Arch. Pharm. Chem. Life Sci. 2014, 347, 174–184
Novel Indolalkyl Arenes as Antidepressants
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C-4), 115.5 and 115.6 (C–C, C-100), 115.7 and 116.0 (CH, C-300 and
C-500), 123.8 (CH, C-2), 127.5 and 127.6 (CH, C-200 and C-600), 128.4 and
128.1 (C–C, C-100), 130.3 (C–C, C-8), 131.0 (CH–N, C-40), 133.2 (C–N,
C-3), 150.9 (C–N, C-60), 156.5 and 159.6 (C–F, C-6), 161.2 and 164.4
(C–F, C-400). Anal. calcd. for C20H17F2N3: C, 71.20; H, 5.08; N, 12.46;
Found: C, 71.12; H, 5.13; N, 12.54.
5-Fluoro-3-[3-(5-{trifluoromethyl}-1H-pyrazolyl)propyl]-1H-
indole (11b)
Prepared from 5-(trifluoromethyl)-1H-pyrazole (0.078 g, 0.58 mmol),
anhydrous potassium carbonate (0.080 g, 0.58 mmol) and 3-(5-
fluoro-3-indolyl)propyl-4-methylbenzenesulfonate derivative 2b
(0.200 g, 0.58 mmol). The crude was purified by column
chromatography (hexane/AcOEt 2:1), 61% yield, oil. IR cmꢀ1
:
3422 (N–H), 3058 (C–H arom.), 2937–2853 (C–H aliph.), 1628
1-[3-(3-Indolyl)propyl]-5-fluoro-1H-indazole (10a)
1
0
–
–
(C N), 1487 (C C), 1239 (CF ). H NMR (CDCl ): 2.17 (q, 2H, H-2 ,
–
–
Prepared from 5-fluoro-1H-indazole (0.083 g, 0.61 mmol), anhy-
drous potassium carbonate (0.083 g, 0.61 mmol), and 3-(3-indolyl)-
3
3
J ¼ 7.0), 2.60 (t, 2H, H-10, J ¼ 7.0 Hz), 4.09 (t, 2H, H-30, J ¼ 6.9 Hz),
6.42 (s, 1H, H-7), 6.83 (t, 1H, H-7, J ¼ 9.0), 6.93 (s, 1H, H-2), 7.07
(d, 1H, H-4, J ¼ 9.6), 7.17 (m, 1H, H-60), 7.30 (s, 1H, H-50), 8.57 (s, 1H,
NH). 13C NMR (CDCl3): 22.2 (CH2, C-10), 30.6 (CH2, C-20), 52.5 (CH2,
C-30), 103.6 and 103.9 (CH, C-50), 104.6 and 104.7 (CH, C-5), 110.4
and 110.7 (CH, C-7), 112.3 and 112.4 (CH, C-4), 114.6 and 114.7
(C–C, C-1), 116.5, 120.0, 123.6 and 127.8 (C–F, CF3), 124.1 (CH, C-2),
127.9 (C–C, C-8), 131.0 (CH–N, C-60), 133.4 (C–N, C-3), 141.8, 142.3,
142.8 and 143.3 (C–CF, C-40), 156.4 and 159.5 (C–F, C-6). Anal.
calcd. for C15H13F4N3: C, 57.88; H, 4.21; N, 13.50; Found: C, 57.71;
H, 4.17; N, 13.44.
propyl-4-methylbenzenesulfonate
derivative
2a
(0.200 g,
0.61 mmol). The crude was purified by column chromatography
(hexane/AcOEt 2:1), 36% yield, m.p.: 106–107°C. IR cmꢀ1: 3411
–
–
(N–H), 3058 (C–H arom.), 2931–2873 (C–H aliph.), 1616 (C N),
1
0
–
1504 (C C). H NMR (CDCl ): 2.33 (q, 2H, H-2 , J ¼ 7.2), 2.74 (t, 2H,
–
3
H-10, J ¼ 7.2 Hz), 4.38 (t, 2H, H-30, J ¼ 6.9 Hz), 6.91 (s, 1H, H-7), 7.05–
7.22 (m, 4H, H-2, H-5, H-6 and H-80), 7.32 (m, 2H, H-4 and 100), 7.51
(d, 1H, H-70, J ¼ 7.8), 7.96 (s, 1H, H-40), 8.10 (s, 1H, NH). 13C NMR
(CDCl3): 21.8 (CH2, C-10), 27.6 (CH2, C-20), 50.7 (CH2, C-30), 108.4,
108.6, 110.2, 110.3, 111.5, 111.6, 111.9, 118.8, 119.5, 120.4, 123.1,
125.2, 126.3, 130.3, 136.4, 138.2, 147.5, 154.8. Anal. calcd. for
C18H16FN3: C, 73.70; H, 5.50; N, 14.32; Found: C, 73.68; H, 5.51;
N, 14.28.
