Arch. Pharm. Chem. Life Sci. 2013, 346, 596–609
4-Phenoxy-6,7-disubstituted Quinolines and Semicarbazones
605
(E)-N1-(4-Fluorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 17
Anal. calcd. for C31H30F3N5O5 (%): C, 61.08; H, 4.96; N, 11.49.
Found (%): C, 61.01; H, 4.97; N, 11.44.
(E)-N1-(2-Bromo-4-fluorophenyl)-N4-(3-fluoro-4-
(6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)-
benzylidene)semicarbazide 22
1
White solid (87.1%), m.p.: 205–208°C. H NMR (300 MHz, DMSO-
d6) d 10.93 (s, 1H), 9.24 (s, 1H), 8.48 (d, J ¼ 5.1 Hz, 1H), 7.99 (s, 1H),
7.89–7.97 (m, 3H), 7.63–7.67 (m, 1H), 7.55 (s, 1H), 7.39–7.47 (m,
2H), 7.28 (t, J ¼ 8.7 Hz, 2H), 6.47 (d, J ¼ 5.1 Hz, 1H), 4.21 (t,
J ¼ 6.3 Hz, 2H), 3.96 (s, 3H), 3.60–3.63 (m, 4H), 2.30–2.64 (br, 6H),
1.96–2.05 (m, 2H). MS (ESI) m/z: 592.4, 593.5 [MþH]þ. Anal. calcd.
for C31H31F2N5O5 (%): C, 62.94; H, 5.28; N, 11.84. Found (%): C,
62.91; H, 5.29; N, 11.80.
