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6.3.7. (Z)-1-(4-chlorophenyl)-4-(((3-fluoro-4-((6-methoxy-7-(3-
morpholinopropoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-3-
methyl-1H-pyrazol-5(4H)-one (18)
6.3.12. (Z)-4-(((3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperidin-1-
yl)propoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one (23)
Light yellow solid, 72% yield. mp: 142–143 °C. 1H NMR
(400 MHz, CDCl3) d 11.51 (brs, 1H), 8.52 (d, J = 3.9 Hz, 1H), 7.99
(d, J = 8.7 Hz, 2H), 7.86 (s, 1H), 7.56 (s, 1H), 7.46 (s, 1H), 7.36 (dd,
J = 17.1, 8.6 Hz, 3H), 7.18 (d, J = 10.6 Hz, 1H), 7.10 (d, J = 8.5 Hz,
1H), 6.42 (d, J = 4.3 Hz, 1H), 4.29 (t, J = 6.3 Hz, 2H), 4.06 (s, 3H),
3.74 (t, 4H), 2.59 (t, J = 7.0 Hz, 2H), 2.50 (s, 4H), 2.34 (s, 3H),
2.19–2.10 (m, 2H). ESI-MS m/z: 646.2 (M + H)+. Anal. calcd. for C34-
H33ClFN5O5 (%):C, 63.20; H, 5.15; N, 10.84. Found (%): C, 65.73; H,
5.37; N, 10.96.
Light yellow solid, 71% yield. mp 145–147 °C. 1H NMR
(400 MHz, CDCl3) d 11.42 (brs, 1H), 8.52 (d, J = 4.8 Hz, 1H), 7.94
(d, J = 8.7 Hz, 2H), 7.86 (s, 1H), 7.54–7.48 (m, 4H), 7.45 (d,
J = 13.0 Hz, 1H), 7.34 (t, J = 8.5 Hz, 1H), 7.17 (dd, J = 10.7, 1.9 Hz,
1H), 7.12 (d, J = 8.6 Hz, 1H), 6.43 (d, J = 5.0 Hz, 1H), 4.29 (t,
J = 6.6 Hz, 2H), 4.05 (s, 3H), 2.92 (d, J = 11.2 Hz, 2H), 2.58 (t,
J = 7.3 Hz, 2H), 2.38 (s, 3H), 2.20–2.14 (m, 2H), 1.98 (t, J = 11.2 Hz,
2H), 1.68 (d, J = 12.5 Hz, 2H), 1.31–1.22 (m, 3H), 0.97 (d,
J = 6.3 Hz, 3H). ESI-MS m/z: 624.4 (M + H)+. Anal. calcd. for
C36H38FN5O4 (%):C, 69.32; H, 6.14; N, 11.23. Found (%): C, 69.33;
6.3.8. (Z)-1-(3-chloro-4-fluorophenyl)-4-(((3-fluoro-4-((6-methoxy-
7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)amino)
methylene)-3-methyl-1H-pyrazol-5(4H)-one (19)
H, 6.17; N, 11.26.
6.3.13. (Z)-1-(3-chloro-4-fluorophenyl)-4-(((3-fluoro-4-((6-methoxy-
7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)
amino)methylene)-3-methyl-1H-pyrazol-5(4H)-one (24)
Light yellow solid, 74% yield. mp 122–123 °C. 1H NMR
(400 MHz, CDCl3) d 11.45 (br, 1H), 8.53 (d, J = 4.8 Hz, 1H), 7.97
(dd, J = 11.9, 7.4 Hz, 1H), 7.88 (s, 1H), 7.83–7.73 (m, 1H), 7.57 (s,
1H), 7.47 (s, 1H), 7.36 (t, J = 8.5 Hz, 1H), 7.25–7.15 (m, 2H), 7.11
(d, J = 9.3 Hz, 1H), 6.43 (d, J = 4.9 Hz, 1H), 4.30 (t, J = 6.5 Hz, 2H),
4.06 (s, 3H), 3.79–3.70 (m, 4H), 2.60 (t, J = 7.0 Hz, 2H), 2.51 (s,
4H), 2.34 (s, 3H), 2.20–2.11 (m, 2H). ESI-MS m/z: 664.2 (M + H)+.
Anal. calcd. for C34H32ClF2N5O5 (%):C, 61.49; H, 4.86; N, 10.55.
Found (%): C, 61.50; H, 4.89; N, 10.56.
