2054
H.M. Shallal, W.A. Russu / European Journal of Medicinal Chemistry 46 (2011) 2043e2057
NMR (DMSO-d6):
d
3.34e3.78 (br, m, 10H), 7.17e7.29 (m, 6H), 7.48
of 20 was confirmed using HPLC (96.02%, Rt ¼ 14.823). 1H NMR
(t, J ¼ 7.92 Hz, 1H), 7.65 (ddd, J ¼ 0.96 Hz, J ¼ 6.96 Hz, J ¼ 8.88 Hz,
1H), 7.8 (d, J ¼ 7.56 Hz, 1H), 7.87 (m. 1H), 7.98 (m, 1H), 8.02 (s, 1H),
8.31 (s, 2H), 8.56 (d, J ¼ 7.92 Hz, 1H), 8.62 (s, 1H), 9.92 (s, 1H). 13C
(DMSO-d6): d 1.12 (t, 3H), 2.43 (q, 2H), 3.32e3.78 (m, 8H), 7.51e7.65
(m, 6H), 7.89 (m, 2H), 8.12 (m, 2H), 8.27 (s, 2H), 8.47 (m, 2H), 8.6 (d,
J ¼ 8.28 Hz, 1H), 10.0 (s, 1H). 13C NMR (DMSO-d6):
d 15.54, 21.88,
NMR (DMSO-d6):
d
34.53, 41.5, 43.25, 43.78, 46.9, 115.15, 120.82,
43.59, 114.04, 121.22, 123.07, 124.92, 126.07, 127.91, 128.17, 128.47,
130.28, 130.33, 133.36, 138.16, 140.74, 150.53, 157.1, 157.77, 158.94,
160.22, 169.11. MS: calcd 515.24 for C31H29N7O [M]þ; found, 515.89
122.17, 122.96, 123.18, 126.12, 126.38, 127.86, 128.34, 128.56, 128.67,
133.13, 139.23, 140.87, 149.7, 154.36, 157.67, 157.81, 160.17, 169.02.
MS: calcd 501.23 for C30H27N7O [M]þ; found, 501.95 [M] þ
.
[M] þ
.
3.1.19. (4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl)(4-(quinazolin-
4-ylamino)phenyl)methanone (17)
3.1.23. (4-(5-Ethylpyrimidin-2-yl)piperazin-1-yl)(4e((2-phenyl-
quinazolin-4 ylamino)methyl)phenyl)methanone (21)
Compound 17 was prepared from intermediate 2 (90 mg,
0.354 mmol) and intermediate 8 (93 mg, 0.354 mmol) following the
procedure used in the preparation of compound 13. The product
obtained was a white solid (135 mg, 76%); mp: 245e247 ꢁC. The
purity of 17 was confirmed using HPLC (96.73%, Rt ¼ 14.952). 1H
Compound 21 was prepared from intermediate 1 (120 mg,
0.625 mmol) and intermediate 12 (221 mg, 0.625 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (105 mg, 20%); mp: 207e208 ꢁC. The
purity of 21 was confirmed using HPLC (97.08%, Rt ¼ 15.735). 1H
NMR (DMSO-d6):
d
3.05e3.8 (br, m, 10H), 7.18e7.31 (m, 5H), 7.5 (d,
NMR (DMSO-d6): d 1.1 (t, 3H), 2.41 (q, 2H), 3.34e3.76 (m, 8H), 4.97
J ¼ 8.64 Hz, 2H), 7.67 (ddd, J ¼ 1.38, Hz, J ¼ 7.2 Hz, J ¼ 8.1 Hz, 1H),
7.82 (d, J ¼ 8.28 Hz, 1H), 7.89 (ddd, J ¼ 1.2 Hz, J ¼ 6.96 Hz,
J ¼ 8.28 Hz, 1H), 8.04 (d, J ¼ 8.64 Hz, 2H), 8.32 (s, 2H), 8.65 (d,
J ¼ 8.1 Hz, 1H), 8.67 (s, 1H), 10.01 (s, 1H). 13C NMR (DMSO-d6):
(d, J ¼ 5.82 Hz, 2H), 7.4e7.55 (m, 8H), 7.79 (m, 2H), 8.25 (s, 2H), 8.33
(m, 1H), 8.43 (m, 2H), 8.98 (t, J ¼ 5.82 Hz, 1H). 13C NMR (DMSO-d6):
d
15.56, 21.88, 41.4, 43.26, 43.56, 46.85, 113.79, 122.68, 124.94,
125.45, 127.24, 127.31, 127.84, 128.2, 130.3, 132.83, 134.26, 138.52,
141.51, 149.98, 157.1, 159.15, 159.59, 160.16, 169.11. MS: calcd 529.26
d
34.50, 43.52, 45.38, 115.20, 121.73, 122.87, 123.11, 126.08, 126.35,
þ
for C32H31N7O [M]þ; found, 529.88 [M]
.
