L.Z. Chen, H.Y. Shu, J. Wu et al.
European Journal of Medicinal Chemistry 213 (2021) 113174
þ
DMSO‑d
6
)
d
162.73, 160.22, 158.00, 153.57 (2C), 138.57, 136.49,
C
24
H
24
O
3
N
3
S [M þ H] , 434.1533; found 434.1531.
1
5
34.19, 132.15, 128.25, 124.97, 112.21, 105.21 (2C), 66.51 (2C), 60.54,
(E)-N-(4-methylbenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
pyrimidin-4-amine (22o). White solid, yield: 68.1%, mp: 179e180 C.
H NMR (600 MHz, CDCl
ꢀ
6.42 (2C), 46.27 (2C). HR-MS (ESI): calcd for C21
24
H N
3
O
4
S [M þ
þ
1
H] , 414.1482; found 414.1480.
3
)
d
7.89 (d, J ¼ 15.8 Hz, 1H), 7.69 (d,
(
E)-N-(p-tolyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-
J ¼ 5.3 Hz,1H), 7.41 (d, J ¼ 5.3 Hz,1H), 7.35 (d, J ¼ 7.9 Hz, 2H), 7.20 (d,
J ¼ 7.8 Hz, 2H), 7.14 (d, J ¼ 15.8 Hz, 1H), 6.87 (s, 2H), 5.12 (t,
J ¼ 5.2 Hz, 1H), 4.94 (d, J ¼ 5.5 Hz, 2H), 3.91 (s, 6H), 3.88 (s, 3H), 2.37
ꢀ
1
4
(
-amine (22h). White solid, yield: 71.4%, mp: 137e138 C. H NMR
600 MHz, DMSO‑d
10.49 (s, 1H), 8.34 (d, J ¼ 4.9 Hz, 1H), 7.89 (d,
J ¼ 15.8 Hz, 1H), 7.68 (d, J ¼ 7.1 Hz, 2H), 7.49 (d, J ¼ 5.3 Hz, 1H), 7.30
6
) d
1
3
3
(s, 3H). C NMR (151 MHz, CDCl ) d 161.47, 160.93, 156.90, 153.50
(
3
d, J ¼ 8.0 Hz, 2H), 7.19 (d, J ¼ 15.8 Hz, 1H), 7.02 (s, 2H), 3.87 (s, 6H),
(2C), 138.87, 137.63, 136.59, 135.68, 132.39, 130.98, 129.62 (2C),
128.22, 128.18 (2C), 125.50, 113.39, 104.68 (2C), 61.09, 56.25 (2C),
45.05, 21.27. HR-MS (ESI): calcd for C25
448.1689; found 448.1690.
.71 (s, 3H), 2.36 (s, 3H). HR-MS (ESI): calcd for C24
24
H O
3
N
3
S [M þ
þ
þ
H] , 434.1542; found 434.1536.
H
26
O
3
N
3
S [M þ H] ,
(
E)-N-(4-isopropylphenyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-
d]pyrimidin-4-amine (22i). White solid, yield: 67.6%, mp:
(E)-N-(4-methoxybenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
pyrimidin-4-amine (22p). White solid, yield: 51.5%, mp: 138e139 C.
ꢀ
1
ꢀ
2
14e215 C. H NMR (600 MHz, CDCl
3
)
d
7.88 (d, J ¼ 15.8 Hz, 1H),
1
7
1
6
.70 (d, J ¼ 5.4 Hz, 1H), 7.53 (d, J ¼ 8.3 Hz, 2H), 7.40 (d, J ¼ 5.4 Hz,
H NMR (600 MHz, CDCl
3
)
d
7.89 (d, J ¼ 15.8 Hz, 1H), 7.67 (dd,
H), 7.30 (d, J ¼ 8.3 Hz, 2H), 7.15 (d, J ¼ 15.8 Hz, 1H), 6.87 (s, 2H),
J ¼ 5.3, 2.3 Hz,1H), 7.41e7.39 (m,1H), 7.37 (d, J ¼ 8.4 Hz, 2H), 7.14 (d,
J ¼ 15.8 Hz, 1H), 6.92e6.88 (m, 2H), 6.86 (s, 2H), 5.19 (d, J ¼ 4.7 Hz,
1H), 4.90 (d, J ¼ 5.3 Hz, 2H), 3.90 (d, J ¼ 1.9 Hz, 6H), 3.88 (s, 3H), 3.80
1
3
.85 (s, 1H), 3.91 (s, 6H), 3.89 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H).
