(3-bromophenyl)methanesulfonyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 4.94 g of 3-bromobenzylsulfonyl chloride were initially charged in 60 ml of dichloromethane and, within 15 minutes, a solution of 5.64 g of bis(2,4-dimethoxybenzyl)amine in 30 ml of dichloromethane and then a solution of 3.82 ml of N,N-diisopropylethylamine in 5 ml of dichloromethane were added dropwise. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation. This gave the product (9.23 g) with a molecular weight of 550.5 g/mol (C25H28BrNO6S). to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution The organic phase was dried over MgSO4 concentrated by rotary evaporation The crude product was purified by means of normal phase chromatography concentrated by rotary evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 9.90 g of 3-bromobenzylsulfonyl chloride were initially charged in 120 ml of dichloromethane, and a solution of 11.55 ml of 2,4-dimethoxybenzylamine in 60 ml of dichloromethane was added dropwise within 15 minutes. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The residue (14.30 g) was used in the next reaction without further purification. to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water The organic phase was dried over MgSO4 concentrated by rotary evaporation The residue (14.30 g) was used in the next reaction without further purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and (3-bromophenyl)methanesulfonyl chloride, the title compound (yield 92%) was obtained in the same manner as that of Example 145.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and (3-bromophenyl)methanesulfonyl chloride, the title compound (yield 92%) was obtained in the same manner as that of Example 145.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 4.94 g of 3-bromobenzylsulfonyl chloride were initially charged in 60 ml of dichloromethane and, within 15 minutes, a solution of 5.64 g of bis(2,4-dimethoxybenzyl)amine in 30 ml of dichloromethane and then a solution of 3.82 ml of N,N-diisopropylethylamine in 5 ml of dichloromethane were added dropwise. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation. This gave the product (9.23 g) with a molecular weight of 550.5 g/mol (C25H28BrNO6S). to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution The organic phase was dried over MgSO4 concentrated by rotary evaporation The crude product was purified by means of normal phase chromatography concentrated by rotary evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 9.90 g of 3-bromobenzylsulfonyl chloride were initially charged in 120 ml of dichloromethane, and a solution of 11.55 ml of 2,4-dimethoxybenzylamine in 60 ml of dichloromethane was added dropwise within 15 minutes. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The residue (14.30 g) was used in the next reaction without further purification. to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water The organic phase was dried over MgSO4 concentrated by rotary evaporation The residue (14.30 g) was used in the next reaction without further purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 9.90 g of 3-bromobenzylsulfonyl chloride were initially charged in 120 ml of dichloromethane, and a solution of 11.55 ml of 2,4-dimethoxybenzylamine in 60 ml of dichloromethane was added dropwise within 15 minutes. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The residue (14.30 g) was used in the next reaction without further purification. to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water The organic phase was dried over MgSO4 concentrated by rotary evaporation The residue (14.30 g) was used in the next reaction without further purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and (3-bromophenyl)methanesulfonyl chloride, the title compound (yield 92%) was obtained in the same manner as that of Example 145.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 4.94 g of 3-bromobenzylsulfonyl chloride were initially charged in 60 ml of dichloromethane and, within 15 minutes, a solution of 5.64 g of bis(2,4-dimethoxybenzyl)amine in 30 ml of dichloromethane and then a solution of 3.82 ml of N,N-diisopropylethylamine in 5 ml of dichloromethane were added dropwise. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation. This gave the product (9.23 g) with a molecular weight of 550.5 g/mol (C25H28BrNO6S). to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 50 ml of 1 N aqueous hydrochloric acid, with 50 ml of saturated aqueous sodium hydrogencarbonate solution and finally with 50 ml of saturated aqueous sodium chloride solution The organic phase was dried over MgSO4 concentrated by rotary evaporation The crude product was purified by means of normal phase chromatography concentrated by rotary evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While cooling with ice, 9.90 g of 3-bromobenzylsulfonyl chloride were initially charged in 120 ml of dichloromethane, and a solution of 11.55 ml of 2,4-dimethoxybenzylamine in 60 ml of dichloromethane was added dropwise within 15 minutes. The reaction mixture was allowed to come to room temperature and stirred for 1 hour. Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water. The organic phase was dried over MgSO4 and concentrated by rotary evaporation. The residue (14.30 g) was used in the next reaction without further purification. to come to room temperature Subsequently, the mixture was washed with 50 ml of water, with 100 ml of 1 N aqueous hydrochloric acid, with 100 ml of saturated aqueous sodium hydrogencarbonate solution and finally once more with 100 ml of water The organic phase was dried over MgSO4 concentrated by rotary evaporation The residue (14.30 g) was used in the next reaction without further purification