754
Vol. 61, No. 7
J=4.4Hz, 4H), 3.32 (t, J=4.8Hz, 4H).
N-(5-Nitroisoquinolin-1-yl)-2,3-dihydrobenzo[b][1,4]-
118.5, 117.2, 108.8, 105.7, 56.9.
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-4-
dioxine-6-carboxamide (11i): Yellow solid, yield 32%; methylbenzamide (2c): Brown solid, yield 27%; MS m/z: 420
1
1H-NMR (DMSO-d6) δ: 11.05 (s, 1H), 8.63 (d, J=7.2Hz, 1H), [M+1]+; H-NMR (DMSO-d6) δ: 10.94 (s, 1H), 8.99 (s, 1H),
8.17 (d, J=8.4Hz, 1H), 7.89 (d, J=8.3Hz, 1H), 7.80 (dd, J=2.1, 8.34 (s, 1H), 8.21 (d, J=4.8Hz, 1H), 8.04–8.01 (m, 1H), 7.93
2.2Hz, 1H), 7.74 (d, J=2.1Hz, 1H), 7.66 (d, J=7.5Hz, 1H), (d, J=8.5Hz, 1H), 7.73–7.66 (m, 5H), 7.40–7.36 (m, 2H), 7.27
7.54–7.51 (m, 1H), 7.18 (d, J=8.5Hz, 1H), 4.44–4.36 (m, 4H).
(t, J=6.8Hz, 1H), 6.87 (d, J=7.4Hz, 1H), 6.13 (s, 1H), 5.82 (s,
4,7-Dimethoxy-N-(5-nitroisoquinolin-1-yl)-1-naphthamide 2H), 2.42 (s, 3H); 13C-NMR (DMSO-d6) δ: 166.9, 160.5, 152.6,
(11j): Yellow solid, yield 23%; 1H-NMR (DMSO-d6) δ: 150.0, 149.0, 146.6, 144.7, 142.0, 139.0, 138.0, 134.0, 130.6,
11.41 (s, 1H), 8.65 (d, J=7.6Hz, 1H), 8.56 (brs, 1H), 8.18 (d, 129.8, 127.7, 126.2, 125.0, 124.6, 123.7, 122.5, 118.2, 117.6,
J=9.2Hz, 3H), 8.06 (brs, 1H), 7.90–7.85 (m, 2H), 7.22 (dd, 112.6, 107.7, 22.7.
J=2.5, 2.6Hz, 1H), 6.98 (d, J=8.2Hz, 1H), 4.05 (s, 3H), 3.80
(s, 3H).
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-3-
(trifluoromethyl)-benzamide (2d): Green solid, yield 57%;
2,5-Dimethyl-N-(5-nitroisoquinolin-1-yl)furan-3- MS m/z: 474 [M+1]+; H-NMR (DMSO-d6) δ: 8.95 (s, 1H),
carboxamide (11k): Pale yellow solid, yield 17%; 1H-NMR 8.57–8.52 (m, 2H), 8.48 (brs, 1H), 8.19 (t, J=8.4Hz, 2H), 8.05
(DMSO-d6) δ: 10.65 (s, 1H), 8.65–8.61 (m, 2H), 8.38 (d, (d, J=5.2Hz, 1H), 7.92–7.88 (m, 2H), 7.75–7.70 (m, 2H), 7.63
J=8.4Hz, 1H), 8.23 (d, J=6.0Hz, 1H), 7.85 (t, J=8.1Hz, 1H), (d, J=7.3Hz, 1H), 7.26 (t, J=7.8Hz, 2H), 6.86 (d, J=7.3Hz,
1
6.76 (s, 1H), 2.49 (s, 3H), 2.30 (s, 3H).
1H), 6.08 (d, J=4.9Hz, 1H), 5.81 (s, 2H); 13C-NMR (DMSO-
N-(5-Nitroisoquinolin-1-yl)thiazole-4-carboxamide
(11l): d6) δ: 166.3, 149.6, 147.0, 145.3, 138.1, 135.7, 135.1, 134.2,
Yellow solid, yield 31%; 1H-NMR (DMSO-d6) δ: 11.11 (s, 132.4, 131.5, 129.6, 129.3, 128.9, 128.8, 127.8, 127.0, 126.1,
1H), 9.33 (s, 1H), 8.66 (d, J=7.5Hz, 2H), 8.61 (s, 1H), 8.47 (d, 125.6, 125.3, 124.8, 124.6, 124.1, 119.4, 108.8, 107.9, 101.9.
