Journal of Medicinal Chemistry
Article
= 5.6 Hz, 1H), 7.63 (s, 1H), 7.48−7.42 (m, 3H), 7.38−7.30 (m, 3H),
3.59−2.86 (m, 8H), 2.70 (br s, 3H), 2.49 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 165.6, 143.1, 140.8, 139.9, 139.4, 138.0, 134.9, 133.9,
133.6, 133.2, 129.1, 128.5, 125.4, 124.8, 123.7, 123.0, 122.6, 122.5,
122.0, 121.7, 120.7, 54.4 (2), 49.4, 44.0 (2), 21.8. HRMS (ESI) m/z
calcd for C27H28N3OS [M + H]+: 442.1953, found: 442.1961.
3-Methyl-N-(5-(5-methylbenzo[b]thiophen-2-yl)-2-(4-methylpi-
perazin-1-yl)phenyl)benzamide (9k). The title compound was
7.70 (d, J = 7.1 Hz, 1H), 7.40−7.32 (m, 3H), 7.27−7.23 (m, 2H), 6.91
(d, J = 7.6 Hz, 1H), 6.79 (s, 1H), 6.53 (dd, J = 2.0, 8.2 Hz, 1H), 3.34−
3.32 (m, 4H), 3.03 (br s, 4H), 2.71 (br s, 3H), 2.44−2.42 (m, 7H),
2.02−1.97 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 165.2, 148.5,
141.7, 140.6, 139.6, 139.0, 135.3, 133.9, 132.8, 129.6, 129.0, 129.0,
128.1, 128.1, 123.8, 123.1, 121.3, 118.8, 114.8, 111.1, 110.6, 55.6, 51.0
(2), 47.9, 45.2, 25.6 (2), 21.7. HRMS (ESI) m/z calcd for C29H35N4O
[M + H]+: 455.2811, found: 455.2811.
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prepared according to general procedure A (14 mg, 23% yield). H
3-Methyl-N-(4-(4-methylpiperazin-1-yl)-4′-(pyrrolidin-1-yl)-[1,1′-
NMR (500 MHz, CDCl3) δ 9.06 (s, 1H), 8.96 (s, 1H), 7.78 (s, 1H),
7.70−7.64 (m, 2H), 7.59−7.53 (m, 2H), 7.47−7.41 (m, 3H), 7.34 (d, J
= 8.2 Hz, 1H), 7.15 (dd, J = 1.3, 8.2 Hz, 1H), 3.95−2.64 (m, 11H),
2.48 (s, 3H), 2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 165.3,
143.8, 141.2, 139.2, 137.0, 135.1, 134.5, 134.1, 133.0, 133.0, 129.0,
129.0, 128.2, 126.4, 123.8, 123.8, 122.3, 122.1, 121.7, 120.0, 117.8, 55.3
(2), 50.5, 44.5, 21.7 (2), 21.6. HRMS (ESI) m/z calcd for
C28H30N3OS [M + H]+: 456.2110, found: 456.2115.
biphenyl]-3-yl)benzamide (9q). The title compound was prepared
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according to general procedure A (18 mg, 29% yield). H NMR (500
MHz, CDCl3) δ 9.45 (br s, 1H), 8.82 (d, J = 1.4 Hz, 1H), 7.80 (s, 1H),
7.72 (d, J = 7.7 Hz, 1H), 7.57−7.54 (m, 2H), 7.44−7.37 (m, 2H), 7.30
(dd, J = 2.0, 8.4 Hz, 1H), 7.27−7.25 (m, 1H), 6.63−6.60 (m, 2H),
3.33−3.31 (m, 4H), 3.08 (br s, 4H), 2.78 (br s, 3H), 2.49 (br s, 3H),
2.47 (s, 4H), 2.03−2.00 (m, 4H); 13C NMR (125 MHz, CDCl3) δ
165.0, 147.6, 139.7, 138.9, 138.6, 135.4, 134.1, 132.7, 128.9, 128.1,
128.0, 127.5, 123.9, 121.6, 121.3, 117.3, 112.1, 55.9, 51.5, 47.8 (2),
45.6, 25.7 (2), 21.7. HRMS (ESI) m/z calcd for C29H35N4O [M +
H]+: 455.2811, found: 455.2815.
