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J Radioanal Nucl Chem (2017) 313:419–428
3-Isobutyl-9-(3-fluoropropoxy)-10-methoxy-3,4,6,7-
8.7 Hz, 1H, H-4), 2.98–2.83 (m, 2H, CH2-7), 2.52–2.37 (m,
4H, –ArCH3 and H-3), 1.80–1.67 (m, 2H, –CH2CH(CH3)2),
1.35–1.27 (m, 1H, –CH(CH3)2), 0.98 (d, J = 6.3 Hz, 3H,
–CH(CH3)2), 0.92 (d, J = 6.3 Hz, 3H, –CH(CH3)2); 13C
NMR (100 MHz, CDCl3) d: 195.50, 156.20, 149.89, 148.67,
145.02, 132.80, 129.87, 128.01, 122.20, 113.34, 109.17,
94.47, 67.79, 66.84, 56.08, 55.83, 49.00, 42.06, 37.48, 28.31,
25.55, 23.47, 21.86, 21.68; MS (ESI) m/z: 500.24 [M?H]?,
522.26 [M?Na]?.
tetrahydro-2H-benzo[a]quinolizine-2-one (6b)
To compound 5 (20.00 mg, 66.45 lmol) in dry DMF
(4 mL), Cs2CO3 (43.32 mg, 132.89 lmol) was added
under nitrogen and the mixture was stirred at room tem-
perature for 20 min. Then a solution of sodium iodide
(19.94 mg, 132.89 lmol) and 1-bromo-3-fluoropropane
(25 lL, 265.78 mmol) was added, and the mixture was
heated at 110 °C for 2 h. After the reaction mixture was
cooled to room temperature, the solvent was evaporated
under vacuum and quenched with H2O (40 mL), and then
the aqueous phase was extracted with dichloromethane
(3 9 40 mL). The combined organic extracts were dried
over anhydrous sodium sulfate, evaporated under vacuum
and purified by column chromatography on silica gel
(dichloromethane/methanol, 100:1.5, v/v) to produce the
fluoride 6b as light yellow solid (16.10 mg, 67.1%). Mp:
3-Isobutyl-9-(3-methanesulfonyloxypropoxy)-10-methoxy-
3,4,6,7-tetrahydro-2H-benzo[a] quinolizine-2-one (7b)
A mixture containing compound 5 (25.00 mg, 83.06 lmol),
1,3-bis(tosyloxy)propane (47.84 mg, 124.58 lmol) and
Cs2CO3 (202.96 mg, 622.92 lmol) in dry acetone (5 mL)
was stirred at 60 °C for 2 h under nitrogen. The reaction
mixture was quenched with H2O (10 mL) and the aqueous
phase was extracted with ethyl acetate (3 9 25 mL). The
combined organic extracts were dried over anhydrous
sodium sulfate and evaporated under vacuum. The crude
product was purified using column chromatography (EtOAc/
hexane, 70:30, v/v) to give compound 7b as yellow solid
(23.20 mg, 54.5%). Mp: 129-131 °C; 1H NMR (400 MHz,
CDCl3) d: 7.76 (d, J = 8.3 Hz, 2H, CH3Ar–H), 7.26 (d,
J = 8.0 Hz, 2H, CH3Ar–H), 7.14 (s, 1H, ArH), 6.61 (s, 1H,
ArH), 5.63 (s, 1H, H-1), 4.26 (t, J = 5.8 Hz, 2H, –OCH2-
CH2CH2OTs), 4.07 (t, J = 6.0 Hz, 2H, –OCH2CH2CH2-
OTs), 3.80 (s, 3H, –OCH3), 3.66 (dd, J = 12.5, 5.3 Hz, 1H,
H-4), 3.45–3.35 (m, 2H, CH2-6), 3.32 (dd, J = 12.5, 8.6 Hz,
1H, H-4), 2.99–2.87 (m, 2H, CH2-7), 2.50–2.42 (m, 1H, H-3),
2.39 (s, 3H, –ArCH3), 2.25–2.14 (m, 2H, –OCH2CH2CH2-
OTs), 1.82–1.65 (m, 2H, –CH2CH(CH3)2), 1.35–1.28 (m,
1H, –CH(CH3)2), 0.98 (d, J = 6.3 Hz, 3H, –CH(CH3)2),
0.93 (d, J = 6.2 Hz, 3H, –CH(CH3)2); 13C NMR (100 MHz,
CDCl3) d: 195.46, 150.50, 148.35, 144.80, 132.86, 129.94,
129.80, 128.79, 128.41, 127.87, 126.00, 121.28, 112.02,
108.73, 94.35, 67.01, 64.45, 56.00, 55.84, 49.06, 42.07,
37.50, 28.87, 28.40, 25.55, 23.49, 21.85, 21.67; MS (ESI)
m/z: 514.25 [M?H]?, 536.31 [M?Na]?.
