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D. P. Iwaniuk et al. / Bioorg. Med. Chem. 17 (2009) 6560–6566
J = 5.4 Hz, 1H), 7.09 (br s, 1H), 7.32 (dd, J = 2.1, 8.7 Hz, 1H), 7.83 (d,
J = 5.3 Hz, 2H), 7.85 (s, 1H), 8.40 (d, J = 5.4 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d = 11.4, 23.8, 26.4, 36.2, 38.7, 46.2, 46.6, 52.4,
98.0, 117.2, 122.1, 125.4, 128.3, 134.8, 149.0, 150.1, 151.9, 176.3;
MS (ESI) m/z calcd for C20H29ClN4O 376.2. Found (M+H)+: 377.3.
J = 5.4 Hz, 1H), 7.35 (dd, J = 2.1, 8.9 Hz, 1H), 7.76 (d, J = 8.9 Hz,
1H), 7.93 (d, J = 2.1 Hz, 1H), 8.51 (d, J = 5.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d = 11.0, 25.2, 26.3, 29.8, 41.7, 46.8, 47.4, 48.9,
99.2, 121.5, 125.2, 128.7, 134.8, 149.2, 150.0, 152.1; MS (ESI) m/z
calcd for C20H31ClN4 362.2. Found (M+H)+: 363.4.
4.3.4. N-(7-Chloro-4-quinolyl)-N-(6-diethylaminohexanoyl)-
1,2-diaminoethane, 5
4.4.4. N-(7-Chloro-4-quinolyl)-N-(6-diethylaminohexyl)-1,2-
diaminoethane, 10
Employing 0.700 g (3.17 mmol) of 16 and 0.62 mL 6-bromo-
hexanoyl chloride (4.14 mmol) in the procedure described above
gave 0.642 g (1.65 mmol, 52%) of 5 as a yellow solid. 1H NMR
(400 MHz, CDCl3) d = 0.95 (t, J = 7.1 Hz, 6H), 1.21–1.29 (m, 2H),
1.35–1.42 (m, 2H), 1.62–1.70 (m, 2H), 2.25–2.29 (m, 4H), 2.44 (q,
J = 7.1 Hz, 4H), 3.34 (m, 2H), 3.68 (m, 2H), 6.23 (d, J = 5.4 Hz, 1H),
7.07 (br s, 1H), 7.32 (dd, J = 2.0, 9.0 Hz, 1H), 7.76 (t, J = 6.0 Hz,
1H), 7.82 (d, J = 2.0 Hz, 1H), 7.84 (s, 1H), 8.39 (d, J = 5.4 Hz, 1H).
13C NMR (100 MHz, CDCl3) d = 11.4, 25.5, 26.7, 27.0, 36.4, 38.7,
46.1, 46.7, 52.5, 98.0, 117.3, 122.1, 125.4, 128.3, 134.8, 149.0,
150.1, 151.8, 176.3; MS (ESI) m/z calcd for C21H31ClN4O 390.2.
Found (M+H)+: 391.3.
Employing 0.300 g (0.77 mmol) of 5 in the procedure described
above gave 0.147 g (0.39 mmol, 51%) of 10 as a yellow oil. 1H NMR
(400 MHz, CDCl3) d = 1.01 (t, J = 7.2 Hz, 6H), 1.25–1.55 (m, 9H),
2.38 (m, 2H), 2.51 (q, J = 7.2 Hz, 4H), 2.64 (m, 2H), 3.02 (m, 2H),
3.30–3.34 (m, 2H), 5.94 (br s, 1H), 6.37 (d, J = 5.4 Hz, 1H), 7.34
(dd, J = 2.1, 8.9 Hz, 1H), 7.71 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 2.1 Hz,
1H), 8.50 (d, J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d = 11.6,
27.0, 27.3, 27.6, 30.2, 41.9, 46.9, 47.2, 49.2, 52.9, 99.2, 117.4,
121.3, 125.2, 128.8, 134.8, 149.2, 149.9, 152.1; MS (ESI) m/z calcd
for C21H33ClN4 376.2. Found (M+H)+: 377.5.
