A. S. Mayhoub et al. / Bioorg. Med. Chem. 20 (2012) 7030–7039
7037
4.5.7. 2-(2,5-Dichlorophenyl)-4-phenylthiazole (9g)
13C NMR (CDCl3) d 168.07, 156.11, 145.28, 134.65, 131.38, 129.00,
128.76, 128.12, 126.59, 126.50, 112.26, 35.59, 33.48, 22.40, 14.05;
CIMS (m/z, rel intensity) 294 (MH+, 100); HRMS (EI), m/z M+
293.1241, Calcd for C19H19NS 293.1238; HPLC purity (C-18 reverse
phase column): 95.04% (methanol/H2O, 95:5).
White solid (51 mg, 31%): mp 86 °C. 1H NMR (CDCl3) d 8.45 (d,
J = 2.4 Hz, 1H), 8.02 (dd, J = 1.5, 8.7 Hz, 2H), 7.66 (s, 1H), 7.64 (d,
J = 2.4 Hz, 1H), 7.49–7.26 (m, 4H); 13C NMR (CDCl3) d 161.54,
155.05, 134.07, 133.44, 133.11, 131.73, 131.12, 130.41, 130.05,
128.79, 128.37, 126.45, 115.10; ESIMS (m/z, rel intensity) 306/
308 (MH+, 100/57); HRMS (ESI), m/z MH+ 305.9906, Calcd for
4.5.14. 4-(3-Methoxyphenyl)-2-phenylthiazole (9n)
C
15H10Cl2NS 305.9911; HPLC purity (C-18 reverse phase column):
White solid (134 mg, 100%): mp 79–80 °C. 1H NMR (CDCl3) d
8.10 (d, J = 2.4 Hz, 1H), 8.07 (d, J = 1.8 Hz, 1H), 7.66 (t, J = 2.4 Hz,
1H), 7.59 (d, J = 7.5 Hz, 1H), 7.49–7.39 (m, 5H), 7.01 (dd, J = 2.4,
7.8 Hz, 1H), 3.91 (s, 3H); 13C NMR (CDCl3) d 167.75, 160.00,
156.05, 135.88, 133.72, 130.08, 129.77, 128.93, 126.62, 118.88,
113.90, 113.02, 112.02, 55.33; ESIMS (m/z, rel intensity) 268
(MH+, 100); HRMS (ESI), m/z MH+ 268.0799, Calcd for C16H14NOS
268.0796; HPLC purity (C-18 reverse phase column): 99.99%
(methanol/H2O, 95:5).
95.19% (methanol/H2O, 95:5).
4.5.8. 2-(5-Chloro-2-methylphenyl)-4-phenylthiazole (9h)
Colorless oil (40 mg, 28%). 1H NMR (CDCl3) d 8.00 (d, J = 7.2 Hz,
1H), 7.85 (d, J = 2. 1 Hz, 1H), 7.56 (s, 1H), 7.47 (t, J = 7.2 Hz, 1H),
7.39 (d, J = 7.5 Hz, 1H), 7.29 (m, 2H), 2.65 (s, 3H); 13C NMR (CDCl3)
d 165.81, 155.79, 135.01, 134.31, 132.86, 131.67, 129.42, 129.20,
128.78, 128.26, 126.39, 113.53, 21.27; ESIMS (m/z, rel intensity)
286/288 (MH+, 100/41); HRMS (ESI), m/z MH+ 286.0464, Calcd for
C
16H13ClNS 286.0457; HPLC purity (C-18 reverse phase column):
4.5.15. 2-(3-Chloro-2-methylphenyl)-4-(3-methoxyphenyl)
thiazole (9p)
96.93% (methanol/H2O, 95:5).
