X. Luan et al. / Bioorg. Med. Chem. 19 (2011) 3312–3319
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4.1.1.5.
6-Chloro-2-methoxy-N-(2-methoxyphenyl)acridin-9-
(100 MHz, DMSO-d6) d 155.31, 153.20, 148.36, 139.93, 138.52,
135.42, 127.68, 127.59, 125.99, 123.35, 120.83, 117.72, 114.50,
111.17, 103.72, 55.59; HRMS(ESI): Calcd for C20H17ClN3O [M+H]+
350.1060. Found: 350.1052.
amine (7c). Yield 82%; mp 279–281 °C; 1H NMR (400 MHz,
DMSO-d6) d 11.18 (s, 1H), 8.10 (d, J = 2.1 Hz, 1H), 8.08 (d,
J = 9.6 Hz, 1H), 8.03 (d, J = 9.3 Hz, 1H), 7.73 (dd, J = 9.3, 2.6 Hz,
1H), 7.69 (d, J = 2.2 Hz, 1H), 7.55 (dd, J = 7.7, 1.5 Hz, 1H),
7.53–7.46 (m, 1H), 7.43 (dd, J = 9.4, 2.2 Hz, 1H), 7.26 (dd,
J = 8.4, 0.9 Hz, 1H), 7.18 (td, J = 7.6, 1.1 Hz, 1H), 3.69 (s, 3H),
3.58 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d 155.66, 153.96,
153.37, 139.30, 138.86, 135.38, 129.50, 128.54, 128.22, 126.94,
126.72, 124.05, 121.42, 120.93, 117.79, 114.52, 112.88, 111.62,
4.1.1.12. 6-Chloro-2-methoxy-N-p-tolylacridin-9-amine (7j).
Yield 71%; mp >300 °C; 1H NMR (400 MHz, DMSO-d6) d 11.30 (s,
1H), 8.09–7.96 (m, 3H), 7.73 (dd, J = 9.2, 2.5 Hz, 1H), 7.69 (s, 1H),
7.44 (dd, J = 9.4, 2.1 Hz, 1H), 7.30–7.43 (m, 4H), 3.72 (s, 3H), 2.38(s,
3H); 13C NMR (100 MHz, DMSO-d6) d 155.39, 151.38, 140.92,
139.68, 137.64, 137.24, 135.25, 130.09, 127.60, 127.18, 123.59,
123.04, 122.21, 119.07, 115.97, 112.83, 103.45, 55.53, 20.51; HRMS-
(ESI): Calcd for C21H18ClN2O [M+H]+ 349.1108. Found: 349.1105.
102.82, 55.68, 55.55; HRMS(ESI): Calcd for
C21H18ClN2O2
[M+H]+ 365.1057. Found: 365.1045.
4.1.1.6.
6-Chloro-N-(2-ethoxyphenyl)-2-methoxyacridin-9-
amine (7d). Yield 68%; mp 193–195 °C; 1H NMR (400 MHz,
DMSO-d6) d 11.15 (s, 1H), 8.13 (d, J = 9.4 Hz, 1H), 7.99 (s, 1H),
7.95 (d, J = 9.3 Hz, 1H), 7.75 (dd, J = 9.3, 2.3 Hz, 1H), 7.67 (s, 1H),
7.61 (d, J = 6.9 Hz, 1H), 7.51–7.42 (m, 2H), 7.29–7.12 (m, 2H), 3.79
(q, J = 6.9 Hz, 2H), 3.68 (s, 3H), 0.68 (t, J = 6.9 Hz, 3H); HRMS(ESI):
Calcd for C22H20ClN2O2 [M+H]+ 379.1213. Found: 379.1213.
4.1.1.13. 6-Chloro-2-methoxy-N-(4-(trifluoromethyl)phenyl)
acridin-9-amine (7k). Yield 66%; mp 287–289 °C; 1H NMR
(400 MHz, DMSO-d6) d 11.36 (s, 1H), 8.19 (s, 1H), 8.11 (d,
J = 9.4 Hz, 2H), 7.75–7.85 (m, 3H), 7.69 (s, 1H), 7.55 (d,
J = 8.9 Hz, 1H), 7.45–7.53 (m, 2H), 3.76 (s, 3H); HRMS(ESI): Calcd
for C21H15ClF3N2O [M+H]+ 403.0825. Found: 403.0817.
