7-bromo-3,4-dihydro-2H-isoquinolin-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7-bromo-3,4-dihydroisoquinolin-1(2H)-one (Intermediate 23-1, 60 mg, 0.265 mmol), 1-fluoro-4-iodobenzene (118 mg, 0.531 mmol), potassium carbonate (36.7 mg, 0.265 mmol) and copper (I) iodide (10.11 mg, 0.053 mmol) in DMF (1.000 mL) was heated at 130° C. for 5 h. The mixture was cooled to rt and filtered through a Celite pad, and the solids were washed with EtOAc. The filtrate was washed with water and brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 90:10 to 60:40 hexane-EtOAc) to give 7-bromo-2-(4-fluorophenyl)-3,4-dihydroisoquinolin-1(2H)-one (40 mg, 47%). 1H NMR (400 MHz, chloroform-d) δ 7.15-7.27 (4H, m), 7.04-7.13 (2H, m), 6.48 (1H, d, J=1.94 Hz), 2.96-3.08 (2H, m), 2.73-2.84 (2H, m). Mass spectrum m/z 320, 322 (M+H)+. The mixture was cooled to rt filtered through a Celite pad the solids were washed with EtOAc The filtrate was washed with water and brine dried concentrated The residue was purified by column chromatography ( eluting with a gradient from 90:10 to 60:40 hexane-EtOAc)

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 7-bromo-3,4-dihydroisoquinolin-1(2H)-one (Intermediate 23-1, 60 mg, 0.265 mmol), 1-fluoro-4-iodobenzene (118 mg, 0.531 mmol), potassium carbonate (36.7 mg, 0.265 mmol) and copper (I) iodide (10.11 mg, 0.053 mmol) in DMF (1.000 mL) was heated at 130° C. for 5 h. The mixture was cooled to rt and filtered through a Celite pad, and the solids were washed with EtOAc. The filtrate was washed with water and brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 90:10 to 60:40 hexane-EtOAc) to give 7-bromo-2-(4-fluorophenyl)-3,4-dihydroisoquinolin-1(2H)-one (40 mg, 47%). 1H NMR (400 MHz, chloroform-d) δ 7.15-7.27 (4H, m), 7.04-7.13 (2H, m), 6.48 (1H, d, J=1.94 Hz), 2.96-3.08 (2H, m), 2.73-2.84 (2H, m). Mass spectrum m/z 320, 322 (M+H)+. The mixture was cooled to rt filtered through a Celite pad the solids were washed with EtOAc The filtrate was washed with water and brine dried concentrated The residue was purified by column chromatography ( eluting with a gradient from 90:10 to 60:40 hexane-EtOAc)

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

実験手順: Sodium azide (0.431 g, 6.63 mmol) was added slowly to a mixture of 6-bromo-2,3-dihydro-1H-inden-1-one (1 g, 4.74 mmol) and methanesulfonic acid (15 mL, 231 mmol) in DCM (30 mL) at 0° C. The mixture was stirred at rt for 15 hrs, then was carefully quenched with 1 M aqueous sodium hydroxide (50 mL). The aqueous layer was extracted with DCM (3×50 mL), and the combined organic layers were washed with water (20 mL) and brine (20 mL), dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 90:10 hexane-EtOAc to EtOAc) to give 7-bromo-3,4-dihydroisoquinolin-1(2H)-one as white solid (650 mg, 61%). 1H NMR (400 MHz, chloroform-d) δ 8.35 (1H, br. s.), 7.08-7.17 (1 H, m), 6.98-7.06 (1H, m), 6.95 (1H, d, J=1.98 Hz), 2.93 (2H, t, J=7.59 Hz), 2.49-2.68 (2H, m). Mass spectrum m/z 226, 228 (M+H)+. was carefully quenched with 1 M aqueous sodium hydroxide (50 mL) The aqueous layer was extracted with DCM (3×50 mL) the combined organic layers were washed with water (20 mL) and brine (20 mL) dried concentrated The residue was purified by column chromatography ( eluting with a gradient from 90:10 hexane-EtOAc to EtOAc)

