R. Kumar et al. / European Journal of Medicinal Chemistry 45 (2010) 5292e5301
5299
(3H, s); 13C NMR (75.4 MHz, CDCl3);
142.8, 142.5, 132.9, 129.4, 119.9, 118.7, 115.9, 115.5, 112.2, 97.3, 57.1,
56.8 and 56.6. HRMS-ESI: m/z [M þ H]þ for C19H17O4N, calculated
324.1230; observed 324.1261.
d
190.2, 155.7, 153.8, 143.9,
0.038 g) and indole (1.26 mmol, 0.147 g) were added. The reaction
mixture was stirred at room temperature till completion of starting
material. After evaporation of acetonitrile, the obtained crude
mixture was purified through recrystallization with methanol and
water to afford 19 as a white solid in 81% yield, m.p. 149e150 ꢀC, 1H
4.2.9. 1-[(4-(4-Bromophenyl)phenyl)]-3-(2,4,5-trimethoxyphenyl)
prop-2-en-1-one (29)
NMR (300 MHz, CDCl3);
d
8.05 (1H, br, s), 7.97 (2H, d, J ¼ 8.2 Hz),
7.45 (3H, d, J ¼ 8.6 Hz), 7.36 (1H, d, J ¼ 7.8 Hz), 7.19 (1H, d,
J ¼ 6.7 Hz), 7.14e7.12 (1H, m), 7.05e7.00 (1H, m), 6.69 (1H, s), 6.56
(1H, s), 5.37 (1H, t, J ¼ 7.3 Hz), 3.90 (3H, s), 3.86 (3H, s), 3.69 (2H, d,
Bright yellow solid (96%), m. p. 137e139 ꢀC, 1H NMR (300 MHz,
CDCl3);
d
8.16e8.07 (3H, m), 7.67e7.48 (7H, m), 7.15 (1H, s), 6.53 (1H,
190.6,
s), 3.95 (3H, s), 3.91 (6H, s); 13C NMR (75.4 MHz, CDCl3);
d
J ¼ 7.50 Hz), 3.65 (3H, s); 13C NMR (75.4 MHz, CDCl3);
d 198.2, 151.1,
155.1, 153.1, 144.0, 143.7, 140.6, 139.3, 138.2, 132.4, 129.5, 129.1, 127.3,
122.8, 120.4, 115.9, 112.0, 97.3, 57.0, 56.7 and 56.4. HRMS-ESI: m/z
[M þ H]þ for C24H21O4Br, calculated 453.0696; observed 453.0766.
148.4, 143.2, 139.3, 136.7, 135.5, 129.8, 128.9, 127.0, 124.0, 122.2,
122.0, 119.7, 119.5, 118.5, 113.5, 111.2, 97.9, 56.9, 56.5, 56.3, 44.9 and
32.5. HRMS-ESI: m/z [M þ H]þ for C26H24O4 ClN, calculated
450.1467; observed 450.1467.
4.3. General procedure for the synthesis of 3-(4-chlorophenyl)-1-
[4-(prop-2-en-1-yloxy)phenyl] prop-2-en-1-one (6)
4.6. General procedure for synthesis of 1-(4-chlorophenyl)-3-
[1-(prop-2-en-1-yl)-1H-indol-3-yl]-3-(2,4,5-trimethoxyphenyl)
propan-1-one (20)
To the solution of chalcone 5 (0.5 g, 1.9 mmol) in dry acetone
(20ml), allylbromide (0.46 g, 3.8mmol)andanhydrousK2CO3 (0.52 g,
3.8 mmol) were added. The reaction mixture was refluxed for 6 h.
