tert-butyl N-[3-[3-aminopropyl(methyl)amino]propyl]carbamate

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

Procedure: Into 180 ml of water, was dissolved 150 g of bis(3-aminopropyl)methylamine followed by 53 g of triethylamine. To the solution, while being cooled in ice and stirred, was added portionwise a solution of 83 g (1/3 equivalent) of 4,6-dimethyl-2-tert-butoxycarbonylthiopyrimidine in 200 ml of dioxane. The mixture was allowed to react at room temperature for 5 hours. The reaction mixture was stripped of the dioxane and triethyl amine by disillation under reduced pressure. The residue was adjusted to pH 2 with 6N hydrochloric acid and washed with chloroform. The aquoues layer was adjusted to pH 13.5 with sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulfate and freed from the solvent by distillation under reduced pressure to yield 60 g (24% yield) of (3-tert-butoxycarbonylaminopropyl)-(3-aminopropyl)methylamine (BOC-APMP). To the solution, while being cooled in ice to react at room temperature for 5 hours washed with chloroform extracted with chloroform The chloroform layer was dried over sodium sulfate freed from the solvent by distillation under reduced pressure

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

Procedure: Into 180 ml of water, was dissolved 150 g of bis(3-aminopropyl)methylamine followed by 53 g of triethylamine. To the solution, while being cooled in ice and stirred, was added portionwise a solution of 83 g (1/3 equivalent) of 4,6-dimethyl-2-tert-butoxycarbonylthiopyrimidine in 200 ml of dioxane. The mixture was allowed to react at room temperature for 5 hours. The reaction mixture was stripped of the dioxane and triethyl amine by disillation under reduced pressure. The residue was adjusted to pH 2 with 6N hydrochloric acid and washed with chloroform. The aquoues layer was adjusted to pH 13.5 with sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulfate and freed from the solvent by distillation under reduced pressure to yield 60 g (24% yield) of (3-tert-butoxycarbonylaminopropyl)-(3-aminopropyl)methylamine (BOC-APMP). To the solution, while being cooled in ice to react at room temperature for 5 hours washed with chloroform extracted with chloroform The chloroform layer was dried over sodium sulfate freed from the solvent by distillation under reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 11-chloro-5-methyl-5H-indolo[3,2-b]quinoline (cf. Bierer et al., J. Med. Chem. 1998, vol. 41, pp. 2754) (61 mg, 0.23 mmol) and [[3-[(3-amino-propyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (84_l, 0.34 mmol) in 2-ethoxyethanol (10 ml) was heated at 120° C. for 10 min. Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%) yielded [3-[methyl-[3-(5-methyl-5H-indolo[3,2-b]quinolin-11-yl-amino)propyl]-amino]propyl]carbamic acid tert-butyl ester (49 mg, 490%) as a foam. 1H NMR [CDCl3—, ppm]: 8.16 (d, J=8.5 Hz, 1H), 7.81 (m, 4H), 7.55-7.48 (m, 2H), 7.21 (m, 1H), 4.51 (s, 3H, NCH3), 4.27 (m, 2H, CH2NO), 3.12 (m, 2H, CH2NHBOC), 2.76 (m, 2H, CH2N(CH3)), 2.63 (m, 2H, CH2N(CH3)), 2.39 (s, 3H, N(CH3)), 2.34 (m, 2H, CH2CN(CH3)), 1.73 (m, 2H, CH2CN(CH3)), 1.37 (s, 9H, C(CH3)3). Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%)

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

Procedure: 1,8-naphthalic anhydride (0.18 g, 0.9 mmol) was added to a solution of [3-[(3-aminopropyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (0.2 g, 0.8 mmol) in absolute ethanol (20 ml). The reaction mixture was heated at reflux overnight. Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1) yielded [3-[[3-(1,3-dioxo-3a,9b-dihydro-1H,3H-benzo[de]isoquinolin-2-yl)propyl]methylamino]propyl]carbamic acid tert-butyl ester (0.37 g, 90%) as a foam. The reaction mixture was heated at reflux overnight Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 11-chloro-5-methyl-5H-indolo[3,2-b]quinoline (cf. Bierer et al., J. Med. Chem. 1998, vol. 41, pp. 2754) (61 mg, 0.23 mmol) and [[3-[(3-amino-propyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (84_l, 0.34 mmol) in 2-ethoxyethanol (10 ml) was heated at 120° C. for 10 min. Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%) yielded [3-[methyl-[3-(5-methyl-5H-indolo[3,2-b]quinolin-11-yl-amino)propyl]-amino]propyl]carbamic acid tert-butyl ester (49 mg, 490%) as a foam. 1H NMR [CDCl3—, ppm]: 8.16 (d, J=8.5 Hz, 1H), 7.81 (m, 4H), 7.55-7.48 (m, 2H), 7.21 (m, 1H), 4.51 (s, 3H, NCH3), 4.27 (m, 2H, CH2NO), 3.12 (m, 2H, CH2NHBOC), 2.76 (m, 2H, CH2N(CH3)), 2.63 (m, 2H, CH2N(CH3)), 2.39 (s, 3H, N(CH3)), 2.34 (m, 2H, CH2CN(CH3)), 1.73 (m, 2H, CH2CN(CH3)), 1.37 (s, 9H, C(CH3)3). Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%)

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

Procedure: 1,8-naphthalic anhydride (0.18 g, 0.9 mmol) was added to a solution of [3-[(3-aminopropyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (0.2 g, 0.8 mmol) in absolute ethanol (20 ml). The reaction mixture was heated at reflux overnight. Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1) yielded [3-[[3-(1,3-dioxo-3a,9b-dihydro-1H,3H-benzo[de]isoquinolin-2-yl)propyl]methylamino]propyl]carbamic acid tert-butyl ester (0.37 g, 90%) as a foam. The reaction mixture was heated at reflux overnight Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1)

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

Procedure: Into 180 ml of water, was dissolved 150 g of bis(3-aminopropyl)methylamine followed by 53 g of triethylamine. To the solution, while being cooled in ice and stirred, was added portionwise a solution of 83 g (1/3 equivalent) of 4,6-dimethyl-2-tert-butoxycarbonylthiopyrimidine in 200 ml of dioxane. The mixture was allowed to react at room temperature for 5 hours. The reaction mixture was stripped of the dioxane and triethyl amine by disillation under reduced pressure. The residue was adjusted to pH 2 with 6N hydrochloric acid and washed with chloroform. The aqueous layer was adjusted to pH 13.5 with sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulfate and freed from the solvent by distillation under reduced pressure to yield 60 g (24% yield) of (3-tert-butoxycarbonylaminopropyl)-(3-aminopropyl)methylamine (BOC-APMP). To the solution, while being cooled in ice to react at room temperature for 5 hours washed with chloroform extracted with chloroform The chloroform layer was dried over sodium sulfate freed from the solvent by distillation under reduced pressure

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

Procedure: Into 180 ml of water, was dissolved 150 g of bis(3-aminopropyl)methylamine followed by 53 g of triethylamine. To the solution, while being cooled in ice and stirred, was added portionwise a solution of 83 g (1/3 equivalent) of 4,6-dimethyl-2-tert-butoxycarbonylthiopyrimidine in 200 ml of dioxane. The mixture was allowed to react at room temperature for 5 hours. The reaction mixture was stripped of the dioxane and triethyl amine by disillation under reduced pressure. The residue was adjusted to pH 2 with 6N hydrochloric acid and washed with chloroform. The aquoues layer was adjusted to pH 13.5 with sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulfate and freed from the solvent by distillation under reduced pressure to yield 60 g (24% yield) of (3-tert-butoxycarbonylaminopropyl)-(3-aminopropyl)methylamine (BOC-APMP). To the solution, while being cooled in ice to react at room temperature for 5 hours washed with chloroform extracted with chloroform The chloroform layer was dried over sodium sulfate freed from the solvent by distillation under reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 11-chloro-5-methyl-5H-indolo[3,2-b]quinoline (cf. Bierer et al., J. Med. Chem. 1998, vol. 41, pp. 2754) (61 mg, 0.23 mmol) and [[3-[(3-amino-propyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (84_l, 0.34 mmol) in 2-ethoxyethanol (10 ml) was heated at 120° C. for 10 min. Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%) yielded [3-[methyl-[3-(5-methyl-5H-indolo[3,2-b]quinolin-11-yl-amino)propyl]-amino]propyl]carbamic acid tert-butyl ester (49 mg, 490%) as a foam. 1H NMR [CDCl3—, ppm]: 8.16 (d, J=8.5 Hz, 1H), 7.81 (m, 4H), 7.55-7.48 (m, 2H), 7.21 (m, 1H), 4.51 (s, 3H, NCH3), 4.27 (m, 2H, CH2NO), 3.12 (m, 2H, CH2NHBOC), 2.76 (m, 2H, CH2N(CH3)), 2.63 (m, 2H, CH2N(CH3)), 2.39 (s, 3H, N(CH3)), 2.34 (m, 2H, CH2CN(CH3)), 1.73 (m, 2H, CH2CN(CH3)), 1.37 (s, 9H, C(CH3)3). Removal of the solvent and purification by chromatography on alumina (CHCl3: MeOH 2%)

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

Procedure: 1,8-naphthalic anhydride (0.18 g, 0.9 mmol) was added to a solution of [3-[(3-aminopropyl)methylamino]propyl]carbamic acid tert-butyl ester previously prepared (Spicer at el., Bioorg. Med. Chem. 2002, vol. 10, p. 19) (0.2 g, 0.8 mmol) in absolute ethanol (20 ml). The reaction mixture was heated at reflux overnight. Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1) yielded [3-[[3-(1,3-dioxo-3a,9b-dihydro-1H,3H-benzo[de]isoquinolin-2-yl)propyl]methylamino]propyl]carbamic acid tert-butyl ester (0.37 g, 90%) as a foam. The reaction mixture was heated at reflux overnight Removal of the solvent and purification by chromatography on alumina (CH2Cl2/MeOH, 50:1)