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Conventional heating
procedure: Tetrahydroindolizinediones 2,
[11]
3,
[12]
or 4
[12]
(2.1
mmol) and 2-aminobenzaldehydes 1a,
[12]
1b,
[12]
or imine 1c
[13]
(2.6
mmol) were added to acetic acid (20 mL) and heated while stirring under
reflux for 8 h (TLC control). The reaction mixture was cooled to
room temperature and the solvent was removed under reduced pressure.
The crude product was diluted in methanol and hydrogen chloride
was bubbled. The products were purified by flash chromatography
(dichloromethane-methanol 8:2→7:3) before recrystallization.
<A NAME="RG18802ST-9">9</A>
Microwave irradiation
procedure: The reaction was carried out in a open monomod Prolabo
Synthewave S402 microwave oven,® (equipped with
a probe that regulates the temperature of the reaction medium) along
with a built-in mechanic stirrer. Quartz vessel was used equipped
with a reflux condenser. Tetrahydroindolizinediones 2-4 (2.1 mmol) and 2-aminobenzaldehydes 1a,
[12]
1b,
[12]
or
imine 1c
[13]
(2.6
mmol) were added to acetic acid (20 mL) and heated at reflux while
stirring under microwave irradiation (60 W) for 15 min (optimized
time). Hydrochlorides were prepared and purified as in the conventional
procedure.
7-Methyl-9-oxo-3-(2-piperidinyl-1-ylethoxy)-9,11-dihydroindolizino[1,2-
b
]quinoline-8-carbonitrile Hydrochloride(5a): 1H NMR (300 MHz,
CDCl3): δ = 1.48 (m, 2 H), 1.65 (m,
4 H), 2.93 (m, 2 H), 4.34 (m, 2 H), 5.25 (s, 2 H), 7.18-7.82
(m, 4 H), 8.32 (s, 1 H). MS: m/z = 274 [M+].
Anal. Calcd. for C24H24N4O2
·1HCl·2H2O:
C, 60.95; H, 6.18; N, 11.85; Cl, 7.50. Found: C, 61.02; H, 6.26;
N, 11.58; Cl, 7.32.
7-Methyl-9-oxo-3-(2-piperidinyl-1-ylethoxy)-9,11-dihydroindolizino[1,2-
b
]quinoline-8-carboxamide Hydrochloride(6a): 1H NMR (300 MHz,
DMSO-d
6): δ = 1.42
(m, 2 H), 1.82 (m, 4 H), 2.50 (s, 3 H), 3.05 (m, 2 H), 3.59 (m,
4 H), 4.63 (m, 2 H), 5.23 (s, 2 H), 7.10 (s, 1 H), 7.42 (dd, 1 H),
7.49 (s, 1 H),7.60 (d, 1 H), 8.09 (d, 1 H), 8.24 (s, 1 H), 8.64
(s, 1 H), 10.22 (s, 1 H). MS: m/z = 418 [M+].
Anal. Calcd. for C24H26N4O3
·1HCl·2.5H2O:
C, 57.65; H, 6.45; N, 11.21; Cl, 17.09. Found: C, 57.89; H, 6.20;
N, 11.53; Cl, 17.11.
N
-[7-Methyl-9-oxo-3-(2-piperidinyl-1-ylethoxy)-9,11-dihydroindolizino[1,2-
b
]quinolin-8-ylmethyl]acetamide Hydrochloride(7a): 1H NMR (300 MHz,
DMSO-d
6): δ = 1.70
(m, 2 H), 1.83 (m, 4 H), 1.95 (s, 3 H), 2.46 (s, 3 H), 3.05 (m,
2 H), 3.58 (m, 4 H), 4.35 (d, 2 H), 4.68 (m, 2 H), 5.26 (s, 2 H),
6.80 (m, 1 H), 7.16 (s, 1 H), 7.43 (dd, 1 H), 7.58 (d, 1 H), 8.09
(d, 1 H), 8.08 (d, 1 H), 8.65 (s, 1 H), 10.85 (s, 1 H). MS: m/z = 446 [M+].
Anal. Calcd. for C26H30N4O3
·1HCl·2H2O:
C, 60.17; H, 6.80; N, 10.79; Cl, 6.83. Found: C, 60.03; H, 7.05;
N, 10.41; Cl, 7.12.
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