b i o c h e m i c a l p h a r m a c o l o g y 7 1 ( 2 0 0 5 ) 6 1 – 6 8
63
138.32, 150.26, 151.87, 157.09; anal. calc. for C20H20ClN3: C,
71.10; H, 5.97; N, 12.44; Cl, 10.49; m/z 337.13457. Found C, 70.92;
H, 5.34; N, 12.04; m/z 337.13438 (M)+.
(1H, t, J = 7.48 Hz, Ar–H, H40), 7.50 (1H, d, J = 7.63 Hz, Ar–H, H60),
7.64–7.57 (2H, m, Ar–H, H6, H30), 8.07 (1H, d, J = 7.32 Hz, Ar–H,
H5), 8.26 (1H, d, J = 7.63 Hz, Ar–H, H7); 13C NMR dC (CDCl3) 52.34
(2C), 52.59 (2C), 61.22, 105.11, 122.38, 124.09, 124.33, 125.06,
127.18, 127.99, 128.70 (2C), 130.90, 133.10, 134.09, 136.98, 144.79,
148.71, 148.94, 158.94; anal. calc. for C22H18BrF6N3: C, 50.99; H,
3.50; N, 8.10; Br, 15.42; F, 21.99; m/z 517.05883. Found C, 50.93; H,
3.52; N, 8.15; m/z 517.05931 (M)+.
2.7.
4-[4-(20-Bromo-benzyl)-piperazin-1-yl]-7-chloro-
quinoline (CMP3)
This compound was prepared from CMP10 (0.5 g, 1.46 mmol),
2-bromobenzaldehyde (0.29 g, 1.61 mmol) and sodium cyano-
borohydride (0.19 g, 3.1 mmol) by the above method to give
CMP3 (1.16 g, 100%) as cream-yellow crystals; mp 90–93 8C
(from EtOH); Rf 0.52 (hexane:ethyl acetate, 1:9); IR (CHCl3): nmax
(cmꢀ1) 3052 (CH Ar), 1576 (C C and C N), 1264 (CN); 1H NMR dH
(400 MHz, CDCl3) 2.83 (4H, t, J = 4.79 Hz, N–CH2, H11, H13), 3.25
(4H, t, J = 4.71 Hz, N–CH2, H10, H14), 3.77 (2H, s, CH2, Ha), 6.84
(1H, d, J = 5.05 Hz, Ar–H, H3), 7.16 (1H, t, J = 7.67 Hz, Ar–H, H50),
7.33 (1H, t, J = 7.49 Hz, Ar–H, H40), 7.43 (1H, dd, J = 8.89, 2.18 Hz,
Ar–H, H6), 7.50 (1H, d, J = 7.67, Ar–H, H60), 7.59 (1H, d, J = 7.84 Hz,
Ar–H, H30), 7.97 (1H, d, J = 9.06 Hz, Ar–H, H5), 8.07 (1H, d,
J = 2.27 Hz, Ar–H, H8), 8.73 (1H, d, J = 5.05 Hz, Ar–H, H2); 13C
NMR dC (CDCl3) 52.24 (2C), 52.91 (2C), 61.74, 108.94, 121.94,
124.79, 125.24, 126.09, 127.27, 128.64, 128.83, 130.86, 132.89,
134.90, 137.19, 150.12, 151.84, 157.04;anal. calc. forC20H19BrClN3:
C, 57.64; H, 4.60; N, 10.08; Br, 19.17; Cl, 8.51; m/z 415.04509.
Found C, 57.52; H, 4.59; N, 9.60; m/z 415.04329 (M)+.
2.10.
1-(20-Bromo-benzyl)-4-phenyl-piperazine (CMP6)
This compound was prepared from phenylpiperazine (0.5 g,
0.47 ml, 3.1 mmol), 2-bromobenzaldehyde (0.63 g, 3.4 mmol)
and sodium cyanoborohydride (0.41 g, 6.5 mmol) by the above
method to give CMP6 (0.437 g, 42%) as cream crystals; mp 109–
113 8C (from EtOH); Rf 0.76 (hexane:ethyl acetate, 1:9); IR
(CHCl3): nmax (cmꢀ1) 3052 (CH Ar), 1599 (C C Ar), 1264 (CN); 1H
NMR dH (400 MHz, CDCl3) 2.70 (4H, t, J = 4.88 Hz, N–CH2, H2, H5),
3.23 (4H, t, J = 4.88 Hz, N–CH2, H3, H6), 3.68 (2H, s, CH2, Ha), 6.85
(1H, t, J = 7.32 Hz, Ar–H, H10), 6.92 (2H, d, J = 7.94 Hz, Ar–H, H12,
H8), 7.12 (1H, t, J = 7.63 Hz, Ar–H, H50), 7.26 (2H, t, J = 8.09, Ar–H,
H9, H11), 7.33 (1H, t, J = 7.32 Hz, Ar–H, H40), 7.55 (1H, d,
J = 7.94 Hz, Ar–H, H60), 7.57 (1H, d, J = 7.94 Hz, Ar–H, H30); 13C
NMR dC (CDCl3) 49.20 (2C), 53.11 (2C), 61.74, 116.04, 116.05 (2C),
116.41, 119.60, 127.23, 128.47, 129.07, 129.12, 130.77, 132.78,
151.39; anal. calc. for C17H19BrN2: C, 61.64; H, 5.78; N, 8.45; Br,
24.12; m/z 330.07316. Found C, 61.79; H, 5.84; N, 8.33; m/z
330.07242 (M)+.
2.8.
7-Chloro-4-[4-(20-iodo-benzyl)-piperzine-1-yl]-
quinoline (CMP4)
This compound was prepared from CMP10 (0.5 g, 1.46 mmol),
2-iodobenzaldehyde (0.38 g, 1.61 mmol) and sodium cyano-
borohydride (0.19 g, 3.1 mmol) by the above method to give
CMP4 (0.18 g, 27%) as a yellow oil; Rf 0.57 (hexane:ethyl acetate,
1:9); IR (CHCl3): nmax (cmꢀ1) 3052 (CH Ar), 1576 (C C and C N),
1264 (C–N); 1H NMR dH (400 MHz, CDCl3) 2.83 (4H, t, J = 4.79 Hz,
N–CH2, H11, H13), 3.25 (4H, t, J = 4.71 Hz, N–CH2, H10, H14), 3.67
(2H, s, CH2, Ha), 6.82 (1H, d, J = 5.05 Hz, Ar–H, H3), 7.14 (1H, t,
J = 7.67 Hz, Ar–H, H50), 7.34 (1H, t, J = 7.49 Hz, Ar–H, H40), 7.43
(1H, dd, J = 8.98, 2.09 Hz, Ar–H, H6), 7.51 (1H, d, J = 7.67 Hz, Ar–H,
H60), 7.86 (1H, d, J = 6.71 Hz, Ar–H, H30), 7.95 (1H, d, J = 9.06 Hz,
Ar–H, H5), 8.03 (1H, d, J = 2.21 Hz, Ar–H, H8), 8.71 (1H, d,
J = 5.05 Hz, Ar–H, H2); 13C NMR dC (CDCl3) 52.22 (2C), 52.76 (2C),
66.34, 100.64, 108.92, 121.91, 125.24, 126.04, 128.02, 128.76,
128.88, 130.39, 134.85, 139.62, 140.15, 150.07, 151.80, 157.05;
anal. calc. for C20H19ClIN3: C, 51.80; H, 4.13; N, 9.06; Cl, 7.64; I,
27.36; m/z 463.03122. Found C, 51.31; H, 4.05; N, 8.80; m/z
463.02897 (M)+.
2.11.
(CMP7)
1-(20-Bromo-benzyl)-4-(10-fluoro-phenyl)-piperazine
This compound was prepared from 4-fluorophenylpiperazine
(0.5 g, 2.7 mmol), 2-bromobenzaldehyde (0.57 g, 3.4 mmol) and
sodium cyanoborohydride (0.37 g, 5.8 mmol) by the above
method to give CMP7 (0.34 g, 35%) as cream crystals; mp 76–
78 8C (from EtOH); Rf 0.76 (hexane:ethyl acetate, 1:9); IR (CHCl3):
nmax (cmꢀ1) 3052 (CH Ar), 1508 (C C Ar), 1264 (CN); 1H NMR dH
(400 MHz, CDCl3) 2.70 (4H, t, J = 4.88 Hz, N–CH2, H2, H5), 3.14
(4H, t, J = 5.04 Hz, N–CH2, H3, H6), 3.68 (2H, s, CH2, Ha), 6.85–6.99
(4H, m, Ar–H, H8, H9, H11, H12), 7.12 (1H, t, J = 7.63 Hz, Ar–H,
H50), 7.30 (1H, t, J = 7.62 Hz, Ar–H, H40), 7.51 (1H, d, J = 7.63 Hz,
Ar–H, H60), 7.56 (1H, d, J = 7.96 Hz, Ar–H, H30); 13C NMR dC (CDCl3)
50.15 (2C), 53.04 (2C), 61.97, 115.18, 115.43, 117.62, 117.76,
124.69, 126.87, 128.34, 130.73, 132.97, 145.82, 155.64, 158.81;
anal. calc. for C17H18BrFN2ꢂ0.1H2O, C, 58.17; H, 5.17; N, 7.98; Br,
22.88; F, 5.44; m/z 348.06374. Found C, 58.26; H, 5.11; N, 7.85; m/z
348.06045 (M)+.
2.9.
4-[4-(20-Bromo-benzyl)-piperazin-1-yl]-2,8-
bis(trifluoromethyl)quinoline (CMP5)
2.12.
1-(20-Bromo-benzyl)-4-(8-ethoxy-phenyl)-piperazine
(CMP8)
This compound was prepared from CMP15 (0.5 g, 1.43 mmol),
2-bromobenzaldehyde (0.29 g, 1.61 mmol) and sodium cyano-
borohydride (0.19 g, 3.1 mmol) by the above method to give
CMP5 (0.39 g, 59%) as cream crystals; mp 131–133 8C (from
1-(2-Ethoxyphenyl)piperazine
monohydrochloride
(1 g,
4.12 mmol) and polymer-supported tetraalkylammonium
carbonate macroporous triethylammonium methylpolystyr-
ene carbonate (MP-carbonate) 2.74 mmol/g loading (3.01 g,
8.24 mmol) were shaken in methanol for 3 h at room
temperature, the resin was removed by filtration and washing
with methanol, the filtrate was concentrated under reduced
pressure to give the free base (0.84 g, 98%).
EtOH); Rf 0.83 (hexane:ethyl acetate, 1:9); IR (CHCl3): nmax (cmꢀ1
)
3052 (CH Ar), 1589 (C C and C N), 1309 (C–F), 1264 (C–N); 1H
NMR dH (400 MHz, CDCl3) 2.83 (4H, t, J = 4.73 Hz, N–CH2, H11,
H13), 3.32 (4H, t, J = 4.88 Hz, N–CH2, H10, H14), 3.76 (2H, s, CH2,
Ha), 7.15 (1H, t, J = 7.78 Hz, Ar–H, H50), 7.22 (1H, s, Ar–H, H3), 7.32