1
White solid (86.6%), m.p.: 206–208°C. H NMR (300 MHz, DMSO-
d6) d 11.14 (s, 1H), 9.31 (s, 1H), 8.50 (d, J ¼ 5.4 Hz, 1H), 8.45 (d,
J ¼ 6.3 Hz, 1H), 8.01 (s, 1H), 7.88–7.93 (dd, J1 ¼ 13.0 Hz, J2 ¼ 1.8
Hz, 1H), 7.63–7.66 (m, 1H), 7.55 (s, 1H), 7.51–7.54 (m, 1H), 7.39–
7.49 (m, 2H), 7.32–7.38 (m, 1H), 6.47 (d, J ¼ 5.4 Hz, 1H), 4.21 (t,
J ¼ 6.3 Hz, 2H), 3.96 (s, 3H), 3.58–3.61 (m, 4H), 2.44–2.48 (m, 2H),
2.33–2.44 (br, 4H), 1.95–2.03 (m, 2H). MS (ESI) m/z: 671.5, 673.4
[MþH]þ. Anal. calcd. for C31H30BrF2N5O5 (%): C, 55.53; H, 4.51; N,
10.44. Found (%): C, 55.53; H, 4.46; N, 10.40.
(E)-N1-(2-Fluorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 18
1
White solid (83.4%), m.p.: 201–203°C. H NMR (300 MHz, DMSO-
(E)-N1-(3-Bromophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 23
d6) d 11.06 (s, 1H), 9.35 (s, 1H), 8.49 (d, J ¼ 5.1 Hz, 1H), 8.20–8.24
(dd, J1 ¼ 12.0 Hz, J2 ¼ 1.8 Hz, 1H), 8.04 (s, 1H), 7.72–7.76 (m, 1H),
7.64–7.69 (m, 1H), 7.52 (s, 1H), 7.46–7.52 (m, 2H), 7.41 (s, 1H), 7.31–
7.38 (m, 1H), 6.80–6.86 (m, 1H), 6.55 (d, J ¼ 5.1 Hz, 1H), 4.22 (t,
J ¼ 6.3 Hz, 2H), 3.95 (s, 3H), 3.57–3.63 (m, 4H), 2.45–2.48 (m, 2H),
2.31–2.42 (br, 4H), 1.94–2.04 (m, 2H). MS (ESI) m/z: 592.5, 593.5
[MþH]þ. Anal. calcd. for C31H31F2N5O5 (%): C, 62.94; H, 5.28; N,
11.84. Found (%): C, 62.93; H, 5.26; N, 11.82.
1
White solid (83.8%), m.p.: 197–200°C. H NMR (300 MHz, DMSO-
d6) d 11.03 (s, 1H), 9.32 (s, 1H), 8.49 (d, J ¼ 5.4 Hz, 1H), 8.05 (s, 1H),
7.95 (s, 1H), 7.89–7.94 (m, 1H), 7.78–7.82 (m, 1H), 7.64–7.67 (m,
1H), 7.60 (m, 1H), 7.55 (s, 1H), 7.37–7.45 (m, 3H), 6.47 (d,
J ¼ 5.4 Hz, 1H), 4.21 (t, J ¼ 6.3 Hz, 2H), 3.96 (s, 3H), 3.58–3.61 (m,
4H), 2.44–2.48 (m, 2H), 2.31–2.43 (br, 4H), 1.94–2.03 (m, 2H). MS
(ESI) m/z: 653.6, 655.5 [MþH]þ. Anal. calcd. for C31H31BrFN5O5 (%):
C, 57.06; H, 4.79; N, 10.73. Found (%): C, 57.03; H, 4.77; N, 10.71.
(E)-N1-(3-Fluorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 19
(E)-N1-(4-Bromophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 24
1
White solid (84.9%), m.p.: 197–198°C. H NMR (300 MHz, DMSO-
d6) d 11.00 (s, 1H), 9.16 (s, 1H), 8.52 (d, J ¼ 5.1 Hz, 1H), 8.20–8.24
(dd, J1 ¼ 12.0 Hz, J2 ¼ 1.5 Hz, 1H), 8.01 (s, 1H), 7.71–7.74 (m, 1H),
7.62–7.69 (m, 1H), 7.53 (s, 1H), 7.48–7.51 (m, 2H), 7.43 (s, 1H), 7.29–
7.37 (m, 1H), 6.81–6.88 (m, 1H), 6.53 (d, J ¼ 5.1 Hz, 1H), 4.21 (t,
J ¼ 6.3 Hz, 2H), 3.96 (s, 3H), 3.58–3.61 (m, 4H), 2.45–2.48 (m, 2H),
2.31–2.42 (br, 4H), 1.94–2.03 (m, 2H). MS (ESI) m/z: 592.4, 593.5
[MþH]þ. Anal. calcd. for C31H31F2N5O5 (%): C, 62.94; H, 5.28; N,
11.84. Found (%): C, 62.93; H, 5.26; N, 11.81.
1
White solid (86.9%), m.p.: 193–196°C. H NMR (300 MHz, DMSO-
d6) d 10.98 (s, 1H), 9.12 (s, 1H), 8.51 (d, J ¼ 5.1 Hz, 1H), 8.20–8.24
(d, J ¼ 12.6 Hz, 1H), 8.00 (s, 1H), 7.70–7.73 (m, 1H), 7.69
(d, J ¼ 8.7 Hz, 2H), 7.47–7.53 (m, 4H), 7.42 (s, 1H), 6.53 (d, J ¼ 5.1 Hz,
1H), 4.21 (t, J ¼ 4.0 Hz, 2H), 3.95 (s, 3H), 3.51–3.66 (br, 4H), 2.31–
2.48 (m, 6H), 1.94–2.03 (m, 2H). MS (ESI) m/z: 653.5, 655.5 [MþH]þ.
Anal. calcd. for C31H31BrFN5O5 (%): C, 57.06; H, 4.79; N, 10.73.
Found (%): C, 57.01; H, 4.77; N, 10.67.
