Journal of Medicinal Chemistry
ARTICLE
(400 MHz, DMSO) δ 7.95 (d, J = 6.8 Hz, 2H), 7.77 (d, J = 7.0 Hz, 2H),
7.58 (s, 2H), 7.40 (d, J = 8.3 Hz, 1H), 6.94 (d, J = 8.6 Hz, 1H), 3.86 (s,
3H), 3.83 (s, 3H), 3.77 (s, 3H). 1H NMR (400 MHz, CDCl3) δ 7.68
(dd, J = 23.7, 8.2 Hz, 5H), 7.59 (d, J = 15.9 Hz, 1H), 7.53 (d, J = 8.8 Hz,
1H), 6.78 (d, J = 8.8 Hz, 1H), 3.94 (s, 4H), 3.92 (s, 6H). 13C NMR (101
MHz, DMSO) δ 190.22, 157.48, 153.53, 142.08, 140.54, 139.21, 130.30
(q, J = 32.2 Hz), 126.26, 126.23, 125.79, 124.48 (q, J = 271.5 Hz),
108.41, 62.17, 60.97, 56.58. LCꢀMS (ESI-TOF): m/z 367.1158
([C19H17 F3O4 þ H]þ calcd 367.1152). Purity 100.00% (tR = 9.05 min).
(E)-1-(2,4,6-Methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)prop-2-
en-1-one (4k). It was obtained as a yellow oil in 86% yield. 1H NMR
(400 MHz, DMSO) δ 7.91 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H),
7.31 (d, J = 16.2 Hz, 1H), 7.11 (d, J = 16.2 Hz, 1H), 6.32 (s, 2H), 3.84 (s,
3H), 3.73 (s, 6H). 13C NMR (101 MHz, DMSO) δ 193.27, 162.66,
158.73, 141.53, 138.97 (d, J = 1.4 Hz), 130.33 (q, J = 32.2 Hz), 126.14 (q,
J = 3.8 Hz), 124.45 (q, J = 271.4 Hz), 111.28, 91.57, 91.40, 56.29, 55.94.
LCꢀMS (ESI-TOF): m/z 367.1152 ([C19H17 F3O4 þ H]þ calcd
367.1152). Purity 96.54% (tR = 8.03 min).
(E)-1-Phenyl-3-(2-nitrophenyl)prop-2-en-1-one (5a). It was ob-
tained as an off-white solid in 46% yield. 1H NMR (400 MHz, DMSO)
δ = 8.24ꢀ8.20 (m, 1H), 8.20ꢀ8.15 (m, 2H), 8.11 (dd, J = 8.1, 1.2 Hz,
1H), 8.00 (d, J = 15.5 Hz, 1H), 7.91 (d, J = 15.5 Hz, 1H), 7.88ꢀ7.81 (m,
1H), 7.76ꢀ7.68 (m, 2H), 7.60 (t, J = 7.6 Hz, 2H). 13C NMR (101 MHz,
DMSO) δ = 189.52, 149.24, 139.03, 137.48, 134.22, 133.98, 131.53,
130.19, 129.98, 129.33, 129.18, 126.83, 125.16. LCꢀMS (ESI-TOF):
m/z 254.0819 ([C15H11NO3 þ H]þ calcd 254.0812). Purity 100.00%
(tR = 6.68 min).
136.03, 134.33, 132.76, 131.63, 131.12, 130.48, 129.55, 125.14, 121.20,
106.68, 99.03, 56.48, 56.13. LCꢀMS (ESI-TOF): m/z 314.1027
([C17H15NO5 þ H]þ calcd 314.1023). Purity 97.57% (tR = 6.62 min).
(E)-1-(2,6-Dimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5f). It was obtained as a white solid in 82% yield. 1H NMR (400 MHz,
DMSO) δ = 8.06 (dd, J = 8.1, 1.2 Hz, 1H), 7.98 (dd, J = 7.8, 1.3 Hz, 1H),
7.78 (ddd, J = 7.8, 1.2, 0.6 Hz, 1H), 7.70ꢀ7.64 (m, 1H), 7.52 (d, J = 16.0
Hz, 1H), 7.40 (t, J = 8.4 Hz, 1H), 6.96 (d, J = 16.0 Hz, 1H), 6.77 (d, J =
8.4 Hz, 2H), 3.75 (s, 7H). 13C NMR (101 MHz, DMSO) δ = 194.37,
157.44, 148.75, 140.06, 134.33, 132.66, 131.72, 131.52, 129.86, 129.66,
125.21, 117.59, 104.80, 56.26. LCꢀMS (ESI-TOF): m/z 314.1024
([C17H15NO5 þ H]þ calcd 314.1023). Purity 100.00% (tR = 5.74 min).
