830
C. Asche et al. / Bioorg. Med. Chem. 13 (2005) 819–837
4.6.6. Methyl 2,6-dihydroxy-5-(3,5-dimethoxybenzyl)-
5H-benzo[b]carbazole-1-carboxylate (8f). 400mg
HÕs), 7.12 (d, J = 8.9Hz, 1H, H-3), 4.89 (t, J = 7.7Hz,
2H, N-CH2–CH2), 4.08 (s, 3H, COOCH3), 3.03 (t,
J = 7.7Hz, 2H, N–CH2–CH2), MS (EI) m/z 411 (M+),
Anal. Calcd for C26H21NO4 (411.45): C, 75.90; H,
5.14; N, 3.40. Found: C, 75.72; H, 5.06; N, 3.47.
(1.29mmol) 4f, 250mg (1.51mmol) 5b, 5mL acetic acid,
395mg (67%), mp 218ꢁC (yellow powder from toluene),
1H NMR (DMSO-d6) (after 24h in solution: 6-hydroxyl
tautomer) d 9.68 and 9.60 (2 · s, 2 · 1H, OH-2, OH-6),
8.21 (ÔdÕ, 1H, H-7), 8.01 (ÔdÕ, 1H, H-10), 7.88 (s, 1H, H-
11), 7.50 (d, J = 8.9Hz, 1H, H-4), 7.44–7.31 (m, 2H, H-
8, H-9), 7.10 (d, J = 8.9Hz, 1H, H-3), 6.31 (d,
J = 2.1Hz, 1H, H-40), 6.26 (d, J = 2.1Hz, 2H, H-20, H-
60), 5.94 (s, 2H, N–CH2), 4.08 (s, 3H, COOCH3), 3.60
(s, 6H, 2 · OCH3); MS (EI) m/z 457 (M+), Anal. Calcd
for C27H23NO6 (457.48): C, 70.89; H, 5.07; N, 3.06.
Found: C, 70.83; H, 5.13; N, 3.01.
4.6.11. Methyl 2,6-dihydroxy-5-[2-(3,4-dimethoxyphen-
yl)ethyl]-5H-benzo[b]carbazole-1-carboxylate (8l). 770
mg (2.38mmol) 4l, 500mg (3.01mmol) 5b, 2mL acetic
acid, 715mg (64%), mp 155ꢁC (yellow needles from ace-
1
tone), H NMR (DMSO-d6) (after 24h in solution: 6-
hydroxyl tautomer) d 9.62 and 9.55 (2 · s, 2 · 1H,
OH-2, OH-6), 8.33 (ÔdÕ, 1H, H-7), 8.00 (ÔdÕ, 1H, H-10),
7.87 (s, 1H, H-11), 7.53 (d, J = 8.8Hz, 1H, H-4), 7.53–
7.35 (m, 2H, H-8, H-9), 7.10 (d, J = 8.8Hz, 1H, H-3),
6.85–6.78 (m, 3H, H-20, H-50 and H-60), 4.87 (t, 2H,
N-CH2–CH2), 4.07 (s, 3H, COOCH3), 3.69 (s, 6H,
2 · OCH3), 2.97 (t, 2H, N–CH2–CH2) MS (EI) m/z
471 (M+), Anal. Calcd for C28H25NO6 (471.51): C,
71.33; H, 5.34; N, 2.97. Found: C, 71.13; H, 5.38; N,
2.97.
4.6.7. Methyl 2,6-dihydroxy-5-(3-methylbenzyl)-5H-
benzo[b]carbazole-1-carboxylate
(8g).
110mg
(0.42mmol) 4g, 90mg (0.54mmol) 5b, 3mL acetic acid,
115mg (67%), mp 191ꢁC (yellow crystals from toluene),
1H NMR (DMSO-d6) (directly after dissolving: 6-keto
tautomer) d 10.05 (s, 1H, OH-2), 8.19 (ÔdÕ, 1H, H-7),
7.70–7.65 (m, 3H, H,4, H-8 and H-9), 7.55–7.47 (m,
1H, H-10), 7.16–7.08 (m, 2H, H-3, H-50), 7.02–6.97
(m, 2H, H-20, H-40), 6.79 (ÔdÕ, 1H, H-60), 6.01 (s, 2H,
N–CH2), 4.35 (s, 2H, CH2-11), 4.04 (s, 3H, COOCH3),
2.20 (s, 3H, CH3) MS (EI) m/z 411 (M+), Anal. Calcd
for C26H21NO4 (411.46): C, 75.90; H, 5.14; N, 3.40.
Found: C, 75.76; H, 5.40; N, 3.33.
4.6.12. Methyl 2,6-dihydroxy-5-(3-phenylpropyl)-5H-
benzo[b]carbazole-1-carboxylate (8m). 700mg (2.52
mmol) 4m, 450mg (2.71mmol) 5b, 7mL acetic acid,
725mg (68%), mp 162ꢁC (yellow powder from toluene),
1H NMR (DMSO-d6) (directly after dissolving: 6-hyd-
roxyl tautomer) d 9.53 and 9.49 (2 · s, 2 · 1H, OH-2,
OH-6), 8.29 (ÔdÕ, 1H, H-7), 7.98 (ÔdÕ, 1H, H-10), 7.87
(s, 1H, H-11), 7.47 (d, J = 9.1Hz, 1H, H-4), 7.43–7.18
(m, 7H, aromat. HÕs), 7.13 (d, J = 9.1Hz, 1H, H-3),
4.80–4.73 (m, 2H, N–CH2–CH2–CH2), 4.07 (s, 3H,
COOCH3), 2.70–2.62 (m, 2H, N–CH2–CH2–CH2),
2.16–2.01 (m, 2H, N–CH2–CH2–CH2) MS (EI) m/z
425 (M+), Anal. Calcd for C27H23NO4 (425.49): C,
76.22; H, 5.45; N, 3.29. Found: C, 76.37; H, 5.62; N,
3.17.