N-(5-(Dibenzo[b,d]thiophen-2-yl)-2-(4-methylpiperazin-1-yl)-
phenyl)-3-methylbenzamide (9l). The title compound was prepared
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according to general procedure A (26 mg, 39% yield). H NMR (500
MHz, CDCl3) δ 9.27 (s, 1H), 8.97 (d, J = 1.4 Hz, 1H), 8.40 (d, J = 1.5
Hz, 1H), 8.28−8.24 (m, 1H), 7.91 (d, J = 8.6 Hz, 1H), 7.88−7.85 (m,
1H), 7.81 (br s, 1H), 7.75 (dd, J = 1.9, 8.4 Hz, 1H), 7.70 (d, J = 7.1
Hz, 1H), 7.50−7.46 (m, 3H), 7.45−7.40 (m, 3H), 3.26 (br s, 4H),
3.00 (br s, 4H), 2.70 (s, 3H), 2.49 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 165.3, 140.1, 140.1, 139.3, 139.1, 138.8, 137.4, 136.3, 135.8,
135.3, 134.3, 132.9, 129.0, 128.1, 127.0, 126.4, 124.6, 124.0, 123.2,
123.1, 123.0, 122.0, 121.6, 120.2, 118.6, 55.9 (2), 51.5, 45.7, 21.7 (2).
HRMS (ESI) m/z calcd for C31H30N3OS [M + H]+: 492.2110, found:
492.2115.
3-Methyl-N-(4-(4-methylpiperazin-1-yl)-2′-(morpholinomethyl)-
[1,1′-biphenyl]-3-yl)benzamide (9r). The title compound was
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prepared according to general procedure A (27 mg, 42% yield). H
NMR (500 MHz, CDCl3) δ 9.37 (br s, 1H), 8.55 (s, 1H), 7.77 (s,
1H), 7.70 (s, 1H), 7.44−7.28 (m, 7H), 7.13 (d, J = 6.7 Hz, 1H), 3.73
(br s, 4H), 3.36−2.97 (m, 20H); 13C NMR (125 MHz, CDCl3) δ
165.0, 142.6, 140.1, 139.2, 138.9, 135.3, 133.5, 132.8, 130.5, 130.3,
129.0, 128.0, 127.5, 127.3, 125.2, 124.0, 120.8, 120.5, 67.0, 60.1, 56.2
(2), 53.4 (2), 52.1 (2), 46.1, 21.7 (2). HRMS (ESI) m/z calcd for
C30H37N4O2 [M + H]+: 485.2917, found: 485.2924.
3-Methyl-N-(5-(1-methyl-1H-indol-4-yl)-2-(4-methylpiperazin-1-
yl)phenyl)benzamide (9m). The title compound was prepared
according to general procedure A (30 mg, 51% yield). 1H NMR
(500 MHz, CDCl3) δ 9.17 (br s, 1H), 8.86 (s, 1H), 7.73 (s, 1H), 7.61
(d, J = 7.0 Hz, 1H), 7.42 (dd, J = 1.9, 8.3 Hz, 1H), 7.36−7.30 (m, 3H),
7.27−7.22 (m, 2H), 7.19 (dd, J = 1.5, 7.0 Hz, 1H),7.06 (d, J = 3.2 Hz,
1H), 6.74 (d, J = 3.0 Hz, 1H), 3.77 (s, 3H), 3.18 (br s, 4H), 2.91 (br s,
4H), 2.58 (br s, 3H), 2.40 (br s, 3H); 13C NMR (125 MHz, CDCl3) δ
165.2, 139.9, 139.9, 138.9, 137.5, 135.4, 133.7, 133.6, 132.8, 129.6,
129.0, 128.3, 126.8, 124.8, 123.7, 122.0, 121.4, 120.8, 119.6, 108.8,
100.8, 55.3, 50.4, 44.7, 33.2, 21.7. HRMS (ESI) m/z calcd for
C28H31N4O [M + H]+: 439.2498, found: 439.2496.
