K. Kubo et al. / Bioorg. Med. Chem. 11 (2003) 5117–5133
5131
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-bromo-
phenyl)carboxamide (17b). Compound 17b was pre-
pared as described for 3, except using 4-bromobenzoic
acid. Purification was performed by column chromato-
graphy on silica gel eluting with hexane/AcOEt (4/1)
then CHCl3/AcOEt (5/1) to obtain 43 mg (52%). Mp:
224 ꢀC (decomposition); 1H NMR (CDCl3, 400 MHz): d
4.11 (s, 3H), 4.15 (s, 3H), 6.69 (d, J=6.8 Hz, 1H), 7.25 (d,
J=8.8 Hz, 2H), 7.65 (s, 1H), 7.66 (d, J=8.5 Hz, 2H), 7.85
(d, J=8.5 Hz, 2H), 7.95 (d, J=8.8 Hz, 2H), 8.11 (s, 1H),
8.37 (d, J=6.8 Hz, 1H), 8.39 (s, 1H); MS (ESI) m/z 479
(M+), 481 (M++2); HRMS (ESI) (C24H20BrN2O4)
(M+H+) calcd 479.0606, found 479.0637.
1.49–1.57 (m, 2H), 1.78–1.83 (m, 2H), 4.04 (t, J=6.3
Hz, 2H), 4.11 (s, 3H), 4.15 (s, 3H), 6.70 (d, J=6.6 Hz, 1H),
6.99 (d, J=8.8 Hz, 2H), 7.23 (d, J=9.0 Hz, 2H), 7.65 (s,
1H), 7.90 (d, J=8.8 Hz, 2H), 7.90 (d, J=8.8 Hz, 2H), 8.09
(s, 1H), 8.12 (s, 1H), 8.55 (d, J=6.6 Hz, 1H); ESI-MS (m/
+
.
z): 473 (M +1). Anal. (C24H28N2O5 H2O) C, H, N.
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-biphenyl)-
carboxamide (17g). To a solution of 6,7-dimethoxy-4-
(4-aminophenoxy)quinoline (52 mg, 0.18 mmol) and
triethylamine (3 mL) in CH2Cl2 (2 mL) was added 4-
biphenylcarbonyl chloride (80 mg, 0.37 mmol). The
mixture was stirred at room temperature for 6 h. The
reaction mixture was purified by column chromato-
graphy on silica gel eluting CHCl3/acetone (10/1) to
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-trifluoro-
methylphenyl)carboxamide (17c). Compound 17c was
prepared as described for 3, except using 4-tri-
fluoromethylbenzoic acid. Purification was performed
by column chromatography on silica gel eluting with
hexane/AcOEt (4/1) then CHCl3/AcOEt (5/1) to obtain
32 mg (38%). Mp: 240–242 ꢀC; 1H NMR (CDCl3,
400 MHz): d 4.09 (s, 3H), 4.09 (s, 3H), 6.58 (d, J=6.1
Hz, 1H), 7.23 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 7.78 (d,
J=8.1 Hz, 2H), 7.79 (s, 1H), 7.94 (d, J=8.8 Hz, 2H),
8.11 (d, J=8.3 Hz, 2H), 8.39 (d, J=6.1 Hz, 1H), 8.54 (s,
1H); MS (ESI) m/z 469 (M++1). Anal.
(C25H19F3N2O4) C, H, N.
ꢀ
1
obtain 9 mg of 17g (10%). Mp 235–237 C; H NMR
(CDCl3, 400 MHz): d 4.11 (s, 3H), 4.14 (s, 3H), 6.68 (d,
J=6.3 Hz, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.41–7.51 (m,
4H), 7.64 (d, J=8.5 Hz, 2H), 7.64 (s, 1H), 7.74 (d,
J=8.3 Hz, 2H), 7.94 (d, J=8.8 Hz, 2H), 8.03 (d, J=8.5
Hz, 2H), 8.30 (s, 1H), 8.42 (d, J=6.3 Hz, 1H); MS (ESI)
m/z 476 (M++1). Anal. (C30H24N2O4) C, H, N.
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(3,4-dime-
thoxyphenyl)carboxamide (17h). Compound 17h was pre-
pared as described for 3, except using 3,4-
dimethoxybenzoic acid. Purification was performed by
column chromatography on silica gel eluting with hex-
ane/AcOEt (4/1) then CHCl3/AcOEt (5/1) to obtain 7
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-n-butyl-
phenyl)carboxamide(17d). Compound 17d was prepared
as described for 3, except using 4-n-butylbenzoic acid.
