2296
R. Kakadiya et al. / Bioorg. Med. Chem. 18 (2010) 2285–2299
(freshly prepared from 15, 2.81 g, 9 mmol). Yield was 1.78 g
(77%); mp 251–252 °C; 1H NMR (DMSO-d6) d 9.31 (br s, 1H,
NH, exchangeable), 9.21 (br s, 1H, NH, exchangeable), 8.17 (s,
1H, ArH), 7.82 (d, J = 9.1 Hz, 1H, ArH), 7.63 (s, 1H, ArH), 7.44
(dd, J = 2.3 and 9.1 Hz, 1H, ArH), 7.38 (d, J = 8.9 Hz, 2H, ArH),
6.76 (d, J = 8.9 Hz, 2H, ArH), 3.98 (s, 3H, OMe), 3.72–3.73 (m,
8H, 4 ꢀ CH2), 2.58 (s, 3H, Me). Anal. Calcd for (C22H24Cl2N4O2):
C, H, N.
J = 9.2 Hz, 2H, ArH), 6.25 (s, 2H, CH2), 3.73–3.71 (m, 8H, 4 ꢀ CH2).
Anal. Calcd for (C27H24Cl2N4O3): C, H, N.
4.3.8. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[6-chloro-2-
(3-methoxyphenyl)-4-quinolinyl] urea (17h)
Compound 17h was prepared from 6-chloro-2-(3-methoxy-
phenyl)-4-quinolinamine (13h, 1.01 g, 3.5 mmol) and isocyanate
16 (freshly prepared from 15, 1.71 g, 5.6 mmol). Yield, 1.50 g
(78%); mp >300 °C; 1H NMR (DMSO-d6) d 9.21 (1H, s, NH,
exchangeable), 8.98 (1H, s, NH, exchangeable), 8.88 (s, 1H, ArH),
8.30 (d, J = 1.8 Hz, 1H, ArH), 8.05 (d, J = 8.9 Hz, 1H, ArH), 7.78 (dd,
J = 1.9 and 8.9 Hz, 1H, ArH), 7.71 (s, 1H, ArH), 7.67 (d, J = 7.8 Hz,
1H, ArH), 7.48 (t, J = 7.9 Hz, 1H, ArH), 7.38 (d, J = 8.9 Hz, 2H, ArH),
7.09 (dd, J = 2.3 and 8.2 Hz, 1H, ArH), 6.77 (d, J = 9.0 Hz, 2H, ArH),
3.87 (s, 3H, CH3), 3.70–3.73 (m, 8H, 4 ꢀ CH2). Anal. Calcd for
(C27H25Cl3N4O2): C, H, N.
4.3.3. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-(6-methyl[1,3]-
dioxolo[4,5-g] quinolin-8-yl)urea (17c)
Compound 17c was prepared from 6-methyl[1,3]dioxolo-[4,5-
g]quinolin-8-amine (13c, 1.01 g, 5 mmol) and isocyanate 16
(freshly prepared from 15, 2.81 g, 9 mmol). Yield, 1.35 g (58%);
mp 271–272 °C; 1H NMR (DMSO-d6) d 2.54 (s, 3H, Me), 3.71
(m, 8H, 4 ꢀ CH2), 6.23 (s, 2H, CH2), 6.76 (d, J = 8.9 Hz, 2H,
ArH), 7.25 (s, 1H, ArH), 7.35 (d, J = 8.9 Hz, 2H, ArH), 7.71 (s,
1H, ArH), 8.08 (s, 1H, ArH), 9.15. Anal. Calcd for (C22H22Cl2N4O3):
C, H, N.
4.3.9. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[6-methoxy-
2-(3-methoxy-phenyl)-4-quinolinyl]urea (17i)
Compound 17i was prepared from 6-methoxy-2-(3-methoxy-
phenyl)-4-quinolinamine (13i, 0.56 mg, 2 mmol) and isocyanate
16 (freshly prepared from 15, 1.21 g, 3.6 mmol). Yield, 0.80 g
(74%); mp 255–256 °C; 1H NMR (DMSO-d6) d 9.01 (br s, 2H,
exchangeable, 2 ꢀ NH), 8.78 (s, 1H, ArH), 7.99 (d, J = 10.3 Hz, 1H,
ArH), 7.65 (m, 2H, ArH), 7.54 (m, 1H, ArH), 7.43 (m, 4H, ArH),
7.07 (dd, J = 2.2 and 8.1 Hz, 1H, ArH), 6.72 (d, J = 8.8 Hz, 2H, ArH),
4.01 (s, 3H, OMe), 3.87 (s, 3H, OMe), 3.72 (m, 8H, 4 ꢀ CH2). Anal.
