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F. Sobrio et al. / Bioorg. Med. Chem. 8 (2000) 2511±2518
the reaction of 2,4-pentadione (10 g, 0.1 mol) with an
equimolar amount of NaOH (4 g, 0.1 mol) in ethanol
(50 mL). Compound 4 and sodium acetylacetonate were
layer was washed with brine, dried on anhydrous
MgSO4, ®ltered and the solvent evaporated. To a resi-
due dissolved in absolute ethanol, sulfuric acid (96%,
0.2 mL) was added and the reaction mixture heated to
re¯ux for 18 h. Then the solution was made alkaline
with NaOH (1 N). Ethanol was removed and the
extraction performed with ethyl acetate (3Â100 mL);
the organic layers were washed with brine, dried on
anhydrous MgSO4, ®ltered and the solvent evaporated.
After chromatography on a silica gel column (eluent:
CH2Cl2:CH3OH:Et3N, 98.5:1:0.5), 1.25 g of 9 was
obtained as orange crystals (67%). Melting point: 81±
82 ꢁC. Rf=0.7 (CH2Cl2:MeOH (90:10)). Elemental ana-
lysis C27H35N3O4: required C, 69.65%; H, 7.58%; N,
9.02%, found C, 69.71%; H, 7.72%; N, 8.87%. 1H
NMR (CDCl3): 7.98 (d, 1H, J=8.4 Hz), 7.92 (s, 1H),
7.55±7.50 (m, 2H), 7.4 (s, 1H), 7.0 (d, 1H, J=9.5 Hz),
6.15 (s, 1H), 4.20±4.40 (m, 1H), 3.85±3.55 (m, 4H), 3.1
(dm, 2H, J=11.6 Hz), 2.75 (qd, 2H, J=12.6, 3.2 Hz),
2.5 (s, 3H), 2.41 (s, 3H), 2.38 (s, 3H), 2.15 (t, 2H,
J=10.2 Hz), 1.9 (d, 2H, J=12.2 Hz), 1.25 (t, 6H, 7 Hz).
13C NMR (CDCl3): 141.6, 129.9, 129.5, 129.1, 126.5,
125, 123, 118.3, 111.6, 98.9, 63.75, 56, 54.1, 46.35, 30.5,
21.4, 15.2, 12.25.
2
freshly prepared and dried under reduced pressure (10
mbar) at 60 ꢁC for 4 h before use. Under a nitrogen
current, 4 (2.92 g; 10.65 mmol) was dissolved in dry
dimethylformamide (18 mL) (DMF was bubbled by
nitrogen for 5 min before use) then acetylacetonate (6.42
g; 52.6 mmol) and cuprous iodide (2.23 g; 11.7 mmol)
were added, the reaction mixture was stirred and heated
for 6 h at 100 ꢁC. Aqueous NaOH (10 mL, 1 N) was
added at 100 ꢁC and the reaction stirred for 16 h more
at room temperature. The solution was extracted with
ethyl acetate, washed with brine, dried on anhydrous
Na2SO4, ®ltered, and the solvent evaporated. After
chromatography on a silica gel column (eluent: heptane:
ethyl acetate 50:50), 1.9 g of 5 as a pale yellow oil (71%)
were isolated. Rf=0.25 (heptane:ethyl acetate (50:50)).
1H NMR (CDCl3): 7.89 (d, 1H, J=8.2 Hz), 7.61 (d, 1H,
J=1.9 Hz), 7.33 (dd, 1H, J=8.2 Hz, 1.9 Hz), 6.47 (s,
1H), 4.05 (m, 4H), 3.82 (s, 2H), 2.22 (s, 3H).13C NMR
(CDCl3): 204.3, 147.6, 139.8, 133.6, 130.7, 128.8, 125,
99.5, 65.3, 50.1, 29.9.
3-(3-[1,3]Dioxolan-2-yl-4-nitrophenyl)-pentane-2,4-dione
(6). 0.19 g (yield 6%). Rf=0.55 (heptane:ethyl acetate
(50:50)). H NMR (CDCl3): 7.95 (d, 1H, J=8.2 Hz),
7.60 (d, 1H, J=1.9 Hz), 7.34 (dd, 1H, J=8.2 Hz; 1.9
Hz), 6.47 (s, 1H), 4.03 (m, 4H), 3.4 (s, 1H), 1.90 (s, 6H).
13C NMR (CDCl3): 190.6, 147.95, 142.3, 133.75, 132.4,
130.5, 125.1, 113.7, 99.4, 65.45, 24.3.
