Y. Shan et al. / European Journal of Medicinal Chemistry 104 (2015) 139e147
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7.35e7.29 (m, 2H), 6.84 (s, 1H), 4.35 (s, 2H), 3.80e3.51 (m, 6H),
3.81e3.42 (m, 8H), 2.35 (s, 3H). HRMS ESI: calculated for
C
3.29e3.17 (m, 2H). HRMS ESI: calculated for
C25H22ClN5O2
26H25N5O2 [M þ H]þm/z ¼ 440.2087; found 440.2079.
[M þ H]þm/z ¼ 460.1540; found 460.1560.
5.1.16. 4-(4-{[4-(4-chlorobenzoyl)piperazin-1-yl]carbonyl}phenyl)-
1H-indazol-3-amine (11k)
5.1.10. 4-(4-{[4-(2-bromobenzoyl)piperazin-1-yl]carbonyl}phenyl)-
1H-indazol-3-amine (11e)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (þ11a): Yield
67%; Mp.: 292e294 ꢀC; ESI-MS (m/z): 460.10 (M þ H) ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
60%; Mp.: 105e107 ꢀC; ESI-MS (m/z): 502.10 (MꢁH)þ; 1H NMR
(400 MHz, DMSO)
d 11.82 (s, 1H), 7.58e7.55 (m, 4H), 7.53 (s, 2H),
(400 MHz, DMSO)
d
11.85 (s, 1H), 7.70 (d, J ¼ 7.7 Hz, 1H), 7.63e7.52
7.48 (d, J ¼ 8.1 Hz, 2H), 7.32 (s,1H), 7.31 (d, J ¼ 2.1 Hz,1H), 6.87e6.82
(m, 4H), 7.48 (t, J ¼ 6.9 Hz, 1H), 7.39 (d, J ¼ 7.6 Hz, 2H), 7.34e7.27 (m,
2H), 6.84 (s, 1H), 4.36 (s, 2H), 3.86e3.41 (m, 6H), 3.33e3.13 (m, 2H).
HRMS ESI: calculated for C25H22BrN5O2 [M þ H]þm/z ¼ 504.1035;
found 504.1023.
(m, 1H), 4.35 (s, 2H), 3.80e3.42 (m, 8H). HRMS ESI: calculated for
C
25H22ClN5O2 [M þ H]þm/z ¼ 460.1540; found 460.1521.
5.1.17. 4-(4-{[4-(2-methoxybenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-amine (11l)
5.1.11. 4-(4-{[4-(3,5-dimethoxybenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-amine (11f)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
49%; Mp.: 233e234 ꢀC; ESI-MS (m/z): 454.15 (M ꢁ H)þ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
71%; Mp.: 149e151 ꢀC; ESI-MS (m/z): 484.30 (MꢁH)þ; 1H NMR
(400 MHz, DMSO)
d 11.82 (s, 1H), 7.61e7.50 (m, 4H), 7.45e7.36 (m,
1H), 7.34e7.28 (m, 2H), 7.23 (d, J ¼ 7.0 Hz, 1H), 7.15e7.06 (m, 1H),
7.01 (t, J ¼ 7.2 Hz, 1H), 6.90e6.80 (m, 1H), 4.35 (s, 2H), 3.82 (s, 3H),
3.77e3.37 (m, 6H), 3.30e3.14 (m, 2H). HRMS ESI: calculated for
(400 MHz, DMSO)
d 11.83 (s, 1H), 7.56 (m, 4H), 7.36e7.26 (m, 2H),
6.85 (s, 1H), 6.57 (m, 3H), 4.35 (s, 2H), 3.77 (s, 6H), 3.36e3.74 (m,
8H). HRMS ESI: calculated for C27H27N5O4 [M þ H]þm/z ¼ 486.2141;
found 486.2125.
C
26H25N5O3 [M þ H]þm/z ¼ 456.2036; found 456.2018.
5.1.18. 4-(4-{[4-(2-methylbenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-amine (11m)
5.1.12. 4-[4-({4-[3-(trifluoromethyl)benzoyl]piperazin-1-yl}
carbonyl)phenyl]-1H-indazol-3-amine (11g)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
57%; Mp.: 193e195 ꢀC; ESI-MS (m/z): 438.25 (M ꢁ H)þ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (þ11a): Yield
68%; Mp.: 239e240 ꢀC; ESI-MS (m/z): 492.20 (M ꢁ H) ; 1H NMR
(400 MHz, DMSO)
d 11.82 (s, 1H), 7.63e7.50 (m, 4H), 7.37e7.31 (m,
(400 MHz, DMSO)
d
11.83 (s, 1H), 7.85 (d, J ¼ 7.3 Hz, 1H), 7.81 (s, 1H),
2H), 7.31e7.28 (m, 2H), 7.28e7.24 (m, 1H), 7.24e7.19 (m, 1H),
6.89e6.78 (m, 1H), 4.35 (s, 2H), 3.86e3.37 (m, 6H), 3.31e3.11 (m,
2H), 2.23 (s, 3H). HRMS ESI: calculated for C26H25N5O2 [M þ H]þ m/
z ¼ 440.2087; found 440.2079.
