Ellipticine-Like 11H-Pyrido[a]carbazoles
9- and 10-Chloro-6,11-dihydro-5H-pyrido[3,4-a]carbazoles 19
and 20 (mixture): Prepared from hydrazone 18. Yield 77%; Rf =
0.38 (EtOAc); 1H NMR (300 MHz, [D6]DMSO): d=2.42 (m, 4H, 6-
and 6’-CH2), 3.28 (m, 2H, 5- and 5’-CH2), 7.14 (m, 2H, J=8.6, 8.4 Hz,
7- and 7’-H), 7.23 (m, 1H, J=8.0 Hz, 8-H), 7.45 (dd, 1H, J=8.0 Hz,
9-H), 7.58 (m, 1H, 10’-H), 7.61 (d, 1H, J=8.6 Hz, 8’-H), 7.90 (m, 1H,
4- and 4’-H), 8.68 (d,1H, 3’-H), 8.09 (s, 2H, 1- and 1’-H), 9.80 ppm (s,
2H, NH and NH’); HRMS (ESI): m/z [M+H]+ calcd for C15H12ClN2:
255.0689, found: 255.0610; Anal. calcd for C15H11ClN2: C 70.73, H
4.35, N 11.00, found: C 71.12, H 4.28, N 11.33.
tate was removed by filtration. The filtrate was dried (Na2SO4), fil-
tered and concentrated in vacuo, and the solid residue was puri-
fied by flash chromatography (CHCl3/MeOH/NH3 90:1: 0.1).
2-(5-Chloro-7,8,9,10-tetrahydro-11H-pyrido[3,2-a]carbazol-11-yl)-
N,N-diethylethanamine (7a): Yield 91%; Rf =0.45 (CHCl3/MeOH
9:1); mp: 114–1168C; 1H NMR (300 MHz, [D6]DMSO): d=0.85 (t,
6H, J=7.3 Hz, 2CH3), 1.80 (m, 2H, J=5.5, 1.5 Hz, 8-H2), 1.90 (m, 2H,
J=5.5, 1.5 Hz, 9-H2), 2.46 (q, 4H, J=7.3 Hz, 2CH2), 2.71 (t, 4H, J=
6.5 Hz, 7-H2 and 10-H2), 2.84 (t, 2H, J=6.3 Hz, CH2), 4.51 (t, 2H, J=
6.9 Hz, N-CH2), 7.64 (dd, 1H, J=4.2, 8.6 Hz, 2-H), 8.04 (s, 1H, 6-H),
8.78 (dd, 1H, J=1.7, 8.6 Hz, 1-H), 8.8 ppm (dd, 1H, J=1.7, 4.2 Hz,
3-H); 13C NMR (300 MHz, CDCl3): d=11.5, 20.9, 22.4, 23.3, 24.8, 47.5,
52.1, 108.9, 118.8, 120.6, 120.7, 122.1, 124.9, 127.0, 128.3, 135.4,
141.6, 146.7 ppm; HRMS (ESI): m/z [M+H]+ calcd for C21H27ClN3:
356.1894, found: 356.1939; Anal. calcd for C21H26ClN3: C 70.87, H
7.36, N 11.81, found: C 71.50, H 7.59, N 11.44.
General procedure for the synthesis of 5-chloro-pyridocarba-
zoles 6a,b, 23 and 24: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ; 2 equiv for 6a and 6b; 1 equiv for 23 and 24) was added to
a solution of 5a,b, 23 or 24 (1.1–1.2 g, 4.1–4.2 mmol) in benzene
(35 mL). The mixture was heated at reflux for 24 h under a N2 at-
mosphere (completion monitored by TLC: CHCl3/MeOH 9:1). The
reaction was filtered, the filtrate was concentrated in vacuo, and
the residue was purified by flash chromatography (CHCl3/MeOH
9:1) to give the desired products.
2-(5-Chloro-7,8,9,10-tetrahydropyrido[3,4-a]carbazol-11-yl)-N,N-
diethylethanamine (7b): Yield 62%; Rf =0.33 (CHCl3/MeOH/NH3
1
90:1:0.2); mp: 117–1188C; H NMR (300 MHz, [D6]DMSO): d=1.80
5-Chloro-11H-pyrido[3,2-a]carbazole (6a): Yield 35%; Rf =0.45
(CHCl3/MeOH 9:1); mp: 236–2408C (dec); 1H NMR (300 MHz,
[D6]acetone): d=7.31 (m, 1H, J=8.2, 1.4 Hz, 8-H), 7.46 (m, 1H, J=
8.2, 1.4 Hz, 9-H), 7.66 (dq, 1H, J=8.2, 1.4 Hz, 0.77 Hz, 10-H), 7.69
(dd, 1H, J=4.2, 8.6 Hz, 2-H), 8.27 (td, 1H, J=8.2, 1.4, 0.8 Hz, 7-H),
8.65 (s, 1H, 6-H), 8.94 (dd, 1H, J=1.7, 8.6 Hz, 1-H), 9.02 (dd, 1H, J=
1.7, 4.2 Hz, 3-H), 11.59 (s, 1H, N-H); 13C NMR (300 MHz, [D6]acetone)
d=111.8, 112.6, 120.2, 120.8, 121.7, 122.2, 122.8, 124.3, 126.7,
127.6, 132.6, 142.9, 145.3, 150.3 ppm; HRMS (ESI): m/z [M+H]+
calcd for C15H10ClN2: 253.0533, found: 253.0456; Anal. calcd for
C15H9ClN2: C 71.29, H 3.59, N 11.09, found: C 71.05, H 3.49, N 10.86.
