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3.57–3.60 (1H, m, C(5) H), 5.79 (1H, s, (C10b) H), 7.00–7.25
(4H, m, Ph); m/z 191 (M+, 20%), 115 (60), 104 (100); anal.
found: C, 69.07; H, 6.80; N, 6.91. Calc. for C11H13NS: C, 69.11;
H 6.49; N 7.30%.
m, C(5, 6, 8, 9) H), 4.26 (2H, d, J 8.8, C(15) H), 7.14–7.78 (8H,
m, Ph); 13C NMR (62.5 MHz; CDCl3) δ (ppm) 13.16 IJCH2CH3),
26.13 (C9), 32.81 (C15), 33.07 (C5), 34.34 IJCH2CH3), 54.17
(C8), 60.91 (C6), 120.53 (C13), 121.96 (C9a), 123.68 (C10),
123.79 (C11), 126.71 (C12), 127.03 (C3), 127.32 (C2), 129.02
(C9b), 130.29 (C4), 130.66 (C1), 138.28 (C13a), 138.96 (C14a),
140.00 (C4a), 141.32 (C15a), 156.40 (CO); m/z 365 (M+, 35%),
249 (70), 234 (80), 115 (75), 104 (100); anal. found: C, 71.93;
H, 6.36; N, 3.72. Calc. for C22H23NO2S: C, 72.30; H, 6.34; N,
3.83%.
General procedure for the synthesis of carbamate derivatives
21, 31, and 38
A solution of the given amounts of the respective quinolizine
derivative (2 mmol) in dry THF (30 mL) was cooled in metha-
nol/dry ice at −80 °C. To the solution, 1 g (10 mmol) of ethyl-
chloroformate was added under inert atmosphere. The reac-
tion mixture was stirred for 4 h and then a solution of 0.37 g
(6 mmol) of sodium cyanoborohydride in dry THF (20 mL)
was added after cooling again to −80 °C. The reaction mixture
was allowed to reach to room temperature and stirred for 48
h. It was then treated with 2 N NaOH (100 mL), and the
organic layer was separated, washed with a brine solution (2
× 30 mL), and the organic solvent was then evaporated under
reduced pressure. The residue obtained was purified by silica
gel column chromatography using hexane : EtOAc 3 : 1.
General procedure for the synthesis of the azecine derivatives
4, 5, and 6
To an ice-cooled suspension of LiAlH4 (1 g, 2.6 mmol) in dry
THF (15 mL), a solution of the respective carbamate deriva-
tive (6 mmol) in dry THF (10 mL) was added while stirring
under inert atmosphere. The ice bath was then removed and
the reaction mixture was heated to reflux for 3 h. It was then
allowed to cool to room temperature and the excess
unreacted LiAlH4 was quenched with the careful addition of
saturated Rochelle solution under inert atmosphere and with
cooling in an ice bath until no H2 evolves. The reaction mix-
ture was then filtered, washed with dry THF, and the filtrate
was evaporated under reduced pressure. The obtained resi-
due was subjected to a purification process by silica gel chro-
matography using hexane : EtOAc 3 : 2.
Ethyl 4,5,6,7,8,13-hexahydrobenzoijd]thienoij2,3-g]azecine-6-
carboxylate (21)
Yellow oil (0.4 g, 62%); 1H NMR (250 MHz; CDCl3) δ (ppm)
0.92 (3H, t, J 7, CH2CH3), 2.67–3.57 (8H, m, C(4, 5, 7, 8) H),
3.74 (2H, q, J 7, CH2CH3), 4.14 (2H, d, J 10, C(13) H), 6.70
(1H, d, J 5, C(3) H), 6.80 (1H, d, J 5, C(2) H), 7.01–7.20 (4H,
m, Ph); 13C NMR (62.5 MHz; CDCl3) δ (ppm) 14.20 IJCH2CH3),
28.47 (C4), 32.50 (C13), 32.83 (C7), 34.05 IJCH2CH3), 53.92
(C5), 61.00 (C7), 122.54 (C3a), 126.73 (C10), 126.98 (C11),
130.19 (C9), 130.36 (C12), 131.14 (C3), 135.87 (C2), 138.45
(C13a), 138.59 (C8a), 139.27 (C12a), 156.48 (CO); m/z 315 (M+,
20%), 211 (30), 184 (60), 115 (80), 104 (100); anal. found: C,
68.31; H, 6.41; N, 4.42. Calc. for C18H21NO2S: C, 68.54; H
6.71; N 4.44%.
