5-bromo-8-chloro-9-azatricyclo[8.1.1.02,7]dodeca-2(7),3,5,8-tetraene

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 10-L 4-necked round-bottom flask was placed 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene (260 g, 960.99 mmol, 1.00 equiv), 2-methylpropan-2-ol (6000 mL), and 2,2-dimethoxyethan-1-amine (600 g, 5.71 mol, 6.00 equiv). The resulting solution was stirred at 85° C. for 5 h, cooled to room temperature and concentrated under vacuum. The residue was washed with 2×500 mL water and extracted with 3×500 mL of ethyl acetate. The organic layers were combined and concentrated under vacuum to afford 340 g (crude) of 5-bromo-N-(2,2-dimethoxyethyl)-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraen-8-amine as a black oil. Into a 10-L 4-necked round-bottom flask was placed cooled to room temperature concentrated under vacuum The residue was washed with 2×500 mL water extracted with 3×500 mL of ethyl acetate concentrated under vacuum

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 10-L 4-necked round-bottom flask was placed 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene (260 g, 960.99 mmol, 1.00 equiv), 2-methylpropan-2-ol (6000 mL), and 2,2-dimethoxyethan-1-amine (600 g, 5.71 mol, 6.00 equiv). The resulting solution was stirred at 85° C. for 5 h, cooled to room temperature and concentrated under vacuum. The residue was washed with 2×500 mL water and extracted with 3×500 mL of ethyl acetate. The organic layers were combined and concentrated under vacuum to afford 340 g (crude) of 5-bromo-N-(2,2-dimethoxyethyl)-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraen-8-amine as a black oil. Into a 10-L 4-necked round-bottom flask was placed cooled to room temperature concentrated under vacuum The residue was washed with 2×500 mL water extracted with 3×500 mL of ethyl acetate concentrated under vacuum

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 5000-mL 3-necked round-bottom flask was placed 5-bromo-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one (223 g, 884.55 mmol, 1.00 equiv), PhCH3 (3500 mL), PCl5 (560 g, 2.69 mol, 3.00 equiv), and DIPEA (275 g, 3.00 equiv). The resulting solution was stirred at 85° C. for 5 h and quenched by the addition of 300 g of DIPEA. The solids were filtered out and the filtrate was concentrated under vacuum to afford 260 g (crude) of 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene as a black oil. Into a 5000-mL 3-necked round-bottom flask was placed quenched by the addition of 300 g of DIPEA The solids were filtered out the filtrate was concentrated under vacuum

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 10-L 4-necked round-bottom flask was placed 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene (260 g, 960.99 mmol, 1.00 equiv), 2-methylpropan-2-ol (6000 mL), and 2,2-dimethoxyethan-1-amine (600 g, 5.71 mol, 6.00 equiv). The resulting solution was stirred at 85° C. for 5 h, cooled to room temperature and concentrated under vacuum. The residue was washed with 2×500 mL water and extracted with 3×500 mL of ethyl acetate. The organic layers were combined and concentrated under vacuum to afford 340 g (crude) of 5-bromo-N-(2,2-dimethoxyethyl)-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraen-8-amine as a black oil. Into a 10-L 4-necked round-bottom flask was placed cooled to room temperature concentrated under vacuum The residue was washed with 2×500 mL water extracted with 3×500 mL of ethyl acetate concentrated under vacuum

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 5000-mL 3-necked round-bottom flask was placed 5-bromo-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one (223 g, 884.55 mmol, 1.00 equiv), PhCH3 (3500 mL), PCl5 (560 g, 2.69 mol, 3.00 equiv), and DIPEA (275 g, 3.00 equiv). The resulting solution was stirred at 85° C. for 5 h and quenched by the addition of 300 g of DIPEA. The solids were filtered out and the filtrate was concentrated under vacuum to afford 260 g (crude) of 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene as a black oil. Into a 5000-mL 3-necked round-bottom flask was placed quenched by the addition of 300 g of DIPEA The solids were filtered out the filtrate was concentrated under vacuum