1476.2, 1430.5, 1349.7, 1307.2, 1252.2, 1209.6, 1175.9, 1091.7, 853.5, 766.0; 1H NMR (400 MHz, CDCl3) δ 11.98
(s, 1H), 8.50 (d, J = 5.2 Hz, 1H), 8.33 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 8.04 (dd, J = 12.0 Hz, 2.4 Hz, 1H), 7.59 (m,
3H), 7.41 (m, 6H), 7.26 (t, J = 8.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.46 (d, J = 5.2 Hz, 1H), 4.27 (t, J = 6.4 Hz,
2H), 4.05 (s, 3H), 3.14 (br, 2H), 2.82 (br, 2H), 2.25 (m, 4H), 1.72 (br, 2H), 1.48 (br, 3H), 0.98 (d, J = 5.6 Hz, 3H);
MS (ESI) m/z(%): 706.4 [M+H]+; Anal. calcd. for C40H37F2N5O5 (%): C, 68.07; H, 5.28; N, 9.92. Found (%): C,
68.18; H, 5.22; N, 9.99.
6.6.20. 4-(4-chlorophenyl)-N-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yl)oxy)ph
enyl)-3-oxo-3,4-dihydroquinoxaline-2-carboxamide (38)
Yield: 83.8%; M.p.: 194.5–195.8 °C; 1H NMR (400 MHz, CDCl3) δ 11.96 (s, 1H), 8.51 (d, J = 4.8 Hz, 1H), 8.33 (d,
J = 8.0 Hz, 1H), 8.04 (dd, J = 12.0 Hz, 2.4 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.58 (m, 3H), 7.46 (m, 2H), 7.34 (d, J
= 8.4 Hz, 2H), 7.26 (t, J = 8.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 4.8 Hz, 1H), 4.27 (t, J = 6.4 Hz, 2H),
4.06 (s, 3H), 2.94 (m, 2H), 2.57 (m, 2H), 2.16 (m, 2H), 1.98 (m, 2H), 1.65 (m, 2H), 1.27 (m, 3H), 0.94 (d, J = 6.4
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 159.93, 158.74, 155.51, 153.17, 152.33, 149.89, 148.72, 146.93, 144.28,
137.90, 137.77, 136.58, 136.42, 136.33, 134.21, 133.66, 133.26, 132.99, 132.34, 131.07, 129.26, 125.67, 123.79,
116.66, 115.59, 110.10, 109.87, 108.77, 102.33, 99.53, 67.62, 56.15, 55.44, 54.02, 34.31, 30.81, 26.51, 21.89; MS
(ESI) m/z(%): 722.4 [M+H]+; Anal. calcd. for C40H37ClFN5O5 (%): C, 66.52; H, 5.16; N, 9.70. Found (%): C, 66.78;
H, 5.29; N, 9.89.
6.6.21. N-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-4-(2-fluoroph
enyl)-3-oxo-3,4-dihydroquinoxaline-2-carboxamide (39)
Yield: 64.9%; M.p.: 131.5–132.6 °C; IR (KBr) cm-1: 3409.3, 2917.6, 2796.7, 1704.9, 1625.7, 1557.6, 1499.2,
1476.8, 1432.1, 1349.9, 1307.0, 1248.2, 1214.7, 1175.9, 1089.2, 849.9, 762.9; 1H NMR (400 MHz, CDCl3) δ 11.91
(s, 1H), 8.50 (d, J = 5.2 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H), 8.03 (dd, J = 12.0 Hz, 2.4 Hz, 1H), 7.54 (m, 9H), 7.23 (t,
J = 8.8 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.46 (d, J = 5.2 Hz, 1H), 4.26 (t, J = 6.4 Hz, 2H), 4.02 (s, 3H), 3.36 (br,
2H), 3.02 (br, 2H), 2.44 (m, 4H), 1.65 (m, 5H), 1.01 (d, J = 6.0 Hz, 3H); MS (ESI) m/z(%): 706.2 [M+H]+; Anal.
calcd. for C40H37F2N5O5 (%): C, 68.07; H, 5.28; N, 9.92. Found (%): C, 68.29; H, 5.35; N, 10.03.
6.6.22. 4-(2-chlorophenyl)-N-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yl)oxy)ph
enyl)-3-oxo-3,4-dihydroquinoxaline-2-carboxamide (40)
1
Yield: 71.2%; M.p.: 162.2–163.6 °C; H NMR (400 MHz, CDCl3) δ 11.96 (s, 1H), 8.52 (d, J = 5.2 Hz, 1H),
8.35 (d, J = 8.0 Hz, 1H), 8.06 (dd, J = 12.0 Hz, 2.0 Hz, 1H), 7.79 (m, 1H), 7.54 (m, 8H), 7.26 (t, J = 8.4 Hz, 1H),
6.71 (d, J = 8.4 Hz, 1H), 6.48 (d, J = 5.2 Hz, 1H), 4.29 (t, J = 6.8 Hz, 2H), 4.04 (s, 3H), 3.60 (br, 2H), 3.26 (m, 2H),
2.60 (m, 4H), 1.91 (br, 5H), 1.07 (d, J = 6.4 Hz, 3H); MS (ESI) m/z(%): 722.4 [M+H]+; Anal. calcd. for
C40H37ClFN5O5 (%): C, 66.52; H, 5.16; N, 9.70. Found (%): C, 66.75; H, 5.26; N, 9.82.
6.6.23. N-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-4-(4-fluoroph
enyl)-3-oxo-3,4-dihydroquinoxaline-2-carboxamide (41)
Yield: 68.1%; M.p.: 125.0–126.8 °C; IR (KBr) cm-1: 3418.1, 2926.8, 1695.5, 1621.4, 1541.9, 1507.8, 1479.3,
1432.0, 1349.8, 1305.9, 1250.3, 1209.7, 1169.8, 1091.9, 854.3, 762.7; 1H NMR (400 MHz, CDCl3) δ 11.99 (s,
1H), 8.50 (d, J = 5.2 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.05 (dd, J = 12.0 Hz, 2.0 Hz, 1H), 7.59 (m, 3H), 7.43 (m,
6H), 7.26 (t, J = 8.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.46 (d, J = 5.2 Hz, 1H), 4.28 (t, J = 6.4 Hz, 2H), 4.05 (s,
3H), 3.20-2.61 (m, 10H), 2.54 (s, 3H), 2.17 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.51, 162.01, 160.00,
158.83, 155.65, 153.15, 152.22, 149.83, 148.72, 146.78, 144.28, 137.81, 136.48, 134.44, 133.66, 133.01, 132.31,
130.67, 129.84, 125.64, 123.78, 118.06, 117.83, 116.70, 115.65, 110.13, 109.90, 108.67, 102.35, 99.58, 67.01,
56.14, 54.55, 54.50, 51.94, 45.17, 26.13; MS (ESI) m/z(%): 707.2 [M+H]+; Anal. calcd. for C39H36F2N6O5 (%): C,
66.28; H, 5.13; N, 11.89. Found (%): C, 66.48; H, 5.23; N, 11.80.
6.6.24. 4-(4-chlorophenyl)-N-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)p