3-methoxy-4-morpholin-4-ylaniline

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: 1-Fluoro-2-methoxy-4-nitro-benzene using Morpholine was converted in an analogous manner to Example 171b, to 4-(2-Methoxy-4-nitro-phenyl)-morpholine, which was converted in an analogous manner to Example 31f, to 3-Methoxy-4-morpholin-4-yl-phenylamine, which was converted, in an analogous procedure to Example 1d, to (2,5-Dichloro-pyrimidin-4-yl)-(3-methoxy-4-morpholin-4-yl-phenyl)-amine, which was converted to the title compound in an analogous manner to Example 61e using 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (52 mg, 0.00018 mol). Product isolated as an off-white solid (0.053 g, 48%). MP: 203-206° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.07 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.16-7.12 (m, 1H), 7.12-7.09 (m, 1H), 6.95 (s, 1H), 6.90 (d, 1H, J=8.6 Hz), 6.61 (s, 1H), 3.93-3.89 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.26 (br s, 2H), 3.13 (s, 3H), 3.10-3.05 (m, 4H), 2.97 (s, 3H), 2.90-2.82 (m, 2H), 2.75-2.56 (m, 6H). MS: 596.24 (MH)+.

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

実験手順: 1-Fluoro-2-methoxy-4-nitro-benzene using Morpholine was converted in an analogous manner to Example 171b, to 4-(2-Methoxy-4-nitro-phenyl)-morpholine, which was converted in an analogous manner to Example 31f, to 3-Methoxy-4-morpholin-4-yl-phenylamine, which was converted, in an analogous procedure to Example 1d, to (2,5-Dichloro-pyrimidin-4-yl)-(3-methoxy-4-morpholin-4-yl-phenyl)-amine, which was converted to the title compound in an analogous manner to Example 61e using 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (52 mg, 0.00018 mol). Product isolated as an off-white solid (0.053 g, 48%). MP: 203-206° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.07 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.16-7.12 (m, 1H), 7.12-7.09 (m, 1H), 6.95 (s, 1H), 6.90 (d, 1H, J=8.6 Hz), 6.61 (s, 1H), 3.93-3.89 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.26 (br s, 2H), 3.13 (s, 3H), 3.10-3.05 (m, 4H), 2.97 (s, 3H), 2.90-2.82 (m, 2H), 2.75-2.56 (m, 6H). MS: 596.24 (MH)+.

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-methoxy-4-nitro-phenyl)-morpholine (Step A, 1.0 g, 4.2 mmol) in EtOH (25 mL) at 20° C. was added Pd/C (100 mg). The flask was capped with a rubber septum and H2 pressure applied through a balloon/needle. The reaction was stirred at 20° C. for 12 h, filtered through sand/Celite® and concentrated. Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH) afforded 3-methoxy-4-morpholin-4-yl-phenylamine as a purple solid. The flask was capped with a rubber septum and H2 pressure filtered through sand/Celite® concentrated Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH)

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: 1-Fluoro-2-methoxy-4-nitro-benzene using Morpholine was converted in an analogous manner to Example 171b, to 4-(2-Methoxy-4-nitro-phenyl)-morpholine, which was converted in an analogous manner to Example 31f, to 3-Methoxy-4-morpholin-4-yl-phenylamine, which was converted, in an analogous procedure to Example 1d, to (2,5-Dichloro-pyrimidin-4-yl)-(3-methoxy-4-morpholin-4-yl-phenyl)-amine, which was converted to the title compound in an analogous manner to Example 61e using 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (52 mg, 0.00018 mol). Product isolated as an off-white solid (0.053 g, 48%). MP: 203-206° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.07 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.16-7.12 (m, 1H), 7.12-7.09 (m, 1H), 6.95 (s, 1H), 6.90 (d, 1H, J=8.6 Hz), 6.61 (s, 1H), 3.93-3.89 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.26 (br s, 2H), 3.13 (s, 3H), 3.10-3.05 (m, 4H), 2.97 (s, 3H), 2.90-2.82 (m, 2H), 2.75-2.56 (m, 6H). MS: 596.24 (MH)+.

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-methoxy-4-nitro-phenyl)-morpholine (1.0 g, 4.2 mmol, Step B) in EtOH (25 mL) at 20 ° C was added Pd/C (100 mg). The flask was capped with a rubber septum and H2 pressure was applied through a balloon/needle. The reaction mixture was stirred at 20° C. for 12 h, filtered through sand/Celite® and concentrated. Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH) afforded 3-methoxy-4-morpholin-4-yl-phenylamine as a purple solid. The flask was capped with a rubber septum and H2 pressure filtered through sand/Celite® concentrated Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH)

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

実験手順: 1-Fluoro-2-methoxy-4-nitro-benzene using Morpholine was converted in an analogous manner to Example 171b, to 4-(2-Methoxy-4-nitro-phenyl)-morpholine, which was converted in an analogous manner to Example 31f, to 3-Methoxy-4-morpholin-4-yl-phenylamine, which was converted, in an analogous procedure to Example 1d, to (2,5-Dichloro-pyrimidin-4-yl)-(3-methoxy-4-morpholin-4-yl-phenyl)-amine, which was converted to the title compound in an analogous manner to Example 61e using 2-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (52 mg, 0.00018 mol). Product isolated as an off-white solid (0.053 g, 48%). MP: 203-206° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 8.07 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.16-7.12 (m, 1H), 7.12-7.09 (m, 1H), 6.95 (s, 1H), 6.90 (d, 1H, J=8.6 Hz), 6.61 (s, 1H), 3.93-3.89 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.26 (br s, 2H), 3.13 (s, 3H), 3.10-3.05 (m, 4H), 2.97 (s, 3H), 2.90-2.82 (m, 2H), 2.75-2.56 (m, 6H). MS: 596.24 (MH)+.

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(2-methoxy-4-nitro-phenyl)-morpholine (Step A, 1.0 g, 4.2 mmol) in EtOH (25 mL) at 20° C. was added Pd/C (100 mg). The flask was capped with a rubber septum and H2 pressure applied through a balloon/needle. The reaction was stirred at 20° C. for 12 h, filtered through sand/Celite® and concentrated. Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH) afforded 3-methoxy-4-morpholin-4-yl-phenylamine as a purple solid. The flask was capped with a rubber septum and H2 pressure filtered through sand/Celite® concentrated Purification by chromatography of the crude mixture (97:3 CH2Cl2:MeOH)