4840
P. Barraja et al. / Bioorg. Med. Chem. 18 (2010) 4830–4843
C23H18N2O5S2: C, 59.21; H, 3.89; N, 6.00. Found: C, 59.00; H, 4.01;
N, 5.89. When the same reaction was carried out at rt was obtained
a complex mixture which, after column chromatography (eluent
DCM/EtOAc 9:1), furnished intermediate 8 as brown oil.
yield 55%; mp: 251–252 °C; IR: t ;
3359 (NH), 1654 (CO) cmꢀ1 1H
NMR: d 2.68 (2H, t, J = 6.7 Hz, CH2), 2.79 (2H, t, J = 6.7 Hz, CH2),
6.34 (1H, d, J = 2.7 Hz, H-3), 7.29 (1H, d, J = 2.7 Hz, H-2), 7.32–
7.67 (8H, m, Ar), 7.90–7.96 (2H, d, J = 8.0 Hz, H-20 and H-60), 8.15
(1H, s, H-6), 10.10 (1H, s, NH); 13C NMR: d 22.0 (t), 26.5 (t), 99.5
(d), 108.6 (s), 109.5 (d), 112.1 (s), 119.0 (s), 121.6 (s), 124.5 (d),
127.4 (d), 127.9 (d), 128.7 (d), 129.3 (d), 130.9 (d), 133.0 (d),
133.6 (s), 138.6 (s), 140.9 (s), 156.4 (CO). Anal calcd for
C23H18N2O3S: C, 68.64; H, 4.51; N, 6.96. Found: C, 68.40; H, 4.80;
N, 7.06.
4.1.12.2. 1-Phenylsulfonyl-6-[2-(phenylsulfonyl)-propanenitrile]-
1,4,5,6-tetrahydro-7H-indole-7-one (8). Yield 40%; IR:
t 2362
(CN), 1693 (CO) cmꢀ1
;
1H NMR: d 2.53–2.72 (4H, m, 2ꢁ CH2),
5.86 (1H, d, J = 10.7 Hz, CH), 6.02 (1H, d, J = 10.7 Hz, CH), 6.36
(1H, d, J = 2.6 Hz, H-3), 7.15–8.08 (11H, m, Ar and H-2); 13C NMR:
d 23.7 (t), 34.3 (t), 111.0 (d), 125.5 (d), 128.1 (d), 128.4 (d), 128.5
(d), 128.8 (s), 129.2 (s), 129.3 (d), 131.6 (d), 133.3 (d), 134.4 (s),
134.6 (d), 136.8 (d), 137.6 (s), 147.7 (s), 143.7 (s), 162.8 (CO). Anal
calcd for C23H18N2O5S2: C, 59.21; H, 3.89; N, 6.00. Found: C, 59.04;
H, 4.12; N, 6.12.
4.1.12.7. 1-(p-Methyl-benzyl)-7-(phenylsulfonyl)-1,4,5,9-tetrahy
dro-8H-pyrrolo[3,2-h]quinolin-8-one (9g). This product was ob-
tained from the reaction of 7g with phenylsulfonylacetonitrile after
32 h reflux. The crude precipitate was purified by column chroma-
tography (Sepacore Büchi) using DCM/AcOEt 9:1 as eluent. Yellow
By refluxing in ethanol this intermediate, the cyclized com-
pound 9a, in 45% yield, was obtained.
solid; yield 40%; mp: 178–180 °C; IR: t ;
3217 (NH), 1626 (CO) cmꢀ1
1H NMR: d 2.19 (3H, s, CH3), 2.64 (2H, t, J = 7.5 Hz, CH2), 2.80
(2H, t, J = 7.5 Hz, CH2), 5.71 (2H, s, CH2), 6.04 (1H, d, J = 2.5 Hz, H-
3), 7.02–7.10 (5H, m, Ar and H-2), 7.55–7.67 (3H, m, Ar), 7.90–
7.95 (2H, m, Ar), 8.00 (1H, s, H-6), 11.56 (1H, s, NH); 13C NMR: d
20.6 (q), 21.6 (t), 50.7 (t), 99.5 (d), 105.2 (d), 107.2 (d), 124.6 (s),
126.9 (d), 127.7 (d), 128.8 (d), 128.9 (d), 129.8 (s), 133.1 (d),
136.2 (s), 137.2 (s), 140.5 (s), 141.2 (s), 152.5 (s), 158.0 (s), 174.0
(CO). Anal calcd for C25H22N2O3S: C, 69.75; H, 5.15; N, 6.51. Found:
C, 69.55; H, 5.02; N, 6.64.