4.5. Representative procedure for the synthesis of compounds
11–15
4.4. Representative procedure for the synthesis of compounds
6–10
To a solution of 6 (0.070 g, 0.22 mmol) in 5 mL of glacial acetic
acid, NaBH4 (0.293 g, 7.7 mmol) was added at 0 °C and the reaction
temperature was increased to 60 °C. After 48 h, the reaction mix-
ture was cooled, basified with saturated NaOH, extracted with
CH2Cl2 and washed with brine. The combined organic layers were
dried over anhydrous MgSO4 and concentrated in vacuo. Purifica-
tion by flash chromatography using CH2Cl2/hexanes (1:1 v/v) as
the mobile phase gave 11 (0.029 g, 0.080 mmol, 37% yield) as a yel-
low oil.
A solution of 1 (0.300 g, 0.90 mmol) in 10 mL of THF was heated
to reflux and borane–dimethyl sulfide complex (0.45 mL,
5.4 mmol) was added. After 2.5 h, 6 M HCl (1.45 mL, 9.0 mmol)
and 2 mL of water were added and the mixture was heated to re-
flux for 1.5 h. The clear solution was cooled to room temperature,
basified with saturated NaOH and extracted with a 1:1 mixture
of CH2Cl2 and CHCl3. The combined organic layers were dried over
anhydrous MgSO4 and concentrated in vacuo. Purification by flash
chromatography using EtOH/hexanes/Et3N (1:1:0.1 v/v) as the mo-
bile phase gave 6 (0.224 g, 0.70 mmol, 78% yield) as a brown oil.
4.5.1. N-(7-Chloro-4-quinolyl)-N0-ethyl-N0-(2-diethylamino-
ethyl)-1,2-diaminoethane, 11
1H NMR (400 MHz, CDCl3) d = 0.99 (t, J = 7.1 Hz, 6H), 1.06 (t,
J = 7.1 Hz, 3H), 2.53–2.64 (m, 10H), 2.83 (t, J = 5.5 Hz, 2H), 3.24
(m, 2H), 6.34 (d, J = 5.4 Hz, 1H), 6.36 (br s, 1H), 7.32 (dd, J = 2.1,
8.9 Hz, 1H), 7.77 (d, J = 8.9 Hz, 1H), 7.92 (d, J = 2.1 Hz, 1H), 8.50
(d, J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d = 11.3, 11.9, 40.0,
47.3, 47.5, 50.6, 50.8, 99.1, 117.6, 121.8, 124.8, 134.6, 149.2,
150.0, 152.1; MS (ESI) m/z calcd for C19H29ClN4 348.2. Found
(M+H)+: 349.1.
4.4.1. N-(7-Chloro-4-quinolyl)-N-(2-diethylaminoethyl)-1,2-
diaminoethane, 6
1H NMR (400 MHz, CDCl3) d = 1.01 (t, J = 7.1 Hz, 6H), 2.50–2.58
(m, 6H), 2.70 (t, J = 5.8 Hz, 2H), 3.02 (t, J = 5.8 Hz, 2H), 3.33 (m,
2H), 5.97 (br s, 1H), 6.38 (d, J = 5.4 Hz, 1H), 7.34 (dd, J = 2.1,
8.9 Hz, 1H), 7.73 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 2.1 Hz, 1H), 8.51
(d, J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d = 11.7, 42.0, 46.8,
47.0, 47.4, 52.5, 99.1, 117.4, 121.4, 125.1, 128.6, 134.7, 149.1,
149.9, 152.0; MS (ESI) m/z calcd for C17H25ClN4 320.2. Found
(M+H)+: 321.1.
4.5.2. N-(7-Chloro-4-quinolyl)-N0-ethyl-N0-(4-diethylaminobu-
tyl)-1,2-diaminoethane, 13
Employing 0.100 g (0.29 mmol) of 8 in the procedure described
above gave 0.086 g (0.23 mmol, 80%) of 13 as a light yellow oil. 1H
NMR (400 MHz, CDCl3) d = 0.99 (t, J = 7.1 Hz, 6H), 1.07 (t, J = 7.1 Hz,
3H), 1.46–1.48 (m, 4H), 2.39 (m, 2H), 2.43–2.48 (m, 4H), 2.52 (m,
2H), 2.59 (m, 2H), 2.81 (t, J = 5.6 Hz, 2H), 3.24 (m, 2H), 6.06 (br s,
1H), 6.35 (d, J = 5.3 Hz, 1H), 7.34 (dd, J = 2.0, 8.9 Hz, 1H), 7.64 (d,
J = 8.9 Hz, 1H), 7.93 (d, J = 2.0 Hz, 1H), 8.51 (d, J = 5.3 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d = 11.6, 11.9, 25.0, 25.4, 39.7, 46.8, 46.9,
51.1, 52.8, 52.9, 99.3, 117.4, 121.0, 125.2, 128.7, 134.7, 149.1,
149.8, 152.1; MS (ESI) m/z calcd for C21H33ClN4 376.2. Found
(M+H)+: 377.4.
4.4.2. N-(7-Chloro-4-quinolyl)-N-(4-diethylaminobutyl)-1,2-
diaminoethane, 8
Employing 0.300 g (0.83 mmol) of 3 in the procedure described
above gave 0.101 g (0.29 mmol, 35%) of 8 as yellow oil. 1H NMR
(400 MHz, CDCl3) d = 1.01 (t, J = 7.2 Hz, 6H), 1.53–1.56 (m, 4H),
2.45 (m, 2H), 2.53 (q, J = 7.2 Hz, 4H), 2.68 (m, 2H), 3.03 (m, 2H),
3.34 (m, 2H), 6.10 (br s, 1H), 6.36 (d, J = 5.4 Hz, 1H), 7.34 (dd,
J = 2.1, 8.9 Hz, 1H), 7.79 (d, J = 8.9 Hz, 1H), 7.92 (d, J = 2.1 Hz, 1H),
8.50 (d, J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d = 11.4, 24.8,
28.1, 41.8, 46.7, 47.3, 49.2, 52.7, 99.0, 117.5, 121.6, 125.2, 128.6,
134.8, 149.2, 149.9, 152.0; MS (ESI) m/z calcd for C19H29ClN4
348.2. Found (M+H)+: 349.2.
4.5.3. N-(7-Chloro-4-quinolyl)-N0-ethyl-N0-(5-
diethylaminopentyl)-1,2-diaminoethane, 14
4.4.3. N-(7-Chloro-4-quinolyl)-N-(5-diethylaminopentyl)-1,2-
diaminoethane, 9
Employing 0.100 g (0.28 mmol) of 9 in the procedure described
above gave 0.075 g (0.19 mmol, 70%) of 14 as a light yellow oil. 1H
NMR (400 MHz, CDCl3) d = 0.98 (t, J = 7.1 Hz, 6H), 1.07 (t, J = 7.1 Hz,
3H), 1.29 (m, 2H), 1.42–1.54 (m, 4H), 2.33 (m, 2H), 2.45–2.51 (m,
6H), 2.60 (q, J = 7.1 Hz, 4H), 2.81 (t, J = 5.6 Hz, 2H), 3.24 (m, 2H),
6.07 (br s, 1H), 6.36 (d, J = 5.2 Hz, 1H), 7.34 (dd, J = 2.1, 8.9 Hz,
1H), 7.63 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 2.1 Hz, 1H), 8.51 (d,
Employing 0.300 g (0.80 mmol) of 4 in the procedure described
above gave 0.170 g (0.47 mmol, 59%) of 9 as a yellow oil. 1H NMR
(400 MHz, CDCl3) d = 1.07 (t, J = 7.2 Hz, 6H), 1.37 (m, 2H), 1.52–
1.57 (m, 4H), 2.48 (m, 2H), 2.61 (q, J = 7.2 Hz, 4H), 2.68 (t,
J = 7.0 Hz, 2H), 3.04 (m, 2H), 3.34 (m, 2H), 5.99 (br s, 1H), 6.38 (d,