Molecules 2017, 22, 1624
8 of 11
1
1
1
5
56.6, 154.9, 153.2, 148.7, 147.5, 139.9, 136.0, 132.0, 130.1, 128.2, 127.2, 125.0, 122.5, 120.3, 117.7, 117.4,
−
1
09.5, 107.8, 103.2, 67.6, 66.6, 56.3, 55.4, 53.9, 26.3. IR νmax (KBr) cm : 3321, 2949, 1621, 1599, 1513,
+
426, 1241, 1140, 1111, 1064, 959, 921, 859, 819. HRMS (ESI-TOF) for C H ClFN O [M + H] : Calcd:
30
30
4
3
49.1990, found: 549.2006.
(
E)-7-Methoxy-6-(3-morpholinopropoxy)-4-(4-(3-bromo-4-fluorostyryl)phenylamino)quinazoline (6f). Yellow
◦
1
solid, Yield 73%. m.p.: 213.6~215.1 C. For H-NMR (300 MHz, DMSO-d )
(
2
1
5
δ
(ppm): 9.55 (s, 1H), 8.50
s, 1H), 7.86–7.97 (4H), 7.61–7.63 (3H), 7.14–7.40 (4H), 4.20 (bs, 2H), 3.95 (s, 3H), 3.59 (bs, 4H), 2.40 (6H),
.00 (bs, 2H). For 13C-NMR (75 MHz, DMSO-d6)
(ppm): 159.4, 156.6, 154.9, 153.2, 148.8, 147.5, 139.9,
36.3, 132.1, 131.1, 130.1, 127.9, 127.2, 124.9, 122.6, 117.5, 117.2, 109.5, 107.8, 103.3, 67.7, 66.7, 56.3, 55.4,
6
δ
−
1
3.9, 26.4. IR νmax (KBr) cm : 3321, 2945, 1622, 1600, 1513, 1472, 1426, 1241, 1140, 1111, 958, 859, 818.
+
HRMS (ESI-TOF) for C H BrFN O [M + H] : Calcd: 593.1485, found: 593.1494.
30
30
4
3
(
E)-7-Methoxy-6-(3-morpholinopropoxy)-4-(4-(4-fluoro-3-methylstyryl)phenylamino)quinazoline (6g). Yellow
◦
1
solid, Yield 67%. m.p.: 199.9~201.4 C. For H-NMR (300 MHz, DMSO-d )
δ
(ppm): 9.54 (s, 1H), 8.49
6
(
2
s, 1H), 7.85–7.86 (3H), 7.43–7.62 (4H), 7.10–7.20 (4H), 4.18–4.22 (t, 2H), 3.94 (s, 3H), 3.57–3.60 (t, 4H),
.34–2.47 (m, 6H), 2.27 (s, 3H), 1.98–2.02 (m, 2H). For 13C-NMR (75 MHz, DMSO-d6)
δ (ppm): 162.2,
1
1
2
58.9, 156.6, 154.9, 153.3, 148.7, 147.4, 139.5, 134.0,132.5, 129.7, 128.3, 127.0, 126.4, 126.1, 125.0, 124.7,
−
1
22.6, 115.8, 115.5, 109.5, 107.7, 103.2, 67.6, 66.6, 56.3, 55.4, 53.9, 26.3, 14.7. IR νmax (KBr) cm : 3324,
947, 1599, 1513, 1426, 1239, 1210, 1139, 1112, 960, 855, 819, 606. HRMS (ESI-TOF) for C H FN O
31
33
4
3
+
[M + H] : Calcd: 529.2537, found: 529.2549.
