1182 E. PALMA ET AL.
Evaporation of the eluate afforded the product as a
white solid. Yield: 0.08 g, 83%. 1H-NMR (CD3OD): d
5.88 (s, H(4)pz, 1H); 4.26 (t, CH2, 2H); 3.97–3.87 (m,
CH2, 2H); 3.44 (t, CH2, 2H); 3.26–3.17 (m, CH2, 2H);
2.27 (s, CH3, 3H), 2.17 (s, CH3, 3H), 1.96–1.85 (m, CH2,
2H); 1.25 (t, CH3, 3H). 13C NMR (CD3OD) d 149.9 (C(3/
5)pz), 141.7 (C(3/5)pz), 106.7 (C(4)pz), 61.1 (d,
J ¼ 5:7 Hz, POCH2CH3), 45.1 (d, J ¼ 26:2 Hz, H2CP),
25.8 (CH2), 25.2 (CH2), 24.0 (CH2), 17.1 (d, J ¼ 6:6 Hz,
H(4)pz, 1H); 3.98 (t, CH2-a, 2H); 3.71–3.53 (m, CH2-e,
2H); 2.96–2.86 (m, CH2-b, 1H); 2.80 (t, CH2-c+CH2-f,
2H+1H); 2.60–2.46 (m, CH2-f0, 1H); 2.36–2.26 (m, CH2-
b0, 1H), 2.08 (s, CH3, 3H), 1.98 (s, CH3, 3H), 1.92–1.76
(m, CH2-d, 1H); 1.68–1.59 (m, CH2-d0, 1H); 13C-NMR
(D2O) d 148.2 (C(3/5)pz), 140.8 (C(3/5)pz), 104.5
(C(4)pz), 61.0 (d, 1JPC ¼ 19 Hz, C-e), 54.0 (d,
2
3JPC ¼ 2 Hz, C-c) 53.4 (d, JPC ¼ 4 Hz, C-b), 51.4 (d,
1
1JPC ¼ 13 Hz, C-f), 45.6 (C-a), 19.1 (d, JPC ¼ 10 Hz, C-
POCH2CH3), 13.4 (CH3), 10.7 (CH3). 31P NMR (CD3OD):
d), 11.4 (CH3), 9.5 (CH3). 31P-NMR (D2O): d ꢁ28.5.
FTICR-MS(þ) m/z: 242 ½M þ Hꢀþ. See identification
system for NMR assignment in Scheme 2.
%
d 20.8. Anal. Calc. for C11H21N3O3PNa: C, 44.44; H,
7.12; N, 14.13. Found: C, 45.11; H, 6.57; N, 14.07.
ESI-MS (þ): m/z 276 ½M þ Hꢀþ, 298 ½M þ Naꢀþ. Reten-
tion time (RP-HPLC): 9.7 min.
Synthesis of [Re(CO)3(k3-L4)] (6)
Synthesis of 2-(3,5-dimethyl-1H-pyrazol-1-yl)-N-(2-
phosphinoethyl)ethanamine (4)
To a solution of [Re(CO)3(H2O)3]Br (0.047 g, 0.12 mmol)
in MeOH (10 mL) L4 (0.032 g, 0.012 mmol) was added,
and the resulting mixture was refluxed overnight. After
evaporation of the solvent, the residue obtained was
dried under vacuum and analyzed by RP-HPLC. The
crude product revealed a mixture of unreacted Re
precursor (retention time: 6.3 min), free L4 (retention
time: 9.7 min) and complex 6 as two isomers (retention
time: isomer a – 18.6 min, isomer b – 18.9 min). The
isomers were separated and isolated by RP-HPLC. Yield
(both isomers): 30 mg, 46%.
The compound has been prepared according to a
slightly modified reported method9: To a stirred cold
(08C) solution of LiAlH4 (2.2 mL, 1 M solution in diethyl
ether), a suspension of the diethyl phosphonate 3
(0.328 g, 1.08 mmol) in dry diethyl ether (24 mL) in a
nitrogen atmosphere was added. The reaction was
allowed to react for 4 h at room temperature; the
mixture was cooled to 08C and the excess of LiAlH4
was eliminated by slow addition of cold aqueous brine
solution (20 mL), followed by the addition of aqueous
KOH solution (10%, 20 mL). The organic layer was
separated, the aqueous layer was extracted with ether
(1 ꢃ 20 mL) and CH2Cl2 (2 ꢃ 25 mL), and the organic
phases were collected and washed with brine (80 mL).
