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4.1.20. (E)-2-(4-(ethyl(methyl)amino)benzylidene)-5-methoxy-6-
4.1.26. 6-(4-(cyclohexylamino)butoxy)-5-methoxy-2,3-dihydro-
(2-(piperidin-1-yl)ethoxy)-2,3-dihydro-1H-inden-1-one (13)
1H-inden-1-one (16c)
Yellow solid; Yield: 66%; M.p. 132.0e132.9 ꢀC; 1H NMR
Yield: 70%. 1H NMR (400 MHz, CDCl3)
d
7.20 (s, 1H), 6.88 (s, 1H),
(400 MHz, CDCl3)
d
7.47 (d, J ¼ 9.1 Hz, 3H), 7.28 (s, 1H), 6.88 (s, 1H),
4.09 (dt, J ¼ 9.8, 4.9 Hz, 2H), 3.94 (s, 3H), 3.11 (m, 2H), 2.67 (dd,
J ¼ 9.7, 4.0 Hz, 2H), 2.55 (m, 7H), 2.03 (dt, J ¼ 13.1, 6.6 Hz, 2H), 1.63
(s, 5H), 1.60 (m, 4H). ESI-MS m/z: 332.1 [MþH]þ
6.64 (d, J ¼ 8.9 Hz, 2H), 4.13 (t, J ¼ 6.3 Hz, 2H), 3.91e3.86 (m, 3H),
3.81 (s, 2H), 3.43e3.35 (m, 2H), 2.94e2.88 (m, 3H), 2.78 (t,
J ¼ 6.3 Hz, 2H), 2.45 (s, 4H), 1.53 (dd, J ¼ 11.0, 5.5 Hz, 4H), 1.38
(d, J ¼ 5.2 Hz, 2H), 1.09 (t, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3)
4.1.27. General procedures for the preparation of 17ae17c
d
193.26, 155.11, 149.72, 148.72, 144.38, 133.32, 132.62, 131.72,
Sodium hydroxide (0.35 g, 8.75 mmol) and 4-(dimethylamino)
130.45, 123.07, 111.77, 107.48, 106.55, 66.82, 57.57, 56.18, 54.93,
46.56, 37.38, 32.37, 25.92, 24.21, 11.49. HRMS (ESI) m/z calcd
for C27H34N2O3, 435.2642; found, 435.2663 Purity: 96.5% (by
HPLC).
benzaldehyde (3.5 mmol) were added to a solution of 16
(1.75 mmol) in methanol. After the mixture was stirred at room
temperature for 2e5 h, the solid was filtered, chromatographed on
silica gel, and eluted with petroleum/ethyl acetate (10:1e1:1) as the
eluent to afford the proposed compound.
4.1.21. (E)-5-methoxy-2-(4-(methyl(propyl)amino)benzylidene)-6-
(2-(piperidin-1-yl)ethoxy)-2,3-dihydro-1H-inden-1-one (14)
Yellow solid; Yield: 70%; M.p. 123.0e123.8 ꢀC; 1H NMR
4.1.28. (E)-6-(2-(cyclohexylamino)ethoxy)-2-(4-(dimethylamino)
benzylidene)-5-methoxy-2,3-dihydro-1H-inden-1-one (17a)
Yellow solid; Yield: 75%; M.p. 143.5e144.3 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.54 (d, J ¼ 6.4 Hz, 3H), 7.35 (d, J ¼ 2.0 Hz, 1H),
(400 MHz, CDCl3)
d
7.57 (d, J ¼ 9.1 Hz, 3H), 7.36 (s, 1H), 6.97 (s, 1H),
6.96 (s, 1H), 6.73e6.65 (m, 2H), 4.21 (dd, J ¼ 6.0, 3.9 Hz, 2H), 3.95 (d,
J ¼ 2.2 Hz, 3H), 3.88 (s, 2H), 3.34 (t, J ¼ 6.2 Hz, 2H), 3.01 (d,
J ¼ 2.2 Hz, 3H), 2.85 (dd, J ¼ 5.9, 3.8 Hz, 2H), 2.53 (s, 4H), 1.62 (d,
J ¼ 4.8 Hz, 6H), 1.45 (s, 2H), 0.94 (td, J ¼ 7.2, 2.2 Hz, 3H). 13C NMR
6.74 (d, J ¼ 8.7 Hz, 2H), 4.20 (m, 2H), 3.96 (d, J ¼ 4.2 Hz, 3H), 3.89 (d,
J ¼ 21.4 Hz, 2H), 3.12 (m, 2H), 3.05 (s, 6H), 2.49 (d, J ¼ 8.2 Hz, 1H),
1.75 (d, J ¼ 9.1 Hz, 2H), 1.38 (m, 8H); 13C NMR (101 MHz, CDCl3)
d
193.21, 155.20, 150.92, 148.66, 144.59, 133.31, 132.45, 131.58,
(101 MHz, CDCl3)
d 193.26, 155.06, 150.00, 148.69, 144.37, 133.37,
130.87, 123.30, 111.88, 108.44, 65.51, 56.59, 56.08, 46.85, 45.55,
39.99, 33.41, 26.14, 25.00. HRMS (ESI) m/z calcd for C27H34N2O3,
435.2642; found, 435.2659 Purity: 98.0% (by HPLC).
