X. Fan, J. Li, L. Long et al.
European Journal of Medicinal Chemistry 222 (2021) 113564
(400 MHz, CDCl3)
d
9.23 (s, 1H), 8.22 (s, 1H), 7.60 (d, J ¼ 7.8 Hz, 1H),
4.3.17. N-(2-(1H-indol-3-yl)ethyl)-2-((2-chlorophenyl)amino)
benzamide (NP17)
7.30 (d, J ¼ 8.1 Hz, 1H), 7.22 (dd, J ¼ 8.7, 1.1 Hz, 1H), 7.20e7.14 (m,
3H), 7.10 (dd, J ¼ 7.9, 0.7 Hz, 1H), 7.08e7.03 (m, 4H), 6.93 (d,
J ¼ 2.1 Hz, 1H), 6.63e6.56 (m, 1H), 6.28 (t, J ¼ 5.5 Hz, 1H), 3.70 (q,
J ¼ 6.5 Hz, 2H), 3.02 (t, J ¼ 6.7 Hz, 2H), 2.29 (s, 3H). 13C NMR
white solid (78% yield), mp 135.3e136.5 ꢁC. 1H NMR (400 MHz,
Acetone-d6)
d 10.11 (s, 1H), 10.07 (s, 1H), 8.08e7.99 (m, 1H), 7.65 (t,
J ¼ 7.1 Hz, 2H), 7.54e7.48 (m, 1H), 7.48e7.44 (m, 1H), 7.41e7.36 (m,
2H), 7.36e7.31 (m, 1H), 7.28e7.24 (m, 1H), 7.23e7.21 (m, 1H),
7.12e7.06 (m, 1H), 7.01 (d, J ¼ 7.1 Hz, 1H), 6.99e6.92 (m, 1H),
6.89e6.82 (m, 1H), 3.77e3.68 (m, 2H), 3.09 (t, J ¼ 7.3 Hz, 2H). 13C
(101 MHz, CDCl3)
d 169.5, 145.8, 138.6, 136.3, 132.1, 132.0, 129.7,
127.4, 127.1, 122.1, 122.1, 121.3, 119.3, 118.6, 117.8, 117.3, 114.8, 112.6,
111.3, 39.9, 25.1, 20.7. HRMS (ESI-TOF) Calcd for C24H23NaN3O [M þ
Na]þ 392.1733, found 392.1740. The purity was 96.7% by HPLC
analysis.
NMR (101 MHz, Acetone-d6) d 169.6, 144.2, 139.7, 137.5, 132.3, 130.7,
129.1, 128.4, 128.2, 124.7, 123.2, 122.8, 121.9, 121.3, 119.9, 119.2, 119.1,
119.1, 116.7, 113.2, 112.0, 41.1, 25.9. HRMS (ESI-TOF) Calcd for
C
23H20NaClN3O [M þ Na]þ 412.1187, found 412.1190. The purity was
4.3.13. N-(2-(1H-indol-3-yl)ethyl)-2-((4-methoxyphenyl)amino)
benzamide (NP13)
96.9% by HPLC analysis.
yellow solid (89% yield), mp 134.8e135.8 ꢁC. 1H NMR (400 MHz,
4.3.18. N-(2-(1H-indol-3-yl)ethyl)-2-((2-bromophenyl)amino)
benzamide (NP18)
CDCl3)
d
9.20 (s, 1H), 8.19 (s, 1H), 7.63 (d, J ¼ 7.8 Hz, 1H), 7.35 (d,
J ¼ 8.1 Hz, 1H), 7.24e7.19 (m, 1H), 7.19e7.15 (m, 2H), 7.14e7.10 (m,
3H), 7.07e7.03 (m, 1H), 7.01 (d, J ¼ 2.2 Hz, 1H), 6.89e6.82 (m, 2H),
6.60e6.54 (m, 1H), 6.25 (t, J ¼ 5.3 Hz, 1H), 3.78 (s, 3H), 3.74 (q,
J ¼ 6.6 Hz, 2H), 3.07 (t, J ¼ 6.6 Hz, 2H). 13C NMR (101 MHz, CDCl3)
white solid (79% yield), mp 147.9e148.5 ꢁC. 1H NMR (400 MHz,
Acetone-d6)
d 10.07 (s, 1H), 10.03 (s, 1H), 8.06e7.98 (m, 1H),
7.68e7.61 (m, 3H), 7.51e7.45 (m, 1H), 7.40e7.37 (m, 1H), 7.36e7.32
(m, 2H), 7.32e7.26 (m, 1H), 7.22 (d, J ¼ 2.3 Hz, 1H), 7.14e7.05 (m,
1H), 7.00 (t, J ¼ 7.1 Hz, 1H), 6.92e6.88 (m, 1H), 6.89e6.80 (m, 1H),
3.72 (q, J ¼ 7.0 Hz, 2H), 3.09 (t, J ¼ 7.3 Hz, 2H). 13C NMR (101 MHz,
d
169.6, 155.8, 147.1, 136.3, 134.2, 132.1, 127.3, 127.2, 124.3, 122.2,
122.1, 119.5, 118.7, 116.8, 116.7, 114.5, 114.1, 112.8, 111.3, 55.4, 39.9,
25.2. HRMS (ESI-TOF) Calcd for C24H23NaN3O2 [M þ Na]þ 408.1682,
found 408.1687. The purity was 98.1% by HPLC analysis.