127.75, 127.8, 128.3, 128.51, 130.34, 133.12, 140.59, 140.83, 149.69,
154.27, 157.57, 157.78, 160.13, 169.09. MS: calcd 501.23 for
C30H27N7O [M]þ; found, 501.74 [M] þ
.
3.1.24. (4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl)(3-(2-phenylq-
uinazolin-4-ylamino)phenyl)methanone (22)
3.1.20. (4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl)(4-((quinazolin-
4-ylamino)methyl)phenyl)methanone (18)
Compound 22 was prepared from intermediate 2 (120 mg,
0.472 mmol) and intermediate 10 (160 mg, 0.472 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (135 mg, 23%); mp: 214e215 ꢁC. The
purity of 22 was confirmed using HPLC (95.38%, Rt ¼ 18.948). 1H
Compound 18 was prepared from intermediate 2 (102 mg,
0.405 mmol) and intermediate 9 (113 mg, 0.405 mmol) following
the general procedure used in the preparation of 13. The product
obtained was a white solid (40 mg, 19%); mp: 99e101 ꢁC. The purity
of 18 was confirmed using HPLC (96.14%, Rt ¼ 15.95). 1H NMR
NMR (DMSO-d6):
d 3.37e3.83 (br, m, 10H), 7.2e7.32 (m, 6H),
7.44e7.67 (m, 5H), 7.91 (m, 2H), 8.1 (ddd, J ¼ 0.9 Hz, J ¼ 2.1 Hz,
(DMSO-d6):
d
3.37e3.83 (br, m, 10H), 4.89 (d, J ¼ 5.82 Hz, 2H),
J ¼ 8.28 Hz, 1H), 8.2 (m, 1H), 8.32 (s, 2H), 8.47 (m, 2H), 8.62 (d,
7.22e7.34 (m, 5H), 7.43 (d, J ¼ 8.28 Hz, 2H), 7.49 (d, J ¼ 8.28 Hz, 2H),
7.6 (ddd, J ¼ 1.2 Hz, J ¼ 6.72 Hz, J ¼ 8.28 Hz,1H), 7.76 (dd, J ¼ 0.84 Hz,
J ¼ 7.56 Hz, 1H), 7.84 (ddd, J ¼ 1.2 Hz, J ¼ 6.72 Hz, J ¼ 8.28 Hz, 1H),
8.34 (s, 2H), 8.36 (d, J ¼ 7.92 Hz, 1H), 8.51 (s, 1H), 8.94 (t, J ¼ 5.82 Hz,
J ¼ 8.28 Hz, 1H), 10.0 (s, 1H). 13C NMR (DMSO-d6):
d 34.53, 41.46,
43.84, 46.95, 113.99, 120.65, 121.84, 122.89, 122.98, 123.02, 126.07,
126.11, 127.88, 128.17, 128.33, 128.54, 128.66, 128.78, 130.3, 131.43,
132.01, 133.34, 136.11, 138.18, 139.54, 140.85, 150.49, 157.77, 157.85,
158.92, 160.15, 169.14. MS: calcd 577.26 for C36H31N7O [M]þ; found,
1H). 13C NMR (DMSO-d6):
d 34.49, 43.23, 114.86, 122.61, 122.89,
125.74, 126.09, 127.07, 127.2, 127.54, 128.31, 128.53, 132.62, 134.23,
140.83, 141.09, 149.17, 155.02, 157.77, 159.36,þ160.1, 169.1. MS: calcd
577.55 [M] þ
.
