Molecules 2020, 25, 77
20 of 31
was purified by column chromatography (SiO
CH Cl
CDCl
H, aromatic), 7.13 (s, 1H, aromatic), 7.06 (d, J = 8.4 Hz, 1H, aromatic), 6.82 (s, 1H, aromatic), 6.67 (d,
J = 8.4 Hz, 2H, aromatic), 4.01 (t, J = 6.4 Hz, 4H), 3.92 (s, 3H, OCH ), 3.57 (s, 2H, NCH Ph), 3.20 (dd, J
), 2.95 (m, 2H), 2.65 (m, 2H), 2.03 (m, 2H), 1.92–1.65 (m,
H), 1.45 (m, 5H), 1.42–1.23 (m, 7H); C NMR (100 MHz, CDCl , Figure S42) δ 207.8, 190.4, 159.3,
55.7, 152.0, 148.8, 148.5 (2 carbons), 145.8, 140.4, 130.4 (2 carbons), 129.5, 129.3 (2 carbons), 129.1, 128.2
2
gel, pure CH
2
Cl
2
to CH
2
Cl
2
:MeOH/19:1; R
f
0.39 in
1
2
2
:MeOH/19:1) to yield compound 15d (58 mg, 95%) as an orange solid: H NMR (400 MHz,
3
, Figure S41) δ 7.77 (d, J = 15.2 Hz, 1H, HC=CH-Ph), 7.56–7.48 (m, 4H, aromatic), 7.38–7.24 (m,
7
3
2
1
=
7
1
17.2 Hz, J
2
= 8.0 Hz, 1H), 3.03 (s, 6H, N(CH
3 2
)
1
3
3
(
2 carbons), 127.3, 122.6, 120.6, 119.0, 116.9, 113.4, 111.8 (2 carbons), 107.4, 105.4, 69.0, 68.1, 63.1, 56.2,
5
2
3.5 (2 carbons), 45.3, 40.1 (2 carbons), 38.6, 34.2, 33.4, 32.4, 31.4, 29.3 (2 carbons), 29.2, 28.9, 25.95,
+
5.85; m/z calcd for C48
H58
N
2
O5
742.4; found 743.4 [M + H] .
(
E)-2-((1-Benzylpiperidin-4-Yl)Methyl)-6-((10-(3-(3-(4-(Dimethylamino)Phenyl)Acryloyl)Phenoxy)Decyl)
Oxy)-5-Methoxy-2,3-Dihydro-1H-Inden-1-One (15e) (SGT689). A solution of compound 14 (30 mg, 0.082
mmol), compound 4e (48 mg, 0.099 mmol), and K CO (34 mg, 0.24 mmol) in anhydrous DMF (5 mL)
was heated at 80 °C overnight. The reaction mixture was then diluted with H O, and extracted with
EtOAc (3×). The combined organic layers were washed with H O (3×) and brine (3×), dried over
anhydrous MgSO , filtered, and concentrated under reduced pressure. The crude product obtained
was purified by column chromatography (SiO
CH Cl
CDCl
H, aromatic), 7.13 (s, 1H, aromatic), 7.07 (d, J = 8.4 Hz, 1H, aromatic), 6.81 (s, 1H, aromatic), 6.67 (d,
J = 8.4 Hz, 2H, aromatic), 4.01 (t, J = 6.8 Hz, 4H, 2×OCH CH ), 3.91 (s, 3H, OCH ), 3.54 (s, 2H, NCH Ph),
= 8.0 Hz, 1H), 3.03 (s, 6H, N(CH ), 2.92 (m, 2H), 2.65 (m, 2H), 2.01 (m, 2H),
.92-1.65 (m, 7H), 1.43 (m, 5H), 1.31 (m, 11H); C NMR (100 MHz, CDCl , Figure S44) δ 207.8, 190.4,
2
3
2
2
4
2
gel, pure CH
2
Cl
2
to CH
2
Cl
2
:MeOH/19:1; R
f
0.39 in
1
2
2
:MeOH/19:1) to yield compound 15e (42 mg, 67%) as a yellow solid: H NMR (400 MHz,
3
, Figure S43) δ 7.77 (d, J = 15.6 Hz, 1H, HC=CH-Ph), 7.56–7.48 (m, 4H, aromatic), 7.38–7.24 (m,
7
2
2
3
2
3
1
1
1
6
2
.20 (dd, J
1
= 17.2 Hz, J
2
3 2
)
1
3
3
59.3, 155.7, 152.0, 148.8, 148.5 (2 carbons), 145.8, 140.4, 130.4 (2 carbons), 129.4, 129.3 (2 carbons),
29.2, 128.2 (2 carbons), 127.2, 122.6, 120.6, 119.0, 116.9, 113.4, 111.8 (2 carbons), 107.4, 105.4, 69.0, 68.2,
3.2, 56.2, 53.6 (2 carbons), 45.3, 40.1 (2 carbons), 38.6, 34.2, 33.3, 32.6, 31.5, 29.7 (2 carbons), 29.4, 29.3,
9.2, 28.9, 26.0, 25.9; m/z calcd for C50
+
H62
N
2
O5
770.5; found 771.3 [M + H] .
