azepan-4-ol

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:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-bromo-3-chlorosulfonyl-benzoate (7.22 g, 23.03 mmol, 1.00 Eq) in DCM (100 mL) was added azepan-4-ol (2.65 g, 23.03 mmol, 1.00 Eq) and TEA (2.33 g, 23.03 mmol, 1.00 Eq). The resulting mixture was stirred at 25° C. until the starting material was consumed. The solvent was removed and the residue was purified by silica gel chromatography (PE:EA=1:1) to give desired compound methyl 4-bromo-3-(4-hydroxyazepan-1-yl)sulfonyl-benzoate (7.00 g, 17.85 mmol, 77.49% yield). LCMS: 393/395 [M+1]. was consumed The solvent was removed the residue was purified by silica gel chromatography (PE:EA=1:1)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-bromo-3-chlorosulfonyl-benzoate (7.22 g, 23.03 mmol, 1.00 Eq) in DCM (100 mL) was added azepan-4-ol (2.65 g, 23.03 mmol, 1.00 Eq) and TEA (2.33 g, 23.03 mmol, 1.00 Eq). The resulting mixture was stirred at 25° C. until the starting material was consumed. The solvent was removed and the residue was purified by silica gel chromatography (PE:EA=1:1) to give desired compound methyl 4-bromo-3-(4-hydroxyazepan-1-yl)sulfonyl-benzoate (7.00 g, 17.85 mmol, 77.49% yield). LCMS: 393/395 [M+1]. was consumed The solvent was removed the residue was purified by silica gel chromatography (PE:EA=1:1)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 4-bromo-3-chlorosulfonyl-benzoate (7.22 g, 23.03 mmol, 1.00 Eq) in DCM (100 mL) was added azepan-4-ol (2.65 g, 23.03 mmol, 1.00 Eq) and TEA (2.33 g, 23.03 mmol, 1.00 Eq). The resulting mixture was stirred at 25° C. until the starting material was consumed. The solvent was removed and the residue was purified by silica gel chromatography (PE:EA=1:1) to give desired compound methyl 4-bromo-3-(4-hydroxyazepan-1-yl)sulfonyl-benzoate (7.00 g, 17.85 mmol, 77.49% yield). LCMS: 393/395 [M+1]. was consumed The solvent was removed the residue was purified by silica gel chromatography (PE:EA=1:1)

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a round bottom flask was added azepan-4-ol (300 mg, 2.60 mmol), 1-fluoro-4-nitrobenzene (368 mg, 2.60 mmol), Cs2CO3 (1018 mg, 3.13 mmol) and DMF (5 mL). The reaction was stirred at 100° C. for 10 hrs. The reaction was diluted with EtOAc (50 ml), washed with water (4×20 ml) and saturated aqueous NaCl (25 ml). The organic layer was dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/He) to give the product, 1-(4-nitrophenyl)azepan-4-ol (480 mg, 2.032 mmol, 78% yield) as a light yellow solid. Anal. Calcd. for C12H16N2O3 m/z 236.2, found: 237.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.18-8.03 (m, 2H), 6.71-6.57 (m, 2H), 4.00 (br. s., 1H), 3.74-3.60 (m, 1H), 3.60-3.41 (m, 3H), 2.22-2.01 (m, 2H), 1.95-1.72 (m, 4H); 13C NMR (101 MHz, CDCl3) δ ppm 153.41, 136.89, 126.38, 110.02, 69.88, 49.24, 44.00, 35.87, 34.96, 21.59. washed with water (4×20 ml) and saturated aqueous NaCl (25 ml) The organic layer was dried over MgSO4 filtered concentrated The resulting residue was purified eluting with a gradient of 0-100% EtOAc/He)

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

実験手順: This compound is synthesized analogously to example 150 from 4-isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)-piperidin-4-yl]-amide, 190 and azepan-4-ol.

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

実験手順: This compound is synthesized analogously to example 150 from 4-isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)-piperidin-4-yl]-amide, 190 and azepan-4-ol.

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

実験手順: A solution of 58 mg (0.51 mmol) azepan-4-ol in 5 ml dimethylacetamide was stirred with 45 mg (1.52 mmol) 80 percent sodium hydride for 45 minutes at room temperature. Then 150 mg (0.51 mmol) 6-fluoro-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one in dimethylacetamide was added. The reaction mixture was heated to 80° C. for 3 days during which additional amounts of azepan-4-ol and sodium hydride were added until complete conversion of the 6-fluoro-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one was obtained. The reaction mixture was slowly added to 10 ml water and after 1 h of stirring the product was isolated by filtration and dried overnight in vacuum. 82 mg of 6-(azepan-4-yloxy)-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one were obtained. was obtained was isolated by filtration dried overnight in vacuum

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

実験手順: This compound is synthesized analogously to example 150 from 4-isobutoxy-1H-indole-2-carboxylic acid [1-(2-hydroxy-ethyl)piperidin-4-yl]-amide, 190 and azepan-4-ol.