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(s, 1H), 8.50 (d, J = 5.4 Hz, 1H), 8.12 (d, J = 8.1 Hz, 2H), 8.06 (s, 1H),
7.89–7.95 (dd, J1 = 13.5 Hz, J2 = 2.4 Hz, 1H), 7.81 (d, J = 8.1 Hz, 2H),
7.64–7.67 (m, 1H), 7.55 (s, 1H), 7.40–7.46 (m, 2H), 6.48 (d,
J = 5.4 Hz, 1H), 4.21 (t, J = 6.0 Hz, 2H), 3.96 (s, 3H), 3.60 (t, 4H),
2.46–2.49 (m, 2H), 2.32–2.44 (br, 4H), 1.95–2.03 (m, 2H). MS
(ESI) m/z: 642.3, 643.3 (M+). Anal. Calcd for C32H31F4N5O5 (%): C,
59.90; H, 4.87; N, 10.92. Found (%): C, 59.86; H, 4.87; N, 10.89.
1.46–1.71 (m, 3H), 0.95 (d, J = 6.0 Hz, 3H). MS (ESI) m/z: 604.2,
605.2, 606.2 (M+). Anal. Calcd for C33H35F2N5O4 (%): C, 65.66; H,
5.84; N, 11.60. Found (%): C, 65.61; H, 5.81; N, 11.56.
7.1.14.11. (E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(4-methylpiperi-
din-1-yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-chloroben-
zylidene)semicarbazide (22c).
White solid, yield: 86.5%. Mp:
216–218 °C. 1H NMR (300 MHz, DMSO-d6) d 10.99 (s, 1H), 9.27 (s,
1H), 8.49 (d, J = 5.4 Hz, 1H), 7.98 (s, 1H), 7.89–7.94 (m, 3H), 7.63–
7.66 (m, 1H), 7.55 (s, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.38–7.44 (m,
2H), 6.47 (d, J = 5.4 Hz, 1H), 4.19 (t, J = 6.3 Hz, 2H), 3.96 (s, 3H),
2.86–2.95 (m, 2H), 2.52–2.57 (m, 2H), 1.94–2.04 (m, 4H), 1.57–
1.62 (m, 2H), 1.27–1.43 (br, 1H), 1.06–1.23 (m, 2H), 0.90 (d,
J = 6.3 Hz, 3H). MS (ESI) m/z: 620.3, 622.4 (M+). Anal. Calcd for
7.1.14.6.
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-fluorobenzylid-
ene)semicarbazide (21a). White solid, yield: 86.1%. Mp:
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(piperidin-1-
211–213 °C. 1H NMR (300 MHz, DMSO-d6) d 10.77–11.18 (br,
1H), 9.12–9.43 (br, 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.99 (s, 1H), 7.89–
7.97 (m, 3H), 7.63–7.68 (m, 1H), 7.54 (s, 1H), 7.38–7.44 (m, 2H),
7.28 (t, J = 9.0 Hz, 2H), 6.47 (d, J = 5.1 Hz, 1H), 4.19 (t, J = 6.6 Hz,
2H), 3.96 (s, 3H), 2.43 (t, J = 6.9 Hz, 2H), 2.26–2.40 (br, 4H), 1.89–
2.01 (m, 2H), 1.44–1.56 (m, 4H), 1.31–1.44 (m, 2H). MS (ESI) m/z:
590.4, 591.3, 592.3 (M+). Anal. Calcd for C32H33F2N5O4 (%): C,
65.18; H, 5.64; N, 11.88. Found (%): C, 65.12; H, 5.60; N, 11.87.
C33H35ClFN5O4 (%): C, 63.92; H, 5.69; N, 11.29. Found (%): C,
63.88; H, 5.68; N, 11.26.
7.1.14.12.
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(pyrrolidin-1-
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(benzylidene)semi-
carbazide (23a).
White solid, yield: 83.8%. Mp: 195–196 °C.
7.1.14.7.
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(benzylidene)semi-
carbazide (21b). White solid, yield: 83.9%. Mp: 200–202 °C.
