T. Prashanth et al. / European Journal of Medicinal Chemistry 87 (2014) 274e283
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AreH), 9.8 (s, 1H, COOH). LC-MS m/z 284 (Mþ1). Anal. Calcd for
was washed with water (25 mL ꢁ 3), dried over anhydrous sodium
sulphate, concentrated to a syrupy liquid and recrystallized twice
from diethyl ether to afford compounds 10aen in good yield.
10a: 2-(4-Benzoyl-2-methyl-phenoxy)-N-(4-phenyl-thiazol-2-
yl)-acetamide. Yield 77%. mp 110e112 ꢀC. FT-IR (KBr, cmꢂ1): 1675
C
17H16O4: C, 71.82; H, 5.67. Found: C, 71.80; H, 5.70%.
6c: Yield 85%. mp 114e116 ꢀC. FT-IR (KBr, cmꢂ1): 1650 (C]O),
1730 (acid C]O), 3450e3540 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
d
2.3 (s, 3H, CH3), 4.44 (s, 2H, OCH2), 6.9e7.55 (m, 7H, AreH), 9.3 (s,
1H, COOH). LC-MS m/z 288 (Mþ1). Anal. Calcd for C16H13FO4: C,
(C]O), 1698 (C]N), 3176 (NeH). 1H NMR (DMSO-d6):
d
2.49 (s, 3H,
CH3), 5.0 (s, 2H, OCH2), 6.8e7.9 (m, 14H, AreH), 9.85 (s, 1H, NH). 13
NMR (CDCl3): 194.2, 169.3, 164.2, 162.3, 155.8, 138.4, 133.0, 132.4,
66.66; H, 4.55. Found: C, 66.63; H, 4.59%.
C
6d: Yield 82%. mp 140e142 ꢀC. FT-IR (KBr, cmꢂ1): 1655 (C]O),
1725 (acid C]O), 3410e3520 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
d
131.9, 131.5, 130.3, 129.2, 128.7, 128.4, 127.5, 124.2, 113.9, 108.5, 66.9,
16.4. LC-MS m/z 429.1 (Mþ1). Anal. Calcd for C25H20N2O3S: C,
70.07; H, 4.70; N, 6.54; S, 7.48. Found: C, 70.01; H, 4.72; N, 6.51; S,
7.49%.
d
2.3 (s, 3H, CH3), 2.6 (s, 3H, CH3), 4.46 (s, 2H, OCH2), 7.4e7.8 (m, 7H,
AreH), 9.7 (s, 1H, COOH). LC-MS m/z 284 (Mþ1). Anal. Calcd for
C
17H16O4: C, 71.81; H, 5.67. Found: C, 71.85; H, 5.69%.
6e: Yield 75%. mp 120e122 ꢀC. FT-IR (KBr, cmꢂ1): 1675 (C]O),
10b:
2-(4-Benzoyl-2-methyl-phenoxy)-N-[4-(4-methoxy-
1730 (acid C]O), 3455e3550 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
phenyl)-thiazol-2-yl]-acetamide. Yield 72%. mp 115e117 ꢀC. FT-IR
d
2.4 (s, 3H, CH3), 4.46 (s, 2H, OCH2), 7.3e7.9 (m, 7H, AreH), 9.6 (s,
(KBr, cmꢂ1): 1675 (C]O), 1698 (C]N), 3176 (NeH). 1H NMR
1H, COOH). LC-MS m/z 348 (Mþ1). Anal. Calcd for C16H13BrO4: C,
(DMSO-d6):
d
2.49 (s, 3H, CH3), 3.76 (s, 3H, OCH3), 5.0 (s, 2H, OCH2),
194.3,
55.04; H, 3.75. Found: C, 55.04; H, 3.79%.
6.8e7.9 (m, 13H, AreH), 9.85 (s, 1H, NH). 13C NMR (CDCl3):
d
6f: Yield 80%. mp 112e115 ꢀC. FT-IR (KBr, cmꢂ1): 1655 (C]O),
1733 (acid C]O), 3450e3540 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
169.3, 164.2, 162.3, 160.6, 156.1, 138.4, 132.4, 131.9, 131.5, 130.3,
128.5, 125.3, 124.2, 114.8, 113.9, 108.4, 66.9, 55.8, 16.4. LC-MS m/z
459.1 (Mþ1). Anal. Calcd for C26H22N2O4S: C, 68.10; H, 4.84; N, 6.11;
S, 6.99. Found: C, 68.09; H, 4.81; N, 6.13; S, 6.98%.
d
2.3 (s, 3H, CH3), 4.44 (s, 2H, OCH2), 6.9e7.55 (m, 7H, AreH), 9.2 (s,
1H, COOH). LC-MS m/z 288 (Mþ1). Anal. Calcd for C16H13FO4: C,
66.66; H, 4.55. Found: C, 66.63; H, 4.59%.
