A. Cappelli et al. / Bioorg. Med. Chem. 10 (2002) 779–801
795
2
2
1
H), 2.19–2.23 (m, 5H), 2.43–2.58 (m, 2H), 3.28 (m,
H), 4.33 (s, 2H), 4.50–4.73 (m, 3H), 7.48 (t, J=7.4,
H), 7.65 (t, J=8.1, 1H), 7.90 (d, J=8.3, 1H), 8.93 (d,
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-
9-(n-propyloxy)-1H-pyrrolo[3,4-b]quinolin-1-one (8e).
This compound was prepared from g-bromoester 16e
(reaction time 8 h) and was purified by flash chromato-
J=9.0, 1H). Anal. (C H N O ) C, H, N.
2
2
2
27
3
ꢁ
1
graphy (yield 16%; mp 125–126 C). H NMR (CDCl ):
3
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3,4,5-tet-
rahydro-5-(n-propyl)-1H-pyrrolo[3,4-c]quinolin-1,4-dione
1.09 (t, J=7.4, 3H), 1.46–1.66 (m, 4H), 1.82–1.99 (m,
2H), 2.07–2.23 (m, 5H), 2.42–2.57 (m, 2H), 3.25 (m,
2H), 4.43 (s, 2H), 4.71 (m, 1H), 4.95 (t, J=6.9, 2H), 7.51
(
30). This compound was prepared from crude g-bro-
moester 29 (reaction time 15 h) and was purified by flash
chromatography (yield over two steps: 26%).An ana-
lytical sample was obtained by washing with diethyl
(t, J=7.2, 1H), 7.75 (m, 1H), 7.97 (d, J=8.4, 1H), 8.39
+
(m, 1H).MS:
m/z 365 (M , 24).Anal.
.
(C H N O 0.33 H O) C, H, N.
2
2
27
3
2
2
ꢁ
1
ether: mp 145–148 C. H NMR (CDCl ): 1.07 (t,
3
J=7.4, 3H), 1.45–1.65 (m, 4H), 1.71–1.90 (m, 2H),
endo-2-[8-Methyl-8-azabicyclo[3.2.1]oct-3-yl]-2,3-dihydro-
4-(n-propyl)-pyrrolo[3,4-b]quinolin-1,9(1H,4H)-dione (35).
This compound was prepared from g-bromoester 34
(reaction time 22 h) and was purified by washing with
diethyl ether (yield 27%).An analytical sample was
obtained by recrystallization from ethanol–ethyl ace-
2
(
.16–2.23 (m, 5H), 2.42–2.57 (m, 2H), 3.26 (m, 2H), 4.32
m, 4H), 4.61 (m, 1H), 7.27–7.43 (m, 2H), 7.61 (m, 1H),
.96 (d, J=7.7, 1H). MS: m/z 365 (M , 33).Anal.
+
8
(
.
C H N O 0.5 H O) C, H, N.
22 27 3 2 2
ꢁ
1
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-
H-benz[f]isoindol-1-one (8a). This compound was pre-
tate: mp 198 C dec. H NMR (CDCl ): 1.08 (t, J=7.4,
3
1
3H) 1.60–1.80 (m, 4H), 1.84–2.03 (m, 2H), 2.16–2.28 (m,
5H), 2.41–2.56 (m, 2H), 3.32 (m, 2H), 4.02 (t, J=7.8,
2H), 4.29 (s, 2H), 4.46 (m, 1H), 7.34–7.43 (m, 2H), 7.60–
7.69 (m, 1H), 8.49–8.54 (m, 1H). MS (FAB): m/z 366
(M+1, 100).Anal.(C 22H N O ) C, H, N.
pared from crude g-bromoester 16a (reaction time 20 h)
and was purified by flash chromatography (yield over
two steps: 30%).An analytical sample was obtained by
ꢁ
1
recrystallization from ethyl acetate: mp 217–218 C. H
NMR (CDCl ): 1.48–1.66 (m, 4H), 2.15–2.24 (m, 5H),
27
3
2
3
2
1
.42–2.58 (m, 2H), 3.27 (m, 2H), 4.47 (s, 2H), 4.68 (m,
H), 7.47–7.59 (m, 2H), 7.84–7.90 (m, 2H), 7.96–8.01
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-1,2-dihydro-
3H-benz[e]isoindol-3-one (9a). This compound was pre-
pared from crude g-bromoester 17a (reaction time 17 h)
and was purified by flash chromatography (yield over
two steps: 52%).An analytical sample was obtained by
+
(
(
m, 1H), 8.32 (s, 1H). MS: m/z 306 (M , 18).Anal.
.
C H N O 0.25 H O) C, H, N.