132.59, 131.74, 130.36, 122.94, 111.64, 107.48, 106.49, 66.66, 57.57,
56.17, 54.90, 54.10, 38.37, 32.38, 25.87, 24.20, 20.16, 11.43. HRMS
(ESI) m/z calcd for C28H36N2O3, 449.2799; found, 449.2817 Purity:
96.9% (by HPLC).
4.1.29. (E)-6-(3-(cyclohexylamino)propoxy)-2-(4-(dimethylamino)
benzylidene)-5-methoxy-2,3-dihydro-1H-inden-1-one (17b)
Yellow solid; Yield: 80%; M.p. 108.9e109.7 ꢀC; 1H NMR
4.1.22. (E)-2-(4-(dipropylamino)benzylidene)-5-methoxy-6-(2-
(piperidin-1-yl)ethoxy)-2,3-dihydro-1H-inden-1-one (15)
Yellow solid; Yield: 76%; M.p. 128.0e128.9 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.57 (d, J ¼ 8.9 Hz, 3H), 7.34 (s, 1H), 6.97 (s, 1H),
6.74 (d, J ¼ 8.7 Hz, 2H), 4.16 (t, J ¼ 6.2 Hz, 2H), 3.96 (s, 3H), 3.91 (s,
2H), 3.04 (s, 6H), 2.87 (t, J ¼ 6.7 Hz, 2H), 2.57 (m, 1H), 2.11 (m, 2H),
1.91 (d, J ¼ 12.1 Hz, 2H), 1.74 (dd, J ¼ 12.1, 4.1 Hz, 2H), 1.62 (d,
(400 MHz, CDCl3)
d
7.54 (d, J ¼ 7.5 Hz, 3H), 7.36 (s, 1H), 6.96 (s, 1H),
6.67 (d, J ¼ 8.3 Hz, 2H), 4.21 (t, J ¼ 6.3 Hz, 2H), 3.95 (d, J ¼ 8.0 Hz,
3H), 3.90 (s, 2H), 3.34e3.27 (m, 4H), 2.85 (t, J ¼ 6.2 Hz, 2H), 2.52 (s,
4H), 1.68e1.59 (m, 8H), 1.45 (d, J ¼ 4.8 Hz, 2H), 0.96 (t, J ¼ 7.3 Hz,
J ¼ 11.7 Hz, 1H), 1.34 (m, 6H); 13C NMR (101 MHz, CDCl3)
d 192.38,
155.12, 150.99, 148.70, 144.41, 133.33, 132.45, 130.79, 128.82, 123.31,
111.96, 107.45, 68.12, 56.76, 56.14, 44.15, 40.07, 33.16, 32.37, 30.56,
26.08, 25.02.ESI-MS m/z: 449.3 [MþH]þ
6H). 13C NMR (101 MHz, CDCl3)
d 193.27, 155.00, 149.02, 148.67,
144.32, 133.41, 132.71, 131.77, 130.07, 122.49, 111.48, 107.46, 106.44,
66.67, 57.57, 56.17, 54.90, 52.75, 32.40, 25.90, 24.22, 20.47, 11.38.
HRMS (ESI) m/z calcd for C30H40N2O3, 477.3112; found, 477.3123
Purity: 96.6% (by HPLC).
