E.M.H. Ali, R.F.A. El-Telbany, M.S. Abdel-Maksoud et al.
European Journal of Medicinal Chemistry 215 (2021) 113277
(400 MHz, CDCl3)
d
8.06 (d, J ¼ 1.4 Hz, 1H), 8.04 (d, J ¼ 5.2 Hz, 2H),
1H), 7.25 (s, 1H), 7.13 (d, J ¼ 8.2 Hz, 1H) [AreH], 6.80 (brs, 1H, NH),
7.89 (d, J ¼ 7.1 Hz, 2H), 7.72 (s, 1H), 7.70 (s, 1H), 7.48e7.43 (m, 3H),
7.28 (d, J ¼ 7.2 Hz, 2H), 7.14e7.12 (m, 1H), 7.11 (s, 1H) [AreH], 6.76
(brs, 1H, NH), 6.51 (brs, 1H, NH), 5.93 (brs, 1H, NH), 3.91 (s, 3H,
OCH3), 3.54 (brs, 2H, CH2CH2CH2NHSO2), 3.04 (brs, 2H,
CH2CH2CH2NHSO2), 1.77 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
6.20 (brs, 2H, 2 NH), 3.91 (s, 3H, OCH3), 3.53 (s, 2H,
CH2CH2CH2NHSO2), 3.01 (s, 2H, CH2CH2CH2NHSO2), 1.75 (s, 2H,
CH2CH2CH2NHSO2); 13C NMR (100 MHz, CDCl3)
d
155.0,132.5,130.1,
129.7, 129.1, 128.9, 126.8, 126.2, 122.8, 122.2, 113.1, 106.5, 56.3
(OCH3), 40.2 (CH2CH2CH2NHSO2), 38.0 (CH2CH2CH2NHSO2), 29.7
(CH2CH2CH2NHSO2); LC/MS 575.6 (Mþ þ 1).
(100 MHz, CDCl3)
120.1, 116.1, 114.8, 106.0, 101.2 [AreC], 56.4 (OCH3), 40.2
d 143.7, 130.0, 128.9, 127.4, 126.3, 126.2, 126.2,
4.1.3.1.11. 4-Chloro-N-(3-((4-(4-(4-chloro-3-methoxyphenyl)-2-
phenyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)propyl)benzene-
sulfonamide (19b). Yield: 65%; mp: 121e124 ꢀC; 1H NMR (400 MHz,
(CH2CH2CH2NHSO2),
38.1
(CH2CH2CH2NHSO2),
29.6
(CH2CH2CH2NHSO2); LC/MS 626.9 (Mþ þ 1).
4.1.3.1.6. 3-Fluoro-N-(3-((4-(4-(4-fluoro-3-methoxyphenyl)-2-
phenyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)propyl)benzene-
sulfonamide (18f). Yield: 68%; mp: 103e106 ꢀC. 1H NMR (400 MHz,
CDCl3)
d
8.07e8.02 (m, 3H), 7.67 (d, J ¼ 7.2 Hz, 2H), 7.43 (t, J ¼ 7.2 Hz,
4H), 7.38 (d, J ¼ 7.8 Hz, 2H), 7.23 (s, 1H), 7.11 (d, J ¼ 8.0 Hz, 1H)
[AreH], 6.74 (brs, 1H, NH), 6.31 (brs, 1H, NH), 5.59 (brs, 1H, NH),
3.88 (s, 3H, OCH3), 3.49 (brs, 2H, CH2CH2CH2NHSO2), 3.00 (brs, 2H,
CH2CH2CH2NHSO2), 1.73 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
CDCl3)
d
8.07e8.03 (m, 3H), 7.57 (d, J ¼ 7.2 Hz, 1H), 7.49e7.40 (m,
5H), 7.29e7.25 (m, 2H), 7.24e7.22 (m, 1H), 7.13 (d, J ¼ 8 Hz, 2H)
[AreH], 6.75 (brs, 1H, NH), 6.40 (brs, 1H, NH), 5.90 (brs, 1H, NH),
3.90 (s, 3H, OCH3), 3.55 (brs, 2H, CH2CH2CH2NHSO2), 3.04 (brs, 2H,
CH2CH2CH2NHSO2), 1.77 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
(100 MHz, CDCl3)
d 155.0, 147.5, 138.9, 138.6, 130.1, 129.6, 129.3,
129.0, 128.9, 128.3, 126.0, 122.7, 122.2, 113.1, 106.7 [AreC], 56.2
(OCH3), 40.1 (CH2CH2CH2NHSO2), 37.8 (CH2CH2CH2NHSO2), 29.9
(CH2CH2CH2NHSO2); LC/MS 610.7 (Mþ þ 1).
