Z. Xu et al. / European Journal of Medicinal Chemistry 85 (2014) 27e42
39
126e127 ꢀC. 1H NMR (CDCl3, 600 MHz)
d
3.81 (s, 3H, OCH3), 4.10 (s,
5-benzyl-4-(2,4-dichlorophenyl)-N-(4-methoxybenzyl)thiazol-2-
2H, ArCH2), 4.41 (s, 2H, ArCH2), 5.46 (s, 1H, NH), 6.27 (d, J ¼ 3.2 Hz,
1H, ArH), 6.32 (t, J ¼ 2.5 Hz, 1H, ArH), 6.95e6.86 (m, 2H, ArH), 7.23
(d, J ¼ 14.1 Hz, 3H, ArH), 7.31 (t, J ¼ 7.6 Hz, 2H, ArH), 7.38e7.35 (m,
1H, ArH), 7.53e7.49 (m, 2H, ArH); 13C NMR (151 MHz, CDCl3)
amine (25) was obtained as a slightly yellow solid in 69% yield. 1H
NMR (DMSO-d6, 600 MHz) d 3.73 (s, 3H, OCH3), 3.75 (s, 2H, CH2), 4.30
(d, J ¼ 5.4 Hz, 2H, CH2), 6.88 (d, J ¼ 7.8 Hz, 2H, ArH), 7.10 (d, J ¼ 7.2 Hz,
2H, ArH), 7.18 (t, J ¼ 7.2 Hz,1H, ArH), 7.26 (dd, J1 ¼10.8 Hz, J2 ¼ 8.4 Hz,
4H, ArH), 7.43 (d, J ¼ 8.4 Hz, 1H, ArH), 7.49e7.46 (m, 1H, ArH),
7.73e7.70 (m,1H, ArH), 7.92 (t, J ¼ 5.4 Hz,1H, NH); 13C NMR (151 MHz,
d
166.74,159.05,151.23,147.03,142.17, 140.55, 129.70,128.57, 128.18,
127.77, 126.48, 118.91, 113.73, 110.36, 107.66, 55.26, 42.59, 32.89;
ESI-MS m/z 377 [MþH]þ.
CDCl3) d 168.05,167.99,158.98, 143.49,140.07, 134.85, 134.49,133.12,
5-benzyl-4-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)thiazol-2-
amine (19) was obtained as a yellow solid in 75% yield, m.p.
132.66, 129.66, 129.53, 128.61, 128.58, 128.49, 128.24, 126.88, 126.52,
122.49, 113.92, 55.27, 49.13, 32.91; ESI-MS m/z 455 [MþH]þ.
5-benzyl-4-(2,5-dimethoxyphenyl)-N-(4-methoxybenzyl)thiazol-
2-amine (26) was obtained as a white solid in 65.1% yield, m.p.
145e146 ꢀC. 1H NMR (CDCl3, 600 MHz)
d 3.80 (s, 3H, OCH3), 4.08 (s,
2H, ArCH2), 4.42 (s, 2H, ArCH2), 6.01 (br, 1H, NH), 6.95e6.82 (m. 2H,
ArH), 7.28e7.19 (m, 4H, ArH), 7.30 (t, J ¼ 7.5 Hz, 2H, ArH), 7.51e7.46
(m, 2H, ArH), 7.73e7.70 (m, 1H, ArH), 8.53 (dd, J1 ¼ 4.7 Hz,
J2 ¼ 1.6 Hz, 1H, ArH), 8.62e8.56 (m, 1H, ArH); 13C NMR (151 MHz,
162.3e163.8 ꢀC. 1H NMR (CDCl3, 600 MHz)
d 3.65 (s, 3H, OCH3), 3.69
(s, 3H, OCH3), 3.72 (s, 3H, OCH3), 3.73 (s, 2H, ArCH2),4.28 (d, 2H,
J ¼ 5.8 Hz, ArCH2), 6.83 (d, J ¼ 3.2 Hz, 1H, ArH), 6.92e6.86 (m, 3H),
6.99 (d, J ¼ 9.0 Hz, 1H, ArH), 7.11 (dd, J1 ¼ 7.9 Hz, J2 ¼ 1.4 Hz, 2H,
ArH), 7.16 (td, J1 ¼ 7.2 Hz, J2 ¼ 1.3 Hz, 1H, ArH), 7.28e7.23 (m, 4H,
ArH), 7.78 (t, J ¼ 5.8 Hz, 1H, NH); 13C NMR (151 MHz, CDCl3)
CDCl3) d 167.28,159.14,149.02,148.79,140.31,135.15,133.54,129.67,
128.59, 128.13, 126.54, 123.45, 118.74, 113.75, 55.23, 47.01, 32.82;
ESI-MS m/z 388 [MþH]þ.
