480
M. Paige et al. / Bioorg. Med. Chem. 22 (2014) 478–487
by silica gel column chromatography eluting with methylene chlo-
ride as methanol as the mobile phase.
1H), 5.91(s, 1H), 3.89 (s, 3 H), 3.45 (m, 2H), 2.90 (m, 2H). 13C NMR
(100.17 MHz, CDCl3) d: 181.4, 181.2, 155.1, 154.0, 149.2, 147.2,
134.7, 130.5, 130.2, 127.7, 127.3 126.2, 122.8, 112.4, 102.2, 56.2,
43.6, 33.1.
2.4.1. 2-((3,5-Dibromo-4-hydroxyphenethyl)amino)
naphthalene-1,4-dione (18)
Yield: 0.056 g (0.13 mmol, 20% yield).
2.4.8. 7-((3-Bromo-4-methoxyphenethyl)amino)quinoline-5,8-
dione (21e)
1H NMR (400 MHz, DMSO-d6) d: 9.78 (s, 1H), 7.95 (m, 2H), 7.80
(dd, J = 1.5, 7.5 Hz, 1H), 7.75 (dd, J = 1.5, 7.5 Hz, 2H), 7.51 (s, 2H),
5.81 (s, 1H), 3.41 (m, 2H), 2.91 (t, J = 7.3 Hz, 2H). 13C NMR
(100.17 MHz, DMSO-d6) d: 182.1, 181.8, 148.9, 148.1, 134.7,
133.4, 133.0, 132.4, 132.0, 130.2, 125.8, 125.2, 111.7, 99.7, 42.8,
31.5.
Yield: 0.036 g (0.093 mmol, 15%).
1H NMR (400 MHz, CDCl3) d: 9.00 (d, 1H), 8.31 (d, 1H), 7.57 (m,
1H), 7.58 (m, 1H), 7.47 (m, 1H), 7.06 (m, 1H), 6.92 (m, 1H), 5.95 (s,
1H), 5.90 (s, 1H), 3.84 (s, 3 H), 3.41 (m, 2H), 2.87 (m, 2H). 13C NMR
(100.17 MHz, CDCl3) d: 181.6, 180.5, 155.5, 153.8, 149.0, 147.1,
134.9, 130.7, 130.0, 127.5, 127.1 126.5, 122.4, 112.2, 102.4, 56.4,
43.1, 32.7.
2.4.2. 7-((3,5-Dibromo-4-hydroxyphenethyl)amino)
isoquinoline-5,8-dione (19)
Yield: 0.028 g (0.13 mmol, 20% yield).
2.4.9. 7-((3,4-Dihydroxyphenethyl)amino)quinoline-5,8-dione
(21g)
1H NMR (400 MHz, DMSO-d6) d: 9.15 (d, J = 1.9 Hz, 1H), 9.07
(dd, J = 1.9, 8.1 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 7.41
(s, 2H), 5.92 (s, 1H), 3.44 (m, 2H), 2.87 (t, J = 7.3, 2H). 13C NMR
(100.17 MHz, DMSO-d6) d: 181.7, 180.9, 150.4, 149.2, 148.5,
145.1, 140.3, 139.9, 133.6, 133.1, 130.1, 112.2, 100.6, 41.3, 31.4.
Yield: 0.018 g (0.055 mmol, 10%).
1H NMR (400 MHz, DMSO-d6) d: 8.97 (d, 1H), 8.71 (s, 1H), 8.34
(d, 1H), 7.63 (m, 1H), 7.42 (s, 1H), 6.86 (d, 1H), 6.73 (m, 2H), 5.92 (s,
1H), 3.35 (m, 2H), 2.78 (m, 2H). 13C NMR (100.17 MHz, DMSO-d6)
d: 181.8, 180.4, 155.7, 150.4, 148.2, 145.9, 145.1, 136.3, 134.7,
132.0, 130.3, 123.7, 116.2, 115.5, 100.7, 41.1, 31.6.
2.4.3. 6-((3,5-Dibromo-4-hydroxyphenethyl)amino)
phthalazine-5,8-dione (20a)
Yield: 0.072 g (0.13 mmol, 20% yield).
