R. Romagnoli et al. / European Journal of Medicinal Chemistry 108 (2016) 39e52
49
2.60; found: C, 48.78; H, 3.89; N, 2.48.
6.1.3.8. 2-Iodo-N-(2-(3,4,5-trimethoxybenzoyl)benzofuran-7-yl)acet-
amide (12). Following general procedure B, the crude residue pu-
rified by flash chromatography using ethyl acetate: petroleum
ether 1:1 (v:v) as eluent furnished 12 as a white solid. Yield: 78%;
6.1.3.3. 2-Iodo-N-[7-methoxy-2-(3,4,5-trimethoxybenzoyl)-1-
benzofuran-5-yl]acetamide (7). Following general procedure B, the
crude residue purified by flash chromatography using ethyl acetate:
petroleum ether 1:1 (v:v) as eluent furnished 7 as a yellow solid.
mp 193e195 ꢁC. 1H NMR (d6-DMSO)
d: 3.81 (s, 2H), 3.89 (s, 6H), 3.93
(s, 3H), 7.32 (s, 2H), 7.66 (d, J ¼ 8.4 Hz, 1H), 7.96 (s, 1H), 8.76 (t,
J ¼ 8.4 Hz, 1H), 9.09 (d, J ¼ 8.4 Hz,1H), 11.2 (bs, 1H). 13C NMR (CDCl3)
Yield: 71%; mp 190e191 ꢁC. 1H NMR (d6-DMSO)
d: 3.79 (s, 3H), 3.85
d: 1.49, 55.91 (2C), 56.02, 102.25, 103.22, 107.06 (2C), 126.21, 129.76,
(s, 2H), 3.88 (s, 6H), 3.97 (s, 3H), 7.22 (d, J ¼ 1.6 Hz, 1H), 7.29 (s, 2H),
130.01, 132.13, 135.66, 139.75, 141.56, 145.07, 148.01, 152.48, 166.51,
183.34. MS (ESI): [Mþ1]þ ¼ 496.1. Anal. calcd for C20H18INO6 C,
48.50; H, 3.66; N, 2.83; found: C, 48.30; H, 3.51; N, 2.63.
7.80 (d, J ¼ 1.6 Hz,1H), 7.88 (s,1H),10.5 (bs,1H). 13C NMR (d6-DMSO)
d: 1.44, 55.96 (2C), 60.12 (2C), 102.94, 104.45, 106.72 (2C), 117.38
(2C), 128.20, 131.67, 135.82, 141.52, 141.66, 144.96, 151.64, 152.65,
166.54, 181.97. MS (ESI): [Mþ1]þ
¼
526.6. Anal. calcd for
6.1.3.9. 2-Iodo-N-(2-(3,4,5-trimethoxybenzoyl)-1H-indol-3-yl)acet-
amide (13). Following general procedure B, the crude residue pu-
rified by flash chromatography using ethyl acetate: petroleum
ether 4:6 (v:v) as eluent furnished 13 as a cream colored solid.
C
21H20INO7 C, 48.02; H, 3.84; N, 2.67; found: C, 47.91; H, 3.70; N,
2.49.
Yield: 83%; mp 215e217 ꢁC. 1H NMR (CDCl3)
d: 3.90 (s, 6H), 3.93 (s,
6.1.3.4. 2-Iodo-N-(2-(3,4,5-trimethoxybenzoyl)benzofuran-4-yl)acet-
amide (8). Following general procedure B, the crude residue puri-
fied by flash chromatography using ethyl acetate: petroleum ether
4:6 (v:v) as eluent furnished 8 as a green solid. Yield: 78%; mp
5H), 7.05 (s, 2H), 7.16 (t, J ¼ 8.4 Hz, 1H), 7.38 (m, 2H), 8.13 (d,
J ¼ 8.4 Hz, 1H), 8.61 (bs, 1H), 10.1 (bs, 1H). 13C NMR (CDCl3)
: ꢂ1.04,
d
56.46 (2C), 61.11, 106.10 (2C), 112.00, 121.13 (2C), 120.96, 121.07,
122.55, 124.94, 125.05, 127.66, 133.23, 136.26, 153.44, 165.71, 187.34.
MS (ESI): [Mþ1]þ ¼ 495.3. Anal. calcd for C20H19IN2O5 C, 48.60; H,
3.87; N, 5.63; found: C, 48.34; H, 3.67; N, 5.38.
