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K.D. Thomas et al. / European Journal of Medicinal Chemistry 46 (2011) 5283e5292
4.5.10. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
(2-fluoro-4-methoxy-benzylidene)-hydrazide (5j)
4.5.16. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
pyridin-4-ylmethylene-hydrazide (5p)
Appearance: white solid; m.p. 334.2 ꢀC; IR (KBr, cmꢁ1
)
n
: 3430
(OeH), 3248 (NH), 1672 (C]O), 1607 (C]N), 1164 (CeF); 1H NMR
(300 MHz, CDCl3) ppm 3.83 (s, 3H, OCH3), 6.913 (m, 2H, ArH), 7.68
Appearance: pale yellow solid; m.p. 351.5 ꢀC; 1H NMR
(300 MHz, CDCl3)
d
ppm 7.61 (t, 1H, ArH, J ¼ 7.8 Hz), 8.16 (d, 1H,
d
ArH, J ¼ 7.5 Hz), 8.20e8.23 (m, 4H, ArH), 8.55 (d, 1H, ArH,
J ¼ 7.8 Hz), 8.65 (s, 1H, ArH,), 8.73 (s, 1H, C]NH), 10.52 (br s, 1H,
OH), 12.78 (s, 1H, NH); LC/MS (ESI) m/z 361.09 (M þ 1).
(t, 1H, ArH, J ¼ 7.5 Hz), 7.84 (t, 1H, ArH, J ¼ 8.7 Hz), 8.22 (d, 1H, ArH,
J ¼ 7.2 Hz), 8.49 (s, 1H, ArH), 8.62 (t, 1H, ArH, J ¼ 8.55 Hz), 8.73 (s,
1H, ArH), 12.14 (br s, 1H, OH), 12.89 (s, 1H, NH); 13C NMR (CDCl3,
75 MHz)
d
56.39,101.83,102.16,111.90,112.13,114.63,114.77,125.02,
4.5.17. 4-Hydroxy-N0-[(E)-(4-methylphenyl)methylidene]-8-
(trifluoromethyl)quinoline-3-carbohydrazide (5q)
125.74, 127.66, 128.10, 131.49, 135.53, 141.70, 145.88, 160.54, 160.87,
162.70, 162.85, 163.87, 175.65; LC/MS (ESI) m/z 408.09 (M þ 1).
Appearance: white solid; m.p. 292.6e292.9 ꢀC; 1H NMR
(300 MHz, CDCl3)
d ppm 2.34 (s, 3H, CH3), 7.03 (d, 2H, ArH,
4.5.11. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
[4-(1,1,2,2-tetrafluoro-ethoxy)-benzylidene]-hydrazide (5k)
Appearance: pale yellow solid; m.p. 283.6e283.7 ꢀC; 1H NMR
J ¼ 9.0 Hz), 7.64 (d, 2H, ArH, J ¼ 9.0 Hz), 7.72 (s, 1H, ArH), 8.25 (d,
1H, ArH, J ¼ 7.2 Hz), 8.39 (s, 1H, ArH), 8.63 (d, 1H, ArH, J ¼ 7.8 Hz),
8.74 (s, 1H, C]NH), 12.24 (br s, 1H, OH), 12.86 (s, 1H, NH); 13C NMR
(300 MHz, CDCl3)
d
ppm 6.68e7.05 (m, 2H, ArH), 7.68 (t, 1H, ArH,
(CDCl3, 75 MHz) d 21.23, 112.0, 112.36, 114.77, 117.82, 118.24, 122.11,
J ¼ 7.5 Hz), 7.84 (t, 1H, ArH, J ¼ 8.7 Hz), 8.22 (d, 1H, ArH, J ¼ 7.2 Hz),
8.49 (s, 1H, ArH), 8.62 (t, 1H, ArH, J ¼ 8.55 Hz), 8.73 (s, 1H, ArH),
12.14 (br s, 1H, OH), 12.89 (s, 1H, NH); 13C NMR (CDCl3, 75 MHz)
124.95, 125.73, 127.33, 127.62, 129.30, 131.47, 135.41, 145.70,
148.55, 154.36, 160.13, 160.62, 161.39, 175.71, 175.99; LC/MS (ESI)
m/z 374.11 (M þ 1).
d
108.28,111.61, 116.90, 117.78, 118.20, 119.64, 122.03, 123.41, 124.99,
125.65, 126.53, 127.53, 131.11, 131.41, 131.60, 135.32, 136.98, 145.86,
147.13, 148.88, 160.99,175.68; LC/MS (ESI) m/z 475.9 (M þ 1).