HRMS (ESI) m/z calcd for C28H36N2O3, 449.2799; found,
449.2821 Purity: 97.1% (by HPLC).
4.1.30. (E)-6-(4-(cyclohexylamino)butoxy)-2-(4-(dimethylamino)
benzylidene)-5-methoxy-2,3-dihydro-1H-inden-1-one (17c)
Yellow solid; Yield: 82%; M.p. 146.5e147.1 ꢀC; 1H NMR
4.1.23. General procedures for the preparation of 16ae16c
Cyclohexylamine (2.4 mol) was added to a solution of 4
(0.8 mmol) in 20 ml of acetonitrile, and the mixture was refluxed
for 2 h. After the solvent was removed in vacuum, the crude
product was purified on silica gel using petroleum/ethyl acetate as
the eluent to give compounds 16ae16c.
(400 MHz, CDCl3)
d
7.46 (d, J ¼ 9.0 Hz, 3H), 7.23 (s, 1H), 6.87 (s, 1H),
6.63 (d, J ¼ 8.8 Hz, 2H), 4.00 (t, J ¼ 6.6 Hz, 2H), 3.92 (m, 3H), 3.78 (s,
2H), 2.94 (s, 6H), 2.62 (t, J ¼ 7.2 Hz, 2H), 2.43 (m, 1H), 1.87 (m, 4H),
1.68 (m, 4H), 1.08 (ddt, J ¼ 37.6, 24.6, 12.3 Hz, 6H); 13C NMR
(101 MHz, CDCl3)
d 193.30, 155.15, 150.95, 148.80, 144.24, 133.23,
132.42, 131.61, 130.74, 123.45, 111.94, 107.40, 68.88, 56.81, 56.17,
46.53, 40.05, 33.58, 32.34, 26.95, 26.17, 25.08. HRMS (ESI) m/z calcd
for C29H38N2O3, 463.2955; found, 463.2978 Purity: 99.3% (by HPLC).
4.1.24. 6-(2-(cyclohexylamino)ethoxy)-5-methoxy-2,3-dihydro-
1H-inden-1-one (16a)
Yield: 50%. 1H NMR (400 MHz, CDCl3)
d 7.19 (m, 1H), 6.89 (m,
1H), 4.01 (t, J ¼ 5.3 Hz, 2H), 3.82 (s, 3H), 3.05 (m, 4H), 2.60 (m, 2H),
2.39 (dd, J ¼ 21.1, 7.0 Hz, 1H), 2.14 (s, 1H), 1.80 (d, J ¼ 10.4 Hz, 2H),
1.63 (dd, J ¼ 11.1, 5.2 Hz, 2H), 1.23 (m, 7H). ESI-MS m/z: 304.2
[MþH]þ
4.1.31. (E)-5-methoxy-2-(4-methoxybenzylidene)-6-(2-(piperidin-
1-yl)ethoxy)-2,3-dihydro-1H-inden-1-one (18)
To a solution of 5a (1.75 mmol) in methanol, sodium hydroxide
(0.35 g, 8.75 mmol) and 4-methoxybenzaldehyde (3.5 mmol) was
added. After the mixture was stirred at room temperature for
2e5 h, the solid was filtered, and chromatographed on silica gel and
eluted with Petroleum/ethyl acetate (10:1e1:1) as an eluent to
afford the proposed compound.
4.1.25. 6-(3-(cyclohexylamino)propoxy)-5-methoxy-2,3-dihydro-
1H-inden-1-one (16b)
Yield: 62%. 1H NMR (400 MHz, CDCl3)
d 7.17 (s, 1H), 6.94 (s, 1H),
4.21 (t, J ¼ 5.5 Hz, 2H), 3.99 (s, 3H), 3.33 (t, J ¼ 5.7 Hz, 2H), 3.10 (m,
2H), 2.72 (m, 2H), 2.44 (dt, J ¼ 12.0, 6.2 Hz, 2H), 2.25 (d, J ¼ 11.3 Hz,
2H), 1.71 (d, J ¼ 14.8 Hz, 2H), 1.65 (d, J ¼ 11.3 Hz, 2H), 1.29 (dd,
J ¼ 21.5, 9.0 Hz, 6H). ESI-MS m/z: 318.2 [MþH]þ
Yellow solid; Yield: 86%; M.p. 137.3e138.2 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
7.61 (d, J ¼ 8.6 Hz, 2H), 7.56 (s, 1H), 7.36 (s, 1H),
6.97 (d, J ¼ 6.1 Hz, 3H), 4.21 (t, J ¼ 6.2 Hz, 2H), 3.97 (s, 3H), 3.92 (s,
2H), 3.86 (s, 3H), 2.85 (t, J ¼ 6.2 Hz, 2H), 2.53 (s, 4H),1.61 (s, 4H),1.45