T. Xu, J. Zhang, C. Yang et al.
European Journal of Medicinal Chemistry 219 (2021) 113424
4.11.25. 1-(3-chlorophenyl)-3-(4-hydroxybenzyl)urea (4b)
C
14H11FN4NaO [M þ Na]þ: 293.0809, found: 293.0804.
White powder; yield 95%; m.p. 184e186 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d
9.26 (s, 1H),8.68 (s, 1H),7.68 (t, J ¼ 1.89 Hz, 1H),7.21 (m,
4.11.32. 1-(1H-benzo[d]imidazole-2-yl)-3-(4-(trifluoromethyl)
phenyl)urea (11b)
2H), 7.10 (d, J ¼ 8.26 Hz, 2H), 6.93 (m, 1H), 6.71 (d, J ¼ 8.26 Hz, 2H),
6.54 (t, J ¼ 5.73 Hz, 1H), 4.17 (d, J ¼ 5.73 Hz, 2H); 13C NMR (100 MHz,
White powder; yield 91%; m.p. 197e200 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d 156.7, 155.4, 142.5, 133.6, 130.7, 130.6, 129.0 (2C), 121.1,
DMSO‑d6)
d
11.41 (s, 1H), 9.76 (s, 1H), 7.83 (d, J ¼ 8.60 Hz, 2H), 7.63
117.4,116.5,115.5 (2C), 42.8; HRMS (ESI)þ: calcd for C14H13ClN2NaO2
(d, J ¼ 8.60 Hz, 2H), 7.35 (m, 2H), 7.09 (m, 2H); 13C NMR (100 MHz,
[M þ Na]þ: 299.0558, found: 299.0561.
DMSO‑d6)
d 157.3, 151.0, 144.4, 133.4, 126.4 (2C), 126.4, 123.7 (2C),
121.8, 118.4 (2C), 112.9, 112.5 (2C); HRMS (ESI)þ: calcd for
C
15H11F3N4NaO [M þ Na]þ: 343.0777, found: 343.0778.
4.11.26. 1-(3-fluorophenyl)-3-(4-hydroxybenzyl)urea (5b)
White powder; yield 97%; m.p. 167e169 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d 9.26 (s, 1H), 8.70 (s, 1H), 7.46 (m, 1H), 7.23 (q,
4.11.33. 1-(3-fluorophenyl)-3-(4-(trifluoromethyl)phenyl)urea
(12b)
J ¼ 7.78 Hz, 1H), 7.10 (d, J ¼ 8.41 Hz, 2H), 7.02 (dd, J ¼ 8.20 Hz,
1.30 Hz, 1H), 6.70 (m, 3H), 6.53 (t, J ¼ 5.80 Hz, 1H), 4.17 (d,
White powder; yield 90%; m.p. 188e191 ꢁC; 1H NMR (400 MHz,
J
¼
5.73 Hz, 2H); 13C NMR (100 MHz, DMSO‑d6)
d 164.1
DMSO‑d6)
d 9.16 (s, 1H), 9.03 (s, 1H), 7.65 (m, 4H), 7.49 (m, 1H), 7.32
(J ¼ 240.96 Hz), 156.7, 155.4, 142.9, 142.8, 130.6, 130.5, 129.0, 115.5
(2C), 113.8 (J ¼ 2.53 Hz), 107.6 (J ¼ 21.42 Hz), 104.6 (J ¼ 26.64 Hz),
42.8; HRMS (ESI)þ: calcd for C14H13FN2NaO2 [M þ Na]þ: 283.0853,
found: 283.0851.
(m, 1H), 7.15 (m, 1H), 6.81 (m, 1H); 13C NMR (100 MHz, DMSO‑d6)
d
164.1(J ¼ 241.07 Hz), 152.6, 143.7, 141.7, 141.6, 130.9, 130.8, 126.6
(J ¼ 3.37 Hz), 126.5 (J ¼ 3.65 Hz), 122.3 (J ¼ 31.72 Hz), 118.5, 114.6
(J ¼ 2.36 Hz),108.9 (J ¼ 21.41 Hz),105.5 (J ¼ 26.69 Hz); HRMS (ESI)þ:
calcd for C14H10F4N2NaO [M þ Na]þ: 321.0621, found: 321.0629.