1
167–168 °C; H NMR (400 MHz, CDCl3) d: 7.17 (s, 1H,
ArH), 6.69 (s, 1H, ArH), 5.63 (s, 1H, H-1), 4.67 (dt,
J = 47.0, 5.6 Hz, 2H, –CH2F), 4.19 (t, J = 6.3 Hz, 2H,
–OCH2-), 3.85 (s, 3H, –OCH3), 3.66 (dd, J = 12.5, 5.3 Hz,
1H, H-4), 3.46–3.35 (m, 2H, CH2-6), 3.31 (dd, J = 12.5,
8.6 Hz, 1H, H-4), 3.02–2.85 (m, 2H, CH2-7), 2.50–2.40 (m,
1H, H-3), 2.34–2.14 (m, 2H, –OCH2CH2CH2F), 1.83–1.66
(m, 2H, –CH2CH(CH3)2), 1.36–1.22 (m, 1H, –CH(CH3)2),
0.98 (d, J = 6.3 Hz, 3H, –CH3), 0.92 (d, J = 6.3 Hz, 3H,
–CH3); 13C NMR (100 MHz, CDCl3) d: 195.46, 156.44,
150.78, 148.45, 128.84, 121.19, 112.00, 108.84, 94.33,
81.43, 79.79, 64.84, 64.79, 56.12, 55.84, 49.06, 42.08,
37.50, 30.41, 30.21, 28.43, 25.56, 23.48, 21.86; MS (ESI)
m/z: 362.34 [M?H]?, 384.28 [M?Na]?.
3-Isobutyl-9-(3-methanesulfonyloxyethoxy)-10-methoxy-
3,4,6,7-tetrahydro-2H-benzo[a] quinolizine-2-one (7a)
A mixture containing compound 5 (25.00 mg, 83.06 lmol),
1,2-bis(tosyloxy)ethane (46.09 mg, 124.58 lmol) and
Cs2CO3 (202.96 mg, 622.92 lmol) in dry acetone (5 mL)
was stirred at 60 °C for 2 h under nitrogen. The reaction
mixture was quenched with H2O (10 mL) and the aqueous
phase was extracted with ethyl acetate (3 9 25 mL). The
combined organic extracts were dried over anhydrous
sodium sulfate and evaporated under vacuum. The crude
product was purified using column chromatography (EtOAc/
hexane, 50:50, v/v) to give compound 7a as yellow solid
(19.20 mg, 46.3%). Mp: 133-134 °C; 1H NMR (400 MHz,
CDCl3) d: 7.81 (d, J = 8.3 Hz, 2H, CH3Ar–H), 7.33 (d,
J = 8.0 Hz, 2H, CH3Ar–H), 7.15 (s, 1H, ArH), 6.64 (s, 1H,
ArH), 5.62 (s, 1H, H-1), 4.39 (dd, J = 5.8, 4.1 Hz, 2H,
–OCH2CH2OTs), 4.27 (dd, J = 5.8, 4.2 Hz, 2H, –OCH2-
CH2OTs), 3.82 (s, 3H, –OCH3), 3.66 (dd, J = 12.5, 5.3 Hz,
1H, H-4), 3.44–3.35 (m, 2H, CH2-6), 3.31 (dd, J = 12.6,
Radiochemistry
Fluorine-18 was produced on a HM-7 cyclotron (Sumitomo
Heavy Industries Ltd., Japan) and passed through a Sep-
Pak Light QMA cartridge. The fluoride ions were eluted
from the QMA cartridge with 1.0 mL solution of acetoni-
trile (0.8 mL) and water (0.2 mL) containing potassium
carbonate (2.0 mg) and Kryptofix 222 (13.0 mg). The
solution was evaporated at 105 °C under a flow of nitrogen
and the residue was azeotropically dried with 1.0 mL
acetonitrile. Then, 1.0 mg of the corresponding tosylated
precursor 7a/7b dissolved in 1.0 mL DMSO was added to
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