5
14 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 3
Calas et al.
Ta ble 3. Physicochemical and Spectral Data for Synthesized Compounds
compd
yield (%)
mp (°C)
201
215-220
74
186
204
209
104
155
160
63
1H NMR (δ in ppm)
0.90 (t,3H); 1.05 (m,10H); 1.5 (m,2H); 3.2 (s,9H); 3.3 (m,2H)a
E2a
E70
E25
E24
E27
E26
E60
E11
E12
E35
E36
E34
48
86
70
52
61
72
51
61
38
62
65
61
a
1.2 (m,8H); 1.5 (m,2H); 1.6 (m,2H); 2.5 (t,2H); 3.4 (s,9H); 3.5 (m,2H); 7.1 (m,3H); 7.2 (m,2H)
a
0.70 (t,3H); 1.1 (m,6H); 1.5 (m,2H); 2.0 (m,4H); 3.1 (s,3H); 3.35 (m,2H); 3.5 (m,4H)
0.80 (t,3H); 1.2 (m,18H); 1.65 (m,2H); 2.2 (m,4H); 3.2 (s,3H); 3.6 (m,2H); 3.7 (m,4H)a
a
0.65 (t,3H); 1.05 (m,22H); 1.55 (m,2H); 2.05 (m,4H); 3.05 (s,3H); 3.45 (m,2H); 3.6 (m,4H)
a
0.78 (t,3H); 1.15 (m,26H); 1.7 (m,2H); 2.23 (m,4H); 3.21 (s,3H); 3.55 (m,2H); 3.75 (m,4H)
0.8 (t,3H); 1.4 (m,15H); 1.6 (m,2H); 3.3 (m,8H)a
a
0.8 (t,3H); 1.4 (m,35H); 1.7 (m,2H); 3.3 (m,8H)
0.8 (t,3H); 1.3 (m,39H); 1.6 (m,2H); 3.2 (m,8H)a
a
0.9 (t,3H); 1.3 (m,18H); 1.8 (m,2H); 3.4 (s,6H); 3.5 (m,2H); 4.4 (d,2H); 5.8 (m,2H); 6,0 (m,1H)
70
105
0.8 (t,3H); 1.2 (m,18H); 1.7 (m,2H); 3.0 (t,1H);3.35 (s,6H); 4.0 (t,2H); 4.7 (d,2H)a
0.8 (t,3H); 1.15 (m,18H); 1.55 (m,2H); 2.15 (t,1H); 2.3 (s,3H); 2.7 (td,2H); 3.2 (s,6H); 3.3 (m,2H);
.5 (t,2H); 7.1 (d,2H); 7.7 (d,2H)a
3
a
a
E37
E38
F 2a
F 25
65
70
70
68
20
0.8 (t,3H); 1.25 (m,18H); 1.7 (m,2H); 3.2 (s,3H); 3.3 (m,2H); 4.25 (m,4H); 5.7 (m,4H); 5.9 (m,2H)
49-51
116-118
203-204
0.9 (t,3H); 1.3 (m,18H); 1.9 (m,2H); 3.0 (t,2H); 3.5 (s,3H); 3.7 (m,2H); 4.7 (m,4H)a
0.80 (t,3H); 1.2 (m,10H); 1.6 (m,2H); 3.2 (s,6H); 3.4 (m,2H); 3.55 (m,2H); 3.9 (m,2H); 4.85 (t,1H)
0.90 (t,3H); 1.32 (m,26H); 1.75 (m,2H); 3.41 (s,6H); 3.60 (m,2H); 3.80 (m,2H); 4.15 (m,2H);
c
5
.10 (m,1H)
F 32
F 30
43
73
hygroscopic
60
0.8 (t,3H); 1.2 (d,3H); 1.3 (m,4H); 1.7 (m,2H); 3.3 (s,6H); 3.4 (m,2H); 3.8 (m,2H); 4.4 (m,1H);
a
4
.9 (m,1H)
0.8 (t,3H); 1.2 (d,3H); 1.3 (m,18H); 1.7 (m,2H); 3.3 (s,6H) 3.4 (m,2H);3.8 (m,2H); 4.4 (m,1H);
a
5
.0 (m,1H)
b
G5
61
88
52
70
60
67
63
50
10
227-230
130 (dec)
162
198
205
204
180
145
170
1.4 (m,24H); 1.8 (m,4H); 3.2 (s,18H); 3.3 (t,4H)
b
G12
G14
G15
G19
G24
G25
G94
G74
1.4 (m,18H); 1.5 (m,8H); 1.85 (m,4H); 3.7 (m,16H)
1.3 (m,16H); 1.4 (t,18H); 1.7 (m,4H); 3.5 (m,16H)b
b
1.25 (m,18H); 1.38 (m,24H); 1.82 (m,4H); 3.32 (m,16H)
1.2 (s,34H); 1.35 (t,18H); 1.5 (m,4H); 3.4 (m,16H)
a
1.40 (m,16H); 1.85 (m,4H); 2.2 (m,8H); 3.15 (s,6H); 3.55 (m,12H)b
1.45 (m,24H); 1.93 (m,4H); 2.38 (m,8H); 3.20 (s,6H); 3.63 (m,12H)
b
1.3 (m,16H); 1.7 (m,4H); 3.15 (s,12H); 3.40 (m,4H); 4.1 (t,2H); 4.5 (d,4H)a
1.3 (m,16H); 1.65 (m,4H); 2.3 (s,6H); 2.75 (td,4H); 3.1 (t,2H); 3.25 (m,4H); 3.45 (t,4H); 7.1 (d,2H);
a
7
.5 (d,2H)
a
G84
H5
75
60
70
80
80
76
45
pasty
120
195
235
235
128
262
1.2 (t,12H); 1.3 (m,16H); 1.6 (m,4H); 3.15 (m,4H); 3.25 (q,8H); 4.0 (d,4H); 5.6 (m,4H); 6.0 (m,2H)
1.45 (m,36H); 1.85 (m,4H); 3.5 (m,16H); 4.15 (t,4H)b
0.8 (t,6H); 1.25 (m,36H); 1.75 (m,4H); 2.75 (m,2H); 3.5 (s,12H); 3.9 (m,8H)
a
G40
G41
G44
G45
TA1
a
0.9 (t,6H); 1.3 (m,40H); 1.65 (m,4H); 1.75 (m,4H); 3.5 (s,12H); 3.7 (m,8H)
0.8 (t,6H); 1.3 (m,52H); 1.7 (m,4H); 1.8 (m,4H); 3.5 (s,12H); 3.7 (m,8H)a
a
0.9 (t,6H); 1.3 (m,60H); 1.65 (m,4H); 1.75 (m,4H); 3.6 (s,12H); 3.7 (m,8H)
1.5 (m,40H); 3.3 (m,24H)b
a
In CDCl3. b In D2O. c In DMSO-d6.
methylpyrrolidine was added to 1.1 equiv of halogenated
derivative (1-bromohexane for E25, 1-bromododecane for E24,
reflux for 18 h. The solvent was removed and the salt
recrystallized from a mixture of methanol and diethyl ether
or ethanol and diethyl ether or acetone and diethyl ether.
1
-bromotetradecane for E27, 1-bromohexadecane for E26) or
to 0.55 equiv of dihalogenated derivative (1,12-dibromodode-
cane for G24, 1,16-dibromohexadecane for G25) in 100 mL of
ethanol. The solution was heated under reflux for 24 h. The
solvent was removed and the salt was recrystallized from a
G12: Anal. (C20
C, H, N. G15: Anal. (C28
Br ) C, H, N.
N,N-Dim eth yl-N-(2-p r op yn yl)-1-d od eca n a m in iu m Io-
d id e (E36). 20 mmol of 1-iodododecane was added to a solution
of 15 mmol of 3-dimethylaminopropyne in 60 mL of anhydrous
acetone. The solution was heated under reflux for 24 h; the
solvent was removed and the salt recrystallized from acetone.
H
46
N
2
Br
2
) C, H, N. G14: Anal. (C24
54 2 2
H N Br )
H
62
N
2
2
Br ) C, H, N. G19: Anal.
(C32
H
72
N
2
2
mixture of methanol and diethyl ether. E25: Anal. (C11
NBr) C, H, N. E24: Anal. (C17 36NBr) C, H, N. E27: Anal.
40NBr) C, H, N. E26: Anal. (C21 44NBr) C, H, N. G24:
) C, H, N. G25: Anal. (C26 Br ) C, H,
24
H -
H
(C
19
H
H
Anal. (C22
N.
H
46
N
2
Br
2
H
54
N
2
2
Anal. (C17H34NI) C, H, N.
N,N,N-Tr ieth yl-1-h exan am in iu m Br om ide (E60), N,N,N-
Tr ieth yl-1-h exadecan am in iu m Br om ide (E11), an d N,N,N-
Tr ieth yl-1-octa d eca n a m in iu m Br om id e (E12). 5 g (50
mmol) of triethylamine was added to 1.1 equiv of halogenated
derivative (1-bromohexane for E60, 1-bromohexadecane for
E11, 1-bromooctadecane for E12) in 100 mL of ethanol. The
solution was heated under reflux for 18 h. The solvent was
removed and the salt was recrystallized from a mixture of
methanol and diethyl ether or ethanol and diethyl ether.
N,N-Dim et h yl-N-(2-h yd r oxyp r op yl)-1-p en t a n a m in i-
u m Br om id e (F 32) a n d N,N-Dim eth yl-N-(2-h yd r oxyp r o-
p yl)-1-d od eca n a m in iu m Br om id e (F 30). 20 mmol of halo-
genated derivative (1-bromopentane for F 32, 1-bromododecane
for F 30) was added to a solution of 15 mmol of 1-dimethy-
lamino-2-propanol in 50 mL of ethanol. The solution was
heated under reflux for 12 h; the solvent was removed and
the salt recrystallized from ethanol-diethyl ether. F 32: Anal.
(C10H24NOBr) C, H, N. F 30: Anal. (C17H38NOBr) C, H, N.
E60: Anal. (C12
H, N. E12: Anal. (C24
N,N,N,N′,N′,N′-Hexa eth yl-1,8-octa n ed ia m in iu m Dibr o-
m id e (G12), N,N,N,N′,N′,N′-Hexa eth yl-1,12-d od eca n ed i-
a m in iu m Dibr om id e (G14), N,N,N,N′,N′,N′-Hexa eth yl-
H
28NBr) C, H, N. E11: Anal. (C22
52NBr) C, H, N.
H
48NBr) C,
N-(2-Hydr oxyeth yl)-N,N-dim eth yl-1-octan am in iu m Br o-
m id e (F 2a ) a n d N-(2-H yd r oxyet h yl)-N,N-d im et h yl-1-
h exa d eca n a m in iu m Br om id e (F 25). 0.12 mol of 2-(di-
methylamino)ethanol and 0.11 mol of the corresponding bro-
minated derivative (1-bromooctane for F 2a , 1-bromohexade-
cane for F 25) were added to 100 mL of methanol and heated
under reflux conditions for 20 h. The solvent was removed and
the crude product recrystallized from a mixture of methanol
H
1
,16-h exa d eca n ed ia m in iu m Dibr om id e (G15), a n d
N,N,N,N′,N′,N′-Hexaeth yl-1,21-h en eicosan ediam in iu m Di-
br om id e (G19). 10 g (0.1 mol) of triethylamine was added to
a solution of 25 mmol of dihalogenated derivative (1,8-
dibromooctadecane for G12, 1,12-dibromododecane for G14,
and diethyl ether. F 2a : Anal. (C12
Anal. (C16 36NOBr) C, H, N.
H28NOBr) C, H, N. F 25:
H
1
,16-dibromohexadecane for G15, 1,21-dibromoheneicosane21
N,N-Dim eth yl-N-(2-p r op en yl)-1-d od eca n a m in iu m Br o-
m id e (E35). 10 mmol of 3-bromopropene was added to a
for G19) in 100 mL of ethanol. The solution was heated under