4.1.1.7.
amine (7e). Yield 74%; mp 280–281 °C; 1H NMR (400 MHz,
DMSO-d6) 11.33 (s, 1H), 8.05 (d, J = 1.9 Hz, 1H), 8.01 (t,
J = 9.4 Hz, 2H), 7.72 (d, J = 7.5 Hz, 2H), 7.42 (dd, J = 9.4, 2.0 Hz, 1H),
7.38 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.9 Hz, 2H), 4.09 (q, J = 6.9 Hz,
2H), 3.74 (s, 3H), 1.36 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz,
6-Chloro-N-(4-ethoxyphenyl)-2-methoxyacridin-9-
4.1.1.146-Chloro-2-methoxy-N-(4-(trifluoromethoxy)phenyl) acri-
din-9-amine (7l).
d
Yield 66%; mp 288–290 °C; 1H NMR (400 MHz, DMSO-d6) d 8.09
(d, J = 9.1 Hz, 1H), 8.01 (s, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.57 (d,
J = 8.1 Hz, 1H), 7.35–7.45(m, 4H), 7.25 (d, J = 7.9 Hz, 2H), 3.66 (s,
3H). 13C NMR (100 MHz, DMSO-d6) d 155.36, 149.63, 144.33,
141.82, 138.81, 137.01, 127.44, 126.71, 124.01, 123.91, 123.49,
122.53, 122.33, 121.37, 120.21, 118.83, 117.33, 116.29, 114.93,
DMSO-d6)
d 157.49, 155.45, 153.07, 139.91, 138.43, 135.77,
133.29, 127.80, 127.68, 126.13, 123.58, 120.99, 117.88, 115.51,
114.77, 111.42, 103.57, 63.42, 55.67, 14.48; HRMS(ESI): Calcd for
103.42, 55.23; HRMS(ESI): Calcd for
419.0774. Found: 419.0772.
C
21H15ClF3N2O2 [M+H]+
C
22H20ClN2O2 [M+H]+ 379.1213. Found: 379.1202.
4.1.1.8. 6-Chloro-2-methoxy-N-(3,4,5-trimethoxyphenyl)acri-
din-9-amine (7f). Yield 80%; mp 251–253 °C; 1H NMR
(400 MHz, DMSO-d6) d 11.38 (s, 1H), 8.12 (s, 1H), 8.07 (t,
J = 9.6 Hz, 2H), 7.74 (d, J = 9.2 Hz, 2H), 7.47 (d, J = 9.4 Hz, 1H),
6.85 (s, 2H), 3.77 (s, 3H), 3.72 (s, 3H), 3.71 (s, 6H); 13C NMR
(100 MHz, DMSO-d6) d 155.56, 153.62, 153.18, 139.64, 138.65,
136.62, 136.36, 135.69, 128.19, 127.80, 123.80, 120.78, 117.70,
115.04, 111.75, 103.48, 102.77, 60.18, 56.23, 55.73, 40.13, 39.92,
39.71, 39.50, 39.29, 39.08, 38.88; HRMS(ESI): Calcd for
4.1.1.15.
6-Chloro-N-(2-fluorophenyl)-2-methoxyacridin-9-
amine (7m). Yield 69%; mp 280–282 °C; 1H NMR (400 MHz,
DMSO-d6) d 11.33 (s, 1H), 8.15 (s, 1H), 8.13–8.04 (m, 2H), 7.76
(d, J = 9.3 Hz, 1H), 7.71 (s, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.50 (d,
J = 9.4 Hz, 2H), 7.43 (dd, J = 14.4, 7.1 Hz, 2H), 3.72 (s, 3H); 13C
NMR (100 MHz, DMSO-d6) d 157.45, 156.55, 154.98, 154.08,
139.94, 139.56, 136.30, 129.81, 129.74, 129.20, 128.03, 127.28,
126.40, 126.37, 125.22, 121.68, 118.58, 117.53, 117.33, 115.75,
112.64, 103.31, 56.30; HRMS(ESI): Calcd for
C20H15ClFN2O
C
23H22ClN2O4 [M+H]+ 426.1268. Found: 425.1267.
[M+H]+ 353.0857. Found: 353.0847.
4.1.1.9. 3-(6-Chloro-2-methoxyacridin-9-ylamino)phenol (7g).
