◦
1
salt 4a (0.70 g, 98%) as a white solid; mp: 191 C; H NMR
(CDCl3, 300 MHz) d 9.32 (1H, s), 9.31 (1H, s), 8.70 (1H, brs, J=
5.6 Hz), 7.52 (1H, s), 7.31 (6H, m), 4.62 (2H, d, J= 5.6 Hz), 4.51
(3H, s), 4.23 (3H, s), 4.06 (3H, s); 13C NMR (CDCl3, 75 MHz) d
161.7, 159.6, 152.9, 142.9, 138.5, 137.7, 128.9, 128.6, 127.7, 126.5,
126.2, 108.4, 98.0, 90.0, 58.2, 57.3, 46.3, 44.5; IR (KBr) n = 3344,
3064, 1660, 1511, 1274, 1167, 1032, 640 cm-1; Anal. Calcd for
C21H21F3N2O6S: C, 51.85; H, 4.35; N, 5.76; S, 6.59. Found: C,
51.76; H, 4.36; N, 5.72; S, 6.38.
148.2, 144.7, 140.6, 139.2, 132.9, 128.8, 128.0, 127.5, 113.1, 98.2,
97.6, 56.4, 56.3, 43.8, 39.0, 26.6; IR (CHCl3) n = 3392, 1665, 1602,
1578, 1519, 1237, 1101, 1032 cm-1; HRMS (IC+) m/z [M + H+]:
calcd for C20H23N203, 339.1709; found, 339.1715
Ethyl 4-(1,4-dihydro-6,7-dimethoxy-1-methylquinoline-3-carbo-
nylamino)butanoate (1b). Prepared according to procedure C
from NaHCO3 (0.29 g, 3.44 mmol), Na2S2O4 (0.43 g, 2.86 mmol)
and quinolinium salt 4b (0.29 g, 0.57 mmol). Compound 1b (0.20 g,
97%) was obtained as a yellow oil; 1H NMR (CDCl3, 300 MHz)
d 7.20 (1H, s), 6.58 (1H, s), 6.32 (1H, s), 5.55 (1H, brs), 4.11
(2H, q, J = 7.2 Hz), 3.87 (3H, s), 3.82 (3H, s), 3.72 (2H, s), 3.39
(2H, q, J = 7.2 Hz) 3.21 (3H, s), 2.39 (2H, t, J = 7.2 Hz), 1.89
(2H, quint, J = 7.2 Hz), 1.25 (3H, t, J = 7.2 Hz); 13C NMR
(CDCl3, 75 MHz) d 173.1, 167.2, 148.0, 144.3, 139.1, 133.4, 113.7,
113.3, 99.2, 99.0, 60.1, 56.2, 56.1, 51.6, 41.4, 31.1, 26.4, 25.2,
14.5. MS (ESI+) m/z 363 [M + H+], 333, 247, 203, 188, 160, 115;
UV/vis (methanol) 348 nm; HRMS (IC+) m/z [M + H+]: calcd for
C19H27N205, 363.1920; found, 363.1927
3-(Ethoxycarbonylpropylaminocarbonyl)-6,7-dimethoxy-1-me-
thylquinolinium triflate (4b). Quinolinium salt 4b (0.56 g, 97%)
was obtained from quinoline 3b (0.40 g, 1.15 mmol) and methyl
trifluoromethanesulfonate (143 mL, 1.26 mmol) according to
◦
1
procedure B. mp 152 C; H NMR (CDCl3, 300 MHz) d 9.43
(1H, s), 9.30 (1H, s), 8.31 (1H, brt, J = 5.3 Hz), 7.55 (1H, s),
7.51 (1H, s), 4.69 (3H, s), 4.25 (3H, s), 4.12 (2H, m), 4.06 (3H,
s), 3.48 (2H, m), 2.41 (2H, t, J = 7.5 Hz), 1.98 (2H, quint, J =
7.2 Hz), 1.24 (3H, t, J = 7.1 Hz); 13C NMR (CDCl3, 75 MHz) d
173.6, 161.8, 159.6, 153.0, 144.3, 142.9, 137.9, 126.6, 126.3, 108.5,
98.1, 60.8, 58.2, 57.3, 45.5, 40.2, 32.0, 24.7, 14.5. IR (KBr) n =
3408, 2940, 1722, 1678, 1511, 1266, 1028 cm-1; Anal. Calcd for
C20H25F3N2O8S: C, 47.06; H, 4.94; N, 5.49; S, 6.28. Found: C,
47.03; H, 4.96; N, 5.54; S; 6.30; UV/vis (methanol) 262, 362 nm;
MS(ESI+) m/z: 361.33 [M-TfO-]+.
