Brief Articles
Journal of Medicinal Chemistry, 2007, Vol. 50, No. 10 2537
(quint., 2H), 3.65 (t, 2H), 4.23 (t, 2H), 7.1 (d, J ) 8.7 Hz, 2H),
7.80-7.83 (m, 2H), 8.08-8.13 (m, 3H), 8.24 (d, J ) 8.4 Hz, 1H),
8.27-8.30 (m, 1H), 8.34-8.37 (m, 1H), 11.23 (s, 1H).
8.12 (d, J ) 8.8 Hz, 2H), 8.24 (d, J ) 8.4 Hz, 1H), 8.29-8.31 (m,
1H), 8.35-8.37 (m, 1H), 11.23 (s, 1H). 13C NMR (100.5 MHz,
CDCl3): δ ppm 53.6, 55.5, 80.7, 115.4, 117.8, 122.0, 125.3, 126.5,
127.6, 128.3, 128.8, 133.3, 133.8, 134.1, 134.5, 149.8, 156.0, 161.6,
182.7, 185.4. HR-MS (M + 1)+ calcd, 468.1946; found, 468.1923.
Anal. (C28H25N3O4‚H2O) for C, H, N.
General Procedure for the Synthesis of Compounds 2-7.
Compound 2b (1 equiv) was added to a stirred solution of
appropriate amine (2 equiv) in dry acetone containing excess (5
equiv) anhydrous K2CO3. The reaction was continued under
refluxing condition for 12-15 h until TLC indicated complete
disappearance of 2b. After removal of acetone, the reaction mixture
was washed with water and the crude product was extracted in
chloroform. The organic layer was collected and dried over
anhydrous Na2SO4, and then the solvent was evaporated. Column
chromatography on silica gel yielded the pure product as a
hygroscopic solid upon elution with 2-5% MeOH in CHCl3. The
yields of all the compounds ranged from 50 to 70%.
4-[(3-(1-Imidazolyl))propyloxy]phenyl-1H-anthra[1,2-d]imi-
1
dazole-6,11-dione (6). H NMR (400 MHz, CDCl3): δ ppm 2.3
(quint., 2H), 4.01 (t, 2H), 4.24 (t, 2H), 6.95 (s, 1H), 7.06 (d, J )
8.8 Hz, 2H), 7.09 (s, 1H), 7.52 (s, 2H), 7.80-7.83 (m, 2H), 8.09
(d, J ) 8.4 Hz, 1H), 8.12 (d, J ) 8.8 Hz, 2H), 8.24 (d, J ) 8.4 Hz,
1H), 8.28-8.30 (m, 1H), 8.35-8.37 (m, 1H), 11.23 (s, 1H). 13C
NMR (100.5 MHz, CDCl3): δ ppm 30.7, 43.4, 64.0, 115.1, 117.8,
118.9, 121.7, 122.0, 125.3, 126.5, 127.6, 128.3, 128.9, 129.8, 131.3,
133.3, 133.5, 133.7, 134.1, 134.4, 137.3, 149.7, 156.6, 161.0, 182.7,
185.3. HR-MS (M + 1)+ calcd, 449.1613; found, 449.1611. Anal.
(C27H20N4O3‚2H2O) for C, H, N.
4-[(3-Diethylamino)propyloxy]phenyl-1H-anthra[1,2-d]imida-
zole-6,11-dione (2). 1H NMR (400 MHz, CDCl3): δ ppm 1.41 (t,
6H), 2.2 (quint., 2H), 3.2 (quart., 4H), 3.26 (t, 2H), 4.15 (t, 2H),
7.05 (d, J ) 8.7 Hz, 2H), 7.81-7.83 (m, 2H), 8.09 (d, J ) 8.6 Hz,
1H), 8.12 (d, J ) 8.7 Hz, 2H), 8.29 (d, J ) 8.7 Hz, 1H), 8.30-
8.31 (m, 1H), 8.34-8.36 (m, 1H), 11.26 (br s, 1H). 13C NMR (100.5
MHz, CD3OD + CDCl3): δ ppm 25.7, 32.5, 43.0, 55.5, 65.3, 114.4,
120.8, 121.2, 125.0, 126.5, 128.0, 129.1, 133.0, 133.3, 133.5, 133.8,
157.4, 161.2, 182.3, 183.5. HR-MS (M + 1)+ calcd, 454.2130;
found, 454.2137. Anal. (C28H27N3O3‚3H2O) for C, H, N.
4-[(3-(1-Tetrazolyl))propoxy]phenyl-1H-anthra[1,2-d]imida-
zole-6,11-dione (7). 1H NMR (300 MHz, CDCl3): δ ppm 2.6
(quint., 2H), 4.15 (t, 2H), 4.95 (t, 2H), 7.06 (d, J ) 8.7 Hz, 2H),
7.80-7.83 (m, 2H), 8.09 (d, J ) 8.4 Hz, 1H), 8.12 (d, J ) 8.7 Hz,
2H), 8.23 (d, J ) 8.4 Hz, 1H), 8.28-8.30 (m, 1H), 8.34-8.36 (m,
1H), 8.55 (s, 1H), 11.23 (s, 1H). 13C NMR (100.5 MHz, CDCl3):
