1-bromo-3-isocyanato-2-methylbenzene

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

実験手順: Under ice-cooling, to N,N-dimethylformamide 220 mL was added anhydrous aluminum chloride 19.7 g and the resulting mixtures were stirred for fifteen minutes. Thereto was added sodium azide 9.6 g and the resulting mixtures were stirred for fifteen minutes and thereto was then added 1-bromo-3-isocyanato-2-methylbenzene 30.3 g and the resulting mixtures were heated at 80° C. for five hours. After cooling the mixtures, to a mixture of sodium nitrite 33 g, water 2 L and ice 500 g was added the reaction solutions with stirring. The mixtures were acidified with 10% hydrochloric acid and were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, and were dried over anhydrous magnesium sulfate and were then concentrated under reduced pressure to give 1-(2-methyl-3-bromophenyl)-1,4-dihydrotetrazole-5-one 31.4 g. the resulting mixtures were stirred for fifteen minutes After cooling the mixtures was added the reaction solutions with stirring were extracted with ethyl acetate The organic layers were washed with water and saturated saline were dried over anhydrous magnesium sulfate were then concentrated under reduced pressure

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

実験手順: Under ice-cooling, to N,N-dimethylformamide 220 mL was added anhydrous aluminum chloride 19.7 g and the resulting mixtures were stirred for fifteen minutes. Thereto was added sodium azide 9.6 g and the resulting mixtures were stirred for fifteen minutes and thereto was then added 1-bromo-3-isocyanato-2-methylbenzene 30.3 g and the resulting mixtures were heated at 80° C. for five hours. After cooling the mixtures, to a mixture of sodium nitrite 33 g, water 2 L and ice 500 g was added the reaction solutions with stirring. The mixtures were acidified with 10% hydrochloric acid and were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, and were dried over anhydrous magnesium sulfate and were then concentrated under reduced pressure to give 1-(2-methyl-3-bromophenyl)-1,4-dihydrotetrazole-5-one 31.4 g. the resulting mixtures were stirred for fifteen minutes After cooling the mixtures was added the reaction solutions with stirring were extracted with ethyl acetate The organic layers were washed with water and saturated saline were dried over anhydrous magnesium sulfate were then concentrated under reduced pressure

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

実験手順: A mixture of 1-bromo-2-methyl-3-aminobenzene 25.0 g, triphosgene 60.0 g and toluene 400 mL was stirred with heating under reflux for three hours. The reaction mixtures after standing to cool were concentrated under reduced pressure to give 1-bromo-3-isocyanato-2-methylbenzene 30.3 g. with heating under reflux for three hours to cool were concentrated under reduced pressure

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

実験手順: A mixture of 1-bromo-2-methyl-3-aminobenzene 25.0 g, triphosgene 60.0 g and toluene 400 ml was stirred with heating under reflux for three hours. The reaction mixture after standing to cool was concentrated under reduced pressure to give 1-bromo-3-isocyanato-2-methylbenzene 30.3 g. with heating under reflux for three hours to cool was concentrated under reduced pressure

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

実験手順: Anhydrous aluminium chloride 19.7 g was added to N,N-dimethylformamide 220 ml under ice-cooling, and the resulting mixture was stirred for fifteen minutes. Thereto was added sodium azide 9.6 g and the resulting mixture was stirred for fifteen minutes. Thereto was then added 1-bromo-3-isocyanato-2-methylbenzene 30.3 g and the resulting mixture was heated at 80° C. for five hours. After cooling, the reaction solutions was added to a mixture of sodium nitrite 33 g, water 2 L and ice 500 g with stirring. The reaction mixture was acidified with 10% hydrochloric acid and was extracted with ethyl acetate. The organic layer was washed with water and saturated saline and then was dried over anhydrous magnesium sulfate and was then concentrated under reduced pressure to give 1-(2-methyl-3-bromophenyl)-1,4-dihydrotetrazole-5-one 31.4 g. cooling the resulting mixture was stirred for fifteen minutes After cooling with stirring was extracted with ethyl acetate The organic layer was washed with water and saturated saline was dried over anhydrous magnesium sulfate was then concentrated under reduced pressure

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 3-((4-methoxybenzyl)amino)-2-(phenylselanyl)propanoate (3.68 g, 9.73 mmol), 1-bromo-3-isocyanato-2-methylbenzene (2.27 g, 10.7 mmol), and K2CO3 (0.672 g, 4.86 mmol) in DMF (49 mL) was heated at 65° C. for 5 h. The cooled mixture was partitioned between water and EtOAc. And the organic phase was washed with brine, dried and concentrated to provide 3-(3-bromo-2-methylphenyl)-1-(4-methoxybenzyl)-5-(phenylselanyl)dihydropyrimidine-2,4(1H,3H)-dione as a light brown solid (5.43 g), used without further purification. Mass spectrum m/z 557, 559, 561 (M+H)+. The cooled mixture was partitioned between water and EtOAc And the organic phase was washed with brine dried concentrated

