W. Xiang, T. Cheng-hao, W. Guo-lan, and L. Jie-feng
Vol 000
J = 7.45 Hz), 7.73 (d, 2H, J = 8.60 Hz), 7.63–7.43 (m, 5H),
8.65 (t, 1H, J = 5.72 Hz), 7.94 (d, 1H, J = 7.45 Hz),
7.60–7.16 (m, 11H), 6.87 (t, 1H, J = 7.45 Hz), 4.39 (t,
2H, J = 6.30 Hz), 3.55 (dd, 2H, J = 5.75 Hz, 6.85 Hz),
7
2
.31 (d, 1H, J = 4.02 Hz), 7.23 (d, 3H, J = 8.55 Hz), 4.26 (t,
H, J = 6.85 Hz), 3.46 (dd, 2H, J = 8.00 Hz, 8.60 Hz), 2.53
13
13
(
s, 3H); C NMR (125 MHz, DMSO-d , ppm): δ 170.54,
2.43 (s, 3H), 2.24 (s, 3H); C NMR (125 MHz, DMSO-
6
1
1
1
3
62.92, 162.35, 160.65, 148.39, 147.84, 143.84, 139.27,
34.96, 133.02, 132.11, 131.89, 130.04, 128.25, 127.77,
26.96, 125.59, 123.81, 122.98, 121.65, 117.96, 113.47,
d6, ppm): δ 170.68, 163.02, 162.56, 160.92, 148.78,
148.30, 139.78, 137.99, 134.85, 130.49, 129.16, 129.09,
128.71, 128.53, 127.00, 125.53, 124.56, 123.42, 123.32,
+
9.21, 37.99, 12.74; MS (ESI) m/z: 584.4 ([M + H] );
120.02, 117.82, 112.64, 37.88, 37.87, 21.70, 12.33; MS
+
Anal. Calcd for C H ClF N O : C 57.59%, H 3.62%, N
(ESI) m/z: 480.3 ([M
+
H] ); Anal. Calcd for
2
8
21
3 5 4
1
1.99%; found: C 57.63%, H 3.69%, N 12.02%.
3
C H N O : C 70.13%, H 5.25%, N 14.60%; found: C
28 25 5 3
-(2-Chlorophenyl)-N-(2-(2-((4-chlorophenyl)amino)-4-
oxoquinazolin-3(4H)-yl)ethyl)-5-methylisoxazole-4-carboxamide
7
0.23%, H 5.29%, N 14.72%.
5-Methyl-N-(2-(4-oxo-2-(p-tolylamino)quinazolin-3(4H)-yl)
1
(
8e).
Offwhite solid; H NMR (500 MHz, DMSO-d ,
ethyl)-3-phenylisoxazole-4-carboxamide (8i).
White solid;
6
1
ppm): δ 9.09 (s, 1H), 8.52 (d, 1H, J = 5.70 Hz), 7.95 (d,
H, J = 7.45 Hz), 7.66–7.18 (m, 11H), 4.25 (t, 2H,
J = 6.57 Hz), 3.45 (dd, 2H, J = 6.30 Hz, 6.85 Hz), 2.53
H NMR (500 MHz, DMSO-d , ppm) δ: 8.78 (s, 1H),
6
1
8
.68 (t, 1H, J = 5.72 Hz), 7.93 (d, 1H, J = 6.85 Hz),
7.61–7.36 (m, 8H), 7.24 (d, 1H, J = 8.55 Hz) 7.17 (t, 1H,
J = 7.45 Hz), 7.11 (d, 2H, J = 8.60 Hz), 4.39 (t, 2H,
J = 7.15 Hz), 3.56 (dd, 2H, J = 6.30 Hz, 5.70 Hz), 2.43
13
(s, 3H); C NMR (125 MHz, DMSO-d , ppm): δ
6
1
1
1
70.54, 162.93, 162.35, 160.66, 148.431, 147.08, 139.00,
34.94, 133.02, 132.11, 131.96, 130.05, 128.66, 128.32,
27.79, 127.09, 126.95, 125.57, 123.75, 123.34, 117.90,
13
(s, 3H), 2.25 (s, 3H); C NMR (125 MHz, DMSO-d6,
ppm) δ: 170.60, 163.02, 162.56, 160.92, 148.91, 148.48,
113.49, 38.03, 37.99, 12.75; MS (ESI) m/z: 534.2
1
37.22, 134.81, 132.98, 130.47, 129.30, 129.16, 128.53,
+
+
([M + H] ), 557.2 ([M + Na] ); Anal. Calcd for
127.00, 125.43, 123.24, 123.13, 117.72, 112.69, 107.22,
C H Cl N O : C 60.68%, H 3.96%, N 13.11%; found:
C 60.63%, H 3.99%, N 13.12%.
N-(2-(2-((4-Chlorophenyl)amino)-4-oxoquinazolin-3(4H)-yl)
27
21
2
5
3
39.21, 37.87, 21.02, 12.33; MS (ESI) m/z: 480.3
+
(
[M + H] ); Anal. Calcd for C H N O : C 70.13%, H
2
8 25 5 3
5
.25%, N 14.60%; found: C 70.18%, H 5.29%, N 14.72%.
ethyl)-5-methyl-3-phenylisoxazole-4-carboxamide (8f).
