N'-[2-(3-aminopropylamino)ethyl]propane-1,3-diamine

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

Procedure: A solution of 87.2 g of 1,10-diamino-4,7-diazadecane in 500 ml of toluene was admixed with 72.3 g of a 40% aqueous glyoxal solution, and the mixture was refluxed, with a water separator fitted, for 3 hours. When the solution was cooled, a solid precipitated out which was filtered off with suction, washed three times with 50 ml of toluene each time and dried under reduced pressure. This gave 34.9 g of pale yellow needles. separator fitted, for 3 hours When the solution was cooled a solid precipitated out which was filtered off with suction washed three times with 50 ml of toluene each time dried under reduced pressure

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 l) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF--H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141°-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF

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

Procedure: Bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-(6-propyl-tert-BOCamino)}ethane (13b), N,N′-Bis(3-aminopropyl)-1,2-ethanediamine (11h) (0.16 g, 0.85 mmol) was added to a stirred solution of indenobenzopyran 4d (0.46 g, 1.87 mmol) in CHCl3 (150 mL) and the reaction mixture was stirred under reflux for 72 h, providing bisindenoisoquinoline 12 h as a crude intermediate. Upon allowing the reaction mixture to cool to room temperature, Et3N (0.6 mL, 4.24 mmol) and Boc2O (0.56 g, 2.60 mmol) were added to the reaction mixture and the mixture was allowed to stir at room temperature for 8 h. The crude reaction mixture was purified by flash column chromatography (SiO2/20% EtOAc in hexane, then 1-5% MeOH in CHCl3) to provide Boc-protected bisindenoisoquinoline 13b (550 mg, 76%) as an orange solid: mp 106-108° C. 1HNMR (CDCl3) δ 8.60 (bs, 2H), 8.23 (bs, 2H), 7.65 (bs, 2H), 7.55 (d, J=6.7 Hz, 2H), 7.40-7.32 (m, 8H), 4.48 (bs, 4H), 3.45 (bs, 8H), 2.12 (bs, 4H), 1.44 (s, 9H), 1.39 (s, 9H); ESIMS m/z (rel intensity) 835 (MH+, 22), 735 (MH+-Boc, 100). Anal. Calcd for C50H50N4O8.0.3H2O: C, 71.46; H, 6.07; N, 6.67. Found: C, 71.15; H, 6.19; N, 6.61. under reflux for 72 h

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 l) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF-H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141°-2° C.; 1H NMR (CDCl3) δ1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF-H2O

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

Procedure: A solution of 87.2 g of 1,10-diamino-4,7-diazadecane in 500 ml of toluene was admixed with 72.3 g of a 40% aqueous glyoxal solution, and the mixture was refluxed, with a water separator fitted, for 3 hours. When the solution was cooled, a solid precipitated out which was filtered off with suction, washed three times with 50 ml of toluene each time and dried under reduced pressure. This gave 34.9 g of pale yellow needles. separator fitted, for 3 hours When the solution was cooled a solid precipitated out which was filtered off with suction washed three times with 50 ml of toluene each time dried under reduced pressure

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

Procedure: A solution of 87.2 g of 1,10-diamino-4,7-diazadecane in 500 ml of toluene was admixed with 72.3 g of a 40% aqueous glyoxal solution, and the mixture was refluxed, with a water separator fitted, for 3 hours. When the solution was cooled, a solid precipitated out which was filtered off with suction, washed three times with 50 ml of toluene each time and dried under reduced pressure. This gave 34.9 g of pale yellow needles. separator fitted, for 3 hours When the solution was cooled a solid precipitated out which was filtered off with suction washed three times with 50 ml of toluene each time dried under reduced pressure

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 l) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF--H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141°-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 l) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF--H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141°-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF

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

Procedure: Bis-1,2-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-(6-propyl-tert-BOCamino)}ethane (13b), N,N′-Bis(3-aminopropyl)-1,2-ethanediamine (11h) (0.16 g, 0.85 mmol) was added to a stirred solution of indenobenzopyran 4d (0.46 g, 1.87 mmol) in CHCl3 (150 mL) and the reaction mixture was stirred under reflux for 72 h, providing bisindenoisoquinoline 12 h as a crude intermediate. Upon allowing the reaction mixture to cool to room temperature, Et3N (0.6 mL, 4.24 mmol) and Boc2O (0.56 g, 2.60 mmol) were added to the reaction mixture and the mixture was allowed to stir at room temperature for 8 h. The crude reaction mixture was purified by flash column chromatography (SiO2/20% EtOAc in hexane, then 1-5% MeOH in CHCl3) to provide Boc-protected bisindenoisoquinoline 13b (550 mg, 76%) as an orange solid: mp 106-108° C. 1HNMR (CDCl3) δ 8.60 (bs, 2H), 8.23 (bs, 2H), 7.65 (bs, 2H), 7.55 (d, J=6.7 Hz, 2H), 7.40-7.32 (m, 8H), 4.48 (bs, 4H), 3.45 (bs, 8H), 2.12 (bs, 4H), 1.44 (s, 9H), 1.39 (s, 9H); ESIMS m/z (rel intensity) 835 (MH+, 22), 735 (MH+-Boc, 100). Anal. Calcd for C50H50N4O8.0.3H2O: C, 71.46; H, 6.07; N, 6.67. Found: C, 71.15; H, 6.19; N, 6.61. under reflux for 72 h

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 1) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF-H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF-H2O

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 1) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF-H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4 H), 2.41 (s, 6 H), 2.43 (s, 6 H), 2.97 (quart, J=6.6 Hz, 4 H), 3.15 (t, J=6.6 Hz, 4 H), 3.22 (s, 4 H), 5.31 (t, J=6.5 Hz, 2 H), 7.28 (d, J=8.3 Hz, 4 H), 7.32 (d, J=8.3 Hz, 4 H), 7.66 (d, J=8.3 Hz, 4 H), 7.72 (d, J=8.3 Hz, 4 H). maintaining the temperature ≤50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF-H2O

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

Procedure: To a stirred solution of p-toluenesulfonyl chloride (460 g, 2.41 mole) in pyridine (1.5 l) at 0° C. was added a solution of 1,5,8,12-tetraazadodecane (100 g, 0.574 mole) in pyridine (100 ml) under a dry argon atmosphere, maintaining the temperature <50° C. The addition required 1 h. The mixture was allowed to cool to room temperature and was stirred for 2 h. H2O (3 l) was slowly added to the cooled (ice bath) mixture. The resulting brown solid was filtered and washed thoroughly with H2O. The crude product was purified by recrystallization from DMF-H2O to give 238 g (53% yield) of the product as a crude granular solid: mp 141°-2° C.; 1H NMR (CDCl3) δ 1.78 (quint, J=6.2 Hz, 4H), 2.41 (s, 6H), 2.43 (s, 6H), 2.97 (quart, J=6.6 Hz, 4H), 3.15 (t, J=6.6 Hz, 4H), 3.22 (s, 4H), 5.31 (t, J=6.5 Hz, 2H), 7.28 (d, J=8.3 Hz, 4H), 7.32 (d, J=8.3 Hz, 4H), 7.66 (d, J=8.3 Hz, 4H), 7.72 (d, J=8.3 Hz, 4H). maintaining the temperature <50° C The addition required 1 h cooled (ice bath) mixture The resulting brown solid was filtered washed thoroughly with H2O The crude product was purified by recrystallization from DMF-H2O