6-Methyl-4,5,6,7,8,13-hexahydrobenzoijd]thienoij2,3-g]azecine
(4)
1
Yellow oil (1.10 g, 70%); H NMR (250 MHz; CDCl3) δ (ppm)
2.22 (3H, s, N-Me), 2.59–2.87 (8H, m, C(4, 5, 7, 8) H), 4.35
(2H, s, C(13) H), 6.72 (1H, d, J 5, C(3), H), 7.03(1H, d, J 5,
C(2), H), 7.06–7.18 (4H, m, Ph); 13C NMR (62.5 MHz; CDCl3)
δ (ppm) 29.42 (C4), 32.84 (C13), 35.00 (C8), 46.20 (N-Me),
59.51 (C5), 59.59 (C7), 121.63 (C3a), 126.35 (C10), 126.50
(C11), 129.93 (C9), 130.21 (C12), 130.30 (C3), 137.37 (C2),
139.66 (C13a), 139.78 (C8a), 140.28 (C12a); m/z 257 (M+,
25%), 115 (95), 199 (60), 184 (100), 165 (70), 152 (90); anal.
found: C, 74.59; H, 6.98; N, 5.38. Calc. for C16H19NS: C, 74.66;
H, 7.44; N, 5.44%.
Ethyl 4,5,6,7,8,13-hexahydrobenzoijd]thienoij3,2-g]azecine-6-
carboxylate (31)
1
Yellow oil (0.37 g, 59%); H NMR (250 MHz; CDCl3) δ (ppm)
0.95 (3H, t, J 7, CH2CH3), 2.66–3.56 (8H, m, C(4, 5, 7, 8) H),
3.75 (2H, q, J 7, CH2CH3), 3.96 (2H, d, J 7, C(13) H), 6.82–7.28
(6H, m, C(1, 2, 9, 10, 11, 12) H); 13C NMR (62.5 MHz; CDCl3)
δ (ppm) 14.20 IJCH2CH3), 27.83 (C8), 31.57 (C13), 32.72 (C4),
33.99 IJCH2CH3), 54.23 (C7), 60.98 (C5), 121.58 (C13a), 126.60
(C10), 126.94 (C11), 130.23 (C9), 130.58 (C12), 131.28 (C1),
136.65 (C2), 137.14 (C3a), 139.04 (C8a), 139.19 (C12a), 156.50
(CO); m/z 315 (M+, 15%), 211 (25), 184 (70), 115 (85), 104
(100); anal. found: C, 68.21; H, 6.53; N, 4.35. Calc. for
C18H21NO2S: C, 68.54; H, 6.71; N 4.44%.
6-Methyl-4,5,6,7,8,13-hexahydrobenzoijd]thienoij3,2-g]azecine
(5)12
1
Yellow oil (1.13 g, 73%); H NMR (250 MHz; CDCl3) δ (ppm)
2.26 (3H, s, N-Me), 2.65–3.09 (8H, m, C(4, 5, 7, 8) H), 4.34
(2H, s, C(13) H), 6.92 (1H, d, J 5.8, C(1) H), 7.01–7.26 (4H, m,
Ph) 7.31 (1H, d, J 5.8, C(2) H); 13C NMR (62.5 MHz; CDCl3) δ
(ppm) 29.91 (C8), 33.71 (C13), 34.88 (C4), 46.29 (N-Me), 59.41
(C7), 60.67 (C5), 121.45 (C13a), 126.28 (C10), 129.93 (C11),
130.37 (C9), 130.49 (C12), 131.36 (C1), 137.77 (C2), 138.32
(C3a), 139.94 (C8a), 140.35 (C12a); m/z 257 (M+, 25%), 199
(40), 184 (100), 165 (60), 152 (80), 115 (90); anal. found: C,
74.38; H, 7.05; N, 5.48. Calc. for C16H19NS: C, 74.66; H, 7.44;
N, 5.44%.
Ethyl 5,6,7,8,9,15-hexahydrobenzoijd]benzothieno ij2,3-g]-
azecine-7-carboxylate (38)
Yellow oil (0.5 g, 69%); 1H NMR (250 MHz; CDCl3) δ (ppm)
0.93 (3H, t, CH2CH3), 2.06 (2H, brs, CH2CH3), 2.75–3.73 (8H,
Med. Chem. Commun.
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