2.4.10. 7-((3,4,5-Trihydroxyphenethyl)amino)quinoline-5,8-
dione (21h)
1H NMR (400 MHz, DMSO-d6) d: 9.71 (s, 1H), 9.60 (s, 1H), 7.91
(s, 1H), 7.45 (s, 2H), 5.95 (s, 1H), 3.47 (m, 2H), 2.84 (t, J = 7.1 Hz,
2H). 13C NMR (100.17 MHz, DMSO-d6) d: 181.7, 180.9, 150.4,
149.2, 148.5, 145.1, 140.3, 139.9, 133.6, 133.1, 130.1, 112.2,
100.6, 41.3, 31.4.
1H NMR (400 MHz, DMSO-d6) d: 8.94 (d, 1H), 8.32 (d, 1H), 7.61
(m, 1H), 7.51 (s, 1H), 6.42 (s, 2H), 5.92 (s, 1H), 3.41 (m, 2H), 2.84
(m, 2H). 13C NMR (100.17 MHz, DMSO-d6) d: 181.3, 180.2, 154.1,
149.2, 148.1, 147.3, 136.2, 133.1, 132.5, 127.4, 126.4, 109.8,
100.3, 41.7, 32.0.
2.4.4. 7-(Phenethylamino)quinoline-5,8-dione (21a)
Yield: 0.048 g (0.17 mmol, 79%).
2.4.11. 7-((3,4-Dimethoxyphenethyl)amino)quinoline-5,8-dione
(21i)
1H NMR (400 MHz, DMSO-d6) d: 9.01 (d, J = 4.6 Hz, 1H), 8.32 (d,
J = 8.0 Hz, 1H), 7.72 (dd, J = 4.6, 8.0 Hz, 1H), 7.60 (t, J = 6.1 Hz, 1H),
7.40 (dd, J = 4.1, 8.2 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.27 (dd, J = 1.8,
4.2 Hz, 1H), 5.90 (s, 1H), 3.34 (q, J = 6.7 Hz, 2H), 2.81 (t, J = 7.3 Hz,
2H). 13C NMR (100.17 MHz, DMSO-d6) d: 181.5, 180.0, 154.5,
149.2, 148.5, 147.8, 133.8, 133.5, 127.4, 127.1, 126.4, 111.8,
101.1, 42.9, 31.6.
Yield: 0.014 g (0.043 mmol, 12%).
1H NMR (400 MHz, CDCl3) d: 8.91 (d, 1H), 8.40 (d, 1H), 7.61 (m,
1H), 6.83 (m, 3 H), 6.03 (s, 1H), 5.91 (s, 1H), 3.81 (s, 3 H), 3.79 (s, 3
H), 3.40 (m, 2H), 2.92 (m, 2H). 13C NMR (100.17 MHz, CDCl3) d:
181.4, 180.3, 153.2, 149.3, 148.1, 146.7, 140.0, 134.1, 132.0,
130.8, 130.0, 128.3, 120.7 111.7, 111.6, 100.4, 56.0, 59.4, 44.0, 33.9
2.4.5. 7-((3-Chlorophenethyl)amino)quinoline-5,8-dione (21b)
Yield: 0.013 g (0.041 mmol, 11%).
2.4.12. 7-((3,4-Bis(benzyloxy)phenethyl)amino)quinoline-5,8-
dione (21j)
1H NMR (400 MHz, DMSO-d6) d: 8.95(d, J = 4.5 Hz, 1H), 8.31 (d,
J = 7.9 Hz, 1H), 7.74 (dd, J = 4.5, 7.9 Hz, 1H), 7.60 (t, J = 6.0, 1H), 7.49
(d, J = 8.1 Hz, 1H), 7.34 (dd, J = 4.2, 8.0 Hz, 1H), 7.31 (d, J = 4.2 Hz,
1H), 7.17 (d, J = 1.9 Hz, 1H), 5.91 (s, 1H), 3.26 (q, J = 6.5 Hz, 2H),
2.82 (t, J = 7.1 Hz, 2H). 13C NMR (100.17 MHz, DMSO-d6) d: 181.5,
180.0, 154.5, 148.5, 147.8, 140.9, 134.2, 133.8, 133.7, 130.0,
129.1, 127.3, 126.0, 125.9, 101.3, 42.8, 31.7.