5-benzyl-4-(4-methoxyphenyl)-N-(naphthalen-2-ylmethyl)thia-
zol-2-amine (20) was obtained as a yellow solid in 73% yield, m.p.
d 167.25, 159.02, 153.36, 151.36, 143.82, 140.90, 129.91, 128.93,
128.37, 128.30, 126.21, 125.24, 122.03, 116.72, 114.71, 113.94, 112.51,
56.13, 55.70, 55.25, 49.24, 33.16; ESI-MS m/z 447 [MþH]þ.
5-benzyl-4-(furan-2-yl)-N-(4-methoxybenzyl)thiazol-2-amine
(27) was obtained as a white solid in 95% yield. 1H NMR (CDCl3,
145e146 ꢀC. 1H NMR (CDCl3, 600 MHz)
d 3.80 (s, 3H, OCH3), 4.08 (s,
2H, ArCH2), 4.42 (s, 2H, ArCH2), 6.01 (br, 1H, NH), 6.92e6.84 (m, 2H,
ArH), 7.24e7.20 (m, 3H, ArH), 7.29 (t, J ¼ 7.6 Hz, 2H, ArH), 7.56e7.43
(m, 5H, ArH), 7.87e7.74 (m, 4H, ArH); 13C NMR (151 MHz, CDCl3)
300 MHz)
d 3.72 (s, 3H, OCH3), 4.23 (s, 2H, ArCH2), 4.32 (d,
d
167.56, 159.08, 140.44, 135.15, 133.30, 132.82, 129.69, 128.58,
J ¼ 5.4 Hz, 2H, ArCH2), 6.55e6.53 (m, 1H, ArH), 6.60 (d, J ¼ 3.0 Hz,
1H, ArH), 6.88 (d, J ¼ 8.4 Hz, 2H, ArH), 7.24e7.19 (m, 3H, ArH),
7.32e7.26 (m, 4H, ArH), 7.70 (s, 1H, ArH), 7.94 (br, 1H, NH); 13C NMR
128.41, 128.16, 127.82, 127.67, 126.49, 126.19, 126.10, 125.87, 125.54,
118.54, 113.74, 55.21, 49.92, 32.86; ESI-MS m/z 388 [MþH]þ.
5-benzyl-4-(2-fluorophenyl)-N-(4-methoxybenzyl)thiazol-2-
amine (21) was obtained as a white solid in 43% yield. 1H NMR
(151 MHz, CDCl3)
d 167.27, 159.10, 150.52, 141.54, 140.31, 137.52,
129.61, 128.88, 128.54, 128.33, 126.48, 120.74, 114.02, 111.10, 107.94,
(DMSO-d6, 600 MHz)
d
3.72 (s, 3H, OCH3), 3.81 (s, 2H, CH2), 4.30 (d,
55.25, 49.28, 32.61; ESI-MS m/z 377 [MþH]þ.