δ ppm 29.0, 49.9, 64.4, 115.2, 117.9, 121.7, 122.0, 125.3, 126.5,
127.6, 128.4, 128.8, 133.3, 133.5, 133.7, 134.1, 134.4, 149.7, 152.9,
156.6, 161.0, 182.6, 185.3. ESI-MS (M + 1)+ calcd, 451.2; found,
451.2. Anal. (C25H18N6O3‚1.25H2O) for C, H, N.
4-[(3-(4-(2-Hydroxyethyl)-1-piperazinyl))propyloxy]phenyl-
1
1H-anthra[1,2-d]imidazole-6,11-dione (3). H NMR (400 MHz,
CD3OD): δ ppm 2.05 (quint., 2H), 2.54-2.66 (m, 10H), 3.32 (t,
2H), 3.72 (t, 2H), 4.19 (t, 2H), 7.05 (d, J ) 8.8 Hz, 2H), 7.7-7.84
(m, 2H), 7.92 (d, J ) 8.4 Hz, 1H), 8.10 (d, J ) 8.8 Hz, 2H), 8.20-
8.30 (m, 3H). 13C NMR (100.5 MHz, CD3OD): δ ppm 25.4, 51.7,
52.0, 54.2, 57.5, 59.0, 65.4 114.0, 120.0, 120.9, 125.6, 126.2, 127.6,
128.6, 132.5, 132.9, 133.0, 133.4, 157.0, 169.9, 182.0, 183.3. HR-
MS (M + 1)+ calcd 511.2345; found, 511.2351. Anal. (C30H30N4O4‚
3.5H2O) for C, H, N.
4-[(3-(4-Methyl-1-piperazinyl))propyloxy]phenyl-1H-anthra-
[1,2-d]imidazole-6,11-dione (4). 1H NMR (400 MHz, CDCl3): δ
ppm 2.05 (quint., 2H), 2.46 (s, 3H), 2.64-2.71 (m, 10H), 4.12 (t,
2H), 7.07 (d, J ) 8.8 Hz, 2H), 7.81-7.83 (m, 2H), 8.09 (d, J )
8.6, 1H), 8.11 (d, J ) 8.8 Hz, 2H), 8.23 (d, J ) 8.6 Hz, 1H), 8.28-
8.30 (m, 1H), 8.35-8.37 (m, 1H), 11.23 (s, 1H). 13C NMR (100.5
MHz, CDCl3): δ ppm 26.4, 45.3, 52.1, 54.5, 54.7, 66.2, 115.2,
117.8, 121.2, 122.0, 125.2, 126.5, 127.6, 128.3, 128.7, 133.5, 133.7,
134.1, 134.4, 149.8, 156.7, 161.6, 182.6, 185.3. HR-MS (M + 1)+
calcd, 481.2239; found, 481.2242. Anal. (C29H28N4O3‚3H2O) for
C, H, N.
For the synthesis of compounds 8 and 9, 1,2-diminoanthraquino-
ne and 2- or 3-pyridinecarboxaldehyde were taken in a 1:1 ratio in
dry PhNO2 and heated at 120 °C for 15-17 h until TLC indicated
the completion of the reaction. Precipitation of the product with
petroleum ether and repeated washing with the same removed
nitrobenzene completely to yield the pure products in almost 65%
yield.
2-Pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione (8). 1H NMR
(300 MHz, CDCl3): δ ppm 7.45 (t, 1H), 7.80-7.83 (m, 2H), 7.9
(t, 1H), 8.17 (d, J ) 8.4 Hz, 1H), 8.26 (d, J ) 8.4 Hz, 1H), 8.30-
8.37 (m, 2H), 8.46 (d, 1H), 8.76 (m, 1H). 13C NMR (100.5 MHz,
CDCl3): 118.8, 121.9, 122.4, 125.6, 126.5, 127.2, 127.4, 133.2,
133.6, 133.9, 134.3, 137.4, 137.5, 146.7, 149.0, 149.5, 155.8, 182.9,
184.4. HR-MS (M + Na)+ calcd, 348.0749; found, 348.0700. Anal.
(C20H11N3O2‚H2O) for C, H, N.
3-Pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione (9). 1H NMR
(400 MHz, CDCl3): δ ppm 7.56-7.57 (m, 1H), 7.84-7.85 (m,
2H), 8.19 (d, J ) 8.6 Hz, 1H), 8.28-8.38 (m, 3H), 8.53 (d, 1H),
8.81 (d, 1H), 9.43 (br s, 1H). 13C NMR (100.5 MHz, CDCl3): 118.9,
122.0, 124.1, 125.1, 125.4, 126.4, 127.2, 129.1, 133.0, 133.4, 133.8,
134.3, 135.5, 147.8, 148.5, 150.8, 154.4, 182.8, 184.3. HR-MS (M
+ 1)+ calcd, 326.0929; found, 326.0934. Anal. (C20H11N3O2‚H2O)
for C, H, N.
4-[(3-(4-Morpholinyl))propyloxy]phenyl-1H-anthra[1,2-d]imi-
dazole-6,11-dione (5). 1H NMR (400 MHz, CDCl3): δ ppm 2.06
(quint., 2H), 2.54-2.62 (m, 6H), 3.77 (t, 4H), 4.15 (t, 2H), 7.09
(d, J ) 8.8 Hz, 2H), 7.8-7.84 (m, 2H), 8.10 (d, J ) 8.4 Hz, 1H),
Scheme 1a
a Reagents, conditions, and yields: (i) 4-(Me2N(CH2)3O)-C6H5CHO (1b), dry PhNO2, 130 °C, 16 h, 50%; (ii) 4-OH-C6H5CHO, dry PhNO2, 120 °C,
20 h, 60%; (iii) Br(CH2)3Br, K2CO3, dry acetone, reflux, 12 h, 60%; (iv) amine (RH), K2CO3, dry acetone, reflux, 12-15 h, 50-70%; (v) 2- or 3-pyridine
carboxaldehyde (R′CHO), dry PhNO2, 120 °C, 15-17 h, 65%.