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Arch. Pharm. Chem. Life Sci. 2008, 341, 351–356
oxychloride (20 mL). The reflux was continued for 12 h and evap-
oration under reduced pressure afforded a residue which was
taken up in water (150 mL), alkalized to pH 9–10 with conc. aq.
ammonia, and extracted with methylene chloride. The extract
was dried over magnesium sulfate. After evaporation of the sol-
vent, the solid was purified by column chromatography on silica
gel and eluted with methylene chloride/methanol, 97 : 3, v/v.
The pure base was obtained by evaporating the fractions con-
taining the expected product. Yield: 88%; mp.: 247–2488C. Anal.
calcd. for C24H21N3O4: C, 69.39; H 5.10; N 10.11. Found: C, 69.17; H
5.26; N 9.97. 1H-NMR (DMSO-d6) d: 2.71 (s, 3H, 5-CH3), 2.93 (m, 2H,
4-CH2), 3.74 (m, 6H, 29-OCH3, 9-OCH3), 3.93 (m, 2H, 3-CH2), 6.96
(dd, J8-7 = 8.7 Hz, J8-10 = 2.4 Hz, 1H, 8-H), 7.37 (d, J7-8 = 8.7 Hz, 1H, 7-
8.9 Hz, 1H, 7-H), 7.66 (d, J59-69 = 7.9 Hz, 1H, 69-H), 7.77 (d, J10-8 =
2.4 Hz, 1H, 10-H), 8.02 (s, 1H, 39-H), 8.04 (d, J59-69 = 8.1 Hz, 1H, 59-H),
8.07 (d, J4-3 = 6.2 Hz, 1H, 4-H), 8.21 (s, 1H, 11-H), 8.46 (d, J3-4
=
6.2 Hz, 1H, 3-H).
Method B: Compound 7 was aromatized to derivative 3a using
a procedure described for compound 8. Yield: 50%; mp.: 2758C.
5,6-Dimethyl-9-hydroxy-1-(2'-methoxy-49-nitro)phenyl-
6H-pyrido[4,3-b]carbazole 3b
Compound 3a (0.21 g, 0.5 mmol) was dissolved in 100 mL of
methylene chloride and boron tribromide (10 mL) was added
dropwise at –708C. The reaction mixture was stirred under
nitrogen at normal pressure for 2.5 h, maintaining a tempera-
ture of –708C. Then, the mixture was stirred at room tempera-
ture for 12 h and evaporated to dryness. The residue was taken
up in water (50 mL), basified with conc. aq. ammonia, extracted
with methylene chloride, and then dried over magnesium sul-
fate. After evaporation of the solvent, the solid was purified by
chromatography on a silica gel column and eluted with methyl-
ene chloride/methanol, 99 : 1, v/v. By evaporation of the frac-
tions containing the expected product, the pure base was thus
obtained. Yield: 13%; mp.: 160–1618C. Anal. calcd. for
C24H19N3O4: C, 69.72; H, 4.63; N, 10.16. Found: C, 69.44; H, 5.34;
H), 7.43 (s, 1H, 11-H), 7.47 (d, J10-8 = 2.4 Hz, 1H, 10-H), 7.57 (d, J69-59
8.2 Hz, 1H, 69-H), 7.91 (d, J39-59 = 2.1 Hz, 1H, 39-H), 7.98 (dd, J59-39
2.1 Hz, J59-69 = 8.2 Hz, 1H, 59-H), 11.21 (s, 1H, 6-H).
=
=
5,6-Dimethyl-9-methoxy-1-(2'-methoxy-49-nitro)phenyl-
3,4-dihydro-6H-pyrido[4,3-b]carbazole 7
A mixture of compound 6 (0.82 g, 2 mmol), dry potassium carbo-
nate (0.5 g), dimethyl carbonate (20 mL), dimethylformamide
(2 mL), and a trace of 18-crown-6 was refluxed with stirring for
12 h. After evaporation to dryness, the residue was taken up in
water, alkalized with conc. aq. ammonia, and extracted with
methylene chloride. The extract was then dried over magnesium
sulfate. Evaporation of the solvent provided a solid residue,
which was purified by chromatography on a silica gel column
and eluted with methylene chloride to give 0.35 g (41%) of com-
pound 7, mp. 2498C. Anal. calcd. for C25H23N3O4: C, 69.92; H, 5.40;
N, 9.78. Fund: C, 70.05; H, 5.55; N, 9.52. 1H-NMR (DMSO-d6) d: 2.74
(s, 3H, 5-CH3), 2.88 (m, 2H, 4-CH2), 3.76 (m, 6H, 29-OCH3, 9-OCH3),
1
N, 9.95. H-NMR (DMSO-d6) d: 3.07 (s, 3H, 5-CH3), 3.76 (s, 3H, 29-
OCH3), 4.09 (s, 3H, 6-CH3), 7.01 (dd, J8-7 = 8.7 Hz, J8-10 = 2.3 Hz, 1H, 8-
H), 7.40 (d, J7-8 = 8.7 Hz, 1H, 7-H), 7.45 (d, J10-8 = 2.3 Hz, 1H, 10-H),
7.62 (m, 1H, 6-H), 7.86 (m, 2H, 39-H, 59-H), 8.04 (d, J4-3 = 6.2 Hz, 1H,
4-H), 8.14 (s, 1H, 11-H), 8.45 (d, J3-4 = 6.2 Hz, 1H, 3-H), 9.10 (s, 1H, 9-
OH).
5,6-Dimethyl-9-methoxy-1-(49-amino-29-methoxy)phenyl-
3.96 (m, 2H, 3-CH2), 4.09 (s, 3H, 6-CH3), 7.02 (dd, J8-7 = 8.8 Hz, J8-10
=
6H-pyrido[4,3-b]carbazole 3c
2.4 Hz, 1H, 8-H), 7.47 (m, 3H, 7-H, 10-H, 11-H), 7.58 (d, J69-59 = 8.2 Hz,
1H, 69-H), 7.90 (d, J39-59 = 2.1 Hz, 1H, 39-H), 7.98 (dd, J59-39 = 2.1 Hz, J59-69
= 8.2 Hz, 1H, 59-H).
Compound 3a (0.85 g, 2 mmol) was dissolved in 150 mL of gla-
cial acetic acid and 10% palladium on charcoal (80 mg) was
added. The mixture was heated to 508C and maintained at this
temperature under hydrogen at normal pressure for 1h. The cat-
alyst was filtered off, the solvent was evaporated to dryness, and
the solid was purified by column chromatography on silica gel
and eluted with methylene chloride/methanol, 97 : 3, v/v. By
evaporating the fractions containing the expected product, the
pure base was obtained. Yield: 98%; mp.: 143–1458C. Anal. calcd.
for C25H23N3O2: C, 75.55; H, 5.83; N, 10.57. Found: C, 75.37; H,
6.01; N, 10.34.1H-NMR (DMSO-d6) d: 3.05 (s, 3H, 5-CH3), 3.54 (s, 3H,
29-OCH3) 3.82 (s, 3H, 9-OCH3), 4.10 (s, 3H, 6-CH3), 5.39 (s, 2H, 49-
9-Methoxy-5-methyl-1-(2'-methoxy-49-nitro)phenyl-6H-
pyrido[4,3-b]carbazole 8
Compound 6 (2.07 g, 5 mmol) was refluxed in diphenyl ether
(50 mL) in the presence of 10% palladium on charcoal (0.30 g) for
3 h. The catalyst was filtered off and the filtrate was cooled and
diluted with 100 mL of hexane. The resulting precipitate was col-
lected, washed with hexane, and purified by chromatography
on silica gel column and eluted with methylene chloride to give
0.95 g (46%) of 8; mp.: 2828C. Anal. calcd. for C24H19N3O4: C,
NH2), 6.33 (dd, J5'-3' = 1.8 Hz, J59-69 = 8.0 Hz , 1H, 59-H), 6.42 (d, J39-59
1.8 Hz, 1H, 39-H), 7.04 (d, J69-59 = 8.0 Hz, 1H, 69-H), 7.14 (dd, J8-7
8.8 Hz, J8-10 = 2.4 Hz, 1H, 8-H), 7.49 (d, J7-8 = 8.8 Hz, 1H, 7-H), 7.58 (d,
J10-8 = 2.4 Hz, 1H, 10-H), 7.89 (d, J4-3 = 6.2 Hz, 1H, 4-H), 8.30 (s, 1H,
11-H), 8.37 (d, J3-4 = 6.2 Hz, 1H, 3-H).
=
=
1
69.72; H, 4.63; N, 10.16. Found: C, 69.47; H, 4.78; N, 10.40. H-
NMR (DMSO-d6) d: 2.84 (s, 3H, 5-CH3), 3.78 (s, 3H, 29-OCH3), 3.79 (s,
3H, 9-OCH3), 7.11 (dd, J8-7 = 8.7 Hz, J8-10 = 2.4 Hz, 1H, 8-H), 7.42 (d, J7-
8 = 8.7 Hz, 1H, 7-H), 7.65 (d, J69-59 = 8.0 Hz, 1H, 69-H), 7.77 (d, J10-8
=
2.4 Hz, 1H, 10-H), 7.99 (d, J4-3 = 6.2 Hz, 1H, 4-H), 8.04 (m, 2H, 39-H,
59-H), 8.20 (s, 1H, 11-H), 8.45 (d, J3-4 = 6.2 Hz, 1H, 3-H).
5,6-Dimethyl-9-hydroxy-1-(49-amino-29-methoxy)phenyl-
6H-pyrido[4,3-b]carbazole 3d
5,6-Dimethyl-9-methoxy-1-(2'-methoxy-49-nitro)phenyl-
6H-pyrido[4,3-b]carbazole 3a
A mixture of compound 3c (0.158 g, 0.4 mmol) and hydrobromic
acid (40 mL) was heated under reflux with stirring for 1 h. After
evaporation to dryness, the residue was suspended in 50 mL of
water. The resulting mixture was basified with conc. aq. ammo-
nia and extracted with methylene chloride, then, the organic
layer was dried over magnesium sulfate. After evaporating the
solvent, the solid residue was purified by chromatography on a
silica gel column and eluted with methylene chloride/methanol,
Method A: Compound 3a was synthesized using a similar proce-
dure described for 7, starting from 8. Yield: 84%; mp.: 275–
2768C. Anal. calcd. for C25H21N3O4: C, 70.25; H, 4.95; N, 9.83.
Found: C, 70.10; H, 5.10; N, 9.51. 1H-NMR (DMSO-d6) d: 3.09 (s, 3H,
5-CH3), 3.77 (s, 3H, 29-OCH3) 3.80 (s, 3H, 9-OCH3), 4.13 (s, 3H, 6-
CH3), 7.16 (dd, J8-7 = 8.8 Hz, J8-10 = 2.4 Hz, 1H, 8-H), 7.51 (d, J7-8
=
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