157.29, 156.39, 151.20, 148.61 (2C),
42.10, 134.14, 131.93 (2C), 130.34, 127.83, 127.38, 122.96, 122.24
C
6
NMR (151 MHz, DMSO‑d ) d
13
1
(d, J ¼ 2.3 Hz, 3H). C NMR (151 MHz, CDCl
3
) d 161.26, 160.71,
(
(
4
2C), 120.09, 119.82, 108.19, 99.92 (2C), 56.16 (2C), 51.37, 28.97, 19.27
159.20, 156.65, 153.31 (2C), 138.67, 136.40, 132.21, 130.86, 130.53,
129.41 (2C), 128.05, 125.33, 114.17 (2C), 113.23, 104.38 (2C), 60.96,
þ
2C). HR-MS (ESI): calcd for C26
H
28
O
3
N
3
S [M þ H] , 462.1846; found
62.1845.
56.07 (2C), 55.33, 44.59. HR-MS (ESI): calcd for C25
H] , 464.1649; found 464.1643.
H
26
N
3
O
4
S [M þ
þ
(
E)-N-(4-methoxyphenyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
ꢀ
pyrimidin-4-amine (22j). White solid, yield: 59.3%, mp: 106e107 C.
H NMR (600 MHz, CDCl
(E)-N-(4-chlorobenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
1
3
)
d
7.86 (d, J ¼ 15.8 Hz, 1H), 7.65 (d,
pyrimidin-4-amine (22q). White solid, yield: 71.5%, mp:
ꢀ
1
J ¼ 5.4 Hz, 1H), 7.47e7.43 (m, 2H), 7.37 (d, J ¼ 5.4 Hz, 1H), 7.13 (d,
J ¼ 15.8 Hz, 1H), 7.03 (s, 1H), 6.96 (d, J ¼ 8.7 Hz, 2H), 6.85 (s, 2H),
136e137 C. H NMR (600 MHz, DMSO‑d ) d 10.28 (s, 1H), 8.42 (d,
6
J ¼ 5.3 Hz, 1H), 8.09 (d, J ¼ 15.7 Hz, 1H), 7.54 (d, J ¼ 5.2 Hz, 1H), 7.52
(d, J ¼ 8.2 Hz, 2H), 7.43 (d, J ¼ 8.2 Hz, 2H), 7.22 (dd, J ¼ 15.7, 2.6 Hz,
13
3
3
.90 (s, 6H), 3.88 (s, 3H), 3.86 (s, 3H). C NMR (101 MHz, CDCl )
1
3
d
1
162.02, 160.93, 158.60, 156.79, 153.37 (2C), 138.77, 136.71, 133.41,
32.10,129.74,128.14,127.48,124.48 (2C),114.28 (2C),112.47,104.52
1H), 7.04 (s, 2H), 4.96 (d, J ¼ 5.5 Hz, 3H), 3.87 (s, 6H), 3.73 (s, 2H).
C
6
NMR (101 MHz, DMSO‑d ) d 157.02, 155.87, 153.67 (2C), 147.82,
(
[
2C), 60.99, 56.12 (2C), 55.58. HR-MS (ESI): calcd for C24
H
24
O
4
N
3
S
143.28, 140.27, 139.05, 137.60, 132.40, 130.44, 130.31 (2C), 128.93
þ
M þ H] , 450.1482; found 450.1483.
(2C), 119.33, 118.87, 114.67, 106.21 (2C), 60.68, 56.50 (2C), 44.17. HR-
þ
(
E)-N-(4-(trifluoromethyl)phenyl)-2-(3,4,5-trimethoxystyryl)
MS (ESI): calcd for C24
468.1139.
H23ClO
3
N
3
S [M þ H] , 468.1145; found
thieno[3,2-d]pyrimidin-4-amine (22k). White solid, yield: 47.2%,
mp: 145e146 C. H NMR (600 MHz, DMSO‑d
ꢀ
1
6
)
d
11.49 (s, 1H), 8.49
(E)-N-(2-chlorobenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
pyrimidin-4-amine (22r). White solid, yield: 51.5%, mp: 167e168 C.
ꢀ
(
d, J ¼ 5.3 Hz, 1H), 8.19 (d, J ¼ 8.4 Hz, 2H), 8.00 (d, J ¼ 15.9 Hz, 1H),
1
7
1
C
.85 (d, J ¼ 8.6 Hz, 2H), 7.62 (d, J ¼ 5.4 Hz, 1H), 7.34 (d, J ¼ 15.9 Hz,
H NMR (600 MHz, CDCl
3
)
d
7.87 (d, J ¼ 15.8 Hz, 1H), 7.69 (d,
H), 7.03 (s, 2H), 3.85 (s, 6H), 3.72 (s, 3H). HR-MS (ESI): calcd for
J ¼ 5.3 Hz, 1H), 7.56e7.52 (m, 1H), 7.43e7.41 (m, 1H), 7.40 (s, 1H),
7.25e7.22 (m, 2H), 7.12 (d, J ¼ 15.8 Hz, 1H), 6.86 (s, 2H), 5.39 (t,
þ
24
H
(
21
3
F O
3
N
3
S [M þ H] , 488.1257; found 488.1251.
1
3
E)-4-((2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-4-yl)
J ¼ 5.7 Hz, 1H), 5.07 (d, J ¼ 5.9 Hz, 2H), 3.91 (s, 6H), 3.88 (s, 3H).
C
ꢀ
1
amino)phenol (22l). White solid, yield: 53.7%, mp: 154e155 C. H
3
NMR (151 MHz, CDCl ) d 161.19, 160.76, 156.61, 153.33 (2C), 138.67,
NMR (600 MHz, DMSO‑d
6
)
d
10.63 (s, 1H, OH), 9.72 (s, 1H, NH), 8.32
136.53, 135.99, 133.65, 132.19, 131.00, 130.07, 129.61, 128.94, 127.92,
(
s, 1H, ArH), 7.93 (d, J ¼ 15.6 Hz, 1H, ¼CH), 7.47 (d, J ¼ 5.0 Hz, 3H,
127.05, 125.28, 113.34, 104.46 (2C), 60.95, 56.09 (2C), 42.69. HR-MS
þ
ArH), 7.18 (d, J ¼ 15.8 Hz, 1H, ¼CH), 7.01 (s, 2H, ArH), 6.90 (d,
(ESI): calcd for C24
H
23ClN
3
O
3
S [M þ H] , 468.1134; found 468.1148.
J ¼ 8.6 Hz, 2H, ArH), 3.87 (s, 6H, CH
3
), 3.72 (s, 3H, CH
3
). HR-MS (ESI):
(E)-N-(furan-2-ylmethyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
þ
ꢀ
calcd for C23
22
H O
4
N
3
S [M þ H] , 436.1334; found 436.1328.
pyrimidin-4-amine (22s). White solid, yield: 63.4%, mp: 172e173 C.
1
(
E)-N-methyl-N-phenyl-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]
H NMR (600 MHz, CDCl
3
)
d
7.90 (d, J ¼ 15.8 Hz, 1H), 7.68 (d,
pyrimidin-4-amine (22m). White solid, yield: 50.7%, mp:
J ¼ 5.3 Hz, 1H), 7.43e7.37 (m, 2H), 7.14 (d, J ¼ 15.7 Hz, 1H), 6.87 (s,
2H), 6.40e6.32 (m, 2H), 5.26 (s, 1H), 4.97 (d, J ¼ 5.4 Hz, 2H), 3.90 (s,
ꢀ
1
1
7
87e188 C. H NMR (600 MHz, CDCl
.51e7.46 (m, 4H), 7.41e7.38 (m, 2H), 7.27 (d, J ¼ 5.4 Hz, 1H), 7.18 (d,
J ¼ 15.8 Hz, 1H), 6.90 (s, 2H), 3.93 (s, 6H), 3.89 (s, 3H), 3.74 (s, 3H).
