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C. Aubry et al. / Bioorg. Med. Chem. 17 (2009) 6073–6084
dt, estimated J 7.8 and 0.6), 7.58 (1H, dd, J 7.5 and 0.6), 7.88 (1H, s).
13C NMR (75 MHz, CDCl3) d 23.10 (CH2), 28.73 (CH2), 49.85 (CH2),
53.09 (CH2), 107.05 (CH), 111.33 (CH), 113.93 (Cq), 117.52 (CH),
118.80 (CH), 119.37 (CH), 121.81 (CH), 122.05 (CH), 124.57 (CH),
127.47 (CH), 127.58 (Cq), 130.17 (Cq), 136.34 (Cq), 152.47 (Cq). m/
z (FAB+) 262 M+ (found: C, 82.41; H, 6.90; N, 10.49; M+ 262.14696.
C18H18N2 requires C, 82.24; H, 6.92; N, 10.68; M 262.14700).
CDCl3) d 3.01 (2H, t, J 8.1), 3.12 (2H, t, J 8.4), 3.46 (2H, t, J 8.1),
3.52 (2H, t, J 8.4), 6.44 (1H, d, J 8.1), 7.06–7.10 (3H, m), 7.21–7.33
(2H, m), 7.40 (1H, d, J 8.1), 7.72 (1H, d, J 7.5), 7.95 (1H, s). 13C
NMR (75 MHz, CDCl3) d 22.98 (CH2), 28.49 (CH2), 49.73 (CH2),
53.13 (CH2), 107.42 (CH), 111.33 (CH), 113.81 (Cq), 118.75 (CH),
119.47 (CH), 121.77 (CH), 122.17 (CH), 124.71 (CH), 127.06 (CH),
127.50 (Cq), 131.99 (Cq), 136.31 (Cq), 151.11 (Cq), one quaternary
13C is not observed. m/z (FAB+) 296 M+ (found: M+ 296.10802.
C18H17ClN2 requires M 296.10803).
4.2.4.2. 3-[2-(2,3-Dihydro-indol-1-yl)-ethyl]-5-fluoro-1H-indol
9f. Prepared from 8f. Tan solid. Yield 94%. Melting point 107–
108 °C. 1H NMR (300 MHz, CDCl3) d 2.87–2.95 (4H, 2 distorted t, esti-
mated J 8.0), 3.29–3.38 (4H, 2 distorted t, estimated J 8.0), 6.42 (1H,
d, J 7.8), 6.57 (1H, t, J 7.2), 6.86 (1H, td, J 9.0 and 1.8), 6.96–7.01 (3H,
m), 7.14–7.20 (2H, m), 7.86 (br s, 1H). 13C NMR (75 MHz, CDCl3) d
23.05 (CH2), 28.65 (CH2), 49.62 (CH2), 53.05 (CH2), 103.67 (CH, d, J
23.5), 106.87 (CH), 110.42 (CH, d, J 26.3), 111.77 (CH, d, J 9.9),
114.31 (Cq, d, J 4.5), 117.47 (CH), 123.49 (CH), 124.49 (CH), 127.38
(CH), 127.93 (Cq, d, J 9.6), 130.04 (Cq), 132.73 (Cq), 152.32 (Cq),
157.80 (Cq, d, J 234.5). 19F NMR (282 MHz, CDCl3) d ꢀ124.69. m/z
(FAB+) 280 M+ (found: C, 77.30; H, 6.36; N, 9.59; M+ 280.13751.
C18H17FN2 requires C, 77.12; H, 6.11; N, 9.99% ; M 280.13758).
4.2.4.7. 3-[2-(5-Methyl-2,3-dihydro-indol-1-yl)-ethyl]-1H-indole
9k. Prepared from 8k. Yellow oil. Yield 99%. 1H NMR (300 MHz,
CDCl3) d 2.17 (3H, s), 2.84 (2H, t, J 8.1), 2.95 (2H, distorted t, esti-
mated J 7), 3.29 (2H, t, J 8.1), 3.31 (2H, t, J 8.4), 6.36 (1H, d, J 7.8),
6.79 (1H, d, J 7.8), 6.84 (1H, s), 6.89 (1H, d, J 2.4), 7.04 (1H, td, J
6.9 and 1.2), 7.10 (1H, td, J 6.9 and 1.2), 7.20 (1H, dd, J 7.5 and
1.2), 7.55 (1H, dd, J 7.2 and 0.3), 7.80 (1H, br s). 13C NMR
(75 MHz, CDCl3) d 20.80 (CH3), 23.09 (CH2), 28.79 (CH2), 50.41
(CH2), 53.48 (CH2), 107.16 (CH), 111.26 (CH), 114.12 (Cq), 118.83
(CH), 119.37 (CH), 121.72 (CH), 122.06 (CH), 125.51 (CH), 126.97
(Cq), 127.60 (CH + Cq), 130.52 (Cq), 136.31 (Cq), 150.36 (Cq). m/z
(FAB+) 276 M+ (found: M+ 276.16269. C19H20N2 requires
276.16265).
