Med Chem Res
5-Oxo-N-(4-nitrophenyl)-2,3-dihydroimidazo[1,2-
b]isoquinoline-1(5H)-carboxamide (16)
7.19–7.30 (4H, m, H–Ar), 6.96 (1H, s, H-10), 4.23 (4H, bs, H-2,
H-3). 13C NMR (DMSO-d6, 75 MHz) d: 159.5 (C-5), 152.1 (C-
11), 140.7 (C–F), 139.3 (C-10a), 138.7 (C-9a), 132.4 (C-9),
128.5 (C-6), 126.2 (C-7; C-8), 125.9 (C-16; C-12), 123.8 (C-
5a), 123.3 (C-15), 121.4 (C-17), 120.9 (C-14), 87.6 (C-10), 44.1
(C-2), 42.5 (C-3). HRESIMS calcd for C18H14FN3O2 [M?H]?
324.1148, found 324.1166. Anal. Calcd. For C18H14FN3O2: C,
66.87; H, 4.36; N, 13.0. Found: C, 66.93; H, 4.01; N, 13.12.
Reaction time: 6 h, yellowish needles (ethyl acetate), yield:
0.71 g, 76 %, mp: 249–251 °C. IR mmax (KBr): 3339 (N–H
amide), 1739 (C=O, urea), 1701 (C=O), 1568 (N-CO), 1550
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and 1350 (–NO2), 847 and 748 (C–H Ar) cm-1. H NMR
(DMSO-d6, 300 MHz) d: 10.18 (1H, s, NH (urea)), 8.20 (2H,
d, J = 9.0 Hz, H-14, H-16), 7.92 (1H, d, J = 8.2 Hz, H-6),
7.72 (2H, d, J = 9.0 Hz, H–Ar, H-13, H-17), 7.39 (1H, dt,
J = 8.2 Hz, J = 1.1 Hz, H–Ar), 7.26 (1H, d, J = 7.1 Hz, H–
Ar), 7.19 (1H, dt, J = 7.1, 1.1 Hz, H–Ar,) 7.01 (1H, s, H-10),
3.34-4.08 (4H, m, H-3, H-2). 13C NMR (DMSO-d6, 75 MHz)
d: 155.09 (C-5), 144.61 (C-11), 143.25 (C-10a), 142.15 (C-
15), 136.15 (C-9a), 132.58 (C-12), 128.24 (C-9), 127.25 (C-
6), 126.92 (C-7; C-8), 125.40 (C-14; C-16), 124.25 (C-5a),
120.50 (C-13; C-17), 89.79 (C-10), 50.32 (C-3), 45.25 (C-2).
HRESIMS calcd for C18H14N4O4 [M ? H]? 351.1093, found
351.1105. Anal. Calcd. ForC18H14N4O4:C, 61.71;H, 4.03;N,
15.99. Found: C, 61.48; H, 3.79; N, 15.61.
3,8-Dioxo-1,2,3,5,6-hexahydrobenzo[c]imidazo[1,2,3-
ij][1,8]naphthyridine-1-carboxylic acid (19)
A mixture of compound 1 (0.5 g, 2.7 mmol) and maleic
anhydride (1.6 g, 16 mmol) in 15 mL of acetone was
heated at reflux with stirring for 2 h. The mixture was
allowed to rise to room temperature, and the crystalline
solid was collected and crystallized from ethanol to yield
0.61 g (80 %). IR mmax (KBr): 2900 (O–H), 2850 (C–H),
5-Oxo-N-(4-methylphenyl)-2,3-dihydroimidazo[1,2-
b]isoquinoline-1(5H)-carboxamide (17)
Reaction time: 4 h, white needles (ethanol), yield: 0.18 g,
21 %, mp: 265–267 °C (d). IR mmax (KBr): 3340 (N–H amide),
1725 (C=O, urea), 1699 (NC=O), 840 and 752 (C–H Ar) cm-1
.
