Full Papers
doi.org/10.1002/cmdc.202000752
ChemMedChem
1
solid; yield: 52%; mp: 274°C (dec.); H NMR (200 MHz, [D ]DMSO) δ:
C H BrFN O (MW: 439.24): C, 54.69; H, 2.75; N, 12.76; found: C,
20 12 4 2
54.55; H, 2.60; N, 13.00.
6
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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3
4
5
6
7
8
9
0
1
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8
9
0
1
2
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6
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8
9
0
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5
6
7
3
6
.85 (s, 3H, CH ), 4.03 (s, 3H, OCH ), 6.92 (dd, J=8.9, 2.4 Hz, 1H, H-
’), 7.46 (d, J=8.9 Hz, 1H, H-7’), 7.55- 7.60 (m, 2H, H-6 and H-4’),
7.70 (d, J=8.7 Hz, 1H, H-7), 8.35 (d, J=2.8 Hz, 1H, H-2’), 8.46 (d, J=
1.6 Hz, 1H, H-4), 9.16 (s, 1H, H-2), 11.93 (s, 1H, NH); C NMR
50 MHz, [D ]DMSO) δ: 33.9 (q), 55.2 (q), 101.7 (s), 102.0 (d), 112.0
s), 112.8 (d), 113.2 (d), 113.6 (d), 116.4 (s), 123.6 (d), 124.8 (s), 126.6
d), 128.1 (s), 130.0 (d), 131.7 (s), 136.3 (s), 143.2 (d), 154.8 (s), 165.4
3
3
[
3-(5-Bromo-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](5-bromo-1-methyl-1H-
1
3
indol-3-yl)methanone (1l). R =0.66 (CH Cl /EtOAc 7:3); yellow solid;
f
2
2
1
yield: 73%; mp: 294°C (dec.); H NMR (200 MHz, [D ]DMSO) δ: 4.04
6
(
(
(
(
6
(
s, 3H, CH ), 7.42 (dd, J=8.6, 1.8 Hz, 1H, H-6’), 7.54-7.60 (m, 2H, H-6
3
and H-7), 7.70 (d, J=8.6 Hz, 1H, H-7’), 8.21 (d, J=1.8 Hz, 1H, H-4’),
8.46 (d, J=1.6 Hz, 1H, H-4), 8.49 (s, 1H, H-2’), 9.16 (s, 1H, H-2), 12.28
À 1
s), 169.2 (s), 170.3 (s); IR (KBr): ν˜=3312 (NH), 1623 cm (CO);
1
3
(
(
(
s, 1H, NH); C NMR (50 MHz, [D ]DMSO) δ: 33.9 (q), 101.5 (s), 112.0
6
elemental analysis calcd (%) for C H BrN O (MW: 451.27): C,
21
15
4
3
s), 113.7 (d), 114.5 (d), 116.4 (s), 122.6 (d), 123.5 (d), 125.3 (d), 125.9
55.89; H, 3.35; N, 12.42; found: C, 56.02; H, 3.61; N, 12.08.
s), 126.6 (d), 128.1 (s), 131.2 (d), 135.6 (s), 136.3 (s), 143.2 (d), 158.7
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
À 1
[
3-(5-Methoxy-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](1-methyl-1H-indol-
(s), 164.9 (s), 169.4 (s), 170.1 (s); IR (KBr): ν˜=3341 (NH), 1617 cm
3
-yl)methanone (1h). R =0.79 (CH Cl /EtOAc 7:3); yellow solid; yield:
(CO); elemental analysis calcd (%) for C H Br N O (MW: 500.14): C,
f
2
2
20 12
2
4
2
1
56%; mp: 247°C (dec.); H NMR (200 MHz, [D ]DMSO) δ: 3.86 (s, 3H,
48.03; H, 2.42; N, 11.20; found: C, 48.12; H, 2.60; N, 11.05; HRMS: m/
6
+
CH
), 4.04 (s, 3H, OCH
3
), 6.92 (dd, J=8.9, 2.3 Hz, 1H, H-6’), 7.36 –
z=498.94 [M+H] ; t
= 3.84 min (>99% purity).