(t, 6H, 2CH3), 1.85 (m, 4H, 8-H2 and 9-H2), 2.68 (m, 4H, 2CH2), 2.71
(t, 2H, J=6.5 Hz, 10-H2) 2.88 (t, 2H, 7-H2), 4.87 (t, 2H, J=7.6 Hz,
CH2), 7.3 (s, 1H, 5-H), 8.6 (d, 1H, J=5.5 Hz, 4-H), 8.9 (d, 1H, J=
8.6 Hz, 3-H), 9.9 ppm (s, 1H, 1-H); 13C NMR (300 MHz, CDCl3): d=
11.5, 20.8, 23.5, 23.5, 24.6, 47.5, 52.1, 109.9, 117.3, 126.8, 129.6,
131.4, 132.9, 134.2, 134.6, 144.2, 148.7 ppm; HRMS (ESI): m/z [M+
H]+ calcd for C21H27ClN3: 356.1894, found: 356.1935; Anal. calcd for
C21H26ClN3: C 70.87, H 7.36, N 11.81, found: C 71.92, H 7.58, N
11.51.
5-Chloro-11-methyl-7,8,9,10-tetrahydro-11H-pyrido[3,4-a]carba-
zole (9): Yield 59%; Rf =0.55 (CHCl3/MeOH 9:1); mp: 245–2478C;
1H NMR (300 MHz, [D6]DMSO): d=1.73 (t, 4H, J=4.6, 4.8 Hz, 8-H2
and 9-H2), 2.74 (t, 2H, J=5.7 Hz, 7-H2), 2.82 (t, 2H, J=6.3, 5.0 Hz,
10-H2), 4.13 (s, 3H, CH3), 8.06 (t, 2H, J=5.7, 2.3 Hz, 6-H, 4-H), 8.58
(d, 1H, J=5.5 Hz, 3-H), 9.95 ppm (s, 1H, 1-H); 13C NMR (300 MHz,
CDCl3): d=29.8, 20.8, 22.5, 23.5, 24.6, 108.6, 117.3, 126.8, 129.6,
131.4, 132.9, 134.2, 135.6, 144.2, 148.7 ppm; HRMS (ESI): m/z [M+
H]+ calcd for C16H16ClN2: 271.1002, found: 271.1164; Anal. calcd for
C16H15ClN2: C 70.98, H 5.58, N 10.35, found: C 71.12, H 5.43, N
10.02.
5-Chloro-11H-pyrido[3,4-a]carbazole (6b): Yield 41%; Rf =0.73
(CHCl3/MeOH 9:1); mp: 2558C (dec); 1H NMR (300 MHz,
[D6]DMSO): d=7.46 (m, 1H, J=8.6, 1.6 Hz, 8-H), 7.61 (m, 1H, J=
8.6, 1.6 Hz, 9-H), 7.66 (td, 1H, J=8.6, 1.6, 0.8 Hz, 10-H), 7.72 (d, 1H,
J=5.5 Hz, 4-H), 8.27 (td, 1H, J=8.6, 1.6, 0.8 Hz, 7-H), 8.60 (s, 1H, 6-
H), 8.65 (d, 1H, J=5.9 Hz, 3-H), 9.7 (s, 1H, 1-H), 12.78 ppm (brs,
1H, N-H); 13C NMR (300 MHz, [D6]DMSO): d=111.1, 119.8, 117.3,
119.8, 121.4, 121.7, 123.3, 129.5, 131.4, 132.8, 134.2, 134.5, 141.3,
144.2, 148.7 ppm; HRMS (ESI): m/z [M+H]+ calcd for C15H10ClN2:
253.0533, found: 253.0429; Anal. calcd for C15H9ClN2: C 71.29, H
3.59, N 11.09, found: C 70.72, H 3.42, N 10.79.