Acetone-d6)
d 169.5, 144.3, 141.1, 137.5, 134.0, 132.3, 129.1, 128.8,
128.4, 123.3, 123.2, 121.9, 121.3, 119.8, 119.5, 119.2, 119.2, 116.7, 115.3,
113.2, 112.0, 41.1, 25.9. HRMS (ESI-TOF) Calcd for C23H20NaBrN3O
[M þ Na]þ 456.0682, found 456.0687. The purity was 95.6% by HPLC
analysis.
4.3.14. N-(2-(1H-indol-3-yl)ethyl)-2-((4-(trifluoromethyl)phenyl)
amino)benzamide (NP14)
white solid (72% yield), mp 121.1e122.8 ꢁC. 1H NMR (400 MHz,
CDCl3)
d
9.50 (s, 1H), 8.09 (s, 1H), 7.63 (d, J ¼ 7.9 Hz, 1H), 7.49 (d,
4.3.19. N-(2-(1H-indol-3-yl)ethyl)-2-((4-butylphenyl)amino)
benzamide (NP20)
J ¼ 8.3 Hz, 2H), 7.46e7.40 (m, 1H), 7.40e7.35 (m, 1H), 7.30 (t,
J ¼ 7.8 Hz, 1H), 7.26e7.21 (m, 2H), 7.21e7.17 (m, 2H), 7.13 (t,
J ¼ 7.5 Hz, 1H), 7.05 (s, 1H), 6.79 (t, J ¼ 7.5 Hz, 1H), 6.24 (t, J ¼ 5.8 Hz,
1H), 3.76 (q, J ¼ 6.0 Hz, 2H), 3.09 (t, J ¼ 6.5 Hz, 2H). 13C NMR
white solid (70% yield), mp 143.9e144.2 ꢁC. 1H NMR (400 MHz,
CDCl3)
d
9.22 (s, 1H), 8.15 (s, 1H), 7.61 (d, J ¼ 7.8 Hz, 1H), 7.33e7.30
(m, 1H), 7.26e7.23 (m, 1H), 7.20e7.16 (m, 3H), 7.13e7.08 (m, 5H),
6.96 (d, J ¼ 2.3 Hz, 1H), 6.63e6.58 (m, 1H), 6.25 (t, J ¼ 5.8 Hz, 1H),
3.72 (q, J ¼ 6.5 Hz, 2H), 3.04 (t, J ¼ 6.6 Hz, 2H), 2.58e2.54 (m, 2H),
1.62e1.54 (m, 2H), 1.40e1.31 (m, 2H), 0.93 (t, J ¼ 7.3 Hz, 3H). 13C
(75 MHz, CDCl3) d 169.2,145.1, 143.2,136.4,132.0,127.6, 127.2, 126.5
(q, J ¼ 3.7 Hz), 124.5 (q, J ¼ 270.9 Hz), 122.8 (d, J ¼ 32.8 Hz), 122.3,
122.1, 120.6, 119.7, 119.6, 118.6, 118.0, 116.9, 112.7, 111.3, 40.1, 25.1.
HRMS (ESI-TOF) Calcd for C24H20NaF3N3O [M þ Na]þ 446.1451,
found 446.1467. The purity was 97.7% by HPLC analysis.
NMR (101 MHz, CDCl3)
d 169.5, 145.9, 139.0, 137.2, 136.4, 132.0,
129.1, 127.4, 127.2, 122.1, 122.1, 121.2, 119.4, 118.6, 118.0, 117.4, 115.1,
112.8, 111.3, 40.0, 35.0, 33.7, 25.2, 22.3, 13.9. HRMS (ESI-TOF) Calcd
for C27H30N3O [M þ H]þ 412.2383, found 412.2389. The purity was
97.1% by HPLC analysis.
