Reaction Steps
Electrophilic Bromination of Sampangine: Preparation of 4-Bromo-7H-naphtho[1,2,3-ij] [2,7]naphthyridin-7-one [4-Bromosampangine, 5] and 4-Bromo-5-ethoxy-7H-naphtho[1,2,3-ij][2,7]naphthyridin-7-one[4-Bromo-5-ethoxysampangine, 20]. A mixture of pyridinium bromide perbromide (4.80 g, 15.0 mmol) and sampangine (2.32 g, 10.0 mmol) in CHCl3 (100 mL) was heated at reflux for 24 h. After cooling, the mixture was poured into a separatory funnel and washed with saturated aqueous NaHCO3 solution (2×250 mL). The organic layer was dried (K2CO3) and concentrated to dryness. The residual solids were subjected to flash silica gel chromatography while eluting with CHCl3 to give pure 4-bromosampangine (5) (2.00 g, 64%) and 4-bromo-5-ethoxysampangine (20) (0.05 g, 1%). An analytical sample of 20 was obtained by crystallization from CHCl3. Compound 5: mp 244°-246° C.; IR (KBr) 1670, 1590, 1400, 1320, 1310, 1275, 1230, 980, 790, 755, 720 cm-1 ; 1H NMR (CDCl3) δ 7.72 (ddd, 1H, J=7.9, 7.9, 1.4 Hz), 7.86 (ddd, 1H, J=7.9, 7.9, 1.4 Hz), 7.96 (d, 1H, J=5.9 Hz), 8.46 (dd, 1H, J=7.9, 1.4 Hz), 8.85 (dd, 1H, J=7.9, 1.4 Hz), 8.99 (d, 1H, J=5.9 Hz), 9.28 (s,1H); 13C NMR (CDCl3) 118.3 (1), 120.5 (0), 123.7 (0), 125.8 (1), 128.7 (1), 131.8 (1), 132.3 (0), 135.0 (1), 135.1 (0), 138.6 (0), 146.7 (0), 148.6 (1), 150.2 (1), 151.7 (0), 181.6 (0) ppm; Anal. (exact mass, HREIMS) calcd for C15H7BrN2O m/e 309.9741, found 309.9747; Anal. calcd for C15H7BrN2O: C 57.90, H 2.27, N 9.00; found C 57.70, H 2.27, N 9.26. Compound 20: mp 200°-201° C.; IR (KBr) 1670, 1592, 1570, 1430, 1382, 1365, 1330, 1270, 1212, 1080, 1070, 1042, 980, 845, 762, 755, 720, 710, 635 cm-1 ; 1H NMR (CDCl3) δ 1.56 (t, 3H, J=7.1 Hz), 4.79 (q, 2H, J=7.1 Hz), 7.67 (ddd, 1H, J=7.3, 7.3, 1.4 Hz), 7.79 (ddd, 1H, J=7.3, 7.3, 1.4 Hz), 7.82 (d, 1H, J=6.1 Hz), 8.36 (dd, 1H, J=7.3, 1.4 Hz), 8.72 (d, 1H, J=6.1 Hz), 8.75 (dd, 1H, J=7.3, 1.4 Hz); 13C NMR (CDCl3) 14.6 (3), 64.7 (2), 107.4 (0), 117.5 (0), 117.8 (1), 125.5 (1), 128.2 (1), 131.4 (1), 132.2 (0), 134.5 (1), 135.0 (0), 140.9 (0), 144.6 (0), 147.2 (1), 151.7 (0), 159.9 (0), 181.4 (0) ppm; Anal. calcd for C17H11BrN2O: C 57.48, H 3.12, N 7.88; found C 57.09, H 3.37, N 7.75.