(E)-1-(2,5-Dimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5g). It was obtained as a yellow solid in 49% yield. 1H NMR (400 MHz,
D2O) δ = 8.09 (dd, J = 8.1, 1.1 Hz, 1H), 7.97 (d, J = 7.7 Hz, 1H),
7.85ꢀ7.76 (m, 2H), 7.73ꢀ7.65 (m, 1H), 7.41 (d, J = 15.8 Hz, 1H), 7.16
(d, J = 1.8 Hz, 2H), 7.09 (t, J = 1.8 Hz, 1H), 3.84 (s, 3H), 3.76 (s, 3H).
13C NMR (101 MHz, D2O) δ = 191.59, 153.41, 152.61, 137.66, 134.31,
131.31, 131.11, 130.19, 129.56, 128.86, 125.14, 119.67, 114.33, 114.32,
56.74, 55.96. LCꢀMS (ESI-TOF): m/z 314.1029 ([C17H15NO5 þ H]þ
calcd 314.1023). Purity 100.00% (tR = 6.63 min).
(E)-1-(3,4-Dimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5h). It was obtained as a yellow solid in 17% yield. 1H NMR (400 MHz,
DMSO) δ = 8.20 (d, J = 7.8 Hz, 1H), 8.10 (dd, J = 8.1, 1.0 Hz, 1H),
7.99ꢀ7.88 (m, 3H), 7.84 (t, J = 7.6 Hz, 1H), 7.74ꢀ7.67 (m, 1H), 7.62
(d, J = 2.0 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H).
1H NMR (400 MHz, CDCl3) δ = 8.06ꢀ 8.12 (m, 2H), 7.74 (d, J = 7.7
Hz, 1H), 7.72ꢀ7.65 (m, 2H), 7.62 (d, J = 1.7 Hz, 1H), 7.56 (t, J = 7.2 Hz,
1H), 7.31 (d, J = 15.7 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 3.99 (s, 3H),
3.98 (s, 3H). 13C NMR (101 MHz, D2O) δ = 187.54, 153.92, 149.23,
149.15, 137.91, 134.06, 131.25, 130.35, 130.26, 129.89, 126.80, 125.02,
124.14, 111.33, 111.21, 56.22, 56.00. LCꢀMS (ESI-TOF): m/z
314.1027 ([C17H15NO5 þ H]þ calcd 314.1023). Purity 100.00%
(tR = 5.63 min).
(E)-1-(3,5-Dimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5i). It was obtained as an off-white solid in 57% yield. 1H NMR (400
MHz, DMSO) δ = 8.21 (dd, J = 7.8, 1.3 Hz, 1H), 8.10 (dd, J = 8.1, 1.2
Hz, 1H), 7.98 (d, J = 15.5 Hz, 1H), 7.89ꢀ7.80 (m, 2H), 7.74ꢀ7.68 (m,
1H), 7.28 (d, J = 2.3 Hz, 2H), 6.82 (t, J = 2.3 Hz, 1H), 3.85 (s, 6H). 13C
NMR (101 MHz, DMSO) δ = 189.21, 161.19, 149.24, 139.53, 139.25,
134.18, 131.52, 130.15, 130.09, 126.89, 125.13, 106.91, 105.89, 56.05.
LCꢀMS (ESI-TOF): m/z 314.1024 ([C17H15NO5 þ H]þ calcd
314.1023). Purity 100.00% (tR = 7.21 min).
(E)-1-(3,4,5-Trimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5j). It was obtained as an off-white solid in 31% yield. 1H NMR (400
MHz, DMSO) δ = 8.13 (dd, J = 27.6, 8.0 Hz, 2H), 7.97 (d, J = 15.4 Hz,
1H), 7.92ꢀ7.79 (m, 2H), 7.70 (t, J = 7.7 Hz, 1H), 7.42 (s, 2H), 3.88 (s,
6H), 3.76 (s, 3H). 13C NMR (101 MHz, DMSO) δ = 188.38, 153.39,
149.18, 142.64, 139.01, 134.20, 132.84, 131.45, 130.35, 130.12, 126.80,
125.16, 106.80, 60.66, 56.65. LCꢀMS (ESI-TOF): m/z 344.1130
([C18H17NO6 þ H]þ calcd 344.1129). Purity 99.00% (tR = 6.25 min).
(E)-1-(2,3,4-Trimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5k). It was obtained as a light white solid in 32% yield. 1H NMR (400
MHz, DMSO) δ = 8.07 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 7.6 Hz, 1H),
7.85ꢀ7.75 (m, 2H), 7.67 (t, J = 7.7 Hz, 1H), 7.43 (dd, J = 12.2 Hz, 3.2
Hz, 2H), 6.95 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H), 3.84 (s, 3H), 3.77 (s, 3H).
LCꢀMS (ESI-TOF): m/z 344.1127 ([C18H17NO6 þ H]þ calcd
344.1129). Purity 100.00% (tR = 6.52 min).
(E)-1-(2-Methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one (5b).