2-(5-Chloro-pyrido[3,2-a]carbazol-11-yl)-N,N-diethylethanamine
1
(8a): Yield 30%; Rf =0.41 (CHCl3/MeOH 9:1); mp: >3008C; H NMR
9- and 10-Chloro-11H-pyrido[3,4-a]carbazoles 23 and 24 (mix-
ture): Yield 25%; Rf =0.50 (CHCl3/MeOH 9:1); 1H NMR (300 MHz,
[D6]DMSO): d=7.34 (m, 2H, J=8.6, 8.4 Hz, 5 and 5’-H), 7.48 (m, 1H,
J=8.4 Hz, 8-H), 7.70 (m, 4H, J=8.2 Hz, 7-, 7’-,10’-, 9-H), 7.91 (m,
2H, 4- and 4’-H), 8.23 (d, 1H, J=8.4 Hz, 8’-H), 8.47 (m, 1H, 6’-H)
8.68 (d, 2-H, J=5.2, 3- and 3’-H), 8.81 (d, 1H, J=8.4, 6-H), 9.78 (s,
1H, 1-H), 9.98 (s, 1H, 1’-H), 12.83 (s, 1H, N-H), 13.02 ppm (s, 1H,
NH’); HRMS (ESI): m/z [M+H]+ calcd for C15H10ClN2: 253.0533,
found: 253.0532; Anal. calcd for C15H9ClN2: C 71.29, H 3.59, N 11.09,
found: C 70.82, H 3.51, N 10.75.
(300 MHz, [D6]acetone): d=0.91 (t, 6H, J=7.3 Hz, 2CH3), 2.59 (q,
4H, J=7.3 Hz, 2CH2), 3.02 (t, 2H, J=6.3 Hz, CH2), 5.00 (t, 2H, J=
6.3 Hz, N-CH2), 7.35 (m, 1H, J=8.2, 1.4 Hz, 8-H), 7.56 (m, 1H, J=8.2,
1.4 Hz, 9-H), 7.74 (dd, 1H, J=4.2, 8.6 Hz, 2-H), 7.80 (dq, 1H, J=8.2,
1.4, 0.8 Hz, 7-H) 8.30 (dq, 1H, J=8.2, 1.4, 0.8 Hz, 10-H), 8.70 (s, 1H,
6-H), 9.03 (dd, 1H, J=1.7, 4.2 Hz, 3-H), 9.21 ppm (dd, 1H, J=1.7,
8.6 Hz, 1-H); 13C NMR (300 MHz, [D6]acetone): d=12.5, 45.9, 49.0,
53.0, 111.8, 112.6, 120.2, 120.8, 121.7, 122.2, 122.8, 124.3, 126.7,
127.6, 132.6, 142.9, 145.3, 150.3 ppm; HRMS (ESI): m/z [M+H]+
calcd for C21H23ClN3: 352.1581, found: 352.1498; Anal. calcd for
C21H22ClN3: C 71.68, H 6.30, N 11.94, found: C 72.08, H 6.50, N
11.64.
General procedure for the synthesis of 11-N-substituted pyrido-
carbazoles 7a,b, 8a,b, 9, 15, 21, 22, 25, 26 and 28: A cooled solu-
tion of pyridocarbazole (100–300 mg, 0.22–0.66 mmol) in acetone
(15–60 mL) was treated with powdered KOH (200–600 mg, 11.22–
33.66 mmol) and stirred at 08C until a color change from brown to
green was observed (15–20 min). 2-Chloro-N,N-diethylethylami-
ne·HCl (200–600 mg, 1.16 mmol; for 9, CH3I was used 1.16 mmol)
was then added and, after 30 min, the temperature was increased
to reflux under an inert atmosphere. Upon completion (TLC CHCl3/
MeOH/NH3 90:1:0.2), toluene was added and the resultant precipi-
2-(5-Chloro-11H-pyrido[3,4-a]carbazol-11-yl)-N,N-diethylethana-
mine (8b): Yield 25%; Rf =0.72 (CHCl3/MeOH 9:1); mp: >3008C;
1H NMR (300 MHz, [D6]DMSO): d=1.85 (t, 6H, 2CH3), 2.68 (m, 4H,
2CH2), 2.88 (t, 2H, J=7.6, CH2), 4.87 (t, 2H, J=7.6, CH2), 7.32 (s, 1H,
6-H), 7.44 (m, 1H, J=8.6, 8.4 Hz, 8-H), 7.46 (d, 1H, J=8.8 Hz, 7-H),
7.78 (d, 1H, J=5.5 Hz, 4-H), 8.61 (d, 1H, J=5.5 Hz, 3-H), 8.95 (d,
1H, J=8.6 Hz,10-H), 9.9 ppm (s, 1H, 1-H); 13C NMR (300 MHz,
[D6]DMSO): d=12.9, 45.9, 49.0, 53.0, 110.3, 120.8, 119.3, 121.8,
ChemMedChem 2011, 6, 1872 – 1883
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