3-Methyl-N-(4-(4-methylpiperazin-1-yl)-3′-(morpholinomethyl)-
[1,1′-biphenyl]-3-yl)benzamide (9s). The title compound was
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prepared according to general procedure A (15 mg, 23% yield). H
NMR (500 MHz, CDCl3) δ 9.44 (br s, 1H), 8.87 (d, J = 1.9 Hz, 1H),
7.80 (s, 1H), 7.73 (d, J = 7.3 Hz, 1H), 7.63 (s, 1H), 7.57 (d, J = 7.3
Hz, 1H), 7.45−7.31 (m, 6H), 3.78 (s, 4H), 3.65 (s, 3H), 3.11 (s, 4H),
2.82 (br s, 3H), 2.56 (br s, 4H), 2.52 (br s, 3H), 2.48 (s, 3H); 13C
NMR (125 MHz, DMSO-d6) δ 165.1, 140.9, 139.6, 139.0, 138.8,
135.0, 133.9, 132.8, 129.2, 128.9, 128.0, 127.4, 123.6, 123.0, 121.5,
118.7, 77.3, 77.0, 76.8, 65.6, 62.6, 55.2 (2), 52.8 (2), 50.4 (2), 44.7,
21.5 (2). HRMS (ESI) m/z calcd for C30H37N4O2 [M + H]+:
485.2917, found: 485.2924.
3-Methyl-N-(5-(1-methyl-1H-indol-6-yl)-2-(4-methylpiperazin-1-
yl)phenyl)benzamide (9n). The title compound was prepared
according to general procedure A (39 mg, 66% yield). 1H NMR
(500 MHz, CDCl3) δ 9.26 (br s, 1H), 8.86 (s, 1H), 7.74 (s, 1H), 7.64
(d, J = 6.5 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.52 (s, 1H), 7.39−7.33
(m, 4H), 7.29 (d, J = 8.2 Hz, 1H),7.02 (d, J = 3.0 Hz, 1H), 6.43 (d, J =
3.0 Hz, 1H), 3.79 (s, 3H), 3.14 (br s, 4H), 2.85 (br s, 4H), 2.57 (br s,
3H), 2.41 (br s, 3H); 13C NMR (125 MHz, CDCl3) δ 165.3, 41.0,
139.1, 139.0, 137.4, 135.4, 134.5, 134.0, 132.9, 129.8, 129.0, 128.1,
128.2, 123.8, 123.2, 121.5, 121.2, 119.4, 118.9, 108.0, 101.0, 56.5 (2),
50.8, 45.0, 33.1 (2), 21.7. HRMS (ESI) m/z calcd for C28H31N4O [M
+ H]+: 439.2498, found: 439.2496.
N-(5-(1H-Indol-5-yl)-2-(4-methylpiperazin-1-yl)phenyl)-3-methyl-
benzamide (9o). The title compound was prepared according to
general procedure A (27 mg, 47% yield). 1H NMR (500 MHz, CDCl3)
δ 9.54 (s, 1H), 8.91 (d, J = 1.9 Hz, 1H), 8.35 (s, 1H), 7.87 (s, 1H),
7.78 (s, 1H), 7.72 (d, J = 7.4 Hz, 1H), 7.46 (dd, J = 1.6, 8.5 Hz, 1H),
7.39−7.32 (m, 4H), 7.24 (d, J = 8.2 Hz, 1H), 7.16 (d, J = 2.6 Hz, 1H),
6.54−6.53 (m, 1H), 2.97 (s, 4H), 2.61 (br s, 4H), 2.43 (s, 3H), 2.35
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 165.9, 141.0, 139.0, 138.9,
135.7, 134.8, 133.2, 132.8, 131.8, 128.8, 128.4, 128.3, 127.9, 125.2,
125.1, 123.6, 123.3, 121.2, 118.9, 111.4, 102.1, 55.0 (2), 50.2, 29.6,
21.2 (2). HRMS (ESI) m/z calcd for C27H28N4O [M + H]+: 425.2341,
found: 425.2328.