Light yellow solid, 72% yield. mp 136–138 °C. 1H NMR
(400 MHz, CDCl3) d 11.48 (brs, 1H), 8.52 (d, J = 4.8 Hz, 1H), 7.96
(dd, J = 11.0, 8.5 Hz, 1H), 7.89 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.56
(s, 1H), 7.44 (s, 1H), 7.36 (t, J = 8.5 Hz, 1H), 7.20 (q, J = 9.1 Hz,
2H), 7.11 (d, J = 9.1 Hz, 1H), 6.43 (d, J = 5.0 Hz, 1H), 4.27 (t,
J = 6.7 Hz, 2H), 4.06 (s, 3H), 2.93 (d, J = 11.3 Hz, 2H), 2.56 (t,
J = 7.4 Hz, 2H), 2.35 (s, 3H), 2.20–2.10 (m, 2H), 1.96 (t, J = 11.3 Hz,
2H), 1.64 (d, J = 12.6 Hz, 2H), 1.31–1.24 (m, 3H), 0.94 (d,
J = 6.2 Hz, 3H). ESI-MS m/z: 676.4 (M + H)+. Anal. calcd. for
6.3.9. (Z)-4-(((3-fluoro-4-((6-methoxy-7-(3-(piperidin-1-yl)propoxy)
quinolin-4-yl)oxy)phenyl)amino)methylene)-3-methyl-1-phenyl-1H-
pyrazol-5(4H)-one (20)
C36H36ClF2N5O4 (%):C, 63.95; H, 5.37; N, 10.36. Found (%):
C,63.98; H, 5.39; N, 10.39.
Light yellow solid, 74% yield. mp: 132–133 °C. 1H NMR
(400 MHz, CDCl3) d 11.61 (brs, 1H), 8.52 (d, J = 4.9 Hz, 1H), 8.01
(d, J = 8.0 Hz, 2H), 7.87 (s, 1H), 7.56 (s, 1H), 7.49–7.40 (m, 3H),
7.34 (t, J = 8.4 Hz, 1H), 7.19 (t, J = 10.9 Hz, 2H), 7.09 (d, J = 8.7 Hz,
1H), 6.42 (d, J = 5.1 Hz, 1H), 4.27 (t, J = 6.6 Hz, 2H), 4.05 (s, 3H),
2.54 (t, J = 7.2 Hz, 2H), 2.43 (s, 4H), 2.35 (s, 3H), 2.15 (dt, J = 11.7,
5.9 Hz, 2H), 1.67–1.55 (m, 4H), 1.46 (d, J = 4.1 Hz, 2H). ESI-MS m/
z: 610.5 (M + H)+. Anal. calcd. for C35H36FN5O4 (%):C, 68.95; H,
5.95; N, 11.49. Found (%): C, 68.97; H, 5.97; N, 11.56.
6.3.14. (Z)-4-(((3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-
yl)propoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one (25)
Light yellow solid, 70% yield. mp 152–153 °C. 1H NMR
(400 MHz, CDCl3) d 11.56 (brs, 1H), 8.53 (d, J = 3.4 Hz, 1H), 8.01
(d, J = 8.0 Hz, 2H), 7.87 (s, 1H), 7.56 (s, 1H), 7.48–7.39 (m, 3H),
7.35 (t, J = 8.5 Hz, 1H), 7.20 (t, J = 9.5 Hz, 2H), 7.10 (d, J = 9.3 Hz,
1H), 6.43 (d, J = 4.0 Hz, 1H), 4.28 (t, J = 6.6 Hz, 2H), 4.06 (s, 3H),
2.54 (br, J = 14.3, 10.9, 5.6 Hz, 10H), 2.36 (s, 3H), 2.31 (s, 3H),
2.15 (dt, J = 13.4, 6.7 Hz, 2H). ESI-MS m/z: 625.6 (M + H)+. Anal.
calcd. for C35H37FN6O4 (%):C, 67.29; H, 5.97; N, 13.45. Found (%):
C, 67.33; H, 5.99; N, 13.46.
6.3.10. (Z)-4-(((3-fluoro-4-((6-methoxy-7-(3-(piperidin-1-
yl)propoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-3-methyl-1-
(2-(trifluoromethyl)phenyl)-1H-pyrazol-5(4H)-one (21)
Light yellow solid, 71% yield. mp: 125–126 °C. 1H NMR
(400 MHz, CDCl3) d 11.42 (br, 1H), 8.52 (d, J = 5.1 Hz, 1H), 7.90 (s,
1H), 7.57–7.49 (m, 2H), 7.44 (d, J = 11.8 Hz, 1H), 7.37–7.30 (m,
2H), 7.27–7.20 (m, 2H), 7.18–7.13 (m, 1H), 7.09–7.05 (m, 1H),
6.42 (d, J = 5.0 Hz, 1H), 4.27 (t, J = 6.5 Hz, 2H), 4.05 (s, 3H),
2.59–2.50 (m, 2H), 2.43 (d, J = 1.3 Hz, 4H), 2.35 (s, 3H), 2.15 (dt,
J = 13.6, 6.8 Hz, 2H), 1.61 (dt, J = 10.7, 5.4 Hz, 4H), 1.46 (d,
J = 4.7 Hz, 2H). ESI-MS m/z: 678.69 (M + H)+. Anal. calcd. for
6.3.15. (Z)-4-(((3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-
yl)propoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-1-(4-
fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (26)
Light yellow solid, 78% yield. mp 135–136 °C. 1H NMR
(400 MHz, CDCl3) d 11.42 (brs, 1H), 8.51 (d, J = 4.9 Hz, 1H), 7.93
(d, J = 8.5 Hz, 2H), 7.87 (s, 1H), 7.57–7.50 (m, 3H), 7.45 (d,
J = 12.7 Hz, 1H), 7.36 (t, J = 8.5 Hz, 1H), 7.19 (d, J = 10.7 Hz, 1H),
7.11 (d, J = 8.6 Hz, 1H), 6.43 (d, J = 4.9 Hz, 1H), 4.27 (t, J = 6.5 Hz,
2H), 4.06 (s, 3H), 2.53 (br, J = 16.2, 13.0, 7.1 Hz, 10H), 2.35 (s, 3H),
2.30 (s, 3H), 2.19–2.13(m, J = 12.6, 6.3 Hz, 2H). ESI-MS m/z: 643.4
(M + H)+. Anal. calcd. for C35H36F2N6O4 (%):C, 65.41; H, 5.65; N,
13.08. Found (%): C, 65.43; H, 5.67; N, 13.16.
C36H35F4N5O4 (%):C, 63.80; H, 5.21; N, 10.33. Found (%): C, 63.81;
H, 5.27; N, 10.36.
6.3.11. (Z)-1-(3,4-difluorophenyl)-4-(((3-fluoro-4-((6-methoxy-7-(3-
(piperidin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)amino)methylene)-
3-methyl-1H-pyrazol-5(4H)-one (22)
Light yellow solid, 78% yield. mp 137–139 °C. 1H NMR
(400 MHz, CDCl3) d 11.42 (brs, 1H), 8.52 (d, J = 5.1 Hz, 1H), 7.90
(s, 1H), 7.57–7.49 (m, 2H), 7.44 (d, J = 11.8 Hz, 1H), 7.37–7.30 (m,
1H), 7.27–7.20 (m, 2H), 7.18–7.13 (m, 1H), 7.09–7.05 (m, 1H),
6.42 (d, J = 5.0 Hz, 1H), 4.27 (t, J = 6.5 Hz, 2H), 4.05 (s, 3H), 2.59–
2.50 (m, 2H), 2.43 (d, J = 1.3 Hz, 4H), 2.35 (s, 3H), 2.15 (dt,
J = 13.6, 6.8 Hz, 2H), 1.61 (dt, J = 10.7, 5.4 Hz, 4H), 1.46 (d,
J = 4.7 Hz, 2H). ESI-MS m/z: 646.6 (M + H)+. Anal. calcd. for C35H34-
F3N5O4 (%):C, 65.11; H, 5.31; N, 10.85. Found (%): C, 65.13; H, 5.37;
N, 10.86.
6.3.16. (Z)-1-(3-chloro-4-fluorophenyl)-4-(((3-fluoro-4-((6-methoxy-
7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-
yl)oxy)phenyl)amino)methylene)-3-methyl-1H-pyrazol-5(4H)-one
(27)
Light yellow solid, 77% yield. mp 135–136 °C. 1H NMR
(400 MHz, CDCl3) d 11.48 (brs, 1H), 8.53 (d, J = 5.1 Hz, 1H), 8.16
(dd, J = 7.4, 1.1 Hz, 1H), 7.99–7.91 (m, 1H), 7.88 (s, 1H), 7.56 (s,
1H), 7.46 (s, 1H), 7.36 (t, J = 7.0 Hz, 1H), 7.19 (dd, J = 10.4, 6.5 Hz,
2H), 7.11 (d, J = 8.5 Hz, 1H), 6.43 (d, J = 5.1 Hz, 1H), 4.28 (t,
J = 6.6 Hz, 2H), 4.06 (s, 3H), 2.55 (br, 10H), 2.35 (s, 3H), 2.31 (s, 3H),