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V.R. Rao et al. / European Journal of Medicinal Chemistry 57 (2012) 344e361
112.2, 118.6, 118.9, 119.1 (2), 119.3, 120.8 (2), 126.3, 127.5, 130.5,
132.1, 135.2, 135.3, 139.9, 152.8 (2), 173.4, 176.2; HRESIMS m/z
574.2320 [Mþ þ Na] (calcd. for C33H33N3O5 574.2312). Anal. HPLC
[tR (min) (content)]: 7.49 (95.9%) from solvent a or 9.25 (95.7%)
from solvent b.
139.4, 153.0 (2), 172.8, 175.6. HRESIMS m/z 732.3435 [Mþ þ H]
(calcd. for C47H45N3O5 732.3432). Anal. HPLC [tR (min) (content)]:
8.31 (97.8%) from solvent a or 9.94 (97.1%) from solvent b.
4.5.10. 1-(3-(3,4,5-Trimethoxyphenyl)-3-(2-methyl-1H-indol-3-yl)
propanoyl)-4-(2-methyl-1H-indol-3-yl)piperidin-2-one (3d)
As a pale indigo solid, mp: 110 ꢀC; IR (KBr) nmax: 600, 674, 744,
838, 921, 1006, 1125, 1175, 1244, 1330, 1424, 1459, 1505, 1590, 1691,
4.5.6. 1-(3-(3,4,5-Trimethoxyphenyl)-3-(1-methyl-1H-indol-3-yl)
propanoyl)-5,6-dihydropyridin-2(1H)-one (2b)
As a pale yellow solid, mp: 165 ꢀC.; IR (KBr) nmax: 770, 1001, 1125,
2361, 2932, 3396 and 3738 cmꢃ1. 1H NMR (300 MHz, CDCl3):
d ppm
1188, 1278, 1317, 1460, 1504, 1646, 2852 and 2923 cmꢃ1
.
1H NMR
1.66e1.86 (2H, m), 2.26 (3H, d, J ¼ 6.4 Hz), 2.41 (3H, d, J ¼ 3.5 Hz),
2.46e2.66 (1H, m), 2.83e3.17 (1H, m), 3.18e3.57 (2H, m), 3.73 (6H,
s), 3.79 (3H, s), 3.81e3.91 (1H, m), 4.01e4.21 (1H, m), 4.89 (1H, m),
6.566 (2H, s), 6.99e7.15 (4H, m), 7.18e7.33 (3H, m), 7.62 (1H, m),
(300 MHz, CDCl3):
d ppm 2.10e2.23 (2H, m), 3.65e3.73 (2H, m),
3.74 (3H, s), 3.78 (3H, s), 3.80 (6H, s), 3.80e3.94 (2H, m), 4.83 (1H, t,
J ¼ 7.3 Hz), 5.92e5.98 (1H, td, J ¼ 9.8,1.5 Hz), 6.59 (2H, s), 6.78e6.87
(1H, m), 6.88 (1H, br s) 7.02e7.08 (1H, m), 7.26 (1H, d, J ¼ 8.2 Hz),
7.53e7.57 (1H, d, J ¼ 8.1 Hz), 7.15e7.22 (1H, m). 13C NMR (75 MHz,
7.99 (NH, br s), 8.06 (NH, br s). 13C NMR (75 MHz, CDCl3):
d 28.5,
30.0, 31.2, 38.6, 39.2, 40.6, 43.9, 44.7, 55.9 (2), 60.6, 104.7 (2), 110.4,
110.5, 112.0, 112.5, 118.5, 119.1, 119.2, 119.3, 120.6, 126.4, 127.5, 130.5,
132.2, 135.2, 135.3, 136.0, 140.0, 140.1, 152.8 (2), 173.4, 176.1. HRE-
SIMS m/z 602.2620 [Mþ þ Na] (calcd. for C35H37N3O5 602.2625).
Anal. HPLC [tR (min) (content)]: 6.11 (95.2%) from solvent a or 9.70
(95.3%) from solvent b.
CDCl3):
d 24.5, 29.6, 32.6, 41.2, 45.0, 56.0 (2), 60.7, 104.9 (2), 109.0,
117.5, 118.8 (2), 119.4, 121.6, 125.5 (2), 126.1, 127.0, 136.2, 137.1, 139.9,
145.4, 152.4 (2), 165.5, 174.9. HRESIMS m/z 471.1901 [Mþ þ Na]
(calcd. for C26H28N2O5 471.1890). Anal. HPLC [tR (min) (content)]:
8.99 (94.2%) from solvent a or 9.06 (96.8%) from solvent b.
4.5.7. 1-(3-(3,4,5-Trimethoxyphenyl)-3-(1-methyl-1H-indol-3-yl)
propanoyl)-4-(1-methyl-1H-indol-3-yl)piperidin-2-one (3b)
As a pale yellow solid, mp: 183 ꢀC; IR (KBr) nmax: 665, 743, 819,
1011, 1126, 1175, 1233, 1326, 1375, 1422, 1464, 1505, 1590, 1689,
4.5.11. 1-(3-(3,4,5-Trimethoxyphenyl)-3-(2-phenyl-1H-indol-3-yl)
propanoyl)-4-(2-phenyl-1H-indol-3-yl)piperidin-2-one (3e)
As a pale white solid, mp: 150 ꢀC; IR (KBr) nmax: 861, 609, 666,
700, 744, 770, 836, 921, 1006, 1125, 1175, 1242, 1320, 1422, 1455,
2852, and 2927 cmꢃ1. 1H NMR (300 MHz, CDCl3):
d
ppm 1.67e1.88
1501, 1592, 1687, 2845, 2928, 3056 and 3394 cmꢃ1
.
1H NMR
(1H, m), 1.97e2.10 (1H, m), 2.52e2.71 (1H, m), 2.74e2.96 (1H, m),
2.23e3.58 (2H, m), 3.63e3.97 (18H, m), 4.77 (1H, m), 6.52e6.63
(2H, m), 6.66e6.80 (1H, m), 6.82e6.95 (1H, m), 6.97e7.11 (2H,
m), 7.13e7.33 (4H, m), 7.40e7.58 (2H, m). 13C NMR (75 MHz, CDCl3):
(300 MHz, CDCl3): d ppm 1.50e1.74 (1H, m), 1.78e1.96 (1H, m),
2.30e2.61 (1H, m), 2.77e3.04 (1H, m), 3.05e3.34 (2H, m), 3.43e
3.65 (1H, m), 3.69 (6H, s), 3.79 (3H, s), 3.85e4.28 (2H, m), 5.04
(1H, m), 6.61 (1H, s), 6.62 (1H, s), 7.01e7.12 (1H, m), 7.12e7.23 (2H,
m), 7.27e7.34 (1H, m), 7.34e7.49 (10H, m), 7.50e7.58 (2H, d,
J ¼ 7.9 Hz), 7.68e7.81 (1H, m), 7.97 (1H, s), 8.10 (NH, br s), 8.11 (NH,
d
29.7, 29.4, 30.0, 32.7, 40.1, 41.4, 43.4, 45.5, 56.2 (2), 60.2, 105.6 (2),
109.0, 109.0, 116.6, 117.6, 118.7, 118.9, 119.0 (2), 119.1, 119.7, 121.7 (2),
122.1, 124.6, 126.1, 126.5, 126.5, 127.2, 136.5, 137.2, 139.9, 153.0 (2),
br s). 13C NMR (75 MHz, CDCl3):
d 29.0, 29.6, 31.3, 37.6, 40.8, 44.4,
172.2, 175.5. HRESIMS m/z 602.2617 [Mþ
C
þ
Na] (calcd. for
35H37N3O5 602.2625). Anal. HPLC [tR (min) (content)]: 7.48 (96.4%)
from solvent a or 6.62 (97.9%) from solvent b.
55.9 (2), 60.7, 104.7 (2), 105.9, 106.6, 110.9, 111.1, 111.3, 112.0, 113.2,
113.4, 119.6, 119.8, 120.5, 121.3, 122.0, 122.2, 124.9, 125.9, 126.3,
128.0, 128.1, 128.2, 128.7, 128.8, 130.3, 131.7, 132.7, 134.9, 136.1, 137.6,
140.1,152.9 (2), 160.1,173.2. HRESIMS m/z 742.2685 [Mþ þ K] (calcd.
for C45H41N3O5 742.2678). Anal. HPLC [tR (min) (content)]: 4.63
(98.8%) from solvent a or 3.71 (95.1%) from solvent b.
