N'-(2-aminoethyl)-N'-methylethane-1,2-diamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0° C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0° C. over a period of 15 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×23 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate. The resulting reaction mixture warmed to room temperature After stirring at room temperature for 2 h The organic layer was washed with brine (3×23 mL) dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0° C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0° C. over a period of 15 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×23 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate. The resulting reaction mixture warmed to room temperature After stirring at room temperature for 2 h The organic layer was washed with brine (3×23 mL) dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0° C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0° C. over a period of 15 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×25 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate. The resulting reaction mixture warmed to room temperature After stirring at room temperature for 2 h The organic layer was washed with brine (3×25 mL) dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0° C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0° C. over a period of 15 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×25 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate. The resulting reaction mixture warmed to room temperature After stirring at room temperature for 2 h The organic layer was washed with brine (3×25 mL) dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-chloro-3-methoxy-5,9-diaza-benzo[c]fluoren-7-one (Reference Example 1c-2) (21 mg) and N-methyl-2,2′-diaminodiethylamine (WAKO PURE CHEMICAL: 3.3 mg) and potassium carbonate (10 mg) was suspended in N,N-dimethylformamide (0.5 ml) and stirred at 90° C. for thirteen hours under nitrogen gas. The mixture was evaporated to dryness. The residue was purified by silica gel column chromatography developed by dichloromethane-methanol=30:1 and dichloromethane-methanol-ammonia water (25%)=30:1:0.4. The desired product was obtained as a reddish powder. The mixture was evaporated to dryness The residue was purified by silica gel column chromatography

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-chloro-3-methoxy-5,9-diaza-benzo[c]fluoren-7-one (Reference Example 1c-2) (21 mg) and N-methyl-2,2′-diaminodiethylamine (WAKO PURE CHEMICAL: 3.3 mg) and potassium carbonate (10 mg) was suspended in N,N-dimethylformamide (0.5 ml) and stirred at 90° C. for thirteen hours under nitrogen gas. The mixture was evaporated to dryness. The residue was purified by silica gel column chromatography developed by dichloromethane-methanol=30:1 and dichloromethane-methanol-ammonia water (25%)=30:1:0.4. The desired product was obtained as a reddish powder. The mixture was evaporated to dryness The residue was purified by silica gel column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N1-(2-Aminoethyl)-N1-methylethane-1,2-diamine (5.0 g, 42.7 mmol) was dissolved in 100 mL of CH2Cl2 and cooled to 0° C. A solution of di-tert-butylcarbonate (0.93 g, 4.27 mmol) in CH2Cl2 (10 mL) was then added dropwise at 0° C. over a period of 15 mm. The resulting reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature. After stirring at room temperature for 2 h, the reaction mixture was diluted with CH2Cl2 (100 mL). The organic layer was washed with brine (3×25 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 1.1 g of tert-butyl 2-((2-aminoethyl)(methyl)amino)ethylcarbamate. The resulting reaction mixture warmed to room temperature After stirring at room temperature for 2 h The organic layer was washed with brine (3×25 mL) dried (Na2SO4) concentrated under reduced pressure

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

Procedure: To a solution of N1-(2-aminoethyl)-N1-methylethane-1,2-diamine (10.58 g, 90 mmoles) in DCM (350 mL) was added slowly a solution of 2-nitrobenzene-1-sulfonyl chloride dissolved in DCM (50 mL). After 2 h at RT, the reaction mixture (RM) was washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel with a gradient of methanol in DCM (0 to 10%), yielding to 6.9 g of N-(2-((2-aminoethyl)(methyl)-amino)ethyl)-2-nitrobenzenesulfonamide 6a and 3.9 g of N,N′-(2,2′-(methylazanediyl)-bis(ethane-2,1-diyl))bis(2-nitrobenzenesulfonamide) 6b; m/z (6a)=303 (M+H)+, m/z (6b)=488 (M+H)+. the reaction mixture (RM) was washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography on silica gel with a gradient of methanol in DCM (0 to 10%)

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

Procedure: To a solution of N1-(2-aminoethyl)-N1-methylethane-1,2-diamine (10.58 g, 90 mmoles) in DCM (350 mL) was added slowly a solution of 2-nitrobenzene-1-sulfonyl chloride dissolved in DCM (50 mL). After 2 h at RT, the reaction mixture (RM) was washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel with a gradient of methanol in DCM (0 to 10%), yielding to 6.9 g of N-(2-((2-aminoethyl)(methyl)-amino)ethyl)-2-nitrobenzenesulfonamide 6a and 3.9 g of N,N′-(2,2′-(methylazanediyl)-bis(ethane-2,1-diyl))bis(2-nitrobenzenesulfonamide) 6b; m/z (6a)=303 (M+H)+, m/z (6b)=488 (M+H)+. the reaction mixture (RM) was washed with water dried over MgSO4 filtered concentrated The residue was purified by flash chromatography on silica gel with a gradient of methanol in DCM (0 to 10%)

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

Procedure: A mixture of 8.20 g (72.0 mmol) of N-(2-aminoethyl)-N-methyl-1,2-ethanediamine and 6.80 g (24.0 mmol) of 1-(3,5-diamino-6-bromopyrazinoyl)imidazole in 48 ml of tetrahydrofuran was stirred at ambient temperature for 30 minutes. The solution was evaporated and the residue triturated with ether. There was obtained 5.85 g (17.6 mmol, 73%) of 3,5-diamino-N-[2-[(2-aminoethyl)methylamino]ethyl]-6-bromopyrazinecarboxamide; mp 148°-150° C. The solution was evaporated the residue triturated with ether