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4.1.6.11. N-(4-((4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)
4.1.7.3. 4-(((2-(Diethylamino)ethyl)amino)methyl)-N-(4-methyl-3-
phenyl)carbamoyl)phenyl)nicotinamide (13k). Yield 72%. 1H NMR
((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide(14c).
(400 MHz, DMSO-d6)
d
10.71 (s, 1H), 10.15 (s, 1H), 9.29 (s, 1H), 9.15
Yield 79%. 1H NMR (400 MHz, DMSO-d6)
d 10.22 (s,1H), 9.28 (s, 1H),
(s, 1H), 8.98 (s, 1H), 8.70 (s, 2H), 8.52 (s, 2H), 8.35 (s, 1H), 8.10e7.95
(m, 5H), 7.60e7.45 (m, 4H), 7.23 (s,1H), 2.24 (s, 3H). HRMS (ESI, m/z)
[MþH]þ calcd for C29H24N7O2: 502.1991, found: 502.1987.
8.98 (s, 1H), 8.70 (s, 1H), 8.51 (s, 2H), 8.10 (s, 1H), 7.98 (s, 2H),
7.58e7.44 (m, 5H), 7.23 (s, 1H), 3.95 (s, 2H), 2.78 (s, 8H), 2.23 (s, 4H),
1.07 (s, 6H). 13C NMR (101 MHz, DMSO-d6)
d 165.61, 162.08, 161.68,
159.93, 151.83, 148.67, 142.83, 138.26, 137.72, 134.91, 134.23, 132.70,
130.46, 128.72, 128.15, 128.08, 124.24, 117.81, 117.35, 107.98, 52.21,
51.11, 47.00, 45.30, 18.14, 11.19. HRMS (ESI, m/z) [MþH]þ calcd for
4.1.6.12. 3-Acrylamido-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-
2-yl)amino)phenyl)benzamide (13l). Yield 55%. 1H NMR (400 MHz,
C30H36N7O: 510.2981, found: 510.2986.
DMSO-d6) d 10.38 (s,1H), 10.23 (s,1H), 9.27 (s, 1H), 8.98 (s, 1H), 8.68
(s,1H), 8.50 (dd, J ¼ 10.5, 5.9 Hz, 2H), 8.16 (s,1H), 8.07 (s,1H), 7.92 (s,
1H), 7.65 (s, 1H), 7.48 (t, J ¼ 22.1 Hz, 4H), 7.21 (d, J ¼ 7.7 Hz, 1H),
6.64e6.33 (m, 1H), 6.29 (d, J ¼ 16.7 Hz, 1H), 5.79 (d, J ¼ 7.8 Hz, 1H),
2.23 (s, 3H). HRMS (ESI, m/z) [MþH]þ calcd for C26H23N6O2:
451.1882, found: 451.1886.
4.1.7.4. N-(4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)
phenyl)-4-(((2-(pyrrolidin-1-yl)ethyl)amino)methyl)benzamide
(14d). Yield 78%. 1H NMR (400 MHz, DMSO-d6)
d 10.22 (s, 1H), 9.29
(s, 1H), 8.98 (s, 1H), 8.69 (s, 1H), 8.52 (s, 2H), 8.11 (s, 1H), 7.97 (s, 2H),
7.72e7.31 (m, 5H), 7.22 (s, 1H), 3.93 (s, 2H), 2.86 (s, 8H), 2.24 (s, 3H),
1.83 (s, 4H). 13C NMR (101 MHz, DMSO-d6)
d 165.56, 162.08, 161.67,
4.1.6.13. 3-Acrylamido-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-
159.95, 151.85, 148.67, 142.31, 138.25, 137.67, 134.90, 134.33, 132.69,
130.47, 128.85, 128.13, 124.25, 117.79, 117.32, 107.99, 53.73, 53.58,
51.87, 45.16, 23.30, 18.12. HRMS (ESI, m/z) [MþH]þ calcd for
2-yl)amino)phenyl)-5-(trifluoromethyl)benzamide (13m). Yield 67%.
1H NMR (400 MHz, DMSO-d6)
d 10.94 (s, 1H), 10.49 (s, 1H), 9.31 (s,
1H), 9.00 (s, 1H), 8.72 (s, 1H), 8.51 (dd, J ¼ 13.1, 6.6 Hz, 2H), 8.43 (d,
J ¼ 5.5 Hz, 2H), 8.08 (s, 1H), 8.03 (s, 1H), 7.61e7.37 (m, 3H), 7.25 (d,
J ¼ 8.3 Hz, 1H), 6.54 (dd, J ¼ 17.1, 10.1 Hz, 1H), 6.35 (d, J ¼ 16.7 Hz,
1H), 5.85 (d, J ¼ 10.1 Hz, 1H), 2.25 (s, 3H). HRMS (ESI, m/z) [MþH]þ
calcd for C27H22F3N6O2: 519.1756, found: 519.1751.
C30H34N7O: 508.2825, found: 508.2829.
4.1.7.5. 4-(((2-Hydroxyethyl)amino)methyl)-N-(4-methyl-3-((4-
(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide (14e).
Yield 83%. 1H NMR (400 MHz, DMSO-d6)
10.19 (s, 1H), 9.29 (s, 1H),
d
8.98 (s, 1H), 8.69 (s, 1H), 8.52 (s, 2H), 8.11 (s, 1H), 7.95 (s, 2H),
4.1.6.14. N-(4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)
7.52e7.43 (m, 5H), 7.22 (s, 1H), 4.69 (s, 1H), 3.91 (s, 2H), 3.54 (s, 2H),
phenyl)-3-propionamido-5-(trifluoromethyl)benzamide
(13n).
2.69 (s, 2H), 2.24 (s, 3H). 13C NMR (101 MHz, DMSO-d6)
d 165.80,
Yield 72%. 1H NMR (400 MHz, DMSO-d6)
d
10.44 (s, 2H), 9.28 (d,
162.09, 161.66, 159.92, 151.82, 148.65, 145.23, 138.28, 137.71, 134.90,
133.79, 132.69, 130.52, 128.22, 128.01, 124.24, 117.69, 117.27, 108.00,
60.85, 52.96, 51.49, 18.11, ꢂ15.38. HRMS (ESI, m/z) [MþH]þ calcd for
J ¼ 1.5 Hz, 1H), 9.01 (s, 1H), 8.75e8.61 (m, 1H), 8.51 (dd, J ¼ 15.3,
6.6 Hz, 2H), 8.34 (s, 1H), 8.30 (s, 1H), 8.07 (s, 1H), 7.99 (s, 1H), 7.50
(ddd, J ¼ 20.3, 9.9, 5.0 Hz, 3H), 7.24 (d, J ¼ 8.4 Hz, 1H), 4.04 (dd,
J ¼ 13.5, 6.5 Hz, 1H), 2.40 (q, J ¼ 7.5 Hz, 2H), 2.25 (s, 3H), 1.12 (t,
J ¼ 7.5 Hz, 3H). HRMS (ESI, m/z) [MþH]þ calcd for C27H24F3N6O2:
521.1913, found: 521.1917.
C26H27N6O2: 455.2195, found: 455.2191.
4.1.8. Compounds 15a-r were prepared following the synthetic
procedure of 13a
4.1.8.1. 4-((N-(2-(Dimethylamino)ethyl)acrylamido)methyl)-N-(4-
methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide
4.1.7. Compounds 14b-e were prepared following the synthetic
procedure of 14a
(15a). Yield 67%. 1H NMR (400 MHz, DMSO-d6)
d 10.23 (s, 1H), 9.27
(s, 1H), 9.00 (s, 1H), 8.68 (d, J ¼ 3.3 Hz, 1H), 8.14e7.85 (m, 3H),
7.54e7.29 (m, 5H), 7.20 (d, J ¼ 8.3 Hz, 1H), 6.73 (dd, J ¼ 16.5, 10.3 Hz,
1H), 6.23 (dd, J ¼ 16.8, 10.6 Hz, 1H), 5.80e5.70 (m, 1H), 4.83 (s, 1H),
4.67 (s, 1H), 3.67 (s, 2H), 3.14 (s, 2H), 2.69 (s, 6H), 2.22 (s, 3H). HRMS
(ESI, m/z) [MþH]þ calcd for C31H34N7O2: 536.2774, found: 536.2771.
4.1.7.1. 4-(((2-(Dimethylamino)ethyl)amino)methyl)-N-(4-methyl-3-
((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide
(14a).
Compound 11a (5 mmol, 2.14 g) and N1,N1-dimethylethane-1,2-
diamine (15 mmol, 1.32 g) in 15 mL DMF were stirred at room
temperature overnight. The solvents were removed under vacuum
and the residue was purified by silica gel flash chromatography
(DCM: MeOH ¼ 10: 1) to give compound 14a (1.9 g, yield 79%). 1H
4.1.8.2. 4-((N-(2-(Dimethylamino)ethyl)propionamido)methyl)-N-
(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benza-
mide (15b). Yield 56%. 1H NMR (400 MHz, DMSO-d6)
d 10.20 (s,1H),
NMR (400 MHz, DMSO-d6)
d 10.19 (s, 1H), 9.27 (s, 1H), 8.97 (s, 1H),
8.68 (s, 1H), 8.51e8.47 (m, 2H), 8.09 (s, 1H), 7.95 (s, 2H), 7.63e7.32
9.29 (s, 1H), 9.00 (s, 1H), 8.69 (s, 1H), 8.52e8.48 (m, 2H), 8.09 (s, 1H),
7.99e7.91 (m, 2H), 7.54e7.37 (m, 5H), 7.22 (d, J ¼ 8.4 Hz,1H), 4.70 (s,
1H), 4.63 (s, 1H), 3.50e3.30 (m, 4H), 2.69e2.24 (m, 11H), 1.06e0.98
(m, 5H), 7.20 (s, 1H), 3.91 (s, 2H), 2.74 (s, 2H), 2.63 (s, 2H), 2.33 (s,
6H), 2.22 (s, 3H). 13C NMR (101 MHz, DMSO-d6)
d 165.57, 162.07,
(m, 3H). 13C NMR (101 MHz, DMSO-d6)
d 174.78, 165.56, 162.07,
161.67, 159.94, 151.84, 148.66, 142.36, 138.25, 137.67, 134.90, 134.33,
132.69, 130.46, 128.86, 128.13, 124.25, 117.80, 117.32, 107.98, 57.17,
51.99, 45.07, 44.88, 18.13. HRMS (ESI, m/z) [MþH]þ calcd for
161.63, 159.93, 151.80, 148.61, 141.47, 138.24, 137.64, 134.92, 132.68,
130.45, 128.71, 128.34, 127.87, 126.83, 124.26, 117.78, 117.39, 108.01,
54.16, 53.78, 50.45, 42.97, 42.06, 41.15, 26.14, 18.10, 12.56, 9.61.
HRMS (ESI, m/z) [MþH]þ calcd for C31H36N7O2: 538.2930, found:
538.2936.
C
28H32N7O: 482.2668, found: 482.2663.
4.1.7.2. 4-((Isopentylamino)methyl)-N-(4-methyl-3-((4-(pyridin-3-
yl)pyrimidin-2-yl)amino)phenyl)benzamide (14b). Yield 86%. 1H
NMR (400 MHz, DMSO-d6)
d
10.23 (s, 1H), 9.29 (s, 1H), 8.98 (s, 1H),
4.1.8.3. (E)-4-((N-(2-(Dimethylamino)ethyl)but-2-enamido)methyl)-
N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)ben-
8.69 (s, 1H), 8.52 (s, 2H), 8.22e7.83 (m, 4H), 7.61e7.44 (m, 5H), 7.22
(d, J ¼ 6.3 Hz, 1H), 4.01 (s, 2H), 2.74 (s, 2H), 2.24 (s, 3H), 1.63 (s, 1H),
zamide (15c). Yield 76%.1H NMR (400 MHz, DMSO-d6)
d 10.22 (s,
1.47 (s, 2H), 0.88 (s, 6H). 13C NMR (101 MHz, DMSO-d6)
d
165.39,
1H), 9.29 (s, 1H), 8.99 (s, 1H), 8.70 (s, 1H), 8.50 (d, J ¼ 7.6 Hz, 2H),
8.10e7.99 (m, 3H), 7.61e7.27 (m, 5H), 7.22 (s, 1H), 6.83 (s, 1H), 6.46
(d, J ¼ 7.3 Hz, 1H), 4.74 (s, 2H), 3.68 (s, 2H), 3.19 (s, 2H), 2.76 (s, 6H),
162.08, 161.66, 159.94, 151.84, 148.66, 138.26, 138.09, 137.61, 135.18,
134.90, 132.69, 130.48, 129.96, 128.25, 124.25, 117.82, 117.37, 107.99,
50.60, 45.89, 35.43, 25.92, 22.74, 18.13. HRMS (ESI, m/z) [MþH]þ
calcd for C29H33N6O: 481.2716, found: 481.2719.
2.24 (s, 3H), 1.87 (s, 3H). 13C NMR (101 MHz, DMSO-d6)
d 165.58,
162.07, 161.68, 159.94, 151.86, 148.68, 142.32, 138.29, 137.61, 134.90,