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argon. After the addition, the mixture was warmed to
room temperature and stirred for 20 h. The solution was
diluted with CH2Cl2 and washed with a saturated
NH4Cl aqueous solution, and the organic layer was
dried over Na2SO4. Evaporation of the solvent afforded
a crude which was chromatographed (hexane–AcOEt
4:6) to yield the triflate 3 (232 mg, 76%) as pale yellow
crystals. (Found: C, 37.51; H, 2.60; N, 7.37; S, 8.27.
C12H9F3SN2O7 requires: C, 37.70; H, 2.37; N, 7.33; S,
8.39); mp 146–148 ꢀC; nmax (KBr): 1600, 1427, 1239,
1033 cmꢁ1; dH (CDCl3, 300 MHz) 9.09 (d, J=4.6 Hz,
1H), 7.46 (s, 1H), 7.45 (d, J=4.6 Hz, 1H), 4.13 (s, 3H),
4.01 (s, 3H). dC (CDCl3, 75 MHz) 153.5, 152.3 (two sig-
nals), 144.4, 142.0, 141.5, 118.6 (q, J=321 Hz), 118.2,
116.2, 103.9, 64.5, 56.9.
(CDCl3, 300 MHz) 8.86 (br. s, 1H), 7.79 (d, J=7.5 Hz,
1H), 7.46 (m, 3H), 7.27 (m, 1H), 7.19 (t, J=6.7 Hz, 1H),
6.01 (s, 1H), 4.10 (s, 3H), 2.95 (s, 3H), 1.29 (s, 9H). dC
(CDCl3, 75 MHz) 152.8, 148.9, 147.1, 142.1, 138.2,
135.9, 131.5, 130.2, 129.4, 128.9, 126.4, 124.9, 123.3,
123.2, 121.7, 104.3, 80.5, 59.7, 56.6, 27.9.
4-(2-tertButyloxycarbonylaminophenyl)-6-(2,2-dimethyl-
4,6-dioxo-1,3-dioxan-5-ylidene-methylamino)-5,8-dimeth-
oxyquinoline (7). A solution of Meldrum’s acid (519 mg,
3.6 mmol) in triethyl ortoformate (8 mL) was refluxed
for 2 h under argon. The reaction mixture was added to
compound 6 (1.18 g, 3 mmol) and the solution thus
obtained was refluxed for 4 h. After cooling to 0 ꢀC, the
precipitated crystals were filtered and washed with
methanol to yield compound 7 as a yellow solid (750
mg, 72%). (Found: C, 63.14; H, 5.68; N, 7.58.
C29H31N3O8 requires: C, 63.38; H, 5.69; N, 7.65); mp
292–294 ꢀC; nmax (KBr): 3114, 1702, 1676, 1618, 1271
cmꢁ1; dH (CDCl3, 300 MHz) 8.95 (d, J=4.2 Hz, 1H),
8.74 (d, J=14.4 Hz, 1H), 7.90 (d, J=7.6 Hz, 1H), 7.44
(t, J=7.3 Hz, 1H), 7.37 (d, J=4.2 Hz, 1H), 7.26 (m,
1H), 7.17 (t, J=7.3 Hz, 1H), 7.07 (s, 1H), 5.91 (s, 1H),
4.19 (s, 3H), 3.09 (s, 3H), 1.75 (s, 6H), 1.30 (s, 9H); dC
(CDCl3, 75 MHz): 165.1, 163.6, 154.3, 152.8, 150.3,
148.8, 142.8, 139.6, 137.8, 135.9, 131.6, 129.4, 129.1,
128.7, 126.4, 123.2, 122.8, 121.5, 105.3, 95.7, 88.2, 80.5,
61.9, 56.8, 28.1, 27.1, 27.0.
4-Bromo-5,8-dimethoxy-5-nitroquinoline (4). A suspen-
sion of the triflate 3 (400 mg, 1.05 mmol) and lithium
bromide (273 mg, 3.15 mmol) in 1,4-dioxane (4 mL) was
refluxed for 2 h under argon. After cooling to room
temperature, the mixture was diluted with AcOEt and
washed with H2O and the organic layer was dried over
Na2SO4. Evaporation of the solvent gave the bromo
derivative 4 (328 mg, 100%), as pale yellow crystals.
(Found: C, 42.43; H, 2.93; N, 8.93. C11H9BrN2O4
requires: C, 42.20; H, 2.90; N, 8.95); mp 180–182 ꢀC;
nmax (KBr): 1602; 1492; 1360; 1242; 1005 cmꢁ1; dH
(CDCl3, 300 MHz) 8.69 (d, J=4.6 Hz, 1H), 7.85 (d,
J=4.6 Hz, 1H), 7.35 (s, 1H), 4.08 (s, 3H), 3.92 (s, 3H).
dC (CDCl3, 75 MHz) 152.2, 150.6, 143.6, 143.5, 141.3,
130.1, 123.1, 103.0, 100.5, 64.5, 56.7.
