Molecules 2009, 14
878
4.26 (q, 2H, J = 7.2 Hz, OCH2), 7.11 (dd, 1H, J = 6.8 Hz, J = 7.2 Hz, Ar-H), 7.39 (s, 2H, Ph-H), 7.57
(dd, 1H, J = 8.8 Hz, J = 6.8 Hz, Ar-H), 7.66 (d, 1H, J = 8.8 Hz, Ar-H), 8.08 (s, 1H, Ar-H), 8.66 (bs,
1H, NH), 9.17 (d, 1H, J = 7.2 Hz, Ar-H); 13C-NMR (CDCl3): δ = 14.4, 56.4, 60.9, 61.0, 105.1, 105.1,
110.6, 116.9, 122.0, 128.4, 129.4, 134.2, 140.2, 141.5, 143.7, 153.3, 154.9, 165.3, 166.9; IR: ν 3462,
3328, 2939, 1720, 1678, 1587, 1487, 1336, 1216, 1126, 1009, 772 cm-1; MS (ESI): m/z 449.0 [M +
Na]+.
Ethyl 1-[3-(3,4-dimethoxyphenyl)acrylamido]-4-oxo-4H-quinolizine-3-carboxylate (7b): Yield 85%;
1
m.p.: 105-107°C; H-NMR (DMSO-d6): δ 1.30 (t, 3H, J = 7.2 Hz, CH3), 3.81 (s, 3H, OCH3), 3.83 (s,
3H, OCH3), 4.26 (q, 2H, J = 7.2 Hz, CH2), 6.81 (d, 1H, J = 15.6 Hz, CH=CH), 7.03 (d, 1H, J = 8.4 Hz,
Ar-H), 7.21 (d, 1H, J = 8.4 Hz, Ar-H), 7.26 (s, 1H, Ar-H), 7.51 (dd, 1H, J = 6.4 Hz, J = 7.2 Hz, Ar-H),
7.55 (d, 1H, J = 15.6 Hz, Ar-H), 7.86 (d, 1H, J = 8.8 Hz, Ar-H), 7.96 (dd, 1H, J = 7.2 Hz, J = 8.0 Hz,
Ar-H), 8.26 (s, 1H, Ar-H), 9.30 (d, 1H, J = 7.2 Hz, Ar-H), 9.89 (s, 1H, NH); 13C-NMR (DMSO-d6): δ
14.8, 55.9, 56.0, 60.5, 103.7, 110.6, 111.1, 112.2, 118.2, 119.4, 122.3, 122.4, 127.9, 129.8, 135.8,
139.0, 141.1, 143.1, 149.4, 150.9, 154.1, 165.3, 165.9; IR: ν 3436, 3226, 2935, 1702, 1677, 1595,
1491, 1377, 1236, 1114, 1026, 768 cm-1; MS (ESI): m/z 445.0 [M + Na]+.
General procedure for the synthesis of 9a,b
To a suspension of 7a or 7b (0.5 mmol) in 80% methanol (20 mL) was added NaOH (5 mmol). The
reaction mixture was heated to reflux till the starting 7a or 7b disappeared according to monitoring by
TLC. After evaporation of the solvent under reduced pressure, the remaining solid was dissolved in
water (20 mL) and the clear solution was acidified with 1 mol/L HCl to pH 1 and the resulting
suspension extracted with CH2Cl2. The combined organic layer was dried over anhydrous MgSO4
followed by filtration. The desired 9a or 9b were finally obtained as solids by column chromatography
(eluents: CH3OH/CHCl3 = 1:30)
1-(3,4,5-Trimethoxyphenylcarbonylamino)-4-oxo-4H-quinolizine-3-carboxylic acid (9a): Yield 92%;
m.p.: 280-282°C; 1H-NMR (DMSO-d6): δ 3.67 (s, 3H, OCH3), 3.80 (s, 6H, OCH3), 7.33 (s, 2H, Ar-H),
7.64 (dd, 1H, J = 7.2 Hz, J = 6.8 Hz, Ar-H), 7.94 (d, 1H, J = 8.8 Hz, Ar-H), 8.02 (dd, 1H, J = 6.8 Hz, J
=8.8 Hz, Ar-H ), 8.29 (s, 1H, Ar-H), 9.30 (d, 1H, J = 7.2 Hz, Ar-H), 10.29 (s, 1H, NH), 13.96 (s, 1H,
COOH); 13C-NMR (DMSO-d6): δ 56.6, 60.6, 103.9, 105.9, 115.2, 105.9, 115.2, 120.2, 123.3, 129.1,
129.7, 136.6, 138.2, 141.0, 143.0, 153.2, 159.0, 166.1, 166.5; IR: ν 3440, 3115, 2924, 2853, 1696,
1657, 1615, 1587, 1496, 1453, 1364, 1292, 1123 cm-1; MS (ESI): m/z 397.0 [M - H]-.
1-(3,4-Dimethoxystyrylcarboxylamino)-4-oxo-4H-quinolizine-3-carboxylic acid (9b): Yield 91%; m.p.:
306-308°C; 1H-NMR (DMSO-d6): δ 3.82 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 6.84 (d, 1H, J = 16.0 Hz,
CH=CH), 7.03 (d, 1H, J = 8.4 Hz, Ar-H), 7.23 (d, 1H, J = 8.4 Hz, Ar-H), 7.27 (s, 1H, Ar-H), 7.58 (d,
1H, J = 16.0 Hz, Ar-H), 7.70-7.74 (m, 1H, Ar-H), 8.10-8.12 (m, 2H, Ar-H), 8.44 (s, 1H, Ar-H), 9.37 (d,
13
1H, J = 7.2 Hz, Ar-H), 10.11 (s, 1H, NH), 14.13 (s, 1H, OH); C-NMR (DMSO-d6): δ 56.0, 56.1,
103.9, 110.9, 112.4, 115.5, 119.3, 120.0, 122.3, 122.8, 127.9, 136.3, 136.9, 141.4, 142.1, 149.5, 151.1,