Calcd for (C28H28Cl2N4O3): C, H, N.
4.3.4. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[6-(dimethyl-
amino)-2-methyl-4-quinolinyl]urea (17d)
Compound 17d was prepared from 4-amino-6-dimethylamino-
2-methylquinoline (13d, 1.03 g, 5 mmol) and isocyanate 16
(freshly prepared from 15, 2.89 g, 9 mmol). Yield, 1.53 g (65%);
mp 267–268 °C; 1H NMR (DMSO-d6) d 10.27 (1H, br s, NH,
exchangeable), 9.98 (1H, br s, NH, exchangeable), 8.33 (s, 1H,
ArH), 7.82 (d, J = 9.4 Hz, 1H, ArH), 7.55–7.58 (m, 1H, ArH), 7.44 (s,
1H, ArH), 7.40 (d, J = 8.9 Hz, 2H, ArH), 6.77 (d, J = 8.9 Hz, 2H,
ArH), 3.72–3.73 (m, 8H, 4 ꢀ CH2), 3.14 (s, 6H, 2 ꢀ Me), 2.66 (s,
3H, Me). Anal. Calcd for (C23H27Cl2N5O): C, H, N.
4.3.10. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[6-(3-
methoxyphenyl) [1,3]dioxolo [4,5-g]quinolin-8-yl]urea (17j)
Compound 17j was prepared from 6-(3-methoxy-phenyl)-
[1,3]dioxolo[4,5-g]quinolin-8-amine (13j, 0.75 g, 2.5 mmol) and
isocyanate 16 (freshly prepared from 15, 1.40 g, 4.5 mmol). Yield,
0.95 g (69%); mp 202–203 °C; 1H NMR (DMSO-d6) d 8.91 (s, 1H,
NH, exchangeable), 8.89 (s, 1H, NH, exchangeable), 8.68 (s, 1H,
ArH), 7.65–7.61 (m, 2H, ArH), 7.57 (s, 1H, ArH), 7.44 (t, J = 7.8 Hz,
1H, ArH), 7.38–7.36 (m, 3H, ArH), 7.04 (dd, J = 8 and 2.4 Hz, 1H,
ArH), 6.76 (d, J = 8.8 Hz, 2H, ArH), 6.25 (s, 2H, CH2), 3.86 (s, 3H,
OMe), 3.73–3.72 (m, 8H, 4 ꢀ CH2). Anal. Calcd for (C28H26Cl2N4O4):
C, H, N.
4.3.5. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[2-methyl-6-
(1-pyrrolidinyl)-4-quinolinyl]urea (17e)
Compound 17e was prepared from 2-methyl-6-(pyrrolidin-1-
yl)-quinolin-4-amine (13e, 0.46 g, 2 mmol) and isocyanate 16
(freshly prepared from 15, 1.21 g, 3.6 mmol). Yield, 0.61 g (63%);
mp 255–256 °C; 1H NMR (DMSO-d6) d 11.83 (s, 1H, NH, exchange-
able), 9.56 (s, 1H, NH, exchangeable), 7.70 (d, J = 8.8 Hz, 1H, ArH),
7.47 (d, J = 8.4 Hz, 2H, ArH), 7.16–7.05 (m, 1H, ArH), 7.05 (s, 1H,
ArH), 6.76 (d, J = 8.8 Hz, 2H, ArH), 6.67 (s, 1H, ArH), 3.72 (m, 8H,
4 ꢀ CH2), 3.34 (m, 4H, 2 ꢀ CH2), 2.56 (s, 3H, Me), 2.00 (m, 4H,
2 ꢀ CH2). Anal. Calcd for (C25H29Cl2N5O): C, H, N.
