Med Chem Res
(1H, t, J = 7.6 Hz, Ar-H), 7.12–7.20 (4H, m, Ar-H), 7.28
(2H, t, J = 7.6 Hz, Ar-H), 7.51 (2H, m, H-14 and H-21),
7.81 (1H, d, J = 2.8 Hz, H-13), 8.00 (1H, s, H-18), 10.97
(1H, s, CONHCO), 11.86 (1H, d, J = 2.0 Hz, NH). 13C
NMR (100 MHz, DMSO-d6) δ 31.3 (CH2CH2Ph), 31.8
(CH2CH2Ph), 50.7 (NCH2), 103.9 (C-8), 110.6 (C-9), 112.3
(C-17), 119.5, 121.2, 121.8, 123.8, 124.8, 125.9, 127.5,
128.2, 128.3, 129.4, 131.0, 136.4, 139.2, 141.0, 172.6
(C=O), 172.6 (C=O). HRMS (MALDI) Calcd. for
C24H20N4O2 [M+H]+ 397.1659; found, 397.1659.
filtered and concentrated in vacuo. The residue was dis-
solved in ethyl acetate and washed twice with saturated
solution of NH4Cl. The organic layer was dried, con-
centrated in vacuo, and the residue was purified by column
chromatography on silica gel eluted with DCM/MeOH
(25:1–10:1) to give compounds C1–C3.
3-(1H-indol-3-yl)-4-(1-(3-phenylpropyl)-1H-imidazol-4-
yl)-1H-pyrrole-2,5-dione (C1) Yield 31%, a yellow solid.
1H NMR (400 MHz, DMSO-d6)
δ 2.07 (2H, m,
CH2CH2Ph), 2.54 (2H, buried t, J = 8.0 Hz, CH2CH2Ph),
4.06 (2H, t, J = 6.8 Hz, NCH2), 6.86 (1H, t, J = 7.6 Hz, Ar-
H), 7.09 (2H, t, J = 7.2 Hz, Ar-H), 7.21 (3H, d, J = 7.2 Hz,
Ar-H), 7.30 (2H, t, J = 7.2 Hz, Ar-H), 7.42 (1H, d, J = 8.0
Hz, Ar-H), 7.69 (1H, s, Ar-H), 7.80 (1H, s, H-20), 8.07 (1H,
d, J = 2.4 Hz, H-13), 10.90 (1H, s, CONHCO), 11.69 (1H,
3-(1H-indol-3-yl)-4-(1-(3-(pyridin-4-yl)propyl)-1H-pyra-
zol-4-yl)-1H-pyrrole-2,5-dione (B2) Yield 27%, a yellow
solid. 1H NMR (400 MHz, DMSO-d6) δ 2.03 (2H, m,
CH2CH2Py), 2.48 (2H, buried t, CH2CH2Py), 4.10 (2H, t, J
= 6.6 Hz, NCH2), 6.84–6.92 (2H, m, Ar-H), 7.12–7.18 (3H,
m, Ar-H), 7.50–7.52 (2H, m, H-14 and H-21), 7.82 (1H, d,
J = 2.4 Hz, H-13), 7.95 (1H, s, H-18), 8.28–8.62 (2H, m,
Py-CHNCH), 10.95 (1H, s, CONHCO), 11.85 (1H, s, NH).
13C NMR (100 MHz, DMSO-d6) δ 30.6 (CH2CH2Py), 31.5
(CH2CH2Py), 51.1 (NCH2), 104.4 (C-8), 111.2 (C-9), 112.8
(C-17), 120.0, 121.7, 122.2, 124.3, 125.3, 128.1, 129.9,
131.5, 136.9, 139.8, 149.9 (Py-CHNCH), 150.5 (Py-
CHNCH), 173.1 (C=O), 173.1 (C=O). HRMS (MALDI)
Calcd. for C23H19N5O2 [M+Na]+ 398.1612; found,
398.1615.
s, NH). 13C NMR (100 MHz, DMSO-d6)
δ 32.4
(CH2CH2Ph), 32.6 (CH2CH2Ph), 46.4 (NCH2), 105.5 (C-8),
112.1 (C-17), 119.7, 121.9, 122.3, 123.2, 126.1, 126.4,
126.4, 128.7, 128.8, 129.2, 131.1, 131.9, 136.6, 138.4,
141.4 (C-25), 173.1 (C=O), 173.3 (C=O). HRMS
(MALDI) Calcd. for C24H20N4O2 [M+Na]+ 397.1659;
found, 397.1656.
