T. Prashanth, et al.
Biomedicine&Pharmacotherapy112(2019)108707
189–192 °C. FT-IR (KBr, cm−1): 1665 (C]O). 1730 (acid, C]O),
3330–3380 (OH). 1H NMR (400 MHz) (DMSO-d6): δ 6.8–8.2 (m, 4H,
Ar–H), 9.1 (s, 1H, coumarin ring-H), 13.2 (s, 1H, COOH). 13C NMR
(100 MHz) (DMSO-d6) δ: 113.1, 121.5, 122.2, 125.5, 126.8, 128.4,
142.5, 150.1, 159.4, 166.2.LC–MS m/z 191.1 (M+1). Anal. Calcd. For
10.38%.
12c: 7-Fluoro-2-oxo-2H-chromene-3-carboxylic acid N'-[2-(qui-
nolin-8-yloxy)-acetyl]-hydrazide: Yield: 80%. mp 182–184 °C. FT-IR
(KBr, cm−1): 1630 (C]O), 1670 (C]O, amide), 3115–3220 (NH-NH).
1H NMR (400 MHz) (DMSO-d6): δ 5.0 (s, 2H, OCH2), 7.2–8.6 (m, 9H,
Ar–H), 9.10 (s, 1H, coumarin ring-H), 11.09 (s, 1H, -NH−CO) 12.36 (s,
1H, -NH of COCH2). 13C NMR (100 MHz) (DMSO-d6) δ: 68.7, 107.2,
109.6, 112.2, 114.1, 117.8, 120.4, 121.8, 126.8, 128.4, 129.3, 135.7,
138.5, 138.8, 149.0, 151.7, 155.4, 159.4, 162.5, 165.9, 166.3. LC–MS:
m/z 408.1 (M+1). Anal. Calcd. For C21H14FN3O5: C, 61.92; H, 3.46; N,
10.32. Found: C, 61.97; H, 3.49; N, 10.35%.
12d: 7-Methoxy-2-oxo-2H-chromene-3-carboxylic acid N'-[2-(qui-
nolin-8-yloxy)-acetyl]-hydrazide: Yield: 87%. mp 190–192 °C. FT-IR
(KBr, cm−1): 1630 (C]O), 1670 (C]O, amide), 3105–3210 (NH-NH).
1H NMR (400 MHz) (DMSO-d6): δ 3.7 (s, 3H, OCH3), 5.0 (s, 2H, OCH2),
7.2–8.2 (m, 9H, Ar–H), 9.10 (s, 1H, coumarin ring-H), 11.09 (s, 1H,
-NH−CO) 12.36 (s, 1H, -NH of COCH2). 13C NMR (100 MHz) (DMSO-
d6) δ: 55.8, 68.7, 107.2, 107.6, 111.0, 114.1, 114.5, 120.4, 121.8,
126.8, 127.8, 129.3, 135.7, 138.5, 138.8, 149.0, 151.1, 155.4, 159.4,
160.2, 165.9, 166.3. LC–MS: m/z 420.3 (M + 1). Anal. Calcd. For
C
10H6O4: C, 63.16; H, 3.18. Found: C, 63.10; H, 3.10%.
11b: 8-Methyl-2-oxo-2H-chromene-3-carboxylic acid: Yield: 84%.
mp 199–200 °C. FT-IR (KBr, cm−1): 1660 (C]O). 1725 (acid, C]O),
3325–3375 (OH). 1H NMR (400 MHz) (DMSO-d6): δ2.3 (s, 3H,
Ar−CH3), 6.8–8.2 (m, 3H, Ar–H), 9.1 (s, 1H, coumarin ring-H), 13.2 (s,
1H, COOH). 13C NMR (100 MHz) (DMSO-d6) δ: 18.7, 113.1, 122.1,
123.8, 125.4, 128.6, 131.7, 142.5, 150.4, 159.4, 166.2.LC–MS m/z
205.0 (M+1). Anal. Calcd. For C11H8O4: C, 64.70; H, 3.95. Found: C,
64.79; H, 3.90%.
11c: 7-Fluoro-2-oxo-2H-chromene-3-carboxylic acid: Yield: 89%.
mp 212–223 °C. FT-IR (KBr, cm−1): 1660 (C]O). 1735 (acid, C]O),
3320–3370 (OH), 1H NMR (400 MHz) (DMSO-d6): δ 6.8–8.2 (m, 3H,
Ar–H), 9.1 (s, 1H, coumarin ring-H), 13.2 (s, 1H, COOH). 13C NMR
(100 MHz) (DMSO-d6) δ: 109.6, 112.2, 113.1, 117.8, 128.4, 142.5,
151.7, 159.4, 162.5, 166.2. LC–MS m/z 209.1 (M + 1). Anal. Calcd. For
C
10H5FO4: C, 57.70; H, 2.42. Found: C, 57.62; H, 2.48%.
C22H17N3O6: C, 63.01; H, 4.09; N, 10.02. Found: C, 63.07; H, 4.02; N,
11d: 7-Methoxy-2-oxo-2H-chromene-3-carboxylic acid: Yield: 91%.
10.08%.
mp 184–186 °C. FT-IR (KBr, cm−1): 1655 (C]O), 1715 (acid, C]O),
3320–3370 (OH).1H NMR (400 MHz) (DMSO-d6): δ3.7 (s, 3H, OCH3),
6.8–8.2 (m, 3H, Ar–H), 9.1 (s, 1H, coumarin ring-H), 13.2 (s, 1H,
COOH). 13C NMR (100 MHz) (DMSO-d6) δ: 55.8, 113.1, 113.9, 119.1,
123.2, 126.5, 141.8, 142.5, 157.0, 159.4, 166.2. LC–MS m/z 221.0 (M
+1). Anal. Calcd. For C11H8O5: C, 60.00; H, 3.66. Found: C, 60.10; H,
3.70%.
2.1.7. General procedure for the synthesis of 2-oxo-2H-chromene-3-
carboxylic acid (4-phenyl-thiazol-2-yl)-amide analogs (13a-f)
To compounds [2-oxo-2H-chromene-3-carboxylic acids] (11a–d,
0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was
added at 25–30 °C, followed by the addition of compound (7a-b,
0.0037 mol) and the mixture was stirred at 25–30 °C for 30 min. The
reaction was cooled to 0–5 °C and TBTU (0.0037 mol) was added over a
period of 30 min while maintaining the temperature below 5 °C. The
reaction was stirred overnight and the completion of the reaction was
monitored by TLC using chloroform:methanol (9:1) as an eluent. The
reaction mixture was diluted with 20 mL of dichloromethane and wa-
shed with 1.5 N hydrochloric acid (20 mL). Then the organic layer was
washed with water (3 × 25 mL), dried over anhydrous sodium sul-
phate, concentrated to a syrupy liquid and recrystallized twice from
diethyl ether to afford compounds 13a-f in good yields.
13a: 2-Oxo-2H-chromene-3-carboxylic acid (4-phenyl-thiazol-2-yl)-
amide: Yield: 87%. mp 202–204 °C. FT-IR (KBr, cm−1): 1630 (C]O),
1670 (C]O, amide), 3145–3185 (N-H). 1H NMR (400 MHz) (DMSO-
d6): δ 7.0–7.8 (m, 10H, Ar–H), 8.3 (s, 1H, coumarin ring-H), 9.5 (s, 1H,
NH). 13C NMR (100 MHz) (DMSO-d6) δ: 100.0, 114.2, 121.5, 122.3,
125.5, 126.8, 127.5, 128.4, 128.8, 129.3, 133.1, 138.6, 148.2, 150.2,
159.5, 163.1, 164.3. LC–MS m/z 349.1 (M+1). Anal. Calcd. For C19H12
N2O3S: C, 65.50; H, 3.47; N, 8.04; S, 9.20. Found: C, 65.56; H, 3.51; N,
8.01; S, 9.26%.
13b: 2-Oxo-2H-chromene-3-carboxylic acid [4-(4-methoxy-phenyl)-
thiazol-2-yl]-amide: Yield: 82%. mp 185–187 °C. FT-IR (KBr, cm−1):
1635 (C]O), 1675 (C]O, amide), 3125–3165 (N-H). 1H NMR
(400 MHz) (DMSO-d6): δ 3.7 (s, 3H, OCH3), 7.0–7.8 (m, 9H, Ar–H), 8.3
(s, 1H, coumarin ring-H), 9.5 (s, 1H, NH). 13C NMR (100 MHz) (DMSO-
d6) δ: 55.8, 99.9, 114.1, 114.8, 121.5, 122.2, 125.5, 126.8, 128.5,
138.5, 148.1, 150.1, 159.4, 160.6, 163.0, 164.2. LC–MS m/z 379.1
(M + 1). Anal. Calcd. For C20H14 N2O4S: C, 63.48; H, 3.73; N, 7.40; S,
8.47. Found: C, 63.42; H, 3.68; N, 7.46; S, 8.41%.
2.1.6. General procedure for the synthesis of 2-oxo-2H-chromene-3-
carboxylic acid N'-[2-(quinolin-8-yloxy)-acetyl]-hydrazide analogs (12a-
d)
To compounds [2-oxo-2H-chromene-3-carboxylic acid] (11a-d,
0.0037 mol) in dry dichloromethane (15 mL), lutidine (1.2 vol.) was
added at 25–30 °C, followed by the addition of compound (4,
0.0037 mol) and the mixture was stirred at 25–30 °C for 30 min. The
reaction was cooled to 0–5 °C and TBTU (0.0037 mol) was added over a
period of 30 min while maintaining the temperature below 5 °C. The
reaction was stirred overnight and monitored by TLC using chloroform:
methanol (9:1) as an eluent. The reaction mixture was diluted with
20 mL of dichloromethane and washed with 1.5 N hydrochloric acid
(20 mL). The organic layer was washed with water (3 × 25 mL), dried
over anhydrous sodium sulphate, concentrated to a syrupy liquid and
recrystallized twice from diethyl ether to afford compounds 12a-d in
good yields.
12a: 2-Oxo-2H-chromene-3-carboxylic acid N'-[2-(quinolin-8-
yloxy)-acetyl]-hydrazide: Yield: 85%. mp 180–184 °C. FT-IR (KBr,
cm−1): 1630 (C]O), 1670 (C]O, amide), 3100–3205 (NH-NH). 1H
NMR (400 MHz) (DMSO-d6): δ 5.0 (s, 2H, OCH2), 7.2–8.6 (m, 10H,
Ar–H), 9.08 (s, 1H, coumarin ring-H), 11.0 (s, 1H, eNHeCO) 12.3 (s,
1H, eNH of COCH2). 13C NMR (100 MHz) (DMSO-d6) δ: 68.7, 107.2,
114.1, 120.4, 121.5, 121.8, 122.2, 125.5, 126.8, 128.4, 129.3, 135.7,
138.5, 138.8, 149.0, 150.1, 155.4, 159.4, 166.3, 165.9, 166.4. LC–MS:
m/z 390.4 (M+1). Anal. Calcd. For C21H15N3O5: C, 64.78; H, 3.88; N,
10.79. Found: C, 64.71; H, 3.81; N, 10.71%.
12b: 8-Methyl-2-oxo-2H-chromene-3-carboxylic acid N'-[2-(qui-
nolin-8-yloxy)-acetyl]-hydrazide: Yield: 86%. mp 120–122 °C. FT-IR
(KBr, cm−1): 1630 (C]O), 1670 (C]O, amide), 3110–3215 (NH-NH).
1H NMR (400 MHz) (DMSO-d6): δ 2.3 (s, 3H, Ar−CH3), 5.0 (s, 2H,
OCH2), 7.0–8.6 (m, 9H, Ar–H), 9.10 (s, 1H, coumarin ring-H), 11.09 (s,
1H, -NH−CO) 12.36 (s, 1H, -NH of COCH2). 13C NMR (100 MHz)
(DMSO-d6) δ: 18.7, 68.7, 107.2, 114.1, 120.4, 120.6, 121.8, 122.1,
123.8, 125.4, 126.8, 129.3, 131.7, 135.7, 138.5, 138.8, 149.0, 150.4,
155.4, 159.4, 166.3. 165.9.LC–MS: m/z 404.1 (M + 1). Anal. Calcd. For
13c: 8-Methyl-2-oxo-2H-chromene-3-carboxylic acid (4-phenyl-
thiazol-2-yl)-amide: Yield: 85%. mp 160–162 °C. FT-IR (KBr, cm−1):
1630 (C]O), 1670 (C]O, amide), 3115–3145 (N-H). 1H NMR
(400 MHz) (DMSO-d6): δ2.3 (s, 3H, Ar−CH3), 7.0–7.8 (m, 9H, Ar–H),
8.3 (s, 1H, coumarin ring-H), 9.5 (s, 1H, NH). 13C NMR (100 MHz)
(DMSO-d6) δ: 18.7, 99.9, 114.1, 122.1, 123.8, 125.4, 127.5, 128.6,
128.8, 129.3, 131.7, 133.0, 138.5, 148.1, 150.4, 159.4, 163.0, 164.2.
LC–MS m/z 363.1 (M + 1). Anal. Calcd. For C20H14 N2O3S: C, 66.28; H,
3.89; N, 7.73; S, 8.85. Found: C, 66.22; H, 3.83; N, 7.77; S, 8.89%.
C
22H17N3O5: C, 65.50; H, 4.25; N, 10.42. Found: C, 65.51; H, 4.21; N,
13d:
8-Methyl-2-oxo-2H-chromene-3-carboxylic
acid
[4-(4-
3