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S. Kumar et al. / Bioorg. Med. Chem. 20 (2012) 4237–4244
4
2
(d, JCF = 3 Hz), 114.6, 114.4, 114.3, 114.1 (d, JCF = 22 Hz), 111.8,
108.8, 106.0, 69.0, 21.0; DART MS m/z calculated for C23H17FO4
(M+) 376.11; found 376.12. Anal. Calcd for C23H17FO4: C, 73.40;
H, 4.55. Found: C, 73.43; H, 4.53.
NMR (300 MHz, DMSO-d6): d 13.14 (br s, 1H, COOH), 7.89 (d,
J = 8 Hz, 2H, Ar-H), 7.88 (s, 1H, Ar-H), 7.83 (d, J = 8 Hz, 1H, Ar-H),
7.73–7.59 (m, 4H, Ar-H), 7.34 (d, J = 8 Hz, 2H, Ar-H), 7.11 (dd,
J = 2, 9 Hz, 1H, Ar-H), 5.28 (s, 2H, OCH2), 2.39 (s, 3H, CH3); 13C
NMR (75 MHz, DMSO-d6): 165.1, 160.8, 155.6, 148.7, 140.6,
132.1, 130.3, 130.0, 129.6, 129.4, 129.2, 129.0 128.5, 126.9, 124.9,
5.4.12. 5-[(3-Iodobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B12)
1
124.9, 124.7 (q, JCF = 272 Hz), 124.5, 124.4, 114.8, 112.3, 109.6,
Mp 140–142 °C, yield 89%; IR (cmꢀ1): 1674, 1597, 1558, 1458,
1412, 1381, 1288, 1196, 1095, 1026, 818, 779, 687, 663; 1H NMR
(300 MHz, DMSO-d6): d 7.99 (d, J = 8 Hz, 2H, Ar-H), 7.87 (s, 1H,
Ar-H), 7.71 (d, J = 8 Hz, 1H, Ar-H), 7.60–7.51 (m, 3H, Ar-H), 7.30
(d, J = 8 Hz, 2H, Ar-H), 7.21 (t, J = 8 Hz, 1H, Ar-H), 7.03 (dd, J = 2,
9 Hz, 1H, Ar-H), 5.13 (s, 2H, OCH2), 2.38 (s, 3H, CH3); 13C NMR
(75.5 MHz, DMSO-d6): 166.7, 154.8, 148.0, 139.9, 139.2, 136.4,
136.0, 130.5, 128.9, 128.6, 127.0, 126.9, 113.9, 111.4, 106.3, 94.7,
68.8, 20.9; DART MS m/z calculated for C23H17IO4 (M+) 484.02;
found 484.05. Anal. Calcd for C23H17IO4: C, 57.04; H, 3.54. Found:
C, 57.04; H, 3.50.
106.6, 69.5, 21.5; DART MS m/z calculated for C24H17F3O4 (M+)
426.11; found 426.13. Anal. Calcd for C24H17F3O4: C, 67.60; H,
4.02. Found: C, 67.64; H, 4.00.
5.4.17. 5-[(3,4-Difluorobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B17)
Mp 201–203 °C, yield 88%; IR (cmꢀ1): 1674, 1612, 1582, 1520,
1458, 1288, 1196, 1095, 1018, 941, 818, 779; 1H NMR (300 MHz,
DMSO-d6): 7.87 (d, J = 8 Hz, 2H, Ar-H), 7.59 (d, J = 9 Hz, 2H, Ar-H),
7.56 (d, J = 3 Hz, Ar-H), 7.48–7.32 (m, 4H, Ar-H), 7.08 (dd, J = 3,
9 Hz, Ar-H), 5.15 (s, 2H, OCH2), 2.38 (s, 3H, CH3); 13C NMR
1
(75.5 MHz, DMSO-d6): 165.1, 161.0, 155.6, 149.7 (dd, JCF = 251,
1
2
5.4.13. 5-[(4-Bromobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B13)
2JCF = 30 Hz), 149.5 (dd, JCF = 245, JCF = 29 Hz), 148.7, 140.7,
3
4
135.4 (dd, JCF = 5, JCF = 4 Hz), 129.6, 129.2, 128.4, 126.9, 124.9
Mp 225–226 °C, yield 82%; IR (cmꢀ1): 1674, 1582, 1458, 1366,
1281, 1188, 1095, 1011, 949, 849, 810, 764; 1H NMR (300 MHz,
DMSO-d6): d 13.02 (br s, 13.02, 1H, COOH), 7.88 (d, J = 8 Hz, 2H,
Ar-H), 7.60 (d, J = 8 Hz, 2H, Ar-H), 7.58–7.57 (m, 2H, Ar-H), 7.46
(d, J = 8 Hz, 2H, Ar-H), 7.34 (d, J = 8 Hz, 2H, Ar-H), 7.08 (dd, J = 2,
9 Hz, 1H, Ar-H), 5.16 (s, 2H, OCH2), 2.40 (s, 3H, CH3); 13C NMR
(75.5 MHz, DMSO-d6): 165.0, 161.0, 155.7, 148.6, 140.7, 137.1,
131.8, 130.2, 129.6, 129.2, 128.4, 126.9, 121.3, 114.9, 112.3,
109.4, 69.6, 21.5; DART MS m/z calculated for C23H17BrO4 (M+)/
(M+2+) 436.03/438.03; found 436.05/438.05. Anal. Calcd for
(dd, JCF = 7, JCF = 4 Hz), 117.9 (d, JCF = 17 Hz), 117.1 (d,
2JCF = 17 Hz), 114.9, 112.3, 109.3, 106.6, 69.1, 21.5; DART MS m/z
calculated for C23H16F2O4 (M+) 394.10; found 394.12. Anal. Calcd
for C23H16F2O4: C, 70.05; H, 4.09. Found: C, 70.06; H, 4.07.
3
4
2
5.4.18. 5-[(4-Fluorobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B18)
Mp 218–220 °C, yield 85%; IR (cmꢀ1): 1674, 1605, 1582, 1512,
1458, 1366, 1281,1227, 1188, 1095, 1011, 941, 825, 779; 1H NMR
(300 MHz, DMSO-d6): d 7.86 (d, J = 8 Hz, 2H, Ar-H), 7.59–7.51 (m,
4H, Ar-H), 7.32 (d, J = 8 Hz, 2H, Ar-H), 7.22 (t, J = 9 Hz, 2H, Ar-H),
7.06 (dd, J = 3, 9 Hz, 1H, Ar-H), 5.13 (s, 2H, OCH2), 2.38 (s, 3H,
CH3); 13C NMR (75.5 MHz, DMSO-d6): 165.09, 162.21 (d,
C
23H17BrO4: C, 63.17; H, 3.92. Found: C, 63.20; H, 3.91.
5.4.14. 5-[(3-Chlorobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B14)
4
1JCF = 244 Hz), 161.0, 155.8, 148.6, 140.7, 133.8 (d, JCF = 3 Hz),
Mp 184–186 °C, yield 81%; IR (cmꢀ1): 1674, 1605, 1574, 1458,
1366, 1281, 1196, 1095, 1026, 957, 818, 771, 679; 1H NMR
(300 MHz, DMSO-d6): d 13.02 (br s, 1H, COOH), 7.88 (d, J = 8 Hz,
2H, Ar-H), 7.62–7.57 (m, 3H, Ar-H), 7.47–7.42 (m, 3H, Ar-H), 7.34
(d, J = 8 Hz, 2H, Ar-H), 7.10 (dd, J = 2, 9 Hz, 1H, Ar-H), 5.21 (s, 2H,
OCH2), 2.41 (s, 3H, CH3); 13C NMR (75.5 MHz, DMSO-d6): 164.5,
160.4, 155.1, 148.1, 140.1, 139.7, 133.0, 130.2, 129.4, 129.1,
128.7, 127.8, 127.6, 127.2, 126.4, 126.1, 114.4, 111.8, 108.8,
106.0, 68.9, 21.0; DART MS m/z calculated for C23H17ClO4 (M+)
392.08; found 392.09. Anal. Calcd for C23H17ClO4: C, 70.32; H,
4.36. Found: C, 70.35; H, 4.34.
130.6 (d, JCF = 8 Hz), 129.6, 129.2, 128.3, 126.8, 115.7 (d,
3
2JCF = 21 Hz), 114.9, 112.3, 109.3, 106.5, 69.7, 21.5; DART MS m/z
calculated for C23H17FO4 (M+) 376.11; found 376.13. Anal. Calcd
for C23H17FO4: C, 73.40; H, 4.55. Found: C, 73.43; H, 4.55.
5.4.19. 5-[(2-Bromobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B19)
Mp 180–182 °C, yield 83%; IR (cmꢀ1): 1666, 1612, 1450, 1366,
1257, 1180, 1095, 1011, 949, 833, 756; 1H NMR (300 MHz,
DMSO-d6): d 7.88 (d, J = 8 Hz, 2H, Ar-H), 7.69 (dd, J =1, 8 Hz, 1H,
Ar-H), 7.65–7.57 (m, 4H, Ar-H), 7.44 (dt, J = 1, 8 Hz, 1H, Ar-H),
7.34 (d, J = 8 Hz, 1H, Ar-H), 7.30–7.28 (m, 1H, Ar-H), 7.09 (dd,
J = 2, 9 Hz, 1H, Ar-H), 5.19 (s, 2H, OCH2), 2.39 (s, 3H, CH3); 13C
NMR (75.5 MHz, DMSO-d6): 165.0, 161.0, 155.7, 148.7, 140.7,
136.4, 133.1, 130.7, 130.6, 129.6, 129.2, 128.4, 126.9, 123.3,
114.9, 112.4, 109.4, 106.5, 70.2, 21.5; DART MS m/z calculated for
5.4.15. 5-[(2,6-Difluorobenzyl)oxy]-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B15)
Mp 186–187 °C, yield 90%; IR (cmꢀ1): 1674, 1597, 1543, 1458,
1265, 1203, 1095, 1011, 833, 748; 1H NMR (300 MHz, DMSO-d6):
d 13.07 (br s, 1H, COOH), 7.90 (d, J = 8 Hz, 2H, Ar-H), 7.62–7.48
(m, 3H, Ar-H), 7.34 (d, J = 8 Hz, 2H, Ar-H), 7.18 (t, J = 8 Hz, 2H, Ar-
H), 7.06 (dd, J = 2, 9 Hz, 1H, Ar-H), 5.19 (s, 2H, OCH2), 2.40 (s, 3H,
CH3); 13C NMR (75.5 MHz, DMSO-d6): 165.1, 161.8 (d,
C
23H17BrO4 (M+)/(M+2+) 436.03/438.03; found 436.06/438.05.
Anal. Calcd for C23H17BrO4: C, 63.17; H, 3.92. Found: C, 63.20; H,
3.88.
1JCF = 249 Hz), 161.6 (d, JCF = 249 Hz), 161.0, 155.6, 148.8, 140.7,
132.1 (t, JCF = 11 Hz), 129.6, 129.2, 128.4, 126.9, 115.0, 113.1,
112.8, 112.4 (d, JCF = 25 Hz), 112.4, 112.2 (d, JCF = 25 Hz), 112.1,
109.5, 106.8, 59.1, 21.5; DART MS m/z calculated for C23H16F2O4
(M+) 394.10; found 394.11. Anal. Calcd for C23H16F2O4: C, 70.07;
H, 4.09. Found: C, 70.05; H, 4.10.
5.4.20. 5-([1,10-Biphenyl]-3-ylmethoxy)-2-(4-methylphenyl)-1-
benzofuran-3-carboxylic acid (B20)
1
3
2
2
Mp 150–152 °C, yield 80%; IR (cmꢀ1): 1674, 1605, 1551, 1504,
1458, 1288, 1196, 1095, 1018, 825, 795, 756, 702; 1H NMR
(300 MHz, DMSO-d6): d 7.94 (d, J = 8 Hz, 2H, Ar-H), 7.78 (s, 1H,
Ar-H), 7.68 (d, J = 8 Hz, 2H, Ar-H), 7.64–7.61 (m, 2H, Ar-H), 7.56
(d, J = 9 Hz, 1H, Ar-H), 7.50–7.35 (m, 5H, Ar-H), 7.31 (d, J = 8 Hz,
2H, Ar-H), 7.07 (dd, J = 3, 9 Hz, 1H, Ar-H), 5.23 (s, 2H, OCH2), 2.37
(s, 3H, CH3); 13C NMR (75.5 MHz, DMSO-d6): 165.7, 159.3, 155.7,
148.5, 140.8, 140.4, 140.1, 138.4, 129.5, 129.4, 129.3, 129.2,
129.0, 128.0, 127.3, 127.2, 126.6, 126.5, 114.7, 112.1, 111.3,
5.4.16. 2-(4-Methylphenyl)-5-{[3-(trifluoromethyl)benzyl]oxy}-
1-benzofuran-3-carboxylic acid (B16)
Mp 165–166 °C, yield 84%; IR (cmꢀ1): 1674, 1605, 1535, 1504,
1466, 1327, 1288, 1203, 1126, 1165, 1103, 887, 818, 764; 1H