3
)
d
7.94 (d, J ¼ 15.8 Hz, 1H),
13
3
6H), 3.88 (s, 3H). C NMR (101 MHz, CDCl ) d 161.20, 160.85, 156.41,
153.38 (2C), 151.55, 142.39, 138.68, 136.51, 132.23, 131.03, 128.04,
1
3
C NMR (151 MHz, CDCl
3
)
d
161.80, 160.74, 157.44, 153.54 (2C),
125.34, 113.44, 110.61, 107.91, 104.46 (2C), 60.99, 56.11 (2C), 37.98.
þ
1
1
43.89, 138.88, 136.31, 133.29, 132.50, 129.78, 129.68 (2C), 128.65,
HR-MS (ESI): calcd for C22
424.1337.
H
22
N
3
O
4
S [M þ H] , 424.1326; found
28.43, 124.17 (2C), 114.20 (2C), 104.71, 61.11, 56.29 (2C), 39.66. HR-
þ
MS (ESI): calcd for C24
4
H N
24 3
O
3
S [M þ H] , 434.1533; found
(E)-N-(pyridin-4-ylmethyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-
d]pyrimidin-4-amine (22t). White solid, yield: 55.2%, mp:
34.1527.
ꢀ
1
(
E)-N-benzyl-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-4-
191e192 C. H NMR (600 MHz, CDCl
3
)
d
8.54 (d, J ¼ 4.8 Hz, 2H),
ꢀ
1
amine (22n). White solid, yield: 68.3%, mp: 140e141 C. H NMR
600 MHz, CDCl
7.88 (d, J ¼ 15.7 Hz, 1H), 7.70 (d, J ¼ 5.3 Hz, 1H),
.46 (d, J ¼ 8.4 Hz, 2H), 7.43 (s, 1H), 7.39 (t, J ¼ 7.5 Hz, 2H), 7.33 (t,
J ¼ 7.4 Hz, 1H), 7.14 (d, J ¼ 15.7 Hz, 1H), 6.87 (s, 2H), 5.16 (s, 1H), 4.99
7.72 (d, J ¼ 15.8 Hz, 1H), 7.70 (s, 1H), 7.41 (d, J ¼ 5.2 Hz, 1H), 7.33 (d,
(
7
3
) d
J ¼ 4.8 Hz, 2H), 7.08 (d, J ¼ 15.8 Hz, 1H), 6.79 (s, 2H), 5.84 (t,
J ¼ 5.2 Hz, 1H), 4.97 (d, J ¼ 5.6 Hz, 2H), 3.87 (s, 6H), 3.86 (s, 3H). HR-
þ
MS (ESI): calcd for C23
435.1484.
23
H O
3
N
4
S [M þ H] , 435.1485; found
13
(
d, J ¼ 5.5 Hz, 2H), 3.91 (s, 6H), 3.88 (s, 3H). C NMR (151 MHz,
CDCl 161.31, 160.79, 156.75, 153.35 (2C), 138.75, 138.60, 136.50,
32.20, 130.86, 128.79 (2C), 127.98 (2C), 127.69, 125.35, 113.21,
04.55 (2C), 60.91, 56.09 (2C), 45.11. HR-MS (ESI): calcd for
3
)
d
(E)-4-(benzyloxy)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimi-
dine (22u). Benzyl alcohol (86.4 mg, 0.8 mmol) and anhydrous
K CO (132 mg, 0.96 mmol) were added to anhydrous DMF (5 mL)
2 3
1
1
21