After consumption of starting chalcone (monitored on TLC), reaction
mixture was filtered to remove K2CO3. The filtrate was vacuum
evaporated and washed with hexane to remove excess of allyl
bromide. The obtained crude solid was recrystallized with methanol
to obtain 6 as a white solid in 69% yield, m.p. 119e120 ꢀC, 1H NMR
To a solution of 19 (0.67 mmol, 0.3 g) in dry THF (15 ml), KOH
(2 mmol, 0.112 g), allyl bromide (1.34 mmol, 0.161 g) and CTAB
(20 mol%, 0.048 g) were added. The reaction mixture was stirred till
completion of starting material. After evaporation of THF, the crude
reaction mixture was washed with hot water and then hexane to
remove the excess of allyl bromide. The obtained crude product on
recrystallization with diethyl ether afforded 20 as a white solid in
(300 MHz, CDCl3);
d
8.05 (2H, d, J ¼ 8.0 Hz), 7.77 (1H, d, J ¼ 16.2 Hz),
7.58e7.49 (3H, m), 7.40 (2H, d, J ¼ 8.9 Hz), 7.02 (2H, d, J ¼ 8.04 Hz),
79% yield, m. p. 126e127 ꢀC, 1H NMR (300 MHz, CDCl3);
d 7.94 (2H,
6.14e6.01 (1H, m), 5.48e5.31 (2H, m), 4.64(2H, d, J ¼ 5.1Hz);13C NMR
d, J ¼ 8.2 Hz), 7.42e7.40 (3H, m), 7.28 (1H, d, J ¼ 7.3 Hz), 7.19e7.14
(1H, m), 7.03e7.00 (2H, m), 6.70 (1H, s), 6.54 (1H, s), 6.02e5.95 (1H,
m), 5.35 (1 H, t, J ¼ 7.1 Hz), 5.19 (1H, d, J ¼ 10.0), 5.05 (1H, d,
J ¼ 17.3 Hz), 4.70 (2H, s), 3.88 (3H, s), 3.84 (3H, s), 3.65 (5H, s); 13C
(75.4 MHz, CDCl3); d 188.7, 162.9, 142.7, 136.5, 134.0, 132.9, 131.4, 131.2,
129.8, 129.5, 122.7, 118.5,115.0 and 69.3. HRMS-ESI: m/z [M þ H]þ for
C18H15ClO2, calculated 299.0833; observed 299.0833.
NMR (75.4 MHz, CDCl3);
d 198.4, 151.3, 148.6, 143.4, 139.5, 137.1,
4.4. General procedure for synthesis of 1-(4-chlorophenyl)-3-(2,4,5-
trimethoxyphenyl)propan-1-one (17) and 1-(4-chlorophenyl)-3-
(2,4,5-trimethoxyphenyl)-propan-1-ol (18)
135.9, 134.1, 130.0, 129.1, 127.8, 126.0, 124.4, 122.1, 120.1, 119.3, 117.6,
117.2, 113.7, 109.8, 98.2, 57.1, 56.7, 56.5, 49.0, 45.2 and 32.7. HRMS-
ESI: m/z [M þ H]þ for C29H28O4ClN, calculated 490.1780; observed
490.1780.
