2-bromo-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (174b) (341 mg, 0.66 mmol), 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (305b) (84.0 mg, 0.37 mmol), K2PO4 (420 mg, 1.98 mmol), X-Phos (Strem Chemicals, Inc., 17.5 mg, 0.037 mmol), and Pd2dba3 (Aldrich, 16.8 mg, 0.018 mmol) in a mixture of dioxane (3.0 mL) and water (0.60 mL) was stirred under argon at 105° C. for 1.5 h. The reaction mixture was subsequently diluted with DCM (10 mL) and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (128 mg, 0.35 mmol, 96% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.77 (1H, br. s.), 7.83 (1H, dd, J=7.4, 1.0 Hz), 7.56 (1H, dd, J=7.8, 1.0 Hz), 7.32 (2H, t, J=7.7 Hz), 7.09 (1H, d, J=2.7 Hz), 6.01 (1H, s), 3.21 (2H, dd, J=8.5, 4.6 Hz), 3.02 (2H, t, J=6.5 Hz), 2.55 (3H, s), 1.92-2.01 (2H, m), 1.58 (9H, s). m/z (ESI, +ve) 364.2 (M+H)+. concentrated onto silica gel Chromatographic purification (silica gel, 0-100% EtOAc/hexanes

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

実験手順: Thionyl chloride (0.06 mL, 0.90 mmol) was added to a solution of 2-bromo-6,7-dihydro-1H-indol-4(5H)-one oxime (305a) (186 mg, 0.81 mmol) in THF (8.0 mL) at 25° C., and the resulting solution was stirred at 25° C. for 18 h. The reaction mixture was then diluted with EtOAc (40 mL), sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (102 mg, 0.44 mmol, 55% yield) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.59 (1H, br. s.), 7.36 (1H, t, J=4.5 Hz), 6.27 (1H, d, J=2.7 Hz), 3.09-3.16 (2H, m), 2.82 (2H, t, J=6.6 Hz), 1.82-1.91 (2H, m). m/z (ESI, +ve) 228.9/231.1 (M+H)+. sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL) dried over Na2SO4 filtered concentrated in vacuo Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM)

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

実験手順: Thionyl chloride (0.06 mL, 0.90 mmol) was added to a solution of 2-bromo-6,7-dihydro-1H-indol-4(5H)-one oxime (305a) (186 mg, 0.81 mmol) in THF (8.0 mL) at 25° C., and the resulting solution was stirred at 25° C. for 18 h. The reaction mixture was then diluted with EtOAc (40 mL), sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (102 mg, 0.44 mmol, 55% yield) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.59 (1H, br. s.), 7.36 (1H, t, J=4.5 Hz), 6.27 (1H, d, J=2.7 Hz), 3.09-3.16 (2H, m), 2.82 (2H, t, J=6.6 Hz), 1.82-1.91 (2H, m). m/z (ESI, +ve) 228.9/231.1 (M+H)+. sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL) dried over Na2SO4 filtered concentrated in vacuo Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (174b) (341 mg, 0.66 mmol), 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (305b) (84.0 mg, 0.37 mmol), K2PO4 (420 mg, 1.98 mmol), X-Phos (Strem Chemicals, Inc., 17.5 mg, 0.037 mmol), and Pd2dba3 (Aldrich, 16.8 mg, 0.018 mmol) in a mixture of dioxane (3.0 mL) and water (0.60 mL) was stirred under argon at 105° C. for 1.5 h. The reaction mixture was subsequently diluted with DCM (10 mL) and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (128 mg, 0.35 mmol, 96% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.77 (1H, br. s.), 7.83 (1H, dd, J=7.4, 1.0 Hz), 7.56 (1H, dd, J=7.8, 1.0 Hz), 7.32 (2H, t, J=7.7 Hz), 7.09 (1H, d, J=2.7 Hz), 6.01 (1H, s), 3.21 (2H, dd, J=8.5, 4.6 Hz), 3.02 (2H, t, J=6.5 Hz), 2.55 (3H, s), 1.92-2.01 (2H, m), 1.58 (9H, s). m/z (ESI, +ve) 364.2 (M+H)+. concentrated onto silica gel Chromatographic purification (silica gel, 0-100% EtOAc/hexanes

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

実験手順: Thionyl chloride (0.06 mL, 0.90 mmol) was added to a solution of 2-bromo-6,7-dihydro-1H-indol-4(5H)-one oxime (305a) (186 mg, 0.81 mmol) in THF (8.0 mL) at 25° C., and the resulting solution was stirred at 25° C. for 18 h. The reaction mixture was then diluted with EtOAc (40 mL), sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-bromo-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one (102 mg, 0.44 mmol, 55% yield) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.59 (1H, br. s.), 7.36 (1H, t, J=4.5 Hz), 6.27 (1H, d, J=2.7 Hz), 3.09-3.16 (2H, m), 2.82 (2H, t, J=6.6 Hz), 1.82-1.91 (2H, m). m/z (ESI, +ve) 228.9/231.1 (M+H)+. sequentially washed with saturated aq. NaHCO3 (2×30 mL) and brine (20 mL) dried over Na2SO4 filtered concentrated in vacuo Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM)