H. Hasegawa et al. / Bioorg. Med. Chem. 13 (2005) 3721–3735
3731
powder in 73% yield. mp 130–132 °C (from diethyl
for C19H29N3O: C, 72.34; H, 9.26; N, 13.32. Found:
C, 72.19; H, 9.19; N, 13.22.
1
ether); H NMR (CDCl3, 270 MHz) d 7.86 (br s, 1H),
7.33 (m, 1H), 7.15 (dd, J = 2.0, 8.3 Hz, 1H), 7.07 (d,
J = 2.0 Hz, 1H), 6.71 (d, J = 8.3 Hz, 1H), 6.29 (dd,
J = 2.0, 3.0 Hz, 1H), 6.17 (d, J = 3.3 Hz, 1H), 5.59
(s, 1H), 3.84 (m, 1H), 3.15 (m, 1H), 2.27–2.48 (m, 2H),
2.23 (s, 6H), 1.84–2.01 (m, 2H); Anal. Calcd for
C17H20N3O2ClÆ1/3H2O: C, 60.09; H, 6.13; N, 12.37.
Found: C, 59.94; H, 6.05; N, 12.33.
5.3.9. 4-Benzyl-3-[3-(dimethylamino)propyl]-3,4-dihydro-
quinazolin-2(1H)-one (9i). The title compound was pre-
pared from 15i to give 9i as a white powder in 77%.
mp 122–124 °C (from diethyl ether); H NMR (CDCl3,
270 MHz) d 7.11–7.22 (m, 4H), 6.79–6.90 (m, 3H),
6.59–6.64 (m, 3H), 4.62 (dd, J = 5.0, 7.0 Hz, 1H), 3.99
(qn, J = 7.0 Hz, 1H), 2.94 (m, 3H), 2.18 (s, 6H), 2.15–
2.35 (m, 2H), 1.74 (m, 2H); Anal. Calcd for
C20H25N3OÆ1/10H2O: C, 73.86; H, 7.81; N, 12.92.
Found: C, 73.81; H, 7.77; N, 12.88.
1
5.3.4. 3-[3-(Dimethylamino)propyl]-4-(2-thienyl)-3,4-di-
hydroquinazolin-2(1H)-one (9d). The title compound
was prepared from 15d to give 9d as a white powder
in 54% yield. mp 144–146 °C (from diethyl ether/
CHCl3); 1H NMR (CDCl3, 270 MHz) d 7.45 (br s,
1H), 7.16–7.24 (m, 2H), 7.08 (m, 1H), 6.90–7.02 (m,
3H), 6.76 (d, J = 7.9 Hz, 1H), 5.79 (s, 1H), 3.84 (m,
1H), 3.15 (m, 1H), 2.75 (m, 2H), 2.54 (s, 3H), 2.52 (s,
3H), 1.95–2.11 (m, 2H); Anal. Calcd for C17H21N3O-
SÆ1/5H2O: C, 64.00; H, 6.76; N, 13.17. Found: C,
64.27; H, 6.76; N, 13.16.
5.3.10. 3-[3-(Dimethylamino)propyl]-4-(2-naphthyl)-3,4-
dihydroquinazolin-2(1H)-one (9j). The title compound
was prepared from 15j to give 9j as a solid in 75% yield.
1H NMR (CDCl3, 270 MHz) d 7.95 (br s, 1H), 7.75–7.85
(m, 4H), 7.47 (m, 3H), 7.12 (m, 1H), 7.02 (br d,
J = 7.0 Hz, 1H), 6.76–6.88 (m, 2H), 5.72 (s, 1H), 3.90
(m, 1H), 2.98 (m, 1H), 2.17–2.32 (2H, m), 2.17 (m,
6H), 1.66–1.88 (m, 2H); HRMS (EI) M+ calcd for
C23H25N3O 359.1997, found 359.1981.
5.3.5. 3-[3-(Dimethylamino)propyl]-4-(2-pyridyl)-3,4-di-
hydroquinazolin-2(1H)-one (9e). The title compound
was prepared from 15e to give 9e as a white powder in
53% yield. mp 128–129 °C (from CH2Cl2/diethyl ether);
1H NMR (CDCl3, 270 MHz) d 8.54 (m, 1H), 7.91 (m,
1H), 7.63 (m, 1H), 7.12–7.32 (m, 4H), 6.90 (m, 1H),
6.77 (m, 1H), 5.71 (s, 1H), 3.92 (m, 1H), 3.00 (m, 1H),
2.33 (m, 2H), 2.24 (m, 6H), 1.87 (m, 2H); Anal. Calcd
for C18H22N4OÆ1/4H2O: C, 68.66; H, 7.20; N, 17.79.
Found: C, 68.41; H, 7.17; N, 17.68.
5.3.11. 3-(4-Methylpentyl)-4-phenyl-3,4-dihydroquinazo-
lin-2(1H)-one (9k). The title compound was prepared
from 15k to give 9k as a white solid in 91% yield. mp
148–151 °C (diethyl ether/hexane); 1H NMR (CDCl3,
270 MHz) d 7.23–7.35 (m, 5H), 7.10–7.16 (m, 1H),
7.02 (d, J = 7.6 Hz, 1H), 6.85–6.91 (m, 1H), 6.68–6.72
(m, 1H), 5.47 (s, 1H), 3.79–3.90 (m, 1H), 2.74–2.85 (m,
1H), 1.44–1.65 (m, 4H), 1.13–1.17 (m, 1H), 0.84 (d,
J = 6.6 Hz, 6H); Anal. Calcd for C20H24N2OÆ1/5H2O:
C, 76.99; H, 7.88; N, 8.98. Found: C, 77.18; H, 7.84;
N, 8.95.
5.3.6. 3-[3-(Dimethylamino)propyl]-4-methyl-3,4-dihydro-
quinazolin-2(1H)-one (9f). The title compound was pre-
pared from 15f to give 9f as a white powder in 84%
yield. mp 79–81 °C (from diethyl ether/hexane); 1H
NMR (DMSO-d6, 300 MHz) d 9.17 (s, 1H), 7.07–7.13
(m, 2H), 6.86 (dt, J = 0.9, 7.5 Hz, 1H), 6.78 (d,
J = 7.5 Hz, 1H), 4.55 (q, J = 6.4 Hz, 1H), 3.64–3.74
(m, 1H), 2.90–2.99 (m, 1H), 2.16–2.28 (m, 2H), 2.13 (s,
6H), 1.57–1.70 (m, 2H), 1.22 (d, J = 6.4 Hz, 3H); Anal.
Calcd for C14H21N3O: C, 67.98; H, 8.56; N, 16.99.
Found: C, 67.58; H, 8.55; N, 16.98.
5.3.12. 3-(2-Ethoxyethyl)-4-phenyl-3,4-dihydroquinazo-
lin-2(1H)-one (9l). The title compound was prepared
from 15l to give 9l as a white powder in 64% yield. mp
118–119 °C (from diethyl ether/hexane); 1H NMR
(CDCl3, 270 MHz) d 8.11 (br s, 1H), 7.22–7.52 (m,
5H), 6.73–7.15 (m, 4H), 5.73 (s, 1H), 4.02 (m, 1H),
3.41–3.70 (m, 4H), 3.08 (m, 1H), 1.16 (t, J = 7.0 Hz,
3H); Anal. Calcd for C18H20N2O2Æ1/5H2O: C, 72.07;
H, 6.85; N, 9.34. Found: C, 72.30; H, 6.76; N, 9.41.
5.3.7. 4-Isopropyl-3-[3-(dimethylamino)propyl]-3,4-dihy-
droquinazolin-2(1H)-one (9g). The title compound was
prepared from 15g to give 9g as an oil in 76%
5.3.13. N,N-Diethyl-2-(2-oxo-4-phenyl-1,4-dihydroquin-
azolin-3(2H)-yl)acetamide (9m). The title compound
was prepared from 15m to give 9m as a white powder
in 86% yield. mp 142–144 °C (from EtOH); H NMR
(CDCl3, 270 MHz) d 7.60 (br s, 1H), 7.26–7.38 (m,
5H), 7.06–7.13 (m, 1H), 6.82–6.86 (m, 4H), 6.70 (m,
1H), 5.83 (s, 1H), 4.94 (ABq, J = 16.0 Hz, 1H), 3.29
(ABq, J = 16.0 Hz, 1H), 3.12–3.42 (m, 4H), 1.13 (t,
J = 7.0 Hz, 3H), 1.08 (t, J = 7.0 Hz, 3H); Anal. Calcd
for C20H23N3O2Æ1/5H2O: C, 70.44; H, 6.92; N, 12.32.
Found: C, 70.73; H, 6.84; N, 12.31.
1
yield. H NMR (CDCl3, 270 MHz) d 7.33 (br s, 1H),
1
7.17 (m, 1H), 6.96 (m, 2H), 6.70 (m, 1H), 4.20 (d,
J = 5.0 Hz, 1H), 4.03 (m, 1H), 3.09 (m, 1H), 2.18 (s,
6H), 2.10–2.31 (m, 3H), 1.76 (m, 2H), 0.94 (d,
J = 7.0 Hz, 1H), 0.78 (d, J = 7.0 Hz, 3H); HRMS (EI)
M+ calcd for C16H25N3O2 275.1997, found 275.1987.
5.3.8. 4-Cyclohexyl-3-[3-(dimethylamino)propyl]-3,4-di-
hydroquinazolin-2(1H)-one (9h). The title compound
was prepared from 15h to give 9h as a white powder
1
in 11% yield. mp 124–125 °C (from EtOH); H NMR
5.3.14. 3-[2-(Benzylamino)ethyl]-4-phenyl-3,4-dihydroquin-
azolin-2(1H)-one (9n). The title compound was prepared
from 15n to give 9n as a white powder in 47% yield. mp
102–104 °C (from diethyl ether/EtOH); 1H NMR
(CDCl3, 270 MHz) d 7.63 (br s, 1H), 7.21–7.34 (m,
(CDCl3, 270 MHz) d 7.65 (br s, 1H), 7.17 (m, 1H),
6.94 (m, 2H), 6.73 (m, 1H), 4.16 (d, J = 5.0 Hz, 1H),
4.04 (m, 1H), 3.02 (m, 1H), 2.28 (m, 2H), 2.17 (s, 6H),
1.72 (m, 7H), 1.04 (m, 5H), 0.80 (m, 1H); Anal. Calcd