(100 MHz, CDCl3)
d 163.6, 161.1, 158.6, 153.9, 147.7, 130.9, 129.8,
128.9, 126.1, 122.6, 122.0, 119.8, 116.2, 114.1, 106.4 [AreC], 56.3
(OCH3), 40.1 (CH2CH2CH2NHSO2), 37.9 (CH2CH2CH2NHSO2), 29.8
(CH2CH2CH2NHSO2); LC/MS 577 (Mþ þ 1).
4.1.3.1.12. 4-Bromo-N-(3-((4-(4-(4-chloro-3-methoxyphenyl)-2-
phenyl-1H-imidazol-5-yl)pyrimidin-2-yl)amino)propyl)benzene-
sulfonamide (19c). Yield: 70%; mp: 135e138 ꢀC; 1H NMR (400 MHz,
4.1.3.1.7. N-(3-((4-(4-(4-Fluoro-3-methoxyphenyl)-2-phenyl-1H-
i m i d a z o l - 5 - y l ) p y r i m i d i n - 2 - y l ) a m i n o ) p r o p y l ) - 4 -
methylbenzenesulfonamide (18g). Yield: 60%; mp: 109e111 ꢀC; 1H
CDCl3) d 8.06e8.01 (m, 3H), 7.57e7.54 (m, 4H), 7.45e7.40 (m, 3H),
7.37 (d, J ¼ 8.4 Hz, 1H), 7.23 (d, J ¼ 1.6 Hz, 1H), 7.10 (d, J ¼ 7.2 Hz, 1H)
[AreH], 6.72 (brs, 1H, NH), 6.33 (brs, 1H, NH), 5.54 (brs, 1H, NH),
3.88 (s, 3H, OCH3), 3.49 (brs, 2H, CH2CH2CH2NHSO2), 3.00 (brs, 2H,
CH2CH2CH2NHSO2), 1.73 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
NMR (400 MHz, CDCl3)
d
8.08 (d, J ¼ 6.8 Hz, 2H), 8.01 (d, J ¼ 5.2 Hz,
1H), 7.65 (d, J ¼ 7.6 Hz, 2H), 7.45e7.37 (m, 3H), 7.29e7.27 (m, 2H),
7.25e7.23 (m, 2H), 7.11 (d, J ¼ 8.8 Hz, 2H) [AreH], 6.72 (brs, 1H, NH),
(100 MHz, CDCl3)
d 157.2, 155.0, 147.5, 139.1, 132.3, 130.1, 129.6,
6.02 (brs, 2H,
2
NH), 3.89 (s, 3H, OCH3), 3.52 (brs, 2H,
129.1, 128.9,128.4,127.4, 126.0,122.7, 122.2,113.1, 106.8 [AreC], 56.3
(OCH3), 40.1 (CH2CH2CH2NHSO2), 37.7 (CH2CH2CH2NHSO2), 29.9
(CH2CH2CH2NHSO2); LC/MS 654.7 (Mþ þ 1).
CH2CH2CH2NHSO2), 2.99 (brs, 2H, CH2CH2CH2NHSO2), 1.75 (brs, 2H,
CH2CH2CH2NHSO2); 13C NMR (100 MHz, CDCl3)
d
143.3, 136.9,
129.7, 128.9, 126.9, 126.2, 116.2, 116.0, 114.6, 106.3 [AreC], 56.3
(OCH3), 40.2 (CH2CH2CH2NHSO2), 38.0 (CH2CH2CH2NHSO2), 29.7
(CH2CH2CH2NHSO2); LC/MS 573.1 (Mþ þ 1).
4.1.3.1.13. N-(3-((4-(4-(4-Chloro-3-methoxyphenyl)-2-phenyl-
1 H - i m i d a z o l - 5 - yl ) p y r i m i d i n - 2 - y l ) a m i n o ) p r o p yl ) - 4 -
fluorobenzenesulfonamide (19d). Yield: 62%; m.p.: 137e140 ꢀC; 1H
4.1.3.1.8. N-(3-((4-(4-(4-Fluoro-3-methoxyphenyl)-2-phenyl-1H-
i m i d a z o l - 5 - y l ) p y r i m i d i n - 2 - y l ) a m i n o ) p r o p y l ) - 4 -
methoxybenzenesulfonamide (18h). Yield: 68%; mp: 113e115 ꢀC; 1H
NMR (400 MHz, CDCl3)
d
8.03 (d, J ¼ 5.6 Hz, 1H), 8.01e7.99 (m, 2H),
7.71 (s, 2H), 7.41e7.37 (m, 3H), 7.32 (d, J ¼ 8.0 Hz, 1H), 7.19 (d,
J ¼ 1.2 Hz, 1H), 7.09e7.05 (m, 3H) [AreH], 6.70 (brs, 1H, NH), 6.33
(brs, 1H, NH), 3.82 (s, 3H, OCH3), 3.41 (brs, 2H, CH2CH2CH2NHSO2),
NMR (400 MHz, CDCl3)
d
8.07 (d, J ¼ 6.8 Hz, 2H), 8.01 (d, J ¼ 5.2 Hz,
1H), 7.69 (d, J ¼ 8.4 Hz, 2H), 7.45e7.40 (m, 3H), 7.27 (d, J ¼ 8.0 Hz,
2H), 7.11 (d, J ¼ 8.8 Hz, 2H), 6.89 (d, J ¼ 8.8 Hz, 2H) [AreH], 6.71 (brs,
1H, NH), 5.98 (brs, 2H, 2 NH), 3.88 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
3.51 (brs, 2H, CH2CH2CH2NHSO2), 2.98 (t,
CH2CH2CH2NHSO2), 1.74 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
(100 MHz, CDCl3) 162.8, 153.8, 147.7, 131.5, 129.7, 129.0, 128.9,
122.0, 116.2, 116.0, 114.6, 114.2, 106.3, 56.3 (OCH3), 55.6 (OCH3), 40.1
2.94
(brs,
2H,
CH2CH2CH2NHSO2),
1.67
(brs,
2H,
CH2CH2CH2NHSO2); 13C NMR (100 MHz, CDCl3)
d
166.2,162.0,157.4,
154.9,147.5,136.1,130.1,129.6,129.1,128.9,126.0,122.6,122.2,116.4,
113.1, 106.8 [AreC], 56.2 (OCH3), 40.1 (CH2CH2CH2NHSO2), 37.7
(CH2CH2CH2NHSO2), 29.8 (CH2CH2CH2NHSO2); LC/MS 594
(Mþ þ 1).
J
¼
4.4 Hz, 2H,
d
4.1.3.1.14. N-(3-((4-(4-(4-Chloro-3-methoxyphenyl)-2-phenyl-
1H-imidazol-5-yl)pyrimidin-2-yl)amino)propyl)-4-(trifluoromethyl)
benzenesulfonamide (19e). Yield: 64%; m.p.: 129e132 ꢀC; 1H NMR
(CH2CH2CH2NHSO2),
38.0
(CH2CH2CH2NHSO2),
29.7
(CH2CH2CH2NHSO2); LC/MS 588.8 (Mþ þ 1).