4.1.12.3. 1-(Phenylsulfonyl)-1,4,5,9-tetrahydro-8H-pyrrolo[3,2-
h]quinolin-7-carbonitrile-8-one (9c). This product was obtained
from the reaction of 7a with cyanoacetamide after 32 h reflux.
The yellow solid precipitated was recrystallized from ethanol;
yield 13%; mp: 309–311 °C; IR:
t 3309 (NH), 2220 (CN), 1653
(CO) cmꢀ1
;
1H NMR: d 2.69–2.92 (4H, m, 2ꢁ CH2), 6.85 (1H, s, H-
3), 7.61–7.77 (4H, m, Ar and H-2), 7.96 (2H, d, J = 8.0 Hz, H-20
and H-60), 8.04 (1H, s, H-6), 12.06 (1H, s, NH); 13C NMR: d 20.3
(t), 25.0 (t), 99.5 (d), 112.2 (s), 113.5 (d), 117.0 (s), 125.0 (s),
126.7 (d), 128.3 (s), 129.8 (d), 131.9 (s), 133.8 (d), 138.8 (s),
141.3 (s), 148.4 (d), 159.5 (CO). Anal calcd for C18H13N3O3S: C,
61.53; H, 3.73; N, 11.96. Found: C, 61.32; H, 3.60; N, 12.20.
4.1.12.8. 1-(p-Methoxy-benzyl)-7-(phenylsulfonyl)-1,4,5,9-tetra
hydro-8H-pyrrolo[3,2-h]quinolin-8-one (9h). This product was
obtained from the reaction of 7h with phenylsulfonylacetonitrile
after 32 h reflux. The crude precipitate was purified by column
chromatography (Sepacore Büchi) using DCM/AcOEt 9:1 as eluent.
4.1.12.4.
1-Methyl-7-(phenylsulfonyl)-1,4,5,9-tetrahydro-8H-
pyrrolo[3,2-h]quinolin-8-one (9d). This product was obtained
from the reaction of 7d with phenylsulfonylacetonitrile after 24 h
reflux. The yellow solid precipitated was recrystallized from etha-
Yellow solid; yield 45%; mp: 154–156 °C; IR:
t 3315 (NH), 1635
(CO) cmꢀ1 1H NMR: d 2.64 (2H, t, J = 7.5 Hz, CH2), 2.78 (2H, t,
;
J = 7.5 Hz, CH2), 3.34 (3H, s, CH3), 5.68 (2H, s, CH2), 6.04 (1H, d,
J = 2.5 Hz, H-3), 6.80 (2H, d, J = 8.0 Hz, H-300 and H-500), 7.08 (1H,
d, J = 2.5 Hz, H-2), 7.12 (2H, d, J = 8.0 Hz, H-200 and H-600), 7.56–
7.68 (3H, m, Ar), 7.93 (2H, d, J = 8.6 Hz, H-20 and H-60), 8.00 (1H,
s, H-6), 11.59 (1H, s, NH); 13C NMR: d 21.6 (t), 27.5 (t), 50.3 (t),
54.9 (q), 99.5 (d), 107.2 (d), 113.6 (d), 114.4 (s), 121.1 (s), 126.7
(d), 128.4 (d), 128.9 (d), 129.6 (s), 131.1 (s), 133.1 (d), 133.7 (d),
136.8 (s), 141.2 (s), 145.0 (s), 158.0 (s), 158.4 (CO). Anal calcd for
C25H22N2O4S: C, 67.25; H, 4.97; N, 6.27. Found: C, 67.05; H, 5.18;
N, 6.00.
nol; yield 55%; mp: 208–209 °C; IR:
t ;
3320 (NH), 1635 (CO) cmꢀ1
1H NMR: d 2.51 (2H, t, J = 6.9 Hz, CH2), 2.82 (2H, t, J = 6.9 Hz, CH2),
3.94 (3H, s, CH3), 6.00 (1H, d, J = 2.4 Hz, H-3), 6.93 (1H, d, J = 2.4 Hz,
H-2), 7.54–7.72 (3H, m, Ar), 7.92 (2H, d, J = 8.0 Hz, H-20 and H-60),
8.03 (1H, s, H-6), 11.47 (1H, s, NH); 13C NMR: d 21.6 (t), 27.4 (t),
36.2 (q), 99.5 (d), 102.3 (s), 106.6 (d), 117.4 (s), 124.6 (s), 127.6
(d), 128.0 (d), 128.8 (d), 129.3 (s), 133.0 (d), 141.2, (s), 141.3 (s),
157.9 (CO). Anal calcd for C18H16N2O3S: C, 63.51; H, 4.74; N, 8.23.
