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DMSO-d6) d 11.79 (s, 1H), 9.65 (s, 1H), 8.45 (s, 1H), 8.18 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.77–7.80 (m, 1H), 7.41 (t, J = 8.0 Hz,
1H), 7.35 (s, 1H), 6.83–6.90 (m, 1H), 6.36 (d, J = 16.0 Hz, 1H), 2.95
(t, J = 12.0 Hz, 2H), 2.77 (t, J = 8.0 Hz, 2H), 2.19–2.34 (m, 2H),
1.20–1.29 (m, 2H). ESI-MS m/z 468 [M+H]+.
6.1.43. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4-ethylpiperazin-1-yl)but-2-enamide (9t)
According to general method to synthesize compounds 9a–z,
compound 9t was synthesized in 71% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.09 (s, 1H), 9.84 (s, 1H), 8.45 (s, 1H), 8.22 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.82–7.86 (m, 1H), 7.48 (s, 1H), 7.42
(t, J = 8.0 Hz, 1H), 6.80–6.87 (m, 1 H), 6.47 (d, J = 16.0 Hz, 1H),
3.35 (s, 10H), 3.24 (d, J = 4.0 Hz, 2H), 1.16 (t, J = 8.0 Hz, 3H). ESI-
MS m/z 475 [M+H]+.
6.1.37. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(piperidin-1-yl)but-2-enamide (9n)
According to general method to synthesize compounds 9a–z,
compound 9n was synthesized in 50% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.35 (s, 1H), 9.87 (s, 1H), 8.44 (s, 1H), 8.21 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.81–7.86 (m, 1H), 7.53 (s, 1H), 7.39
(t, J = 4.0 Hz, 1H), 6.90–6.96 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H),
3.79 (s, 2H), 2.96 (s, 4H), 1.52–1.72 (m, 6H). ESI-MS m/z 446
[M+H]+.
6.1.44. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4-isopropylpiperazin-1-yl)but-2-enamide
(9u)
According to general method to synthesize compounds 9a–z,
compound 9u was synthesized in 68% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.13 (s, 1H), 9.86 (s, 1H), 8.45 (s, 1H), 8.21(dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.82–7.86 (m, 1H), 7.48 (s, 1H), 7.39
(t, J = 8.0 Hz, 1H), 6.78–6.83 (m, 1 H), 6.48 (d, J = 16.0 Hz, 1H),
3.35 (s, 8H), 3.24 (d, J = 4.0 Hz, 2H), 2.80–2.98 (m, 1H), 1.16 (s,
6H). ESI-MS m/z 490 [M+H]+.
6.1.38. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(6-oxo-2-azabicyclo[2.2.2]octan-2-yl)but-2-
enamide (9o)
According to general method to synthesize compounds 9a–z,
compound 9o was synthesized in 60% yield. 1H NMR (400 MHz,
DMSO-d6) d 11.86 (s, 1H), 9.71 (s, 1H), 8.44 (s, 1H), 8.18 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.78–7.81 (m, 1H), 7.38–7.42 (m, 1H),
6.90–6.96 (m, 1H), 6.48 (d, J = 12.0 Hz, 1H), 3.48 (s, 2H), 3.44 (d,
J = 4.0 Hz, 2H), 2.65 (dd, J1 = 4.0 Hz, J2 = 4.0 Hz, 2H), 2.08 (d,
J = 16.0 Hz, 2H), 1.98 (t, J = 4.0 Hz, 2H), 1.49 (q, J = 8.0 Hz, 2H),
1.20 (s, 1H). ESI-MS m/z 486 [M+H]+.
6.1.45. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-morpholinobut-2-enamide (9v)
According to general method to synthesize compounds 9a–z,
compound 9v was synthesized in 67% yield. 1H NMR (400 MHz,
DMSO-d6) d 11.82 (s, 1H), 9.68 (s, 1H), 8.44 (s, 1H), 8.17 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.77–7.81 (m, 1H), 7.40 (s, 1H), 6.80–
6.87 (m, 1H), 6.36 (d, J = 16.0 Hz, 1H), 3.59 (t, J = 16.0 Hz, 4H), 3.15
(d, J = 8.0 Hz, 2H), 2.39 (t, J = 8.0 Hz, 4H). ESI-MS m/z 448 [M+H]+.
6.1.39. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4-fluoropiperidin-1-yl)but-2-enamide (9p)
According to general method to synthesize compounds 9a–z,
compound 9p was synthesized in 71% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.34 (s, 1H), 10.01 (s, 1H), 8.42 (s, 1H), 8.24 (d,
J = 8.0 Hz, 1H), 7.86–7.89 (m, 1H), 7.59 (s, 1H), 7.38 (t, J = 8.0 Hz,
1H), 6.85–6.88 (m, 1H), 6.55 (d, J = 16.0 Hz, 1H), 4.68 (d,
J = 16.0 Hz, 1H), 2.32–2.52 (m, 6H), 1.78–1.98 (m, 4H). ESI-MS m/
z 484 [M+H]+.
