8250
C. He, S. J. Lippard / Tetrahedron 56 (2000) 8245±8252
(d, J8.0 Hz, 2H), 8.52 (d, J5.0 Hz, 2H). 13C NMR
(CDCl3, 75 MHz) d 38.7, 49.3, 55.8, 120.5, 121.2, 121.3,
123.3, 136.4, 137.1, 149.3, 155.3, 160.1, 164.1. HRMS
(1FAB): Calcd for M1, 1399.2297; Found, 1399.2301.
1H NMR (CDCl3, 300 MHz) d 2.88±3.00 (m, 16H), 4.00 (s,
4H), 6.94±7.02 (m, 8H), 7.24 (d, J8.2 Hz, 2H), 7.40±7.46
(m, 4H), 7.81 (d, J8.2 Hz, 2H), 8.39 (d, J5.0 Hz, 4H).
13C NMR (CDCl3, 75 MHz) d 36.3, 54.6, 61.3, 120.5, 121.1,
121.2, 123.5, 136.1, 136.5, 149.1, 154.8, 160.5, 164.7.
HRMS (1FAB): Calcd for (M1H)1, 609.3454; Found,
609.3450.
2,7-Bis{2-[2-(1-methyl)benzimidazolylethyl]-N-benzyl-
aminomethyl}-1,8-naphthyridine (BBBAN, 5). To a solu-
tion of 1,8-naphthyridine-2,7-dicarboxaldehyde (340 mg,
1.83 mmol) in methanol (50 mL) was added 1-methyl-2-
(2-aminoethyl)benzimidazole dihydrochloride (906 mg,
3.65 mmol, 13) and triethylamine (1.85 g, 18.3 mmol).
The solution was allowed to stir for 5 h. To this solution
was added NaBH4 (285 mg, 7.5 mmol) and the reaction was
allowed to stir overnight. The reaction was quenched by
addition of 6 M HCl to adjust the pH to 2. Brine (100 mL)
was added and the pH of the solution was adjusted to ,11
with 30% aqueous NaOH solution. Methanol was removed
under reduced pressure. The aqueous solution was extracted
with CH2Cl2 (2£100 mL). The CH2Cl2 extracts were
combined and dried over anhydrous MgSO4. Volatiles
were removed under reduced pressure. The product
2,7-bis{2-[2-(1-methyl)benzimidazolylethyl]aminomethyl}-
1,8-naphthyridine (14) was puri®ed by ¯ash chromato-
graphy (silica, 94:6/acetonitrile/30% ammonium hydroxide
in water) as a light pink solid (2.5 g, 73%). 1H NMR
(CDCl3, 250 MHz) d 3.18 (t, J7.0 Hz, 4H), 3.34 (t,
J7.0 Hz, 4H), 3.73 (s, 6H), 4.29 (s, 4H), 7.24±7.30 (m,
6H), 7.59 (d, J8.3 Hz, 2H), 7.71±7.75 (m, 2H), 8.12 (d,
J8.3 Hz, 2H). To a solution of 14 (300 mg, 0.6 mmol) in
acetonitrile (30 mL) was added benzyl bromide (203 mg,
1.2 mmol) and anhydrous K2CO3 (830 mg, 6.0 mmol).
The solution was allowed to stir overnight. The solvent
was removed under reduced pressure. The residue was
extracted with 40 mL of methylene chloride and washed
with 1 M aqueous Na2CO3 solution (2£50 mL). The organic
portion was dried over anhydrous MgSO4. Volatiles were
removed under reduced pressure. The residue was puri®ed
by ¯ash chromatography (silica, 19:1/acetonitrile/30%
ammonium hydroxide in water) as a light yellow solid
(200 mg, 49%), mp 65.5±67.08C. 1H NMR (CDCl3,
250 MHz) d 2.97±3.05 (m, 8H), 3.27 (s, 6H), 3.66 (s,
4H), 3.99 (s, 4H) 7.05±7.18 (m, 16H), 7.54 (d, J8.5 Hz,
2H), 7.58±7.61 (m, 2H), 7.79 (d, J8.5 Hz, 2H). 13C
NMR (CDCl3, 75 MHz) d 25.6, 29.5, 51.5, 58.8, 60.4,
108.8, 118.8, 120.4, 121.6, 121.8, 126.9, 128.1, 128.3,
128.6, 135.6, 136.6, 138.9, 142.3, 153.2, 154.5, 164.0.
HRMS (1FAB): Calcd for (M1H)1, 685.3767; Found,
685.3760.