J=8.3Hz, 1H), 8.27 (d, J=6.0Hz, 1H), 7.86 (t, J=8.0Hz, 1H).
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-4-
1-(4-Methoxyphenyl)-N-(5-nitroisoquinolin-1-yl)- chloro-3-(trifluoromethyl)benzamide (2e): Brown solid, yield
5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (11m): Yellow 91%; MS m/z: 508 [M+1]+; 1H-NMR (CDCl3) δ: 15.61 (s,
1
solid, yield 50%; H-NMR (DMSO-d6) δ: 11.42 (s, 1H), 8.64 1H), 8.98 (d, J=7.8Hz, 1H), 8.81 (s, 1H), 8.55 (d, J=8.9Hz,
(d, J=7.6Hz, 1H), 8.54–8.47 (m, 3H), 8.46 (s, 1H), 7.88 (t, 1H), 8.38 (d, J=5.2Hz, 1H), 7.83 (d, J=7.5Hz, 1H), 7.78–7.75
J=8.0Hz, 1H), 7.48 (d, J=8.7Hz, 2H), 7.12 (d, J=8.8Hz, 2H). (m, 2H), 7.63 (d, J=8.0Hz, 1H), 7.41–7.36 (m, 2H), 7.17 (d,
General Procedure for the Preparation of N-(5-Ami- J=7.6Hz, 1H), 6.98 (d, J=7.4Hz, 1H), 6.65 (s, 1H), 6.32 (s,
noisoquinolin-1-yl)-substituted 2-Carboxamides (12a–m) 1H), 5.06 (s, 2H); 13C-NMR (DMSO-d6) δ: 166.8, 165.1, 150.2,
According to the procedure described for 6a–o, compounds 149.3, 146.3, 142.6, 140.8, 139.8, 137.9, 135.9, 133.0, 130.8,
12a–m were obtained from the corresponding 11a–m in 128.5, 127.6, 125.3, 122.9, 122.0, 119.7, 116.6, 112.8, 110.8,
38–85% yield.
108.2, 106.8, 104.2, 103.9, 102.2.
General Procedure for the Preparation of N-(5-
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-2,4-
((8-Nitroquinolin-4-yl)amino)isoquinolin-1-yl)-substituted bis(trifluoromethyl)benzamide (2f): Yellow solid, yield 79%;
1
2-Carboxamides (13a–m) According to the procedure de- MS m/z: 542 [M+1]+; H-NMR (DMSO-d6) δ: 12.06 (s, 1H),
scribed for 5a–o, compounds 13a–m were obtained from the 9.18 (s, 1H), 8.29 (d, J=6.7Hz, 1H), 8.23–8.16 (m, 3H), 8.11
corresponding 12a–m. 13a: 27%; 13b: 25%; 13c: 22%; 13d: (d, J=4.8Hz, 2H), 7.79–7.76 (m, 2H), 7.61 (d, J=8.2Hz, 1H),
25%; 13e: 23%; 13f: 28%; 13g: 19%; 13h: 22%; 13i: 25%; 13j: 7.46 (s, 1H), 7.26 (t, J=7.6Hz, 1H), 6.86 (d, J=7.3Hz, 1H),
31%; 13k: 26%; 13l: 20%; 13m: 17%.
6.10 (d, J=4.9Hz, 1H), 5.82 (s, 2H); 13C-NMR (DMSO-d6)
General Procedure for the Preparation of Target Com- δ: 167.7, 149.5, 147.0, 145.3, 138.1, 136.2, 134.2, 130.3, 130.1,
pounds (2a–m) The target compounds 2a–m were prepared 129.7, 129.5, 128.5, 127.6, 127.2, 126.9, 126.8, 125.6, 125.0,
from the corresponding 13a–m as described for 1a–o.