4.5.8. 1-(3-(1-Benzyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)
propanoyl)-5,6-dihydropyridin-2(1H)-one (2c)
As a pale indigo solid, mp: 95 ꢀC; IR (KBr) nmax: 819, 1124, 1460,
1638, 2055, 2362, 2851, 2922, 1444, 1496, 1536, 1610, 1653, 1740,
4.5.12. 1-(3-(5-Iodo-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)
propanoyl)-5,6-dihydropyridin-2(1H)-one (2f)
2857, 2921 and 3414 cmꢃ1. 1H NMR (300 MHz, CDCl3):
d ppm 2.06e
2.20 (2H, m), 3.64e3.74 (2H, m), 3.77 (6H, s), 3.78 (3H, s), 3.81e3.93
(2H, m), 4.86 (1H, t, J ¼ 7.5 Hz), 5.29 (2H, s), 5.90e5.96 (1H, td,
J ¼ 9.6, 1.7 Hz), 6.57 (2H, s), 6.76e6.84 (1H, m), 6.99e7.09 (4H, m),
As a pale white solid, mp: 180 ꢀC; IR (KBr) nmax: 590, 656, 784,
814, 878, 909, 1000, 1133, 1179, 1231, 1301, 1328, 1360, 1387, 1458,
1504,1588, 1684, 2361, 2828, 2926, 2994, 3055, 3400 cmꢃ1. 1H NMR
7.10e7.16 (1H, m), 7.19e7.31(H, m), 7.50e7.57 (1H, d, J ¼ 7.9 Hz). 13
C
(300 MHz, CDCl3): d ppm 2.16e2.25 (2H, m), 3.61e3.79 (2H, m),
NMR (75 MHz, CDCl3):
d
29.6, 41.3, 45.3, 49.9, 56.0 (2), 60.0, 104.9
3.80 (9H, s), 3.81e3.95 (2H, m), 4.78 (1H, t, J ¼ 7.7 Hz), 5.95e6.01
(1H, td, J ¼ 9.8, 1.7 Hz), 6.56 (2H, s), 6.82e6.90 (1H, m), 7.02 (1H,
br d, J ¼ 2.2 Hz), 7.09e7.14 (1H, d, J ¼ 8.4 Hz), 7.38e7.43 (1H, dd,
J ¼ 8.4, 1.7 Hz), 7.87 (1H, d, J ¼ 1.3 Hz), 8.09 (NH, br s). 13C NMR
(2), 109.6, 118.2, 119.1, 119.6, 121.9, 125.4, 125.6, 126.5 (2), 127.4,
127.5, 128.6 (2), 136.2, 136.8, 137.7, 139.9, 145.3 (2), 152.9 (2), 165.5,
174.9. HRESIMS m/z 547.2225 [Mþ þ Na] (calcd. for C32H32N2O5
547.2203). Anal. HPLC [tR (min) (content)]: 4.28 (97.8%) from
solvent a or 9.32 (96.7%) from solvent b.
(100 MHz, CDCl3):
d 24.7, 39.4, 41.4, 45.1, 55.9 (2), 61.0, 105.0 (2),
113.2, 118.3, 122.2, 125.7, 128.1, 129.2, 130.3, 130.5, 135.5, 136.2,
139.4,145.4,152.8 (2), 165.5,174.8. HRESIMS m/z 599.0456 [Mþ þ K]
(calcd. for C25H25IN2O5 599.0440). Anal. HPLC [tR (min) (content)]:
10.27 (94.9%) from solvent a or 9.31 (96.0%) from solvent b.
4.5.9. 1-(3-(1-Benzyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)
propanoyl)-4-(1-benzyl-1H-indol-3-yl)piperidin-2-one (3c)
As a pale indigo solid, mp: 110 ꢀC; IR (KBr) nmax: 744, 1008, 1124,
1176, 1236, 1328, 1460, 1502, 1640, 2063, 2924 cmꢃ1
.
1H NMR
4.5.13. 1-(3-(5-Iodo-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)
propanoyl)-4-(5-iodo-1H-indol-3-yl)piperidin-2-one (3f)
(300 MHz, CDCl3):
d ppm 1.64e1.81 (1H, m), 1.96e2.18 (1H, m),
2.48e2.65 (1H, m), 2.80e2.91 (1H, m), 3.231e3.49 (2H, m), 3.58e
3.71 (2H, m), 3.75 (10H, br s), 4.79 (1H, t, J ¼ 7.7 Hz), 5.21 (2H, s),
5.29 (2H, s), 6.54 (2H, br s), 6.93e7.13 (9H, m), 7.13e7.31 (9H, m),
As a pale white solid, mp 201 ꢀC; IR (KBr) nmax: 664, 770, 877,
1002, 1124, 1175, 1222, 1307, 1387, 1421, 1458, 1505, 1591, 1686,
2361, 2851, 2923 and 3419 cmꢃ1. 1H NMR (300 MHz, CDCl3):
d ppm
7.44e7.52 (2H, d, J ¼ 7.5 Hz). 13C NMR (75 MHz, CDCl3):
d
29.4, 29.8,
1.75e1.90 (1H, m), 2.08e2.20 (1H, m), 2.58e2.74 (1H, m), 2.88e
3.00 (1H, dd, J ¼ 17.3, 5.8 Hz), 3.30e3.40 (1H, m), 3.48e3.76 (3H,
m), 3.82 (6H, s), 3.83 (3H, s), 3.84e3.98 (1H, m), 4.77 (1H, t,
J ¼ 7.5 Hz), 6.55 (1H, s), 6.57 (1H, s), 6.64 (1H, d, J ¼ 1.7 Hz), 7.03 (1H,
30.2, 39.9, 41.6, 43.7, 45.7, 50.0, 56.0 (2), 60.0, 105.0 (2), 109.6, 110.0,
117.5, 118.1, 118.9, 119.4 (2), 119.8 (2), 122.1, 122.3, 124.0, 125.5, 126.5
(2), 126.7 (2), 127.6, 127.7 (2), 128.8 (2), 136.5, 136.9, 137.4, 137.8,