B. R. Cameron et al.
FULL PAPER
4 H), 3.95 (s, 2 H), 7.10–7.20 (m, 1 H), 7.52 (d, J = 7.5 Hz, 1 H),
7.64 (dt, J = 7.5, 1.7 Hz, 1 H), 8.51 (d, J = 4.7 Hz, 1 H) ppm.
(19 mL) and H2O (6 mL) was added LiOH·H2O (0.270 g,
6.4 mmol). The mixture was stirred at room temperature for 17 h
in the absence of light. The solution was acidified with 2 n HCl
and the solvent was removed in vacuo. The crude material was
purified on Dowex cation exchange resin (H+ form, 50W-200 mesh)
to afford product 19 (0.172 g, 78%). 1H NMR (300 MHz, D2O,
25 °C): δ = 4.02 (s, 2 H), 4.15 (s, 2 H), 5.39 (s, 2 H), 7.95 (d, J =
7.5 Hz, 1 H), 8.25 (d, J = 7.2 Hz, 1 H), 8.46 (dd, J = 7.2, 7.5 Hz,
1 H) ppm. 13C NMR (300 MHz, D2O, 25 °C): δ = 50.27, 50.56,
127.02, 128.74, 147.29, 152.83, 156.73, 173.22, 173.46 ppm. ES-
MS: m/z = 313 [M + H]+.
N-Carboxymethyl-N-{2-[(carboxymethyl)(pyridin-2-ylmethyl)-
amino]ethyl}aminoacetic Acid (13): The title compound 13 (3.24 g,
73%) was prepared as a yellow solid from 12 (4.14 g, 8.35 mmol)
and TFA (30 mL) by a procedure analogous to the hydrolysis step
1
for compound 6. H NMR (300 MHz, D2O, 25 °C): δ = 3.00–3.15
(m, 2 H), 3.20–3.30 (m, 2 H), 3.59 (s, 4 H), 4.04 (s, 2 H), 4.51 (s, 2
H), 7.50 (m, 1 H), 7.61 (d, J = 7.7 Hz, 1 H), 7.98 (dt, J = 7.7,
1.6 Hz, 1 H) 8.63 (d, J = 5.0 Hz, 1 H ). C14H19N3O6·1.8TFA: calcd.
C 39.83, H 3.95, N 7.92; found C 38.85, H 4.19, N 8.06.
Preparation of 20: Compound 20 (0.064 g, 28%) was prepared as
a yellow solid from 19 (0.157 g, 0.48 mmol) and K2[RuCl5(H2O)]
(0.172 g, 0.46 mmol) by a procedure analogous to that described
Preparation of 14: Complex 14 (0.26 g, 43%) was prepared as a
yellow/orange solid from 13 (0.75 g, 1.30 mmol) and K2[Ru-
Cl5(OH2)] (0.5 g, 1.3 mmol) by an analogous procedure to that de-
for compound 4. IR (CsI): ν (cm–1) = 1709 (CO H), 1632, 1607
˜
scribed for compound 4. IR (CsI) ν (cm–1): 1730 (CO H), 1688,
2
˜
2
(CO2–), 341 (Ru–Cl). ES-MS: m/z = 402 (100) [M – Cl – H]–.
C11H10Cl2KN2O6Ru·2H2O (512.9): calcd. C 25.74, H 2.75, N 5.46,
Cl 13.81; found C 25.56, H 2.64, N 5.06, Cl 12.97.
1618 (CO2–), 320 (Ru–Cl). ES-MS: m/z = C14H17ClN3O6Ru·
0.5H2O (469.0): calcd. C 35.87, H 3.87, N 8.96, Cl 7.56; found C
35.86, H 3.79, N 8.98, Cl 7.58.
Synthesis of Complex 24 [KRu(19-H2)Cl2] via 22 and 23
Synthesis of Complex 16 {[Ru(15-H2)Cl2]Cl}: To a solution of com-
pound 15 (H2bped·2HCl)[43] (1.0 g, 2.50 mmol) in water (10 mL,
pH = 4) was added a solution of K2[RuCl5(OH2)] (0.838 g,
2.50 mmol) in HCl (minimum volume, 1 mm). The reaction mixture
was heated to reflux temperature for 1.5 h. The dark green solution
was reduced to approximately one half the original volume and on
slow evaporation a yellow-orange solid precipitated from the reac-
tion mixture. This was collected by filtration and re-crystallised
from H2O/EtOH to yield orange microcrystalline solid 16 (0.37 g,
tert-Butyl N-(tert-Butoxycarbonylmethyl)-N-{[6-(hydroxymethyl)py-
ridin-2-yl]methyl}aminoacetate (22): The mesylate intermediate
(3.61 g, 100%) was prepared as a brown oil from 6-(hydroxymeth-
yl)pyridine-2-carbaldehyde (21)[45] (2.30 g, 1.7 mmol), methanesul-
fonyl chloride (2.12 g, 1.8 mmol), and triethylamine (5.08 g,
50 mmol) by an analogous procedure to that described for com-
1
pound 18. H NMR (300 MHz, CDCl3, 25 °C): δ = 3.15 (s, 3 H),
5.43 (s, 2 H), 7.70 (m, 1 H), 7.97 (m, 2 H), 10.05 (s, 1 H) ppm.
Reaction of the mesylate (3.61 g, 1.7 mmol) with di-tert-butyl imin-
odiacetate[46] (3.706 g, 1.5 mmol) following conditions similar to
the first step in the synthesis of compound 19 afforded, after col-
umn chromatography on silica gel (hexanes/EtOAc, 4:1), the alde-
26%). IR (CsI) ν (cm–1) = 1726 (CO H). ES-MS: m/z = 458 (100)
˜
2
[M – 2Cl – 2H]+, 414 (50) [M – 2Cl – H – CO2H]+, 370 (75) [M –
2Cl – 2(CO2H)]+. C18H22Cl3N4O4Ru (565.0): C 38.21, H 3.92, N
9.90, Cl 18.80; found C 38.21, H 3.96, N 9.90, Cl 18.79.
1
hyde as a colorless oil (2.25 g, 45%). H NMR (300 MHz, CDCl3,
Synthesis of Complex 20 {[KRu(19-H2)Cl2]} via 18 and 19
25 °C): δ = 1.46 (s, 18 H), 3.50 (s, 4 H), 4.14 (s, 2 H), 7.85 (m, 1
H), 7.94 (m, 1 H), 10.05 (s, 1 H) ppm. The aldehyde (2.25 g,
6.2 mmol) was reduced in MeOH (60 mL) under nitrogen with so-
dium borohydride (0.235 g, 6.2 mmol). The reaction was heated to
60 °C with stirring, and after 1 h the solvent was removed in vacuo
and the residue was partitioned between H2O (30 mL) and CH2Cl2
(30 mL). The aqueous phase was separated and extracted with
CH2Cl2 (3×40 mL) and the combined organic extracts were dried
(MgSO4) and the solvents evaporated in vacuo to afford the pro-
duct 22 (2.16 g, 38 % for 3 steps) as a colorless oil. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.46 (s, 18 H), 3.48 (s, 4 H), 3.98 (t,
J = 4.5 Hz, 1 H), 4.05 (s, 2 H), 4.72 (d, J = 4.5 Hz, 2 H), 7.08 (d,
J = 6.0 Hz, 1 H), 7.53 (d, J = 9.0 Hz, 1 H), 7.66 (dd, J = 6.0,
9.0 Hz, 1 H) ppm. 13C NMR (300 MHz, CDCl3, 25 °C): δ = 28.57,
56.22, 59.88, 64.13, 81.47, 119.04, 122.02, 137.64, 158.25, 158.65,
170.90 ppm. ES-MS: m/z = 367 [M + H]+.
