Molecules 2016, 21, 1637
10 of 16
mixture was stirred at room temperature overnight. The solution typically gave a white solid as
precipitate. The solid was filtered, washed several times with absolute ethanol, and dried under
vacuum to give the pure target compounds 11a–b, e–f.
2-(3-Aminopropylamino)-N-(3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)acetamide dihydrochloride
(
11a). Yield: 85%, white solid. 1H-NMR (D2O)
δ
: 7.75 (t, J = 8.0 Hz, 4H, Ar-H), 7.28~7.31 (m, 2H,
CH2), 3.69 (t, J = 6.0 Hz, 2H, 1 CH2), 3.24 (t, J = 6.4 Hz, 2H, 1 CH2), 3.17
CH2), 3.07 (t, J = 8.0 Hz, 2H, 1 CH2), 2.05~2.13 (m, 2H, 1 CH2), 1.70~1.75
: 165.68, 163.82, 134.54, 130.66, 129.61, 126.46, 125.19, 119.01,
2HCl]+. Anal. calcd. for
Ar-H), 3.91 (s, 2H, 1
×
×
×
(t, J = 8.0 Hz, 2H, 1
×
×
×
(m, 2H, 1 × CH2); 13C-NMR (D2O)
δ
48.09, 44.60, 37.94, 37.21, 36.54, 26.57, 23.68; ESI-MI m/z: 369.3 [M + 1
−
C20H26Cl2N4O3·0.4H2O: C 53.55%, H 6.02%, N 12.49%; found: C 53.65%, H 5.93%, N 12.26%.
2-(3-(3-Aminopropylamino)propylamino)-N-(3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)acetamide
1
trihydrochloride (11b). Yield: 85%, white solid. H-NMR (D2O)
δ
: 7.82 (t, J = 7.6 Hz, 4H, Ar-H), 7.36
CH2), 3.27 (t, J = 6.4 Hz, 2H,
CH2), 2.13~2.17 (m, 2H, 1 CH2),
CH2); 13C-NMR (D2O)
: 165.62, 163.98, 134.63,
130.76, 129.71, 126.52, 125.32, 119.10, 48.10, 44.71, 44.57, 44.47, 37.96, 37.21, 36.50, 26.57, 23.73, 22.61;
ESI-MI m/z: 426.3 [M + 1 0.35: C 51.04%, H 6.46%,
3HCl]+. Anal. calcd. for C23H34Cl3N5O3
N 12.94%; found: C 51.04%, H 6.78%, N 12.97%.
(t, J = 7.2 Hz, 2H, Ar-H), 3.93 (s, 2H, 1
CH2), 3.15~3.22 (m, 6H, 3 CH2), 3.08 (t, J = 7.6 Hz, 2H, 1
2.06~2.10 (m, 2H, 1 CH2), 1.73~1.76 (m, 2H, 1
×
CH2), 3.74 (t, J = 6.0 Hz, 2H, 1
×
1
×
×
×
×
×
×
δ
−
·
2-(3-(4-(3-Aminopropylamino)butylamino)propylamino)-N-(3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)
acetamide tetrahydrochloride (11e). Yield: 85%, white solid. 1H-NMR (D2O)
: 7.97 (d, J = 6.8 Hz, 4H, Ar-H),
7.48 (t, J = 7.2 Hz, 2H, Ar-H), 3.93 (s, 2H, 1 CH2), 3.83 (t, J = 5.6 Hz, 2H, 1 CH2), 3.28 (t, J = 6.4 Hz
2H, 1 CH2), 3.05~3.21 (m, 12H, 6 CH2), 2.10~2.18 (m, 2H, 1
CH2), 2.04~2.07 (m, 2H, 1 × CH2),
1.76~1.81 (m, 6H, 3 : 165.63, 164.45, 134.63, 130.99, 130.01, 126.69, 125.78,
CH2); 13C-NMR (D2O)
119.55, 48.10, 47.03, 46.98, 44.52, 44.43, 38.00, 37.26, 36.52, 26.63, 23.72, 22.75, 22.63; ESI-MI m/z: 497.4
[M + 1 0.25H2O: C 50.12%, H 6.93%, N 12.99%; found:
4HCl]+. Anal. calcd. for C27H44Cl4N6O3
C 50.37%, H 6.65%, N 12.70%.
δ
×
×
,
×
×
×
×
δ
−
·
2-(4-(4-(4-Aminobutylamino)butylamino)butylamino)-N-(3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)
1
acetamide tetrahydrochloride (11f). Yield: 85%, white solid. H-NMR (D2O)
δ
: 7.71~7.76 (m, J = 8.0 Hz,
CH2), 3.19 (t,
CH2), 1.65~1.71 (m,
: 165.80, 164.53, 134.87, 131.06, 130.19, 126.75, 125.96, 119.74, 47.99,
46.91, 46.81, 38.81, 38.06, 38.02, 37.30, 37.28, 26.69, 26.65, 26.64, 23.92, 22.80, 22.76; ESI-MI m/z: 525.3
[M + 1 1.05H2O: C 50.52%, H 7.32%, N 12.19%; found:
4HCl]+. Anal. calcd. for C29H48Cl4N6O3
4H, Ar-H), 7.28 (t, J = 8.0 Hz, 2H, Ar-H), 3.82 (s, 2H, 1
J = 6.4 Hz, 2H, 1 CH2), 2.99~3.06 (m, 10H, 5 CH2), 2.92 (t, J = 7.6 Hz, 2H, 1
14H, 7
CH2); 13C-NMR (D2O)
×
CH2), 3.64 (t, J = 7.2 Hz, 2H, 1
×
×
×
×
×
δ
−
·
C 50.60%, H 7.12%, N 12.42%.
3.4. General Procedure for the Synthesis of 17b–d
3.4.1. Synthesis of Compounds 14a–b
Intermediates 12, 13 were prepared by a modified previously reported procedure [26,27].
Compound 13 (1.13 g, 5 mmol) added portion wise to 1,3-dibromopropane or 1,4-dibromobutane
(10 mmol) in acetone (30 mL). The solution was refluxed for 12 h; after cooling and filtration, the
solvent was removed under vacuo to give a solid. The latter was recrystallized from ethanol to afford
compound 14a–b.
1
5-Bromo-2-(3-bromopropyl)isoindoline-1,3-dione (14a), Yield: 70%, H-NMR (CDCl3)
δ: 7.97 (d, 1H,
J = 1.8 Hz, Ar-H), 7.85~7.87 (m, 1H, Ar-H), 7.72 (d, 1H, J = 8.0 Hz, Ar-H), 3.71 (t, 2H, J = 6.0 Hz,
1 × CH2), 3.44 (t, 2H, J = 6.4 Hz, 1 × CH2), 1.82~1.91 (m, 4H, 1 × CH2). ESI-MS m/z: 345.9 [M + 1]+.