4.1.3.1.9. N-(3-((4-(4-(4-Fluoro-3-methoxyphenyl)-2-phenyl-1H-
imidazol-5-yl)pyrimidin-2-yl)amino)propyl)naphthalene-1-
sulfonamide (18i). Yield: 65%; mp: 135e137 ꢀC; 1H NMR (400 MHz,
(400 MHz, CDCl3)
d
8.00 (d, J ¼ 4.8 Hz, 1H), 7.95 (s, 2H), 7.78 (s, 2H),
7.62 (d, J ¼ 8.0 Hz, 2H), 7.30 (s, 3H), 7.23 (d, J ¼ 6.8 Hz, 1H), 7.13 (s,
1H), 6.98 (d, J ¼ 7.2 Hz, 1H) [AreH], 6.65 (brs, 1H, NH), 3.72 (s, 3H,
OCH3), 3.34 (brs, 2H, CH2CH2CH2NHSO2), 2.90 (brs, 2H,
CH2CH2CH2NHSO2), 1.60 (brs, 2H, CH2CH2CH2NHSO2); 13C NMR
CDCl3)
d
8.63 (d, J ¼ 3.8 Hz,1H), 8.2 (d, J ¼ 4.8 Hz,1H), 8.07e8.03 (m,
4H), 7.92 (d, J ¼ 7.4 Hz, 1H), 7.59e7.55 (m, 2H), 7.50 (d, J ¼ 8.2 Hz,
1H), 7.46e7.42 (m, 3H), 7.29e7.28 (m, 2H), 7.13 (d, J ¼ 8.2 Hz, 2H)
[AreH], 6.71 (brs, 1H, NH), 6.35 (brs, 1H, NH), 5.65 (brs, 1H, NH),
3.90 (s, 3H, OCH3), 3.52 (brs, 2H, CH2CH2CH2NHSO2), 3.01 (t,
(100 MHz, CDCl3)
d 162.2, 157.6, 154.8, 147.6, 143.7, 134.1, 129.9,
128.8,127.3, 126.2, 124.6,122.4,121.9, 119.2,113.1, 106.9 [AreC], 56.0
(OCH3), 40.2 (CH2CH2CH2NHSO2), 29.9 (CH2CH2CH2NHSO2), 21.0
(CH2CH2CH2NHSO2); LC/MS 644.9 (Mþ þ 1).
J
¼
3.8 Hz, 2H, CH2CH2CH2NHSO2), 1.70 (brs, 2H,
CH2CH2CH2NHSO2); 13C NMR (100 MHz, CDCl3)
d
151.4, 147.7, 134.2,
4.1.3.1.15. N-(3-((4-(4-(4-Chloro-3-methoxyphenyl)-2-phenyl-
1 H - i m i d a z o l - 5 - yl ) p y r i m i d i n - 2 - y l ) a m i n o ) p r o p yl ) - 3 -
fluorobenzenesulfonamide (19f). Yield: 71%; m.p.: 136.5e139.5 ꢀC;
129.7, 129.1, 128.9, 128.3, 126.8, 126.0, 124.3, 122.0, 116.2, 114.6,
106.3, 56.3, 40.1 (CH2CH2CH2NHSO2), 37.9 (CH2CH2CH2NHSO2),
30.1 (CH2CH2CH2NHSO2); LC/MS 609.8 (Mþ þ 1).
1H NMR (400 MHz, CDCl3)
d
8.04 (d, J ¼ 5.6 Hz, 1H), 8.04e7.99 (m,
4.1.3.1.10. N-(3-((4-(4-(4-Chloro-3-methoxyphenyl)-2-phenyl-
1H-imidazol-5-yl)pyrimidin-2-yl)amino)propyl)benzenesulfonamide
(19a). Yield: 69%; mp: 122e125 ꢀC; 1H NMR (400 MHz, CDCl3)
2H), 7.50 (s, 1H), 7.42e7.37 (m, 4H), 7.32 (d, J ¼ 8.4 Hz, 1H),
7.22e7.19 (m, 2H), 7.06 (d, J ¼ 8.0 Hz, 1H) [AreH], 6.69 (brs, 1H, NH),
6.49 (brs, 1H, NH), 3.82 (s, 3H, OCH3), 3.44 (brs, 2H,
CH2CH2CH2NHSO2), 2.98 (brs, 2H, CH2CH2CH2NHSO2), 1.69 (brs, 2H,
d
8.12 (d, J ¼ 3.8 Hz, 2H), 7.96 (s, 1H), 7.79 (d, J ¼ 7.2 Hz, 2H), 7.54 (t,
J ¼ 6.8 Hz, 2H), 7.46 (d, J ¼ 7.2 Hz, 2H), 7.46e7.41 (m, 3H), 7.29 (s,
CH2CH2CH2NHSO2); 13C NMR (100 MHz, CDCl3)
d 163.6, 161.1, 157.4,
12