Journal of Medicinal Chemistry
Article
113.81, 48.34, 47.68, 26.79, 19.89. ESI m/z: 343 [M − H]+. Anal.
(C19H24N2O4) C, H, N.
described for 7a and purified by recrystallization from ethanol. Yellow
solid, mp 153−154 °C. H NMR (300 MHz, DMSO-d6): δ 9.44 (s,
1
1,3-Diallyl-(4-hydroxybenzylidene)pyrimidine-2,4,6-
(1H,3H,5H)-trione (9b). Synthesized in 94% yield starting from 15
and 4-hydroxybenzaldehyde following the procedure described for 7a
and purified by recrystallization from ethanol. Yellow solid, mp 166−
1H), 8.27 (s, 1H), 8.10 (d, J = 2.2 Hz, 1H), 7.72 (dd, J = 8.6, 2.2 Hz,
1H), 7.07 (d, J = 8.6 Hz, 1H), 5.91−5.79 (m, 2H), 5.21−5.09 (m,
4H), 4.47−4.43 (m, 4H), 3.89 (s, 3H). 13C NMR (75 MHz, DMSO-
d6): δ 163.29, 161.28, 158.34, 154.33, 151.28, 147.02, 133.88, 133.77,
131.66, 126.62, 121.58, 117.61, 117.54, 115.79, 112.54, 57.02, 44.90,
44.29. ESI m/z: 341 [M − H]+ Anal. (C18H18N2O5) C, H, N.
1,3-Dibenzyl-5-(4-hydroxy-3-methoxybenzylidene)-
pyrimidine-2,4,6(1H,3H,5H)-trione (7e). Synthesized in 98% yield
starting from 13 and 4-hydroxy-3-methoxybenzaldehyde following the
procedure described for 7a and purified by recrystallization from
ethanol. Yellow solid, mp 169−170 °C. 1H NMR (300 MHz, DMSO-
d6): δ 10.63 (brs, 1H), 8.38 (s, 1H), 8.23 (d, J = 2.1 Hz, 1H), 7.90 (dd,
J = 8.6, 2.1 Hz, 1H), 7.36−7.22 (m, 10H), 6.91 (d, J = 8.6 Hz, 1H),
5.06 (s, 4H), 3.80 (s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 162.52,
160.63, 157.71, 153.43, 146.92, 137.00, 132.26, 128.21, 127.28, 127.00,
124.12, 118.37, 115.34, 113.51, 55.59, 44.85, 44.31. ESI m/z: 441 [M
− H]+. Anal. (C26H22N2O5) C, H, N.
1,3-Diisobutyl-5-(4-hydroxy-3-methoxybenzylidene)-
pyrimidine-2,4,6(1H,3H,5H)-trione (8e). Synthesized in 98% yield
starting from 14 and 4-hydroxy-3-methoxybenzaldehyde following the
procedure described for 7a and purified by recrystallization from
ethanol. Yellow solid, mp 108−109 °C. 1H NMR (300 MHz, DMSO-
d6): δ 10.56 (brs, 1H), 8.33 (s, 1H), 8.21 (d, J = 2.0 Hz, 1H), 7.89 (dd,
J = 8.4, 2.0 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H), 3.73 (d, J =
7.3 Hz, 4H), 2.10−1.98 (m, 2H), 0.89 (d, J = 6.7 Hz, 12H). 13C NMR
(75 MHz, DMSO-d6): δ 162.72, 160.90, 157.00, 153.08, 151.11,
146.89, 131.83, 124.15, 118.33, 115.30, 113.78, 55.63, 48.32, 47.67,
26.81, 19.90. ESI m/z: 373 [M − H]+. Anal. (C20H26N2O5) C, H, N.
1,3-Diallyl-5-(4-hydroxy-3-methoxybenzylidene)pyrimidine-
2,4,6(1H,3H,5H)-trione (9e). Synthesized in 93% yield starting from
15 and 4-hydroxy-3-methoxybenzaldehyde following the procedure
described for 7a and purified by recrystallization from ethanol. Yellow
solid, mp 130−132 °C. 1H NMR (300 MHz, DMSO-d6): δ 10.60 (brs,
1H), 8.34 (s, 1H), 8.28 (d, J = 2.0 Hz, 1H), 7.89 (dd, J = 8.6, 2.0 Hz,
1H), 6.92 (d, J = 8.6 Hz, 1H), 5.93−5.80 (m, 2H), 5.20−5.09 (m,
4H), 4.47−4.44 (m, 4H), 3.83 (s, 3H). 13C NMR (75 MHz, DMSO-
d6): δ 162.13, 160.28, 157.29, 153.28, 150.03, 146.93, 132.60, 132.15,
124.12, 118.39, 116.26, 115.32, 113.58, 55.64, 43.59, 43.02. ESI m/z:
341 [M − H]+. Anal. (C18H18N2O5) C, H, N.