10c:
2-[2-Methyl-4-(4-methyl-benzoyl)-phenoxy]-N-(4-
6g: Yield 75%. mp 128e130 ꢀC. FT-IR (KBr, cmꢂ1): 1655 (C]O),
1740 (acid C]O), 3410e3520 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
phenyl-thiazol-2-yl)-acetamide. Yield 78%. mp 150e152 ꢀC. FT-IR
(KBr, cmꢂ1): 1675 (C]O), 1698 (C]N), 3176 (NeH). 1H NMR
d
4.46 (s, 2H, OCH2), 7.3e7.9 (m, 8H, AreH), 9.9 (s, 1H, COOH). LC-
(DMSO-d6):
d
2.49 (s, 6H, CH3), 5.0 (s, 2H, OCH2), 6.8e7.9 (m, 13H,
194.6, 169.3, 164.2,
MS m/z 333 (Mþ1). Anal. Calcd for C15H11BrO4: C, 53.76; H, 3.31.
AreH), 9.85 (s, 1H, NH). 13C NMR (CDCl3):
d
Found: C, 53.74; H, 3.36%.
162.3, 155.2, 142.1, 135.4, 133.0, 131.9, 131.5, 130.2, 129.2, 128.7,
128.3, 127.5, 124.2, 113.9, 105.2, 66.9, 21.3, 16.7. LC-MS m/z 443.1
(Mþ1). Anal. Calcd for C26H22N2O3S: C, 70.57; H, 5.01; N, 6.33; S,
7.25. Found: C, 70.54; H, 5.04; N, 6.30; S, 7.26%.
6h: Yield 75%. mp 128e130 ꢀC. FT-IR (KBr, cmꢂ1): 1655 (C]O),
1740 (acid C]O), 3410e3520 cmꢂ1 (acid OH). 1H NMR (DMSO-d6):
d
4.46 (s, 2H, OCH2), 7.3e7.9 (m, 8H, AreH), 9.9 (s, 1H, COOH). LC-
MS m/z 333 (Mþ1). Anal. Calcd for C15H11BrO4: C, 53.76; H, 3.31.
10d: N-[4-(4-Methoxy-phenyl)-thiazol-2-yl]-2-[2-methyl-4-(4-
methyl-benzoyl)-phenoxy-acetamide. Yield 81%. mp 137e139 ꢀC.
FT-IR (KBr, cmꢂ1): 1675 (C]O), 1698 (C]N), 3176 (NeH). 1H NMR
Found: C, 53.74; H, 3.36%.
4.1.5. General procedure for the synthesis of 2-amino-4-phenyl
thiazoles (9aeb)
(DMSO-d6):
d
2.49 (s, 6H, CH3), 3.76 (s, 3H, OCH3), 5.0 (s, 2H, OCH2),
194.5,
6.8e7.9 (m, 12H, AreH), 9.85 (s, 1H, NH). 13C NMR (CDCl3):
d
2-Amino-4-phenyl thiazoles (9aeb) were synthesized by using
substituted acetophenones (7aeb) (0.0037 mol) and thiourea (8)
(0.004 mol). The reaction mixture was refluxed for 16 h in the
presence of iodine (0.0074 mol) and ethanol as a solvent. The
product was basified with sodium hydroxide solution to get the
white solid. The product was recrystallized from ethanol to get
needle like crystals [31].
169.3,164.2,162.3,160.6,155.1,142.1,135.4,131.9,131.5,130.2,128.6,
128.3, 125.3, 124.2, 114.8, 113.9, 107.4, 66.9, 55.8, 22.1, 16.4. LC-MS
m/z 473.1 (Mþ1). Anal. Calcd for C27H24N2O4S: C, 68.62; H, 5.12;
N, 5.93; S, 6.79. Found: C, 68.60; H, 5.15; N, 5.91; S, 6.80%.
10e: 2-[4-(4-Fluoro-benzoyl)-2-methyl-phenoxy]-N-(4-phenyl-
thiazol-2-yl)-acetamide. Yield 83%. mp 160e162 ꢀC. FT-IR (KBr,
cmꢂ1): 1675 (C]O), 1698 (C]N), 3176 (NeH). 1H NMR (DMSO-d6):
9a: 2-Amino-4-phenyl thiazole. Yield 90%. mp 148e149 ꢀC. FT-
d
2.49 (s, 3H, CH3), 5.0 (s, 2H, OCH2), 6.8e7.9 (m,13H, AreH), 9.85 (s,
IR (KBr, cmꢂ1): 1698 (C]N), 3376 (NeH). 1H NMR (DMSO-d6):
1H, NH). 13C NMR (CDCl3):
d
194.1, 169.3, 166.6, 164.2, 162.3, 160.6,
d
6.8e7.6 (m, 6H, AreH), 7.8 (bs, 2H, NH2). LC-MS m/z 177 (Mþ1).