3-Methyl-N-(4-(4-methylpiperazin-1-yl)-4′-(morpholinomethyl)-
[1,1′-biphenyl]-3-yl)benzamide (9t). The title compound was
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prepared according to general procedure A (17 mg, 27% yield). H
NMR (500 MHz, CDCl3) δ 9.30 (br s, 1H), 8.85 (s, 1H), 7.79 (s,
1H), 7.69 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 7.9 Hz, 2H), 7.49 (br s,
2H), 7.45−7.40 (m, 2H), 7.35 (s, 2H), 3.94−3.64 (m, 7H), 3.36−2.97
(m, 8H), 2.62 (br s, 6H), 2.48 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 165.2, 139.9, 139.1, 138.9, 135.2, 134.1, 132.9, 130.6, 129.2, 129.0,
128.1, 127.7, 127.6, 123.9, 122.8, 121.6, 118.6, 66.1, 62.7, 55.7 (2),
53.1 (2), 51.0 (2), 45.3, 21.8 (2). HRMS (ESI) m/z calcd for
C30H37N4O2 [M + H]+: 485.2917, found: 485.2920.
3-Methyl-N-(5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-(4-methyl-
piperazin-1-yl)phenyl)benzamide (9u). The title compound was
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prepared according to general procedure A (13 mg, 21% yield). H
NMR (500 MHz, CDCl3) δ 9.29 (s, 1H), 8.70 (d, J = 1.9 Hz, 1H),
7.83 (s, 1H), 7.79 (s, 1H), 7.68 (d, J = 6.8 Hz, 1H), 7.51 (s, 2H), 7.50
(s, 2H), 7.44−7.39 (m, 3H), 7.34 (d, J = 8.1 Hz, 1H), 7.22 (dd, J = 2.0,
8.2 Hz, 1H), 3.23 (br s, 4H), 2.98 (br s, 4H), 2.65 (s, 3H), 2.51 (s,
3H), 2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 165.3, 139.6,
139.2, 139.6, 137.1, 135.8, 135.0, 133.5, 132.9, 132.6, 129.3, 129.2,
128.8, 128.2, 128.0, 125.2, 123.7, 123.3, 121.6, 121.2, 54.5, 49.7 (2),
43.7, 21.5 (2), 12.1. HRMS (ESI) m/z calcd for C29H32N5O [M +
H]+: 466.2607, found: 466.2608.
N-(5-(1-Isopentyl-1H-pyrazol-4-yl)-2-(4-methylpiperazin-1-yl)-
phenyl)-3-methylbenzamide (9v). The title compound was prepared
3-Methyl-N-(4-(4-methylpiperazin-1-yl)-3′-(pyrrolidin-1-yl)-[1,1′-
1
biphenyl]-3-yl)benzamide (9p). The title compound was prepared
according to general procedure A (11 mg, 18% yield). H NMR (500
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according to general procedure A (9 mg, 15% yield). H NMR (500
MHz, CDCl3) δ 9.28 (br s, 1H), 8.72 (d, J = 1.8 Hz, 1H), 7.79 (d, J =
0.6 Hz, 1H), 7.78 (br s, 1H), 7.71 (s, 1H), 7.67 (d, J = 7.2 Hz, 1H),
MHz, CDCl3) δ 9.45 (br s, 1H), 8.85 (d, J = 1.6 Hz, 1H), 7.77 (s, 1H),
L
J. Med. Chem. XXXX, XXX, XXX−XXX