Purification was performed by column chromatography
on silica gel eluting with hexane/AcOEt (4/1) then
CHCl3/AcOEt (5/1) to obtain 65 mg (78%). Mp: 135 ꢀC;
1H NMR (CDCl3, 400 MHz): d 0.95(t, J=7.3 Hz, 3H),
1.33–1.42 (m, 2H), 1.60–1.67 (m, 2H), 2.97 (t, J=7.6 Hz,
2H), 4.09 (s, 3H), 4.10 (s, 3H), 7.60 (d, J=6.1 Hz, 1H),
7.22 (d, J=9.0 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 7.61 (s,
1H), 7.78(s, 1H), 7.83 (d, J=9.0 Hz, 2H), 7.84 (d, J=8.3
Hz, 2H), 8.03 (s, 1H), 8.46 (d, J=5.9 Hz, 1H); MS (ESI)
m/z 457 (M++1). Anal. (C28H28N2O4) C, H, N.
1
mg (8%). H NMR (CDCl3, 400 MHz): d 3.96 (s, 3H),
3.97 (s, 3H), 4.06 (s, 3H), 4.07 (s, 3H), 6.52 (d, J=5.4
Hz, 1H), 6.93 (d, J=8.3 Hz, 1H), 7.21 (d, J=9.0 Hz,
2H), 7.47 (dd, J=2.0, 8.3 Hz, 1H), 7.54 (d, J=2.0 Hz,
1H), 7.58 (s, 1H), 7.80 (d, J=9.0 Hz, 2H), 8.01 (s, 1H),
8.19 (s, 1H), 8.47 (d, J=5.6 Hz, 1H); MS (ESI) m/z 461
(M++1). Anal. (C26H24N2O6) C, H, N.
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-acetyl-
phenyl)carboxamide (17i). Compound 17i was prepared
as described for 3, except using 4-acetylbenzoic acid.
Purification was performed by column chromatography
on silica gel eluting with hexane/AcOEt (4/1) then
CHCl3/AcOEt (5/1) to obtain 43 mg (53%). Mp: 210 ꢀC
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-nitrophe-
nyl)carboxamide (17e). Compound 17e was prepared as
described for 3, except using 4-nitrobenzoic acid. Puri-
fication was performed by column chromatography on
silica gel eluting with hexane/AcOEt (4/1) then CHCl3/
AcOEt (5/1) to obtain 60 mg (77%). Mp 253 ꢀC
(decomposition); 1H NMR (CDCl3, 400 MHz): d 4.09(s,
3H), 4.12 (s, 3H), 6.64 (d, J=5.9 Hz, 1H), 7.25 (d,
J=9.0 Hz, 2H), 7.33 (s, 1H), 7.63 (s, 1H), 7.65 (s, 1H),
7.90 (d, J=8.8 Hz, 2H), 8.15 (d, J=9.0 Hz, 2H), 8.35
(d, J=8.8 Hz, 2H), 8.51 (d, J=5.9 Hz, 1H); MS (ESI)
m/z 446 (M++1); HRMS (ESI) (C24H20N3O6)
(M+H+) calcd 446.1352, found 446.1340.
1
(decomposition); H NMR (CDCl3, 400 MHz): d 2.67
(s, 3H), 4.09 (s, 3H), 4.10 (s, 3H), 6.59 (d, J=5.9 Hz,
1H), 7.24 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 7.77 (s, 1H),
7.90 (d, J=8.5 Hz, 2H), 8.05 (d, J=8.8 Hz, 2H), 8.08
(d, J=8.5 Hz, 2H), 8.36 (s, 1H), 8.43 (d, J=5.9 Hz,
1H); MS (ESI) m/z 443 (M++1); HRMS (ESI)
(C26H23N2O5) (M+H+) calcd 443.1607, found
443.1606.
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-2-thiophene-
carboxamide (17j). Compound 17j was prepared as
described for 3, except using 2-thiophenecaroboxylic
acid. Purification was performed by column chromato-
graphy on silica gel eluting with hexane/AcOEt (4/1)
N-{4-[6,7-Dimethoxy-4-quinolyl]oxy}phenyl}-(4-n-butox-
yophenyl)carboxamide (17f). Compound 17f was pre-
pared as described for 3, except using 4-butoxybenzoic
acid. Purification was performed by column chromato-
graphy on silica gel eluting with hexane/AcOEt (4/1)
1
then CHCl3/AcOEt (5/1) to obtain 37 mg (54%). H
NMR (CDCl3, 400 MHz): d 4.09 (s, 3H), 4.09 (s, 3H),
6.58 (d, J=6.1 Hz, 1H), 7.16 (dd, J=3.9, 5.1 Hz, 1H), 7.20
(d, J=8.8 Hz, 2H), 7.58 (dd, J=1.2, 5.1 Hz, 1H), 7.61 (s,
1H), 7.81 (s, 1H), 7.84 (dd, J=1.2, 3.9 Hz, 1H), 7.87 (d,
J=8.8 Hz, 2H), 8.24 (s, 1H), 8.49 (d, J=5.9 Hz, 1H); MS
1
then CHCl3/AcOEt (5/1) to obtain 34 mg (41%). H
NMR (CDCl3, 400 MHz): d 1.00 (t, J=7.3 Hz, 3H),