Yield: 0.079 g (0.24 mmol, 39%).
1H NMR (400 MHz, CDCl3) d: 9.01 (d, 1H), 8.18 (d, 1H), 7.60 (m,
1H), 7.58–7.20 (m, 10 H), 6.81–6.74 (m, 3 H), 5.91 (s, 1H), 5.08 (d, 4
H), 3.41 (m, 2H), 2.91 (m, 2H). 13C NMR (100.17 MHz, CDCl3) d:
181.9, 180.4, 154.9, 149.1, 148.8, 148.3, 147.3, 137.9, 137.8,
134.3, 132.4, 128.8, 128.7, 128.2, 128.1, 128.0, 127.9, 127.8,
126.9, 121.8, 115.7, 115.2, 101.3, 70.7, 70.6, 43.8, 33.4.
2.4.6. 7-((3-Bromophenethyl)amino)quinoline-5,8-dione (21c)
Yield: 0.031 g (0.087 mmol, 24%).
2.4.13. 7-((3,5-Dichloro-4-hydroxyphenethyl)amino)quinoline-
5,8-dione (21k)
1H NMR (400 MHz, DMSO-d6) d: 8.97 (d, J = 4.7 Hz, 1H), 8.34 (d,
J = 8.0 Hz, 1H), 7.76 (dd, J = 4.8, 8.0 Hz, 1H), 7.49 (d, J = 7.9 Hz, 1H),
7.34 (dd, J = 1.9, 7.9 Hz, 1H), 7.31 (d, J = 4.1 Hz, 1H), 7.17 (d,
J = 4.1 Hz, 1H), 5.94 (s, 1H), 5.82 (s, 1H), 3.42 (q, J = 6.6, 2H), 2.82
(t, J = 7.1, 2H). 13C NMR (100.17 MHz, DMSO-d6) d: 182.3, 181.4,
155.1, 149.2, 148.3, 141.1, 135.2, 132.7, 130.1, 129.4, 128.7,
128.1, 126.7, 121.0, 101.3, 42.8, 31.7.
Yield: 0.13 g (0.41 mmol, 57%).
1H NMR (400 MHz, DMSO-d6) d: 8.92 (d, 1H), 8.32 (d, 1H), 7.61
(m, 1H), 7.51 (s, 1H), 7.28 (s, 2H), 5.91 (s, 1H), 3.39 (m, 2H), 2.81
(m, 2H). 13C NMR (100.17 MHz, DMSO-d6) d: 181.5, 180.0, 154.5,
149.0, 148.7, 147.9, 133.9, 133.5, 132.5, 127.4, 126.4, 111.8,
101.9, 42.9, 31.6.
2.4.14. 7-((3,5-Difluoro-4-hydroxyphenethyl)amino)quinoline-
5,8-dione (21l)
2.4.7. 7-((3-Chloro-4-methoxyphenethyl)amino)quinoline-5,8-
dione (21d)
Yield: 0.063 g (0.189 mmol, 30%).
Yield: 0.015 g (0.087 mmol, 10%)
1H NMR (400 MHz, DMSO-d6) d: 9.91 (s, 1H), 8.97 (d, J = 4.3 Hz,
1H), 8.27 (d, J = 8.0 Hz, 1H), 7.71 (dd, J = 4.3, 8.0 Hz, 1H), 7.51 (s,
1H), 7.01 (d, J = 9.4 Hz, 2H), 5.89 (s, 1H), 3.41 (q, J = 6.6 Hz, 2H),
1H NMR (400 MHz, CDCl3) d: 9.01 (d, 1H), 8.34 (d, 1H), 7.55 (m,
1H), 7.60 (m, 1H), 7.21 (m, 1H), 7.05 (m, 1H), 6.90 (m, 1H), 5.96 (s,