Methyl 6-(Methylsulfonyloxymethyl)pyridine-2-carboxylate (18): To
a stirred solution of compound 17[44] (0.220 g, 1.30 mmol) and tri-
ethylamine (0.400 g, 4.00 mmol) in CH2Cl2 (13 mL) cooled in an
ice bath was added dropwise methanesulfonyl chloride (0.180 g,
1.60 mmol). After 30 min the reaction was quenched with saturated
aqueous NaHCO3 (15 mL) and the aqueous phase was separated
and extracted with CH2Cl2 (3×15 mL). The combined organic ex-
tracts were dried (MgSO4) and the solvent was evaporated in vacuo
to afford product 18 (0.347 g, 100%) as a yellow-orange oil. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 3.15 (s, 3 H), 4.01 (s, 3 H),
5.44 (s, 2 H), 7.70 (d, J = 6.0 Hz, 1 H), 7.92 (dd, J = 6.0, 9.0 Hz,
1 H), 8.12 (d, J = 9.0 Hz, 1 H) ppm.
6-{[Bis(carboxymethyl)amino]methyl}pyridine-2-carboxylic Acid
(19): To a stirred solution of compound 18 (0.323 g, 1.3 mmol) and
iminodiacetic acid dimethyl ester (0.191 g, 1.2 mmol) in DMF was
added K2CO3 (0.359 g, 2.6 mmol) and the reaction mixture was
stirred at 35 °C for 16 h. The solvent was removed in vacuo and
partitioned between H2O (10 mL) and CH2Cl2 (15 mL). The aque-
ous portion was extracted with CH2Cl2 (3×15 mL), and the com-
bined organic extracts were dried (MgSO4) and the solvents evapo-
rated in vacuo. The crude material was purified by column
chromatography (CH2Cl2/MeOH, 19:1) on silica gel to afford the
ester-protected precursor (0.200 g, 49 %) as a colorless oil. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 3.70 (s, 6 H), 3.97 (s, 3 H),
4.16 (s, 4 H), 5.36 (s, 2 H), 7.51 (d, J = 9.0, 1 H), 7.84 (dd, J = 6.0,
9.0, 1 H), 8.02 (d, J = 6.0 Hz, 1 H) ppm. 13C NMR (300 MHz,
CDCl3, 25 °C): δ = 49.48, 52.63, 53.32, 68.46, 124.46, 124.79,
138.25, 155.93, 157.31, 165.88, 170.09 ppm. To a 0 °C solution of
the ester-protected precursor (0.200 g, 0.65 mmol) in MeOH
N-Carboxymethyl-N-{[6-(hydroxymethyl)pyridin-2-yl]methyl}amino-
acetic Acid (23): Compound 23 (0.492 g, 100%) was prepared as a
white solid from 22 (2.10 g, 5.7 mmol) and TFA (10 mL) by a pro-
cedure analogous to the hydrolysis step for compound 6. 1H NMR
(300 MHz, D2O, 25 °C): δ = 3.64 (s, 4 H), 4.28 (s, 2 H), 4.85 (s, 2
H), 7.69 (br. s, 2 H), 8.27 (t, J = 8.0 Hz, 1 H) ppm. 13C NMR
(300 MHz, D2O, 25 °C): δ = 55.98, 60.07, 123.75, 125.19, 147.02,
152.72, 155.65, 174.85 ppm. ES-MS: m/z 255 [M + H]+.
Preparation of 24: The title compound 24 (0.035 g, 24%) was pre-
pared as a yellow solid from 23 (0.152 g, 0.32 mmol) and
K2[RuCl5(H2O)] (0.118 g, 0.32 mmol) by a procedure analogous to
compound 4. IR (CsI) ν (cm–1) = 1657, 1630 (CO ), 316 (Ru–Cl).
–
˜
2
ES-MS: m/z = 446 (100) [M – H + Na]–. C11H12Cl2KN2O5Ru·
2694
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2005, 2685–2697