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(piperidin-1-
1H NMR (300 MHz, DMSO-d6) d 10.92 (s, 1H), 9.23 (s, 1H), 8.49
(d, J = 5.4 Hz, 1H), 8.00 (s, 1H), 7.95 (dd, J1 = 13.5 Hz, J2 = 2.4 Hz,
1H), 7.86–7.90 (m, 2H), 7.65–7.68 (m, 1H), 7.55 (s, 1H), 7.38–
7.48 (m, 5H), 6.47 (dd, J1 = 5.4 Hz, J2 = 0.9 Hz, 1H), 4.21 (t,
J = 6.3 Hz, 2H), 3.96 (s, 3H), 2.58 (t, J = 7.2 Hz, 2H), 2.40–2.48 (m,
4H), 1.95–2.01 (m, 2H), 1.65–1.73 (m, 4H). MS (ESI) m/z: 558.6,
559.6 (M+). Anal. Calcd for C31H32FN5O4 (%): C, 66.77; H, 5.78; N,
12.56. Found (%): C, 66.69; H, 5.76; N, 12.53.
1H NMR (300 MHz, DMSO-d6) d 10.83–11.05 (br, 1H), 9.14–9.34
(br, 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.99 (s, 1H), 7.94 (dd, J1 = 13.5 Hz,
J2 = 2.4 Hz, 1H), 7.86–7.89 (m, 2H), 7.64–7.68 (m, 1H), 7.55 (s,
1H), 7.38–7.48 (m, 5H), 6.47 (d, J = 5.1 Hz, 1H), 4.19 (t, J = 6.3 Hz,
2H), 3.96 (s, 3H), 2.43 (t, J = 6.9 Hz, 2H), 2.25–2.39 (br, 4H), 1.92–
2.01 (m, 2H), 1.46–1.55 (m, 4H), 1.32–1.45 (m, 2H). MS (ESI) m/z:
571.3, 572.4 (M+). Anal. Calcd for C32H34FN5O4 (%): C, 67.23; H,
6.00; N, 12.25. Found (%): C, 67.16; H, 5.99; N, 12.23.
7.1.14.13.
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-fluorobenzylid-
ene)semicarbazide (23b). White solid, yield: 85.1%. Mp:
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(pyrrolidin-1-
7.1.14.8.
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-chlorobenzyli-
dene)semicarbazide (21c). White solid, yield: 89.4%. Mp:
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(piperidin-1-
211–213 °C. 1H NMR1H NMR (300 MHz, DMSO-d6) d 10.92 (s,
1H), 9.24 (s, 1H), 8.50 (d, J = 5.1 Hz, 1H), 7.99 (s, 1H), 7.89–7.97
(m, 3H), 7.63–7.66 (m, 1H), 7.55 (s, 1H), 7.38–7.44 (t, J = 9.0 Hz,
2H), 7.25–7.31 (t, J = 9.0 Hz, 2H), 6.47 (d, J = 5.1 Hz, 1H), 4.23 (t,
J = 6.0 Hz, 2H), 3.97 (s, 3H), 2.62–2.86 (m, 6H), 2.01–2.10 (m, 2H),
1.69–1.82 (m, 4H). 13C NMR (600 MHz, DMSO-d6) d 164.1, 162.5,
159.9, 154.7, 153.5, 153.1, 152.2, 149.4, 146.8, 140.8, 131.4,
129.8, 129.7, 124.2, 116.8, 116.1, 116.0, 115.0, 109.1, 108.7,
108.6, 102.4, 99.5, 66.8, 56.2, 53.7 (2C), 52.3, 27.1, 23.4 (2C). MS
(ESI) m/z: 576.2, 577.2 (M+). Anal. Calcd for C31H31F2N5O4 (%): C,
64.69; H, 5.43; N, 12.17. Found (%): C, 64.66; H, 5.40; N, 12.16.
214–217 °C. 1H NMR (300 MHz, DMSO-d6) d 10.88–11.39 (br,
1H), 9.34–9.61 (br, 1H), 8.49 (d, J = 5.4 Hz, 1H), 7.98 (s, 1H), 7.88–
7.95 (m, 3H), 7.61–7.65 (m, 1H), 7.54 (s, 1H), 7.51 (d, J = 8.7 Hz,
2H), 7.38–7.44 (m, 2H), 6.46 (d, J = 5.4 Hz, 1H), 4.19 (t, J = 6.3 Hz,
2H), 3.96 (s, 3H), 2.43 (t, J = 7.2 Hz, 2H), 2.30–2.40 (br, 4H), 1.92–
2.01 (m, 2H), 1.45–1.55 (m, 4H), 1.36–1.42 (m, 2H). MS (ESI) m/z:
606.3, 608.3, 609.2 (M+). Anal. Calcd for C32H33ClFN5O4 (%): C,
63.41; H, 5.49; N, 11.56. Found (%): C, 63.38; H, 5.48; N, 11.54.
7.1.14.9. (E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(4-methylpiperi-
din-1-yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(benzyli-
7.1.14.14.
yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-chlorobenzyli-
dene)semicarbazide (23c). White solid, yield: 79.7%. Mp:
(E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(pyrrolidin-1-
dene)semicarbazide (22a).