1-[3-(3-Indolyl)propyl]-2-(2-nitrophenyl-)1H-benzo[d]-
imidazole (12a)
Prepared from 2-(2-nitrophenyl)-1H-benzo[d]imidazole (0.200 g,
0.84 mmol), anhydrous potassium carbonate (0.116 g, 0.84 mmol),
and 3-(3-indolyl)propyl-4-methylbenzenesulfonate derivative 2a
(0.275 g, 0.84 mmol). The crude was purified by column
chromatography (hexane/AcOEt 2:1), 92% yield, m.p.: 161–
1-(3-(5-Fluoro-1H-indol-3-yl)propyl)- 5-fluoro-1H-indazole
(10b)
Prepared from 5-fluoro-1H-indazole (0.80 g, 0.58 mmol), anhy-
drous potassium carbonate (0.080 g, 0.58 mmol), and 3-(5-fluoro-3-
indolyl)propyl-4-methylbenzenesulfonate derivative 2b (0.200 g,
0.58 mmol). The crude was purified by column chromatography
(hexane/AcOEt 2:1), 36% yield, m.p.: 106–107°C. IR cmꢀ1: 3411
–
162°C. IR cmꢀ1: 3451 (N–H), 3057 (C–H arom.), 2937–2852
1
–
(C–H aliph.), 1530 (NO asim), 1364 (NO sim), 1448 (C C). H NMR
–
2
2
(DMSO-d6): 2.07 (q, 2H, H-20, J ¼ 7.5), 2.64 (t, 2H, H-10, J ¼ 7.2 Hz),
4.21 (t, 2H, H-30, J ¼ 7.5 Hz), 6.92 (m, 2H, H-5 and H-7), 7.05 (t, 1H,
H-6, J ¼ 7.2), 7.29 (m, 4H, H-2, H-4, H-80and 100), 7.64–7.76 (m, 5H,
H-70, H-90, 200, 300 and 400 J ¼ 7.8), 8.13 (d, 1H, H-500, J ¼ 6.9), 10.7 (s,
1H, NH). 13C NMR (DMSO-d6): 21.3 (CH2, C-10), 28.9 (CH2, C-20), 43.2
(CH2, C-30), 110.4 (CH, C-100), 110.8 (CH, C-4), 112.4 (C–C, C-1), 117.6
(CH, C-70), 117.7 (CH, C-7), 118.8 (CH, C-6), 120.4 (C–H, C-5), 121.8
(CH, C-80), 121.7 (CH, C-90), 122.2 (C–C, C-100), 124.1 (CH, C-200), 124.4
(CH, C-2), 126.3 (C–C, C-8), 130.8 (CH, C-500), 131.4 (CH, C300),
132.8 (CH, C-400), 134.4 (C–C, C-3), 135.8 (C–C, C-50), 142.1
(C–C–NO2, C-600), 148.2 (C–C, C-60), 148.4 (N–C–N, C-40). Anal.
calcd. for C24H20N4O2: C, 72.81; H, 5.08; N, 14.23; Found: C, 71.97;
H, 5.11; N, 14.27.
(N–H), 3056 (C–H arom.), 2933–2875 (C–H aliph.), 1613 (C N),
–
1
0
–
–
1505 (C C). H NMR (CDCl ): 2.33 (q, 2H, H-2 , J ¼ 7.2), 2.74 (t, 2H,
3
H-10, J ¼ 7.2 Hz), 4.38 (t, 2H, H-30, J ¼ 6.9 Hz), 6.91 (s, 1H, H-7), 7.05–
7.22 (m, 4H, H-2, H-5, H-6 and H-80), 7.32 (m, 2H, H-4 and 100), 7.51
(d, 1H, H-70, J ¼ 7.8), 7.96 (s, 1H, H-40), 8.10 (s, 1H, NH). 13C NMR
(CDCl3): 21.8 (CH2, C-10), 28.8 (CH2, C-20), 51.4 (CH2, C-30), 106.4,
109.6, 109.9, 110.0, 112.5, 112.6, 120.4, 123.1, 125.7, 130.3, 133.3,
132.5, 136.4, 136.5, 144.8, 146.8, 154.3, 154.8. Anal. calcd. for
C18H15F2N3: C, 69.44; H, 4.86; N, 13.50; Found: C, 69.33; H, 4.90;
N, 13.62.
