May 2009
Syntheses and Fluorescent Properties of 2-Amino Substituted
6,7-Dimethoxy-4-(trifluoromethyl)quinolines
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(0.532 g, 1 mmol) and conc. hydrochloric acid (7 mL) in
methanol (8 mL) was heated under TLC monitoring for 5 h
under reflux. The reaction mixture was cooled to room temper-
ature, the formed solid filtered by suction and washed with
excess of water until pH of 7 was reached. The yield was
0.262 g (96%), yellowish green crystals, m.p. 283–284ꢀC
(ethanol); IR: 3345 s, 3090 s, 1680 s, 1647 m, 1618 w, 1520
prisms, m.p. 272–273ꢀC (acetone); IR: 3366 w, 2933 m, 1647
w, 1625 w, 1603 s, 1575 w cmꢂ1 1H NMR (CDCl3): d 3.33
;
and 3.41 (2 dd, J ¼ 5.7 and 13.9 Hz, 2H, CH2), 3.99 and 4.05
(2 s, 6H, 2 OMe), 5.09 (dd, 5.8 and 6.7 Hz, 1H, CH), 6.87 (d,
J ¼ 5.9 Hz, 1H, amide-NH), 7.18–7.24 (m, 6H, ArH),
7.30 and 7.33, (2 s, 2H, ArH), 7.37 (d, J ¼ 8.2 Hz, 2H, ArH),
7.75 (d, J ¼ 8.3 Hz, 2H, ArH), 10.20 (s, 1H, 2-NH); MS: m/z
(%) ¼ 541 (11, M þ 2), 540 (47, M þ 1), 539 (100, M), 538
(35, M ꢂ 1), 391 (14); Anal. Calcd. for C28H24F3N3O5
(539.52): C, 62.34; H, 4.48; N, 7.79; Found C, 61.91; H, 4.37;
N, 7.63.
m cmꢂ1 1H NMR (DMSO-d6): d 3.87 and 3.94 (2 s, 6H,
;
OMe), 7.09 (s, 1H, ArH), 7.32 (s, 1H, ArH), 7.38 (s, 1H,
ArH), 8.62 (s, b, 2H, NH2); Anal. Calcd. for C12H11F3N2O2
(272.23): C, 52.95; H, 4.07; N, 10.29; Found: C, 52.65; H,
3.78; N, 10.02.
N-(4-{[6,7-Dimethoxy-4-(trifluoromethyl)quinolin-2-yl]am-
ino}benzoyl)glycylglycylglycine (12). To a solution of glycyl-
glycyl-glycine (38 mg, 0.2 mmol) in dimethyl-sulfoxide/water
(9:1, 2.5 mL), a solution of OSu-ester 10 (98 mg, 0.2 mmol)
in dimethylsulfoxide/water (9:1, 2.5 mL) was added dropwise
at room temperature. Then aq. pH 7 buffer (0.75 mL) was
added, the mixture stirred for 14 h at 50ꢀC, poured into water
(25 mL), and then acidified with conc. hydrochloric acid to pH
¼ 1–2. A solid separated, which was filtered by suction and
washed with excess of water to afford 75 mg (53%) of yellow
prisms, m.p. 238–239ꢀC (acetone); IR: 3338 s, 3306 s, 3117
m, 3088 m, 2961 w, 2925 m, 1721 s, 1662 s, 1625 w, 1605 s,
4-{[6,7-Dimethoxy-4-(trifluoromethyl)quinolin-2-yl]amino}
benzoic acid (9). A mixture of 4-(quinolin-2-yl)aminobenzoate
4b (0.420 g, 1 mmol) and 1M aq. sodium hydroxide solution
(2 mL) in ethanol (20 mL) was heated for 7 h under reflux,
then the solvent was removed under reduced pressure and the
residue dissolved in water (10 mL) under cooling. The mixture
was acidified with conc. hydrochloric acid to pH ¼ 1–2, the
resulting precipitate filtered by suction and washed with excess
of water. The yield was 0.310 g (80%), yellow prisms, m.p.
275–276ꢀ C (ethyl acetate); IR: 3457 s, 2940 w, 1677 s, 1624
w, 1600 s, 1526 s cmꢂ1 1H NMR (DMSO-d6): d 3.87 and
;
1
3.96 (2 s, 6H, 2 OMe), 7.10 (s, 1H, ArH), 7.36 (s, 1H, ArH),
7.38 (s, 1H, ArH), 7.91 (d, J ¼ 8.6 Hz, 2H, ArH), 8.04 (d, J
¼ 8.6 Hz, 2H, ArH), 9.95 (s, 1H, NH), 12.54 (s, 1H, OH);
MS: m/z (%) ¼ 393 (18, M þ 1), 392 (100, M), 377 (12);
Anal. Calcd. for C19H15F3N2O4 (392.34): C, 58.17; H, 3.85; N,
7.14; Found: C, 57.82; H, 3.76; N, 7.00.