125.0, 123.5, 123.4, 123.3, 121.3, 119.5, 108.8, 107.9, 102.1.
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-3,4-
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-3,5-
dimethoxybenzamide (2a): Brown solid, yield 16%; MS m/z: bis(trifluoromethyl)benzamide (2g): Pale brown solid, yield
1
466 [M+1]+; 1H-NMR (DMSO-d6) δ: 10.91 (s, 1H), 8.99 92%; MS m/z: 542 [M+1]+; H-NMR (CDCl3) δ: 14.31 (s, 1H),
(s, 1H), 8.20 (d, J=5.1Hz, 1H), 7.79–7.71 (m, 7H), 7.62 (d, 8.97 (d, J=7.9Hz, 1H), 8.89 (s, 2H), 8.35 (d, J=5.0Hz, 1H),
J=8.4Hz, 1H), 7.27 (t, J=7.8Hz, 1H), 7.12 (d, J=8.5Hz, 1H), 8.00 (s, 1H), 7.83 (d, J=7.1Hz, 1H), 7.78 (d, J=8.0Hz, 1H),
6.87 (d, J=6.9Hz, 1H), 6.12 (d, J=5.1Hz, 1H), 5.82 (s, 2H), 7.46 (d, J=7.1Hz, 1H), 7.35–7.31 (m, 2H), 7.20 (d, J=6.9Hz,
3.86 (s, 6H); 13C-NMR (DMSO-d6) δ: 167.0, 162.7, 155.8, 1H), 6.96 (d, J=6.2Hz, 1H), 6.81 (s, 1H), 6.30 (d, J=4.9Hz,
150.3, 146.1, 140.8, 134.2, 130.8, 130.1, 129.6, 129.0, 128.5, 1H), 5.06 (s, 2H); 13C-NMR (DMSO-d6) δ: 167.3, 165.8, 152.3,
127.3, 127.1, 126.9, 126.6, 125.2, 125.0, 124.6, 123.7, 123.3, 152.0, 148.0, 145.7, 144.0, 140.5, 137.9, 135.0, 132.8, 130.9,
122.9, 121.0, 115.8, 109.8, 56.5.
127.7, 125.9, 125.5, 123.6, 122.9, 120.6, 119.9, 115.7, 110.0,
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-3,5- 107.8, 106.8, 102.9.
dimethoxybenzamide (2b): Brown solid, yield 9%; MS m/z:
N-(5-(8-Aminoquinolin-4-ylamino)isoquinolin-1-yl)-3-
466 [M+1]+; 1H-NMR (DMSO-d6) δ: 10.97 (s, 1H), 8.96 morpholino-5-(trifluoromethyl)benzamide (2h): Brown solid,
(s, 1H), 8.20 (d, J=5.1Hz, 2H), 7.75–7.71 (m, 3H), 7.62 (d, yield 21%; MS m/z: 559 [M+1]+; H-NMR (DMSO-d6) δ: 8.95
1
J=8.0Hz, 1H), 7.35 (s, 1H), 7.26 (t, J=7.7Hz, 1H), 7.08–7.06 (s, 1H), 8.23 (d, J=5.2Hz, 1H), 8.12 (brs, 1H), 8.02 (s, 1H),
(m, 1H), 6.87 (d, J=7.6Hz, 1H), 6.73 (s, 1H), 6.11 (d, 7.91 (s, 1H), 7.71 (m, 4H), 7.62 (d, J=8.2Hz, 1H), 7.42–7.37
J=5.1Hz, 1H), 5.82 (s, 2H); 13C-NMR (DMSO-d6) δ: 166.9, (m, 2H), 7.26 (t, J=7.8Hz, 1H), 6.86 (d, J=7.4Hz, 1H), 6.09
161.6, 160.8, 157.7, 152.6, 150.0, 148.0, 146.0, 144.7, 140.6, (d, J=5.0Hz, 1H), 5.82 (s, 2H), 3.80 (t, J=4.2Hz, 4H), 3.32 (t,
140.0, 138.3, 135.4, 132.6, 128.1, 126.8, 125.0, 124.4, 122.5, J=3.8Hz, 4H); 13C-NMR (DMSO-d6) δ: 165.9, 164.8, 150.8,