4.6. General procedure for the synthesis of 2-{[4-hydroxy-8-
(trifluoromethyl)quinolin-3-yl]carbonyl}hydrazinecarbothioamide
derivatives (6aee)
4.5.12. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
(2-methylsulfanyl-benzylidene)-hydrazide (5l)
A
suspension of 4 (1 mmol), substituted isothiocyanates
Appearance: white solid; m.p. 369.3e370.5 ꢀC (decomp); 1H
(1.5 mmol) and a catalytic amount of pyridine (0.2 mmol) in
ethanol (10 mL) was heated under reflux on oil bath for 3 h. Reac-
tion completion was monitored by TLC. After the completion of the
reaction, the solvent was concentrated and the solid thus obtained
was recrystallized from ethanol.
NMR (300 MHz, CDCl3) d ppm 2.52 (s, 3H, SCH3), 7.28 (m, 1H, ArH),
7.44 (d, 2H, ArH, J ¼ 3.9 Hz), 7.70 (t, 1H, ArH, J ¼ 7.8 Hz), 7.86 (d, 1H,
ArH, J ¼ 7.8 Hz), 8.25 (d, 1H, ArH, J ¼ 7.5 Hz), 8.64 (d, 1H, ArH,
J ¼ 8.1 Hz), 8.76 (s, 2H, ArH), 12.23 (s, 1H, OH), 12.98 (s, 1H, NH); 13C
NMR (CDCl3, 75 MHz)
d 111.88, 117.27, 117.69, 118.10, 118.45, 118.52,
122.07, 124.21, 125.69, 127.52, 127.86, 128.12, 129.04, 129.30, 130.83,
130.86, 130.93, 131.0, 131.06, 131.23,131.61, 135.49, 137.44, 139.54,
144.73, 163.72, 175.17; LC/MS (ESI) m/z 406.08 (M þ 1).
4.6.1. 2-{[4-Hydroxy-8-(trifluoromethyl) quinolin-3-yl]carbonyl}-
N-(pyridin-3-yl)hydrazinecarbothioamide (6a)
Appearance: white solid; m.p. 222.7e223 ꢀC; 1H NMR
(300 MHz, CDCl3)
d
ppm 7.61 (t, 1H, ArH, J ¼ 7.8 Hz), 8.16 (d, 1H,
4.5.13. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
(5-fluoro-2-hydroxy-benzylidene)-hydrazide (5m)
ArH, J ¼ 7.5 Hz), 8.20e8.23 (m, 2H, ArH), 8.27e8.29 (m, 2H, ArH),
8.55 (d, 1H, ArH, J ¼ 7.8 Hz), 8.65 (s, 1H, ArH), 9.30 (br s, 1H, NH),
9.95 (br s, 1H, NH), 10.52 (br s, 1H, OH), 12.78 (s, 1H, NH); LC/MS
(ESI) m/z 408.07 (M þ 1).
Appearance: white solid; m.p. 396.8e397.2 ꢀC (decomp); 1H
NMR (300 MHz, CDCl3)
d
ppm 6.94 (dd, 1H, ArH, J ¼ 4.8 Hz), 7.16 (m,
1H, ArH), 7.37 (d, 1H, ArH, J ¼ 3.1 Hz), 7.70 (t, 1H, ArH, J ¼ 8.1 Hz),
8.25 (d, 1H, ArH, J ¼ 7.5 Hz), 8.66 (m, 2H, ArH), 8.75 (s, 1H, ArH),
11.01 (s, 1H, OH), 13.06 (s, 1H, NH); LC/MS (ESI) m/z 393.9 (M þ 1).
