M. Cao, et al.
Bioorganic&MedicinalChemistry28(2020)115715
56.49, 54.87, 46.06, 29.49. Anal. Calcd for C27H28ClN7O4S2, C, 52.82;
H, 4.60; N, 15.97. Found: C, 52.81; H, 4.60; N, 15.97.
J = 5.6 Hz, 6H). 13C NMR (101 MHz, DMSO‑d6) δC: 162.84, 158.51,
156.97, 155.45, 150.26, 135.34, 134.80, 131.05, 128.04, 127.42,
127.29, 127.04, 126.70, 126.19, 125.06, 121.55, 115.80, 113.21,
109.47, 107.74, 105.63, 56.90, 55.27, 46.46, 29.90. Anal. Calcd for
4.1.9.7. N-(2-((5-chloro-2-((4-(2-(4-(2-hydroxyethyl)piperazine-1-
carbonyl)-1H-pyrrol-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)
phenyl)methanesulfonamide (11i). Yield: 68.4%; m. p.:192.4–194.1 °C.
MS (ESI) m/z: 639.2 [M−H]−; 1H NMR (400 MHz, DMSO‑d6) δH: 9.34
(s, 1H), 8.63 (s, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H),
7.83 (d, J = 8.6 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.33 (t, J = 7.4 Hz,
1H), 7.25 (t, J = 7.1 Hz, 1H), 7.16 (s, 1H), 6.89 (d, J = 2.1 Hz, 1H),
6.63 (s, 1H), 6.43 (d, J = 2.2 Hz, 1H), 6.27–6.23 (m, 1H), 4.42 (s, 1H),
3.83 (s, 3H), 3.45 (d, J = 4.6 Hz, 6H), 2.95 (s, 3H), 2.33 (t, J = 6.0 Hz,
4H), 2.27 (s, 2H). 13C NMR (151 MHz, DMSO‑d6) δC: 161.73, 157.48,
155.98, 154.47, 149.24, 134.32, 133.85, 129.79, 128.76, 126.97,
126.69, 126.48, 125.95, 125.28, 124.08, 120.53, 114.73, 112.25,
108.46, 106.66, 104.57, 59.87, 58.19, 55.86, 55.33, 52.74, 28.90.
Anal. Calcd for C29H33ClN8O5S, C, 54.33; H, 5.18; N, 17.48. Found: C,
54.33; H, 5.19; N, 17.48.
C
27H30ClN7O4S, C, 55.52; H, 5.18; N, 16.79. Found: C, 55.52; H, 5.18;
N, 16.79.
4.1.9.12. N-(2-((5-chloro-2-((4-(2-(3-hydroxyazetidine-1-carbonyl)-1H-
pyrrol-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)
methanesulfonamide (11n). Yield: 63.4%; m. p.:173.8–174.9 °C. MS
(ESI) m/z: 582.8 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 9.31 (s,
1H), 8.66 (s, 1H), 8.19 (s, 1H), 8.06 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H),
7.77 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 7.7 Hz, 1H), 7.36 (t, J = 7.4 Hz,
1H), 7.26 (t, J = 7.5 Hz, 1H), 7.11 (s, 1H), 6.93 (d, J = 1.9 Hz, 1H),
6.63 (d, J = 2.5 Hz, 1H), 6.61 (s, 1H), 4.49 (s, 1H), 3.83 (s, 3H), 3.38 (s,
4H), 2.96 (s, 3H). 13C NMR (151 MHz, DMSO‑d6) δC: 159.54, 156.42,
154.76, 153.30, 147.66, 134.16, 132.82, 128.34, 126.14, 125.84,
125.79, 125.75, 125.48, 124.63, 124.06, 118.96, 115.25, 112.05,
107.21, 106.76, 103.34, 58.72, 54.61, 40.26, 27.17. Anal. Calcd for
4.1.9.8. N-(2-((5-chloro-2-((2-methoxy-4-(2-(4-methylpiperidine-1-
carbonyl)-1H-pyrrol-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)
methanesulfonamide (11j). Yield: 80.4%; m. p.:177.7–178.1 °C. MS
(ESI) m/z: 608.9 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 9.31
(s, 1H), 8.64 (s, 1H), 8.19 (s, 1H), 8.01 (s, 1H), 7.91 (s, 1H), 7.83 (s,
1H), 7.43 (s, 1H), 7.33 (s, 1H), 7.25 (s, 1H), 7.15 (s, 1H), 6.90 (s, 1H),
6.65 (s, 1H), 6.40 (s, 1H), 6.25 (s, 3H), 3.83 (s, 4H), 3.39 (s, 3H), 2.95
(s, 4H), 1.53 (s, 3H), 0.82 (s, 1H). Anal. Calcd for C29H32ClN7O4S, C,
57.08; H, 5.29; N, 16.07. Found: C, 57.09; H, 5.29; N, 16.07.
C26H26ClN7O5S, C, 53.47; H, 4.49; N, 16.78. Found: C, 53.47; H, 4.49;
N, 16.79.
4.1.9.13. N-(2-((5-chloro-2-((4-(2-(4-hydroxypiperidine-1-carbonyl)-1H-
pyrrol-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)
methanesulfonamide (11o). Yield: 78.1%; m. p.:193.4–195.7 °C. MS
(ESI) m/z: 610.8 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 9.36 (s,
1H), 8.70 (s, 1H), 8.17 (s, 1H), 7.95 (s, 2H), 7.85 (s, 1H), 7.38 (s, 1H),
7.22 (s, 1H), 7.15 (s, 1H), 6.90 (s, 1H), 6.63 (s, 2H), 6.41 (s, 1H), 6.25
(s, 1H), 4.76 (s, 3H), 3.83 (s, 1H), 3.68 (s, 2H), 3.13 (s, 5H), 1.63 (s,
2H), 0.85 (s, 2H). Anal. Calcd for C28H30ClN7O5S, C, 54.95; H, 4.94; N,
16.02. Found: C, 54.94; H, 4.94; N, 16.02.
4.1.9.9. 1-(4-((5-chloro-4-((2-(methylsulfonamido)phenyl)amino)
pyrimidin-2-yl)amino)-3-methoxyphenyl)-N-(2-hydroxyethyl)-1H-pyrrole-
2-carboxamide (11k). Yield: 68.1%; m. p.:166.6–168.4 °C. MS (ESI) m/
z: 570.8 [M−H]−; 1H NMR (400 MHz, DMSO‑d6) δH: 9.30 (s, 1H), 8.60
(s, 1H), 8.18 (s, 1H), 8.03 (t, J = 5.7 Hz, 1H), 7.98 (s, 1H), 7.93 (d,
J = 7.8 Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H),
7.35 (t, J = 7.7 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 2.0 Hz,
1H), 6.90 (d, J = 2.1 Hz, 1H), 6.80 (dd, J = 3.6, 1.5 Hz, 1H), 6.64 (dd,
J = 8.5, 1.9 Hz, 1H), 6.22–6.19 (t, 1H), 4.69 (t, J = 5.6 Hz, 1H), 3.80
(s, 3H), 3.44 (q, J = 6.1 Hz, 2H), 3.20 (q, J = 6.0 Hz, 2H), 2.96 (s, 3H).
13C NMR (151 MHz, DMSO‑d6) δC: 161.19, 158.07, 156.41, 154.95,
149.31, 135.80, 134.47, 129.98, 127.79, 127.49, 127.44, 127.40,
127.13, 126.28, 125.70, 120.60, 116.90, 113.69, 108.86, 108.41,
104.99, 60.37, 56.26, 41.91, 28.82. Anal. Calcd for C25H26ClN7O5S,
C, 52.49; H, 4.59; N, 17.14. Found: C, 52.49; H, 4.58; N, 17.14.
4.1.9.14. 2-((5-chloro-2-((2-methoxy-4-(2-(piperidine-1-carbonyl)-1H-
pyrrol-1-yl)phenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide
(12c). Yield: 76.1%; m. p.:188.4–190.7 °C. MS (ESI) m/z: 558.8
[M−H]−; 1H NMR (400 MHz, DMSO‑d6) δH: 11.66 (s, 1H), 8.79 (d,
J = 4.4 Hz, 1H), 8.65 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 8.20 (s, 1H),
7.89 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.8 Hz,
1H), 7.20 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H),
6.83 (dd, J = 8.5, 2.0 Hz, 1H), 6.41 (d, J = 2.6 Hz, 1H), 6.27 (t,
J = 3.0 Hz, 1H), 3.84 (s, 3H), 3.43 (s, 4H), 2.81 (d, J = 4.4 Hz, 3H),
1.53 (s, 2H), 1.36 (s, 4H). 13C NMR (100 MHz, DMSO‑d6) δC: 169.37,
162.40, 158.41, 155.54, 155.13, 151.06, 139.73, 135.83, 132.01,
128.43, 127.32, 127.05, 124.34, 123.05, 122.37, 121.76, 121.10,
115.27, 112.26, 109.04, 107.36, 105.72, 63.55, 56.31(2C), 26.77
(2C), 26.09, 24.45. Anal. Calcd for C29H30ClN7O3, C, 62.18; H, 5.40;
N, 17.51. Found: C, 62.19; H, 5.40; N, 17.51.
4.1.9.10. 1-(4-((5-chloro-4-((2-(methylsulfonamido)phenyl)amino)
pyrimidin-2-yl)amino)-3-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-
carboxamide (11l). Yield: 66.7%; m. p.:169.2–171.4 °C. MS (ESI) m/z:
554.7 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 9.31 (s, 1H), 8.61 (s,
1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.90 (s, 1H), 7.80 (s, 0H), 7.42 (s, 1H),
7.32 (s, 0H), 7.26 (s, 1H), 7.15 (s, 1H), 6.91 (s, 1H), 6.60 (s, 1H), 6.45
(s, 1H), 6.25 (s, 1H), 3.82 (s, 3H), 2.94 (s, 6H), 2.91 (s, 3H). 13C NMR
(101 MHz, DMSO‑d6) δC: 162.60, 158.27, 156.73, 155.20, 150.02,
135.10, 134.55, 130.81, 127.80, 127.17, 127.05, 126.79, 126.45,
125.95, 124.82, 121.30, 115.56, 112.97, 109.23, 107.50, 105.39,
56.65, 55.03, 29.66. Anal. Calcd for C25H26ClN7O4S, C, 54.01; H,
4.71; N, 17.62. Found: C, 54.00; H, 4.71; N, 17.63.
4.1.9.15. 2-((5-chloro-2-((2-methoxy-4-(2-(4-methylpiperazine-1-
carbonyl)-1H-pyrrol-1-yl)phenyl)amino)pyrimidin-4-yl)amino)-N-
methylbenzamide (12d). Yield: 67.5%; m. p.:199.1–201.3 °C. MS (ESI)
m/z: 573.8 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 11.65 (s, 1H),
8.77 (s, 1H), 8.65 (s, 1H), 8.32 (s, 1H), 8.20 (s, 1H), 7.88 (s, 1H), 7.74
(s, 1H), 7.48 (s, 1H), 7.22 (s, 1H), 7.12 (s, 1H), 6.95 (s, 1H), 6.83 (s,
1H), 6.45 (s, 1H), 6.28 (s, 1H), 3.85 (s, 3H), 3.46 (s, 4H), 2.81 (s, 3H),
2.09 (s, 4H), 1.04 (d, J = 154.1 Hz, 3H). Anal. Calcd for C29H31ClN8O3,
C, 60.57; H, 5.42; N, 19.50. Found: C, 60.57; H, 5.43; N, 19.49.
4.1.9.11. 1-(4-((5-chloro-4-((2-(methylsulfonamido)phenyl)amino)
pyrimidin-2-yl)amino)-3-methoxyphenyl)-N,N-diethyl-1H-pyrrole-2-
carboxamide (11m). Yield: 75.1%; m. p.:165.5–167.9 °C. MS (ESI) m/z:
582.8 [M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 9.31 (s, 1H), 8.62 (s,
1H), 8.18 (s, 1H), 7.95 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.81 (d,
J = 8.5 Hz, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H),
7.25 (t, J = 7.4 Hz, 1H), 7.12 (s, 1H), 6.90 (s, 1H), 6.61 (d, J = 8.3 Hz,
1H), 3.82 (s, 3H), 3.31 (d, J = 6.6 Hz, 4H), 2.94 (s, 4H), 1.01 (t,
4.1.9.16. 2-((5-chloro-2-((4-(2-(4-ethylpiperazine-1-carbonyl)-1H-pyrrol-
1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide
(12e). Yield: 71.2%;m. p.:187.6–189.4 °C. MS (ESI) m/z: 587.8
[M−H]−. 1H NMR (400 MHz, DMSO‑d6) δH: 11.65 (s, 1H), 8.76 (d,
J = 4.5 Hz, 1H), 8.65 (d, J = 8.2 Hz, 1H), 8.30 (s, 1H), 8.20 (s, 1H),
7.89 (d, J = 8.5 Hz, 1H), 7.75 (dd, J = 7.8, 1.0 Hz, 1H), 7.48 (t,
J = 7.4 Hz, 1H), 7.22–7.20 (m, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.94 (d,
J = 2.2 Hz, 1H), 6.84 (dd, J = 8.5, 2.3 Hz, 1H), 6.45 (dd, J = 3.6,
8