4.3.15. N-(2-(1H-indol-3-yl)ethyl)-2-((4-(dimethylamino)phenyl)
amino)benzamide (NP15)
white solid (70% yield), mp 131.1e132.5 ꢁC.1H NMR (400 MHz,
4.3.20. N-(2-(1H-indol-3-yl)ethyl)-2-(pyridin-3-ylamino)
benzamide (NZ1)
CDCl3)
d
9.12 (s, 1H), 8.14 (s, 1H), 7.66 (d, J ¼ 7.8 Hz, 1H), 7.38 (d,
J ¼ 8.1 Hz, 1H), 7.25e7.20 (m, 1H), 7.19e7.10 (m, 5H), 7.06 (d,
J ¼ 2.2 Hz,1H), 7.02 (d, J ¼ 8.0 Hz,1H), 6.79e6.72 (m, 2H), 6.59e6.52
(m, 1H), 6.23 (t, J ¼ 5.0 Hz, 1H), 3.77 (q, J ¼ 6.6 Hz, 2H), 3.10 (t,
white solid (68% yield), mp 163.3e164.1 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d
10.82 (s, 1H), 9.73 (s, 1H), 8.72 (t, J ¼ 5.4 Hz, 1H), 8.44 (s,
1H), 8.24e8.07 (m, 1H), 7.65 (d, J ¼ 7.8 Hz, 1H), 7.62e7.54 (m, 2H),
7.38e7.26 (m, 4H), 7.21e7.17 (m, 1H), 7.06 (t, J ¼ 7.5 Hz, 1H), 6.97 (t,
J ¼ 7.4 Hz, 1H), 6.94e6.85 (m, 1H), 3.54 (q, J ¼ 6.7 Hz, 2H), 2.96 (t,
J ¼ 6.6 Hz, 2H), 2.94 (s, 6H). 13C NMR (101 MHz, CDCl3)
d 169.7,
148.0, 147.7, 136.4, 132.1, 130.9, 127.3, 127.2, 124.9, 122.2, 122.1, 119.5,
118.7, 116.4, 116.1, 114.1, 113.7, 113.0, 111.3, 41.1, 39.9, 25.3. HRMS
(ESI-TOF) Calcd for C25H26NaN4O [M þ Na]þ 421.1999, found
421.2004. The purity was 98.6% by HPLC analysis.
J ¼ 7.4 Hz, 2H). 13C NMR (101 MHz, DMSO‑d6)
d 169.0, 143.8, 142.8,
141.9, 136.7, 132.3, 129.3, 129.1, 127.7, 125.9, 124.4, 123.1, 121.4, 120.6,
119.5, 118.7, 118.7, 115.8, 112.3, 111.8, 40.6, 25.4. HRMS (ESI-TOF)
Calcd for C22H20NaN4O [M þ Na]þ 379.1529, found 379.1537. The
purity was 95.7% by HPLC analysis.
4.3.16. N-(2-(1H-indol-3-yl)ethyl)-2-((3,4,5-trimethoxyphenyl)
amino)benzamide (NP16)
yellow solid (86% yield), mp 166.7e167.4 ꢁC. 1H NMR (400 MHz,
4.3.21. N-(2-(1H-indol-3-yl)ethyl)-2-((2-methylpyridin-3-yl)
amino)benzamide (NZ2)
CDCl3)
d
9.31 (s, 1H), 8.29 (s, 1H), 7.63 (d, J ¼ 7.9 Hz, 1H), 7.37 (d,
J ¼ 8.1 Hz, 1H), 7.29 (d, J ¼ 8.2 Hz, 1H), 7.24e7.18 (m, 3H), 7.12 (t,
J ¼ 7.5 Hz,1H), 7.06e7.03 (m,1H), 6.65 (t, J ¼ 7.4 Hz,1H), 6.42 (s, 2H),
6.28 (t, J ¼ 5.3 Hz, 1H), 3.82 (s, 3H), 3.78 (s, 6H), 3.76e3.72 (m, 2H),
white solid (74% yield), mp 162.4e163.8 ꢁC. 1H NMR (400 MHz,
Acetone-d6)
d
10.09 (s, 1H), 9.92 (s, 1H), 8.13 (dd, J ¼ 4.7, 1.3 Hz, 1H),
8.08e8.01 (m, 1H), 7.69e7.67 (m, 1H), 7.66e7.59 (m, 1H), 7.63 (s,
1H), 7.40e7.36 (m, 1H), 7.36e7.26 (m, 1H), 7.23 (d, J ¼ 2.3 Hz, 1H),
7.18e7.15 (m, 1H), 7.14e7.11 (m, 1H), 7.10e7.06 (m, 1H), 7.04e6.97
(m, 1H), 6.82e6.76 (m, 1H), 3.76e3.69 (m, 2H), 3.10 (t, J ¼ 7.2 Hz,
3.08 (t, J ¼ 6.6 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d 169.5, 153.6,
145.7, 137.5, 136.4, 133.4, 132.1, 127.4, 127.1, 122.2, 122.2, 119.5, 118.6,
118.1,117.6, 115.2,112.7, 111.3, 98.6, 61.0, 56.0, 40.0, 25.2. HRMS (ESI-
TOF) Calcd for C26H27NaN3O4 [M þ Na]þ 468.1894, found 468.1900.
The purity was 95.8% by HPLC analysis.
2H), 2.50 (s, 3H). 13C NMR (101 MHz, Acetone-d6)
d 169.9, 151.3,
145.7, 143.2, 137.5, 136.9, 132.6, 129.1, 128.4, 126.3, 123.2, 122.2,
17