158.0, 134.0, 133.4, 133.0, 131.9, 131.5, 129.2, 128.7, 128.3, 127.5,
124.2, 115.2, 113.9, 106.4, 67.0, 16.6. LC-MS m/z 447.1 (Mþ1). Anal.
Calcd for C25H19FN2O3S: C, 67.25; H, 4.29; N, 6.27; S, 7.18. Found: C,
67.26; H, 4.25; N, 6.29; S, 7.19%.
Anal. Calcd for C9H8N2S: C, 61.33; H, 4.58; N, 15.90; S, 18.19. Found:
C, 61.30; H, 4.56; N, 15.95; S, 18.18%.
9b: 4-(4-Methoxy-phenyl)-thiazol-2-ylamine. Yield 85%. mp
168e170 ꢀC. FT-IR (KBr, cmꢂ1): 1698 (C]N), 3376 (NeH). 1H NMR
(DMSO-d6):
NH2). LC-MS m/z 207 (Mþ1). Anal. Calcd for C10H10N2OS: C, 58.23;
H, 4.89; N, 13.58; S, 15.55. Found: C, 58.22; H, 4.88; N, 13.59; S,
15.56%.
10f: 2-(4-Benzoyl-2,6-dimethyl-phenoxy)-N-(4-phenyl-thiazol-
2-yl)-acetamide. Yield 75%. mp 145e147 ꢀC. FT-IR (KBr, cmꢂ1): 1675
(C]O), 1698 (C]N), 3176 (NeH). 1H NMR (DMSO-d6): d d 2.49 (s,
6H, CH3), 5.0 (s, 2H, OCH2), 6.8e7.7 (m, 13H, AreH), 9.85 (s, 1H, NH).
d 3.5 (s, 3H, OCH3), 6.8e7.6 (m, 5H, AreH), 7.8 (bs, 2H,
13C NMR (CDCl3):
d 194.1, 169.5, 164.2, 161.4, 157.2, 138.4, 133.0,
132.4, 131.8, 130.3, 129.2, 128.7, 128.5, 127.5, 124.1, 107.4, 67.2, 16.1.
LC-MS m/z 443.1 (Mþ1). Anal. Calcd for C26H22N2O3S: C, 70.57; H,
5.01; N, 6.33; S, 7.25. Found: C, 70.53; H, 5.03; N, 6.31; S, 7.26%.
10g: 2-(4-Benzoyl-2,6-dimethyl-phenoxy)-N-[4-(4-methoxy-
phenyl)-thiazol-2-yl]-acetamide. Yield 75%. mp 120e122 ꢀC. FT-IR
(KBr, cmꢂ1): 1675 (C]O), 1698 (C]N), 3176 (NeH). 1H NMR
4.1.6. General procedure for the synthesis of 2-(4-benzoyl-
phenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10aen)
To the compounds 6aeh (0.0037 mol) in dry dichloromethane
(15 mL), lutidine (1.2 vol.) was added at 25e30 ꢀC, followed by the
addition of 9aeb (0.0037 mol) and the mixture was stirred at
25e30 ꢀC for 30 min. The reaction was cooled to 0e5 ꢀC and TBTU
(0.0037 mol) was added over a period of 30 min while maintaining
the temperature below 5 ꢀC. The reaction was stirred overnight and
monitored by TLC using chloroform:methanol (9:1) as an eluent.
The reaction mixture was diluted with 20 mL of dichloromethane
and washed with 1.5 N hydrochloric acid (20 mL). The organic layer
(DMSO-d6):
d
2.49 (s, 6H, CH3), 3.76 (s, 3H, OCH3), 5.0 (s, 2H, OCH2),
194.2,
6.8e7.8 (m, 12H, AreH), 9.85 (s, 1H, NH). 13C NMR (CDCl3):
d
169.6,164.1,161.4, 160.6,157.4, 138.4,132.4,131.8, 131.8,130.3,128.5,
125.3, 124.1, 114.8, 106.2, 55.9, 16.2. LC-MS m/z 473.1 (Mþ1). Anal.
Calcd for C27H24N2O4S: C, 70.57; H, 5.01; N, 6.33; S, 6.79. Found:
70.53; H, 5.03; N, 6.34; S, 6.78%.