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1703 (C=O), 1669 (C=O), 1590 (–N–CO) cm-1. H RMN
1H NMR (DMSO-d6, 300 MHz) d: 8.90 (1H, s, NH (urea)),
8.03(1H, dd, J = 8.1 Hz, J = 1.2 Hz, H-6), 7.53–7.60 (2H, m,
H–Ar), 7.49 (2H, d, J = 8.9 Hz, H-14, H-16), 7.38 (2H, d,
J = 8.9 Hz, H-13, H17), 7.19-7.30 (1H, m, H–Ar), 6.96 (1H, s,
H-10), 4.09 (4H, m, H-2, H-3), 2.22 (3H, s, CH3). 13C NMR
(DMSO-d6, 75 MHz) d: 159.14 (C-5), 155.61 (C-11), 146.84
(C-10a), 138.42 (C-9a), 134.15 (C-12), 132.61 (C-15), 129.77
(C-14; C-16), 128.69 (C-6; C-9), 126.29 (C-7; C-8), 124.25 (C-
5a), 119.90 (C-13; C-17), 89.79 (C-10), 50.32 (C-3), 45.25 (C-
2), 21.13 (CH3). HRESIMS calcd for C19H17N3O2 [M?H]?
320.1399, found 320.1433. Anal. Calcd. For C19H17N3O2: C,
71.46; H, 5.37; N, 13.16. Found: C, 71.14; H, 5.61; N, 13.01.
(DMSO-d6, 300 MHz) d: 12.80 (1H, s, COOH), 8.15 (1H,
d, J = 7.8 Hz, H-6), 7.67 (2H, dd, J = 7.7 Hz, H–Ar),
7.12–7.36 (1H, m, H–Ar), 4.05–4.20 (5H, m, H-2, H-3,
H-aliph), 2.87-2.90 (2H, m, H-aliph). 13C NMR (DMSO-
d6, 75 MHz) d: 174.41 (C-11), 173.67 (C-14), 170.89 (C-
5), 165.73 (C-10a), 134.21 (C-8), 132.59 (C-9a), 130.94
(C-6), 125.70 (C-7), 123.86 (C-5a), 123.06 (C-9), 117.8
(C-7), 48.11 (C-2), 44.61 (C-3), 44.51 (C-12), 40.40 (C-
13). HRESIMS calcd for C15H12N2O4 [M?H]? 285.0875,
found 285.0932. Anal. Calcd. For C15H12N2O4: C, 63.38;
H, 4.25; N, 9.85. Found: C, 63.05; H, 4.34; N, 9.79.
N-(3-(Dimethylamino)propyl)-3,8-dioxo-1,2,3,5,6,8-
hexahydrobenzo[c]imidazo[1,2,3-ij][1,8]
naphthyridine-1-carboxamide (20)
5-Oxo-N-(2-fluorophenyl)-2,3-dihydroimidazo[1,2-
b]isoquinoline-1(5H)-carboxamide (18)
To a suspension of compound 1 (0.5 g, 2.7 mmol) and DMAP
(0.6 g, 4.9 mmol) in 20 mL of CH2Cl2, 2-fluorophenyl isocy-
anate (0.33 mL, 2.7 mmol) was added over a period of several
min and then was stirred at reflux for 2 h. The mixture was
allowed to rise to room temperature, and the crystalline solid
was collected and washed with CH2Cl2. It was obtained as
white needles. Yield: 0.30 g, 35 %. Mp 224–227 °C. 1H NMR
(DMSO-d6) d: 8.89 (1H, s, NH (urea)), 8.08 (1H, dd,
J = 7.9 Hz, J = 0.5 Hz, H-6), 7.47–7.59 (3H, m, H–Ar),
To a solution of compound 19 (0.5 g, 1.83 mmol) in
5 mL of CHCl3, 0.26 mL of triethylamine was added drop-
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