Yield 71%; mp >300 °C; 1H NMR (400 MHz, DMSO-d6) d 11.25 (s,
1H), 9.95 (s, 1H), 8.09 (d, J = 9.4 Hz, 1H), 8.05 (d, J = 1.7 Hz, 1H),
8.00 (d, J = 9.3 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.47 (dd, J = 9.4,
1.9 Hz, 1H), 7.31 (t, J = 8.1 Hz, 1H), 6.90–6.68 (m, 3H), 3.75 (s, 3H);
HRMS(ESI): Calcd for C20H16ClN2O2 [M+H]+ 351.0900. Found:
351.0896.
4.1.1.16.
6-Chloro-N-(2-chlorophenyl)-2-methoxyacridin-9-
amine (7n). Yield 62%; mp 287–289 °C; 1H NMR (400 MHz,
DMSO-d6) d 11.44 (s, 1H), 8.12 (d, J = 14.4 Hz, 1H), 8.07 (d,
J = 8.8 Hz, 1H), 8.00 (d, J = 9.3 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.67
(dd, J = 6.4 Hz 1H), 7.56–7.60 (m, 2H), 7.46–7.54 (m, 2H), 3.65 (s,
3H); 13C NMR (100 MHz, DMSO-d6) d 155.60, 153.00, 139.42,
138.59, 135.50, 130.51, 128.87, 128.74, 127.68, 127.52, 126.83,
124.11, 120.78, 117.68, 115.14, 112.27, 103.18, 55.55; HRMS(ESI):
Calcd for C20H15Cl2N2O [M+H]+ 369.0561. Found: 369.0550.
4.1.1.10. 2-(6-Chloro-2-methoxyacridin-9-ylamino)phenol (7h).
Yield 56%; mp >300 °C; 1H NMR (400 MHz, DMSO-d6) d 11.17 (s, 1H),
10.19 (s, 1H), 8.13 (d, J = 9.2 Hz, 1H), 8.07 (d, J = 2.1 Hz, 1H), 8.01 (d,
J = 9.2 Hz, 1H), 7.75 (s, 1H), 7.72 (dd, J = 9.2, 2.5 Hz, 1H), 7.46 (m, 2H),
7.38–7.28 (m, 1H), 7.03–7.05 (m, 2H), 3.70 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) d 156.13, 154.71, 152.44, 139.85, 139.40,
135.81, 129.96, 128.66, 127.73, 127.67, 127.46, 124.48, 121.36,
120.61, 118.21, 117.39, 115.02, 112.14, 103.52, 56.09; HRMS(ESI):
Calcd for C20H16ClN2O2 [M+H]+ 351.0900. Found: 351.0905.
4.1.2. General procedure for compound 7o–7r
Various anilines/amines (2.50 mmol) were dissolved in dry DMF
(15 mL) and then sodium hydride (2.50 mmol) was added. The
mixture was stirred under argon for 1 h at room temperature.
The compound 6 (1.00 mmol) and potassium iodide (0.25 mmol)
were added. The mixture was stirred overnight and then poured
into water (50 mL), extracted with ethyl acetate to give the crude
product which had been purified by column chromatography using
petroleum ether and ethyl acetate (3:1 v/v) as the eluent.
4.1.1.11. N1-(6-Chloro-2-methoxyacridin-9-yl)benzene-1,4-dia-
mine (7i). Yield 63%; mp >300 °C; 1H NMR (400 MHz, DMSO-d6) d
11.25 (s, 1H), 8.04 (s, 2H), 7.97 (d, J = 9.2 Hz, 1H), 7.72 (s, 1H), 7.65
(d, J = 8.8 Hz, 1H), 7.36 (d, J = 7.7 Hz, 1H), 7.11 (d, J = 8.1 Hz, 2H),
6.71 (d, J = 8.2 Hz, 2H), 5.61 (s, 2H), 3.75 (s, 3H); 13C NMR
4.1.2.1.
6-Chloro-2-methoxy-N-(pyridin-4-yl)acridin-9-amine
(7o). Yield 56%; mp >300 °C; 1H NMR (400 MHz, DMSO-d6) d
9.65 (s, 1H), 8.36–7.82 (m, 5H), 7.55 (s, 2H), 7.27 (s, 1H), 6.62 (s,