1
167 °C. H NMR (300 MHz, DMSO-d6): δ 10.87 (brs, 1H), 8.33−
8.30 (m, 3H), 6.89 (d, J = 8.5 Hz, 2H), 5.91−5.79 (m, 2H), 5.19−5.09
(m, 4H), 4.46−4.43 (m, 4H). 13C NMR (75 MHz, DMSO-d6): δ
163.21, 162.10, 160.16, 157.05, 150.05, 138.29, 132.65, 132.54, 123.74,
116.34, 116.28, 115.48, 113.65, 43.61, 43.02. ESI m/z: 311 [M − H]+.
Anal. (C17H16N2O4) C, H, N.
1,3-Dibenzyl-5-(3,4-dihydroxybenzylidene)pyrimidine-
2,4,6(1H,3H,5H)-trione (7c). Synthesized in 86% yield starting from
13 and 3,4-dihydroxybenzaldehyde following the procedure described
for 7a and purified by recrystallization from EtOAc/hexane. Yellow
solid, mp 165−167 °C. 1H NMR (300 MHz, DMSO-d6); δ 10.53 (brs,
1H), 9.52 (brs, 1H), 8.29 (s, 1H), 8.21 (d, J = 2.0 Hz, 1H), 7.66 (dd, J
= 8.1, 2.0 Hz, 2H), 7.36−7.24 (m, 10H), 6.87 (d, J = 8.1 Hz, 1H), 5.06
(s, 4H). 13C NMR (75 MHz, DMSO-d6): δ 158.07, 152.90, 150.91,
144.85, 137.04, 131.78, 128.23, 127.19, 126.99, 124.27, 121.42, 115.41,
112.93, 44.88, 44.32. ESI m/z: 427 [M − H]+. Anal. (C25H20N2O5) C,
H, N.
5-(3,4-Dihydroxybenzylidene)-1,3-diisobutylpyrimidine-
2,4,6(1H,3H,5H)-trione (8c). Synthesized in 86% yield starting from
14 and 3,4-dihydroxybenzaldehyde following the procedure described
for 7a and purified by recrystallization from EtOAc/hexane. Yellow
solid, mp 184−186 °C. 1H NMR (300 MHz, DMSO-d6): δ 10.43 (brs,
1H), 9.47 (brs, 1H), 8.22 (s, 1H), 8.16 (d, J = 2.0 Hz, 1H), 7.62 (dd, J
= 8.2, 2.0 Hz, 2H), 6.86 (d, J = 8.2 Hz, 1H), 3.70 (d, J = 7.2 Hz, 4H),
2.06−1.96 (m, 2H), 0.87 (d, J = 6.7 Hz, 12H). 13C NMR (75 MHz,
DMSO-d6): δ 158.52, 153.76, 152.38, 146.03, 132.60, 125.50, 122.46,
116.58, 114.51, 49.44, 49.04, 28.02, 21.14. ESI m/z: 359 [M − H]+.
Anal. (C19H24N2O5) C, H, N.
1,3-Diallyl-5-(3,4-dihydroxybenzylidene)pyrimidine-2,4,6-
(1H,3H,5H)-trione (9c). Synthesized in 96% yield starting from 15
and 3,4-dihydroxybenzaldehyde following the procedure described for
7a and purified by recrystallization from EtOAc/hexane. Yellow solid,
mp 132−133 °C. 1H NMR (300 MHz, DMSO-d6): δ 10.43 (brs, 1H),
9.50 (brs, 1H), 8.24 (s, 1H), 8.20 (d, J = 2.1 Hz, 1H), 7.65 (dd, J = 8.4,
2.1 Hz, 2H), 6.87 (d, J = 8.4 Hz, 1H), 5.92−5.79 (m, 2H), 5.19−5.09
(m, 4H), 4.46−4.43 (m, 4H). 13C NMR (75 MHz, DMSO-d6): δ
157.55, 152.67, 150.05, 144.81, 132.63, 131.51, 124.23, 121.31, 116.25,
115.35, 113.04, 43.55, 43.04. ESI m/z: 327 [M − H]+. Anal.
(C17H16N2O5) C, H, N.
1,3-Dibenzyl-5-(3,4-dimethoxybenzylidene)pyrimidine-
2,4,6(1H,3H,5H)-trione (7f). Synthesized in 91% yield starting from
13 and 3,4-dimethoxybenzaldehyde following the procedure described
for 7a and purified by recrystallization from ethanol. Yellow solid, mp
1
173−174 °C. H NMR (300 MHz, DMSO-d6): δ 8.40 (s, 1H), 8.15
1,3-Dibenzyl-5-(3-hydroxy-4-methoxybenzylidene)-
pyrimidine-2,4,6(1H,3H,5H)-trione (7d). Synthesized in 98% yield
starting from 13 and 3-hydroxy-4-methoxybenzaldehyde following the
procedure described for 7a and purified by recrystallization from
ethanol. Yellow solid, mp 192−193 °C. 1H NMR (300 MHz, DMSO-
d6): δ 9.46 (brs, 1H), 8.32 (s, 1H), 8.11 (d, J = 2.2 Hz, 1H), 7.73 (dd, J
= 8.7, 2.2 Hz, 1H), 7.35−7.22 (m, 10H), 7.08 (d, J = 8.7 Hz, 1H), 5.05
(s, 4H), 3.89 (s, 3H). 13C NMR (75 MHz, DMSO-d6): δ 162.41,
160.36, 157.57, 153.22, 150.87, 145.77, 136.99, 136.92, 130.58, 128.20,
127.31, 127.15, 127.01, 126.95, 125.38, 120.42, 114.44, 111.32, 55.78,
44.92, 44.29. ESI m/z: 441 [M − H]+. Anal. (C26H22N2O5) C, H, N.