White solid (35 mg, 21%): mp 70 °C. 1H NMR (CDCl3) d 7.56 (m,
4H), 7.48 (d, J = 7.8 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.23 (t,
J = 7.5 Hz, 1H), 6.92 (dd, J = 7.8, 1.8 Hz, 1H), 3.89 (s, 3H), 2.68 (s,
3H); 13C NMR (CDCl3) d 166.66, 159.98, 155.59, 136.12, 135.68,
135.05, 130.40, 129.79, 128.75, 126.62, 118.79, 114.02, 113.94,
111.93, 55.31, 17.76; CIMS (m/z, rel intensity) 318/316 (MH+, 33/
100); HRMS (EI), m/z M+ 315.0485, Calcd for C17H14ClNOS
315.0480; HPLC purity (C-18 reverse phase column): 95.62%
(methanol/H2O, 95:5).
4.5.9. 2-(2,6-Dichlorophenyl)-4-phenylthiazole (9i)
White solid (118 mg, 72%): mp 85–86 °C. 1H NMR (CDCl3) d 7.97
(dd, J = 1.5, 8.7 Hz, 1H), 7.69 (s, 1H), 7.45–7.28 (m, 6H); 13C NMR
(CDCl3) d 161.20, 155.80, 136.01, 134.15, 132.32, 131.21, 128.75,
128.25, 128.21, 126.53, 115.14; ESIMS (m/z, rel intensity) 306/
308 (MH+, 100/58); HRMS (ESI), m/z MH+ 305.9901, Calcd for
C15H10Cl2NS 305.9911; HPLC purity (C-18 reverse phase column):
97.40% (methanol/H2O, 95:5).
4.5.10. 2-(4-Chloro-2-methylphenyl)-4-phenylthiazole (9j)
White solid (25 mg, 17%): mp 57 °C. 1H NMR (CDCl3) d 8.00 (d,
J = 1.5 Hz, 1H), 7.97 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.54 (s, 1H), 7.45
(dt, J = 1.2, 8.4 Hz, 2H), 7.33 (m, 3H), 2.68 (s, 3H); 13C NMR (CDCl3)
d 166.24, 155.78, 138.49, 135.07, 134.36, 131.39, 130.49, 128.75,
128.19, 126.73, 126.35, 126.21, 113.17, 21.65; CIMS (m/z, rel inten-
sity) 286/288 (MH+, 100/30); HRMS (EI), m/z M+ 285.0383, Calcd
for C16H12ClNS 285.0379; HPLC purity (C-18 reverse phase col-
umn): 99.30% (methanol/H2O, 95:5).
4.5.16. 2-(2,3-Dichlorophenyl)-4-(3-methoxyphenyl)thiazole
(9q)
White solid (82 mg, 48%): mp 93 °C. 1H NMR (CDCl3) d 8.29
(dd, J = 7.5, 1.5 Hz, 1H), 7.64 (s, 1H), 7.59 (dd, J = 3.9, 1.2 Hz,
1H), 7.54 (s, 1H), 7.52 (d, J = 1.5 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H),
7.32 (t, J = 7.8 Hz, 1H), 6.92 (dd, J = 7.8, 1.8 Hz, 1H), 3.89 (s,
3H); 13C NMR (CDCl3) d 162.52, 159.97, 154.81, 135.49, 134.13,
134.02, 131.02, 130.37, 129.79, 129.36, 127.34, 118.84, 115.30,
113.91, 112.03, 55.33; CIMS (m/z, rel intensity) 338/336 (MH+,
67/100); HRMS (EI), m/z M+ 334.9938, Calcd for C16H11Cl2NOS
334.9946; HPLC purity (C-18 reverse phase column): 95.00%
(methanol/H2O, 95:5).
