Reaction Steps
3-Amino-6-(3-bromopropyl)-9-methoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione (81, 420 mg, 1.01 mmol) was dissolved in dioxane (10 mL). Concentrated hydrochloric acid (0.65 mL, 3.3 mmol) was added and the reaction mixture was stirred for 10 min and then cooled down to 0° C. A solution of sodium nitrite (114 mg, 1.65 mmol) in water (5 mL) was slowly added with stirring while the temperature was −20° C. The reaction mixture was stirred for 30 min and then slowly added to a solution of copper (I) iodide (200 mg) and potassium iodide (300 mg) in water (15 mL). The reaction mixture was stirred at room temperature for 8 h and then heated at reflux for 1 h. The reaction mixture was diluted with water (200 mL) and extracted with chloroform (3×100 mL). The combined organic extracts were washed with an aqueous solution of sodium thiosulfate (2×200 mL), aqueous sodium bicarbonate (2×200 mL), water (100 mL) and brine (100 mL). The organic solution was dried over sodium sulfate and the solvent removed under vacuum. The residue was purified by silica gel column chromatography, eluting with chloroform-methanol, 30:1. Compound 82 was obtained as a dark red solid (402 mg, 76%): mp 207-209° C. IR (Film) 2922, 1765, 1655, 1599, 1532, 1478, 1455, 1430, 1379, 1295, 1225, 1047, 969, 812, 788, 691, 666, 592 cm−1; 1H NMR (CDCl3, 500 MHz) δ 8.60 (d, J=1.5 Hz, 1 H), 8.32 (d, J=8.6 Hz, 1 H), 7.93 (dd, J=8.5 Hz, J=1.5 Hz, 1 H), 7.64 (d, J=8.4 Hz, 1H), 7.15 (d, J=2.3 Hz, 1 H), 6.82 (dd, J=8.3 Hz, J=2.4 Hz, 1 H), 4.58 (t, J=7.2 Hz, 2 H), 3.89 (s, 3 H), 3.64 (t, J=6.2 Hz, 2 H), 2.44 (t, J=7.2 Hz, 2 H); 13C NMR (125 MHz, CDCl3) δ 189.3, 162.5, 162.0, 156.6, 142.4, 137.6, 137.0, 131.4, 127.6, 124.7, 124.1, 123.9, 115.8, 111.1, 107.6, 91.2, 55.8, 44.2, 31.1, 30.2; ESIMS m/z (rel intensity) 523 (MH+, 60), 403 [(MH+—C3H6Br)+, 100]; HRESIMS m/z calcd for C20H15NO3IBr 523.9358 (MH+), found, 523.9362 (MH+).
