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I-L. Chen et al. / European Journal of Medicinal Chemistry 59 (2013) 227e234
2.0 Hz, 1HeC(30)), 7.88e7.96 (m, 4H, AreH), 8.25 (d, J ¼ 2.0 Hz, 1He
5.1.14. N-(4-Fluorophenyl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-
yloxy)acetamide (30b)
C(10)), 10.54 (s, 1H, NH), 11.51 (s, 1H, NH); 13C NMR (100 MHz,
DMSO-d6):
d
68.11 (CH2O), 112.91, 118.09, 119.98, 120.85, 121.75,
From 6-[2-(4-fluorophenyl)-2-oxoethoxy]-3,4-dihydroquinolin-
121.88, 122.59, 125.18, 126.54, 127.46, 127.56, 128.33, 128.73, 130.35,
133.23, 135.37, 140.48, 143.84, 161.91 (C]O), 166.35 (C(2)). Anal.
calcd. for C21H16N2O3: C 73.24, H 4.68, N 8.13; found: C 73.18, H 4.65,
N, 8.10.
2(1H)-one (24b) as described for 15: 86% yield. M.p.: 212e213 ꢁC;
1H NMR (400 MHz, DMSO-d6):
d 2.39e2.43 (m, 2HeC(3)), 2.82e
2.86 (m, 2HeC(4)), 4.62 (s, OCH2), 6.78 (d, J ¼ 8.8 Hz, 1HeC(8)),
6.81 (dd, J ¼ 8.8, 2.4 Hz, 1HeC(7)), 6.88 (d, J ¼ 2.4 Hz, 1HeC(5)),
7.14e7.19 (m, 2H, AreH), 7.65e7.69 (m, 2H, AreH), 9.96 (s, 1H,
5.1.10. N-(Naphthalen-2-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-
6-yloxy)acetamide (18)
NH), 10.09 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 25.76
(C(4)), 30.97 (C(3)), 68.27 (CH2O), 113.95, 115.15, 115.86, 116.08,
116.41, 122.27, 122.35, 125.56, 133.11, 135.41, 153.62, 157.75, 160.13,
167.36 (C]O), 170.48 (C(2)). Anal. calcd. for C17H15FN2O3$0.25H2O:
C 64.04, H 4.90, N 8.78; found: C 64.17, H 4.94, N 8.48.
From 6-(2-naphthalen-2-yl-2-oxoethoxy)-3,4-dihydroquinolin-
2(1H)-one (12) as described for 15: 75% yield. M.p.: 236e237 ꢁC; 1H
NMR (400 MHz, DMSO-d6):
d 2.39e2.43 (m, 2HeC(3)), 2.83e2.87
(m, 2HeC(4)), 4.69 (s, 2H, OCH2), 6.80 (d, J ¼ 8.8 Hz, 1HeC(8)),
6.84 (dd, J ¼ 8.8, 2.4 Hz, 1HeC(7)), 6.91 (d, J ¼ 2.4 Hz, 1HeC(5)),
7.40e7.50 (m, 2H, AreH), 7.67e7.70 (m, 1H, AreH), 7.82e7.90 (m,
3H, AreH), 8.33 (m, 1H, AreH), 9.96 (s, 1H, NH), 10.24 (s, 1H, NH);
5.1.15. N-(4-Methoxyphenyl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-
6-yloxy)acetamide (30c)
From 6-[2-(4-methoxyphenyl)-2-oxoethoxy]-3,4-dihydroquinolin-
13C NMR (100 MHz, DMSO-d6):
d 25.77 (C(4)), 30.98 (C(3)), 68.33
2(1H)-one (24c) as described for 15: 86% yield. M.p.: 186e187 ꢁC; 1H
(CH2O), 113.95, 115.16, 116.43, 116.62, 120.99, 125.50, 125.58, 127.16,
128.03, 128.15, 129.05, 130.63, 133.08, 133.98, 136.65, 153.69, 167.70
(C]O), 170.51 (C(2)). Anal. calcd. for C21H18N2O3: C 72.82, H 5.24, N
8.09; found: C 72.67, H 5.24, N 8.05.