Compound 17 was prepared by the chemoselective hydroge-
nation of 14 using silica-supported PdCl2 as catalyst and a combi-
nation of MeOH/HCOOH/H2O [57] as a source of hydrogen. Product
17 was isolated in 82% yield as a viscous liquid. Further, reduction of
17 with NaBH4 [58] afforded the corresponding alcohol (18) in 85%
yield. The NMR data (1H & 13C) of 17 and 18 are given below:
The above two procedures i.e. Sections 4.5 and 4.6, were also
applied on chalcone 27 to provide the Michael adduct i.e. 1-(4-
Bromophenyl)-3-[1-(prop-2-en-1-yl)-1H-indol-3-yl]-3-(2,4,5-tri-
methoxyphenyl)-propan-1-one (27c) in overall 64% yield. Further,
dehydrogenation of 27c into 21 was performed as mentioned
below:
4.4.1. 1-(4-Chlorophenyl)-3-(2,4,5-trimethoxyphenyl)propan-1-one
4.7. General procedure for synthesis of 1-(4-bromophenyl)-3-[1-
(prop-2-en-1-yl)-1H-indol-3-yl]-3-(2,4,5-trimethoxyphenyl)prop-
2-en-1-one (21)
(17)
Viscous liquid,1H NMR (300 MHz, CDCl3);
d
7.92 (2H, d, J ¼ 8.5 Hz),
7.43 (2H, d, J ¼ 8.5 Hz), 6.76 (1H, s), 6.53 (1H, s), 3.89 (3H, s), 3.83 (3H,
s), 3.81 (3H, s), 3.23 (2H, t, J ¼ 7.2 Hz), 3.00 (2H, t, J ¼ 7.60 H); 13C NMR
To a solution of 27c (0.56 mmol, 0.3 g) in dry dioxane (15 ml),
DDQ (0.67 mmol, 0.153 g) was added and stirred at room temper-
ature for overnight. The reaction mixture was extracted with ethyl
acetate (3 ꢁ 15 ml). The combined organic phases were washed
successively with water (2 ꢁ 10 ml), brine (2 ꢁ 5 ml), dried over
anhydrous Na2SO4 and finally evaporated in vacuo. The obtained
crude mixture after passing through a small bed of neutral alumina,
recrystallized with diethyl ether to afford 21 as a reddish solid in
(75.4 MHz, CDCl3);d 199.3, 152.1, 148.7, 143.4, 139.8, 135.8, 130.1, 129.3,
121.2, 115.1, 98.3, 57.2, 56.8, 56.7, 39.9 and 25.9. HRMS-ESI: m/z
[M þ H]þ for C18H19ClO4, calculated 335.1045; observed 335.1041.
4.4.2. 1-(4-Chlorophenyl)-3-(2,4,5-trimethoxyphenyl)-propan-1-ol
(18)
Viscous liquid, 1H NMR (300 MHz, CDCl3);
d 7.35e7.25 (4H, m),
6.70 (1H, s), 6.53 (1H, s), 4.60e4.55 (1H, m), 3.88 (3H, s), 3.83 (3H,
71% yield, m. p. 145e147 ꢀC, 1H NMR (300 MHz, CDCl3);
d 7.89 (1H,
s), 3.82 (3H, s), 2.79e2.62 (2H, m), 2.01e1.89 (2H, m); 13C NMR
d, J ¼ 7.6 Hz), 7.82 (2H, d, J ¼ 8.4 Hz), 7.55 (2H, d, J ¼ 8.2 Hz), 7.44
(1H, s), 7.40 (1H, d, J ¼ 8.6 Hz), 7.28e7.23 (2H, m), 6.99 (1H, s), 6.73
(1H, s), 6.51 (1H, s), 6.01e5.90 (1H, m), 5.25 (1H, d, J ¼ 10.2 Hz), 5.15
(1H, d, J ¼ 17.2 Hz), 4.71 (2H, d, J ¼ 4.9 Hz), 3.93 (3H, s), 3.75 (3H, s),
(75.4 MHz, CDCl3);
d 151.4, 147.9, 143.3, 132.7, 128.3, 127.2, 125.8,
121.3, 114.4, 98.1, 72.5, 56.7, 56.3, 56.2, 39.7 and 25.8.
4.5. General procedure for synthesis of 1-(4-Chlorophenyl)-3-(1H-
3.60 (3H, s); 13C NMR (75.4 MHz, CDCl3);
d 190.7, 151.3, 149.8, 146.9,
indol-3-yl)-3-(2,4,5-trimethoxyphenyl)propan-1-one (19)
143.0, 138.8, 137.7, 132.8, 132.7, 131.5, 130.0, 126.6, 126.3, 122.9,
121.4, 121.2, 120.8, 118.8, 118.1, 114.8, 110.6, 98.0, 56.7, 56.1 and 49.3.
HRMS-ESI: m/z [M þ H]þ for C29H26O4BrN, calculated 532.1112;
observed 532.1115.
To a solution of chalcone 14 (1.05 mmol, 0.35 g) in acetonitrile
(15 ml), catalytic amount of P-toluenesulfonic acid (20 mol%,