M
4.2.4.3. 5-Chloro-3-[2-(2,3-dihydro-indol-1-yl)-ethyl]-1H-indole
9g. Prepared from 8g. Beige solid. Yield 72%. Rf (EtOAc/cyclohex-
ane, 20:80) 0.33. Melting point 110–111 °C. 1H NMR (300 MHz,
CDCl3) d 2.85–2.92 (4H, m), 3.29 (2H, t, J 7.8), 3.32 (2H, t, J 8.4),
6.43 (1H, d, J 7.8), 6.62 (1H, td, J 7.4 and 0.9), 6.86 (1H, d, J 2.4),
6.99–7.05 (4H, m), 7.52 (1H, s), 7.86 (1H, s). 13C NMR (75 MHz,
CDCl3) d 23.02 (CH2), 28.75 (CH2), 49.77 (CH2), 53.15 (CH2),
107.15 (CH), 112.38 (CH), 113.78 (Cq), 117.75 (CH), 118.32 (CH),
122.32 (CH), 123.34 (CH), 124.69 (CH), 125.09 (Cq), 127.54 (CH),
128.73 (Cq), 130.25 (Cq), 134.66 (Cq), 152.44 (Cq). m/z (FAB+)
296 M+ (found: C, 72.96; H, 5.80; N, 9.39; M+ 296.10799.
C18H17ClN2 requires C, 72.84; H, 5.77; N, 9.44; M 296.10803).
4.2.4.8. 5-Fluoro-3-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-
1H-indole 9l. Pale yellow powder. Yield 84%. Rf (EtOAc/petroleum
ether, 1:2) 0.39. Melting point 117–118 °C. 1H NMR (300 MHz,
DMSO) d 2.86 (2H, t, J 8.3), 2.92 (2H, t, J 7.6), 3.29 (2H, t, J 7.6),
3.37 (2H, t, J 8.3), 6.45 (1H, dd, J 8.6 and 4.4), 6.77 (1H, td, J 9.0
and 2.9), 6.86–6.90 (1H, m), 6.94 (1H, dd, J 9.2 and 2.6), 7.31–
7.33 (2H, m), 7.37 (1H, dd, J 8.9 and 4.4), 10.97 (1H, s). 13C NMR
(75 MHz, DMSO) d 22.78 (CH2), 28.52 (CH2), 50.18 (CH2), 53.30
(CH2), 103.41 (CH, d, J 22.6),107.18 (CH, d, J 10.7), 109.45 (CH, d,
J 24.8), 112.27 (CH, d, J 23.7), 112.63 (CH, d, J 10.7), 112.89 (Cq),
113.08 (CH, d, J 22.6), 125.35 (CH), 127.95 (Cq, d, J 9.5), 132.02
(Cq, d, J 8.3), 133.36 (Cq), 149.34 (Cq), 155.92 (Cq, d, J 230.8),
157.20 (Cq, d, J 229.6). 19F NMR (282 MHz, DMSO) d ꢀ128.22,
ꢀ125.54. m/z (ES+) 299 MH+, (ESꢀ) 297 (MꢀH)ꢀ; m/z (FAB+)
298 M+ (found: C, 72.55; H, 5.36; N, 9.38; M+ 298.12816.
C18H16N2F2 requires C, 72.47; H, 5.41; N, 9.39; M 298.12816).
4.2.4.4. 3-[2-(2,3-Dihydro-indol-1-yl)-ethyl]-5-methyl-1H-indole
9h. Prepared from 8h. Dark yellow powder. Yield 92%. Melting
point 100–101 °C. 1H NMR (300 MHz, CDCl3) d 2.40 (3H, s), 2.91
(2H, t, J 8.4), 2.95 (2H, t, J 8.4), 3.31–3.40 (4H, m), 6.44 (1H, d, J
7.8), 6.57 (1H, td, J 7.5 and 0.9), 6.94–7.02 (4H, m), 7.15–7.18
(1H, m), 7.34 (1H, d, J 0.9), 7.77 (1H, br s). 13C NMR (75 MHz, CDCl3)
d 21.57 (CH3), 23.05 (CH2), 28.65 (CH2), 49.73 (CH2), 53.01 (CH2),
106.91 (CH), 110.84 (CH), 113.60 (Cq), 117.34 (CH), 118.43 (CH),
121.76 (CH), 123.66 (CH), 124.44 (CH), 127.35 (CH), 127.76 (Cq),
128.57 (Cq), 130.06 (Cq), 134.59 (Cq), 152.41 (Cq). m/z (FAB+)
276 M+ (found: C, 88.64; H, 7.79; N, 10.78; M+ 276.16259.
C19H20N2 requires C, 88.72; H, 7.84; N, 10.89; M 276.16265).
4.2.4.9. 5-Chloro-3-[2-(5-chloro-2,3-dihydro-indol-1-yl)-ethyl]-
1H-indole 9m. Yellow powder. Yield 69%. Rf (EtOAc/petroleum
ether, 50:50) 0.52. Melting Point 79–81 °C. 1H NMR (300 MHz,
DMSO) d 2.84 (2H, t, J 8.3), 2.92 (2H, t, J 7.6), 3.29 (2H, t, J 7.6),
3.41 (2H, t, J 8.3), 6.45 (1H, d, J 8.4), 6.96 (1H, dd, J 8.4 and 2.1),
7.01 (1H, apparent d, estimated J 1.5), 7.07 (1H, dd, J 8.9 and 2.0),
7.31 (1H, s), 7.38 (1H, d, J 8.7), 7.61 (1H , d, J 1.5), 10.97 (1H, s).
13C NMR (75 MHz, DMSO) d 22.53 (CH2), 28.24 (CH2), 49.37
(CH2), 52.78 (CH2), 107.78 (Cq), 112.43 (CH), 113.34 (CH), 118.02
(Cq), 120.50 (Cq), 121.31 (CH), 123.54 (CH), 124.60 (Cq), 125.14
(CH), 127.06 (CH), 128.87 (CH), 132.41 (Cq), 135.12 (Cq), 151.59
(Cq). m/z (ES+) 331 MH+, (ESꢀ) 329 (MꢀH)ꢀ; m/z (FAB+) 330 M+
(found: C, 65.26; H, 4.72; N, 8.58; M+ 330.06904. C18H16N2F2 re-
quires C, 65.27; H, 4.87; N, 8.46; M 330.06905).
4.2.4.5. 3-[2-(5-Fluoro-2,3-dihydro-indol-1-yl)-ethyl]-1H-indole
9i. Prepared from 8i. Brown solid. Yield 78%. Rf (EtOAc/cyclohex-
ane, 20:80) 0.27. Melting point 134–135 °C. 1H NMR (300 MHz,
CDCl3) d 2.87 (2H, t, J 8.1), 2.97 (2H, t, J 8.3), 3.29 (2H, t, J 8.3),
3.35 (2H, t, J 8.1), 6.29 (1H, dd, J 8.4 and 4.2), 6.63–6.75 (2H, m),
6.97 (1H, s), 7.04–7.16 (2H, m), 7.28 (1H, d, J 7.8), 7.56 (1H, d, J
7.5), 7.89 (1H, br s). 13C NMR (75 MHz, CDCl3) d 23.06 (CH2),
28.72 (CH2), 50.53 (CH2), 53.62 (CH2), 106.95 (CH, d, J 8.2),
111.22 (CH), 112.14 (CH, d, J 23.9), 112.94 (CH, d, J 22.9), 113.98
(Cq), 118.73 (CH), 119.40 (CH), 121.62 (CH), 122.10 (CH), 127.49
(Cq), 131.64 (Cq, d, J 4.1), 136.27 (Cq), 148.70 (Cq), 157.03 (Cq,
weak signal). 19F NMR (282 MHz, CDCl3) d ꢀ127.98. m/z (FAB+)
280 M+ (found: C, 76.95; H, 6.22; N, 9.80; M+ 280.13756.
C18H17FN2 requires C, 77.12; H, 6.11; N, 9.99; M 280.13758).
4.2.4.10. 5-Methyl-3-[2-(5-methyl-2,3-dihydro-indol-1-yl)-
ethyl]-1H-indole 9n. Yellow powder. Yield 82%. Rf (EtOAc/petro-
leum ether, 1:2) 0.58. Melting point 55–56 °C. 1H NMR (300 MHz,
DMSO) d 2.20 (3H, s), 2.44 (3H, s), 2.85 (2H, t, J 8.0), 2.96 (2H, t ,
J 7.7), 3.33 (2H, t, J 8.0) 3.36 (2H, t, J 7.7), 6.45 (1H, d, J 7.7), 6.82
(1H, d, J 7.8), 6.85 (1H, s), 6.95 (1H, dd, J 8.3 and 1.7), 7.19 (1H,
d, J 2.4), 7.31 (1H, d, J 8.1), 7.40 (1H, s), 10.74 (1H, s). 13C NMR
(75 MHz, DMSO) d 20.89 (CH3), 21.81 (CH3), 22.94 (CH2), 28.62
(CH2), 50.34 (CH2), 53.18 (CH2), 107.21 (CH), 111.61 (CH), 112.10
(Cq), 118.33 (CH), 123.00 (CH), 123.14 (CH), 125.52 (CH), 126.03
4.2.4.6. 3-[2-(5-Chloro-2,3-dihydro-indol-1-yl)-ethyl]-1H-indole
9j. Prepared from 8j. Beige solid. Yield 57%. Rf (EtOAc/cyclohex-
ane, 20:80) 0.35. Melting point 113–114 °C. 1H NMR (300 MHz,