R
3
7
7
1
1
.49 (m, 3H, H-5, H-6 and H-7’), 7.56 (d, J=2.3 Hz, 1H, H-4’), 7.67-
[
3-(5-Fluoro-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](1-methyl-1H-indol-3-
.71 (m, 1H, H-7), 8.33 – 8.37 (m, 2H, H-4 and H-2’), 9.12 (s, 1H, H-2),
1.94 (s, 1H, NH); C NMR (50 MHz, [D ]DMSO) δ: 34.1 (q), 55.8 (q),
02.2 (s+d), 102.6 (s), 111.3 (s), 111.9 (d), 113.7 (d), 122.0 (d), 124.0
d), 124.6 (d), 125.4 (s), 126.9 (d), 130.4 (d), 132.2 (s), 138.0 (s), 142.9
13
yl)methanone (1m). R =0.71 (CH Cl /EtOAc 7:3); yellow solid; yield:
f
2
2
6
1
59%; mp: 261°C (dec.); H NMR (200 MHz, [D
]DMSO) δ: 4.04 (s, 3H,
6
CH ), 7.15 (td, J=9.4, 9.1, 2.4 Hz, 1H, H-6’), 7.39-7.43 (m, 2H, H-5 and
3
(
H-6), 7.59 (dd, J=9.1, 4.5 Hz, 1H, H-7’), 7.67-7.78 (m, 2H, H-7 and H-
(d), 155.3 (s), 165.9 (s), 170.1 (s), 170.9 (s); IR (KBr): ν˜=3302 (NH),
À 1
4’), 8.32-8.36 (m, 1H, H-4), 8.49 (s, 1H, H-2’), 9.11 (s, 1H, H-2), 12.18
1
616 cm (CO); elemental analysis calcd (%) for C H N O (MW:
21 16
4
3
13
(
s, 1H, NH); C NMR (50 MHz, [D ]DMSO) δ: 33.7 (q), 102.1 (d, J
=
6
C7a-F
3
72.38): C, 67.73; H, 4.33; N, 15.05; found: C, 67.70; H, 4.51; N, 15.20.
4.5 Hz), 105.2 (d, JC4-F = 23.6 Hz), 111.0 (d, JC6-F = 26.0 Hz), 111.4 (d),
[3-(5-Bromo-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](5-methoxy-1-methyl-
1H-indol-3-yl)methanone (1i). R =0.69 (CH Cl /EtOAc 7:3); yellow
112.7 (s), 113.7 (d, JC7-F = 12.0 Hz), 121.5 (d), 123.6 (d), 124.1 (d),
124.6 (d, JC3a-F = 11.2 Hz), 126.4 (s), 131.5 (d), 133.5 (s), 137.5 (s),
142.5 (d), 158.0 (d, JC5-F = 234.6 Hz), 165.0 (s), 169.7 (s), 170.3 (s); IR
f
2
2
1
solid; yield: 78%; mp: 258°C (dec.); H NMR (200 MHz, [D ]DMSO) δ:
6
À 1
3
7
7
2
.85 (s, 3H, CH ), 4.00 (s, 3H, OCH ), 7.03 (dd, J=8.9, 2.5 Hz, 1H, H-6),
(KBr): ν˜=3284 (NH), 1623 cm (CO); elemental analysis calcd (%)
3
3
.41 (dd, J=8.6, 1.9 Hz, 1H, H-6’), 7.53–7.61 (m, 2H, H-7 and H-7’),
.83 (d, J=2.5 Hz, 1H, H-4), 8.21 (d, J=1.9 Hz, 1H, H-4’), 8.47 (d, J=
for C H FN O (MW: 360.34): C, 66.66; H, 3.64; N, 15.55; found: C,
2
0
13
4
2
66.70; H, 3.60; N, 15.22.