After drying over anhydrous MgSO4, the solvents were
evaporated in the rotary evaporator under reduced
pressure and the colorless oil obtained was vacuum
dried. The product is stable for some weeks if stored at
ꢁ208C. Yield: 0.14 g, 65%. 1H-NMR (CDCl3): d 5.75 (s,
H(4)pz, 1H); 4.03 (t, CH2, 2H); 2.98 (t, CH2, 2H); 2.90 (t,
PH, 1H); 2.74 (q, CH2, 2H); 2.25 (t, PH, 1H); 2.20 (s,
CH3, 3H), 2.17 (s, CH3, 3H), 1.66–1.58 (m, CH2, 2H).
31P NMR (CDCl3): d ꢁ147.1.
Isomer a: 1H-NMR (CD3OD): d 6.22 (s br., 1H, NH),
6.12 (s, 1H, H(4)pz), 4.54 (dd, J ¼ 4:5 Hz, J ¼ 15:4 Hz,
1H, CH2-1), 4.04 (m, 1H, CH2-10), 3.79 (p, J ¼ 7:1 Hz,
2H, OCH2-5), 3.47 (m br, 2H, CH2-4), 3.04 (m, 1H, CH2-
2), 2.74 (m, 1H, CH2-20), 2.52 (s, 3H, CH3), 2.34 (s, 3H,
CH3), 1.79 (m br., 2H, CH2-3), 1.15 (t, J ¼ 7:4 Hz, 3H,
CH3-6). 13C-RMN (CD3OD): d 197.0–194.5 (3 ꢃ CꢄO),
154.5 (C(3/5)pz), 143.9 (C(3/5)pz), 108.4 (C(4)Pz), 62.1
(d, 2JPC ¼ 7:4 Hz, C-5), 52.1 (d, 1JPC ¼ 7:5 Hz, C-4), 50.6
(C-2), ꢅ49.0 (C-1, overlapped with CD3OD as con-
2
firmed by HSQC), 23.8 (d, JPC ¼ 22:3 Hz, C-3), 16.9
(C-6); 15.2 (CH3pz); 11.4 (CH3pz). 31P-NMR (CD3OD):
d 25.6.
Isomer b: 1H-NMR (CD3OD): d 6.22 (s br., 1H, NH),
6.09 (s, 1H, H(4)pz), 4.54 (dd, J ¼ 4:5 Hz, J ¼ 15:4 Hz,
1H, CH2-1,), 4.04 (m, 3H, CH2 ꢁ 10 þ OCH2 ꢁ 5), 3.59
(m br., 2H, CH2-4), 3.04 (m, 1H, CH2-2), 2.74 (m, 1H,
CH2-20), 2.47 (s, 3H, CH3), 2.33 (s, 3H, CH3), 1.85 (m,
2H, CH2-3), 1.37 (t, J ¼ 7:4 Hz, 3H, CH3-6). 13C-RMN
(CD3OD): d 197.0–194.5 (3 ꢃ CꢄO), 154.7 (C(3/5)pz),
Synthesis of {1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]-
1,3-azaphospholidin-3-yl}-methanol (5)
An aqueous solution of formaldehyde (0.040 ml of a
37% solution) was placed in oxygen-free ethanol
(2.5 mL) and purged with nitrogen gas for some
minutes. This solution was added dropwise with
stirring at room temperature to compound 4 (0.048 g,
0.24 mmol). The resulting solution was allowed to react
for 30 min at room temperature. Removal of the solvent
in vacuo afforded compound 5 as a colorless, viscous
oil. Yield: 0.052 g, 92%. 1H-NMR (D2O): d 5.76 (s,
2
143.9 (C(3/5)pz), 108.4 (C(4)Pz), 60.7 (d, JPC ¼ 12:1
1
Hz C-5), 52.6 (d, JPC ¼ 7:5 Hz, C-4), 50.4 (C-2),
ꢅ49.0 (C-1, overlapped with CD3OD as confirmed
by HSQC), 21.9 (d, 2JPC ¼ 22:4 Hz, C-3), 16.8
(C-6), 15.4 (CH3pz), 11.4 (CH3pz). 31P-NMR (CD3OD):
d 23.5. In both isomers, there is occasional overlapping
of some resonances associated with the two isomers, as
confirmed by two-dimensional NMR techniques (1H-1H
Copyright # 2007 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2007; 50: 1176–1184
DOI: 10.1002.jlcr