S. Han et al. / European Journal of Medicinal Chemistry 93 (2015) 16e32
29
98.64%. 1H NMR (CDCl3, 500 MHz):
d
8.86 (s, 1H), 8.81 (d, J ¼ 8.5 Hz,
acetonitrile in water): tR ¼ 4.40 min, 100.0%. 1H NMR (CDCl3,
1H), 7.27e7.21 (m, 2H), 7.16 (d, J ¼ 7.5 Hz,1H), 4.12 (t, J ¼ 6.5 Hz, 2H),
4.09e4.02 (m, 1H), 1.89e1.81 (m, 3H), 1.58e1.51 (m, 2H), 1.19 (d,
J ¼ 6.5 Hz, 3H), 1.01e0.95 (m, 9H). 13C NMR (CDCl3, 125 MHz):
500 MHz):
d
7.85 (s, 1H), 7.22 (t, J ¼ 8.0 Hz, 1H), 7.11 (d, J ¼ 8.0 Hz,
1H), 7.08 (d, J ¼ 7.5 Hz, 1H), 4.11 (t, J ¼ 6.5 Hz, 2H), 3.71 (s, 2H), 3.33
(s, 2H), 1.89e1.83 (m, 2H), 1.67 (s, 4H), 1.60 (s, 2H), 1.57e1.52 (m,
d
161.33, 160.87, 148.44, 146.60, 144.24, 125.07, 120.73, 119.44,
2H), 0.99 (t, J ¼ 7.5 Hz, 3H). 13C NMR (CDCl3, 125 MHz):
d 163.37,
118.72, 116.64, 69.30, 50.64, 32.93, 31.09, 19.21, 18.67, 18.39, 17.55,
157.72, 146.71, 143.89, 142.66, 126.01, 124.68, 119.57, 119.11, 115.51,
69.21, 48.37, 43.02, 31.12, 26.21, 25.40, 24.40, 19.21, 13.86. MS (ESI),
m/z: 330.20 [MþH]þ.
13.86. MS (ESI), m/z: 332.15 [MþH]þ.
4.1.12.16. 8-Butoxy-2-oxo-N-(pentan-3-yl)-2H-chromene-3-
carboxamide (28). Light yellow solid. Yield 78.2%. Mp:
110.2e111.6 ꢁC. HPLC (90% acetonitrile in water): tR ¼ 5.81 min,
4.1.12.22. 6-Bromo-N-cyclohexyl-2-oxo-8-propoxy-2H-chromene-3-
carboxamide (34). Yellow solid. Yield 55.8%. Mp: 158.8e159.8 ꢁC.
HPLC (90% acetonitrile in water): tR ¼ 7.35 min, 97.36%. 1H NMR
96.77%. 1H NMR (CDCl3, 500 MHz):
d
8.87 (s, 1H), 8.66 (d, J ¼ 8.5 Hz,
1H), 7.27e7.22 (m, 2H), 7.17 (d, J ¼ 7.5 Hz,1H), 4.12 (t, J ¼ 6.5 Hz, 2H),
4.02e3.95 (m, 1H), 1.89e1.84 (m, 2H), 1.69e1.61 (m, 2H), 1.58e1.51
(m, 4H), 1.00 (t, J ¼ 7.5 Hz, 3H), 0.95 (t, J ¼ 7.5 Hz, 6H). 13C NMR
(CDCl3, 500 MHz):
d
8.78 (s, 1H), 8.74 (d, J ¼ 7.5 Hz, 1H), 7.37 (d,
J ¼ 2.0 Hz, 1H), 7.24 (d, J ¼ 2.0 Hz, 1H), 4.07 (t, J ¼ 6.5 Hz, 2H),
4.01e3.94 (m, 1H), 2.00e1.96 (m, 2H), 1.95e1.89 (m, 2H), 1.78e1.74
(m, 2H), 1.65e1.61 (m, 1H), 1.45e1.25 (m, 5H), 1.09 (t, J ¼ 7.5 Hz, 3H).
(CDCl3, 125 MHz):
d 161.29, 148.49, 146.61, 144.28, 125.05, 120.75,
119.47, 118.72, 116.69, 69.34, 52.59, 31.09, 27.26, 19.20, 13.84, 10.26.
13C NMR (CDCl3, 125 MHz):
d 160.60, 159.98, 147.28, 147.07, 143.27,
MS (ESI), m/z: 332.14 [MþH]þ.
122.56, 120.33, 119.86, 119.42, 117.47, 71.39, 48.63, 32.70, 25.56,
24.65, 22.30, 10.45. MS (ESI), m/z: 408.10 [MþH]þ.
4.1.12.17. 8-Butoxy-2-oxo-N-(pentan-2-yl)-2H-chromene-3-
carboxamide (29). Yellow solid. Yield 80.6%. Mp: 68.6e69.7 ꢁC.
HPLC (90% acetonitrile in water): tR ¼ 5.99 min, 97.27%. 1H NMR
4.1.12.23. 6-Bromo-8-butoxy-N-cyclohexyl-2-oxo-2H-chromene-3-
carboxamide (35). Yellow solid. Yield 58.5%. Mp: 137.7e138.9 ꢁC.
