Cancers 2021, 13, 1790
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a stream of argon. The general synthesis pathways of the sulfonic derivatives are presented
in Figure 10.
Figure 10. Synthesis pathways of the sulfonic derivatives of styrylquinazolines. (A) 2-OCH3;
2
,4-OCH ; 4-OCH ; (B) 6-Br, 1,3-benzodioxolo; 1,3-benzodioxolo; 4-CH . Conditions: (a) AcOH,
3
3
3
◦
MW 80 W, 140 C; (b) CH Cl , DIPEA, DMAP, RT.
2
2
1
(
BS1) 2-((E)-2-(2-methoxyphenyl)ethenyl)quinazolin-4-yl 1,3-benzodioxole-5-sulfonate H
NMR (500 MHz, (CD ) SO) 8.26 (d, J = 16.2 Hz, 1H), 8.15 (dd, J = 8.0, 1.5 Hz, 1H),
.89 (ddd, J = 8.5, 7.2, 1.6 Hz, 1H), 7.73 (dd, J = 8.3, 1.1 Hz, 1H), 7.63 (dd, J = 7.8
.7 Hz, 1H), 7.56 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H), 7.47 (ddd, J = 8.8, 7.4, 1.7 Hz, 1H),
.17 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 16.3 Hz, 1H), 7.13 (dd, J = 8.0, 1.7 Hz, 1H), 7.08 (td,
J = 7.5, 1.0 Hz, 1H), 7.04 (d, J = 1.6 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.01 (s, 2H),
.94 (s, 3H); 13C NMR (126 MHz, (CD ) SO)
161.16, 158.94, 154.16, 147.71, 146.93,
δ
3
2
7
1
7
,
3
δ
3
2
1
1
43.74, 143.06, 139.23, 136.01, 133.18, 129.90, 127.84, 126.88, 123.54, 123.01, 121.53,
20.59, 119.88, 117.78, 112.61, 107.61, 106.72, 101.55, 56.28; HRMS (ESI) calcd for
−
◦
C H N O S [M − H] 461.0813; found 461.0821; m.p. 223–225 C.
24
18
2
6
(
(
(
BS2) 2-((E)-2-(2-methoxyphenyl)ethenyl)quinazolin-4-yl 6-bromo-1,3-benzodioxole-5-
1
sulfonate H NMR (500 MHz, (CD ) SO)
δ
8.18 (ddd, J = 8.3, 1.5, 0.7 Hz, 1H), 8.08 (ddd,
3
2
J = 8.4, 6.9, 1.4 Hz, 1H), 8.01 (appdt, J = 8.4, 1.0 Hz, 1H), 7.92 (d, J = 16.1 Hz, 1H),
7.86 (s, 1H), 7.78 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.70 (dd, J = 7.7, 1.7 Hz, 1H), 7.62 (s, 1H),
7
1
.41 (ddd, J = 8.9, 7.3, 1.7 Hz, 1H), 7.26 (d, J = 16.0 Hz, 1H), 7.13 (dd, J = 8.4, 1.1 Hz
,
H), 7.03 (apptd, J = 7.5, 1.1 Hz, 1H), 6.12 (s, 2H), 3.95 (s, 3H); 1 C NMR (126 MHz,
3
DMSO)
δ 162.00, 158.43, 152.80, 148.39, 146.40, 141.67, 135.23, 132.10, 128.99, 126.86,
1
26.46, 123.66, 121.39, 121.27, 113.80, 112.41, 111.15, 109.47, 102.45, 56.16; HRMS (ESI)
−
◦
calcd for C H BrN O S [M + H] 541.0063; found 541.0079; m.p. 149–151 C.
24
17
2
6
BS3) 7-chloro-2-((E)-2-(2-methoxyphenyl)ethenyl)quinazolin-4-yl 4-methylbenzenesulfonate
1
H NMR (500 MHz, (CD ) SO)
δ 8.19 (d, J = 16.2 Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H),
3
2
7
7
.74 (d, J = 2.0 Hz, 1H), 7.61 (dd, J = 7.7, 1.9 Hz, 1H), 7.50 (dd, J = 8.5, 2.1 Hz, 1H),
.49–7.46 (m, 2H), 7.43 (ddd, J = 8.9, 7.5, 1.8 Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 7.13–7.10
(
m, 2H), 7.08 (d, J = 16.2 Hz, 1H), 7.04 (appt, J = 7.3 Hz, 1H), 3.92 (s, 2H), 2.29 (s, 3H);
13
C NMR (126 MHz, (CD ) SO)
δ
161.64, 158.38, 153.86, 150.28, 146.25, 139.60, 138.04,
35.35, 132.05, 128.88, 128.51 (2H), 128.42, 126.76, 126.33, 125.97 (2H), 128.51, 123.65,
21.37, 121.18, 120.25, 112.38, 56.14, 21.25; HRMS (ESI) calcd for C H ClN O S
3
2
1
1
[
24
19
2
4
−
◦
M − H] 465.0681; found 465.0685; m.p. 196–197 C.
1
BS4) 2-((E)-2-(2-methoxyphenyl)ethenyl)quinazolin-4-yl 4-methylbenzenesulfonate H
1
NMR (500 MHz, (CD ) SO)
δ
H NMR (500 MHz, DMSO)
δ
8.26 (d, J = 16.3 Hz, 1H),
3
2
8
.14 (dd, J = 8.0, 1.5 Hz, 1H), 7.88 (ddd, J = 8.5, 7.1, 1.6 Hz, 1H), 7.73 (dd, J = 8.3, 1.1 Hz
,
1H), 7.63 (dd, J = 7.7, 1.7 Hz, 1H), 7.56 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H), 7.49–7.47 (m, 2H),
7
.47 (ddd, J = 6.9, 1.8 Hz, 1H), 7.17 (dd, J = 8.4, 1.1 Hz, 1H), 7.15 (d, J = 16.4 Hz, 1H),
1
3
7
.13–7.11 (m, 1H), 7.08 (td, J = 7.5, 1.0 Hz, 1H), 3.94 (s, 3H), 2.29 (s, 3H); C NMR
161.40, 159.96, 158.05, 153.16, 146.79, 136.23, 134.66, 131.60,
30.57, 129.26, 128.99, 128.40, 128.10, 127.13, 124.08, 123.55, 121.34, 114.50, 112.24,
(126 MHz, (CD ) SO) δ
3 2
1