Original Article
Thieme
1
54.9, 159.0, and 191.2. Finally, the HRMS (+ESI) was C25H20N O2
dried over Na SO . The crude product was purified on a silica gel
column (eluent: hexane/ethyl acetate) to obtain 7(a-d).
3
2
4
+
[
M + H] ; it requires 394.1550, but has 394.1549.
4
-(2′,6′-Dimethyl-4′-cyanophenoxy)-6-(4′′-cyanophenyl)-
4-(2′,6′-Dimethyl-4′-formylphenoxy)-2-chloroquinoline
aminoquinoline (5b)
(7a)
With 59 % yield (2 steps), the synthesis started with 20.0 mg
With 69 % yield, the synthesis started with 1.0g (5.05 mmol) of 6
to obtain 1.1 g of 7a, which consisted of white solid and mp.
(
0.06 mmol) of 4b to obtain 14.5 mg of 5b, which consisted of yel-
1
low solid and mp. 289.5 °C–290.1 °C. 5b was obtained in 40.6 %
154.6°C–156.9°C. The H-NMR (300MHz, CDCl ) conditions were
3
1
overall yield (5 steps from 1). The H-NMR (300 MHz, CDCl ) con-
as follows: 2.23 (s, 6 H), 6.20 (s, 1 H), 7.65 (td, 1 H, J = 7.5, 1.2 Hz),
3
ditions were as follows: δ ppm 2.15 (s, 6 H), 6.20 (d, 1H, J=4.9Hz),
7.75 (s, 2 H), 7.82 (td, 1 H, 7.5, 1.2 Hz), 8.04 (dd, 1 H, 8.3, 0.9 Hz),
6
.61 (bs, 1 H), 7.18 (d, 2 H, J = 8.7 Hz), 7.56 (bs, 2 H), 7.57 (d, 2 H,
J = 2.4 Hz), 7.63 (dd, 1 H, J = 9.0, 2.4 Hz), 8.07–8.15 (m, 2 H), and
.55 (d, 1 H, J = 5.1 Hz). The 13C-NMR (75 MHz, CDCl ) conditions
and 8.4 (dd, 1 H, 8.3, 0.9 Hz). The 13C-NMR (75 MHz, CDCl ) condi-
3
tions were as follows: 16.1, 102.9, 119.5, 121.7, 126.7, 128.5,
131.5, 132.1, 134.4, 148.8, 151.3, 154.6, 161.0, and 191.2. Final-
ly, the HRMS ( + ESI) was C18H15ClNO2 [M + H] + ; it requires
312.0791, but has 312.0791.
8
3
were as follows: δ ppm 16.0, 102.5, 102.5, 108.9, 110.1, 115.8,
1
1
18.3, 119.5, 121.3, 125.1, 130.9, 132.9, 133.2, 133.9, 138.7,
46.7, 147.0, 149.5, 153.7, and 158.5. Finally, the HRMS ( + ESI)
+
4-(2′,6′-Dimethyl-4′-cyanophenoxy)-2-chloroquinoline
was C25H19N O [M + H] ; it requires 391.1553, but has 391.1550.
4
(
7b)
4
(
-(4′-formylphenoxy)-6-(4′′-cyanophenyl)-aminoquinoline
5c)
With 52 % yield (2 steps), the synthesis started with 20.9 mg
0.07 mmol) of 4c to obtain 13.4 mg of 5a, which consisted of yel-
With 62 % yield, the synthesis started with 0.30g (1.51 mmol) of 6
to obtain 0.29 g of 7b, which consisted of white solid and mp.
1
184.3°C–185.0°C. The H-NMR (300MHz, CDCl ) conditions were
3
(
as follows: 2.20 (s, 6 H), 6.2 (s, 1 H), 7.53 (s, 2 H), 7.65 (td, 1 H,
J = 9.2, 1.5 Hz), 7.83 (td, 1 H, J = 9.2, 1.5 Hz), 8.04 (dd, 1 H, J = 8.3,
1.2 Hz), and 8.38 (dd, 1 H, J = 8.3, 1.2 Hz). The 13C-NMR (75 MHz,
low solid and mp. 116.0 °C–117.0 °C. 5c was obtained in 44.2 %
overall yield (5 steps from 1). The H-NMR (400 MHz, CDCl ) con-
1
3
ditions were as follows: δ ppm 6.40 (bs, 1H), 6.75 (d, 1H, J=5.1Hz),
CDCl ) conditions were as follows: 15.9, 102.7, 110.4, 118.1, 119.3,
3
7
2
8
1
.12 (bd, 2 H, J = 8.8 Hz), 7.29 (bd, 2 H, J = 8.6 Hz), 7.51–7.57 (m,
H), 7.59 (dd, 1 H, J = 9.0, 2.6 Hz), 7.91 (d, 1 H, J = 2.5 Hz), 7.96–
.02 (m, 2H), 8.13 (d, 1H, J = 9.0 Hz), 8.69 (d, 1H, J = 5.1 Hz), and
121.6, 126.8, 128.4, 131.5, 132.7, 133.3, 148.8, 151.1, 153.2, and
+
160.7. Finally, the HRMS ( + ESI): C18H14ClN O [M + H] ; it requires
2
309.0795, but has 309.0783.