4.6.2. N-(3-chlorophenyl)-2-{[4-hydroxy-8-(trifluoromethyl)
quinolin-3-yl]carbonyl}hydrazinecarbothioamide (6b)
Appearance: white solid; m.p.178.6e178.9 ꢀC; 1H NMR (300 MHz,
4.5.14. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
(4-methoxy-benzylidene)-hydrazide (5n)
CDCl3)
d
ppm 7.18 (d, 1H, ArH, J ¼ 7.8 Hz), 7.35 (t, 1H, ArH, J ¼ 7.8 Hz),
7.49 (d, 1H, ArH, J ¼ 7.5 Hz) 7.62e7.69 (m, 1H, ArH), 7.78 (s, 1H, ArH),
Appearance: white solid; m.p. 368e368.8 ꢀC (decomp); 1H NMR
8.23 (t, 1H, ArH, J ¼ 8.1 Hz), 8.58e8.67 (m, 2H, ArH), 9.93 (br s, 3H,
(300 MHz, CDCl3)
d
ppm 3.81 (s, 3H, OCH3), 7.036 (d, 2H, ArH,
NH), 10.62 (br s, 1H, OH); 13C NMR (CDCl3, 75 MHz)
d 111.78, 117.83,
J ¼ 9.0 Hz), 7.68 (d, 2H, ArH, J ¼ 9.0 Hz), 7.72 (s, 1H, ArH), 8.25 (d, 1H,
ArH, J ¼ 7.2 Hz), 8.39 (s, 1H, ArH), 8.63 (d, 1H, ArH, J ¼ 7.8 Hz), 8.74
(s, 1H, ArH), 12.24 (br s, 1H, OH), 12.86 (s, 1H, NH); 13C NMR (CDCl3,
118.50, 121.16, 122.11, 123.0, 124.02, 125.74, 127.70, 128.63, 129.34,
130.18, 131.36, 131.46, 131.55, 131.65, 132.73, 135.46, 135.56, 141.27,
141.40,144.96,143.39,163.54,175.34; LC/MS (ESI) m/z 441.03 (M þ 1).
75 MHz)
d 55.77, 112.0, 112.36, 114.77, 117.82, 118.24, 122.11, 124.95,
125.73, 127.33, 127.62, 129.30, 131.47, 135.41, 145.70, 148.55, 154.36,
160.13,160.62,161.39,175.71,175.99; LC/MS (ESI) m/z 390.0 (M þ 1).
4.6.3. N-(2-fluorophenyl)-2-{[4-hydroxy-8-(trifluoromethyl)
quinolin-3-yl]carbonyl}hydrazinecarbothioamide (6c)
Appearance: off white solid; m.p. 187.6e187.8 ꢀC; 1H NMR
4.5.15. 4-Hydroxy-8-trifluoromethyl-quinoline-3-carboxylic acid
(3-hydroxy-4-methoxy-benzylidene)-hydrazide (5o)
(300 MHz, CDCl3) d ppm 7.14e7.25(m, 3H, ArH), 7.61e7.70 (m, 2H,
ArH), 8.23 (t, 1H, ArH, J ¼ 8.1 Hz), 8.58e8.68 (m, 2H, ArH), 9.56 (br s,
Appearance: pale yellow solid; m.p. 287.4 ꢀC; 1H NMR
2H, NH), 9.93e10.01(br s, 1H, NH), 10.62 (br s, 1H, OH); 13C NMR
(300 MHz, CDCl3)
d
ppm 3.81 (s, 3H, OCH3), 6.99 (d, 1H, ArH,
(CDCl3, 75 MHz) d 111.89, 115.82, 116.09, 118.21, 124.36, 124.62,
J ¼ 2.4 Hz), 7.10e7.14 (m, 1H, ArH), 7.29 (d, 1H, ArH, J ¼ 1.5 Hz),
7.63e7.70 (m, 2H, ArH), 8.22e8.29 (m, 2H, ArH), 8.57e8.70 (m, 3H,
ArH), 8.74 (s, 1H, C]NH), 9.30 (br s, 1H, OH), 12.55 (s, 1H, OH), 12.78
124.96, 125.79, 127.53, 127.66, 128.64, 129.35, 131.33, 131.47, 135.60,
144.90, 163.55, 175.35; LC/MS (ESI) m/z 425.6 (M þ 1).
(s, 1H, NH); 13C NMR (CDCl3, 75 MHz)
d
56.11, 112.01, 112.44, 113.14,
4.6.4. 2-{[4-Hydroxy-8-(trifluoromethyl)quinolin-3-yl]carbonyl}-
N-(4-methylphenyl)hydrazinecarbothioamide (6d)
117.91, 118.32, 120.90, 122.13, 124.93, 125.75, 127.64, 131.48, 135.55,
145.79, 147.33, 148.79, 149.24, 150.36, 154.38, 160.17, 160.63, 175.69;
LC/MS (ESI) m/z 406.10 (M þ 1).
Appearance: pale yellow solid; m.p. 196.8e197 ꢀC; 1H NMR
(300 MHz, CDCl3)
d ppm 2.34 (s, 3H, CH3), 7.03 (d, 2H, ArH,