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Davis, D. A. et al.
mL), cooled to 0 °C, and slowly acidified with dilute HCl with stirring. The yellow precipitate was collected by
filtration and dried in vacuo to yield 0.49 g of 23. An additional 0.11 g of product was obtained by continuous
extraction of the filtrate with CH2Cl2 to give a total of 0.60 g (84%) of 23: mp 194–195 °C; IR (KBr) 1710, 1625,
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1505, 1335, 1260, 1230, 740 cm-1; H NMR (DMSO-d6) δ 12.38 (s, 1H), 9.22 (s, 1H), 8.94 (d, J 4.3 Hz, 1H), 7.61
(d, J 4.3 Hz, 1H), 7.50 (m, 2H), 7.41 (m, 1H), 7.20 (m, 1H); 13C NMR (DMSO-d6) δ 183.0, 165.6, 153.6, 151.8,
150.9, 148.6, 136.5, 131.0, 127.1, 124.6, 123.0, 121.6, 121.5, 120.6, 113.2. A satisfactory analysis could not be
obtained for this product so it was used directly in the next step.
6-Bromoindolo[1,2-b][2,7]naphthyridine-5,12-dione (24). A solution of 23 (0.60 g, 1.7 mmol) in Ac2O (25 mL)
was heated at 80 °C for 4 h. After cooling, most of the solvent was removed in vacuo, then H2O (50 mL) and
CH2Cl2 (50 mL) were added. The layers were separated and the aqueous phase was further extracted with
CH2Cl2 (2 x 50 mL). The combined organic phase was washed with H2O (2 x 100 mL) and brine (100 mL), dried
(Na2SO4), and adsorbed onto silica gel. Flash chromatography with EtOAc gave 0.45 g (79%) of 24 as a yellow-
green powder. Recrystallization from CH2Cl2/hexane gave the analytical sample as fine yellow needles: mp
230–232 °C (dec); IR (CHCl3) 2980, 2920, 1705, 1680, 1600, 1535, 1450, 1365, 1335, 1255, 1220 cm-1; 1H NMR
(DMSO-d6) δ 9.35 (s, 1H), 9.16 (d, J 4.7 Hz, 1H), 8.54 (d, J 7.9 Hz, 1H), 8.18 (d, J 4.7 Hz, 1H), 7.75 (m, 2H), 7.56
(m, 1H); 13C NMR (DMSO-d6) δ 174.1, 155.4, 150.0, 147.9, 134.7, 131.4, 131.2, 126.2, 126.0, 122.0, 120.8,
119.0, 118.3, 116.6, 108.7; MS m/e 328 (M++2, 100%), 326 (M+, 100%), 300, 298, 272, 270, 247, 219, 191, 164,
114. Anal. Calcd for C15H7BrN2O2: C, 55.07; H, 2.16; Br, 24.43; N, 8.56; O, 9.78. Found: C, 54.82; H, 2.18; Br,
24.53; N, 8.49; O, 9.88.
6-Dimethylaminoindolo[1,2-b][2,7]naphthyridine-5,12-dione (17a). To a solution of 24 (100 mg, 0.31 mmol)
in THF (25 mL) was added excess Me2NH (25% aqueous solution, 20 mL). The mixture was stirred at rt for 6 h,
during which time the solution became bright orange. The solution was poured into EtOAc (100 mL) and
washed with saturated aqueous NaHCO3 (2 x 50 mL), H2O (2 x 50 mL) and brine (50 mL), then dried (Na2SO4)
and concentrated to give an orange powder. Recrystallization from THF-hexane gave 73 mg (82%) of 17a as
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small orange needles: mp 240–242 °C; IR (CHCl3) 3050, 1680, 1635, 1575, 1545, 1495, 1410, 1370 cm-1; H
NMR (CDCl3) δ 9.62 (s, 1H), 8.98 (d, 1H, J 4.0 Hz), 8.86 (d, 1H, J 9.6 Hz), 8.06 (d, 1H, J 4.0 Hz), 8.00 (d, 1H, J 9.6
Hz), 7.62 (m, 1H), 7.33 (m, 1H), 3.49 (s, 6H); MS m/e 291 (M+), 276 (100%), 262, 249, 233, 220, 192, 164, 102,
77, 44; Anal. Calcd for C17H13N3O2: C, 70.08; H, 4.50; N, 14.42. Found: C, 69.87; H, 4.39; N, 14.41.
6-[N-[2-(Dimethylamino)ethyl]methylamino]indolo[1,2-b][2,7]naphthyridine-5,12-dione (17b). To a solution
of 24 (65 mg, 0.20 mmol) in THF (5 mL) was added excess N,N,N’-trimethylethylenediamine (0.10 mL, 0.78
mmol). The mixture was refluxed for 1 h, during which time the solution became dark orange. The solution
was cooled and poured into EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (2 x 25 mL), H2O (2 x
25 mL) and brine (25 mL), then dried (Na2SO4) and concentrated to give a red powder. Recrystallization from
CH2Cl2-hexane gave 57 mg (83%) of 17b as short red needles: mp 129–131 °C; IR (CHCl3) 2950, 2800, 1675,
1630, 1570, 1530, 1495, 1460, 1410, 1370, 1330 cm-1; 1H NMR (CDCl3) δ 9.62 (s, 1H), 8.99 (d, 1H, J 5.1 Hz), 8.87
(d, 1H, J 8.1 Hz), 8.08 (d, 1H, J 5.1 Hz), 8.01 (d, 1H, J 8.1 Hz), 7.64 (m, 1H), 7.35 (m, 1H), 3.95 (t, 2H), 3.50 (s,
3H), 2.68 (t, 2H), 2.22 (s, 6H); 13C NMR (CDCl3) δ 174.7, 168.0, 157.9, 153.9, 151.0, 150.9, 141.4, 137.5, 131.6,
124.9, 124.5, 124.3, 124.0, 118.5, 118.3, 57.6, 54.8, 45.7, 43.1; MS m/e 348 (M+), 303, 290, 277, 262, 248, 233,
80, 58 (100%); Anal. Calcd for C20H20N4O2 + 0.5 H2O: C, 67.21; H, 5.92; N, 15.67. Found: C, 67.78; H, 5.76; N,
15.23.
6-[3-(Diethylamino)propylylamino]indolo[1,2-b][2,7]naphthyridine-5,12-dione (17c). To a solution of 24 (56
mg, 0.17 mmol) in THF (5 mL) was added excess 3-diethylaminopropylamine (0.10 mL, 0.63 mmol). The
mixture was refluxed for 1 h, during which time the solution became dark orange. The solution was cooled and
poured into EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (2 x 25 mL), H2O (2 x 25 mL) and brine
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