Vol. 27, No. 8 (2015)
Synthesis of 3-Substituted Indolin-2-one Derivatives with Methyl (E)-2-(3-Methoxy)acrylate 2915
1
acrylate (7k): Orange solid; yield: 55 %; m.p.: 66-68 °C; 1H
NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.46 (s, 1H), 7.47 (s,
1H), 7.42-7.28 (m, 4H), 7.23-7.19 (m, 2H), 7.15 (s, 1H), 7.11-
7.05 (m, 2H), 6.91-6.84 (m, 1H), 6.84-6.75 (m, 2H), 6.27 (d,
J = 0.6 Hz, 1H), 3.80 (t, J = 7.4 Hz, 2H), 3.76 (s, 3H), 3.61 (s,
3H), 1.72 (m, 2H), 1.45 (m, 2H), 0.99 (t, J = 7.3 Hz, 3H). IR
(KBr, νmax, cm-1): 3055, 2934, 2863, 1712, 1633, 1603, 1565,
1489, 1447, 1380, 1250, 1206, 1132, 1094, 1050, 985, 844,
753. HR-MS (ESI): Calcd for C33H31N4O6 [M+H]+: 579.2244;
found: 579.2240.
81 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.46 (s,
1H), 7.47 (s, 1H), 7.43-7.28 (m, 4H), 7.21 (q, J = 4. 7 Hz,
2H), 7.15 (s, 1H), 7.12-7.05 (m, 2H), 6.92-6.85 (m, 1H), 6.84-
6.76 (m, 2H), 6.27 (s, 1H), 3.82-3.71 (m, 5H), 3.61 (s, 3H),
1.83-1.72 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H). IR (KBr, νmax
,
cm-1): 3058, 2928, 2872, 2849, 1721, 1633, 1603, 1568, 1492,
1447, 1383, 1359, 1250, 1203, 1130, 1097, 1050, 985, 918,
841, 753, 591, 488. HR-MS (ESI): Calcd for C32H29N4O6
[M+H]+: 565.2087; found: 565.2090.
(E)-Methyl 3-methoxy-2-(2-((6-(4-((5-methyl-2-oxo-1-
propylindolin-3-ylidene)amino)phenoxy)pyrimidin-4-
yl)oxy)phenyl)acrylate (7g): Orange solid; yield: 69 %; m.p.:
72-74 °C; 1H NMR (400 MHz,-CDCl3, TMS) δ (ppm) 8.44 (s,
1H), 7.48 (s, 1H), 7.43-7.38 (m, 1H), 7.36-7.29 (m, 2H), 7.23-
7.11 (m, 4H), 7.11-7.03 (m, 2H), 6.82-6.68 (m, 1H), 6.51 (s,
1H), 6.28 (s, 1H), 3.78-3.70 (m, 5H), 3.60 (s, J = 7.8 Hz, 3H),
2.10 (s, 3H), 1.81-1.70 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H). IR
(KBr, νmax, cm-1): 3058, 2934, 2869, 1721, 1565, 1489, 1447,
1383, 1350, 1250, 1203, 1124, 1053, 985, 841, 812, 762, 659,
614, 558, 511, 461. HR-MS (ESI): Calcd for C33H31N4O6
[M+H]+: 579.2244; found: 579.2247.
(E)-Methyl 2-(2-((6-(4-((1-butyl-5-methyl-2-oxoindo-
lin-3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-
3-methoxyacrylate (7l): Orange solid; yield: 47 %; m.p.: 59-
1
60 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.43 (s,
1H), 7.47 (s, 1H), 7.42-7.36 (m, 1H), 7.36-7.28 (m, 2H), 7.19
(m, 4H), 7.06 (d, J = 8.7 Hz, 2H), 6.75 (m, 1H), 6.51 (s, 1H),
6.27 (s, 1H), 3.81-3.73 (m, 5H), 3.61 (s, 3H), 2.10 (s, 3H),
1.71 (m, 2H), 1.44 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H). IR (KBr,
ν
max, cm-1): 3055, 2952, 2928, 2866, 1712, 1562, 1486, 1444,
1380, 1344, 1250, 1200, 1127, 1053, 985, 918, 817, 765. HR-
MS (ESI): Calcd for C34H33N4O6 [M+H]+: 593.2400; found:
593.2403.
(E)-Methyl 2-(2-((6-(4-((5-fluoro-2-oxo-1-propylin-dolin-
3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-3-
methoxyacrylate (7h): Orange solid; yield: 61 %; m.p.: 81-
(E)-Methyl 2-(2-((6-(4-((1-butyl-5-fluoro-2-oxoindolin-
3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-3-
methoxyacrylate (7m): Orange solid; yield: 49 %; m.p.: 66-
1
83 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.45 (s,
1H), 7.47 (s, 1H), 7.43-7.35 (m, 1H), 7.34-7.28 (m, 2H), 7.25-
7.18 (m, 3H), 7.13 (m, 1H), 7.08 (m, 2H), 6.82 (m, 1H), 6.50
(m, 1H), 6.29 (s, 1H), 3.80-3.72 (m, 5H), 3.62 (s, 3H), 1.76
(m, 2H), 1.03 (t, J = 7.4 Hz, 3H). IR (KBr, νmax, cm-1): 3058,
2940, 2875, 1709, 1636, 1565, 1480, 1450, 1383, 1330, 1250,
1200, 1130, 1100, 1053, 988, 879, 838, 767, 656, 564, 514,
461. HR-MS (ESI): Calcd for C32H28N4O6F [M+H]+: 583.1993;
found: 583.2004.