J ¼ 5.4 Hz, 2H, CH2), 6.89e6.85 (m, 2H, ArH), 7.10 (d, J ¼ 7.8 Hz, 2H,
ArH), 7.17 (t, J ¼ 7.2 Hz, 1H, ArH), 7.21e7.31 (m, 6H, ArH), 7.45e7.41
(m, 2H, ArH), 7.89 (t, J ¼ 5.4 Hz, 1H, NH); 13C NMR (151 MHz, CDCl3)
5-benzyl-N-(4-methoxybenzyl)-4-phenylthiazol-2-amine
(28)
was obtained as a white solid in 91% yield, m.p. 114e115 ꢀC. 1H NMR
(DMSO-d6, 600 MHz) 3.71 (s, 3H, OCH3), 4.05 (s, 2H, ArCH2), 4.33
d
d
167.28, 160.66, 159.07, 141.45, 140.40, 131.79, 129.63, 128.95,
(d, J ¼ 3.0 Hz, 2H, ArCH2), 6.87e6.83 (m, 2H, ArH), 7.16 (d, J ¼ 7.2 Hz,
2H, ArH), 7.21e7.19 (m, 1H, ArH), 7.34e7.24 (m, 5H, ArH), 7.38 (t,
J ¼ 7.8 Hz, 2H, ArH), 7.54 (d, J ¼ 7.8 Hz, 2H, ArH), 7.87 (t, J ¼ 5.4 Hz,
128.38 (d, J ¼ 17.0 Hz), 126.45, 124.03, 123.27, 123.18, 115.98, 115.83,
114.03, 55.26, 49.25, 33.07, 33.05; ESI-MS m/z 405 [MþH]þ.
5-benzyl-4-(4-fluorophenyl)-N-(4-methoxybenzyl)thiazol-2-
amine (22) was obtained as a yellow solid in 93% yield, m.p.
1H, NH);13C NMR (151 MHz, CDCl3)
d 166.95, 159.08, 159.04, 158.23,
132.56, 129.65, 129.14, 128.93, 119.29, 114.00, 113.95, 113.73, 55.26,
55.24, 49.29, 32.07.
139e140 ꢀC. 1H NMR (DMSO-d6, 600 MHz)
d 3.73 (s, 3H, OCH3), 4.05
(s, 2H, ArCH2), 4.34 (d, J ¼ 5.4 Hz, 2H, ArCH2), 6.86 (d, J ¼ 9.0 Hz, 2H,
ArH), 7.18 (d, J ¼ 7.2 Hz, 2H, ArH), 7.24e7.20 (m, 3H, ArH), 7.34e7.28
(m, 4H, ArH), 7.62e7.57 (m, 2H, ArH), 7.93 (br, 1H, NH); 13C NMR
5-(2-methoxybenzyl)-N-(4-methoxybenzyl)-4-phenylthiazol-2-
amine (29) was obtained as a white solid in 96.3% yield, m.p.
144.7e145.2 ꢀC. 1H NMR (DMSO-d6, 600 MHz)
d 3.77 (s, 3H, OCH3),
(151 MHz, CDCl3)
d
166.94, 163.00, 161.36, 159.12, 146.54, 140.32,
3.78 (s, 3H, OCH3), 4.03 (s, 2H, ArCH2), 4.39 (d, 2H, ArCH2), 6.92 (t,
J ¼ 9.00 Hz, 1H, ArH), 6.94 (d, J ¼ 9.00 Hz, 2H, ArH), 7.03 (d,
J ¼ 9.00 Hz,1H, ArH),7.11 (d, J ¼ 6.60 Hz,1H, ArH), 7.27 (t, J ¼ 7.80 Hz,
1H, ArH), 7.34 (d, J ¼ 9.00 Hz, 2H, ArH), 7.35 (t, J ¼ 6.60 Hz, 1H, ArH),
7.43 (t, J ¼ 7.80 Hz, 2H, ArH), 7.60 (d, J ¼ 7.80 Hz, 2H, ArH), 7.98 (t,
131.41, 130.12, 129.71, 128.90, 128.61, 128.11, 126.55, 119.73, 115.27,
115.12, 114.03, 55.27, 49.20, 32.84, 30.90; ESI-MS m/z 405 [MþH]þ.