4.5.11. 2-(4-Bromo-2-methylphenyl)-4-phenylthiazole (9k)
White solid (160 mg, 97%): mp 58 °C. 1H NMR (CDCl3) d 8.02 (d,
J = 1.5 Hz, 1H), 7.99 (s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.52 (s, 1H),
7.50–7.39 (m, 5H), 2.69 (s, 3H); 13C NMR (CDCl3) d 166.33,
155.79, 138.73, 134.39, 131.85, 131.18, 129.22, 128.81, 128.24,
126.40, 123.53, 113.26, 21.74; ESIMS (m/z, rel intensity) 330/332
(MH+, 100/97); HRMS (ESI), m/z MH+ 329.9956, Calcd for
4.5.17. 2-(2,3-Difluorophenyl)-4-(3-methoxyphenyl)thiazole
(9r)
White solid (88 mg, 58%): mp 98 °C. 1H NMR (CDCl3) d 8.20 (m,
1H), 7.62 (s, 1H), 7.60 (m, 1H), 7.56 (d, J = 7.5 Hz, 1H), 7.37 (t,
J = 7.8 Hz, 1H), 7.22 (m, 2H), 6.93 (dd, J = 7.8, 1.8 Hz, 1H), 3.90 (s,
3H); 13C NMR (CDCl3) d 159.98, 158.90, 155.06, 152.45, 149.15,
135.45, 129.78, 124.30, 118.84, 117.96, 114.99, 113.91, 112.06,
55.30; CIMS (m/z, rel intensity) 304 (MH+, 100); HRMS (EI), m/z
M+ 303.0533, Calcd for C16H11F2NOS 303.0529; HPLC purity (C-18
reverse phase column): 96.02% (methanol/H2O, 95:5).
C16H13BrNS 329.9952; HPLC purity (C-18 reverse phase column):
100.00% (methanol/H2O, 95:5).
4.5.12. 2-(2-Bromo-4-methylphenyl)-4-phenylthiazole (9l)
White solid (136 mg, 82%): mp 92 °C. 1H NMR (CDCl3) d 8.13 (d,
J = 7.8 Hz, 1H), 8.50 (d, J = 1.5 Hz, 1H), 8.02 (s, 1H), 7.58 (s, 1H), 7.55
(s, 1H), 7.48 (dt, J = 1.5, 8.4 Hz, 2H), 7.39 (d, J = 7.2 Hz, 1H), 7.22 (dd,
J = 1.0, 8. 1 Hz, 1H), 2.37 (s, 3H); 13C NMR (CDCl3) d 164.77, 154.92,
141.11, 134.48, 131.41, 128.77, 128.50, 128.16, 126.48, 121.33,
114.21, 20.91; CIMS (m/z, rel intensity) 330/332 (MH+, 100/98);
HRMS (EI), m/z M+ 328.9876, Calcd for C16H12BrNS 328.9874; HPLC
purity (C-18 reverse phase column): 100.00% (methanol/H2O,
95:5).
4.5.18. 2-(4-Bromo-2-methylphenyl)-4-(3-methoxyphenyl)
thiazole (9s)
Colorless oil (89 mg, 49%). 1H NMR (CDCl3)
d 7.67 (d,
J = 8.1 Hz, 1H), 7.58 (dd, J = 7.8, 1.5 Hz, 1H), 7.50 (m, 3H), 7.42
(dd, J = 8.4, 1.8 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 6.92 (dd, J = 8.4,
1.8 Hz, 1H), 3.89 (s, 3H), 2.67 (s, 3H); 13C NMR (CDCl3)
d
166.24, 159.95, 155.59, 138.72, 135.72, 134.35, 131.82, 131.18,
129.79, 129.19, 123.51, 118.77, 113.77, 113.56, 112.03, 55.31,
21.66; EIMS (m/z, rel intensity) 362/360 (MH+, 98/100); HRMS
(EI), m/z M+ 358.9979, Calcd for C17H14BrNOS 358.9982; HPLC
purity (C-18 reverse phase column): 97.48% (methanol/H2O,
95:5).
4.5.13. 2-(4-n-Butylphenyl)-4-phenylthiazole (9m)
White solid (101 mg, 68%): mp 47 °C. 1H NMR (CDCl3) d 8.09 (d,
J = 1.5 Hz, 1H), 8.06 (s, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.51 (dt, J = 1.5,
8.7 Hz, 2H), 7.44 (s, 1H), 7.42 (m, 1H), 7.32 (d, J = 8.4 Hz, 2H), 2.71
(t, J = 7.5 Hz, 2H), 1.69 (m, 2H), 1.44 (m, 2H), 1.02 (d, J = 7.5 Hz, 3H);