C. Rochais et al. / European Journal of Medicinal Chemistry 44 (2009) 708e716
713
1132, 1014, 937, 755, 696 cmꢂ1. 1H NMR (400 MHz, CDCl3):
1699 (CO), 1515, 1461, 1340, 1251, 1179, 1026, 809 cmꢂ1
.
d ¼ 11.7 and 11.5 (br s, 1H, NH), 11.5 and 11.4 (br s, 1H, OH),
1H NMR (400 MHz, CDCl3): d ¼ 7.77 (s, 1H, H5), 7.42 (d,
3
0
0
0
0
7.45 (m, 10H, Harom), 7.15 (m, 6H, Harom), 7.07 and 7.04 (d,
2H, JH2 H3 ¼ 8.3 Hz, H2 and H6 ), 6.81 (d, 2H,
3
3
0
0
0
0
1H, JH2NH ¼ 2.9 Hz, H2), 6.89 and 6.87 (d, 1H,
JH3 H2 ¼ 8.3 Hz, H3 and H5 ), 6.67 (m, 2H, Hapyrrole), 6.28
(m, 2H, Hbpyrrole). 13C NMR (100 MHz, CDCl3): d ¼ 161.7,
143.6, 139.1, 134.1, 132.6, 128.7, 127.3, 126.5, 123.1,
120.3, 109.9. MS (EIþ) m/z: 333.1 (100), 331.1 (95), 288 (65).
3
3JH5H6 ¼ 2.7 Hz, H5), 6.58 and 6.37 (d, 1H, JH6H7 ¼ 3.4 Hz,
H7), 6.08 and 6.05 (dd, 1H, 3JH5H6 ¼ 2.7 Hz, 3JH6H7 ¼ 3.4 Hz,
H6), 5.26 (s, 4H, 2 CH2Ph), 3.87 (s, 6H, 2OCH3). 13C NMR
(100 MHz, CDCl3): d (E form) ¼ 149.9, 148.0, 147.8, 139.9,
139.2, 138.9, 137.2, 128.5, 127.8, 127.5, 125.8, 120.0,
119.0, 116.3, 112.8, 112.0, 111.9, 110.8, 105.1, 69.7, 55.7.
MS (EIþ) m/z: 385.1 (M, 15), 294.1 (10), 192.1 (20), 91.0
(100).
6.3.4. 4-(4-Fluorophenyl)-3-(1H-pyrrol-1-yl)-2-furoic acid
(14c)
This compound was obtained from 10c as described for 14b
as brown solid in 85% yield. Mp 208 ꢀC. IR (KBr): n ¼ 3100e
2500 (OH), 1684 (CO), 1603, 1479, 1262, 1162, 934,
829 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.74 (s, 1H,
6.3. Saponification procedure
0
0
0
0
H5), 7.00 (m, 2H, H5 and H6 ), 6.94 (m, 2H, H2 and H3 ),
6.67 (m, 2H, Hapyrrole), 6.28 (m, 2H, Hbpyrrole). 13C NMR
(100 MHz, CDCl3): d ¼ 165.7, 161.7, 159.6, 141.8, 132.2,
130.5, 128.6, 124.8, 120.3, 116.9, 116.5, 115.6, 110.7. MS
(EIþ) m/z: 271.1 (M, 30), 227.1 (Mþ ꢂ CO2H, 67).
6.3.1. 40-(4-Chlorophenyl)-10H-1,30-bipyrrole-20-carboxylic
acid (13a)
A solution of NaOH (0.8 g, 0.02 mol) in water (30 mL) was
added dropwise to a solution of ester 9a (3.1 g, 0.1 mol) in ac-
etone (30 mL). The reaction mixture was heated at 80 ꢀC for
3 h and the acetone was then evaporated under reduced pres-
sure. The aqueous solution was extracted with ether
(2 ꢁ 50 mL), acidified until pH ¼ 1 with an 1 N aqueous
HCl solution and finally extracted with EtOAc
(2 ꢁ 100 mL). The organic layer was washed with brine
(100 mL), dried (MgSO4) and evaporated to give 13a as beige
solid (2.86 g, 100%). Mp 264 ꢀC. IR (KBr): n ¼ 3342 (NH),
2530e2900 (OH), 1751 (CO), 1676, 1649, 1579, 1446,
6.3.5. 4-(4-Methylphenyl)-3-(1H-pyrrol-1-yl)-2-furoic acid
(14d)
This compound was obtained from 10d as described for
14b as brown solid in 90% yield. Mp 189 ꢀC. IR (KBr):
n ¼ 3100e2500 (OH), 1688 (CO), 1609, 1484, 1444, 1267,
1179, 1026, 809 cmꢂ1
.
1H NMR (400 MHz, CDCl3):
3
0
0
0
d ¼ 7.74 (s, 1H, H5), 7.10 (d, 2H, JH2 H3 ¼ 8.1 Hz, H2 and
3
0
0
0
0
0
H6 ), 6.85 (d, 2H, JH3 H2 ¼ 8.1 Hz, H3 and H5 ), 6.69 (m,
2H, Hapyrrole), 6.27 (m, 2H, Hbpyrrole), 3.32 (s, 3H, CH3). 13C
NMR (100 MHz, CDCl3): d ¼ 161.7, 142.6, 136.3, 134.1,
128.5, 126.3, 122.4, 120.7, 117.6, 114.2, 109.9, 25.2. MS
(EIþ) m/z: 267.2 (M, 60), 222.2 (M ꢂ CO2H, 17).