HPLC (87% acetonitrile in water): tR ¼ 11.76 min, 96.82%. 1H NMR
(CDCl3, 500 MHz):
d
8.86 (s, 1H), 8.69 (d, J ¼ 8.0 Hz, 1H), 7.27e7.21
(m, 2H), 7.17 (dd, J ¼ 7.5, 1.5 Hz, 1H), 4.20e4.14 (m, 1H), 4.12 (t,
J ¼ 6.5 Hz, 2H), 1.89e1.84 (m, 2H), 1.60e1.48 (m, 4H), 1.44e1.36 (m,
2H), 1.24 (d, J ¼ 6.5 Hz, 3H), 1.00 (t, J ¼ 7.5 Hz, 3H), 0.93 (t, J ¼ 7.5 Hz,
(CDCl3, 500 MHz):
d
8.78 (s, 1H), 8.74 (d, J ¼ 7.5 Hz, 1H), 7.37 (s, 1H),
7.25 (s, 1H), 4.11 (t, J ¼ 6.5 Hz, 2H), 4.00e3.95 (m, 1H), 2.00e1.97 (m,
2H), 1.90e1.85 (m, 2H), 1.77e1.74 (m, 2H), 1.64e1.61 (m, 1H),
1.58e1.51 (m, 2H), 1.47e1.34 (m, 4H), 1.28e1.25 (m, 1H), 1.01 (t,
3H). 13C NMR (CDCl3, 125 MHz):
d 161.24, 160.80, 148.43, 146.59,
144.26, 125.06, 120.74, 119.44, 118.72, 116.65, 69.32, 45.60, 38.90.
31.07, 20.84, 19.27, 19.20, 13.99, 13.86. MS (ESI), m/z: 332.15
[MþH]þ.
J ¼ 7.5 Hz, 3H). 13C NMR (CDCl3, 125 MHz):
d 160.60, 159.98, 147.32,
147.06, 143.29, 122.55, 120.34, 119.89, 119.42, 117.47, 69.69, 48.62,
32.69, 30.91, 25.56, 24.64, 19.15, 13.80. MS (ESI), m/z: 422.10
[MþH]þ.
4.1.12.18. 8-Butoxy-N-isopropyl-2-oxo-2H-chromene-3-carboxamide
(30). Light yellow solid. Yield 89.2%. Mp: 121.3e122.4 ꢁC. HPLC
(90% acetonitrile in water): tR ¼ 4.80 min, 99.59%. 1H NMR (CDCl3,
4.1.12.24. 6-Bromo-N-cyclohexyl-2-oxo-8-pentyloxy-2H-chromene-
3-carboxamide (36). Yellow solid. Yield 92.0%. Mp: 166.2e167.4 ꢁC.
HPLC (90% acetonitrile in water): tR ¼ 12.32 min, 95.43%. 1H NMR
500 MHz):
d
8.86 (s, 1H), 8.71 (d, J ¼ 6.5 Hz, 1H), 7.25 (dd, J ¼ 7.5,
2.0 Hz,1H), 7.22 (d, J ¼ 8.0 Hz,1H), 7.17 (d, J ¼ 8.0 Hz, 1H), 4.28e4.22
(m,1H), 4.12 (t, J ¼ 6.5 Hz, 2H),1.89e1.84 (m, 2H),1.58e1.51 (m, 2H),
1.27 (d, J ¼ 6.5 Hz, 6H), 1.00 (t, J ¼ 7.5 Hz, 3H). 13C NMR (CDCl3,
(CDCl3, 500 MHz):
d
8.78 (s, 1H), 8.73 (d, J ¼ 7.5 Hz, 1H), 7.37 (d,
J ¼ 1.5 Hz, 1H), 7.24 (d, J ¼ 2.0 Hz, 1H), 4.10 (t, J ¼ 6.5 Hz, 2H),
4.00e3.95 (m, 1H), 2.00e1.97 (m, 2H), 1.93e1.87 (m, 2H), 1.78e1.74
(m, 2H), 1.64e1.62 (m, 1H), 1.51e1.34 (m, 8H), 1.28e1.25 (m, 1H),
125 MHz):
d 161.16, 160.59, 148.38, 146.59, 144.28, 125.04, 120.74,
119.43, 118.73, 116.67, 69.35, 41.87, 31.07, 22.61, 19.19, 13.84. MS
0.95 (t, J ¼ 7.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz):
d 160.61, 159.98,
(ESI), m/z: 304.18 [MþH]þ.
147.31, 147.08, 143.27, 122.53, 120.33, 119.87, 119.38, 117.48, 69.96,
48.63, 32.70, 28.59, 28.03, 25.56, 24.65, 22.39, 14.00. MS (ESI), m/z:
436.14 [MþH]þ.
