T. Shiro et al. / Bioorg. Med. Chem. 21 (2013) 2868–2878
2875
11, respectively. Compound 12: 1H NMR (DMSO-d6, 300 MHz) d
13.73 (0.5H, s), 13.56 (0.5H, s), 11.57 (0.5H, s), 11.41 (0.5H, s),
7.98 (1H, d, J = 8.1 Hz), 7.78 (1H, d, J = 7.2 Hz), 7.63–7.67 (1H, m),
7.50–7.64 (2H, m), 7.25 (1H, s), 7.11 (1H, d, J = 8.1 Hz), 2.66 (2H,
t, J = 7.5 Hz), 1.55–1.65 (2H, m), 1.32 (2H, dt, J = 7.3, 21.4 Hz),
0.90 (3H, t, J = 7.0 Hz); 13C NMR (DMSO-d6, 75 MHz) d 157.8,
155.1, 149.6, 146.9, 144.4, 142.4, 136.6, 132.2, 131.4, 130.1,
127.3, 122.7, 121.6, 115.3, 114.0, 109.5, 35.0, 33.1, 21.8, 13.8; mp
and triturated with IPE/CHCl3 to afford 17 (72.2 mg, 73%) as a
white solid. 1H NMR (DMSO-d6, 300 MHz) d 10.99 (1H, br s), 8.06
(1H, d, J = 8.3 Hz), 8.00 (1H, dd, J = 1.8, 7.5 Hz), 7.66–7.69 (2H, m),
7.62 (1H, d, J = 1.7 Hz), 7.45–7.51 (3H, m), 7.30–7.43 (4H, m); 13C
NMR (DMSO-d6, 75 MHz) d 158.7, 149.0, 140.4, 137.0, 136.4,
132.0, 131.3, 130.2, 129.0, 128.4, 127.2, 126.5, 121.8, 120.0,
116.5, 113.2; mp 335–337 °C; IR (ATR)
m 2950, 1653, 1635, 1419,
1313, 1265, 1244, 1159, 1101, 1039 cmꢁ1; HRMS (ESI+) m/z calcd
for C22H15ClN3O (M+H)+: 372.0898, found: 372.0898; Anal. Calcd
for C22H14ClN3Oꢂ0.50H2O ; C, 69.38; H, 3.97; N, 11.03. Found: C,
69.08; H, 3.81; N, 10.88.
281–283 °C; IR (ATR)
1180, 1049 cmꢁ1
HRMS (ESI+) m/z calcd for C20H19ClN3O
(M+H)+: 352.1211, found: 352.1211; Anal. Calcd for
m 2954, 1647, 1533, 1448, 1329, 1248,
;
C
20H18ClN3Oꢂ0.5H2O; C, 66.57; H, 5.31; N, 11.65. Found: C, 66.66;
H, 5.18; N, 11.49. Compound 13: 1H NMR (DMSO-d6, 300 MHz) d
11.47 (1H, br s), 7.97 (1H, d, J = 8.1 Hz), 7.78–7.83 (1H, m), 7.63–
7.66 (1H, m), 7.47–7.61 (2H, m), 7.23 (1H, s), 7.09 (1H, dd, J = 1.5,
8.1 Hz), 2.67 (2H, t, J = 7.7 Hz), 1.56–1.65 (2H, m), 1.26–1.35 (4H,
m), 0.86 (3H, t, J = 6.9 Hz); 13C NMR (DMSO-d6, 75 MHz) d 142.5,
136.6, 132.1, 132.0, 131.1, 130.2, 127.3, 122.4, 121.6, 115.2, 35.3,
5.1.14. 2-(2-Chlorophenyl)-7-(naphthalen-2-yl)imidazo[4,5-c]
quinolin-4(5H)-one (18), 2-(2-chlorophenyl)-7-(thiophen-2-
yl)imidazo[4,5-c]quinolin-4(5H)-one (19), 2-(2-chlorophenyl)-
7-(furan-2-yl)imidazo[4,5-c]quinolin-4(5H)-one (20), 2-(2-
chlorophenyl)-7-(pyridin-3-yl)imidazo[4,5-c]quinolin-4(5H)-
one (21), and 2-(2-chlorophenyl)-7-(pyridin-4-yl)imidazo[4,5-c]
quinolin-4(5H)-one (22)
The title compounds 18–22 were synthesized from 1 with cor-
responding boronic acid reagents in 71%, 64%, 68%, 63%, and 61%
yield according to the procedure to prepare 17, respectively. Com-
pound 18: 1H NMR (DMSO-d6, 300 MHz) d 13.75 (1H, br s), 11.71
(1H, br s), 8.26 (1H, s), 8.22 (1H, d, J = 8.1 Hz), 8.02–8.08 (2H, m),
7.95–7.98 (1H, m), 7.81–7.87 (3H, m), 7.74 (1H, d, J = 8.1 Hz),
7.63–7.69 (1H, m), 7.55–7.60 (4H, m); 13C NMR (DMSO-d6,
75 MHz) d 139.7, 137.6, 137.2, 137.1, 133.3, 132.4, 132.2, 131.4,
130.2, 129.7, 129.0, 128.7, 128.3, 127.6, 127.4, 126.6, 126.4,
125.5, 125.0, 124.8, 123.6, 122.4, 121.1, 118.2, 114.1; mp 167–
30.9, 30.6, 22.0, 13.9; mp 268–270 °C; IR (ATR)
m 2956, 1649,
1539, 1456, 1329, 1250, 1180, 1051 cmꢁ1; HRMS (ESI+) m/z calcd
for C21H21ClN3O (M+H)+: 366.1368, found: 366.1376; Anal. Calcd
for C21H20ClN3Oꢂ0.25H2O; C, 68.10; H, 5.58; N, 11.35. Found: C,
67.83; H, 5.49; N, 11.29. Compound 14: 1H NMR (DMSO-d6,
300 MHz) d 13.77 (0.5H, br s), 13.61 (0.5H, br s), 11.62 (0.5H, br
s), 11.45 (0.5H, br s), 7.98 (1H, d, J = 7.3 Hz), 7.76–7.81 (1H, m),
7.63–7.69 (1H, m), 7.47–7.57 (2H, m), 7.24 (1H, d, J = 7.3 Hz),
7.11 (1H, d, J = 8.1 Hz), 2.62–2.68 (2H, m), 1.58–1.62 (2H, m),
1.24–1.28 (6H, m), 0.85 (3H, t, J = 6.6 Hz); 13C NMR (DMSO-d6,
75 MHz) d 156.7, 151.3, 147.0, 144.4, 135.7, 131.9, 130.4, 129.7,
128.6, 128.4, 126.9, 124.6, 122.4, 121.2, 115.8, 115.0, 36.1, 32.1,
192 °C (amorphous solid); IR (ATR)
1387, 1269, 1244, 1211, 1173, 1049 cmꢁ1; HRMS (ESI+) m/z calcd
for
26H17ClN3O (M+H)+: 422.1055, found: 422.1055; HPLC;
m 3012, 1653, 1637, 1425,
31.3, 29.3, 22.5, 13.9; mp 267–269 °C; IR (ATR)
m 2925, 1647,
1248, 1180, 1049 cmꢁ1; HRMS (ESI+) m/z calcd for C22H23ClN3O
(M+H)+: 380.1524, found: 380.1530; HPLC; 100% (rt; 2.74 min).
Compound 15: 1H NMR (DMSO-d6, 300 MHz) d 13.77 (0.5H, s),
13.61 (0.5H, s), 11.61 (0.5H, s), 11.44 (0.5H, s), 8.00 (1H, d,
J = 7.9 Hz), 7.75–7.80 (1H, m), 7.63–7.70 (1H, m), 7.50–7.55 (2H,
m), 7.17–7.33 (6H, m), 7.14 (1H, d, J = 7.9 Hz), 4.03 (2H, s); 13C
NMR (DMSO-d6, 75 MHz) d 157.8, 155.0, 149.7, 147.0, 144.2,
141.8, 140.9, 136.9, 135.7, 132.2, 131.3, 130.1, 129.7, 128.8,
128.5, 127.3, 126.1, 123.1, 121.8, 115.8, 114.3, 109.7, 41.2; mp
C
98.4% (rt; 2.57 min). Compound 19: 1H NMR (DMSO-d6,
300 MHz) d 11.14 (1H, br s), 8.02 (1H, d, J = 8.3 Hz), 7.92–7.95
(1H, m), 7.65 (1H, d, J = 1.7 Hz), 7.52–7.56 (3H, m), 7.47–7.49
(1H, m), 7.38–7.41 (2H, m), 7.16 (1H, dd, J = 3.6, 5.0 Hz); 13C NMR
(DMSO-d6, 75 MHz) d 143.6, 136.5, 133.0, 132.0, 131.5, 130.2,
129.3, 128.6, 126.8, 125.5, 123.4, 122.0, 118.7, 111.9; mp 245–
247 °C; IR (ATR)
m 3001, 1653, 1448, 1429, 1387, 1331, 1271,
1242, 1159, 1045 cmꢁ1; HRMS (ESI+) m/z calcd for C20H13ClN3OS
(M+H)+: 378.0462, found: 378.0469; HPLC; 98.7% (rt; 2.10 min).