NMR (400 MHz, DMSO-d6): d 2.39e2.43 (m, 2HeC(3)), 2.82e2.86 (m,
2HeC(4)), 3.72 (s, 3H, OMe), 4.58 (s, 2H, OCH2), 6.78 (d, J ¼ 8.8 Hz, 1He
C(8)), 6.81 (dd, J ¼ 8.8, 2.4 Hz, 1HeC(7)), 6.87 (d, J ¼ 2.4 Hz, 1HeC(5)),
6.88e6.90 (m, 2H, AreH), 7.53e7.55 (m, 2H, AreH), 9.89 (s, 1H, NH),
9.96 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 25.76 (C(4)), 30.97
5.1.11. N-(Naphthalen-2-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-7-
yloxy)acetamide (19)
(C(3)), 55.84 (MeO), 68.30 (CH2O), 113.94, 114.50, 115.15, 116.41, 122.09,
125.55,132.09, 133.04,153.67,156.23,166.92 (C]O),170.52 (C(2)). Anal.
calcd. for C18H18N2O4: C 66.25, H 5.56, N 8.58; found: C 66.15, H 5.58,
N 8.59.
From 7-(2-naphthalen-2-yl-2-oxoethoxy)-3,4-dihydroquinolin-
2(1H)-one (13) as described for 15: 56% yield. M.p.: 247e248 ꢁC; 1H
NMR (400 MHz, DMSO-d6):
d 2.40e2.44 (m, 2HeC(3)), 2.78e2.81
(m, 2HeC(4)), 4.70 (s, 2H, OCH2), 6.56 (d, J ¼ 2.4 Hz, 1HeC(8)),
6.59 (dd, J ¼ 8.0, 2.4 Hz, 1HeC(6)), 7.09 (d, J ¼ 8.0 Hz, 1HeC(5)),
7.40e7.50 (m, 2H, AreH), 7.66e7.69 (m, 1H, AreH), 7.81e7.89 (m,
3H, AreH), 8.32 (d, J ¼ 1.2 Hz, 1H, AreH), 10.08 (s, 1H, NH), 10.29 (s,
5.1.16. N-(Biphenyl-4-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-
yloxy)acetamide (30d)
From 6-(2-biphenyl-4-yl-2-oxoethoxy)-3,4-dihydroquinolin-
2(1H)-one (24d) as described for 15: 83% yield. M.p.: 246e247 ꢁC;
1H, NH); 13C NMR (100 MHz, DMSO-d6):
d
24.71 (C(4)), 31.37 (C(3)),
1H NMR (400 MHz, DMSO-d6):
d 2.39e2.43 (m, 2HeC(3)), 2.83e
67.98 (CH2O), 102.83, 108.32, 116.62, 117.08, 120.98, 125.48, 127.16,
128.01, 128.15, 129.03, 129.11, 130.63, 133.99, 136.70, 139.96, 157.83,
167.48 (C]O), 171.00 (C(2)). Anal. calcd. for C21H18N2O3: C 72.82, H
5.24, N 8.09; found: C 72.81, H 5.25, N 8.04.
2.87 (m, 2HeC(4)), 4.65 (s, 2H, OCH2), 6.80 (d, J ¼ 8.4 Hz, 1He
C(8)), 6.83 (dd, J ¼ 8.4, 2.0 Hz, 1HeC(7)), 6.89 (d, J ¼ 2.0 Hz,
1HeC(5)), 7.33e7.47 (m, 5H, AreH), 7.64e7.76 (m, 4H, AreH),
9.96 (s, 1H, NH), 10.14 (s, 1H, NH); 13C NMR (100 MHz, DMSO-
d6):
d 25.77 (C(4)), 30.97 (C(3)), 68.34 (CH2O), 113.95, 115.16,
5.1.12. N-(Naphthalen-2-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-
8-yloxy)acetamide (20)
116.43, 120.78, 125.58, 126.97, 127.60, 127.79, 129.60, 133.08,
136.05, 138.52, 140.30, 153.68, 167.48 (C]O), 170.52 (C(2)). Anal.
calcd. for C23H20N2O3$0.5H2O: C 72.42, H 5.55, N 7.34; found: C
72.65, H 5.49, N 7.29.
From a mixture of 14 and 14A as described for 15: 60% yield.
