3748
N. Harada et al. / Journal of Organometallic Chemistry 696 (2011) 3745e3749
[Re(CO)3(H2O)3]Br
Re(CO)5Br
in H2O
reflux
1
O
O
CO
CO
HN
CO2Me
CO2Me
K2CO3
in DMF
1
N
CO2Me
N
Br
Re
in H2O/MeOH
(3/2)
O
CO2Me
CO
at 60 o
C
2
O
110 o
C
O
3
O
HN
CO2Et
N
1
HN
CO
CO
Re
in H2O
110 o
C
N
CO
4
N
Re
1
N
H
HN
CO
CO
N
N
in MeOH
100 o
N
CO
C
5
Scheme 1. Synthesis of rhenium tricarbonyl complexes.
CD3OD)
d
¼ 7.35 (d, J ¼ 7.4 Hz, 2H), 7.30 (dd, J ¼ 7.4, 6.9 Hz, 2H), 7.25
J ¼ 7.7 Hz, 2H), 7.42 (t, J ¼ 6.6 Hz, 2H), 4.79 (dd, J ¼ 17.5, 6.0 Hz, 2H),
(d, J ¼ 6.9 Hz, 1H), 3.87 (s, 2H), 3.70 (s, 6H), 3.51 (s, 4H). 13C NMR
4.74 (d, J ¼ 17.2 Hz, 2H). 13C NMR (125 MHz, CDCl3)
d
¼ 61.7, 123.3,
(125 MHz, CDCl3)
d
¼ 51.4, 54.0, 58.0,127.4,128.4,129.0,138.2,171.5.
125.4, 140.2, 151.7, 161.0, 196.0, 196.1. FABeHRMS; found: 470.0515
FABeHRMS; 252.1230 [M þ H]þ for C13H18NO4 calcd 252.1236.
[M]þ for C15H13N3O3Re calcd 470.0498.
4.3.3. Bn-IDAeRe (3) [Re(CO)3{NH(CH2COO)2}]H
4.3.6. Bn-IDAe99mTc (6)
To a solution of 2 (0.70 g) in 1,4-dioxane/water (6 mL/4 mL),
NaOH (0.29 g) was added. The mixture was stirred at 60 ꢀC for
0.4 h. To the mixture was added 6 N HCl to adjust the pH to 7. The
solvent was removed under reduced pressure. The crude sample
was added in a microwave vial and dissolved in 10 mL of water. To
the vial was added 1 (0.40 g). The reaction vial was crimp sealed
prior to microwave heating at 110 ꢀC for 5 min. The reaction
mixture was chilled, and then the precipitate was filtered and
washed with ice-cold water to yield 3 (0.11 mg; 22%). 1H NMR
In the present study, we used [99mTc(CO)3(H2O)3]þ prepared as
previously reported in Ref. [1]. Briefly, Na 99mTcO4 (Technescinti-
10MÒ, Nihon Medi-Physics, Japan) was added into an IsoLinkÒ kit
(Mallinckrodt, Netherlands), and the kit was heated at 100 ꢀC for
20 min (247 MBq/mL). First, 240
m
L of water and 80
99mTc(CO)3(H2O)3]þ were added to 240
L of a methanol solution
M, 7.0 M, or 0.70 M). Next,
mL of
[
m
of 2 (70 mM, 7.0 mM, 0.70 mM, 70
m
m
m
6 M hydrochloric acid was added to the mixture to adjust the pH to
8. The mixture was heated on a microwave reactor or in an oil bath.
HPLC tR; 11.8 min (methanol/water ¼ 80/20).
(500 MHz, DMSO-d6)
d
¼ 7.64 (m, 2H), 7.40 (m, 3H), 4.33 (s, 2H),
3.88 (d, J ¼ 14.89 Hz, 2H), 2.74 (d, J ¼ 14.89 Hz, 2H). ESI-MS; 492
[M]ꢂ for C14H11NO7Re.
4.3.7. PAMAe99mTc (7)
First, 240
added to 240
70 M). Next, 6 M hydrochloric acid was added to the mixture to
mL of water and 80
m
L of [99mTc(CO)3(H2O)3]þ were
4.3.4. PAMAeRe (4)
m
L of methanol solution of PAMAEE (0.70 mM or
1 (0.20 g) and 0.10 g of PAMAEE (Tokyo Chemical Industry,
Japan) were added to a microwave vial and dissolved in water/
methanol (3 mL/0.5 mL). The reaction vial was crimp sealed prior to
microwave heating at 110 ꢀC for 5 min. The reaction mixture was
chilled, and the precipitate was collected by filtration and washed
with dichloromethane to yield 4 (white powder; 0.13 g; 56% yield).
m
adjust the pH to 8. The mixture was heated in a microwave reactor
or in an oil bath. HPLC tR; 19.5 min (methanol/water ¼ from 40/60
to 60/40 over 30 min).
4.3.8. DPAe99mTc (8)
1H NMR (500 MHz, DMSO-d6)
d
¼ 8.81 (d, J ¼ 5.5 Hz, 1H), 8.12 (dt,
First, 40
mL of water and 160
m
L of [99mTc(CO)3(H2O)3]þ were
M or 3.75 M).
J ¼ 7.8, 1.1 Hz,1H), 7.75 (d, J ¼ 7.8 Hz,1H), 7.57 (t, J ¼ 6.6 Hz,1H), 7.22
(t, J ¼ 6.2 Hz, 1H), 4.58 (d, J ¼ 16.7 Hz, 1H), 4.50 (dd, J ¼ 5.1, 16.6 Hz,
1H), 3.65 (dd, J ¼ 8.1, 17.3 Hz, 1H), 3.25 (d, J ¼ 17.3 Hz, 1H). 13C NMR
added to 800
m
L of a methanol solution of DPA (37.5
m
m
Next, 6 M hydrochloric acid was added to the mixture to adjust the
pH to 8. The mixture was heated on a microwave reactor or in an oil
bath. HPLC tR; 33.3 min (methanol/water ¼ from 30/70 to 40/60
over 20 min and then from 40/60 to 80/20 over 20 min) (Scheme 1).
(125 MHz, DMSO-d6)
d
¼ 53.9, 62.0, 123.7, 125.4, 140.2, 152.0, 160.0,
179.5, 197.4, 197.5, 197.8. FABeHRMS; 437.0148 [M þ H]þ for
C11H10N2O5Re calcd 437.0131.
4.3.5. DPAeRe (5) [Re(CO)3{NH(CH2C5H4N)2}]Br
4.4. Analysis by radio-HPLC
1 (75 mg) and 0.37 g of DPA (Tokyo Chemical Industry) were
added to a microwave vial and dissolved with 1 mL of methanol.
The reaction vial was crimp sealed prior to microwave heating at
100 ꢀC for 5 min. 5 was recrystallized from ethyl acetate/hexane
(yellow solid; 69 mg; 77% yield). 1H NMR (500 MHz, DMSO-d6)
Radiochemical yields were calculated from the RI peak area of
the HPLC chart. After reactions, the reaction samples were purified
by HPLC. Then, radioactivity was dynamically plotted to obtain the
RI chart. We calculated (radioactivity of objective compound)/(total
radioactivity) as yield of 99mTc complexes.
d
¼ 8.86 (d, J ¼ 5.4 Hz, 2H), 8.00 (dt, J ¼ 7.7, 1.4 Hz, 2H), 7.62 (d,