(
E)-7-Methoxy-6-(3-morpholinopropoxy)-4-(4-(4-fluorostyryl)phenylamino)quinazoline (6h). Yellow solid,
◦
1
Yield 41%. m.p.: 214.6~216.2 C. For H-NMR (300 MHz, DMSO-d )
7
1
1
5
δ
(ppm): 9.53 (s, 1H), 8.49 (s, 1H),
.86 (3H), 7.61–7.67 (4H), 7.20–7.24 (5H), 4.18–4.20 (t, 2H), 3.94 (s, 3H), 3.59 (bs, 4H), 2.40 (m, 6H),
.99 (m, 2H). For 13C-NMR (75 MHz, DMSO-d6)
(ppm): 163.6, 160.4, 156.6, 154.9, 153.3, 148.8, 147.5,
6
δ
39.6, 134.4, 132.4, 128.6, 128.5, 127.0, 126.3, 122.6, 116.1, 115.9, 109.5, 107.8, 103.3, 67.7, 66.7, 56.3, 55.5,
−
1
3.9, 26.4. IR νmax (KBr) cm : 3316, 2946, 1596, 1515, 1427, 1385, 1234, 1139, 1063, 959, 858. HRMS
+
(
ESI-TOF) for C H FN O [M + H] : Calcd: 515.2380, found: 515.2394.
30
31
4
3
(
E)-7-Methoxy-6-(3-morpholinopropoxy)-4-(4-(4-fluoro-3-trifluoromethylstyryl)phenylamino)quinazoline (6i).
◦
1
Yellow solid, Yield 50%. m.p.: 210.2~212.0 C. For H-NMR (300 MHz, DMSO-d )
δ
(ppm): 9.55
6
(
(
s, 1H), 8.50 (s, 1H), 7.86–7.99 (5H), 7.49–7.66 (3H), 7.26–7.41 (2H), 7.20 (s, 1H), 4.18–4.23 (t, 2H), 3.95
s, 3H), 3.57–3.60 (t, 4H), 2.40–2.51 (m, 6H), 1.98–2.03 (m, 2H). For 1 C-NMR (75 MHz, DMSO-d6)
3
δ
(
1
ppm): 156.6, 155.0, 153.2, 148.8, 147.5, 140.0, 135.2, 135.2, 132.8, 132.7, 132.0, 130.6, 127.3, 125.1, 125.1,
−
1
24.8, 122.5, 122.4, 118.2, 117.9, 109.5, 107.8, 103.3, 67.7, 66.7, 56.3, 55.4, 53.9, 26.4. IR νmax (KBr) cm
:
3
357, 2939, 1619, 1597, 1515, 1424, 1390, 1326, 1241, 1140, 1053, 959, 921, 848. HRMS (ESI-TOF) for
+
C H F N O [M + H] : Calcd: 583.2254, found: 583.2268.
31
30
4
4
3
(
E)-7-Methoxy-6-(3-morpholinopropoxy)-4-(4-(3,4-dimethoxystyryl)phenylamino)quinazoline (6j). Yellow
◦
1
solid, Yield 50%. m.p.: 176.1~179.3 C. For H-NMR (300 MHz, DMSO-d )
δ
(ppm): 9.52 (s, 1H),
.49 (s, 1H), 7.86 (s, 1H), 7.83 (d, 2H, J = 8.4 Hz), 7.61 (d, 2H, J = 8.4 Hz), 7.08–7.25 (5H), 6.97 (d, 1H,
J = 8.3 Hz), 4.18–4.20 (t, 2H), 3.94 (s, 3H), 3.84 (s, 3H), 3.78 (s, 3H), 3.59 (bs, 4H,), 2.40–2.46 (6H),
6
8
1
1
5
.98–2.02 (m, 2H). For 13C-NMR (75 MHz, DMSO-d6)
δ (ppm): 156.1, 154.4, 152.8, 149.0, 148.6, 148.2,
46.9, 138.7, 132.4, 130.3, 127.0, 126.2, 126.0, 122.2, 119.7, 111.9, 109.2, 109.0, 107.3, 102.8, 67.2, 66.2, 55.8,
−
1
5.5, 54.9, 53.4, 25.9. IR νmax (KBr) cm : 3435, 2625, 1589, 1514, 1428, 1243, 1143, 1017, 849. HRMS
+
(
ESI-TOF) for C H N O [M + H] : Calcd: 557.2686, found: 557.2700.
32
36
4
5
3
.2. Biological Evaluation of Anti-Tumour of the Synthesized Compounds
The A431 (human vaginal epidermoid cancer cell line), A549 (human non-small cell lung cancer),
Hela (human cervical cancer cell line), SMMC-7721 and HepG2 (human liver cancer cell line), BGC-823
human poorly differentiated gastric cancer cell line), SK-OV-3 (human ovarian cancer cell), HT-29
(