3-(1H-indol-3-yl)-4-(1-(3-(pyridin-4-yl)propyl)-1H-imida-
zol-4-yl)-1H-pyrrole-2,5-dione (C2) Yield 22%, a yellow
solid. 1H NMR (400 MHz, DMSO-d6) δ 2.07 (2H, m,
CH2CH2Py), 2.55 (2H, t, J = 7.4 Hz, CH2CH2Py), 4.05
(2H, t, J = 7.2 Hz, NCH2), 6.85 (1H, t, J = 7.6 Hz, Ar-H),
7.12–7.00 (2H, m, Ar-H), 7.22 (2H, d, J = 5.6 Hz, Ar-H),
7.40 (1H, d, J = 8.1 Hz, Ar-H), 7.68 (1H, s, Ar-H), 7.78
(1H, s, H-20), 8.05 (1H, d, J = 2.6 Hz, H-13), 8.46 (2H, d,
J = 5.7 Hz, Py-CHNCH), 10.85 (1H, s, CONHCO), 11.64
(1H, s, NH). 13C NMR (100 MHz, DMSO-d6) δ 31.3
(CH2CH2Py), 31.6 (CH2CH2Py), 46.3 (NCH2), 105.5 (C-8),
112.1 (C-17), 119.7, 121.9, 122.3, 123.2, 124.3, 126.1,
126.4, 129.2, 131.1, 131.9, 136.6, 138.4, 150.0 (Py-
CHNCH), 150.3 (Py-CHNCH), 173.1 (C=O), 173.3
(C=O). HRMS (MALDI) Calcd. for C23H19N5O2 [M+H]+
398.1612; found, 398.1609.
3-(1-(3-(3,5-dichlorophenyl)propyl)-1H-pyrazol-4-yl)-4-
(1H-indol-3-yl)-1H-pyrrole-2,5-dione (B3) Yield 43%; a
1
yellow solid. H NMR (400 MHz, DMSO-d6) δ 2.02 (2H,
m, CH2CH2Ph), 2.51 (2H, buried t, CH2CH2Ph), 4.09 (2H,
t, J = 7.2 Hz, NCH2), 6.85 (1H, d, J = 8.0 Hz, Ar-H), 6.91
(1H, t, J = 7.4 Hz, Ar-H), 7.15 (1H, t, J = 7.2 Hz, Ar-H),
7.23 (2H, d, J = 1.6 Hz, Ar-H), 7.42 (1H, d, J = 1.6 Hz, Ar-
H), 7.51–7.53 (2H, m, H-14 and H-21), 7.82 (1H, d, J =
2.8 Hz, H-13), 7.96 (1H, s, H-18), 10.95 (1H, s, CONHCO),
11.85 (1H, s, NH). 13C NMR (100 MHz, DMSO-d6) δ 31.2
(CH2CH2Ph), 31.7 (CH2CH2Ph), 51.0 (NCH2), 104.4 (C-8),
111.2 (C-9), 112.8 (C-17), 120.0, 121.7, 122.2, 124.4,
125.3, 126.1, 127.7, 128.1, 129.9, 131.5, 134.3, 137.0,
139.7, 146.0, 173.1 (C=O), 173.1 (C=O). HRMS
(MALDI) Calcd. for C24H18Cl2N4O2 [M+Na]+ 487.0699;
found, 487.0694.
3-(1-(3-(3,5-dichlorophenyl)propyl)-1H-imidazol-4-yl)-4-
(1H-indol-3-yl)-1H-pyrrole-2,5-dione (C3) Yield 54%, a
1
yellow solid. H NMR (400 MHz, DMSO-d6) δ 2.07 (2H,
General procedure for the synthesis of target molecules
C1–C3
m, CH2CH2Ph), 2.58 (2H, t, J = 7.4 Hz, CH2CH2Ph), 4.04
(2H, t, J = 6.8 Hz, NCH2), 6.86 (1H, t, J = 7.6 Hz, Ar-H),
7.06–7.11 (2H, m, Ar-H), 7.29 (2H, d, J = 1.6 Hz, Ar-H),
7.41–7.43 (2H, m, Ar-H), 7.68 (1H, s, Ar-H), 7.78 (1H, s,
H-20), 8.06 (1H, d, J = 2.4 Hz, H-13), 10.86 (1H, s,
CONHCO), 11.66 (1H, s, NH). 13C NMR (100 MHz,
DMSO-d6) δ 31.8 (CH2CH2Ph), 31.9 (CH2CH2Ph), 46.3
(NCH2), 105.5 (C-8), 112.1 (C-17), 119.7, 121.9, 122.3,
123.2, 126.1, 126.2, 126.4, 127.6, 129.2, 131.1, 131.9,
1M t-BuOK in THF (5 mL) was added to a mixture of
compoud 16 (1 equiv.), compound 17 (2 equiv.), and 4 Å
molecular sieve (100 mg) in anhydrous DMF (10 mL) at 0 °
C under N2 atmosphere, the whole solution was stirred at
room temperatue for 24 h. After the completion of the
reaction (monitored by TLC), the resulting solution was