167e168 ꢁC. 1H NMR (CDCl3)
d
: 3.95 (s, 8H), 3.97 (s, 3H), 7.35 (s, 2H),
7.43 (m, 2H), 7.60 (m,1H), 7.64 (s,1H), 8.12 (bs,1H). 13C NMR (CDCl3)
d
: ꢂ0.53, 56.39 (2C), 61.07, 107.17 (2C), 109.69, 114.24, 115.98 (2C),
120.42, 128.86, 131.68, 131.81, 142.59, 151.48, 153.04, 156.31, 165.51,
182.96. MS (ESI): [Mþ1]þ ¼ 496.6. Anal. calcd for C20H18INO6 C,
48.50; H, 3.66; N, 2.83; found: C, 48.29; H, 3.51; N, 2.62.
6.1.3.10. 2-Iodo-N-(1-methyl-2-(3,4,5-trimethoxybenzoyl)-1H-indol-
3-yl)acetamide (14). Following general procedure B, the crude
residue purified by flash chromatography using ethyl acetate:pe-
troleum ether 4:6 (v:v) as eluent furnished 14 as a yellow solid.
6.1.3.5. 2-Iodo-N-[2-(3,4,5-trimethoxybenzoyl)-1-benzofuran-5-yl]
acetamide (9). Following general procedure B, the crude residue
purified by flash chromatography using ethyl acetate: petroleum
ether 1:1 (v:v) as eluent furnished 9 as a brown solid. Yield: 68%;
Yield: 79%; mp 239e241 ꢁC. 1H NMR (d6-DMSO)
d: 3.58 (s, 2H), 3.74
(s, 3H), 3.79 (s, 6H), 3.81 (s, 3H), 7.07 (s, 2H), 7.16 (t, J ¼ 8.0 Hz, 1H),
7.37 (t, J ¼ 8.0 Hz,1H), 7.55 (d, J ¼ 8.0 Hz, 1H), 7.61 (d, J ¼ 8.0 Hz,1H),
10.0 (bs, 1H). 13C NMR (d6-DMSO)
d: 0.112, 31.69, 56.22 (2C), 60.64,
mp 185e187 ꢁC. 1H NMR (d6-DMSO)
d: 3.79 (s, 3H), 3.86 (s, 2H), 3.89
107.25 (2C), 111.28, 116.93, 120.58 (2C), 122.28, 125.40, 128.82,
133.96, 133.78, 137.37, 142.38, 153.13, 166.95, 187.05. MS (ESI):
[Mþ1]þ ¼ 509.7. Anal. calcd for C21H21IN2O5 C, 48.60; H, 3.87; N,
5.67; found: C, 48.29; H, 3.59; N, 5.40.
(s, 6H), 7.29 (s, 2H), 7.53 (dd, J ¼ 9.2 and 2.0 Hz, 1H), 7.73 (d,
J ¼ 9.2 Hz, 1H), 7.91 (s, 1H), 8.27 (d, J ¼ 2.0 Hz, 1H), 10.5 (bs, 1H). 13
C
NMR (d6-DMSO) d: 1.41, 55.98 (2C), 60.12, 106.68 (2C), 112.41 (2C),
112.97 (2C), 117.30, 120.99, 127.08, 131.74, 135.11, 141.63, 151.72,
152.67, 166.57, 182.18. MS (ESI): [Mþ1]þ ¼ 496.5. Anal. calcd for
6 .1. 3 .11. 2 - I o d o - N - ( 7 - m e t h o x y - 1 - m e t h y l - 2 - ( 3 , 4 , 5 -
trimethoxybenzoyl)-1H-indol-3-yl)acetamide (15). Following gen-
eral procedure B, the crude residue purified by flash chromatog-
raphy using ethyl acetate: petroleum ether 1:1 (v:v) as eluent
furnished 15 as a yellow solid. Yield: 81%; mp 245e247 ꢁC. 1H NMR
C
20H18INO6 C, 48.50; H, 3.66; N, 2.83; found: C, 48.31; H, 3.47; N,
2.63.
6.1.3.6. 2-Iodo-N-(3-methyl-2-(3,4,5-trimethoxybenzoyl)benzofuran-
5-yl)acetamide (10). Following general procedure B, the crude
residue purified by flash chromatography using ethyl acetate: pe-
troleum ether 1:1 (v:v) as eluent furnished 10 as a pink solid. Yield:
(d6-DMSO)
(s, 3H), 6.84 (d, J ¼ 8.8 Hz, 1H), 7.06 (m, 3H), 7.09 (d, J ¼ 8.8 Hz, 1H),
9.96 (bs, 1H). 13C NMR (d6-DMSO)
d: 3.56 (s, 2H), 3.73 (s, 3H), 3.79 (s, 6H), 3.93 (s, 3H), 4.01
d: ꢂ0.45, 34.21, 55.67 (2C), 55.74,
80%; mp 173e175 ꢁC. 1H NMR (d6-DMSO)
d: 2.52 (s, 3H), 3.79 (s,
60.10, 105.58, 106.71 (2C), 112.38, 116.45, 120.61 (2C), 124.00,
126.69, 129.18, 133.02, 141.91, 147.66, 152.59, 166.38, 186.43. MS
(ESI): [Mþ1]þ ¼ 539.3. Anal. calcd for C22H23IN2O6 C, 49.08; H, 4.31;
N, 5.20; found: C, 48.89; H, 4.09; N, 5.03.
3H), 3.86 (s, 6H), 3.88 (s, 2H), 7.33 (s, 2H), 7.55 (dd, J ¼ 8.8 and
2.0 Hz, 1H), 7.69 (d, J ¼ 8.8 Hz, 1H), 8.17 (d, J ¼ 2.0 Hz, 1H), 10.5 (bs,
1H). 13C NMR (d6-DMSO)
d: 1.54, 9.82, 56.06 (2C), 60.23, 107.07 (2C),
110.83, 112.60, 121.20 (2C), 125.99, 128.68, 132.36, 134.98, 141.65,
148.22, 150.20, 152.61, 166.62, 183.77. MS (ESI): [Mþ1]þ ¼ 510.7.
Anal. calcd for C21H20INO6 C, 49.52; H, 3.96; N, 2.75; found: C,
49.37; H, 3.78; N, 2.61.
6.1.3.12. 2-Iodo-N-(2-(3,4-dimethoxybenzoyl)benzofuran-3-yl)acet-
amide (21). Following general procedure B, the crude residue pu-
rified by flash chromatography using ethyl acetate: petroleum
ether 4:6 (v:v) as eluent furnished 21 as a white solid. Yield: 83%;
6.1.3.7. 2-Iodo-N-(2-(3,4,5-trimethoxybenzoyl)benzofuran-6-yl)acet-
amide (11). Following general procedure B, the crude residue pu-
rified by flash chromatography using ethyl acetate: petroleum
ether 1:1 (v:v) as eluent furnished 11 as a yellow solid. Yield: 81%;
mp 174e176 ꢁC. 1H NMR (CDCl3)
d: 4.00 (s, 3H), 4.01 (s, 5H), 4.09 (s,
2H), 7.01 (d, J ¼ 8.4 Hz, 1H), 7.31 (m, 1H), 7.53 (m, 2H), 7.77 (d,
J ¼ 2.0 Hz, 1H), 8.13 (dd, J ¼ 8.4 and 2.0 Hz, 1H), 8.49 (d, J ¼ 8.0 Hz,
1H), 11.2 (bs, 1H). 13C NMR (CDCl3)
d
: ꢂ1.15, 56.15, 56.26, 110.34,
mp 188e190 ꢁC. 1H NMR (d6-DMSO)
d
: 3.78 (s, 3H), 3.88 (s, 8H), 7.27
(s, 2H), 7.42 (dd, J ¼ 8.4 and 1.6 Hz, 1H), 7.78 (d, J ¼ 8.4 Hz, 1H), 7.84
(s, 1H), 8.17 (s, 1H), 10.7 (bs, 1H). 13C NMR (d6-DMSO)
: 1.31, 55.98
111.98, 112.13, 120.85, 123.60, 125.34, 127.33, 127.40, 129.38, 129.78,
138.85, 149.12, 153.76, 154.48, 166.11, 184.06. MS (ESI):
[Mþ1]þ ¼ 466.6. Anal. calcd for C19H16INO5 C, 49.05; H, 3.47; N,
3.01; found: C, 48.79; H, 3.28; N, 2.89.
d
(2C), 60.09, 101.52, 106.58 (2C), 116.38, 117.36, 122.54, 124.06 (2C),
131.94, 139.55, 141.50, 151.28, 152.65, 155.68, 166.95, 181.83. MS
(ESI): [Mþ1]þ ¼ 496.7. Anal. calcd for C20H18INO6 C, 48.50; H, 3.66;
N, 2.83; found: C, 48.27; H, 3.48; N, 2.59.
6.1.3.13. 2-Iodo-N-(2-(4-methoxybenzoyl)benzofuran-3-yl)acet-
amide (22). Following general procedure B, the crude residue