(
E)-2-((1-Benzylpiperidin-4-Yl)Methyl)-6-((12-(3-(3-(4-(Dimethylamino)Phenyl)Acryloyl)Phenoxy)
Dodecyl)Oxy)-5-Methoxy-2,3-Dihydro-1H-Inden-1-One (15f) (SGT679). A solution of compound 14 (30
mg, 0.082 mmol), compound 4f (51 mg, 0.099 mmol), and K CO (34 mg, 0.25 mmol) in anhydrous
DMF (5 mL) was heated at 80 °C overnight. The reaction mixture was then diluted with H O, and
extracted with EtOAc (3×). The combined organic layers were washed with H O (3×) and brine (3×),
dried over anhydrous MgSO , filtered, and concentrated under reduced pressure. The crude product
obtained was purified by column chromatography (SiO gel, pure CH Cl to CH Cl :MeOH/19:1; R
.39 in CH Cl :MeOH/19:1) to yield compound 15f (32 mg, 48%) as an orange oil: H NMR (400 MHz,
CDCl , Figure S45) δ 7.77 (d, J = 15.2 Hz, 1H, HC=CH-Ph), 7.56–7.50 (m, 4H, aromatic), 7.35 (t, J = 8.0
Hz, 1H, aromatic), 7.33–7.28 (m, 6H, aromatic), 7.12 (s, 1H, aromatic), 7.06 (dd, J = 8.0 Hz, J = 2.0 Hz,
H, aromatic), 6.81 (s, 1H, aromatic), 6.67 (d, J = 8.8 Hz, 2H, aromatic), 4.00 (m, 4H), 3.91 (s, 3H, OCH ),
.57 (s, 2H, NCH Ph), 3.19 (dd, J = 17.6 Hz, J = 8.0 Hz, 1H), 3.02 (s, 6H, N(CH ), 2.95 (m, 2H), 2.65
= 14.0 Hz, J = 4.4 Hz, 2H), 2.03 (m, 2H), 1.90–1.75 (m, 5H), 1.73–1.60 (m, 2H), 1.50–1.40 (m, 6H),
.40–1.25 (m, 14H); C NMR (100 MHz, CDCl
2
3
2
2
4
2
2
2
2
2
f
1
0
2
2
3
1
2
1
3
3
2
1
2
3)2
(
dt, J
1
2
1
3
1
1
1
4
3
, Figure S46) δ 207.8, 190.4, 159.3, 155.7, 152.0, 148.8,
48.5 (2 carbons), 145.8, 140.4, 130.4 (2 carbons), 129.5, 129.3 (2 carbons), 129.1, 128.3 (2 carbons), 127.3,
22.6, 120.6, 119.0, 116.9, 113.4, 111.8 (2 carbons), 107.4, 105.4, 69.1, 68.2, 62.9, 56.2, 53.4 (2 carbons),
5.3, 40.1 (2 carbons), 38.6, 34.1, 33.3, 32.3, 31.3, 29.5 (3 carbons), 29.5, 29.4, 29.3, 29.2, 28.9, 26.0, 25.9;
+
m/z calcd for C52
H
66
N
2
O5
798.5; found 799.3 [M + H] .
(
E)-2-((1-Benzylpiperidin-4-Yl)Methyl)-6-(2-(4-(3-(4-(Dimethylamino)Phenyl)Acryloyl)Phenoxy)Ethoxy)-5-
Methoxy-2,3-Dihydro-1H-Inden-1-One (16a) (SGT683). A solution of compound 14 (20 mg, 0.055 mmol),
compound 7a (25 mg, 0.066 mmol), and K CO (23 mg, 0.16 mmol) in anhydrous DMF (5 mL) was
heated at 80 °C overnight. The reaction mixture was then diluted with H O, and extracted with EtOAc
3×). The combined organic layers were washed with H O (3×) and brine (3×), dried over anhydrous
2
3
2
(
2