(E)-N1-(2-Methyl-5-fluorophenyl)-N4-(3-fluoro-4-(6-
methoxy-7-(3-morpholinopropoxy)quinolin-4-yloxy)-
benzylidene)semicarbazide 20
(E)-N1-(4-Chlorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 25
1
White solid (76.9%), m.p.: 191–194°C. H NMR (300 MHz, DMSO-
d6) d 11.04 (s, 1H), 8.69 (s, 1H), 8.51 (d, J ¼ 5.4 Hz, 1H), 8.02–8.07
(m, 2H), 7.67–7.70 (m, 1H), 7.48–7.58 (m, 3H), 7.42 (s, 1H), 7.25 (t,
J ¼ 6.6 Hz, 1H), 6.85–6.92 (m, 1H), 6.54 (d, J ¼ 5.4 Hz, 1H), 4.21 (t,
J ¼ 6.0 Hz, 2H), 3.95 (s, 3H), 3.50–3.66 (br, 4H), 2.31–2.45 (br, 6H),
2.27 (s, 3H), 1.95–2.03 (m, 2H). MS (ESI) m/z: 606.5, 607.6 [MþH]þ.
Anal. calcd. for C32H33F2N5O5 (%): C, 63.46; H, 5.49; N, 11.56.
Found (%): C, 63.44; H, 5.49; N, 11.49.
1
White solid (90.2%), m.p.: 187–188°C. H NMR (300 MHz, DMSO-
d6) d 10.98 (s, 1H), 9.13 (s, 1H), 8.52 (d, J ¼ 4.8 Hz, 1H), 8.19–8.23 (d,
J ¼ 12.0 Hz, 1H), 8.00 (s, 1H), 7.73 (d, J ¼ 8.7 Hz, 3H), 7.47–7.54
(m, 2H), 7.43 (s, 1H), 7.37 (d, J ¼ 8.7 Hz, 2H), 6.54 (d, J ¼ 5.1 Hz,
1H), 4.23 (t, J ¼ 4.0 Hz, 2H), 3.96 (s, 3H), 3.56–3.74 (br, 4H), 2.53–
2.78 (br, 6H), 1.94–2.13 (br, 2H). MS (ESI) m/z: 608.3, 610.3 [MþH]þ.
Anal. calcd. for C31H31ClFN5O5 (%): C, 61.23; H, 5.14; N, 11.52.
Found (%): C, 61.18; H, 5.13; N, 11.51.
(E)-N1-(3,5-Difluorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 21
(E)-N1-(3,5-Dichlorophenyl)-N4-(3-fluoro-4-(6-methoxy-7-
(3-morpholinopropoxy)quinolin-4-yloxy)benzylidene)-
semicarbazide 26
1
White solid (85.0%), m.p.: 220–222°C. H NMR (300 MHz, DMSO-
d6) d 11.06 (s, 1H), 9.29 (s, 1H), 8.50 (d, J ¼ 5.1 Hz, 1H), 8.37–8.45
(m, 1H), 8.05 (s, 1H), 7.88–7.93 (dd, J1 ¼ 13.5 Hz, J2 ¼ 2.4 Hz, 1H),
7.62–7.66 (m, 1H), 7.55 (s, 1H), 7.39–7.45 (m, 2H), 7.31–7.38 (m,
1H), 7.19–7.25 (m, 1H), 6.47 (d, J ¼ 5.1 Hz, 1H), 4.21 (t, J ¼ 6.3 Hz,
2H), 3.96 (s, 3H), 3.59–3.62 (m, 4H), 2.54–2.60 (br, 2H), 2.34–2.48
(br s, 4H), 1.95–2.04 (m, 2H). MS (ESI) m/z: 610.6, 611.7 [MþH]þ.
1
White solid (90.9%), m.p.: 214–215°C. H NMR (300 MHz, DMSO-
d6) d 11.15 (s, 1H), 9.27 (s, 1H), 8.52 (d, J ¼ 5.4 Hz, 1H), 8.19–8.24
(dd, J1 ¼ 12.0 Hz, J2 ¼ 1.5 Hz, 1H), 8.01 (s, 1H), 7.87 (s, 1H), 7.86 (s,
1H), 7.72–7.75 (m, 1H), 7.48–7.53 (m, 2H), 7.42 (s, 1H), 7.22 (m, 1H),
6.53 (d, J ¼ 5.1 Hz, 1H), 4.21 (t, J ¼ 6.3 Hz, 2H), 3.96 (s, 3H),
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