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of methyl 3-((4-methoxybenzyl)amino)-2-(phenylselanyl)propanoate (3.68 g, 9.73 mmol), 1-bromo-3-isocyanato-2-methylbenzene (2.27 g, 10.7 mmol), and K2CO3 (0.672 g, 4.86 mmol) in DMF (49 mL) was heated at 65° C. for 5 h. The cooled mixture was partitioned between water and EtOAc. And the organic phase was washed with brine, dried and concentrated to provide 3-(3-bromo-2-methylphenyl)-1-(4-methoxybenzyl)-5-(phenylselanyl)dihydropyrimidine-2,4(1H,3H)-dione as a light brown solid (5.43 g), used without further purification. Mass spectrum m/z 557, 559, 561 (M+H)+. The cooled mixture was partitioned between water and EtOAc And the organic phase was washed with brine dried concentrated

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

実験手順: A solution of triphosgene (2.25 g, 7.58 mmol) in toluene (27 mL), cooled in an ice-water bath, was treated slowly with a solution of 3-bromo-2-methylaniline (3.00 g, 16.1 mmol) and DIEA (5.6 mL, 32.2 mmol) in toluene (5.4 mL). The resulting suspension was stirred at room temperature for 2 h. The precipitate was removed by filtration and washed with EtOAc. The combined filtrates were diluted with EtOAc, washed with brine, dried and concentrated to provide 1-bromo-3-isocyanato-2-methylbenzene as a brown oil (3.68 g, 98% yield), used without purification. 1H NMR (400 MHz, DMSO-d6) δ 7.49 (dd, J=8.1, 0.9 Hz, 1H), 7.31 (dd, J=7.9, 0.7 Hz, 1H), 7.15 (td, J=8.0, 0.7 Hz, 1H), 2.38 (s, 3H). The precipitate was removed by filtration washed with EtOAc The combined filtrates were diluted with EtOAc washed with brine dried concentrated

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

実験手順: Under ice-cooling, to N,N-dimethylformamide 220 mL was added anhydrous aluminum chloride 19.7 g and the resulting mixtures were stirred for fifteen minutes. Thereto was added sodium azide 9.6 g and the resulting mixtures were stirred for fifteen minutes and thereto was then added 1-bromo-3-isocyanato-2-methylbenzene 30.3 g and the resulting mixtures were heated at 80° C. for five hours. After cooling the mixtures, to a mixture of sodium nitrite 33 g, water 2 L and ice 500 g was added the reaction solutions with stirring. The mixtures were acidified with 10% hydrochloric acid and were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, and were dried over anhydrous magnesium sulfate and were then concentrated under reduced pressure to give 1-(2-methyl-3-bromophenyl)-1,4-dihydrotetrazole-5-one 31.4 g. the resulting mixtures were stirred for fifteen minutes After cooling the mixtures was added the reaction solutions with stirring were extracted with ethyl acetate The organic layers were washed with water and saturated saline were dried over anhydrous magnesium sulfate were then concentrated under reduced pressure

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

実験手順: A mixture of 1-bromo-2-methyl-3-aminobenzene 25.0 g, triphosgene 60.0 g and toluene 400 mL was stirred with heating under reflux for three hours. The reaction mixtures after standing to cool were concentrated under reduced pressure to give 1-bromo-3-isocyanato-2-methylbenzene 30.3 g. with heating under reflux for three hours to cool were concentrated under reduced pressure

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

実験手順: A mixture of 1-bromo-2-methyl-3-aminobenzene 25.0 g, triphosgene 60.0 g and toluene 400 ml was stirred with heating under reflux for three hours. The reaction mixture after standing to cool was concentrated under reduced pressure to give 1-bromo-3-isocyanato-2-methylbenzene 30.3 g. with heating under reflux for three hours to cool was concentrated under reduced pressure

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

実験手順: Anhydrous aluminium chloride 19.7 g was added to N,N-dimethylformamide 220 ml under ice-cooling, and the resulting mixture was stirred for fifteen minutes. Thereto was added sodium azide 9.6 g and the resulting mixture was stirred for fifteen minutes. Thereto was then added 1-bromo-3-isocyanato-2-methylbenzene 30.3 g and the resulting mixture was heated at 80° C. for five hours. After cooling, the reaction solutions was added to a mixture of sodium nitrite 33 g, water 2 L and ice 500 g with stirring. The reaction mixture was acidified with 10% hydrochloric acid and was extracted with ethyl acetate. The organic layer was washed with water and saturated saline and then was dried over anhydrous magnesium sulfate and was then concentrated under reduced pressure to give 1-(2-methyl-3-bromophenyl)-1,4-dihydrotetrazole-5-one 31.4 g. cooling the resulting mixture was stirred for fifteen minutes After cooling with stirring was extracted with ethyl acetate The organic layer was washed with water and saturated saline was dried over anhydrous magnesium sulfate was then concentrated under reduced pressure