The Journal of Organic Chemistry
Article
1H), 7.33 (ddd, J = 8.3, 7.0, 1.1 Hz, 1H), 7.27−7.16 (m, 7H), 7.03
(ddd, J = 7.4, 4.9, 0.9 Hz, 1H), 5.75 (s, 2H), 1.66 (s, 6H). 13C{1H}
NMR (126 MHz, CDCl3) δ 163.1, 161.0, 146.8, 146.4, 141.5, 137.7,
137.3, 137.2, 132.5, 130.9, 128.7, 127.4, 127.0, 125.7, 124.5, 123.7,
121.9, 121.6, 120.0, 119.1, 115.8, 111.0, 57.0, 47.9, 26.8. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C30H27N4O3 491.2083; found
491.2094.
121.5, 120.8, 120.8, 119.0, 118.4, 110.6, 57.2, 47.7, 27.0. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C36H32N3O 522.2545; found
522.2550.
1-Benzyl-3-(4-(dimethylamino)phenyl)-N-(2-(pyridin-2-yl)-prop-
an-2-yl)-1H-indole-2-carboxamide (3r). Purification by flash chro-
matography in petroleum ether/ethyl acetate = 4/1 gave 3r as a pale
yellow oil (5.9 mg, 12%). 1H NMR (500 MHz, CDCl3) δ 8.26 (ddd, J
= 4.8, 1.7, 0.9 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.48−7.43 (m, 3H),
7.39 (d, J = 8.4 Hz, 1H), 7.29−7.26 (m, 1H), 7.23 (dd, J = 6.1, 1.4
Hz, 2H), 7.21−7.17 (m, 2H), 7.15−7.11 (m, 3H), 7.04−6.99 (m,
2H), 6.81 (d, J = 8.7 Hz, 2H), 5.79 (s, 2H), 2.95 (s, 6H), 1.55 (s,
6H). 13C{1H} NMR (126 MHz, CDCl3) δ 164.1, 161.9, 147.8, 138.7,
137.4, 136.6, 136.1, 131.3, 129.5, 128.5, 127.0, 127.0, 126.8, 124.1,
121.2, 121.0, 120.3, 119.6, 119.0, 112.8, 110.3, 57.3, 47.5, 40.7, 27.3.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H33N4O 489.2654;
found 489.2666.
1-Benzyl-3-(2-nitrophenyl)-N-(2-(pyridin-2-yl)propan-2-yl)-1H-
indole-2-carboxamide (3s). Purification by flash chromatography in
petroleum ether/ethyl acetate = 3/1 gave 3s as a dark brown oil (5.6
mg, 11%). 1H NMR (500 MHz, CDCl3) δ 8.15 (ddd, J = 4.8, 1.7, 0.9,
1H), 8.04 (dd, J = 8.2, 1.0, 1H), 7.99 (brs, 1H), 7.64−7.59 (m, 1H),
7.59−7.55 (m, 1H), 7.52−7.45 (m, 2H), 7.37 (d, J = 8.4, 1H), 7.30−
7.27 (m, 2H), 7.26−7.18 (m, 3H), 7.15−7.08 (m, 3H), 7.06−6.99
(m, 2H), 5.88 (d, J = 16.3, 1H), 5.69 (d, J = 16.2, 1H), 1.56 (s, 3H),
1.43 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 163.7, 160.9,
150.4, 147.3, 138.1, 137.2, 136.8, 134.3, 132.6, 132.0, 129.4, 128.6,
127.2, 126.6, 126.3, 124.4, 124.1, 121.5, 121.1, 119.8, 119.0, 113.9,
110.7, 57.2, 47.8, 27.5, 26.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C30H27N4O3 491.2083; found 491.2083.
1-Benzyl-N-(2-(pyridin-2-yl)propan-2-yl)-3-(thiophen-2-yl)-1H-
indole-2-carboxamide (3m). Purification by flash chromatography in
petroleum ether/ethyl acetate = 1/1 gave 3m as a dark purple oil
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(29.0 mg, 64%). H NMR (500 MHz, CDCl3) δ 8.28 (ddd, J = 4.8,
1.7, 0.9 Hz, 1H), 7.76 (s, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.56−7.49
(m, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.35 (dd, J = 5.2, 1.1 Hz, 1H), 7.28
(ddd, J = 8.3, 7.0, 1.1 Hz, 1H), 7.26−7.22 (m, 3H), 7.18 (ddd, J =
11.9, 5.6, 4.2 Hz, 4H), 7.12 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 5.2, 3.5
Hz, 1H), 7.05 (ddd, J = 7.4, 4.9, 1.0 Hz, 1H), 5.76 (s, 2H), 1.62 (s,
6H). 13C{1H} NMR (126 MHz, CDCl3) δ 163.9, 161.2, 147.6, 138.2,
137.1, 136.8, 134.6, 131.7, 128.6, 128.0, 127.3, 127.2, 127.2, 126.9,
126.1, 124.4, 121.5, 121.0, 120.9, 119.1, 110.8, 110.5, 57.3, 47.8, 27.1.
HRMS (ESI-TOF) m/z: calcd for C28H26N3OS [M + H]+ 452.1797;
found 452.1799.
1-Benzyl-3-(1-methyl-1H-pyrazol-4-yl)-N-(2-(pyridin-2-yl)-
propan-2-yl)-1H-indole-2-carboxamide (3n). Purification by flash
chromatography in petroleum ether/ethyl acetate = 1/1 gave 3n as a
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gray brown solid (39.7 mg, 87%), m.p.: 151−152 °C. H NMR (500
MHz, CDCl3) δ 8.32 (ddd, J = 4.9, 1.7, 0.9 Hz, 1H), 7.99 (brs, 1H),
7.76 (d, J = 0.6 Hz, 1H), 7.68−7.62 (m, 2H), 7.59 (td, J = 7.9, 1.8 Hz,
1H), 7.37 (d, J = 8.4 Hz, 1H), 7.27 (ddd, J = 8.3, 7.0, 1.1 Hz, 1H),
7.25−7.20 (m, 3H), 7.19−7.12 (m, 4H), 7.10 (ddd, J = 7.4, 4.9, 0.9
Hz, 1H), 5.75 (s, 2H), 3.87 (s, 3H), 1.67 (s, 6H). 13C{1H} NMR
(126 MHz, CDCl3) δ 163.8, 161.6, 147.4, 139.8, 138.4, 137.3, 137.0,
130.5, 129.8, 128.5, 127.1, 126.9, 126.8, 124.1, 121.7, 120.6, 120.5,
119.2, 113.6, 110.4, 109.0, 57.0, 47.7, 38.9, 27.2. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C28H28N5O 450.2294; found 450.2309.
1-Benzyl-N-(2-(pyridin-2-yl)propan-2-yl)-3-(pyridin-4-yl)-1H-in-
dole-2-carboxamide (3o). Purification by flash chromatography in
petroleum ether/ethyl acetate = 2/1 gave 3o as a yellow solid (23.5
(E)-1-Benzyl-N-(2-(pyridin-2-yl)propan-2-yl)-3-styryl-1H-indole-
2-carboxamide (3t). Purification by flash chromatography in
petroleum ether/ethyl acetate = 3/1 gave 3t as a colorless oil (28.3
1
mg, 60%). H NMR (500 MHz, CDCl3) δ 8.29 (s, 1H), 8.17−8.12
(m, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 16.5 Hz, 1H), 7.64 (td,
J = 7.8, 1.8 Hz, 1H), 7.52 (d, J = 7.4 Hz, 2H), 7.39−7.34 (m, 2H),
7.29 (ddd, J = 10.4, 6.1, 4.7 Hz, 4H), 7.24−7.21 (m, 4H), 7.19−7.17
(m, 1H), 7.16−7.13 (m, 2H), 7.06 (ddd, J = 7.4, 4.9, 0.9 Hz, 1H),
5.70 (s, 2H), 1.82 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3) δ
163.9, 161.5, 147.9, 138.4, 138.2, 137.9, 137.0, 132.8, 129.8, 128.6,
128.6, 127.2, 127.0, 126.9, 126.1, 125.2, 124.3, 121.8, 121.6, 121.2,
121.0, 119.2, 115.2, 110.8, 57.6, 47.7, 27.7. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C32H30N3O 472.2389; found 472.2399.
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mg, 53%), m.p.: 132−133 °C. H NMR (500 MHz, CDCl3) δ 8.59
(brs, 2H), 8.17 (s, 1H), 8.17 (ddd, J = 4.8, 1.7, 0.9 Hz, 1H), 7.72 (d, J
= 8.0 Hz, 1H), 7.63−7.50 (m, 3H), 7.43 (d, J = 8.4 Hz, 1H), 7.34−
7.29 (m, 1H), 7.25−7.12 (m, 7H), 7.05 (ddd, J = 7.4, 4.9, 0.9 Hz,
1H), 5.74 (s, 2H), 1.67 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3) δ
163.2, 161.1, 149.7, 147.1, 142.4, 137.8, 137.3, 137.1, 132.4, 128.6,
127.4, 127.0, 125.6, 125.2, 124.4, 121.8, 121.4, 120.1, 119.0, 115.1,
110.9, 57.0, 47.8, 26.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C29H27N4O 447.2185; found 447.2177.
tert-Butyl (4-(1-Benzyl-2-((2-(pyridin-2-yl)propan-2-yl)-carbamo-
yl)-1H-indol-3-yl)phenyl)carbamate (3u). Purification by flash
chromatography in petroleum ether/ethyl acetate = 3/1 gave 3u as
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a white solid (41.0 mg, 73%), m.p.: 87−88 °C. H NMR (500 MHz,
1-Benzyl-N-(2-(pyridin-2-yl)propan-2-yl)-3-(pyridin-3-yl)-1H-in-
dole-2-carboxamide (3p). Purification by flash chromatography in
petroleum ether/ethyl acetate = 2/1 gave 3p as a sandy beige solid
CDCl3) δ 8.25−8.16 (m, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.56−7.48
(m, 4H), 7.46−7.36 (m, 3H), 7.30−7.26 (m, 1H), 7.25−7.21 (m,
2H), 7.21−7.12 (m, 4H), 7.07 (d, J = 8.1 Hz, 1H), 7.04−6.99 (m,
1H), 6.51 (brs, 1H), 5.77 (s, 2H), 1.59 (s, 6H), 1.53 (s, 9H). 13C{1H}
NMR (126 MHz, CDCl3) δ 163.8, 161.7, 152.6, 147.6, 138.5, 137.5,
137.3, 136.7, 131.2, 130.4, 128.5, 128.5, 127.1, 126.9, 126.6, 124.2,
121.4, 120.7, 120.6, 119.0, 118.5, 118.4, 110.5, 80.6, 57.2, 47.6, 28.4,
27.1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C35H37N4O3
561.2866; found 561.2867.
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(36.2 mg, 81%), m.p.: 148−149 °C. H NMR (500 MHz, CDCl3) δ
8.88 (d, J = 1.7 Hz, 1H), 8.46 (dd, J = 4.8, 1.5 Hz, 1H), 8.13 (s, 1H),
8.08 (dd, J = 4.8, 0.6 Hz, 1H), 7.90 (dt, J = 7.8, 1.9 Hz, 1H), 7.66 (d, J
= 8.0 Hz, 1H), 7.56 (td, J = 7.8, 7.6, 1.8 Hz, 1H), 7.44 (d, J = 8.4 Hz,
1H), 7.34−7.27 (m, 2H), 7.25−7.14 (m, 7H), 7.06−7.01 (m, 1H),
5.78 (s, 2H), 1.65 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3) δ
163.4, 161.3, 151.0, 148.0, 147.2, 138.1, 137.8, 137.3, 137.0, 131.9,
130.2, 128.6, 127.3, 127.1, 126.2, 124.4, 123.3, 121.6, 121.2, 120.2,
119.0, 114.6, 110.8, 57.0, 47.8, 26.9. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C29H27N4O 447.2185; found 447.2180.
1-Benzyl-3-(4-methoxyphenyl)-4-methyl-N-(2-(pyridin-2-yl)-
propan-2-yl)-1H-indole-2-carboxamide (4a). Purification by flash
chromatography in petroleum ether/ethyl acetate = 3/1 gave 4a as an
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off-white solid (38.5 mg, 79%), m.p.: 136−137 °C. H NMR (500
3-([1,1′-Biphenyl]-4-yl)-1-benzyl-N-(2-(pyridin-2-yl)-propan-2-
yl)-1H-indole-2-carboxamide (3q). Purification by flash chromatog-
raphy in petroleum ether/ethyl acetate = 3/1 gave 3q as a white solid
MHz, CDCl3) δ 8.34 (dd, J = 4.8, 0.7 Hz, 1H), 7.48 (td, J = 7.8, 1.8
Hz, 1H), 7.45−7.40 (m, 2H), 7.26 (d, J = 2.0 Hz, 1H), 7.24 (d, J =
7.7 Hz, 2H), 7.22−7.11 (m, 4H), 7.05 (ddd, J = 7.4, 4.9, 0.9 Hz, 1H),
6.99 (d, J = 8.0 Hz, 1H), 6.96−6.89 (m, 3H), 6.84 (d, J = 7.1 Hz,
1H), 5.77 (s, 2H), 3.80 (s, 3H), 2.11 (s, 3H), 1.44 (s, 6H). 13C{1H}
NMR (126 MHz, CDCl3) δ 164.1, 161.7, 159.3, 147.8, 138.7, 137.4,
136.5, 132.7, 132.5, 130.7, 128.5, 128.2, 127.0, 126.9, 125.4, 124.0,
122.0, 121.4, 119.4, 119.0, 113.6, 108.4, 57.3, 55.3, 47.6, 27.3, 20.4.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H32N3O2 490.2495;
found 490.2495.
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(46.4 mg, 89%), m.p.: 146−148 °C. H NMR (500 MHz, CDCl3) δ
8.10 (d, J = 4.6 Hz, 1H), 7.74−7.65 (m, 4H), 7.63 (d, J = 8.2 Hz,
2H), 7.54 (d, J = 7.3 Hz, 2H), 7.48−7.40 (m, 4H), 7.34 (t, J = 7.4 Hz,
1H), 7.32−7.27 (m, 1H), 7.27−7.23 (m, 2H), 7.18 (dd, J = 14.7, 7.3
Hz, 4H), 7.06 (d, J = 8.1 Hz, 1H), 6.93 (ddd, J = 7.4, 4.9, 0.9 Hz,
1H), 5.80 (s, 2H), 1.61 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3) δ
163.7, 161.6, 147.4, 141.0, 140.0, 138.5, 137.4, 136.7, 133.0, 131.0,
130.8, 128.8, 128.9, 127.3, 127.2, 127.2, 127.1, 127.0, 126.5, 124.2,
1798
J. Org. Chem. 2021, 86, 1789−1801