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M. J. Mphahlele et al. / Bioorg. Med. Chem. 24 (2016) 4576–4586
4.6.2. 1-(5-(4-Fluorophenyl)-2-phenyl-1H-indol-7-yl)ethanone
4.6.6. 1-(2-(4-Fluorophenyl)-5-(4-methoxyphenyl)-1H-indol-7-
(6b)
yl)ethanone (6f)
A
mixture of 5b (0.30 g, 0.91 mmol) and PdCl2 (0.03 g,
A mixture of 5f (0.30 g, 0.83 mmol) and PdCl2 (0.03 g,
0.18 mmol) in acetonitrile (30 mL) afforded 6b as a solid (0.22 g,
75%); Rf (10% EtOAc–hexane) 0.32, mp 156–159 °C; mmax (ATR)
3445, 1653, 1588, 1511, 1466, 1448, 1361, 1317, 1293, 1231,
1216, 1155, 1043, 999, 839, 814, 796, 767, 750, 690, 660, 604,
0.17 mmol) in acetonitrile (30 mL) afforded 6f as a solid (0.22 g,
72%); Rf (10% EtOAc–hexane) 0.24, mp 167–170 °C; mmax (ATR)
3433, 1660, 1607, 1515, 1464, 1366, 1230, 1177, 1154, 1031,
1000, 827, 804, 757, 667, 626, 589, 555 cmꢁ1 1H NMR (500 MHz,
;
534, 519 cmꢁ1
;
1H NMR (CDCl3, 500 MHz) 2.79 (3H, s, CH3), 6.90
CDCl3) 2.78 (3H, s, CH3), 3.89 (3H, s, CH3), 6.80 (1H, d, J 2.0 Hz,
H-3), 7.04 (2H, d, J 9.0 Hz, H-300,500), 7.17 (2H, t, J 8.5 Hz, H-30,50),
7.59 (2H, d, J 8.0 Hz, H-200,600), 7.70–7.72 (2H, dd, J 5.5 Hz and
8.5 Hz, H-20,60), 7.93 (1H, s, H-4), 8.00 (1H, s, H-6), 10.60 (1H, s,
NH); 13C NMR (125 MHz, CDCl3) 26.6, 55.4, 99.2, 114.3, 116.1 (d,
(1H, J 2.5 Hz, H-3), 7.19 (2H, t, J 8.5 Hz, H-300,500), 7.38 (1H, t, J
7.5 Hz, H-40), 7.49 (2H, t, J 7.5 Hz, H-30,50), 7.61–7.63 (2H, dd, J
5.5 Hz and 9.0 Hz, H-200,600), 7.77 (2H, d, J 8.5 Hz, H-20,60), 7.91
(1H, d, J 1.5 Hz, H-4), 8.01 (1H, d, J 1.5 Hz, H-6), 10.69 (1H, s,
2
3
NH); 13C NMR (CDCl3, 125 MHz) 26.6, 99.3, 115.7 (d, JCF 21.9),
2JCF 21.8 Hz), 120.1, 124.4, 124.9, 127.2 (d, JCF 7.5 Hz), 128.1 (d,
3
120.1, 124.4, 125.2, 125.4, 128.2 128.9 (d, JCF 7.5 Hz), 129.1,
4JCF 2.8 Hz), 128.4, 131.2, 132.9, 134.2, 135.0, 139.2, 158.9, 162.2
4
131.3, 131.7, 132.1, 135.2, 137.8 (d, JCF 3.8 Hz), 140.3, 162.2 (d,
(d, 1JCF 246.5 Hz), 200.5; HRMS (ES): MH+, found: 360.1400. C23H19
-
1JCF 244.5 Hz), 200.4; HRMS (ES): MH+, found: 330.1280. C22H17
-
NFO+2 requires: 360.1400.
FNO+ requires: 330.1294.
4.6.7. 1-(2-(4-Methoxyphenyl)-5-phenyl-1H-indol-7-yl)
4.6.3. 1-(5-(4-Methoxyphenyl)-2-phenyl-1H-indol-7-yl)
ethanone (6g)
ethanone (6c)
A
mixture of 5g (0.30 g, 0.88 mmol) and PdCl2 (0.03 g,
A
mixture of 5c (0.30 g, 0.89 mmol) and PdCl2 (0.03 g,
0.18 mmol) in acetonitrile (30 mL) afforded 6g as a solid
0.17 mmol) in acetonitrile (30 mL) afforded 6c as a solid (0.21 g,
70%); Rf (10% EtOAc–hexane) 0.22, mp °C; mmax (ATR) 3423, 1654,
1577, 1521, 1480, 1360, 1354, 1332, 1293, 1260, 1199, 999, 834,
(0.20 g, 67%); Rf (10% EtOAc–hexane) 0.22, mp 165–167 °C; mmax
(ATR) 3436, 1653, 1598, 1494, 1460, 1460, 1439, 1366, 1252,
1178, 1155, 1113, 1024, 832, 790, 757, 696, 652, 634, 559,
815, 797, 695, 650, 596, 530 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
456 cmꢁ1 1H NMR (500 MHz, CDCl3) 2.80 (3H, s, CH3), 3.88
;
2.79 (3H, s, CH3), 3.90 (3H, s, CH3), 6.89 (1H, d, J 2.5 Hz, H-3),
7.05 (2H, d, J 8.5 Hz, H-300,500), 7.38 (1H, t, J 7.5 Hz, H-40), 7.49
(2H, t, J 7.5 Hz, H-30,50), 7.60 (2H, d, J 9.0 Hz, H-200,600), 7.77 (2H, d,
J 8.0 Hz, H-20,60), 7.93 (1H, d, J 1.5 Hz, H-4), 8.02 (1H, d, J 1.5 Hz,
H-6), 10.67 (1H, s, NH); 13C NMR (75 MHz, CDCl3) 26.6, 55.4,
99.3, 114.3, 120.1, 124.4, 125.0, 125.4, 128.1, 128.4, 129.1, 131.3,
131.8, 132.8, 134.3, 135.1, 140.2, 158.9, 200.5; HRMS (ES): MH+,
found: 342.1493. C23H20NO+2 requires: 342.1494.
(3H, s, CH3), 6.79 (1H, d, J 2.5 Hz, H-3), 7.02 (2H, d, J 9.0 Hz,
H-30,50), 7.39 (1H, t, J 7.5 Hz, H-400), 7.51 (2H, t, J 7.5 Hz, H-
300,500), 7.68–7.70 (4H, m, H-20,200,60,600), 7.95 (1H, d, J 1.0 Hz, H-
4), 8.05 (1H, s, H-6), 10.61 (1H, s, NH); 13C NMR (125 MHz,
CDCl3) 26.6, 55.4, 98.2, 114.5, 119.9, 124.2, 124.5, 125.1, 126.7,
126.8, 127.4, 128.9, 131.5, 133.0, 135.2, 140.3, 141.7, 159.7,
200.6; HRMS (ES): MH+, found: 342.1490. C23H20NO+2 requires:
342.1494.
4.6.4. 1-(2-(4-Fluorophenyl)-5-phenyl-1H-indol-7-yl)ethanone
4.6.8. 1-(5-(4-Fluorophenyl)-2-(4-methoxyphenyl)-1H-indol-7-
(6d)
yl)ethanone (6h)
A
mixture of 5d (0.30 g, 0.91 mmol) and PdCl2 (0.03 g,
A
mixture of 5h (0.30 g, 0.83 mmol) and PdCl2 (0.03 g,
0.18 mmol) in acetonitrile (10 mL) afforded 6d as a solid (0.21 g,
70%); Rf (10% EtOAc–hexane) 0.34, mp 151–154 °C; mmax (ATR)
3321, 1659, 1585, 1488, 1469, 1364, 1252, 1230, 1215, 1172,
0.17 mmol) in acetonitrile (30 mL) afforded 6h as solid
(0.24 g, 80%); Rf (10% EtOAc–hexane) 0.20, mp 175–176 °C; mmax
a
(ATR) 3428, 1656, 1609, 1512, 1458, 1362, 1299, 1247, 1163,
1155, 1012, 875, 838, 768, 698, 662, 584, 536 cmꢁ1
;
1H NMR
1113, 1029, 832, 788, 759, 669, 626, 573, 528, 519, 463 cmꢁ1
;
(300 MHz, CDCl3) 2.77 (3H, s, CH3), 6.80 (1H, d, J 2.5 Hz, H-3),
7.15 (2H, t, J 8.0 Hz, H-30,50), 7.41–7.43 (1H, m, H-400), 7.52 (2H, t,
J 8.0 Hz, H-300,500), 7.67–7.70 (4H, m, H-20,200,60,600), 7.96 (1H, s, H-
4), 8.04 (1H, s, H-6), 10.61 (1H, s, NH); 13C NMR (125 MHz, CDCl3)
1H NMR (500 MHz, CDCl3) 2.77 (3H, s, CH3), 3.88 (3H, s, CH3),
6.75 (1H, d, J 2.5 Hz, H-3), 7.00 (2H, d, J 8.5 Hz, H-30,50) 7.18
(2H, t, J 8.5 Hz, H-300,500), 7.60–7.62 (2H, dd, J 5.5 Hz and 9.0 H,
H-200,600), 7.67 (2H, d, J 8.5 Hz), 7.85 (1H, d, J 1.5 Hz, H-4), 7.95
(1H, d, J 1.5 Hz, H-6), 10.59 (1H, s, NH); 13C NMR (125 MHz,
2
26.6, 99.4, 116.1 (d, JCF 21.8 Hz), 120.1, 124.6, 125.3, 126.9, 127.1
3
4
2
(d, JCF 8.5 Hz), 127.4, 128.1 (d, JCF 3.7 Hz), 128.8, 128.9 131.2,
CDCl3) 26.6, 55.4, 98.1, 114.5, 115.7 (d, JCF 20.9 Hz), 119.9,
1
3
133.2 135.3, 139.3, 141.6, 162.7 (d, JCF 246.6 Hz), 200.5; HRMS
123.7, 124.4, 124.8, 126.7, 128.8 (d, JCF 7.5 Hz), 131.5, 132.0,
(ES): MH+, found: 330.1304. C22H17NFO+ requires: 330.1294.
135.1, 137.8 (d, JCF 2.9 Hz), 140.4, 159.7, 162.2 (d, JCF
244.6 Hz), 200.4; HRMS (ES): MH+, found: 360.1403. C23H19NFO+2
requires: 360.1400.
4
1
4.6.5. 1-(2,5-Bis(4-fluorophenyl)-1H-indol-7-yl)ethanone (6e)
A
mixture of 5e (0.30 g, 0.86 mmol) and PdCl2 (0.03 g,
0.17 mmol) in acetonitrile (30 mL) afforded 6e as a solid (0.21 g,
70%); Rf (10% EtOAc–hexane) 0.30, mp 160–162 °C; mmax (ATR)
3435, 1651, 1585, 1464, 1364, 1313, 1289, 1223, 1156, 1101,
4.6.9. 1-(2,5-Bis(4-methoxyphenyl)-1H-indol-7-yl)ethanone (6i)
A
mixture of 5i (0.30 g, 0.81 mmol) and PdCl2 (0.03 g,
0.16 mmol) in acetonitrile (30 mL) afforded 6i as a solid (0.21 g,
70%); Rf (10% EtOAc–hexane) 0.18, mp 189–192 °C; mmax (ATR)
3432, 1661, 1591, 1516, 1463, 1367, 1248, 1176, 1157, 1025,
1081, 965, 833, 790, 757, 667, 619, 560, 536, 512 cmꢁ1 1H NMR
;
(500 MHz, CDCl3) 2.78 (3H, s, CH3), 6.81 (1H, d, J 2.5 Hz, H-3),
7.16–7.20 (4H, m, H-30,300,50,500), 7.60–7.62 (2H, dd, J 5.5 and
8.5 Hz, H-20,60), 7.70–7.72 (2H, dd, J 5.5 Hz and 8.5 Hz, H-200,600),
7.90 (1H, d, J 1.5 H, H-4), 7.99 (1H, s, H-6), 10.62 (1H, s, NH); 13C
828, 787, 757, 670, 626, 559, 525 cmꢁ1
;
1H NMR (500 MHz,
CDCl3) 2.78 (3H, s, CH3), 3.88 (3H, s, CH3), 3.89 (3H, s, CH3),
6.77 (1H, d, J 2.5 Hz, H-3), 7.01–7.05 (4H, m, H-30,300,50,500), 7.60
(2H, d, J 8.5 Hz, H-200,600), 7.68 (2H, d, J 8.5 Hz, H-20,60), 7.90
(1H, s, H-4), 7.99 (1H, s, H-6), 10.58 (1H, s, NH); 13C NMR
(125 MHz, CDCl3) 26.6, 55.4, 98.1, 114.3, 114.5, 119.9, 123.9,
124.6, 124.7, 126.8, 128.4 (2 ꢀ C), 131.5, 132.7, 134.4, 125.0,
140.2, 158.9, 159.7, 200.6; HRMS (ES): MH+, found: 372.1597.
2
NMR (75 MHz, CDCl3) 26.6, 99.3, 115.7 (d, JCF 20.9 Hz), 116.1 (d,
3
2JCF 21.8 Hz), 120.1, 124.4, 125.2, 127.2 (d, JCF 8.6 Hz), 128.0 (d,
3
4JCF 2.9 Hz), 128.9 (d, JCF 8.6 Hz), 131.2, 132.3, 135.2, 137.7 (d,
1
1
4JCF 3.8 Hz), 139.4, 162.3 (d, JCF 244.6 Hz), 162.7 (d, JCF
246.5 Hz), 200.4; HRMS (ES): MH+, found: 348.1206. C22H16NF2O+
requires: 348.1200.
C
24H22NO+3 requires: 372.1600.