A. Meguellati et al. / European Journal of Medicinal Chemistry 80 (2014) 579e592
587
J ¼ 8.1, 7.1 Hz, 1H), 7.19 (dd, J ¼ 7.6, 7.1 Hz, 1H), 6.96 (s, 1H), 6.24 (s,
1H), 6.07 (s, 1H), 4.12 (d, J ¼ 7.4 Hz, 2H), 2.25e2.13 (m, 1H), 0.88 (d,
4 . 1. 2 . 2 4 . 2 - ( N - B e n z y l i n d o l - 3 - y l m e t h y l e n e ) - 4 , 6 -
dihydroxybenzofuran-3(2H)-one (28). The crude product was pre-
pared according to procedure A starting from 3 (212 mg,1.28 mmol)
and aldehyde 39g (200 mg, 0.85 mmol). After purification by col-
umn chromatography on silica gel (CH2Cl2/MeOH 9:1) and recrys-
tallization in acetonitrile, the pure product (186 mg, 0.48 mmol,
73%) was obtained as orange crystals. m.p. 280e281 ꢁC; 1H NMR
J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz, DMSO-d6)
d ppm 178.3 (C),167.0
(C), 166.5 (C), 157.9 (C), 145.3 (C), 136.3 (C), 133.2 (CH), 127.1 (C),
122.5 (CH), 120.6 (CH), 119.1 (CH), 110.9 (CH), 107.3 (C), 103.7 (C),
102.2 (CH), 97.5 (CH), 90.5 (CH), 53.2 (CH2), 29.0 (CH), 19.8
(2 ꢃ CH3); LRMS (ESIþ) m/z (%) 350 (100) [MþH]þ; HRMS (ESIþ) m/
z calc. for C21H20NO4 350.1387, found 350.1388.
(400 MHz, DMSO-d6)
d ppm 10.72 (bs, 2H), 8.28 (s, 1H), 7.98 (d,
J ¼ 7.3 Hz,1H), 7.51 (d, J ¼ 7.7 Hz,1H), 7.35e7.16 (m, 7H), 6.97 (s, 1H),
6.21 (s, 1H), 6.05 (s, 1H), 5.58 (s, 2H); 13C NMR (100 MHz, DMSO-d6)
4.1.2.21. 2-[N-(3-methylbut-2-enyl)indol-3-ylmethylene]-4,6-
dihydroxybenzofuran-3(2H)-one (25). The crude product was pre-
d
ppm 178.3 (C), 166.9 (C), 166.6 (C), 158.3 (C), 146.3 (CH), 145.5 (C),
137.4 (C), 135.9 (CH), 133.1 (C), 127.0 (C), 122.6 (2 ꢃ CH), 120.8
(2 ꢃ CH), 119.1 (CH), 118.4 (CH), 110.9 (CH), 109.2 (CH), 107.8 (C),
103.6 (C), 101.8 (CH), 97.5 (CH), 90.3 (CH), 49.5 (CH2); LRMS (ESIþ)
m/z (%) 384 (100) [MþH]þ; HRMS (ESIþ) m/z calc. for C24H18NO4
384.1230, found 384.1230.
pared according to procedure
A starting from 3 (100 mg,
0.60 mmol) and aldehyde 39d (300 mg, 1.41 mmol). After purifi-
cation by column chromatography on silica gel (cyclohexane/EtOAc
1:1), the pure product (173 mg, 0.48 mmol, 80%) was obtained as a
yellow powder. m.p. 251e252 ꢁC; 1H NMR (400 MHz, DMSO-d6)
d
ppm 10.75 (s, 1H), 10.73 (s, 1H), 8.11 (s, 1H), 7.97 (d, J ¼ 7.7 Hz, 1H),
4.1.2.25. 2-(N-3-Methylbenzylindol-3-ylmethylene)-4,6-
dihydroxybenzofuran-3(2H)-one (29). The crude product was pre-
7.48 (d, J ¼ 8.1 Hz, 1H), 7.25 (dd, J ¼ 8.1, 6.9 Hz, 1H), 7.19 (dd, J ¼ 7.7,
6.9 Hz, 1H), 6.96 (s, 1H), 6.23 (s, 1H), 6.06 (s, 1H), 5.43e5.30 (m, 1H),
4.91 (d, J ¼ 6.7 Hz, 2H), 1.87 (s, 3H), 1.73 (s, 3H); 13C NMR (100 MHz,
pared according to procedure
A starting from 3 (200 mg,
1.20 mmol) and aldehyde 39h (200 mg, 0.80 mmol). After purifi-
cation by column chromatography on silica gel (CH2Cl2/MeOH 9:1)
and recrystallization in acetonitrile, the pure product (171 mg,
0.43 mmol, 54%) was obtained as orange crystals. m.p. 262e263 ꢁC;
DMSO-d6)
d ppm 178.3 (C), 166.9 (C), 166.5 (C), 157.9 (C), 145.3 (C),
136.2 (C), 135.8 (CH), 132.5 (C), 127.3 (C), 122.4 (CH), 120.7 (CH),
119.8 (CH), 119.0 (CH), 110.7 (CH), 107.5 (C), 103.6 (C), 102.1 (CH),
97.5 (CH), 90.3 (CH), 44.2 (CH2), 25.3 (CH3), 17.9 (CH3); LRMS (ESIþ)
m/z (%) 362 (100) [M þ H]þ; HRMS (ESIþ) m/z calc. for C22H20NO4
362.1387, found 362.1390.
1H NMR (400 MHz, DMSO-d6)
d ppm 10.74 (bs, 2H), 8.28 (s, 1H),
8.00 (d, J ¼ 7.1 Hz, 1H), 7.52 (d, J ¼ 7.4 Hz, 1H), 7.23e7.04 (m, 6H),
6.99 (s, 1H), 6.23 (s, 1H), 6.08 (s, 1H), 5.54 (s, 2H), 2.27 (s, 3H); 13C
NMR (100 MHz, DMSO-d6)
d ppm 178.3 (C), 166.9 (C), 166.7 (C),
158.3 (C), 145.5 (C), 137.8 (CH), 137.3 (C), 136.0 (C), 133.2 (CH), 128.6
(CH), 128.2 (C), 127.6 (CH), 127.4 (C), 124.2 (CH), 122.6 (CH), 120.8
(CH),119.1 (CH),110.9 (CH), 107.8 (C),103.7 (C),101.9 (CH), 97.6 (CH),
90.3 (CH), 49.6 (CH2), 21.0 (CH3); LRMS (ESIþ) m/z (%) 416 (18)
[MþH2OþH]þ, 398 (100) [MþH]þ; HRMS (ESIþ) m/z calc. for
4.1.2.22. 2-[N-(3-Carboxypropyl)indol-3-ylmethylene]-4,6-
dihydroxybenzofuran-3(2H)-one (26). The crude product was pre-
pared according to procedure
A starting from 3 (100 mg,
0.60 mmol) and aldehyde 39e (191 mg, 0.90 mmol). After purifi-
cation by column chromatography on silica gel (cyclohexane/
EtOAc/AcOH 2:1:0.005), the pure product (127 mg, 0.34 mmol, 56%)
was obtained as a yellow powder. m.p. 253e254 ꢁC; 1H NMR
C25H20NO4 398.1387, found 398.1386.
4.1.2.26. 2-(N-3-Methoxybenzylindol-3-ylmethylene)-4,6-
dihydroxybenzofuran-3(2H)-one (30). The crude product was pre-
(400 MHz, DMSO-d6)
d ppm 12.21 (bs, 1H), 10.76 (bs, 2H), 8.12 (s,
1H), 7.98 (d, J ¼ 7.8 Hz, 1H), 7.59 (d, J ¼ 8.1 Hz, 1H), 7.27 (dd, J ¼ 8.1,
6.8 Hz, 1H), 7.19 (dd, J ¼ 7.8, 6.8 Hz, 1H), 6.96 (s, 1H), 6.24 (s, 1H),
6.07 (s, 1H), 4.33 (t, J ¼ 6.6 Hz, 2H), 2.26 (t, J ¼ 7.2 Hz, 2H), 2.10e1.94
pared according to procedure
A starting from 3 (150 mg,
0.90 mmol) and aldehyde 39i (450 mg, 1.78 mmol). After purifica-
tion by column chromatography on silica gel (cyclohexane/EtOAc
1:1), the pure product (268 mg, 0.65 mmol, 72%) was obtained as a
yellow powder. m.p. 248e249 ꢁC; 1H NMR (400 MHz, DMSO-d6)
(m, 2H); 13C NMR (100 MHz, DMSO-d6)
d ppm 178.3 (C), 173.9 (C),
167.0 (C), 166.5 (C), 157.9 (C), 145.4 (C), 136.0 (C), 132.8 (CH), 127.2
(C),122.6 (CH),120.7 (CH),119.2 (CH),110.5 (CH),107.6 (C),103.6 (C),
102.1 (CH), 97.5 (CH), 90.4 (CH), 45.3 (CH2), 30.7 (CH2), 25.3 (CH2);
LRMS (ESIþ) m/z (%) 380 (100) [MþH]þ; HRMS (ESIþ) m/z calc. for
d
ppm 10.77 (s, 1H), 10.74 (s, 1H), 8.28 (s, 1H), 7.99 (d, J ¼ 7.4 Hz, 1H),
7.52 (d, J ¼ 7.7 Hz, 1H), 7.30e7.12 (m, 3H), 6.97 (s, 1H), 6.91e6.80 (m,
2H), 6.77 (d, J ¼ 7.7 Hz, 1H), 6.22 (s, 1H), 6.07 (s, 1H), 5.54 (s, 2H),
C
21H18NO6 380.1129, found 380.1131.
3.71 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d ppm 178.3 (C), 167.0
(C), 166.6 (C), 159.4 (C), 157.9 (C), 145.6 (C), 139.1 (CH), 136.0 (C),
133.3 (C), 129.9 (CH), 127.4 (C), 122.7 (CH), 120.9 (CH), 119.1
(2 ꢃ CH), 113.2 (CH), 112.5 (CH), 111.0 (CH), 107.9 (C), 103.6 (C), 102.0
(CH), 97.5 (CH), 90.4 (CH), 55.1 (CH3), 49.5 (CH2); LRMS (ESIþ) m/z
(%) 414 (100) [MþH]þ, 338 (2); HRMS (ESIþ) m/z calc. for
4.1.2.23. 2-(N-cyclohexylmethylindol-3-ylmethylene)-4,6-
dihydroxybenzofuran-3(2H)-one (27). The crude product was pre-
pared according to procedure A starting from 3 (207 mg,1.25 mmol,
1.5 equiv.) and aldehyde 39f (200 mg, 0.83 mmol). After purification
by column chromatography on silica gel (CH2Cl2/MeOH 9:1) and
recrystallization in acetonitrile, the pure product (247 mg,
0.72 mmol, 87%) was obtained as orange crystals. m.p. 232e233 ꢁC;
C
25H20NO5 414.1356, found 414.1338.
4.1.2.27. 2-(N-3-Bromobenzylindol-3-ylmethylene)-4,6-
dihydroxybenzofuran-3(2H)-one (31). The crude product was pre-
1H NMR (400 MHz, DMSO-d6)
d
ppm 10.75 (bs, 2H), 8.00 (s, 1H),
7.96 (d, J ¼ 7.5 Hz, 1H), 7.58 (d, J ¼ 7.8 Hz, 1H), 7.25 (dd, J ¼ 7.8,
7.2 Hz,1H), 7.18 (dd, J ¼ 7.5, 7.2 Hz,1H), 6.94 (s, 1H), 6.23 (s,1H), 6.05
(s, 1H), 4.14 (d, J ¼ 7.2 Hz, 2H), 1.88e1.84 (m, 1H), 1.65e1.50 (m, 5H),
pared according to procedure A starting from 3 (100 mg,
0.60 mmol) and N-(3-bromobenzyl)indole-3-carboxaldehyde [30]
(400 mg, 1.27 mmol). After purification by column chromatog-
raphy on silica gel (cyclohexane/EtOAc 1:1), the pure product
(171 mg, 0.37 mmol, 62%) was obtained as a yellow powder. m.p.
1.14e1.01 (m, 5H); 13C NMR (100 MHz, DMSO-d6)
d ppm 178.3 (C),
166.9 (C), 166.7 (C), 158.1 (C), 145.3 (C), 136.4 (C), 133.3 (CH), 127.0
(C),122.4 (CH),120.6 (CH),119.0 (CH),110.8 (CH),107.3 (C),103.7 (C),
102.0 (CH), 97.6 (CH), 90.3 (CH), 52.0 (CH2), 38.2 (CH), 30.1
(2 ꢃ CH2), 25.8 (CH2), 25.1 (2 ꢃ CH2); LRMS (ESIþ) m/z (%) 390 (100)
[M þ H]þ; HRMS (ESIþ) m/z calc. for C24H24NO4 390.1700, found
390.1699.
151e152 ꢁC; 1H NMR (400 MHz, DMSO-d6)
d ppm 10.78 (s, 1H),
10.75 (s, 1H), 8.32 (s, 1H), 7.99 (d, J ¼ 7.3 Hz, 1H), 7.60e7.40 (m, 3H),
7.35e7.13 (m, 4H), 6.98 (s, 1H), 6.22 (d, J ¼ 1.5 Hz, 1H), 6.08 (d,
J ¼ 1.5 Hz, 1H), 5.60 (s, 2H); 13C NMR (100 MHz, DMSO-d6)
d ppm
178.4 (C), 167.0 (C), 166.6 (C), 158.0 (C), 145.8 (C), 136.3 (CH), 136.1