5-[2,5-Dimethyl-1-(1-methyl-4-piperidinyl)-1H-indol-3-yl]-
2-nitrobenzaldehyde (10). Compound 9 (300 mg; 0.64
mmol) in acetone (20 mL) and in presence of HClconc
(100 mL) was stirred at room temperature for 1 h. The
solution was made alkaline with NaOH (5 N). After
extraction with ethyl acetate, the organic layer was dried
on MgSO4, ®ltered and the solvent evaporated. After
chromatography on silica gel column (eluent: CH2Cl2:
CH3OH:Et3N, 98.5:1:0.5), compound 10 (220 mg) was
isolated as red crystals (87%). Melting point: 130±
131ꢁC. Rf=0.35 (CH2Cl2:MeOH (90:10)). Elemental
analysis C23H25N3O3: required C, 70.57%; H, 6.44%;
N, 10.73%; found C, 70.83%; H, 6.61%; N, 10.47%. 1H
NMR (CDCl3): 10.5 (s, 1H), 8.2 (d, 1H, J=8.5 Hz),
7.95 (s, 1H), 7.8 (d, 1H, J=8.45 Hz), 7.6 (d, 1H, J=8.5
Hz), 7.4 (s, 1H), 7.05 (d, 1H, J=8.5 Hz), 4.20±4,40 (m,
1H), 3.1 (dm, 2H, J=11.6 Hz), 2.75 (qd, 2H, J=12.5
Hz, 3.3 Hz), 2.5 (s, 3H), 2.4 (s, 6H), 2.15 (m, 2H), 1.9
(dm, 2H, J=12 Hz). 13C NMR (CDCl3): 189, 146.25,
143.4, 133.6, 132.7, 131.25, 129, 126.2, 124, 123.3, 116.8,
118, 111.6, 54.8, 53.1, 45.25, 29.4, 20.4, 12.3.
1
2 - (2 - Nitrophenyl) - [1,3]dioxolane (7). 0.33 g (yield
1
16%)Rf=0.6 (heptane:ethyl acetate (50:50)). H NMR
(CDCl3): 7.88 (dd, 1H, J=7.9 Hz, 1.2 Hz), 7.80 (dd, 1H,
J=7.7 Hz, 1.4 Hz), 7.60 (td, 1H, J=7.6 Hz, 1.3 Hz),
7.48 (td, 1H, J=7.8 Hz, 1.5 Hz), 6.47 (s, 1H), 4.03 (m,
4H). 13C NMR (CDCl3): 147.85, 132.2, 131.8, 128.6,
126.6, 123.4, 98.56, 64.3.
2-Nitro-5-(2-oxo-propyl)-benzaldehyde (8). To a solution
of 5 (0.5 g, 2 mmol) in THF (20 mL) were added HCl 3
M (5 mL) and water (8 mL). The reaction mixture was
heated at re¯ux for 2 h. The solvent was removed and
the solution extracted with dichloromethane, washed
with water, dried on anhydrous Na2SO4, ®ltered and the
solvent evaporated. The product was recrystallized in
ethyl acetate: 0.35 g of 8 was obtained (85%) as a yellow
solid product. Melting point=72.5±73 ꢁC. Rf=0.7
(ethyl acetate). Elemental analysis C10H9NO4: required
C, 57.97%, H, 4.38%; N, 6.76%; found C, 58.03%, H
4.43%, N, 6.67%. 1H NMR (CDCl3): 10.45 (s, 1H),
8.09 (d, 1H, J=8.3 Hz), 7.73 (d, 1H, J=1.9 Hz), 7.56
(dd, 1H, J=8.3 Hz, 1.9 Hz), 3.89 (s, 2H), 2.26 (s, 3H).
13C NMR (CDCl3): 202.5, 187.2, 147.2, 140.35, 133.85,
130.45, 129.7, 123.8, 48.45, 29.1.
Preparation of nucleophilic [18F]¯uoride ion. No-carrier-
added aqueous [18F]¯uoride was produced via 18O
(p,n)18F nuclear reaction by irradiation of 1.5 mL 18O-
enriched water (95%) on a baby cyclotron (CGR MeV
325). 18F was separated from 18O-enriched water on an
anion exchange resin (Bio-Rad, AG1-X8, 100±200
mesh, chloride form) and recovered by elution with 0.5
mL of aqueous potassium carbonate (5 mg/mL). The
aqueous [18F]¯uoride solution was collected into a con-
ical Reactivial1 containing K2CO3 (4.5 mg; 0.032 mmol)
and aminopolyether Kypto®x 222 [(4,7,13,16,21,24)hex-
aoxa-1,10-diazabicyclo(8,8,8)hexacosane] (22 mg; 0.052
mmol) dissolved in water:acetonitrile mixture (0.1 mL:1
mL). The water was removed azeotropically with ace-
tonitrile under a stream of nitrogen and a dry residue of
3-(3-Diethoxymethyl-4-nitrophenyl)-2,5-dimethyl-1-(1-
methyl-4-piperidinyl)-1H-indole (9). A solution of the
hydrazine 2 (0.873 g; 3.98 mmol) and compound 5 (1 g;
3.98 mmol) in absolute ethanol (20 mL) was stirred and
heated to re¯ux for 18 h. After evaporation of the sol-
vent, ethyl acetate (100 mL) was added. The organic
[K/K222]
+18F was obtained.