3-[3-(5-{Trifluoromethyl}-1H-pyrazolyl)propyl]-1H-indole
(11a)
1-[3-(5-Fluoro-3-indolyl)propyl]-2-(2-nitrophenyl)-1H-
benzo[d]imidazole (12b)
Prepared from 5-(trifluoromethyl)-1H-pyrazole 0.083 g, 0.61mmol),
anhydrous potassium carbonate (0.083 g, 0.61mmol), and 3-(3-
indolyl)propyl-4-methylbenzenesulfonate derivative 2a (0.200g,
0.61mmol). The crude was purified by column chromatography
(hexane/AcOEt 2:1), 55% yield, oil. IR cmꢀ1: 3415 (N–H), 3057 (C–H
Prepared from 2-(2-nitrophenyl)-1H-benzo[d]imidazole (0.200 g,
0.84 mmol), anhydrous potassium carbonate (0.116 g, 0.84 mmol),
and 3-(5-fluoro-3-indolyl)propyl-4-methylbenzenesulfonate deriv-
ative 2b (0.150 g, 0.36 mmol). The crude was purified by column
chromatography (hexane/AcOEt 2:1), 57% yield, m.p.: 161.5–
162°C. IR cmꢀ1: 3453 (N–H), 3064 (C–H arom.), 2957–2860 (C–H
–
–
–
–
arom.), 2939–2852 (C–H aliph.), 1619 (C N), 1493 (C C), 1239
1
(CF3). H NMR (CDCl3): 2.17 (q, 2H, H-20, J ¼ 7.0), 2.60 (t, 2H, H-10,
J ¼ 1H NMR (CDCl3): 2.30 (q, 2H, H-20, J ¼ 7.2), 2.76 (t, 2H, H-10,
J ¼ 7.2 Hz), 4.19 (t, 2H, H-30, J ¼ 7.2 Hz), 6.50 (s, 1H, H-7), 6.97 (s, 1H,
H-5), 7.09–7.24 (m, 2H, H-2 and H-6), 7.35 (d, 2H, H-4 and 60, J ¼ 8.1),
7.54 (d, 1H, H-50, J ¼ 7.8), 8.01 (s, 1H, NH). 13C NMR (CDCl3): 21.8
(CH2, C-10), 30.3 (CH2, C-20), 52.2 (CH2, C-30), 104.1 (CH, C-50), 111.1
(CH, C-4), 114.4 (C–C, C-1), 118.6 (CH, C-7), 119.3 (CH, C-6), 121.6
(C–H, C-5), 122.1 (CH, C-2), 127.1 (C–C, C-8), 130.4 (CH, C-60), 136.3
(C–N, C-3), 141.9 and 142.4 (C–F, C-40). Anal. calcd. for C15H14F3N3:
C, 61.43; H, 4.81; N, 14.33; Found: C, 61.50; H, 4.79; N, 14.30.
aliph.), 1533 (NO2 asym), 1366 (NO2 sym), 1486 (C C). 1H NMR
–
–
(DMSO-d6): 2.03 (q, 2H, H-20, J ¼ 7.5), 2.60 (t, 2H, H-10, J ¼ 7.5 Hz),
4.19 (t, 2H, H-30, J ¼ 7.5 Hz), 6.87 (m, 2H, H-5 and H-7), 7.32 (m, 4H,
H-2, H-4, H-80 and 100), 7.60–7.75 (m, 5H, H-70, H-90, 200, 300 and 400),
8.14 (d, 1H, H-500, J ¼ 6.9), 10.9 (s, 1H, NH). 13C NMR (DMSO-d6): 21.8
(CH2, C-10), 29.1 (CH2, C-20), 44.2 (CH2, C-30), 110.6, 110.8, 112.4,
116.6, 118.7, 120.8, 121.9, 121.5, 122.3, 124.1, 125.0, 126.9, 130.8,
131.8, 132.8, 134.4, 135.8, 142.6, 148.2, 146.7, 149.4, 152.6. Anal.
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