4.11.27. 1-(3-chlorophenyl)-3-(1-phenylethyl)urea (6b)
White powder; yield 90%; m.p. 185e186 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d
8.61 (s, 1H), 7.64 (t, J ¼ 1.97 Hz, 1H), 7.34 (s, 2H), 7.33 (s,
4.11.34. 1-(3,5-bis(trifluoromethyl)benzyl)-3-(3-fluorophenyl)urea
(13b)
2H), 7.22 (m, 2H), 7.14 (m, 1H), 6.92 (m, 1H), 6.72 (q, J ¼ 7.84 Hz, 1H),
4.81 (m,1H),1.39 (d, J ¼ 6.97 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6)
White powder; yield 93%; m.p. 185e188 ꢁC, 1H NMR (400 MHz,
d
154.6, 145.5, 133.6, 130.7, 128.8 (2C), 127.2, 126.3 (2C), 121.1, 117.4,
DMSO‑d6) d 9.01 (s, 1H), 8.01 (s, 2H), 7.98 (s, 1H), 7.44 (m, 1H), 7.25
117.3, 116.4, 49.1, 23.4; HRMS (ESI)þ: calcd for C15H15ClN2NaO [M þ
(q, J ¼ 7.76 Hz, 1H), 7.08 (dd, J ¼ 8.27 Hz, 0.95 Hz, 1H), 6.96 (t,
Na]þ: 297.0765, found: 297.0767.
J ¼ 6.03 Hz, 1H), 6.71 (m, 1H), 4.48 (d, J ¼ 5.94 Hz, 2H); 13C NMR
(100 MHz, DMSO‑d6)
d
161.7(J ¼ 241.00 Hz), 155.6, 144.7, 142.7,
4.11.28. 1-(3-fluorophenyl)-3-(1-phenylethyl)urea (7b)
142.6, 130.5(J ¼ 22.11 Hz), 130.4(J ¼ 20.60 Hz), 128.4(J ¼ 2.82 Hz),
White powder; yield 95%; m.p. 179e181 ꢁC; 1H NMR (400 MHz,
125.2, 122.5, 120.9, 120.8, 114.0, 107.9(J
¼
20.69 Hz),
DMSO‑d6)
(m, 2H), 7.00 (m, 1H), 6.70 (m, 2H), 4.82 (m, 1H), 1.39 (d, J ¼ 6.96 Hz,
3H); 13C NMR (100 MHz, DMSO‑d6)
145.5, 142.7 (J ¼ 11.72 Hz), 130.6, 130.5 (J ¼ 10.28 Hz, 2C), 128.8,
127.2, 126.3 (2C), 113.7 (J ¼ 2.86 Hz), 107.7 (J ¼ 21.31 Hz), 104.8
(J ¼ 27.21 Hz), 49.1, 23.4; HRMS (ESI)þ: calcd for C15H15FN2NaO
[M þ Na]þ: 281.1060, found: 281.1066.
d
8.63 (s, 1H), 7.43 (m, 1H), 7.36 (s, 2H), 7.33 (s, 2H), 7.23
104.8(J ¼ 25.86 Hz), 42.5; HRMS (ESI)þ: calcd for C16H11F7N2NaO
[M þ Na]þ: 403.0652, found:403.0654.
d
161.7 (J ¼ 239.31 Hz), 154.6,
4.11.35. 1-(3,5-bis(trifluoromethyl)benzyl)-3-(4-(trifluoromethyl)
phenyl)urea (14b)
White powder; yield 92%; m.p. 166e167 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d 9.21 (s, 1H), 8.01 (s, 2H), 7.99 (s, 1H), 7.59 (m, 4H), 7.03
(t, J ¼ 6.07 Hz, 1H), 4.50 (d, J ¼ 5.98 Hz, 2H); 13C NMR (100 MHz,
4.11.29. 1-(1-phenylethyl)-3-(p-tolyl)urea (8b)
DMSO‑d6)
d 155.5, 144.6, 144.5, 131.1, 130.8, 130.4, 130.1,
White powder; yield 93%; m.p. 176e178 ꢁC; 1H NMR (400 MHz,
128.4(J ¼ 2.65 Hz), 126.4(J ¼ 3.71 Hz), 125.2, 123.7, 122.5, 121.9,
121.6, 120.9, 117.9, 42.6; HRMS (ESI)þ: calcd for C17H11F9N2NaO
[M þ Na]þ: 453.0620, found: 453.0624.
DMSO‑d6)
d 8.24 (s, 1H), 7.34 (s, 2H), 7.32 (s, 2H), 7.23 (m, 3H), 7.00
(d, J ¼ 8.34 Hz, 2H), 6.53 (d, J ¼ 7.87 Hz, 1H), 4.81 (m, 1H), 2.19 (s,
3H), 1.38 (d, J ¼ 7.01 Hz, 3H); 13C NMR (100 MHz, DMSO‑d6)
d 154.11,
145.7, 138.3, 130.2, 129.5, 128.8, 127.1, 126.3, 118.1, 49.0, 23.6, 20.7;
HRMS (ESI)þ: calcd for C16H18N2NaO [M þ Na]þ: 277.1311, found:
277.1315.
4.11.36. 4-(1-(2-(3-bromobenzoyl)hydrazono)ethyl)-N-(1H-
pyrazol-3-yl)benzamide (1c)
White powder; yield 73%; m.p. 198e199 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
(d, J ¼ 7.34 Hz, 1H), 7.49 (t, J ¼ 8.07 Hz, 1H), 6.04 (d, J ¼ 2.96 Hz, 1H),
5.71 (s, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, DMSO‑d6)
162.3,
d
11.02 (s, 1H), 8.20 (d, J ¼ 2.80 Hz, 1H), 7.98 (m, 6H), 7.80
4.11.30. 1-(4-hydroxybenzyl)-3-(p-tolyl)urea (9b)
White powder; yield 96%; m.p. 192e194 ꢁC; 1H NMR (400 MHz,
d
DMSO‑d6)
d
9.25 (s, 1H), 8.31 (s, 1H), 7.26 (d, J ¼ 8.33 Hz, 2H), 7.10 (d,
157.4, 152.4, 136.9, 134.5, 131.0, 130.8, 128.5, 128.0 (2C), 127.4 (2C),
J ¼ 8.33 Hz, 2H), 7.02 (d, J ¼ 8.24 Hz, 2H), 6.71 (d, J ¼ 8.49 Hz, 2H),
126.5, 125.4, 122.1, 114.4, 66.4, 48.1, 14.9; HRMS (ESI)þ: calcd for
6.37 (t, J ¼ 5.74 Hz, 1H), 4.15 (d, J ¼ 5.72 Hz, 2H), 2.21 (s, 3H); 13C
C
19H16BrN5NaO2 [M þ Na]þ: 448.0379, found: 448.0387.
NMR (100 MHz, DMSO‑d6)
d 156.7, 155.7, 138.4, 130.9, 130.2, 129.5
(2C),129.0 (2C),118.2 (2C),115.5 (2C), 42.8, 20.8; HRMS (ESI)þ: calcd
for C15H16N2NaO2 [M þ Na]þ: 279.1104, found: 279.1107.
4.11.37. 4-(1-(2-(3-fluoro-4-methylbenzoyl)hydrazono)ethyl)-N-
(4-morpholinopyridin-2-yl)benzamide (2c)
4.11.31. 1-(1H-benzo[d]imidazole-2-yl)-3-(3-fluorophenyl)urea
(10b)
White powder; yield 65%; m.p. 234e236 ꢁC; 1H NMR (400 MHz,
DMSO‑d6)
d 10.95 (s, 1H), 10.56 (s, 1H), 8.22 (s, 1H), 8.00 (m, 6H),
White powder; yield 90%; m.p. 161e162 ꢁC; 1H NMR (400 MHz,
7.78 (s,1H), 7.33 (t, J ¼ 7.78 Hz,1H), 6.70 (q, J ¼ 6.04 Hz, 2.28 Hz,1H),
DMSO‑d6)
(m, 2H), 7.29 (m, 2H), 7.07 (m, 2H), 6.78 (m,1H); 13C NMR (100 MHz,
DMSO‑d6)
164.1 (J ¼ 240.32 Hz), 156.6, 150.5, 142.4, 142.3, 133.9,
d
11.32 (s, 1H), 9.63 (s, 1H), 7.65 (d, J ¼ 12.10 Hz, 2H), 7.36
3.74 (m, 4H), 3.29 (m, 4H), 2.41 (s, 3H), 1.20 (s, 3H); 13C NMR
(100 MHz, DMSO‑d6)
d 162.2, 161.9, 161.6, 160.0, 157.1, 153.6, 147.7,
d
141.5, 131.1, 132.8, 130.7, 128.9 (2C), 128.6 (2C), 126.8, 122.2, 113.5,
100.0, 95.1, 66.4 (2C), 52.3 (2C), 14.9, 10.8; HRMS (ESI)þ: calcd for
C26H26FN5NaO3 [M þ Na]þ: 498.1912, found: 498.1904.
130.7, 130.6, 121.7 (2C), 114.6 (J
¼
2.01 Hz), 112.7, 108.5
(J ¼ 20.95 Hz), 105.3 (J ¼ 26.97 Hz); HRMS (ESI)þ: calcd for
17