1
68 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.45 (s,
1H), 7.47 (s, 1H), 7.44-7.28 (m, 3H), 7.25-6.97 (m, 6H), 6.81
(m, 1H), 6.57-6.40 (m, 1H), 6.29 (s, 1H), 3.78 (m, 5H), 3.62
(s, 3H), 1.69 (m, 2H), 1.44 (m, 2H), 0.99 (t, J = 7.1 Hz, 3H).
IR (KBr, νmax, cm-1): 3085, 2957, 2928, 2866, 1709, 1633,
1603, 1565, 1483, 1447, 1380, 1330, 1247, 1203, 1130, 1053,
988, 918, 823, 762. HR-MS (ESI): Calcd for C33H30N4O6F
[M+H]+: 597.2149; found: 597.2142.
(E)-Methyl 2-(2-((6-(4-((5-chloro-2-oxo-1-propylindo-
lin-3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-
3-methoxyacrylate (7i): Orange solid; yield: 65 %; m.p.: 77-
79 °C; 1H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.45 (s,
1H), 7.48 (s, 1H), 7.44-7.37 (m, 1H), 7.32 ( m, 3H), 7.26-7.12
(m, 3H), 7.07 (d, J = 8.6 Hz, 2H), 6.81 (m, 1H), 6.72 (d, J =
2.0 Hz, 1H), 6.30 (s, 1H), 3.80-3.64 (m, 5H), 3.62 (s, 3H),
1.76 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H). IR (KBr, νmax, cm-1):
3063, 2931, 2872, 2852, 1712, 1633, 1600, 1565, 1492, 1444,
1383, 1330, 1250, 1203, 1132, 1050, 988, 921, 838, 765, 606,
544, 514, 458. HR-MS (ESI): Calcd for C32H28N4O6Cl [M+H]+:
599.1697; found: 599.1698.
(E)-Methyl 2-(2-((6-(4-((1-butyl-5-chloro-2-oxoindolin-
3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-3-
methoxyacrylate (7n): Orange solid; yield: 40 %; m.p.: 75-
1
76 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.45 (s,
1H), 7.48 (s, 1H), 7.44-7.37 (m, 1H), 7.36-7.28 (m, 3H), 7.26-
7.11 (m, 3H), 7.07 (d, J = 8.7 Hz, 2H), 6.80 (m, 1H), 6.72 (d,
J = 2.0 Hz, 1H), 6.30 (s, 1H), 3.83-3.66 (m, 5H), 3.62 (s, 3H),
1.78-1.60 (m, 2H), 1.44 (m, 2H), 0.99 (t, J = 7.3 Hz, 3H). IR
(KBr, νmax, cm-1): 3061, 2940, 2869, 1706, 1636, 1600, 1565,
1492, 1444, 1383, 1336, 1250, 1203, 1130, 1056, 991, 838,
815, 767. HR-MS (ESI): Calcd for C33H30N4O6Cl [M+H]+:
613.1854; found: 613.1849.
(E)-Methyl 2-(2-((6-(4-((5-bromo-2-oxo-1-propylindolin-3-
ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-3-
methoxyacrylate (7j): Orange solid; yield: 49 %; m.p.: 76-
(E)-Methyl 2-(2-((6-(4-((5-bromo-1-butyl-2-oxoindo-
lin-3-ylidene)amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-
3-methoxyacrylate (7o): Orange solid; yield: 42 %; m.p.: 90-
92 °C; 1H NMR (400 MHz, CDCl3, TMS) δ 8.46 (s, 1H), 7.52-
7.45 (m, 2H), 7.43-7.37 (m, 1H), 7.36-7.27 (m, 2H), 7.26-
7.12 (m, 3H), 7.07 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 1.9 Hz,
1H), 6.76 (m, 1H), 6.30 (s, 1H), 3.82-3.70 (m, 5H), 3.62 (s,
3H), 1.75-1.64 (m, 2H), 1.44 (m, 2H), 0.98 (t, J = 7.3 Hz,
3H). IR (KBr, νmax, cm-1): 3061, 2940, 2866, 1709, 1633, 1600,
1562, 1492, 1439, 1380, 1330, 1250, 1203, 1130, 1050, 985,
838, 815, 762. HR-MS (ESI): Calcd for C33H30N4O6Br [M+H]+:
657.1349; found: 657.1339.
1
78 °C; H NMR (400 MHz, CDCl3, TMS) δ (ppm) 8.46 (s,
1H), 7.48 (dd, J = 8.0, 2.6 Hz, 2H), 7.43-7.37 (m, 1H), 7.36-
7.28 (m, 2H), 7.25-7.11 (m, 3H), 7.12-6.99 (m, 2H), 6.86 (d,
J = 1.9 Hz, 1H), 6.76 (m, 1H), 6.30 (s, 1H), 3.82-3.65 (m,
5H), 3.62 (s, 3H), 1.76 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H). IR
(KBr, νmax, cm-1): 3063, 2937, 2866, 1712, 1636, 1598, 1562,
1489, 1447, 1380, 1333, 1256, 1206, 1132, 1050, 991, 918,
838, 767. HR-MS (ESI): Calcd for C32H28N4O6 Br [M+H]+:
643.1192; found: 643.1189.
(E)-Methyl 2-(2-((6-(4-((1-butyl-2-oxoindolin-3-ylidene)-
amino)phenoxy)pyrimidin-4-yl)oxy)phenyl)-3-methoxy-