2
0
22
2
2
ꢁ
1
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-
H-pyrrolo[3,4-b]quinolin-1-one (8b). This compound
was prepared from ethyl 2-chloromethyl-3-quinoline-
recrystallization from ethyl acetate: mp 139–140 C. H
NMR (CDCl ): 1.52–1.69 (m, 4H), 2.16–2.24 (m, 5H),
1
3
2.44–2.60 (m, 2H), 3.29 (m, 2H), 4.58–4.75 (m, 3H),
7.54–7.62 (m, 2H), 7.80–7.99 (m, 4H). MS: m/z 306
1
8
carboxylate (16b) (reaction time 25 h) and was purified
by flash chromatography (yield 51%).An analytical
sample was obtained by recrystallization from ethyl
+
(M , 9).Anal.(C H N O) C, H, N.
2
0
22
2
ꢁ
1
acetate: mp 203–204 C. H NMR (CDCl ): 1.47–1.66
3
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-1,2-dihydro-
3H-pyrrolo[3,4-c]quinolin-3-one (9b). This compound
was prepared from crude g-bromoester 17b (reaction
time 15 h) and was purified by washing with diethyl
(
2
(
m, 4H), 2.13–2.24 (m, 5H), 2.45–2.60 (m, 2H), 3.28 (m,
H), 4.52 (s, 2H), 4.75 (m, 1H), 7.61 (t, J=7.4, 1H), 7.82
m, 1H), 7.98 (d, J=9.0, 1H), 8.13 (d, J=8.5, 1H), 8.57
ꢁ
1
(
s, 1H).Anal.(C 19H N O) C, H, N.
21 3
ether (yield over two steps: 45%; mp 195–196 C). H
NMR (CDCl ): 1.49–1.68 (m, 4H), 2.18–2.24 (m, 5H),
3
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-9-chloro-
,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one (8c). This
compound was prepared from g-bromoester 16c (reac-
2.45–2.60 (m, 2H), 3.30 (m, 2H), 4.59–4.73 (m, 3H), 7.65
(t, J=7.3, 1H), 7.78–7.91 (m, 2H), 8.23 (d, J=8.4, 1H),
9.27 (s, 1H). MS: m/z 307 (M , 10).Anal.
.
(C H N O 0.25 H O) C, H, N.
19 21 3 2
2
+
tion time 2 h) and was purified by flash chromatography
ꢁ
yield 10%; mp 192–193 C). H NMR (CDCl ): 1.56–
3
1
(
1
(
.68 (m, 4H), 2.15–2.23 (m, 5H), 2.44–2.59 (m, 2H), 3.27
m, 2H), 4.47 (s, 2H), 4.62 (m, 1H), 7.69 (t, J=7.3, 1H),
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-4-chloro-
1,2-dihydro-3H-pyrrolo[3,4-c]quinolin-3-one (9c). This
compound was prepared from crude g-bromoester 17c
(reaction time 5 h) and was purified by washing with
diethyl ether (yield over two steps: 73%; mp 229–
7
MS: m/z 341 (M , 10).Anal.(C
C, H, N.
.85 (m, 1H), 8.11 (d, J=8.3, 1H), 8.44 (d, J=8.9, 1H).
+
.
H ClN O 0.2 H O)
20 3 2
1
9
ꢁ
31 C. H NMR (CDCl ): 1.58–1.70 (m, 4H), 2.16–2.23
3
1
2
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihy-
dro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one (8d). This
compound was prepared from crude g-bromoester 16d
(m, 5H), 2.43–2.58 (m, 2H), 3.29 (m, 2H), 4.55 (m, 1H),
4.65 (s, 2H), 7.65 (t, J=7.7, 1H), 7.79–7.88 (m, 2H),
8.12 (d, J=8.6, 1H). MS: m/z 341 (M , 35).Anal.
.
(C H ClN O 0.25 H O) C, H, N.
19 20 3 2
+
(
reaction time 3 h) and was purified by flash chromato-
ꢁ
NMR (CDCl ): 1.43–1.64 (m, 4H), 2.14–2.23 (m, 5H),
1
graphy (yield over two steps: 22%; mp 160–161 C). H
endo-2-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-1,2-dihydro-
4-methoxy-3H-pyrrolo[3,4-c]quinolin-3-one (9d). This
compound was prepared from crude g-bromoester 17d
(reaction time 2 h) and was purified by recrystallization
from ethyl acetate (yield over two steps: 48%; mp 179–
3
2
(
.42–2.58 (m, 2H), 3.25 (m, 2H), 4.44 (s, 2H), 4.60–4.78
m, 4H), 7.51 (t, J=7.2, 1H), 7.75 (m, 1H), 7.97 (d,
+
J=8.4, 1H), 8.35 (d, J=8.8, 1H). MS: m/z 337 (M ,
3
.
2).Anal.(C H N O 0.25 H O) C, H, N.
20 23 3 2 2