1
3
.8 Hz, 1H, H-2’), 9.02 (s, 1H, H-2), 12.27 (s, 1H, NH); C NMR
]DMSO) δ: 33.9 (q), 55.4 (q), 101.6 (s), 103.5 (d), 112.4
d), 112.5 (s), 113.4 (d), 113.6 (s), 114.5 (d), 122.6 (d), 125.3 (d), 125.9
[
3-(5-Fluoro-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](5-fluoro-1-methyl-1H-
(50 MHz, [D
6
indol-3-yl)methanone (1n). R =0.65 (CH Cl /EtOAc 7:3); yellow solid;
f
2
2
(
(
(
1
yield: 63%; mp: 265°C (dec.); H NMR (200 MHz, [D ]DMSO) δ: 4.03
6
s), 127.4 (s), 131.1 (d), 132.3 (s), 135.6 (s), 142.2 (d), 156.8 (s), 164.9
s), 169.8 (s), 170.0 (s); IR (KBr): ν˜=3302 (NH), 1610 cm (CO);
À 1
(s, 3H, CH ), 7.15 (td, J=9.2, 9.1, 2.6 Hz, 1H, H-6’), 7.30 (td, J=9.2,
3
9.1, 2.6 Hz, 1H, H-6), 7.60 (dd, J=9.1, 4.6 Hz, 1H, H-7’), 7.71- 7.77 (m,
2H, H-7 and H-4’), 8.01 (dd, J=9.6, 2.6 Hz, 1H, H-4), 8.50 (d, J=
elemental analysis calcd (%) for C H BrN O (MW: 451.27): C, 55.89;
21
15
4
3
H, 3.35; N, 12.42; found: C, 55.70; H, 3.51; N, 12.24; HRMS: m/z=
1
3
+
2.9 Hz, 1H, H-2’), 9.16 (s, 1H, H-2), 12.19 (s, 1H, NH); C NMR
50 MHz, [D ]DMSO) δ: 34.0 (q), 102.1 (d, J = 4.3 Hz), 105.2 (d,
451.04 [M+H] ; t = 3.65 min (>99% purity).
R
(
6
C7’a-F
[
3-(5-Bromo-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](1-methyl-1H-indol-3-
JC4’-F = 25.1 Hz), 106.6 (d, JC4-F = 24.9 Hz), 111.0 (d, JC6’-F = 26.4 Hz),
112.1 (d, JC6-F = 25.7 Hz), 112.5 (d, JC7a-F = 4.2 Hz), 113.1 (d, JC7-F
9.5 Hz), 113.7 (d, JC7’-F = 9.7 Hz), 124.6 (d, JC3’a-F = 11.2 Hz), 127.2 (d,
JC3a-F = 11.1 Hz), 131.5 (d), 133.4 (s), 134.2 (s), 143.5 (d), 158.0 (d, JC5’-F
yl)methanone (1j). R =0.75 (CH Cl /EtOAc 7:3); yellow solid; yield:
4
CH
7
1
=
f
2
2
1
6%; mp: 271 C (dec.); H NMR (200 MHz, [D ]DMSO) δ: 4.04 (s, 3H,
), 7.36-7.47 (m, 3H, H-5, H-6 and H-6’), 7.56 (d, J=8.6 Hz, 1H, H-
’), 7.67- 7.72 (m, 1H, H-7), 8.22 (d, J=1.8 Hz, 1H, H-4’), 8.32-8.37 (m,
H, H-4), 8.48 (d, J=2.8 Hz, 1H, H-2’), 9.11 (s, 1H, H-2), 12.27 (s, 1H,
°
6
3
= 234.1 Hz), 159.6 (d, JC5-F = 235.3 Hz), 165.0 (s), 169.4 (s), 170.1 (s);
À 1
IR (KBr): ν˜=3267 (NH), 1615 cm (CO); elemental analysis calcd
13
NH); C NMR (50 MHz, [D ]DMSO) δ: 33.7 (q), 101.6 (s), 111.4 (d),
(%) for C H F N O (MW: 378.33): C, 63.49; H, 3.20; N, 14.81; found:
6
20 12
2
4
2
1
12.7 (s), 113.7 (s), 114.6 (d), 121.5 (d), 122.6 (d), 123.6 (d), 124.1 (d),
C, 63.60; H, 3.32; N, 15.00.
125.3 (d), 125.9 (s), 126.4 (s), 131.1 (d), 135.6 (s), 137.5 (s), 142.5 (d),
À 1
[3-(5-Fluoro-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](5-methoxy-1-methyl-
164.9 (s), 169.8 (s), 170.2 (s); IR (KBr): ν˜=3376 (NH), 1618 cm (CO);
1
H-indol-3-yl)methanone (1o). R =0.66 (CH Cl /EtOAc 7:3); yellow
f
2
2
elemental analysis calcd (%) for C20
H13BrN O (MW: 421.25): C, 57.02;
4 2
1
solid; yield: 62%; mp: 218°C (dec.); H NMR (200 MHz, [D ]DMSO) δ:
6
H, 3.11; N, 13.30; found: C, 56.92; H, 3.02; N, 13.14; HRMS: m/z=
+
3.86 (s, 3H, CH ), 4.00 (s, 3H, OCH ), 7.04 (dd, J=8.9, 2.5 Hz, 1H, H-6),
3 3
4
21.03 [M+H] ; t = 3.68 min (>99% purity).
R
7
.15 (td, J=9.2, 9.1, 2.6 Hz, 1H, H-6’), 7.55-7.62 (m, 2H, H-7 and H-
[3-(5-Bromo-1H-indol-3-yl)-1,2,4-oxadiazol-5-yl](5-fluoro-1-methyl-1H-
indol-3-yl)methanone (1k). R =0.70 (CH Cl /EtOAc 7:3); yellow solid;
7’), 7.74 (dd, J=9.7, 2.6 Hz, 1H, H-4’), 7.84 (d, J=2.5 Hz, 1H, H-4),
13
8.48 (d, J=2.7 Hz, 1H, H-2’), 9.03 (s, 1H, H-2), 12.18 (s, 1H, NH);
NMR (50 MHz, [D ]DMSO) δ: 33.9 (q), 55.4 (q), 102.1 (d, J =
C7a-F
C
f
2
2
1
yield: 58%; mp: 277°C (dec.); H NMR (200 MHz, [D ]DMSO) δ: 4.04
6
6
(
1
4
s, 3H, CH ), 7.29 (td, J=9.2, 9.2, 2.6 Hz, 1H, H-6), 7.41 (dd, J=8.7,
.9 Hz, 1H, H-6’), 7.55 (d, J=8.7 Hz, 1H, H-7’), 7.73 (dd, J=9.2,
.4 Hz, 1H, H-7), 8.00 (dd, J=9.5, 2.6 Hz, 1H, H-4), 8.20 (d, J=1.9 Hz,
4.5 Hz), 103.5 (d), 105.2 (d, JC4-F = 24.7 Hz), 111.0 (d, JC6-F = 26.1 Hz),
112.4 (d), 112.5 (s), 113.4 (d), 113.7 (d, JC7-F = 9.5 Hz), 124.6 (d, JC3a-F
= 11.1 Hz), 127.4 (s), 131.5 (d), 132.3 (s), 133.4 (s), 142.2 (d), 156.8
(s), 158.0 (d, JC5-F = 234.4 Hz), 165.0 (s), 169.8 (s), 170.0 (s); IR (KBr):
3
1H, H-4’), 8.48 (d, J=2.1 Hz, 1H, H-2’), 9.16 (s, 1H, H-2), 12.27 (s, 1H,
1
3
À 1
NH); C NMR (50 MHz, [D
]DMSO) δ: 34.0 (q), 101.54 (s), 106.6 (d, JC4-
ν˜=3244 (NH), 1618 cm (CO); elemental analysis calcd (%) for
6
=
24.9 Hz), 112.1 (d, JC6-F = 26.4 Hz), 112.5 (d, J = 4.2 Hz), 113.1
F
C7a-F
C H FN O (MW: 390.37): C, 64.61; H, 3.87; N, 14.35; found: C,
21 15
4
3
(
1
d, JC7-F = 10.2 Hz), 113.7 (s), 114.6 (d), 122.6 (d), 125.3 (d), 125.9 (s),
27.2 (d, JC3a-F = 11.3 Hz), 131.1 (d), 134.1 (s), 135.6 (s), 143.6 (d),
64.70; H, 3.70; N, 14.10.
159.6 (d, JC5-F = 236.0 Hz), 164.9 (s), 169.5 (s), 170.1 (s); IR (KBr): ν˜=
(5-Bromo-1-methyl-1H-indol-3-yl)[3-(5-fluoro-1H-indol-3-yl)-1,2,4-oxa-
À 1
3267 (NH), 1615 cm
(CO); elemental analysis calcd (%) for
diazol-5-yl]methanone (1p). R =0.67 (CH Cl /EtOAc 7:3); yellow
f
2
2
1
solid; yield: 59%; mp: 280°C (dec.); H NMR (200 MHz, [D ]DMSO) δ:
6
ChemMedChem 2020, 15, 1–19
14
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