5-benzyl-4-(2,4-difluorophenyl)-N-(4-methoxybenzyl)thiazol-2-
amine (23) was obtained as a slightly yellow solid in 62% yield. 1H
NMR (DMSO-d6, 600 MHz)
d
3.69 (s, 3H, OCH3), 3.78 (s, 2H, CH2),
1H, NH); 13C NMR (151 MHz, CDCl3)
d 167.12, 159.02, 156.98, 147.27,
4.27 (d, J ¼ 5.0 Hz, 2H, CH2), 6.85 (d, J ¼ 8.4 Hz, 2H, ArH), 7.08 (d,
J ¼ 7.2 Hz, 2H, ArH), 7.16e7.12 (m, 2H, ArH), 7.27e7.20 (m, 4H, ArH),
7.28 (td, J1 ¼ 10.2 Hz, J2 ¼ 2.4 Hz, 1H, ArH), 7.47 (dd, J1 ¼ 15.6 Hz,
J2 ¼ 8.4 Hz, 1H, ArH), 7.89 (t, J ¼ 6.0 Hz, 1H, NH). 13C NMR (151 MHz,
135.53, 129.98, 129.35, 128.93, 128.51, 128.20, 127.70, 127.31, 120.55,
119.64, 113.96, 110.11, 55.26, 55.16, 49.20, 27.23; ESI-MS m/z 417
[MþH]þ; IR (KBr, cmꢂ1): 3204 (nNeH), 3099, 2954, 2831, 1582, 1510,
1491, 1460, 1172, 1034, 824, 763, 701.
CDCl3)
d
167.70, 163.53, 161.91, 160.85, 159.08, 140.45, 140.20,
4-((2-(4-methoxybenzylamino)-4-phenylthiazol-5-yl)methyl)ben-
zonitrile (30) was obtained as a white solid in 96% yield, m.p.
132.59, 129.62, 128.78, 128.49, 128.28, 126.52, 123.02, 114.00, 111.33,
104.34, 104.17, 104.00, 55.26, 49.16, 32.97; ESI-MS m/z 423 [MþH]þ.
5-benzyl-4-(2-chlorophenyl)-N-(4-methoxybenzyl)thiazol-2-
138.1e138.9 ꢀC. 1H NMR (DMSO-d6, 600 MHz)
d 3.72 (s, 3H, OCH3),
4.17 (s, 2H, ArCH2), 4.34 (d, 2H, ArCH2), 6.89 (d, J ¼ 8.40 Hz, 2H,
ArH), 7.28 (d, J ¼ 8.40 Hz, 2H, ArH),7.30 (t, 1H, ArH), 7.36e7.39 (m,
4H, ArH), 7.52 (d, J ¼ 7.80 Hz, 2H, ArH), 7.77 (d, J ¼ 7.8 Hz, 2H, ArH),
amine (24) was obtained as a yellow solid in 86% yield. 1H NMR
(DMSO-d6, 600 MHz) d 3.69 (s, 3H, OCH3), 3.71 (s, 2H, CH2), 4.26 (d,
J ¼ 5.4 Hz, 2H, CH2), 6.85 (d, J ¼ 8.4 Hz, 2H, ArH), 7.06 (d, J ¼ 7.2 Hz,
2H, ArH), 7.14 (t, J ¼ 7.2 Hz,1H, ArH), 7.23 (dd, J1 ¼9.0 Hz, J2 ¼ 7.8 Hz,
4H, ArH), 7.39e7.33 (m, 3H, ArH), 7.51 (d, J ¼ 7.8 Hz,1H, ArH), 7.84 (t,
7.98 (br,1H, NH); 13C NMR (151 MHz, CDCl3)
d 167.31, 159.15,145.94,
132.41, 129.46, 128.90, 128.45, 128.37, 127.86, 118.83, 117.35, 114.04,
110.46, 55.27, 49.21, 32.91; ESI-MS m/z 412 [MþH]þ; IR (KBr, cmꢂ1):
3205 (nNeH), 3094, 2972, 2910, 2227, 1586, 1513, 1460, 1434, 1176,
1036, 813, 698.
N-(4-methoxybenzyl)-4-(4-methoxyphenyl)-5-methylthiazol-2-
amine (31) was obtained as a white solid in 79% yield, m.p.
J ¼ 5.4 Hz, 1H, NH). 13C NMR (151 MHz, CDCl3)
d 167.89, 158.94,
144.67, 140.36, 134.58, 134.10, 131.96, 129.85, 129.72, 129.37, 128.81,
128.58, 128.43, 128.30, 126.54, 126.41, 122.07, 113.89, 55.26, 49.06,
32.95; ESI-MS m/z 421 [MþH]þ.