2,7-Bis{bis[2-(2-(5-ethyl)pyridyl)ethyl]aminomethyl}-
1,8-naphthyridine (BEPEAN, 9). The same procedure as
described for the preparation of ligand BPEAN was
followed except that 1,8-naphthyridine-2,7-dicarboxalde-
hyde (0.50 g, 2.69 mmol), bis{2-[2-(5-ethyl)pyridyl]ethyl}-
amine (1.55 g, 5.47 mmol) and sodium triacetoxyboro-
hydride (1.60 g, 7.56 mmol) were used. The ®nal product
was puri®ed by ¯ash chromatography (silica, 70:20:10/
CH3CN/CH2Cl2/30% NH4OH in water) as a brown oil
(0.74 g, 38%). The oil solidi®ed to a brown semisolid
1
after extensive drying under vacuum. H NMR (CDCl3,
300 MHz) d 1.20 (t, J7.2 Hz, 12H), 2.58 (q, J7.2 Hz,
8H), 2.93±3.01 (m, 16H), 4.06 (s, 4H), 6.95 (d, J8.0 Hz,
4H), 7.32 (dd, J8.0 Hz, J02.0 Hz, 4H), 7.36 (d, J
8.5 Hz, 2H), 7.87 (d, J8.5 Hz, 2H), 8.29 (d, J2.0 Hz,
4H). 13C NMR (CDCl3, 75 MHz) d 15.7, 25.9, 35.9, 54.7,
61.3, 120.4, 121.3, 123.0, 135.5, 136.4, 136.4, 148.7, 154.9,
157.8, 164.9. HRMS (1FAB): Calcd for (M1H)1,
721.4706; Found, 721.4693.
2,7-Bis[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyri-
dine (BPMAN, 10). The same procedure as described for
the preparation of ligand BPEAN was followed except that
1,8-naphthyridine-2,7-dicarboxaldehyde (0.40 g, 2.15 mmol),
bis(2-pyridylmethyl)amine (0.90 g, 4.51 mmol) and sodium
triacetoxyborohydride (1.18 g, 5.59 mmol) were used. The
®nal product was puri®ed by recrystallization from CH3CN
1
as a light yellow solid (0.44 g, 37%), mp 171±1738C. H
NMR (CDCl3, 300 MHz) d 3.91 (s, 8H), 4.09 (s, 4H), 7.11±
7.15 (m, 4H), 7.54±7.67 (m, 8H), 7.86 (d, J8.0 Hz, 2H),
8.11 (d, J8.0 Hz, 2H), 8.53 (d, J4.5 Hz, 2H). 13C NMR
(CDCl3, 75 MHz) d 60.6, 60.9, 120.7, 121.8, 122.2, 123.3,
136.5, 137.0, 149.2, 155.0, 159.2, 164.0. HRMS (1FAB):
Calcd for (M1H)1, 553.2828; Found, 553.2838.
2,7-Bis(N,N-diethyl-aminomethyl)-1,8-naphthyridine
(BEAN, 6). The same procedure as described for the
preparation of ligand BPEAN was followed except that
1,8-naphthyridine-2,7-dicarboxaldehyde (350 mg, 1.88
mmol), diethylamine (275 mg, 3.76 mmol) and sodium tri-
acetoxyborohydride (1.07 g, 5.08 mmol) were used. The
®nal product was puri®ed by ¯ash chromatography (silica,
9:1/CH3CN/30% NH4OH in water) and obtained as a brown
2,7-Bis{bis[2-(2-pyridyl)ethyl]aminomethyl}-1,8-naph-
thyridine (BPEAN, 8). To a solution of 1,8-naphthyridine-
2,7-dicarboxaldehyde (0.60 g, 3.22 mmol) in dichloro-
ethane (100 mL) was added bis[2-(2-pyridyl)ethyl]amine
(1.47 g, 6.45 mmol) and sodium triacetoxyborohydride
(1.84 g, 8.70 mmol). The solution was allowed to stir for
12 h under Ar. The reaction was quenched by addition of
1 M aqueous NH4OH (150 mL), and the product was
extracted with CH2Cl2 (2£100 mL). The organic extracts
were combined and dried over anhydrous MgSO4. Volatiles
were removed under reduced pressure. The residue was
puri®ed by ¯ash chromatography (silica, 92:3:5/CH2Cl2/
MeOH/Et3N) as a brown oil (1.0 g, 51%). The oil solidi®ed
to a brown semisolid after extensive drying under vacuum.
1
oil after removing the solvents (300 mg, 53%). H NMR
(CDCl3, 250 MHz) d 1.03 (t, J7.2 Hz, 12H), 2.59 (q,
J7.2 Hz, 8H), 3.91 (s, 4H), 7.75 (d, J8.3 Hz, 2H), 8.07
(d, J8.3 Hz, 2H). 13C NMR (CDCl3, 75 MHz) d 12.3, 47.9,
60.5, 120.4, 121.5, 136.6, 155.0, 165.3. HRMS (1FAB):
Calcd for (M1H)1, 301.2392; Found, 301.2399.
2,7-Bis(N,N-dibenzyl-aminomethyl)-1,8-naphthyridine
(BBAN, 7). The same procedure as described for the
preparation of ligand BPEAN was followed except that
1,8-naphthyridine-2,7-dicarboxaldehyde (275 mg, 1.48
mmol), dibenzylamine (600 mg, 2.96 mmol) and sodium