0.0 (s, 1H). The 13C-NMR (100MHz, CDCl ) conditions were as fol-
3
4
-(4′-formylphenoxy)-2-chloroquinoline (7c)
lows: δ ppm 103.2, 107.2, 108.7, 115.9, 119.4, 120.3, 122.6,
1
1
25.2, 130.9, 132.2, 133.4, 133.9, 138.8, 146.7, 149.4, 159.2,
With 67 % yield, the synthesis started with 0.30g (1.51 mmol) of 6
to obtain 0.29 g of 7c, which consisted of white solid and mp.
60.0, and 190.5. Finally, the HRMS ( + ESI) was C23H16N O2
3
+
1
[
M + H] ; it requires 366.1237, but has 366.1232.
113.9°C–114.2°C. The H-NMR (300MHz, CDCl ) conditions were
3
as follows: 6.64 (s, 1H), 7.35 (d, 2H, J=8.7Hz), 7.61 (td, 1H, J=7.8,
4
(
-(4′-cyanophenoxy)-6-(4′′-cyanophenyl)-aminoquinoline
5d)
With 63 % yield (2 steps), the synthesis started with 20.9 mg
0.07mmol) of 4d to obtain 16.4mg of 5d, which consisted of yellow
1
1
.2 Hz), 7.81 (td, 1 H, J = 7.8, 1.2 Hz), 8.04 (m, 3 H), and 8.26 (dd,
H, J = 8.4, 0.9 Hz). The 13C-NMR (75 MHz, CDCl ) conditions were
3
as follows: 106.5, 120.4, 121.0, 121.8, 126.9, 128.5, 131.6, 132.3,
134.0, 149.0, 151.0, 159.1, 161.9, and 190.5. Finally, the HRMS
(
+
solid and mp. 214.0°C–214.6°C. 5d was obtained in 47.7% overall
yield (5 steps from 1). The H-NMR (300MHz, CDCl ) conditions were
( + ESI) was C16H11ClNO [M + H] ; it requires 284.0478, but has
2
1
284.0465.
3
as follows: δ ppm 6.40 (bs, 1H), 6.73 (d, 1H, J=5.0Hz), 7.11 (bd, 2H,
J=8.64, 7.24 (bd, 2 H, J=8.70), 7.50–7.56 (m, 2 H), 7.58 (dd, 1H,
J=9.2, 2.5Hz), 7.75 (bd, 2H, J=8.7Hz), 7.87 (d, 1H, J=2.4Hz) , 8.12
4
-(4′-cyanophenoxy)-2-chloroquinoline (7d)
With 60 % yield, the synthesis started with 0.30g (1.51 mmol) of 6
to obtain 0.26 mg of 7d, which consisted of white solid and mp.
214.1°C–215.0°C. The H-NMR (300MHz, CDCl ) conditions were
(
d, 1H, J=9Hz), and 8.69 (d, 1H, J=4.98Hz). The 13C-NMR (75MHz,
1
CDCl ) conditions were as follows: δ ppm 103.3, 107.3, 108.5, 108.9,
3
3
116.0, 118.1, 119.4, 120.6, 122.6, 124.0, 125.2, 131.1, 133.9, 134.6,
as follows: 6.63 (s, 1H), 7.32 (d, 2H), 7.60 (t, 1H, J = 7.2 Hz), 7.78–
1
38.9, 146.7, 149.4, and 158.7. Finally, the HRMS ( + ESI) was
7.83 (m, 3 H), 8.02 (d, 1H, J = 8.4 Hz), and 8.22 (d, 1H, J = 8.4 Hz).
+
The 13C-NMR (75 MHz, CDCl ) conditions were as follows: 106.4,
C23H15N O [M+H] ; it requires 363.1240, but has 363.1246.
4
3
1
1
09.6, 117.9, 119.6, 120.2, 121.2, 121.6, 126.9, 128.4, 131.5,
34.4, 134.7, 148.8, 150.8, 157.6, 161.5. Finally, the HRMS (+ESI)
General procedure for the preparation of 2-chloro-4-
phenoxyquinoline 7(a-d)
+
was C16H10ClN O [M+H] ; it requires 281.0482, but has 281.0470
2
A mixture of 2,4-dichloroquinoline (6) (5.05 mmol) and hydroxyl
benzene (5.56 mmol) in DMF (15 mL) with anhydrous cesium car-
bonate (10.10 mmol) was heated in a sealed tube and stirred at
General procedure for the preparation of 2-amino-4-
oxydiarylquinoline 8(a-d)
8
0 °C for 16 h. After cooling, the mixture was poured into ice-wa-
A mixture of 2-chloro-4-phenoxyquinoline 7(a-d) (0.13 mmol),
ter, and the mixture was extracted thrice with ethyl acetate. The
combined organic layers were washed with saturated NaCl and
4-iodobenzonitrile (0.17 mmol), Pd(OAc) (0.01 mmol), SPhos
2
(0.01mmol) and Cs CO (0.20mmol) in DMF (7mL) was stirred and
2
3
Makarasen A et al. Anti-HIV of Amino-oxy-Diarylquinoline … Drug Res 2019; 69: 671–682
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