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

実験手順: A solution of 7-bromo-3,4-dihydro-1(2H)-isoquinolinone (0.679 g, 3.004 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) in 1,2-dimethoxyethane (30 ml) was stirred at room temperature for 0.5 h before addition of 2,4,6-trivinylcyclotriboroxane.pyridine complex (for a synthesis see Kerins, Fergal; O'Shea, Donal F. J. Org. Chem. (2002), 67(14), 4968) (295 mg, 1.218 mmol), K2CO3 (415 mg, 3.004 mmol) and water (10 ml). The reaction was heated at reflux for 1.5 h before cooling to room temperature and addition of water (50 ml). The mixture was extracted with 10% methanol/dichloromethane (3×100 ml), the organic layers were dried with magnesium sulphate and evaporated. Chromatography on silica, eluting with 0-100% ethyl acetate/hexane, gave the product (456 mg, 88%). The reaction was heated at reflux for 1.5 h The mixture was extracted with 10% methanol/dichloromethane (3×100 ml) the organic layers were dried with magnesium sulphate evaporated Chromatography on silica, eluting with 0-100% ethyl acetate/hexane

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7-amino-3,4-dihydro-1(2H)-isoquinolinone, (0.77 g, 4.77 mmol)(for a synthesis see Girard, Yves; Atkinson, Joseph G.; Belanger, Patrice C.; Fuentes, Jose J.; Rokach, Joshua; Rooney, C. Stanley; Remy, David C.; Hunt, Cecilia A J. Org. Chem. (1983), 48(19), 3220) in acetonitrile (10 ml) at 0° C. was added 48% aqueous HBr (10 ml, precooled to 0° C.). The mixture was stirred at 0° C. for 0.5 h before addition of a solution of NaNO2 (0.379 g, 5.49 mmol) in water (2 ml) over 0.4 h. The reaction was then stirred at 0° C. for 0.5 h and then CuBr (0.822 g, 5.726 mmol) was added portionwise over 10 min. The reaction mixture was then warmed to room temperature, stirred at room temperature for 0.5 h and then at 70° C. for 1 h. The reaction mixture was then cooled to 0° C., water (60 ml) was added and the mixture stirred at 0° C. for 1 h before filtering and drying in vacuo. The residue was dissolved in 10% methanol/dichloromethane, dried with magnesium sulphate and evaporated to give the desired product (0.679 g, 63%). The reaction mixture was then warmed to room temperature stirred at room temperature for 0.5 h at 70° C. for 1 h The reaction mixture was then cooled to 0° C. the mixture stirred at 0° C. for 1 h before filtering drying in vacuo The residue was dissolved in 10% methanol/dichloromethane dried with magnesium sulphate evaporated

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

実験手順: A solution of 7-bromo-3,4-dihydro-1(2H)-isoquinolinone (0.679 g, 3.004 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) in 1,2-dimethoxyethane (30 ml) was stirred at room temperature for 0.5 h before addition of 2,4,6-trivinylcyclotriboroxane.pyridine complex (for a synthesis see Kerins, Fergal; O'Shea, Donal F. J. Org. Chem. (2002), 67(14), 4968) (295 mg, 1.218 mmol), K2CO3 (415 mg, 3.004 mmol) and water (10 ml). The reaction was heated at reflux for 1.5 h before cooling to room temperature and addition of water (50 ml). The mixture was extracted with 10% methanol/dichloromethane (3×100 ml), the organic layers were dried with magnesium sulphate and evaporated. Chromatography on silica, eluting with 0-100% ethyl acetate/hexane, gave the product (456 mg, 88%). The reaction was heated at reflux for 1.5 h The mixture was extracted with 10% methanol/dichloromethane (3×100 ml) the organic layers were dried with magnesium sulphate evaporated Chromatography on silica, eluting with 0-100% ethyl acetate/hexane