M.p.: 199e200 ꢁC; 1H NMR (400 MHz, DMSO-d6):
d 2.46e2.50 (m,
2HeC(3)), 2.89e2.93 (m, 2HeC(4)), 4.77 (s, 2H, OCH2), 6.86e7.01
(m, 3H, AreH), 7.45e7.51 (m, 2H, AreH), 7.70 (dd, J ¼ 8.8, 2.0 Hz,
1H, AreH), 7.87e7.94 (m, 3H, AreH), 8.25 (d, J ¼ 2.0 Hz, 1H, AreH),
9.86 (s, 1H, NH), 10.34 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
5.1.17. 2-(2-Oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)-N-
phenylacetamide (31a)
From 7-(2-oxo-2-phenylethoxy)-3,4-dihydroquinolin-2(1H)-one
d
25.69 (C(4)), 31.19 (C(3)), 68.72 (CH2O), 112.11, 118.33, 121.61,
(25a) as described for 15: 84% yield. M.p.: 249e250 ꢁC; 1H NMR
122.12, 122.95, 125.76, 125.87, 127.18, 127.86, 128.09, 128.19, 128.98,
130.93, 133.89, 136.12, 144.98, 167.33 (C]O), 170.80 (C(2)). Anal.
calcd. for C21H18N2O3: C 72.82, H 5.24, N 8.09; found: C 72.45, H
5.18, N 7.99.
(400 MHz, DMSO-d6): d 2.39e2.43 (m, 2HeC(3)), 2.77e2.81 (m, 2He
C(4)), 4.62 (s, 2H, OCH2), 6.53 (d, J ¼ 2.4 Hz, 1HeC(8)), 6.55 (dd,
J ¼ 8.0, 2.4 Hz, 1HeC(6)), 7.09 (d, J ¼ 8.0 Hz, 1HeC(5)), 7.06e7.10 (m,
1H, AreH), 7.30e7.34 (m, 2H, AreH), 7.62e7.64 (m, 2H, AreH), 10.06
(s, 1H, NH), 10.06 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 24.71
5.1.13. 2-(2-Oxo-1,2,3,4-tetrahydroquinolin-6-yloxy)-N-
phenylacetamide (30a)
(C(4)), 31.36 (C(3)), 67.91 (CH2O), 102.80, 108.27, 117.05, 120.39,
124.35, 129.09, 129.40, 139.09, 139.94, 157.80, 167.18 (C]O), 171.00
(C(2)). Anal. calcd. for C17H16N2O3: C 68.91, H 5.44, N 9.45; found: C
68.52, H 5.42, N 9.36.
From
one (24a) as described for 15: 85% yield. M.p.: 222e223 ꢁC; 1H NMR
(400 MHz, DMSO-d6): 2.38e2.42 (m, 2HeC(3)), 2.82e2.86 (m,
6-(2-oxo-2-phenylethoxy)-3,4-dihydroquinolin-2(1H)-
d
2HeC(4)), 4.62 (s, OCH2), 6.78 (d, J ¼ 8.8 Hz, 1HeC(8)), 6.81 (dd,
J ¼ 8.8, 2.4 Hz,1HeC(7)), 6.87 (d, J ¼ 2.4 Hz, 1HeC(5)), 7.06e7.10 (m,
1H, AreH), 7.30e7.34 (m, 2H, AreH), 7.63e7.65 (m, 2H, AreH), 9.95
5.1.18. N-(4-Fluorophenyl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-7-
yloxy)acetamide (31b)
From 7-[2-(4-fluorophenyl)-2-oxoethoxy]-3,4-dihydroquinolin-
(s,1H, NH),10.02 (s,1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 25.78
2(1H)-one (25b) as described for 15: 86% yield. M.p.: 264e265 ꢁC; 1H
(C(4)), 30.97 (C(3)), 68.29 (CH2O), 113.92, 115.13, 116.41, 120.42,
124.38, 125.56, 129.41, 133.07, 139.04, 153.67, 167.39 (C]O), 170.49
(C(2)). Anal. calcd. for C17H16N2O3: C 68.91, H 5.44, N 9.45; found: C
68.84, H, 5.44, N 9.43.
NMR (400 MHz, DMSO-d6): d 2.40e2.44 (m, 2HeC(3)), 2.77e2.81
(m, 2HeC(4)), 4.62 (s, 2H, OCH2), 6.53 (d, J ¼ 2.4 Hz, 1HeC(8)),
6.55 (dd, J ¼ 8.0, 2.4 Hz, 1HeC(6)), 7.08 (d, J ¼ 8.0 Hz, 1HeC(5)),
7.14e7.19 (m, 2H, AreH), 7.64e7.67 (m, 2H, AreH), 10.08