515.24 for C31H29N7O [M]þ; found, 515 [M]
.
3.1.25. (4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl)(4-(2-phenylq-
uinazolin-4-ylamino)phenyl)methanone (23)
3.1.21. (4-(5-Ethylpyrimidin-2-yl)piperazin-1-yl)(2-(3-phenylquin-
azolin-4-ylamino)phenyl)methanone (19)
Compound 23 was prepared from intermediate 2 (120 mg,
0.472 mmol) and intermediate 11 (160 mg, 0.472 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (70 mg,12%); mp: >250 ꢁC. The purity of
23 was confirmed using HPLC (95%, Rt ¼ 18.98). 1H NMR (DMSO-
Compound 19 was prepared from intermediate 1 (120 mg,
0.625 mmol) and intermediate 10 (213 mg, 0.625 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (210 mg, 40%); mp: 204e205 ꢁC. The
purity of 19 was confirmed using HPLC (97.67%, Rt ¼ 15.123). 1H
d6): d 3.38e3.82 (br, m, 10H), 7.21e7.33 (m, 6H), 7.53e7.69 (m, 5H),
7.93 (m, 2H), 8.15 (m. 2H), 8.34 (s, 2H), 8.51 (m, 2H), 8.64 (d,
NMR (DMSO-d6):
d
1.09 (t, 3H), 2.4 (q, 2H), 3.16e3.71 (m, 8H), 7.18
J ¼ 8.28 Hz, 1H), 10.06 (s, 1H). 13C NMR (DMSO-d6):
d 34.56, 43.53,
(d, J ¼ 7.56 Hz, IH), 7.41e7.59 (m, 5H), 7.83 (m, 2H), 8.02 (m, 1H),
114.08, 121.28, 122.95, 123.11, 126.16, 127.98, 128.21, 128.38, 128.54,
128.6, 128.75, 130.29, 130.42, 131.47, 133.44, 138.19, 140.8, 140.89,
150.57, 157.83, 159, 160.18, 169.19. MS: calcd 577.26 for C36H31N7O
8.13 (m, 1H), 8.21 (s, 2H), 8.4 (m, 2H), 8.54 (d, J ¼ 8.22 Hz, 1H), 9.87
(s, 1H). 13C NMR (DMSO-d6):
d 15.36, 21.85, 42.66, 44.25, 114.01,
þ
[M]þ; found, 577.69 [M]
.
120.67, 121.79, 122.86, 125.02, 125.97, 127.9, 128.16, 128.27, 128.6,
130.12, 130.2, 133.23, 136.23, 138.3, 139.59, 150.56, 157.03, 157.92,
159.02, 160.3, 169.2. MS: calcd 515.24 for C31H29N7O [M]þ; found,
3.1.26. (4-(5-Benzylpyrimidin-2-yl)piperazin-1-yl)(4-((2-phenyl-
quinazolin-4-ylamino)methyl)phenyl)methanone (24)
þ
515.84 [M]
.
Compound 24 was prepared from intermediate 2 (120 mg,
0.472 mmol) and intermediate 12 (167 mg, 0.472 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (59 mg, 10%); mp: 216e217 ꢁC. The
purity of 24 was confirmed using HPLC (97.27%, Rt ¼ 19.543). 1H
3.1.22. (4-(5-Ethylpyrimidin-2-yl)piperazin-1-yl)(2-(4-phenylquin-
azolin-4-ylamino)phenyl)methanone (20)
Compound 20 was prepared from intermediate 1 (120 mg,
0.625 mmol) and intermediate 11 (213 mg, 0.625 mmol) following
the same procedure utilized in the preparation of 13. The product
obtained was a white solid (180 mg, 34%); mp: >250 ꢁC. The purity
NMR (DMSO-d6):
d
3.37e3.79 (br, m, 10H), 4.99 (d, J ¼ 5.82 Hz, 2H),
7.19e7.31 (m, 5H), 7.42e7.66 (m, 8H), 7.82 (m, 2H), 8.3 (s, 2H), 8.35