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DOI: 10.1055/s-0029-1219813
A Rapid Microwave-Assisted Procedure for Easy Access to Nx Polydentate Ligands for Potential Application in α-RIT
Publikationsverlauf
Publikationsdatum:
07. April 2010 (online)
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Abstract
Heterocycles bearing a hydrazine moiety react with bisaldehydes or bisketones to afford new Nx polydentate ligands suitable for α-radioimmunotherapy. We developed a fast and efficient method using microwave-assisted technology to obtain chelators with variable size and number of coordination centers which were fully characterized. The complexation efficiency with astatine will be assessed.
Key words
astatine - radioimmunotherapy - pyrimidinone - triazinone - chelating agent
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References
General Procedure
for Ligands L
1-8
To
a 10 mL microwave reaction vessel was placed heterocyclic ring 3 or 4 (0.5 mmol)
and dialdehyde 5 or 8 or diketone 6 or 7 (0.25 mmol)
in MeOH for L
1,2,7,8
(4
mL) or in AcOH for L
3-6
(4
mL). The vial was heated (internal temperature measured by fibre
optic) in a microwave synthesizer (MultiSYNTH®,
Milestone S.r.l.) to 110 ˚C [2 min (110
W) ramp + 15 min irradiation (80 W)] for L
1,2,7,8
or to
130 ˚C [2 min (300 W) ramp + 15
min irradiation (250 W)] for L
3-6
. The solvent was removed
under vacuum, and the solid residue was washed with Et2O.
The product was filtered and dried under vacuum to afford ligands L
1-8
.
Spectroscopic Data of Ligands L
1-8
L
1
:
mp 243-244 ˚C. IR (KBr): 3245, 1733,
1628, 1480, 1193, 1147 cm-¹. ¹H
NMR (TFA): δ = 1.23 [s, 9 H, C(CH3)3],
3.61 (s, 6 H, NCH3), 3.87 (s, 6 H, OCH3),
7.78 (s, 2 H, Har), 8.02 (s, 1 H, Har), 8.52
(s, 2 H, CH), 8.59 (s, 2 H, CHpyr). ¹³C
NMR (TFA): δ = 27.3, 28.4, 33.4, 52.1, 106.5, 122.4,
130.3, 145.6, 148.9, 153.8, 155.7, 156.4, 162.7. MS (MALDI): m/z = 551.42 [M + H]+,
573.31 [M + Na]+.
L
2
:
mp 245-247 ˚C. IR (KBr): 3302, 1674,
1493, 1429, 1303, 1193 cm-¹. ¹H
NMR (TFA): δ = 1.37 [s, 9 H, C(CH3)3],
3.68 (s, 6 H, NCH3), 8.12 (s, 2 H, Har), 8.30
(s, 1 H, Har), 8.50 (s, 2 H, CH), 8.52 (s, 2 H, CHtri). ¹³C
NMR (TFA): δ = 28.5, 33.6, 33.7, 125.7, 130.1,
130.9, 146.3, 153.9, 154.4, 157.0, 161.3. MS (CI-): m/z = 436.2 [M]+.
L
3
:
mp 197-199 ˚C. IR (KBr): 3304, 1723,
1652, 1480, 1189, 1149 cm-¹. ¹H
NMR (TFA): δ = 2.40 (s, 6 H, CH3), 3.66
(s, 6 H, NCH3), 3.87 (s, 6 H, OCH3), 8.57
(s, 2 H, CHpyr). ¹³C NMR
(TFA): δ = 10.7, 27.5, 52.3, 108.4, 145.0, 149.8,
155.1, 160.1, 162.3. MS (CI+): m/z = 447.3 [M + H]+.
L
4
:
mp >250 ˚C. IR (KBr): 3434, 3071, 1691,
1622, 1494, 1291 cm-¹. ¹H
NMR (TFA): δ = 2.52 (s, 6 H, CH3),
3.61 (s, 6 H, NCH3), 8.53 (s, 2 H, CHtri). ¹³C
NMR (TFA): δ = 10.7, 33.9, 146.4, 155.8, 161.0,
162.2; MS (CI+): m/z = 333.0
[M + H]+.
L
5
:
mp 247-249 ˚C. IR (KBr): 3216, 1734,
1627, 1481, 1189, 1148 cm-¹. ¹H
NMR (TFA): δ = 2.73 (s, 6 H, CH3), 3.75
(s, 6 H, NCH3), 3.95 (s, 6 H, OCH3), 8.45
(d, 2 H, J = 8.0
Hz, Har), 8.64 (s, 1 H, Hpyr), 8.81 (t, 1
H, J = 8.0
Hz, Har). ¹³C NMR (TFA): δ = 12.8,
27.9, 52.2, 104.9, 126.4, 146.3, 146.5, 148.1, 150.1, 154.1, 157.7,
163.4. MS (MALDI): m/z = 524.52 [M + H]+,
546.33 [M + Na]+.
L
6
:
mp 211-213 ˚C. IR (KBr): 3220, 1634,
1489, 1303, 1187 cm-¹. ¹H
NMR (TFA): δ = 2.74 (s, 6 H, CH3),
3.66 (s, 6 H, NCH3), 8.55 (d, 2 H, J = 8.0
Hz, Har), 8.65 (s, 1 H, Htri), 8.85 (t, 1
H, J = 8.0
Hz, Har). ¹³C NMR (TFA): δ = 12.4,
34.0, 126.9, 145.0, 146.1, 148.6, 150.9, 157.5, 162.9. MS (CI-):
m/z = 409.2 [M]+.
L
7
:
mp >250 ˚C. IR (KBr): 1733, 1627, 1495,
1191, 1146 cm-¹. ¹H
NMR (TFA): δ = 3.66 (s, 6 H, NCH3),
3.86 (s, 6 H, OCH3), 8.18 (s, 2 H, Har), 8.69
(s, 2 H, Hpyr), 8.72 (d, 2 H, J = 8.5
Hz, Har), 8.84 (d, 2 H, J = 8.5
Hz, Har), 9.15 (s, 2H, CH). ¹³C
NMR (TFA): δ = 28.7, 53.2, 107.8, 123.7, 129.0, 131.9,
137.5, 143.2, 146.4, 147.7, 150.0, 150.9, 151.0, 163.4. MS (MALDI): m/z = 597.41 [M + H]+,
619.22 [M + Na]+.
L
8
:
mp >250 ˚C. IR (KBr): 3212, 1623, 14932,
1306, 1186 cm-¹. ¹H
NMR (TFA): δ = 3.69 (s, 6 H, NCH3),
8.27 (s, 2 H, Har), 8.69 (s, 2 H, Har), 8.61
(s, 2 H, Htri), 8.89 (d, 2 H, J = 8.6 Hz,
Har), 9.06 (s, 2 H, CH), 9.29 (d, 2 H, J = 8.6
Hz, Har). ¹³C NMR (TFA): δ = 33.9,
123.2, 128.0, 130.9, 136.3, 141.8, 147.1, 147.3, 149.7, 156.1, 162.7.
MS (CI-): m/z = 482.2 [M]+.