1568 w, 1531 s cmꢂ1; H NMR (DMSO-d6): d 3.76–3.78 (m,
4H, 2 CH2), 3.87 (s, 3H, OMe), 3.90 (d, J ¼ 5.4 Hz, 2H,
CH2), 3.97 (s, 3H, OMe), 7.11 (s, 1H, ArH), 7.35 and 7.39 (2
s, 2H, ArH), 7.88 (d, J ¼ 8.6 Hz, 2H, ArH), 8.01 (d, J ¼ 8.3
Hz, 2H, ArH), 8.17–8.24 (m, 2H, amide-NH), 8.64 (t, J ¼ 5.3
Hz, 1H, amide-NH), 9.91 (s, 1H, 2-NH); MS: m/z (%) ¼
564 (14, M þ 1), 563 (42, M), 507 (17), 450 (25), 449
(100), 392(85); Anal. Calcd. for C25H24F3N5O7 (563.49):
Calcd. C, 53.29; H, 4.29; N, 12.43; Found C, 53.63; H, 4.29;
N, 12.56.
1[(4-{[6,7-Dimethoxy-4-(trifluoromethyl)quinolin-2-yl]am-
ino}benzoyl)oxy]pyrrolidine-2,5-dione (OSu-ester) (10). N-
Hydroxysuccinimide (0.115 g, 1 mmol) was added slowly with
stirring at 0ꢀC to a solution of 4-(quinolin-2-yl)amino-benzoic
acid 9 (0.392 g, 1 mmol) in dry tetrahydrofuran (20 mL).
Then N,N-diisopropylcarbodiimide (0.125 g, 1 mmol) was
added dropwise with stirring at 0–5ꢀC which formed a yellow-
ish-white precipitate. This mixture was stirred further at 0–5ꢀC
for 14–15 h. The solvent was removed under reduced pressure
and the solid residue obtained was digested in dry tetrahydro-
furan (10 mL), filtered and washed well with dry tetrahydrofu-
ran. Then the solid was stirred in dry ethanol (50 mL) at room
temperature for 30 min to remove N,N-diisopropylurea formed
during the reaction. Suction filtration afforded 0.288 g (59%)
of OSu-ester, pale yellow prisms, m.p. 268–269ꢀC (ethanol);
IR: 3435 s, 3340 s, 3212 m, 1765 s, 1723 s, 1618 w, 1598 s,
1578 w cmꢂ1;1H NMR (CDCl3): d 2.93 (s, 4H, 2 CH2), 4.03
and 4.09 (2 s, 6H, 2 OMe), 7.22 (s, 1H, ArH), 7.25 (s, 1H,
ArH), 7.33 (s, 1H, ArH), 7.77 (d, J ¼ 8.4, 2H, ArH), 8.16 (d,
J ¼ 8.6, 2H, ArH); MS: m/z (%) ¼ 490 (25, M þ 1), 489
(100, M), 392 (10); Anal. Calcd. for C23H18F3N3O6 (489.41):
C, 56.45; H, 3.71; N, 8.59; Found: C, 56.44; H, 3.89; N, 8.30.
N-(4-{[6,7-Dimethoxy-4-(trifluoromethyl)quinolin-2-yl]am-
ino}benzoyl)phenylalanine (11). To a solution of (D,L)pheny-
lalanine (38 mg, 0.2 mmol) in dimethyl-sulfoxide/water (9:1,
2.5 mL), a solution of OSu-ester 10 (98 mg, 0.2 mmol) in
dimethylsulfoxide/water (9:1, 2.5 mL) was added dropwise at
room temperature. Then aq. pH 7 buffer (0.75 mL) was added,
the mixture stirred for 14 h at 50ꢀC, poured into water (25
mL) and then acidified with conc. hydrochloric acid to pH ¼
1–2. A solid separated, which was filtered by suction and
washed with excess of water to afford 85 mg (63%) of yellow
Acknowledgments. This research was supported by scholar-
ships from the Austrian Exchange Service/Academic Coopera-
tion and Mobility Unit (N.S.B. and A.B.A).
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In Proceedings of ECSOC-10, 10th International Electronic Conference
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet