 mmol, 1.00 equiv, 90%) in dichloromethane (20 mL) at 0-5° C. was added triethylamine (1.47 g, 14.55 mmol, 1.00 equiv) followed by dropwise addition of a solution of methyl 3-(chlorocarbonyl)benzoate (3.3 g, 15.00 mmol, 1.20 equiv, 90%) in dichloromethane (10 mL). The resulting solution was then stirred for 3 h at room temperature. The mixture was diluted with 100 mL of dichloromethane, washed with 1×30 mL of 10% sodium bicarbonate and 1×30 mL of brine, dried over sodium sulfate and then concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane:methanol (20:1) to afford 4.4 g (99%) of methyl 3-(methyl(2-morpholinoethyl)carbamoyl)benzoate as a brown solid. washed with 1×30 mL of 10% sodium bicarbonate and 1×30 mL of brine dried over sodium sulfate concentrated under vacuum

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of LiAlH4 (7.72 g, 208.65 mmol, 3.00 equiv) in tetrahydrofuran (60 mL) at 0-5° C. was added dropwise a solution of tert-butyl 2-morpholinoethylcarbamate (16 g, 62.61 mmol, 1.00 equiv, 90%) in tetrahydrofuran (40 mL). The resulting solution was then stirred for 2 h at 70° C. in an oil bath. The reaction was then quenched by the addition of 7.7 mL of water, 7.7 mL of 15% sodium hydroxide, and 23.1 mL of water. The solids were filtered out. The mixture was dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with dichloromethane:methanol (0.5% triethylamine) (20:1) to afford 4.2 g (42%) of N-methyl-2-morpholinoethanamine as a brown oil. The reaction was then quenched by the addition of 7.7 mL of water, 7.7 mL of 15% sodium hydroxide, and 23.1 mL of water The solids were filtered out The mixture was dried over sodium sulfate concentrated under vacuum eluted with dichloromethane