4-tert-Butyloxycarbonylaminobutyric acid 2-(1,4-dihydro-6,7-
dimethoxy-1-methyl-3-carbonylaminoquinoline)-3-methylbutyl ester
(1d). Prepared according to procedure C from NaHCO3 (206 mg,
2.4 mmol), Na2S2O4 (308 mg, 2.0 mmol) and quinolinium salt 4d
(273 mg, 0.4 mmol). Compound 1d (124 mg, 60%) was obtained
as a yellow oil; 1H NMR (CDCl3, 300 MHz) d 7.30 (1H, s), 6.64
(1H, s), 6.37 (1H, s), 5.53 (1H, d, J= 8.3 Hz), 4.84 (1H, brs),
4.23 (3H, m), 3.92 (3H, s), 3.88 (3H, s), 3.73 (2H, s), 3.27 (3H, s),
3.16 (2H, m), 2.40 (2H, m), 1.82 (3H, m), 1.47 (9H, s), 1.01 (6H,
m). HRMS (IC+) m/z [M + H+]: calcd for C27H42N307, 520.3023;
found, 520.3031
N-(1-tert-Butyloxycarbonylaminopropylcarbonyloxy-3-methyl-
butan-2-yl)-3-carbonylamino-6,7-dimethoxy-1-methyl quinolinium
triflate (4d). Quinolinium salt 4d (0.14 g, 82%) was obtained from
quinoline 3d (0.12 g, 0.25 mmol) and methyl trifluoromethane-
sulfonate (28 mL, 0.25 mmol) as a colourless translucent solid,
according to procedure B. mp: 87 ◦C; 1H NMR (DMSO-d6,
300 MHz) d 9.52 (1H, s), 9.32 (1H, s), 8.82 (1H, brd, J= 7.9 Hz),
7.87 (1H, s), 7.69 (1H, s), 6.80 (1H, brt, J= 5.0 Hz), 4.80 (3H, s),
4.30 (1H, m), 4.17 (3H, s), 4.14 (2H, m), 4.02 (3H, s), 2.86 (2H,
m), 2.26 (2H, t, J= 7.3 Hz), 1.94 (1H, m), 1.56 (2H, m), 1.30 (9H,
s), 0.99 (6H, d). 13C NMR (DMSO-d6, 75 MHz) d 173.0, 162.8,
158.0, 155.9, 151.9, 145.7, 141.8, 137.3, 126.0, 125.2, 108.6, 99.2,
77.8, 64.2, 57.8, 56.9, 55.2, 54.4, 45.8, 31.2, 29.4, 28.5, 25.2, 19.7,
19.0; IR (KBr) n = 3355, 2974, 1737, 1705, 1667, 1513, 1281, 1165,
1030 cm-1; Anal. Calcd for C28H40F3N3O10S: C, 50.37; H, 6.04; N,
6.29; S, 4.80. Found: C, 50.39; H, 6.02; N, 6.36; S, 4.74; MS(ESI+)
m/z: 518.33 [M-TfO-]+.
[11C]Methyl triflate12. [11C]Carbon dioxide was produced by
the 14N(p,a)11C nuclear reaction of a gas target filled with nitrogen
containing 0.5% oxygen at pressure of 20 bars irradiated with
16 MeV protons (IBA Cyclone 18/9 cyclotron). The [11C]carbon
dioxide formed was carried by a nitrogen flow through P2O5 and
collected in a stainless loop immersed in liquid argon. Then the
loop was removed from the liquid nitrogen and brought back
to room temperature. The [11C]carbon dioxide was carried by
nitrogen flow into a reactor maintained at 0 ◦C and containing
LiAlH4 in tetrahydrofuran (1M, 200 mL) the◦n tetrahydrofuran
◦
was removed at 140 C and after cooling at 0 C, hydriodic acid
(1.0 mL, 54%) was added. The [11C]methyl iodide was distilled
under stream of nitrogen at 140 ◦C and passed at 200 ◦C through
an oven containing silver triflate-impregnated graphitized carbon
and the [11C]methyl triflate was obtained.
N-Benzyl-1,4-dihydro-6,7-dimethoxy-1-methylquinoline-3-car-
boxamide (procedure C) (1a). A mixture of NaHCO3 (50 mg,
0.62 mmol) and Na2S2O4 (77 mg, 0.51 mmol) was added to a
solution of quinolinium salt 4a (50 mg, 0.10 mmol) dissolved in
a mixture of water (4 mL) and methanol (4 mL) deaerated with
nitrogen. The mixture was stirred in darkness, at room temperature
for 2h. The same amounts of NaHCO3 and Na2S2O4 were added
and the mixture was stirred for an additional time of 30 min.
After addition of ethyl acetate (10 mL) and phase separation, the
aqueous layer was extracted with ethyl acetate (3 ¥ 10 mL) and
the combined organic phases were washed with water (3 ¥ 10 mL).
After drying over MgSO4, solvent was removed under vacuum,
giving 1a (32.7 mg, 94%) as a yellow oil; 1H NMR (CDCl3,
300 MHz) d 7.29 (6H, m), 6.55 (1H, s), 6.34 (1H, s), 5.67 (1H,
brt, J = 5.7 Hz), 4.56 (2H, d, J = 5.7 Hz), 3.88 (3H, s), 3.81 (3H,
s), 3.75 (2H, s), 3.22 (3H, s); 13C NMR (CDCl3, 75 MHz) d 167.7,
N-Benzyl-1,4-dihydro-6,7-dimethoxy-1-[11C]methylquinoline-3-
carboxamide ([11C]1a). [11C]Methyl triflate was trapped at room
temperature into a reactor containing a solution of quinoline 3a
(1 mg, 3.1 mmol) in acetonitrile (150 mL). When all the radioactivity
was collected, a solution of Na2S2O4 (4 mg, 23 mmol) in water
(150 mL) was added in the reactor. After a time of 5 min, a solution
of Na2CO3 (2 mg, 18.9 mmol) in water (150 mL) was added in
the reactor. The resulting mixture was kept for 3 min at room
temperature. The purification was performed by reverse-phase
semi-preparative HPLC (Macherey Nagel nucleosil 100–5 protect1
column 10 ¥ 250 mm, 4 mL/min, l = 254 nm, CH3CN/H2O/Et3N
40:60:0.01). The fraction containing the labelled product [11C]1a
(tR = 16.5 min) was collected into a flask containing water (25 mL).
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 3666–3673 | 3671
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