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7-amino-3,4-dihydro-1(2H)-isoquinolinone, (0.77 g, 4.77 mmol)(for a synthesis see Girard, Yves; Atkinson, Joseph G.; Belanger, Patrice C.; Fuentes, Jose J.; Rokach, Joshua; Rooney, C. Stanley; Remy, David C.; Hunt, Cecilia A J. Org. Chem. (1983), 48(19), 3220) in acetonitrile (10 ml) at 0° C. was added 48% aqueous HBr (10 ml, precooled to 0° C.). The mixture was stirred at 0° C. for 0.5 h before addition of a solution of NaNO2 (0.379 g, 5.49 mmol) in water (2 ml) over 0.4 h. The reaction was then stirred at 0° C. for 0.5 h and then CuBr (0.822 g, 5.726 mmol) was added portionwise over 10 min. The reaction mixture was then warmed to room temperature, stirred at room temperature for 0.5 h and then at 70° C. for 1 h. The reaction mixture was then cooled to 0° C., water (60 ml) was added and the mixture stirred at 0° C. for 1 h before filtering and drying in vacuo. The residue was dissolved in 10% methanol/dichloromethane, dried with magnesium sulphate and evaporated to give the desired product (0.679 g, 63%). The reaction mixture was then warmed to room temperature stirred at room temperature for 0.5 h at 70° C. for 1 h The reaction mixture was then cooled to 0° C. the mixture stirred at 0° C. for 1 h before filtering drying in vacuo The residue was dissolved in 10% methanol/dichloromethane dried with magnesium sulphate evaporated

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: A solution of 7-bromo-3,4-dihydro-1(2H)-isoquinolinone (0.679 g, 3.004 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) in 1,2-dimethoxyethane (30 ml) was stirred at room temperature for 0.5 h before addition of triethenylboroxin.pyridine complex (295 mg, 1.218 mmol), K2CO3 (415 mg, 3.004 mmol) and water (10 ml). The reaction was heated at reflux for 1.5 h before cooling to room temperature and addition of water (50 ml). The mixture was extracted with 10% methanol/dichloromethane (3×100 ml), the organic layers were dried with magnesium sulphate and evaporated. Chromatography on silica, eluting with 0-100% ethyl acetate/hexane, gave the product (456 mg, 88%). The reaction was heated at reflux for 1.5 h The mixture was extracted with 10% methanol/dichloromethane (3×100 ml) the organic layers were dried with magnesium sulphate evaporated Chromatography on silica, eluting with 0-100% ethyl acetate/hexane

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

実験手順: A solution of 7-bromo-3,4-dihydro-1(2H)-isoquinolinone (0.679 g, 3.004 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) in 1,2-dimethoxyethane (30 ml) was stirred at room temperature for 0.5 h before addition of triethenylboroxin.pyridine complex (295 mg, 1.218 mmol), K2CO3 (415 mg, 3.004 mmol) and water (10 ml). The reaction was heated at reflux for 1.5 h before cooling to room temperature and addition of water (50 ml). The mixture was extracted with 10% methanol/dichloromethane (3×100 ml), the organic layers were dried with magnesium sulphate and evaporated. Chromatography on silica, eluting with 0-100% ethyl acetate/hexane, gave the product (456 mg, 88%). The reaction was heated at reflux for 1.5 h The mixture was extracted with 10% methanol/dichloromethane (3×100 ml) the organic layers were dried with magnesium sulphate evaporated Chromatography on silica, eluting with 0-100% ethyl acetate/hexane

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

実験手順: A solution of 7-bromo-3,4-dihydro-1(2H)-isoquinolinone (0.679 g, 3.004 mmol) and tetrakis(triphenylphosphine)palladium(0) (174 mg, 0.150 mmol) in 1,2-dimethoxyethane (30 ml) was stirred at room temperature for 0.5 h before addition of triethenylboroxin.pyridine complex (295 mg, 1.218 mmol), K2CO3 (415 mg, 3.004 mmol) and water (10 ml). The reaction was heated at reflux for 1.5 h before cooling to room temperature and addition of water (50 ml). The mixture was extracted with 10% methanol/dichloromethane (3×100 ml), the organic layers were dried with magnesium sulphate and evaporated. Chromatography on silica, eluting with 0-100% ethyl acetate/hexane, gave the product (456 mg, 88%). The reaction was heated at reflux for 1.5 h The mixture was extracted with 10% methanol/dichloromethane (3×100 ml) the organic layers were dried with magnesium sulphate evaporated Chromatography on silica, eluting with 0-100% ethyl acetate/hexane