Found: C, 63.72; H, 4.95; N, 8.02.
4.1.12.5. 1-Benzyl-7-(phenylsulfonyl)-1,4,5,9-tetrahydro-8H-pyr
rolo[3,2-h]quinolin-8-one (9e). This product was obtained from
the reaction of 7e with phenylsulfonylacetonitrile after 24 h reflux.
The solid precipitated was purified by column chromatography
(Sepacore Büchi) using DCM/AcOEt 9:1 as eluent. Brown solid;
4.1.12.9. Ethyl 7-(phenylsulfonyl)-1,4,5,9-tetrahydro-8H-pyrrol-
o[3,2-h]quinolin-8-one-2-carboxylate (9i). This product was ob-
tained from the reaction of 7b with phenylsulfonylacetonitrile
after 32 h reflux. The yellow solid precipitated was recrystallized
from ethanol; yield 60%; mp: 322–323 °C; IR:
t 3280 (NH), 3246
yield 45%; mp: 213–214 °C; IR:
t
: 3214 (NH), 1631 (CO) cmꢀ1
;
(NH), 1711 (CO), 1651 (CO) cmꢀ1 1H NMR: d 1.30 (3H, t,
;
1H NMR: d 2.65 (2H, t, J = 7.0 Hz, CH2), 2.83 (2H, t, J = 7.0 Hz,
CH2), 5.79 (2H, s, CH2), 6.06 (1H, d, J = 2.5 Hz, H-3), 7.09 (1H, d,
J = 2.5 Hz, H-2), 7.12–7.28 (5H, m, Ar), 7.54–7.71 (3H, m, Ar),
7.90–7.95 (2H, m, Ar), 8.00 (1H, s, H-6), 11.61 (1H, s, NH); 13C
NMR: d 21.6 (t), 27.5 (t), 50.8 (t), 99.5 (d), 107.3 (d), 114.7 (s),
120.9 (s), 124.4 (s), 126.9 (d), 127.1 (d), 127.7 (d), 128.3 (d),
128.9 (d), 129.7 (s), 133.1 (d), 137.2 (s), 139.3 (s), 141.2 (d),
150.9 (s), 158.1 (CO). Anal calcd for C24H20N2O3S: C, 69.21; H,
4.84; N, 6.73. Found: C, 69.46; H, 4.63; N, 6.50.
J = 7.1 Hz, CH3), 2.67–2.88 (4H, m, 2ꢁ CH2), 4.29 (2H, q, J = 7.1 Hz,
CH2), 6.73 (1H, s, H-3), 7.55–7.72 (3H, m, Ar), 7.98 (2H, d,
J = 8.0 Hz, H-20 and H-60), 8.21 (1H, s, H-6), 12.06 (2H, bs, 2ꢁ
NH); 13C NMR: d 14.2 (q), 20.5 (t), 25.4 (t), 60.3 (t), 110.8 (s),
113.4 (d), 122.8 (s), 123.9 (s), 126.1 (s), 127.9 (d), 128.4 (s), 128.7
(d), 133.1 (d), 140.6 (2ꢁ s), 143.8 (d), 156.5 (CO), 159.8 (CO). Anal
calcd for C20H18N2O5S: C, 60.29; H, 4.55; N, 7.03. Found: C, 59.98;
H, 4.68; N, 6.85.
4.1.12.10. Ethyl 1-methyl-7-(phenylsulfonyl)-1,4,5,9-tetrahy-
4.1.12.6. 1-Phenyl-7-(phenylsulfonyl)-1,4,5,9-tetrahydro-8H-pyr
rolo[3,2-h]quinolin-8-one (9f). This product was obtained from
the reaction of 7f with phenylsulfonylacetonitrile after 32 h reflux.
The crude precipitate was purified by column chromatography
(Sepacore Büchi) using DCM/AcOEt 9:1 as eluent. Yellow solid;
dro-8H-pyrrolo[3,2-h]quinolin-8-one-2-carboxylate
(9j). This
product was obtained from the reaction of 7i with phenylsulfonyl-
acetonitrile after 28 h reflux. The crude precipitate was purified
by column chromatography (Sepacore Büchi) using DCM/AcOEt
9:1 as eluent. Yellow solid; yield 52%; mp: 214–216 °C; IR:
t