7.77 (d, J ¼ 7.1 Hz, 1H), 7.72 (d, J ¼ 7.5 Hz, 1H), 7.63e7.49 (m, 4H),
7.35e7.27 (m, 2H), 6.85 (s, 1H), 4.36 (s, 2H), 3.96e3.37 (m, 8H).
HRMS ESI: calculated for C26H22F3N5O2 [M þ H]þm/z ¼ 494.1804;
found 494.1779.
5.1.19. N-(2-{[4-(3-amino-1H-indazol-4-yl)benzoyl]amino}ethyl)-
3,4-difluorobenzamide (12a)
5.1.13. 4-(4-{[4-(3,4-difluorobenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-Amine (11h)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
52%; Mp.: 288e290 ꢀC; ESI-MS (m/z): 434.15 (M ꢁ H)þ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
56%; Mp.: 197e199 ꢀC; ESI-MS (m/z): 460.20 (M ꢁ H)þ; 1H NMR
(400 MHz, DMSO)
d 11.83 (s, 1H), 8.80e8.69 (m, 2H), 7.98 (d,
(400 MHz, DMSO)
d
11.83 (s, 1H), 7.59e7.52 (m, 6H), 7.36e7.32 (m,
J ¼ 8.3 Hz, 2H), 7.91 (dt, J ¼ 11.5, 7.8, 2.1 Hz, 1H), 7.80e7.73 (m, 1H),
7.62e7.54 (m, 3H), 7.36e7.28 (m, 2H), 6.85 (dd, J ¼ 5.5, 2.3 Hz, 1H),
4.32 (s, 2H), 3.51e3.44 (m, 4H). HRMS ESI: calculated for
2H), 7.31 (d, J ¼ 2.0 Hz, 1H), 6.91e6.78 (m, 1H), 4.36 (s, 2H),
3.77e3.45 (m, 8H). HRMS ESI: calculated for
[M þ H]þm/z ¼ 462.1742; found 462.1744.
C25H21F2N5O2
C
23H19F2N5O2 [M þ H]þ m/z ¼ 436.1585; found 436.1575.
5.1.14. 4-(4-{[4-(4-methoxybenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-amine (11i)
5.1.20. N-(2-{[4-(3-amino-1H-indazol-4-yl)benzoyl]amino}ethyl)-
2-bromobenzamide (12b)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
59%; Mp.: 246e248 ꢀC; ESI-MS (m/z): 454.25 (MꢁH)þ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (þ11a): Yield
64%; Mp.: 179e281 ꢀC; ESI-MS (m/z): 479.05 (M þ H) ; 1H NMR
(400 MHz, DMSO)
d
11.82 (s, 1H), 7.60e7.53 (m, 4H), 7.42 (d,
(400 MHz, DMSO) d 11.86 (s, 1H), 8.65e8.61 (m, 1H), 8.58e8.55 (m,
J ¼ 8.6 Hz, 2H), 7.32 (s,1H), 7.31 (d, J ¼ 1.7 Hz,1H), 7.00 (d, J ¼ 8.4 Hz,
2H), 6.88e6.83 (m, 1H), 4.35 (s, 2H), 3.80 (s, 3H), 3.74e3.46 (m, 8H).
HRMS ESI: calculated for C26H25N5O3 [M þ H]þm/z ¼ 456.2036;
found 456.2015.
1H), 7.99 (d, J ¼ 8.1 Hz, 2H), 7.84 (dd, J ¼ 21.6, 8.0 Hz, 1H), 7.65 (dd,
J ¼ 7.8, 3.5 Hz, 1H), 7.58 (d, J ¼ 8.1 Hz, 2H), 7.47e7.43 (m, 2H),
7.38e7.34 (m, 1H), 7.34e7.32 (m, 1H), 6.90e6.82 (m, 1H), 4.35 (s,
2H), 3.50e3.43 (m, 4H). HRMS ESI: calculated for C23H20BrN5O2
[M þ H]þ m/z ¼ 478.0879; found 478.0872.
5.1.15. 4-(4-{[4-(3-methylbenzoyl)piperazin-1-yl]carbonyl}
phenyl)-1H-indazol-3-amine (11j)
5.1.21. N-(2-{[4-(3-amino-1H-indazol-4-yl)benzoyl]amino}ethyl)-
2-methylbenzamide (12c)
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
53%; Mp.: 209e211 ꢀC; ESI-MS (m/z): 438.15 (M ꢁ H)þ; 1H NMR
This compound was prepared using the same procedure as
described for the preparation of targeted compound (11a): Yield
51%; Mp.: 218e219 ꢀC; ESI-MS (m/z): 412.15(M ꢁ H)þ; 1H NMR
(400 MHz, DMSO)
d 11.82 (s, 1H), 7.59e7.53 (m, 4H), 7.38e7.34 (m,
1H), 7.34e7.32 (m, 1H), 7.31 (d, J ¼ 2.1 Hz, 1H), 7.30e7.26 (m, 1H),
(400 MHz, DMSO) d 11.83 (s, 1H), 8.70e8.64 (m, 1H), 8.41e8.34 (m,
7.25 (s, 1H), 7.22 (d, J ¼ 7.4 Hz, 1H), 6.89e6.81 (m, 1H), 4.35 (s, 2H),
1H), 7.99 (d, J ¼ 8.3 Hz, 2H), 7.58 (d, J ¼ 8.2 Hz, 2H), 7.40e7.35 (m,