White
5
-Methyl-N-(2-(4-oxo-2-((4-(trifluoromethoxy)phenyl)amino)
1
solid; H NMR (500 MHz, DMSO-d , ppm): δ 8.94
6
quinazolin-3(4H)-yl)ethyl)-3-phenylisoxazole-4-carboxamide
1
(
(
s, 1H), 8.64 (s, 1H), 7.95 (d, 1H, J = 7.75 Hz), 7.72
d, 2H, J = 8.00 Hz), 7.59 (d, 3H, J = 6.85 Hz),
(8j). White solid; H NMR (500 MHz, DMSO-d , ppm):
6
δ 9.09 (s, 1H), 8.72 (s, 1H), 7.96 (d, 1H, J = 7.45 Hz), 7.81
(d, 2H, J = 8.05 Hz), 7.59 (d, 3H, J = 7.45 Hz), 7.45–7.18
7
2
.45–7.20 (m, 6H), 4.39 (t, 2H, J = 6.30 Hz), 3.55 (dd,
H, J = 6.3 Hz, 7.45 Hz), 2.41 (s, 3H); C NMR
13
13
(m, 7H), 4.41 (s, 2H), 3.56 (s, 2H), 2.42 (s, 3H); C NMR
(
125 MHz, DMSO-d , ppm): δ 170.61, 163.09, 162.49,
(125 MHz, DMSO-d , ppm): δ 170.57, 163.01, 162.51,
6
6
1
1
1
60.90, 148.50, 148.07, 139.96, 134.92, 130.48, 129.17,
28.73, 128.52, 127.43, 127.02, 125.55, 124.57, 124.13,
23.71, 117.97, 112.63, 37.86, 37.86, 12.30; MS (ESI)
160.92, 158.84, 148.48, 148.11, 144.08, 139.27, 134.49,
130.42, 129.13, 128.57, 128.51, 127.02, 125.57, 123.79,
121.66, 119.73, 118.80, 112.64, 107.29, 43.45, 37.82,
+
+
+
m/z: 500.2 ([M + H] ), 522.2 ([M + Na] ); Anal. Calcd
12.31; MS (ESI) m/z: 550.3 ([M + H] ); Anal. Calcd for
for C H Cl N O : C 64.86%, H 4.44%, N 14.01%;
C H F N O : C 61.20%, H 4.04%, N 12.74%; found:
28 22 3 5 4
27
21
2
5
3
found: C 64.93%, H 4.49%, N 14.02%.
C 61.28%, H 4.09%, N 12.72%.
5
-Methyl-N-(2-(4-oxo-2-(phenylamino)quinazolin-3(4H)-yl)
5-Methyl-N-(2-(4-oxo-2-(p-tolylamino)quinazolin-3(4H)-yl)
ethyl)isoxazole-4-carboxamide (8k). White solid; H NMR
1
ethyl)-3-phenylisoxazole-4-carboxamide (8g). Light yellow
solid; H NMR (500 MHz, DMSO-d , ppm): δ 8.88 (s,
1
(500 MHz, DMSO-d , ppm): δ 8.85 (s, 1H), 8.74 (t, 1H,
6
6
1
H), 8.70 (s, 1H), 7.95 (d, 1H, J = 7.40 Hz), 7.69 (d, 1H,
J = 5.70 Hz), 8.70 (s, 1H), 7.92 (d, 1H, J = 8.05 Hz),
7.59–7.53 (m, 3H), 7.23 (d, 1H, J = 8.00 Hz), 7.17 (t,
1H, J = 7.45 Hz), 7.11 (d, 2H, J = 8.00 Hz), 4.32 (t, 2H,
J = 6.30 Hz), 3.51 (dd, 2H, J = 5.75 Hz, 6.30 Hz), 2.50
J = 7.40 Hz), 7.61 (d, 3H, J = 6.85 Hz), 7.52–7.26 (m,
8
2
1
1
1
3
4
6
4
H), 7.06 (t, 1H, J = 7.17 Hz), 4.39 (s, 2H), 3.50 (s, 2H),
13
.43 (s, 3H); C NMR (125 MHz, DMSO-d , ppm): δ
6
13
70.52, 163.08, 162.58, 160.93, 148.75, 148.50, 148.28,
39.96, 134.86, 130.46, 129.16, 128.87, 128.54, 127.01,
25.52, 123.83, 123.46, 122.77, 117.84, 112.70, 107.24,
(s, 3H), 2.25 (s, 3H); C NMR (125 MHz, DMSO-d ,
6
ppm): δ 172.55, 162.49, 162.29, 149.33, 148.87, 148.48,
137.34, 134.82, 132.72, 129.29, 126.88, 125.44, 123.30,
+
9.23, 37.89, 12.32; MS (ESI) m/z: 466.3 ([M + H] ),
122.61, 117.78, 111.72, 37.53, 37.53, 20.99, 12.33; MS
+
+
88.2 ([M + Na] ); Anal. Calcd for C H N O : C
9.66%, H 4.98%, N 15.04%; found: C 69.63%, H
.99%, N 15.12%.
(ESI) m/z: 404.3 ([M
+
H] ); Anal. Calcd for
2
7 23 5 3
C H N O : C 65.50%, H 5.25%, N 17.36%; found: C
22 21 5 3
65.58%, H 5.29%, N 17.52%.
5
-Methyl-N-(2-(4-oxo-2-(m-tolylamino)quinazolin-3(4H)-yl)
5-Methyl-N-(2-(4-oxo-2-((4-(trifluoromethoxy)phenyl)amino)
ethyl)-3-phenylisoxazole-4-carboxamide (8h). White solid;
quinazolin-3(4H)-yl)ethyl)isoxazole-4-carboxamide (8l).
White
solid; H NMR (500 MHz, DMSO-d , ppm): δ 9.09
6
1
1
H NMR (500 MHz, DMSO-d , ppm): δ 8.76 (s, 1H),
6
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet