Bhattacharya et al.
2-H yd r oxym et h yl-4-N,N-(d im et h yla m in o)p yr id in e-6-
a m in om eth yl-N′-2-N,N-d im eth yla m in oeth yla m in e (10). A
mixture of 0.21 g of (1 mmol) of 7 and 0.088 g (1 mmol) of
N,N-dimethylethylenediamine was taken in 5 mL of dry MeOH
and stirred for 2 h. To this was added 0.19 g of NaBH4 (5
mmol), and the mixture was stirred for another 5 h. Excess
NaBH4 was quenched by dilute HCl at 0 °C. MeOH was
evaporated, and the residue extracted with CHCl3, concen-
trated, and purified by column chromatography (silica gel)
using MeOH/CHCl3 (15:85). The pure product was isolated as
of dry CHCl3 was added 0.3 g (1.5 mmol) of DCC, and the
mixture was stirred at room temperature for 10 min. Next,
0.2 g (0.74 mmol) of n-octadecylamine was added to this, and
the resulting mixture was stirred for 15 h. Then the solvent
from the reaction mixture was evaporated, and the residue
was chromatographed on silica gel using MeOH/CHCl3 (5:95).
Evaporation of the fractions gave pure compound gave a
hygroscopic, white solid (0.27 g, 70%), mp ∼50 °C. IR: (Nujol)
3250, 1640 cm-1 1H NMR: (CDCl3, 200 MHz) δ 0.8 (t, 3H),
.
1.2 (s, 32H), 2.4 (t, 2H), 2.8 (t, 2H), 3.2 (m, 2H), 3.9 (s, 4H),
7.1 (t, 2H), 7.4 (d, 2H), 7.6 (t, 2H), 8.2 (m, 1H), 8.6 (d, 2H).
EI-MS: m/z 522 (M+, 10%) Anal. Calcd for C33H54N4O‚
1.5H2O: C, 72.08; H, 10.45; N, 10.19. Found: C, 72.02; H,
10.61; N, 9.94.
a yellow gum in 73% yield. IR: (neat) 3310 cm-1 1H NMR:
.
(CDCl3, 90 MHz) δ 2.2 (s, 6H), 2.5 (t, 2H), 2.7 (t, 2H), 3.0 (s,
6H), 3.8 (s, 2H), 4.6 (s, 2H), 6.4 (d, 1H), 6.5 (d, 1H). EI-MS:
252 (M+, 10%), 208 (20%), 194 (50%), 181 (100%).
2-H yd r oxym et h yl-4-N,N-(d im et h yla m in o)p yr id in e-6-
am in om eth yl-N′-2-N,N-dim eth ylam in oeth an e-N′-(3-m eth -
yl p r op ion a te) (11a ). Compound 11a was synthesized analo-
gously as described under the synthesis of 9a . Chromatography
on silica gel using MeOH/CHCl3 (5:95) afforded the pure
product as a yellow viscous liquid in 58% yield. IR: (neat) 1730
N -(N ′,N ′-D im e t h y la m in o e t h y l)(2-p y r id y lm e t h y l)-
a m in e (12). To a solution of 1.07 g (10 mmol) of 2-pyridine
carboxaldehyde in 5 mL of dry MeOH was added 0.88 g (10
mmol) of N,N-dimethylethylenediamine, and the mixture was
stirred at room temperature for 2 h. The mixture was cooled
to 0 °C, and 1.89 g (50 mmol) of NaBH4 was added and stirred
for 6 h. Then the reaction mixture was neutralized with dilute
HCl and evaporated to dryness. The residue was extracted
with CHCl3 and concentrated to afford a crude product, which
was purified by column chromatography on silica gel using
MeOH/CHCl3 (8:92) to obtain 7 as a yellow oil (0.85 g, 47%).
IR: (neat) 3340 cm-1. 1H NMR: (CDCl3, 90 MHz) δ 2.2 (s, 6H),
2.5 (t, 2H), 2.7 (t, 2H), 2.9 (s, 1H), 3.9 (s, 2H), 7.1 (t, 1H), 7.4
(d, 1H), 7.7 (t, 1H), 8.5 (d, 1H). EI-MS: m/z 179 (M+, 3%), 58
(100%), 121 (85%), 71 (43%), 92 (30%).
cm-1 1H NMR: (CDCl3, 90 MHz) δ 2.3 (s, 6H), 2.5 (m, 8H),
.
3.0 (s, 6H), 3.6 (d, 3H), 3.9 (s, 2H), 4.6 (s, 2H), 6.4 (s, 1H), 6.6
(s, 1H).
2-H yd r oxym et h yl-4-N,N-(d im et h yla m in o)p yr id in e-6-
a m in om eth yl-N′-2-N,N-d im eth yla m in oeth a n e-N′-(3-p r o-
p ion ic a cid ) (11). Compound 11 was synthesized using
procedure a similar to that used for 9. Purification was
achieved using chromatography on silica gel with MeOH/
CHCl3 (15:85). Pure compound was isolated in 90% yield. IR:
(neat) 1700 cm-1 1H NMR: (CDCl3, 90 MHz) δ 2.3 (s, 6H),
.
2.6 (m, 8H), 3.0 (s, 6H), 4.0 (s, 2H), 4.6 (s, 2H), 6.7 (s, 2H).
Anal. Calcd for C16H28N4O3‚ H2O: C, 56.12; H, 8.83; N, 16.36.
Found: C, 56.51; H, 9.17; N, 15.99.
N-(3-Meth ylp r oion a te)(N′,N′-Dim eth yla m in oeth yl)(2-
p yr id ylm eth yl)a m in e (13a ). Compound 13a was synthesized
using a procedure described for the synthesis of 9a . Chroma-
tography on silica gel using MeOH/CHCl3 (1:9) afforded pure
product as an oil (0.38 g, 60%). IR: (neat) 1720 cm-1. 1H NMR:
(CDCl3, 90 MHz) δ 2.2 (s, 6H), 2.5 (m, 4H), 2.8 (m, 4H), 3.6 (s,
3H), 3.8 (s, 2H), 7.2 (t, 1H), 7.4 (d, 1H), 7.7 (t, 1H), 8.5 (d, 1H).
EI-MS: m/z 265 (M+, 25%), 207 (100%), 58 (55%), 175 (43%),
92 (43%).
2-H yd r oxym et h yl-4-N,N-(d im et h yla m in o)p yr id in e-6-
a m in om eth yl-N′-2-N,N-d im eth yla m in oeth a n e-N′-(3-octa -
d ecyl p r op ion a m id e) (2). To 60 mg (0.185 mmol) of 11 in
dry CHCl3 (5 mL) was added 76 mg of DCC (0.37 mmol), and
the mixture was stirred for 10 min at room temperature. Next,
0.5 g (0.185 mmol) of n-octadecylamine was added, and the
mixture was stirred for 12 h, filtered, concentrated, and
purified by chromatography on silica gel with MeOH/CHCl3
N-(3-P r op ion ic a cid )(N′,N′-d im eth yla m in oeth yl)(2-p y-
r id ylm eth yl)a m in e (13) Compound 13 was prepared follow-
ing the synthetic procedure of 9. Purification was achieved by
column chromatography on silica gel using MeOH/CHCl3 (1:
3). The pure compound was isolated as a solid (0.076 g, 54%).
IR: (neat) 3400, 1710 cm-1. 1H NMR: (CDCl3, 90 MHz) δ 2.5-
2.6 (br m, 6H), 2.8 (s, 6H), 3.2 (t, 2H), 3.8 (s, 2H), 7.2 (t, 1H),
7.5 (d, 1H), 7.6 (t, 1H), 8.2 (d, 1H). EI-MS: m/z 251 (M+, 8%),
58 (100%), 193 (62%), 92 (42%), 121 (40%). Anal. Calcd for
1
(1:9) to afford a solid in 70% yield. IR: (neat) 1630 cm-1. H
NMR: (CDCl3, 200 MHz) δ 0.87 (t, 3H), 1.24 (s, 32H), 1.46 (t,
2H), 2.42 (t, 2H), 2.7 (t, 6H), 2.89-3.11 (m, 6H), 3.17 (s, 6H),
3.78 (s, 2H), 4.67 (s, 2H), 6.54 (s, 1H), 6.56 (s, 1H), 7.62 (br t,
1H). EI-MS: 575 (M+, 5%), 194 (100%), 182 (40%). Anal. Calcd
for C34H65N5O2: C, 70.91; H, 11.38; N, 12.16. Found: C, 70.6;
H, 11.03; N, 12.41.
C
13H21N3O2‚H2O: C, 57.97; H, 8.61; N, 15.6. Found: C, 58.2;
H, 9.0; N, 15.27.
N-(3-Met h ylp r op ion a t e)-b is(2-p yr id ylm et h yl)a m in e
(15a ). Compound 15a was prepared following a method
described for the synthesis of 9a . Chromatography on silica
gel using MeOH/CHCl3 (2:98) furnished a yellow oil (0.49 g,
N-(3-Oct a d ecylp r op a n a m id o)(N′,N′-d im et h yla m in o-
eth yl)(2-p yr id ylm eth yl)a m in e (3). A mixture of 0.13 g of
13 (0.52 mmol) and 0.207 g (1 mmol) of DCC was taken in 10
mL of dry CHCl3, and the mixture was briefly stirred. Next,
0.139 g (0.52 mmol) of n-octadecylamine was added, and the
mixture was stirred for 16 h. Then CHCl3 was stripped from
the mixture to leave a residue purified by chromatography
(silica gel) using MeOH/CHCl3 (8:92). The pure compound was
1
77%). IR: (neat) 1730 cm-1. H NMR: (CDCl3, 90 MHz) δ 2.5
(t, 2H), 2.8 (t, 2H), 3.6 (s, 3H), 4.8 (s, 4H), 7.2 (t, 2H), 7.4 (d,
2H), 7.6 (t, 2H), 8.5 (d, 2H). EI-MS: m/z 285 (M+, 15%), 93
(100%), 193 (90%). This was isolated as hydrochloride and was
recrystallized from EtOAc/hexane to afford a colorless solid
as a trihydrochloride salt. Anal. Calcd for C16H19N3O2.3HCl:
C, 48.68; H, 5.62; N, 10.65. Found: C, 48.69; H, 5.25; N, 11.03.
isolated as a gum (0.086 g, 33%). IR: (neat) 3250, 1640 cm-1
.
1H NMR: (CDCl3, 90 MHz) δ 0.87 (t, 3H), 1.25 (s, 32H), 2.44
(t, 2H), 2.5 (s, 6H), 2.8 (m, 6H), 3.2 (t, 2H), 3.8 (s, 2H), 7.2 (t,
1H), 7.4 (d, 1H), 7.7 (t, 1H), 7.8 (m, 1H), 8.5 (d, 1H). HR-MS:
calcd for C31H58N4O 506.4611, found 506.4635. Anal. Calcd for
N-(3-P r op ion ica cid )b is(2-p yr id ylm et h yl)a m in e (15).
Compound 15 was synthesized using a procedure described
for the synthesis of 9. Final purification was achieved with
column chromatography (silica gel) using MeOH/CHCl3 (15:
85) to give a hygroscopic solid (0.16 g, 66%), mp 104-105 °C.
C
13H58N4O: C, 74.05; H, 11.63; N, 11.14. Found: C, 74.3; H,
11.41; N, 11.52.
1
IR: (Nujol) 3350, 1710 cm-1. H NMR: (CDCl3, 90 MHz) δ 2.6
Kin etic Mea su r em en ts. Solutions of ligands and additives
(CTABr) were prepared in 0.05 M HEPES buffer (µ ) 0.1 KCl).
The metallomicelles were generated in situ by the addition of
an appropriate amount of a given metal salt solution to the
cuvette. The solution was carefully stirred, and the reaction
was initiated by injection of 15 µL of stock solution of PNPH
or PNPDPP in CH3CN. Substrate hydrolysis was followed
(t, 2H), 3.0 (t, 2H), 4.0 (s, 4H), 7.2 (t, 2H), 7.4 (t, 2H), 7.7 (t,
2H), 8.6 (d, 2H). EI-MS: m/z 271 (M+, 25%), 93 (100%), 212
(42%), 193(40%). Anal. Calcd for C15H17N3O2‚H2O: C, 62.27;
H, 6.62; N, 14.52. Found: C, 62.35; H, 6.18; N, 14.86.
N -(3-Oct a d e cylp r op a n a m id o)b is(2-p yr id ylm e t h yl)-
a m in e (4). To a solution of 0.2 g (0.74 mmol) of 15 in 10 mL
2746 J . Org. Chem., Vol. 68, No. 7, 2003