4.6.8. Methyl 5-(2-chlorobenzyl)-2,6-dihydroxy-5H-benzo-
[b]carbazole-1-carboxylate (8h). 400mg (1.41mmol) 4h,
300mg (1.81mmol) 5b, 2mL acetic acid, 380mg (62%),
mp 192ꢁC (yellow powder from toluene), 1H NMR
(DMSO-d6) (after 24h in solution: 6-hydroxyl tautomer)
d 9.65 and 9.59 (2 · s, 2 · 1H, OH-2, OH-6), 8.22–8.18
(m, 1H, H-7), 8.04–8.00 (m, 1H, H-10), 7.91 (s, 1H, H-
11), 7.55–7.51 (m, 1H, H-30), 7.44–7.30 (m, 3H, H-4,
H-8 and H-9), 7.26–7.18 (m, 1H, H-50), 7.15–6.99 (m,
2H, H-3, H-40), 6.20 (ÔdÕ, 1H, H-60), 6.09 (s, 2H, N–
CH2), 4.10 (s, 3H, COOCH3), MS (EI) m/z 431 (M+),
Anal. Calcd for C25H28NO4Cl (431.88): C, 69.53; H,
4.20; N, 3.24. Found: C, 69.34; H, 4.13; N, 3.21.
4.6.13. Methyl 2,6-dihydroxy-5-pyridine-2-ylmethyl-5H-
benzo[b]carbazole-1-carboxylate (8n). 370mg (1.48
mmol) 4n, 260mg (1.57mmol) 5b, 4mL acetic acid,
355mg (60%), mp 185ꢁC (yellow powder from isoprop-
anol), 1H NMR (DMSO-d6) (directly after dissolving: 6-
hydroxyl tautomer) d 10.32 and 9.58 (2 · s, 2 · 1H, OH-
2, OH-6), 8.56–8.53 (m, 1H, H-30), 8.29 (ÔdÕ, 1H, H-7),
8.00 (ÔdÕ, 1H, H-10), 7.88 (s, 1H, H-11), 7.71 (ÔdtÕ, 1H,
H-50), 7.57 (d, J = 8.6Hz, 1H, H-4), 7.47–7.24 (m, 3H,
H-8, H-9 and H-40), 7.11 (d, J = 8.6Hz, 1H, H-3), 7.08
(ÔdÕ, 1H, H-60), 6.03 (s, 2H, N–CH2), 4.08 (s, 3H,
COOCH3), MS (EI) m/z 398 (M+), Anal. Calcd for
C24H18N2O4 (425.49): C, 72.35; H, 4.55; N, 7.03. Found:
C, 72.15; H, 4.67; N, 6.82.
4.6.9. Methyl 5-(2,4-dichlorobenzyl)-2,6-dihydroxy-5H-
benzo[b]carbazole-1-carboxylate (8i). 500mg (1.57mmol)
4i, 300mg (1.81mmol) 5b, 8mL acetic acid, 465mg
(64%), mp 230ꢁC (yellow powder from toluene), 1H
NMR (pyridine-d5) d ꢀ11.80 (ÔsÕ, br s, 2H, OH-2, OH-
6), 8.79–8.72 (m, 2H, H-7, H-10), 8.24–8.20 (m, 1H,
H-10), 6.86 (dd, J = 2.1Hz, J = 8.3Hz, 1H, H-50), 6.57
(d, J = 8.3Hz, 1H, H-60), 6.31 (s, 2H, N–CH2), 4.26 (s,
3H, COOCH3), MS (EI) m/z 466 (M+), Anal. Calcd
for C25H17NO4Cl2 (466.32): C, 64.39; H, 3.67; N, 3.00.
Found: C, 64.64; H, 3.67; N, 3.25.
4.6.14. Methyl 2,6-dihydroxy-5-(4-methoxyphenyl)-5H-
benzo[b]carbazole-1-carboxylate (8p). 420mg (1.58
mmol) 4p, 300mg (1.81mmol) 5b, 8mL acetic acid,
180mg (28%), mp 219ꢁC (green crystals from toluene),
1H NMR (DMSO-d6) (directly after dissolving: 6-hydr-
oxyl tautomer) d 9.65 and 9.17 (2 · s, 2 · 1H, OH-2,
OH-6), 8.20–8.15 (m, 1H, H-7), 8.04–8.00 (m, 1H, H-
10), 7.89 (s, 1H, H-11), 7.42–7.30 (m, 4H, H-8, H-9,
H-20 and H-60), 7.12–7.05 (m, 4H, H-3, H-4, H-30 and
H-50), 4.10 (s, 3H, COOCH3), 3.86 (s, 3H, OCH3), MS
4.6.10. Methyl 2,6-dihydroxy-5-(2-phenethyl)-5H-benzo-
[b]carbazole-1-carboxylate (8k). 340mg (1.29mmol) 4k,
300mg (1.81mmol) 5b, 3mL acetic acid, 360mg (68%),
mp 185ꢁC (yellow needles from acetone), 1H NMR
(DMSO-d6) (after 24h in solution: 6-hydroxyl tautomer)
d 9.64 and 9.56 (2 · s, 2 · 1H, OH-2, OH-6), 8.34 (ÔdÕ,
1H, H-7), 8.00 (ÔdÕ, 1H, H-10), 7.85 (s, 1H, H-11), 7.54
(d, J = 8.9Hz, 1H, H-4), 7.49–7.19 (m, 7H, aromat.