1,3-Diisobutyl-5-(3-hydroxy-4-methoxybenzylidene)-
pyrimidine-2,4,6(1H,3H,5H)-trione (8d). Synthesized in 98% yield
starting from 14 and 3-hydroxy-4-methoxybenzaldehyde following the
procedure described for 7a and purified by recrystallization from
ethanol. Yellow solid, mp 154−155 °C. 1H NMR (300 MHz, DMSO-
d6): δ 9.42 (brs, 1H), 8.25 (s, 1H), 8.06 (d, J = 2.2 Hz, 1H), 7.69 (dd, J
= 8.6, 2.2 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 3.89 (s, 3H), 3.70 (d, J =
7.1 Hz, 4H), 2.14−1.92 (m, 2H), 0.87 (d, J = 6.7 Hz, 12H). 13C NMR
(75 MHz, DMSO-d6): δ 162.55, 160.59, 156.78, 152.91, 151.10,
145.73, 130.17, 125.42, 120.26, 114.71, 111.27, 55.74, 48.38, 47.70,
26.78, 19.90. ESI m/z: 373 [M − H]+. Anal. (C20H26N2O5) C, H, N.
1,3-Diallyl-5-(3-hydroxy-4-methoxybenzylidene)pyrimidine-
2,4,6(1H,3H,5H)-trione (9d). Synthesized in 96% yield starting from
15 and 3-hydroxy-4-methoxybenzaldehyde following the procedure
(d, J = 2.1 Hz, 1H), 7.95 (dd, J = 8.6, 2.1 Hz, 1H), 7.36−7.24 (m, 8H),
7.12 (d, J = 8.6 Hz, 1H), 5.06 (s, 4H), 3.88 (s, 3H), 3.77 (s, 3H). 13C
NMR (75 MHz, DMSO-d6): δ 162.35, 157.21, 153.86, 150.85, 147.77,
136.96, 136.90, 131.28, 128.20, 127.33, 127.29, 127.03, 126.99, 125.21,
116.95, 114.95, 111.11, 55.83, 55.47, 44.91, 44.31. ESI m/z: 455 [M −
H]+. Anal. (C27H24N2O5) C, H, N.
1,3-Diisobutyl-5-(3,4-dimethoxybenzylidene)pyrimidine-
2,4,6(1H,3H,5H)-trione (8f). Synthesized in 91% yield starting from
14 and 3,4-dimethoxybenzaldehyde following the procedure described
for 7a and purified by recrystallization from ethanol. Yellow solid, mp
1
174−175 °C. H NMR (300 MHz, DMSO-d6): δ 8.35 (s, 1H), 8.12
(d, J = 2.1 Hz, 1H), 7.93 (dd, J = 8.7, 2.1 Hz, 1H), 7.12 (d, J = 8.7 Hz,
1H), 3.89 (s, 3H), 3.80 (s, 3H), 3.71 (d, J = 7.2 Hz, 4H), 2.08−1.97
(m, 2H), 0.87 (d, J = 6.7 Hz, 12H). 13C NMR (75 MHz, DMSO-d6): δ
162.53, 160.75, 156.53, 153.59, 151.09, 147.76, 130.86, 125.28, 116.94,
115.21, 111.09, 55.82, 55.52, 48.39, 47.69, 26.86, 26.81, 19.91. ESI m/
z: 387 [M − H]+. Anal. (C21H28N2O5) C, H, N.
1,3-Diallyl-5-(3,4-dimethoxybenzylidene)pyrimidine-2,4,6-
(1H,3H,5H)-trione (9f). Synthesized in 97% yield starting from 15
and 3,4-dimethoxybenzaldehyde following the procedure described for
7a and purified by recrystallization from ethanol. Yellow solid, mp
1
169−170 °C. H NMR (300 MHz, DMSO-d6): δ 8.36 (s, 1H), 8.20
(d, J = 2.1 Hz, 1H), 7.94 (dd, J = 8.7, 2.1 Hz, 1H), 7.12 (d, J = 8.7 Hz,
1H), 5.87−5.81 (m, 2H), 5.21−5.09 (m, 4H), 4.47−4.44 (m, 4H),
2792
J. Med. Chem. 2015, 58, 2779−2798