4.1.12.19. 8-Butoxy-2-oxo-N-(piperidin-1-yl)-2H-chromene-3-
carboxamide (31). Light yellow solid. Yield 19.0%. Mp:
147.8e150.3 ꢁC. HPLC (90% acetonitrile in water): tR ¼ 4.62 min,
4.1.12.25. 6-Bromo-N-cyclohexyl-8-hexyloxy-2-oxo-2H-chromene-3-
carboxamide (37). Yellow solid. Yield 68.2%. Mp: 159.6e161.0 ꢁC.
HPLC (90% acetonitrile in water): tR ¼ 15.83 min, 96.29%. 1H NMR
99.40%. 1H NMR (CDCl3, 500 MHz):
d 9.61 (s, 1H), 8.92 (s, 1H),
7.29e7.24 (m, 2H), 7.19 (dd, J ¼ 7.5, 2.0 Hz, 1H), 4.13 (t, J ¼ 6.5 Hz,
2H), 2.90 (t, J ¼ 4.5 Hz, 4H), 1.91e1.85 (m, 2H), 1.80e1.75 (m, 4H),
1.59e1.52 (m, 2H), 1.50e1.45 (m, 2H), 1.01 (t, J ¼ 7.5 Hz, 3H). 13C
(CDCl3, 500 MHz):
d
8.78 (s, 1H), 8.74 (d, J ¼ 8.0 Hz, 1H), 7.37 (d,
J ¼ 2.0 Hz, 1H), 7.24 (d, J ¼ 1.5 Hz, 1H), 4.10 (t, J ¼ 6.5 Hz, 2H),
4.00e3.94 (m, 1H), 2.00e1.97 (m, 2H), 1.92e1.86 (m, 2H), 1.78e1.74
(m, 2H), 1.64e1.62 (m, 1H), 1.52e1.49 (m, 2H), 1.44e1.39 (m, 2H),
1.38e1.34 (m, 6H), 1.28e1.25 (m, 1H), 0.92 (t, J ¼ 7.0 Hz, 3H). 13C
NMR (CDCl3, 125 MHz):
d 161.02, 158.89, 149.01, 146.61, 144.23,
125.16, 120.76, 119.36, 118.55, 116.79, 69.34, 56.80, 31.07, 25.08,
23.36, 19.20, 13.85. MS (ESI), m/z: 345.20 [MþH]þ.
NMR (CDCl3, 125 MHz):
d 160.59, 159.98, 147.31, 147.07, 143.27,
4.1.12.20. 8-Butoxy-N-morpholino-2-oxo-2H-chromene-3-
carboxamide (32). Yellow solid. Yield 82.0%. Mp: 183.1e183.7 ꢁC.
HPLC (90% acetonitrile in water): tR ¼ 3.69 min, 96.63%. 1H NMR
122.53, 120.32, 119.87, 119.38, 117.47, 69.97, 48.63, 32.70, 31.48,
28.84, 25.57, 24.65, 22.57, 14.05. MS (ESI), m/z: 450.15 [MþH]þ.
(CDCl3, 500 MHz):
d
9.68 (s, 1H), 8.89 (s, 1H), 7.28e7.23 (m, 2H), 7.18
4.1.12.26. 6-Bromo-N-cyclohexyl-8-cyclopropylmethoxy-2-oxo-2H-
chromene-3-carboxamide (38). Yellow solid. Yield 17.0%. Mp:
176.5e177.9 ꢁC. HPLC (90% acetonitrile in water): tR ¼ 7.42 min,
(d, J ¼ 7.5 Hz,1H), 4.12 (t, J ¼ 6.5 Hz, 2H), 3.86 (t, J ¼ 4.5H, 4 Hz), 2.98
(t, J ¼ 4.5 Hz, 4H), 1.89e1.83 (m, 2H), 1.57e1.50 (m, 2H), 0.99 (t,
J ¼ 7.5 Hz, 3H). 13C NMR (CDCl3, 125 MHz):
d
160.99, 159.26, 149.29,
97.25%. 1H NMR (CDCl3, 500 MHz):
d
8.77 (s, 1H), 8.73 (d, J ¼ 7.5 Hz,
146.63, 144.23, 125.26, 120.77, 119.25, 118.20, 116.95, 69.34, 66.31,
1H), 7.37 (d, J ¼ 2.0 Hz, 1H), 7.23 (d, J ¼ 2.0 Hz, 1H), 4.00e3.95 (m,
3H), 1.99e1.96 (m, 2H), 1.77e1.73 (m, 2H), 1.62e1.60 (m, 1H),
1.44e1.33 (m, 5H), 1.27e1.25 (m, 1H), 0.70 (dd, J ¼ 9.0, 5.0 Hz, 2H),
55.76, 31.04, 19.19, 13.85. MS (ESI), m/z: 347.18 [MþH]þ.
4.1.12.21. 8-Butoxy-3-(piperidine-1-carbonyl)-2H-chromen-2-one
(33). White solid. Yield 63.6%. Mp: 124.5e125.8 ꢁC. HPLC (90%
0.40 (dd, J ¼ 5.5, 5.0 Hz, 2H). 13C NMR (CDCl3, 125 MHz):
d 160.59,
159.99, 147.18, 147.09, 143.40, 122.76, 120.40, 119.90, 117.44, 74.83,