1028
M. Staderini et al. / Tetrahedron 69 (2013) 1024e1030
4.2. Synthesis of 9-aminoacridines, 4-aminoquinolines and 4-
aminoquinazolines. General method
1560, 1510, 1420, 1226, 1119, 928 cmꢁ1. Elementalanalysis calcd (%)for
24H22N3: C 68.65, H 5.28, N 10.01; found: C 68.34, H 5.63, N 9.67.
C
The suitable starting heterocycle (1 mmol), the corresponding
amine [1 equiv, except ethylenediamine (4 equiv), imidazole and
benzimidazole (2 equiv)] and 2 equiv of phenol were charged in
a pressure-tight microwave tube containing a stirring bar. The
reaction mixture was submitted to microwave irradiation for
30e45 min at 120 ꢀC, with an irradiation power of 150 W, using
a CEM Discover SP focused microwave reactor. The crude mixture
was diluted with 5 ml of a 10% KOH aqueous solution and stirred
until a precipitate was formed. Filtration afforded a solid was
dried overnight in the presence of P2O5 to give the pure final
products.
4.2.6. 6-Chloro-N-hexyl-2-methoxyacridin-9-amine (6). Yellow solid;
mp: 103 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.10 (d, J¼2.0 Hz, 1H), 8.06
(d, J¼4.7 Hz, 1H), 8.02 (d, J¼4.9 Hz, 1H), 7.46 (dd, J¼9.4, 2.7 Hz, 1H),
7.34 (dd, J¼9.3, 2.1 Hz, 1H), 7.23 (d, J¼2.6 Hz, 1H), 4.72 (br s, 1H), 4.00
(s, 3H), 3.77e3.69 (m, 2H), 1.79 (dt, J¼14.8, 7.3 Hz, 2H), 1.53e1.41 (m,
2H), 1.36e1.30 (m, 4H), 0.90 (t, J¼7.2 Hz, 3H) ppm; 13C NMR (63 MHz,
DMSO)
d 155.4, 150.8, 148.6, 146.5, 133.7, 131.2, 127.6, 126.9, 124.6,
123.0,117.4,114.9, 100.9, 56.0, 49.8, 31.3, 30.8, 26.3, 22.4, 14.2 ppm; IR
(NaCl):
n 1665, 1606, 1561, 1518, 1465, 1433, 1356, 1235, 1112,
1032 cmꢁ1. Elemental analysis calcd (%) for C20H23N2: C 70.06, H 6.76,
N 8.17; found: C 70.39, H 6.80, N 8.51.
4.2.1. 6-Chloro-2-methoxy-N-phenylacridin-9-amine(1). Yellow solid;
4.2.7. N-Benzyl-6-chloro-2-methoxyacridin-9-amine (7). Yellow solid;
mp: 202 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.21 (d, J¼2.0 Hz,1H), 8.11 (d,
mp: 175 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.13 (d, J¼1.9 Hz, 1H), 8.02 (t,
J¼9.4 Hz, 1H), 7.99 (d, J¼9.3 Hz, 1H), 7.48 (dd, J¼9.4, 2.7 Hz, 1H), 7.36
(dd, J¼9.3, 2.1 Hz,1H), 7.30e7.24 (m, 2H), 7.12 (d, J¼2.7 Hz,1H), 6.98 (t,
J¼7.4 Hz, 1H), 6.84 (d, J¼7.6 Hz, 2H), 6.48 (br s, 1H), 3.79 ppm (s,
J¼9.7 Hz, 2H), 7.46e7.39 (m, 6H), 7.33 (dd, J¼9.3, 2.0 Hz, 1H), 7.17 (d,
J¼2.5 Hz,1H), 4.90 (s, 2H), 3.81 (s, 3H) ppm; 13C NMR (63 MHz, CDCl3)
d
156.6, 149.9, 148.6, 147.3, 139.7, 135.3, 131.9, 129.5, 128.7, 128.4, 127.8,
3H) ppm; 13C NMR (63 MHz, acetone)
d
158.0, 149.6, 149.0, 146.8,
125.4,125.32,124.2,118.6,116.7, 99.6, 55.8, 55.1 ppm; IR (NaCl): n 1630,
135.3, 133.0, 130.8, 130.4, 129.5, 127.3, 126.7, 126.5, 122.9, 122.0, 120.8,
1557, 1432, 1345,1228, 1069, 1028, 825 cmꢁ1. Elemental analysis calcd
(%) for C21H17N2: C 72.31, H 4.91, N 8.03; found: C 72.29, H 4.86, N 7.73.
118.4, 101.4, 56.2 ppm; IR (NaCl): n 2356, 1629, 1559, 1493, 1420, 1226,
828, 753 cmꢁ1. Elemental analysis calcd (%) for C20H15N2: C 71.75, H
4.52, N 8.37; found: C 71.43, H 4.24, 7.91.
4.2.8. N-(1-Benzylpiperidin-4-yl)-6-chloro-2-methoxyacridin-9-
amine (8). Yellowsolid; mp: 136 ꢀC; 1HNMR (250MHz, CDCl3)
d 8.12
4.2.2. 6-Chloro-2-methoxy-N-(4-methoxyphenyl)acridin-9-amine
(d, J¼1.8 Hz, 1H), 8.06e7.99 (m, 2H), 7.46 (dd, J¼9.4, 2.6 Hz, 1H),
7.40e7.31 (m, 6H), 7.21 (d, J¼2.5 Hz, 1H), 3.99 (s, 3H), 3.76e3.67 (m,
1H), 3.53 (s, 2H), 2.93 (d, J¼11.3 Hz, 2H), 2.07 (t, J¼10.5 Hz, 4H),
(2). Yellow solid; mp: 302 ꢀC; 1H NMR (250 MHz, CDCl3)
d 8.14 (s,
1H), 8.04 (d, J¼9.4 Hz, 1H), 7.93 (d, J¼9.3 Hz, 1H), 7.43 (dd, J¼9.4,
2.7 Hz, 1H), 7.29 (dd, J¼9.2, 2.0 Hz, 1H), 7.10 (d, J¼2.6 Hz, 1H),
6.92e6.83 (m, 4H), 3.82 (s, 3H), 3.76 (s, 3H) ppm; 13C NMR (63 MHz,
1.83e1.75 (m, 2H) ppm; 13C NMR (63 MHz, CDCl3)
d 156.8, 149.7,
148.3, 147.1, 137.8, 135.5, 131.5, 129.8, 128.7, 128.2, 127.8, 125.7, 125.5,
acetone)
127.3, 126.3, 125.7, 121.6, 121.4, 119.2, 115.7, 101.4, 56.2 ppm; IR
(NaCl):
3306, 1630, 1560, 1507, 1466, 1420, 1362, 1237, 1033 cmꢁ1
d
157.6, 156.4, 149.8, 148.9, 145.3, 140.0, 135.1, 132.9, 129.4,
124.5, 120.2, 118.0, 99.4, 63.5, 57.8, 55.9, 52.9, 34.2 ppm; IR (NaCl): n
1629, 1518, 1466, 1344, 1233, 923 cmꢁ1. Elemental analysis calcd (%)
for C26H26N3: C 72.29, H 6.07, N 9.73; found: C 72.19, 5.73, 9.75.
n
.
Elemental analysis calcd (%) for C21H17N2: C 69.14, H 4.70, N 7.68;
found: C 68.99, H 4.75, N 7.55.
4.2.9. 4-(6-Chloro-2-methoxyacridin-9-yl)morpholine (9). Yellow sol-
id; mp: 260 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.37 (d, J¼9.3 Hz, 1H),
4.2.3. N1-(6-Chloro-2-methoxyacridin-9-yl)-N4,N4-dimethylbenzene-
8.21 (d, J¼1.9 Hz, 1H), 8.12 (d, J¼9.4 Hz, 1H), 7.58 (d, J¼2.7 Hz, 1H),
7.52e7.44 (m, 2H), 4.08 (t, J¼4.4 Hz, 4H), 4.04 (s, 3H), 3.61 (t, J¼4.4 Hz,
1,4-diamine (3). Deep red solid; mp: 198 ꢀC; 1H NMR (250 MHz,
CDCl3)
d
8.12 (d, J¼1.5 Hz, 1H), 8.03 (d, J¼9.4 Hz, 1H), 7.92 (d,
4H) ppm; 13C NMR (63 MHz, CDCl3)
d 157.5, 152.1, 148.9, 148.2, 135.4,
J¼9.3 Hz, 1H), 7.40 (dd, J¼9.1, 2.3 Hz, 1H), 7.25 (dd, J¼11.5, 1.9 Hz,
131.7, 128.5, 127.0, 126.0, 126.0, 125.9, 123.7, 100.4, 68.6, 56.0,
1H), 7.13 (d, J¼2.4 Hz, 1H), 6.96 (d, J¼8.7 Hz, 2H), 6.73 (d,
52.4 ppm; IR (NaCl):
n 1628, 1553, 1466, 1417, 1222, 1113, 1026,
J¼8.8 Hz, 2H), 3.75 (s, 3H), 2.95 (s, 6H) ppm; IR (NaCl):
n
1629,
928 cmꢁ1. Elemental analysis calcd (%) for C18H17N2: C 65.75, H 5.21, N
8.52; found: C 65.69, H 4.82, N 8.39.
1559, 1515, 1474, 1420, 1349, 1260, 1225 cmꢁ1. Elemental analysis
calcd (%) for C22H20N3: C 69.93, H 5.33, N 11.12; found: C 69.78, H
5.65, N 10.74.
4.2.10. N1-(6-Chloro-2-methoxyacridin-9-yl)ethane-1,2-diamine
(10). Yellow solid; mp: 128 ꢀC; 1H NMR (250 MHz, CDCl3)
d 8.18 (d,
4.2.4. 6-Chloro-2-methoxy-N-(4-(piperidin-1-yl)phenyl)acridin-9-
J¼9.3 Hz,1H), 8.10 (d, J¼2.0 Hz, 1H), 8.03 (d, J¼9.2 Hz, 1H), 7.48e7.41
amine (4). Deep red solid; mp: 217 ꢀC; 1H NMR (250 MHz, CDCl3)
(m, 2H), 7.34 (dd, J¼9.3, 2.1 Hz, 1H), 4.00 (s, 3H), 3.78e3.73 (m, 2H),
d
8.14 (s, 1H), 8.04 (d, J¼9.4 Hz, 1H), 7.93 (d, J¼9.3 Hz, 1H), 7.39e7.32
3.04 (t, J¼5.6 Hz, 2H) ppm; IR (NaCl):
n 2922, 1630, 1560, 1518, 1466,
(m, 2H); 7.25e7.21 (m, 2H), 7.15 (s, 1H), 7.04e6.87 (m, 4H), 3.76 (s,
3H), 3.13 (t, J¼5.4 Hz, 4H), 1.75e1.60 (m, 6H) ppm; 13C NMR
1432, 1234, 1073, 1031 cmꢁ1. Elemental analysis calcd (%) for
16H23N3: C 63.68, H 5.34, N 13.92; found: C 63.34, H 5.23, N 13.88.
C
(63 MHz, CDCl3) d 156.2,156.2,154.7,151.0,139.8,130.0,128.0,127.2,
125.0, 124.5, 122.4, 120.9, 119.8, 117.4, 116.5, 115.8, 103.0, 56.1, 50.8,
4.2.11. 6-Chloro-9-(1H-imidazol-1-yl)-2-methoxy acridine (11). Yell-
ow solid; mp: 222 ꢀC; 1H NMR (250 MHz, CDCl3)
26.0, 24.6 ppm; IR (NaCl):
n
1626, 1570, 1508, 1269, 1235, 1157, 1084,
d
8.32 (d, J¼1.2 Hz,
752 cmꢁ1. Elemental analysis calcd (%) for C25H24N3: C 71.85, H 5.79,
N 10.05; found: C 71.70, H 5.53, N 9.72.
1H), 8.21 (d, J¼9.5 Hz, 1H), 7.87 (s, 1H), 7.56 (dd, J¼9.5, 2.8 Hz, 1H),
7.53e7.45 (m, 3H), 7.34 (t, J¼1.2 Hz, 1H), 6.63 (d, J¼2.7 Hz, 1H), 3.85
(s, 3H) ppm; 13C NMR (63 MHz, CDCl3)
d 159.5, 147.8, 147.7, 139.2,
4.2.5. 6-Chloro-2-methoxy-N-(4-morpholinophenyl)acridin-9-amine
136.7,136.1,131.90,130.9,129.6,128.7,127.3,124.7,123.9,122.3,122.2,
(5). Brown solid; mp: 241 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.14 (s,1H),
97.6, 56.1 ppm; IR (NaCl): n 3095, 1635, 1560, 1476, 1423, 1236,
8.05(d,J¼9.2Hz,1H),7.93(d,J¼9.2Hz,1H),7.42(dd, J¼9.4,2.6Hz,1H),
7.29e7.26 (m, 1H, overlapped with the residual CHCl3 signal), 7.12 (d,
J¼2.5 Hz, 1H), 6.93e6.85 (m, 4H), 3.91e3.90 (t, J¼4.7 Hz, 4H), 3.77 (s,
831 cmꢁ1. Elemental analysis calcd (%) for C17H12N3: C 65.92, H 3.90,
N 13.57; found: C 65.90, H 4.03, N 13.39.
3H), 3.12 (t, J¼4.7 Hz, 4H) ppm; 13C NMR (63 MHz, CDCl3)
d
156.7,
4.2.12. 9-(1H-Benzo[d]imidazol-1-yl)-6-chloro-2-methoxyacridine
148.2, 147.3, 143.7, 138.4, 135.5, 131.2, 128.0, 128.0, 125.8, 125.8, 125.3,
(12). Yellow solid; mp: 233 ꢀC; 1H NMR (250 MHz, CDCl3)
d
8.40 (d,
120.6,120.3,118.5,117.6,100.3, 67.3, 55.8, 50.5 ppm; IR (NaCl): n 1630,
J¼1.6 Hz, 1H), 8.30 (d, J¼9.5 Hz, 1H), 8.25 (s, 1H), 8.08 (d, J¼8.1 Hz,