1
It was obtained as a light yellow solid in 49% yield. H NMR (400
MHz, DMSO) δ = 8.09 (dd, J = 8.2, 1.2 Hz, 1H), 7.99 (dd, J = 7.9, 1.2
Hz, 1H), 7.84ꢀ7.76 (m, 2H), 7.73ꢀ7.66 (m, 1H), 7.61ꢀ7.57 (m, 1H),
7.55 (dd, J = 7.7, 1.7 Hz, 1H), 7.42 (d, J = 15.7 Hz, 1H), 7.22 (d, J = 8.0
Hz, 1H), 7.08 (td, J = 7.5, 0.9 Hz, 1H), 3.90 (s, 3H). 13C NMR (101
MHz, DMSO) δ = 192.08, 158.46, 149.07, 137.47, 134.36, 134.07,
131.33, 130.24, 130.22, 129.62, 128.56, 125.20, 121.06, 112.82, 56.32.
LCꢀMS (ESI-TOF): m/z 284.0916 ([C16H13NO4 þ H]þ calcd
284.0917). Purity 97.28% (tR = 6.52 min).
(E)-1-(3-Methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one (5c). It
1
was obtained as an off-white solid in 21% yield. H NMR (400 MHz,
DMSO) δ = 8.18 (d, J = 7.7 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.97 (d, J =
15.5 Hz, 1H), 7.83 (dd, J = 17.6, 11.4 Hz, 2H), 7.75 (d, J = 7.5 Hz, 1H),
7.69 (t, J = 7.6 Hz, 1H), 7.61 (s, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.25 (d, J =
6.4 Hz, 1H), 3.84 (s, 3H). 13C NMR (101 MHz, DMSO) δ = 189.36,
160.02, 149.23, 139.13, 138.91, 134.21, 131.53, 130.50, 130.16, 130.02,
126.91, 125.14, 121.70, 120.06, 113.60, 55.87. LCꢀMS (ESI-TOF): m/
z 284.0918 ([C16H13NO4 þ H]þ calcd 284.0917). Purity 100.00% (tR =
6.91 min).
(E)-1-(4-Methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one (5d).
It was obtained as an off-white solid in 32% yield. 1H NMR (400
MHz, DMSO) δ = 8.17 (t, J = 7.9 Hz, 3H), 8.07 (d, J = 8.1 Hz, 1H),
7.97ꢀ7.85 (m, 2H), 7.81 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.09
1
(d, J = 8.4 Hz, 2H), 3.86 (s, 3H). H NMR (400 MHz, CDCl3) δ =
8.15ꢀ8.00 (m, 3H), 7.74 (d, J = 7.6 Hz, 1H), 7.68 (t, J = 7.6 Hz, 1H),
7.56 (t, J = 7.1 Hz, 1H), 7.32 (d, J = 15.6 Hz, 1H), 7.00 (d, J = 8.9 Hz,
2H), 3.90 (s, 3H). 13C NMR (101 MHz, DMSO) δ = 187.58, 163.98,
149.23, 138.00, 134.15, 131.63, 131.36, 130.38, 130.26, 129.91, 126.89,
125.09, 114.59, 56.08. LCꢀMS (ESI-TOF): m/z 284.0919
([C16H13NO4 þ H]þ calcd 284.0917). Purity 100.00% (tR = 6.55 min).
(E)-1-(2,4-Dimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5e). It was obtained as a yellow solid in 57% yield. 1H NMR (400 MHz,
DMSO) δ = 8.06 (dd, J = 8.2 Hz, 1.2 Hz, 1H), 7.94 (d, J = 7.7 Hz, 1H),
7.82ꢀ7.73 (m, 2H), 7.69ꢀ7.61 (m, 2H), 7.51 (d, J = 15.6 Hz, 1H), 6.68
(d, J = 2.2 Hz, 1H), 6.64 (dd, J = 8.6, 2.3 Hz, 1H), 3.90 (s, 4H), 3.84 (s,
4H). 13C NMR (101 MHz, DMSO) δ = 189.17, 164.87, 161.02, 149.09,
(E)-1-(2,4,6-Trimethoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
(5l). It was obtained as a yellow solid in 61% yield. 1H NMR (400 MHz,
DMSO) δ = 8.03 (dd, J = 8.1 Hz, 1.0, 1H), 7.93 (d, J = 7.7 Hz, 1H), 7.75
(t, J = 7.6 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.53 (d, J = 15.9 Hz, 1H), 6.92
(d, J = 15.9 Hz, 1H), 6.30 (s, 2H), 3.82 (s, 3H), 3.72 (s, 6H). 13C NMR
(101 MHz, DMSO) δ = 193.25, 162.76, 158.80, 148.78, 138.79, 134.30,
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dx.doi.org/10.1021/jm2002348 |J. Med. Chem. 2011, 54, 4147–4159