White solid, yield: 84.4%. Mp:
213–216 °C. 1H NMR (300 MHz MHz, DMSO-d6) d 10.91 (s, 1H),
9.22 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 7.99 (s, 1H), 7.95 (dd,
J1 = 13.5 Hz, J2 = 2.4 Hz, 1H), 7.89 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 2H),
7.68 (m, 1H), 7.55 (s, 1H), 7.38–7.48 (m, 5H), 6.47 (d, J = 5.4 Hz,
1H), 4.19 (t, J = 6.3 Hz, 2H), 3.96 (s, 3H), 2.87 (d, J = 11.7 Hz, 2H),
2.45 (t, J = 7.2 Hz, 2H), 1.84–2.01 (m, 4H), 1.60 (d, J = 11.7 Hz, 2H),
1.23–1.40 (m, 1H), 1.03–1.21 (m, 2H), 0.90 (d, J = 6.3 Hz, 3H). MS
(ESI) m/z: 586.4, 587.4 (M+). Anal. Calcd for C33H36FN5O4 (%): C,
67.68; H, 6.20; N, 11.96. Found (%): C, 67.65; H, 6.17; N, 11.95.
210–212 °C. 1H NMR (300 MHz, DMSO-d6) d 11.00 (s, 1H), 9.28 (s,
1H), 8.49 (d, J = 5.1 Hz, 1H), 7.98 (s, 1H), 7.89–7.94 (m, 3H), 7.63–
7.67 (m, 1H), 7.55 (s, 1H), 7.48–7.52 (m, 2H), 7.38–7.44 (m, 2H),
6.47 (dd, J1 = 5.4 Hz, J2 = 0.9 Hz, 1H), 4.22 (t, J = 6.3 Hz, 2H), 3.96
(s, 3H), 2.65–2.74 (m, 2H), 2.54–2.61 (br, 4H), 1.98–2.07 (m, 2H),
1.65–1.83 (br, 4H). MS (ESI) m/z: 592.1, 593.1, 595.1 (M+). Anal.
Calcd for C31H31ClFN5O4 (%): C, 62.89; H, 5.28; N, 11.83. Found
(%): C, 62.88; H, 5.25; N, 11.79.
7.1.14.15. (E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(piperidin-1-yl)
propoxy)quinolin-4-yloxy)phenyl)-N4-(3,4-difluorobenzylidene)
7.1.14.10. (E)-N1-(3-Fluoro-4-(6-methoxy-7-(3-(4-methylpiperi-
din-1-yl)propoxy)quinolin-4-yloxy)phenyl)-N4-(4-fluorobenzy-
semicarbazide (24).
White solid, yield: 88.6%. Mp: 210–
lidene)semicarbazide (22b).
White solid, yield: 87.7%. Mp:
212 °C. 1H NMR (300 MHz, DMSO-d6) d 11.04 (s, 1H), 9.27 (s, 1H),
8.49 (d, J = 5.4 Hz, 1H), 8.13–8.21 (m, 1H), 7.96 (s, 1H), 7.89 (dd,
J1 = 13.5 Hz, J2 = 2.4 Hz, 1H), 7.61–7.66 (m, 2H), 7.55 (s, 1H),
7.48–7.52 (m, 1H), 7.40–7.45 (m, 2H), 6.47 (d, J = 5.4 Hz, 1H),
4.19 (t, J = 6.3 Hz, 2H), 3.96 (s, 3H), 2.43 (t, J = 7.2 Hz, 2H), 2.36
(br, 4H), 1.92–2.01 (m, 2H), 1.48–1.55 (m, 4H), 1.34–1.44 (m,
2H). MS (ESI) m/z: 608.5, 609.5, 610.5 (M+). Anal. Calcd for
215–218 °C. 1H NMR (300 MHz, DMSO-d6) d 10.96 (s, 1H), 10.28
(br, 1H), 9.30 (s, 1H), 8.58 (d, J = 5.4 Hz, 1H), 8.00 (s, 1H), 7.91–
7.97 (m, 2H), 7.65–7.68 (m, 1H), 7.62 (s, 1H), 7.53 (s, 1H), 7.44 (t,
J = 9.0 Hz, 1H), 7.28 (t, J = 9.0 Hz, 2H), 6.60 (d, J = 5.4 Hz, 1H), 4.29
(t, J = 6.0 Hz, 2H), 3.99 (s, 3H), 3.49–3.53 (m, 2H), 3.19–3.25 (br,
2H), 2.88–2.94 (m, 2H), 2.28–2.38 (m, 2H), 1.77–1.82 (m, 2H),