3-bromo-2-(methylaminomethyl)aniline

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: To a solution of 3-bromo-2-methylaminomethyl-phenylamine from step 3 of Example 3 (2.615 g, 12.2 mmol) in pyridine (50 ml) was added sulfamide (3.5 g, 36.4 mmol). The solution was heated under reflux overnight, and the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate. The organic layer was washed with 2N HCl solution, water, brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-benzo[1,2,6]thiadiazine 2,2-dioxide as a white solid. (2.32 g, 69%) MS: (M+H)+ 277.1. The solution was heated under reflux overnight the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate The organic layer was washed with 2N HCl solution, water, brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine (1.153 g, 5.36 mmol) in CH2Cl2 (50 ml) was added NEt3 (1.5 ml, 10.76 mmol), triphosgen (555 mg, 1.87 mmol) at 0° C. The reaction was allowed to warm up to room temperature and stirred overnight. After the solvent was removed by using a rotary evaporator, the residue was partitioned between water and ethyl acetate. The organic layer was washed by H2O and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one as white solid. (650 mg, 50%) MS: (M+H)+ 241.1. After the solvent was removed a rotary evaporator the residue was partitioned between water and ethyl acetate The organic layer was washed by H2O and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine (1.153 g, 5.36 mmol) in CH2Cl2 (50 ml) was added NEt3 (1.5 ml, 10.76 mmol), triphosgen (555 mg, 1.87 mmol) at 0° C. The reaction was allowed to warm up to room temperature and stirred overnight. After the solvent was removed by using a rotary evaporator, the residue was partitioned between water and ethyl acetate. The organic layer was washed by H2O and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one as white solid. (650 mg, 50%) MS: (M+H)+ 241.1. After the solvent was removed a rotary evaporator the residue was partitioned between water and ethyl acetate The organic layer was washed by H2O and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2-Amino-6-bromo-benzyl)-methyl-carbamic acid tert-butyl ester (371 mg) was dissolved in 50 ml ethanol. To this solution was added 2M ethanolic hydrochloride acid solution (10 ml). The reaction mixture was heated at 100° C. for 30 minutes, at which time the deprotection was completed. The solution was allowed to cool to room temperature and poured into the mixture of saturated NaHCO3 solution and ethyl acetate. The aqueous layer was extracted with EtOAc three times and the organic fractions were concentrated to give 3-bromo-2-methylaminomethyl-phenylamine as a brown oil (1.938 g, 76%). MS: (M+H)+ 217.1. to cool to room temperature The aqueous layer was extracted with EtOAc three times the organic fractions were concentrated

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine from step 3 of Example 3 (2.615 g, 12.2 mmol) in pyridine (50 ml) was added sulfamide (3.5 g, 36.4 mmol). The solution was heated under reflux overnight, and the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate. The organic layer was washed with 2N HCl solution, water, brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-benzo[1,2,6]thiadiazine 2,2-dioxide as a white solid. (2.32 g, 69%) MS: (M+H)+277.1. The solution was heated under reflux overnight the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate The organic layer was washed with 2N HCl solution, water, brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine (1.153 g, 5.36 mmol) in CH2Cl2 (50 ml) was added NEt3 (1.5 ml, 10.76 mmol), triphosgen (555 mg, 1.87 mmol) at 0° C. The reaction was allowed to warm up to room temperature and stirred overnight. After the solvent was removed by using a rotary evaporator, the residue was partitioned between water and ethyl acetate. The organic layer was washed by H2O and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one as white solid. (650 mg, 50%) MS: (M+H)+241.1. After the solvent was removed a rotary evaporator the residue was partitioned between water and ethyl acetate The organic layer was washed by H2O and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine (1.153 g, 5.36 mmol) in CH2Cl2 (50 ml) was added NEt3 (1.5 ml, 10.76 mmol), triphosgen (555 mg, 1.87 mmol) at 0° C. The reaction was allowed to warm up to room temperature and stirred overnight. After the solvent was removed by using a rotary evaporator, the residue was partitioned between water and ethyl acetate. The organic layer was washed by H2O and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one as white solid. (650 mg, 50%) MS: (M+H)+241.1. After the solvent was removed a rotary evaporator the residue was partitioned between water and ethyl acetate The organic layer was washed by H2O and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2-Amino-6-bromo-benzyl)-methyl-carbamic acid tert-butyl ester (371 mg) was dissolved in 50 ml ethanol. To this solution was added 2M ethanolic hydrochloride acid solution (10 ml). The reaction mixture was heated at 100° C. for 30 minutes, at which time the deprotection was completed. The solution was allowed to cool to room temperature and poured into the mixture of saturated NaHCO3 solution and ethyl acetate. The aqueous layer was extracted with EtOAc three times and the organic fractions were concentrated to give 3-bromo-2-methylaminomethyl-phenylamine as a brown oil (1.938 g, 76%). MS: (M+H)+217.1. to cool to room temperature The aqueous layer was extracted with EtOAc three times the organic fractions were concentrated

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: To a solution of 3-bromo-2-methylaminomethyl-phenylamine from step 3 of Example 3 (2.615 g, 12.2 mmol) in pyridine (50 ml) was added sulfamide (3.5 g, 36.4 mmol). The solution was heated under reflux overnight, and the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate. The organic layer was washed with 2N HCl solution, water, brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-benzo[1,2,6]thiadiazine 2,2-dioxide as a white solid. (2.32 g, 69%) MS: (M+H)+ 277.1. The solution was heated under reflux overnight the cooled reaction mixture was partitioned between 2N HCl water solution and ethyl acetate The organic layer was washed with 2N HCl solution, water, brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography

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

実験手順: To a solution of 3-bromo-2-methylaminomethyl-phenylamine (1.153 g, 5.36 mmol) in CH2Cl2 (50 ml) was added NEt3 (1.5 ml, 10.76 mmol), triphosgen (555 mg, 1.87 mmol) at 0° C. The reaction was allowed to warm up to room temperature and stirred overnight. After the solvent was removed by using a rotary evaporator, the residue was partitioned between water and ethyl acetate. The organic layer was washed by H2O and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 5-bromo-3-methyl-3,4-dihydro-1H-quinazolin-2-one as white solid. (650 mg, 50%) MS: (M+H)+ 241.1. After the solvent was removed a rotary evaporator the residue was partitioned between water and ethyl acetate The organic layer was washed by H2O and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by flash chromatography