1291, 1084, 843, 730 cmꢂ1
.
1H NMR (400 MHz, DMSO):
d ¼ 12.5 (br s, 1H, OH), 12.2 (br s, 1H, NH), 7.18 (d, 2H,
3
3
0
0
0
0
JH2 H3 ¼ 8.4 Hz, H2 and H6 ), 7.10 (d, 1H, JH5NH ¼ 3.3 Hz,
H5), 6.83 (d, 2H, 3JH3 H2 ¼ 8.4 Hz, H3 and H5 ), 6.68 (m, 2H,
0
0
0
0
H
apyrrole), 6.24 (m, 2H, Hbpyrrole). 13C NMR (100 MHz,
DMSO): d ¼ 160.7, 131.8, 130.6, 128.3, 127.5, 126.8, 122.8,
120.5, 120.0, 118.1, 108.5. MS (EIþ) m/z: 286.0 (M, 12),
241.0 (M ꢂ COOH, 100), 206.0 (M ꢂ COOH ꢂ Cl, 76).
6.3.6. 4-(4-Methoxyphenyl)-3-(1H-pyrrol-1-yl)-2-furoic acid
(14e)
This compound was obtained from 10e as described for 14b
as brown solid in 80% yield. Mp 200 ꢀC. IR (KBr): n ¼ 3100e
2500 (OH), 1736 (CO), 1681, 1604, 1484, 1247, 1178, 931,
6.3.2. 40-(3,4-Dimethoxyphenyl)-10H-1,30-bipyrrole
-20-carboxylic acid (13g)
730 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.72 (s, 1H,
This compound was obtained from 9g as described for 13a
as beige solid in 100% yield. Mp 230 ꢀC. IR (KBr): n ¼ 3341
(NH), 2300e3100 (OH), 1667 (CO), 1573, 1482, 1438, 1250,
3
0
0
0
0
H5), 6.89 (d, 2H, JH2 H3 ¼ 8.1 Hz, H2 and H6 ), 6.82 (d,
3
0
0
0
0
2H, JH3 H2 ¼ 8.1 Hz, H3 and H5 ), 6.71 (m, 2H, Hapyrrole),
6.28 (m, 2H, Hbpyrrole), 3.79 (s, 3H, OCH3). 13C NMR
(100 MHz, CDCl3): d ¼ 161.7, 159.6, 142.6, 136.3, 134.1,
128.5, 126.3, 122.4, 120.7, 114.2, 109.9, 55.2. MS (EIþ) m/
z: 284.1 (Mþ, 10), 283.1 (M, 80), 238.1 (38).
1
1123, 719 cmꢂ1. H NMR (400 MHz, CDCl3): d ¼ 10.4 (br s,
3
1H, OH), 7.09 (d, 1H, JH5NH ¼ 3.4 Hz, H5), 6.77 (d, 1H,
3
0
0
0
JH5 H6 ¼ 8.2 Hz, H5 ), 6.72 (m, 2H, Hapyrrole), 6.71 (dd, 1H,
4
3
0
0
0
0
0
JH2 H6 ¼ 1.9 Hz, JH5 H6 ¼ 8.2 Hz, H6 ), 6.22 (m, 2H, Hbpyr-
4
0
0
0
JH2 H6 ¼ 1.9 Hz, H2 ), 3.84 (s, 3H, OCH3),
role), 6.21 (d, 1H,
3.61 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3):
d ¼ 161.5, 148.8, 147.6, 127.5, 125.7, 123.0, 122.8, 118.6,
118.5, 117.9, 111.2, 109.6, 108.7, 55.8, 55.5. MS (EIþ) m/z:
312.2 (M, 60), 268.2 (Mþ ꢂ COOH, 100).
6.3.7. 4-(3,4-Dichlorophenyl)-3-(1H-pyrrol-1-yl)-2-furoic
acid (14f)
This compound was obtained from 10f as described for 14b
as brown solid in 76% yield. Mp 232 ꢀC. IR (KBr): n ¼ 3100e
2500 (OH), 1689 (CO), 1615, 1472, 1362, 1251, 1193, 907,
6.3.3. 4-(4-Bromophenyl)-3-(1H-pyrrol-1-yl)-2-furoic
acid (14b)
This compound was obtained from 10b as described for
13a [using EtOH (50 mL) instead of acetone] as brown solid
in 81% yield. Mp 215 ꢀC. IR (KBr): n ¼ 3100e2500 (OH),
816 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.76 (s, 1H,
3
0
0
0
H5), 7.38 (d, 1H, JH5 H6 ¼ 8.3 Hz, H5 ), 7.17 (d, 1H,
4
4
3
0
0
0
0
0
JH2 H6 ¼ 1.7 Hz, H2 ), 6.75 (dd, 1H, JH6 H5 ¼ 8.3 Hz,
0
0
0
JH6 H2 ¼ 1.7 Hz, H6 ), 6.67 (m, 2H, Hapyrrole), 6.28 (m, 2H,
H
bpyrrole). 13C NMR (100 MHz, CDCl3): d ¼ 161.7, 143.0,