Compound 20: 1H NMR (DMSO-d6, 300 MHz) d 13.87 (0.5H, br s),
13.69 (0.5H, br s), 11.78 (0.5H, br s), 11.62 (0.5H, br s), 8.10 (1H,
d, J = 8.3 Hz), 7.76–7.82 (3H, m), 7.61–7.65 (2H, m), 7.50–7.59
(2H, m), 7.00 (1H, d, J = 2.9 Hz), 6.64 (1H, dd, J = 1.7, 3.2 Hz); 13C
NMR (DMSO-d6, 75 MHz) d 157.8, 155.0, 152.6, 150.0, 147.5,
144.0, 143.4, 136.9, 132.2, 131.4, 130.2, 129.6, 128.8, 127.3,
122.3, 118.0, 115.2, 112.3, 110.1, 106.7; mp 182–215 °C (amor-
268–270 °C; IR (ATR)
m 2920, 1655, 1635, 1429, 1394, 1340,
1313, 1267, 1240, 1101, 1043 cmꢁ1; HRMS (ESI+) m/z calcd for
C23H17ClN3O (M+H)+: 386.1055, found: 386.1055; HPLC; 98.5%
(rt; 2.19 min). Compound 16: 1H NMR (DMSO-d6, 300 MHz) d
11.52 (1H, br s), 7.98 (1H, d, J = 8.1 Hz), 7.79 (1H, dd, J = 2.0,
7.0 Hz), 7.65 (1H, d, J = 7.2 Hz), 7.49–7.58 (2H, m), 7.14–7.29 (7H,
m), 2.94 (4H, br s); 13C NMR (DMSO-d6, 75 MHz) d 158.3, 154.7,
152.5, 145.7, 141.6, 141.3, 136.7, 132.2, 131.4, 130.2, 129.8,
128.5, 128.3, 127.4, 125.9, 122.6, 121.6, 115.4, 112.5, 110.6, 37.3,
phous solid); IR (ATR)
1246, 1169, 1047, 1020 cmꢁ1
C
20H13ClN3O2 (M+H)+: 362.0691, found: 362.0691; HPLC; 98.0%
m
2991, 1655, 1425, 1396, 1313, 1271,
36.9; mp 188–202 °C (amorphous solid); IR (ATR)
1635, 1248, 1180, 1049 cmꢁ1
HRMS (ESI+) m/z calcd for
24H19ClN3O (M+H)+: 400.1211, found: 400.1211; Anal. Calcd for
m
3010, 1647,
;
HRMS (ESI+) m/z calcd for
;
C
C
(rt; 1.94 min). Compound 21: 1H NMR (DMSO-d6, 300 MHz) d
13.91 (1H, br s), 11.75 (1H, br s), 8.92 (1H, d, J = 2.4 Hz), 8.62
(1H, dd, J = 1.7, 4.8 Hz), 8.20 (1H, d, J = 8.3 Hz), 8.08–8.12 (1H, m),
7.82 (1H, dd, J = 2.2, 7.0 Hz), 7.74 (1H, d, J = 1.5 Hz), 7.51–7.69
(5H, m); 13C NMR (DMSO-d6, 75 MHz) d 148.8, 147.6, 137.1,
136.7, 135.2, 134.3, 132.2, 131.5, 130.2, 129.6, 127.4, 124.1,
122.6, 120.9, 114.0; mp 266–285 °C (amorphous solid); IR (ATR)
24H18ClN3Oꢂ0.75H2O ; C, 69.73; H, 4.75; N, 10.17. Found: C,
69.66; H, 4.67; N, 9.89.
5.1.13. 2-(2-Chlorophenyl)-7-phenylimidazo[4,5-c]quinolin-
4(5H)-one (17)
A mixture of 1 (100.0 mg, 0.267 mmol), phenyl boronic acid
(48.8 mg, 0.401 mmol), and tetrakis(triphenylphosphine)palla-
dium(0) (Pd(PPh3)4) (30.9 mg, 0.0267 mmol) and Na2CO3
(141.4 mg, 1.34 mmol) in THF/H2O (3.0/0.3 mL) was stirred at re-
flux for 6 h. After cooling to rt, water and AcOEt were added and
the mixture was extracted with AcOEt twice. The combined ex-
tracts were washed with water and brine, dried over Na2SO4. After
filtration, the solvent was removed in vacuo. The residue was puri-
fied by silica gel column chromatography (CHCl3/MeOH = 20/1)
m
3010, 1662, 1448, 1425, 1383, 1350, 1323, 1238, 1194, 1174,
1126, 1049, 1026 cmꢁ1; Anal. Calcd for C21H13ClN4Oꢂ1.00H2O; C,
64.54; H, 3.87; N, 14.34. Found: C, 64.30; H, 3.78; N, 14.11. Com-
pound 22: 1H NMR (DMSO-d6, 300 MHz) d 13.94 (1H, br s), 11.80
(1H, br s), 8.20–8.23 (2H, m), 8.22 (1H, d, J = 8.3 Hz), 7.80–7.83
(2H, m), 7.66–7.75 (4H, m), 7.51–7.61 (2H, m); 13C NMR (DMSO-
d6, 75 MHz) d 150.1, 146.9, 137.0, 136.6, 132.2, 131.5, 130.2,
129.5, 127.4, 122.6, 121.3, 120.7, 114.1; mp 245–275 °C