6.1.46. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(1,1-dioxidothiomorpholino)but-2-enamide
(9w)
According to general method to synthesize compounds 9a–z,
compound 9w was synthesized in 56% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.01 (s, 1H), 9.76 (s, 1H), 8.44 (s, 1H), 8.18 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.79–7.81 (m, 1H), 7.38–7.43 (m, 1H),
6.82–6.86 (m, 1H), 6.45 (d, J = 16.0 Hz, 1H), 3.22 (s, 6H), 3.05 (s,
5H). ESI-MS m/z 496 [M+H]+.
6.1.40. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4,4-difluoropiperidin-1-yl)but-2-enamide
(9q)
According to general method to synthesize compounds 9a–z,
compound 9q was synthesized in 57% yield. 1H NMR (400 MHz,
DMSO-d6) d 11.82 (s, 1H), 9.67 (s, 1H), 8.44 (s, 1H), 8.17 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.73–7.82 (m, 1H), 7.40 (t, J = 8.0 Hz,
1H), 7.37 (s, 1H), 6.81–6.88 (m, 1H), 6.36 (d, J = 12.0 Hz, 1H),
2.52–2.66 (m, 4H), 1.91–2.01 (m, 6H). ESI-MS m/z 482 [M+H]+.
6.1.47. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)but-2-
enamide (9x)
According to general method to synthesize compounds 9a–z,
compound 9x was synthesized in 55% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.01 (s, 1H), 9.72 (s, 1H), 8.46 (s, 1H), 8.19 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.78–7.82 (m, 1H), 7.42 (t, J = 8.0 Hz,
2H), 6.95–7.05 (m, 1H), 6.50 (d, J = 16.0 Hz, 1H), 4.50 (d, J = 4.0 Hz,
2H), 3.71 (s, 1H), 1.22–1.29 (m, 8H). ESI-MS m/z 460 [M+H]+.
6.1.41. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4-(methylthio)piperidin-1-yl)but-2-
enamide (9r)
According to general method to synthesize compounds 9a–z,
compound 9r was synthesized in 54% yield. 1H NMR (400 MHz,
DMSO-d6) d 11.85 (s, 1H), 9.71 (s, 1H), 8.45 (s, 1H), 8.20 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.80–7.85 (m, 1H), 7.36–7.44 (m, 2H),
6.65 (d, J = 8.0 Hz, 1H), 4.50 (d, J = 4.0 Hz, 1H), 3.43–3.48 (m, 2H),
1.99–2.03 (m, 1H), 1.20 (s, 8H). ESI-MS m/z 493 [M+H]+.
6.1.48. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)but-2-
enamide (9y)
According to general method to synthesize compounds 9a–z,
compound 9y was synthesized in 65% yield. 1H NMR (400 MHz,
DMSO-d6) d 9.85 (s, 1H), 8.49 (s, 1H), 8.29 (dd, J1 = 4.0 Hz,
J2 = 4.0 Hz, 1H), 7.86–7.90 (m, 1H), 7.50 (s, 1H), 7.43 (t, J = 8.0 Hz,
1H), 3.98–4.01 (m, 1H), 3.48 (t, J = 8.0 Hz, 4H), 3.03 (t, J = 8.0 Hz,
4H), 2.77–2.83 (q, J = 4.0 Hz, 1H), 2.26 (d, J = 16.0 Hz, 1H), 1.63 (t,
J = 8.0 Hz, 4H). ESI-MS m/z 488 [M+H]+.
6.1.42. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(4-methylpiperazin-1-yl)but-2-enamide (9s)
According to general method to synthesize compounds 9a–z,
compound 9s was synthesized in 70% yield. 1H NMR (400 MHz,
DMSO-d6) d 12.25 (s, 1H), 10.15 (s, 1H), 8.41 (s, 1H), 8.30 (dd,
J1 = 4.0 Hz, J2 = 4.0 Hz, 1H), 7.93–7.97 (m, 1H), 7.69 (s, 1H), 7.37
(t, J = 8.0 Hz, 1H), 6.90 (d, J = 16.0 Hz, 1H), 3.37 (s, 8H), 2.80–2.98
(m, 3H), 2.66 (s, 3H). ESI-MS m/z 461 [M+H]+.
6.1.49. (E)-N-(4-((3-Chloro-4-fluorophenyl)amino)thieno[2,3-d]
pyrimidin-6-yl)-4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)but-2-
enamide (9z)
According to general method to synthesize compounds 9a–z,
compound 9z was synthesized in 72% yield. 1H NMR (400 MHz,