4-(2-Trifluoracetamidophenyl)-6-(2,2-dimethyl-4,6-dioxo-
1,3-dioxan-5-ylidenemethyl-amino)-5,8-dimethoxyquino-
line (8). To a solution of compound 7 (487 mg, 1.2
mmol) in trifluoroacetic acid (8 mL) was added tri-
fluoroacetic anhydride (4 mL) at 0 ꢀC and under argon.
After the addition, the reaction mixture was allowed to
warm to room temperature, stirred for 90 min and eva-
porated. The crude was dissolved in CH2Cl2, washed
with 0.1 M HNaCO3 and a saturated aqueous NaCl
solution, and dried over Na2SO4. Evaporation of the
solvent gave compound 8 (484 mg, 100%), as pale yel-
low crystals. (Found: C, 57.18; H, 4.06; N, 7.41.
C26H22N3O7F3 requires: C, 57.25; H, 4.07; N, 7.70); mp
229–231 ꢀC; nmax (KBr): 3418, 1734, 1684, 1618, 1275
cmꢁ1; dH (CDCl3, 300 MHz) 8.92 (d, J=4.3 Hz, 1H),
8.75 (d, J=14.0 Hz, 1H), 7.83 (d, J=7.5 Hz, 1H), 7.72
(s, 1H), 7.53 (td, J=6.7 and 2.0 Hz, 1H), 7.44 (m, 2H),
7.37 (d, J=4.3 Hz, 1H), 7.10 (s, 1H), 4.16 (s, 3H), 3.06
(s, 3H), 1.73 (s, 3H), 1.72 (s, 3H). dC (CDCl3, 75 MHz):
165.2, 163.4, 155.0, 154.5, 150.3, 148.7, 141.4, 139.1,
136.6, 134.4, 132.9, 129.9, 129.5, 129.0, 126.7, 126.5,
123.6, 121.9, 115.3 (q, J=289 Hz), 105.3, 95.8, 88.5,
62.0, 56.8, 27.1, 26.9.
4-(2-tertButyloxycarbonylaminophenyl)-5,8-dimethoxy-
6-nitroquinoline (5). A suspension of compound 4 (498
mg, 1.6 mmol), tributyl (o-tertbutyloxycarbonyl-
aminophenyl) stannane10 (1.02 g, 2.86 mmol) and
bis(acetonitrile)dichloropalladium (II) (54 mg, 0.21
mmol) in 1,4-dioxane (13 mL) was heated at 55 ꢀC for
14 h, under an argon atmosphere. The cooled reaction
mixture was diluted with AcOEt and washed with H2O,
and the organic layer was dried over Na2SO4. The
resulting crude was chromatographed (CH2Cl2/AcOEt
8:2) to afford compound 5 (680 mg, 100%), as pale yel-
low crystals. (Found: C, 62.11; H, 5.46; N, 9.75.
C22H23N3O6 requires C, 62.11; H, 5.45; N, 9.88); mp
194–196 ꢀC; nmax (KBr): 3222; 1724; 1532; 1508; 1236;
1162 cmꢁ1; dH (CDCl3, 300 MHz) 9.04 (d, J=4.1 Hz,
1H), 7.88 (d, J=7.8 Hz, 1H), 7.41 (m, 3H), 7.19 (m,
2H), 5.95 (s, 1H), 4.13 (s, 3H), 3.17 (s, 3H), 1.30 (s, 9H).
dC (CDCl3, 75 MHz) 152.7, 152.4, 151.5, 145.8, 145.6,
143.0, 140.3, 135.6, 131.9, 129.0, 128.9, 126.7, 126.3,
123.1, 121.6, 102.7, 80.6, 63.1, 56.6, 28.0.
6-Amino-4-(2-tertbutyloxycarbonylaminophenyl)-5,8-di-
methoxyquinoline (6). To a solution of the nitro deriva-
tive 5 (67 mg, 0.16 mmol) in ethanol (5 mL) was added
10% Pd/C (100 mg) and cyclohexene (0.081 mL, 0.8
mmol). After being refluxed for 45 min, the solution was
cooled to room temperature, filtered and evaporated to
yield the amine 6 (62 mg, 100%), as red crystals.
(Found: C, 66.54; H, 6.09; N, 10.42. C22H25N3O4
requires C, 66.82; H, 6.37; N, 10.63); mp 170–172 ꢀC;
nmax (KBr): 3388, 1707, 1618, 1241, 1161 cmꢁ1. dH
4-(2-Trifluoracetamidophenyl)-6-(2,2-dimethyl-4,6-dioxo-
1,3-dioxan-5-ylidenemethylamino)-5,8-quinolinequinone
(9). To a solution of compound 8 (150 mg, 0.27 mmol)
in CH3CN (2.1 mL) was added a solution of ammonium
cerium (IV) nitrate (636 mg, 1.16 mmol) in 2M H2SO4
(3 mL). After stirring for 3 h, the reaction mixture was
partitioned between AcOEt and saturated aqueous
NH4Cl solution. The organic layer was dried over
Na2SO4, and evaporation of the solvent gave a residue
which was purified by flash column chromatography