4.3.11. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[2-(3-
methoxyphenyl)-6-(1-pyrrolidinyl)-4-quinolinyl]urea (17k)
Compound 17k was prepared from 2-(3-methoxy-phenyl)-6-
(pyrrolidin-1-yl)quinolin-4-amine (13k, 0.64 g, 2 mmol) and isocy-
anate 16 (freshly prepared from 15, 1.21 g, 3.6 mmol). Yield, 0.90 g
(78%); mp 166–167 °C; 1H NMR (DMSO-d6) d 9.17 (s, 1H, NH,
exchangeable), 8.86 (s, 1H, NH, exchangeable), 8.70 (s, 1H, ArH),
7.88 (d, J = 9.2 Hz, 1H, ArH), 7.65–7.60 (m, 2H, ArH), 7.46–7.39
(m, 3H, ArH), 7.28 (d, J = 9.2 Hz, 1H, ArH), 7.02 (d, J = 8 Hz, 1H,
ArH), 6.87 (s, 1H, ArH), 6.77 (d, J = 8.8 Hz, 2H, ArH), 3.86 (s, 3H,
OMe), 3.73 (m, 8H, 4 ꢀ CH2), 3.46 (m, 4H, 2 ꢀ CH2), 2.07–2.05 (m,
4H, 2 ꢀ CH2). Anal. Calcd for (C31H33Cl2N5O2): C, H, N.
4.3.6. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-(2-phenyl-4-
quinolinyl)urea (17f)
Compound 17f was prepared from 2-phenylquinolin-4-amine
(13f, 0.55 g, 2.5 mmol) and isocyanate 16 (freshly prepared from
15, 1.40 g, 4.5 mmol). Yield, 0.87 g (73%); mp 194–195 °C; 1H
NMR (DMSO-d6) d 9.22 (s, 1H, NH, exchangeable), 9.07 (s, 1H,
NH, exchangeable), 8.87 (s, 1H, ArH), 8.21 (d, J = 8.4 Hz, 1H, ArH),
8.15 (d, J = 7.6 Hz, 2H, ArH), 8.04 (d, J = 8.4 Hz, 1H, ArH), 7.79 (t,
J = 7.6 Hz, 1H, ArH), 7.66 (t, J = 7.6 Hz, 1H, ArH), 7.58–7.55 (m,
2H, ArH), 7.52–7.50 (m, 1H, ArH), 7.29 (d, J = 8.8 Hz, 2H, ArH),
6.77 (d, J = 8.8 Hz, 2H, ArH), 3.72–3.69 (m, 8H, 4 ꢀ CH2). Anal. Calcd
for (C26H24Cl2N4O): C, H, N.
4.3.12. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-[6-(2-
fluorophenyl)[1,3]dioxolo[4,5-g]quinolin-8-yl]urea (17l)
Compound 17l was prepared from 6-(2-flourophenyl)-
[1,3]dioxolo[4,5-g]quinolin-8-amine (13l, 0.71 g, 2.5 mmol) and
isocyanate 16 (freshly prepared from 15, 1.40 g, 4.5 mmol). Yield,
1.09 g (80%); mp 188–189 °C; 1H NMR (DMSO-d6) d 8.92 (s, 1H,
NH, exchangeable), 8.89 (s, 1H, NH, exchangeable), 8.59–8.58 (m,
1H, ArH), 7.99–7.94 (m, 1H, ArH), 7.59 (s, 1H, ArH), 7.53–7.48 (m,
1H, ArH), 7.38–7.32 (m, 5H, ArH), 6.76 (d, J = 9.2 Hz, 2H, ArH),
6.26 (s, 2H, CH2), 3.72–3.71 (m, 8H, 4 ꢀ CH2). Anal. Calcd for
(C27H23Cl2FN4O3): C, H, N.
4.3.7. N-{4-[Bis(2-chloroethyl)amino]phenyl}-N0-(6-phenyl[1,3]-
dioxolo[4,5-g]quinolin-8-yl)urea (17g)
Compound 17g was prepared from 6-phenyl-[1,3]dioxolo[4,5-
g]quinolin-8-amine (13g, 0.66 g, 2.5 mmol) and isocyanate 16
(freshly prepared from 15, 1.40 g, 4.5 mmol). Yield, 0.85 g (65%);
mp 191–192 °C; 1H NMR (DMSO-d6) d 8.92 (s, 1H, NH, exchange-
able), 8.91 (s, 1H, NH, exchangeable), 8.71 (s, 1H, ArH), 8.08 (d,
J = 7.2 Hz, 2H, ArH), 7.58 (s, 1H, ArH), 7.55–7.51 (m, 2H, ArH),
7.48–7.44 (m, 1H, ArH), 7.38–7.36 (m, 3H, ArH), 6.77 (d,