10.1002/asia.201900468
Chemistry - An Asian Journal
FULL PAPER
Synthesis of intermediate compounds M1-M3
7.32 (d, J = 7.7 Hz, 4H), 7.14–7.07 (m, 8H), 4.37 (q, J = 7.0 Hz, 2H), 1.50
(d, J = 6.8 Hz, 3H); 13C NMR (75 MHz, DMSO-d6)δ: 147.71, 146.50,
136.49, 136.07, 133.73, 130.03, 128.53, 124.61, 124.24, 123.41, 122.18,
120.82, 119.55, 111.49, 105.73, 41.53, 15.73; IR(KBr)ν: 3057, 2976,
2220, 1625, 1576, 1515, 1476, 751 cm-1; HRMS (ESI): m/z[M - H]+ calcd
for C36H27N5 528.2194, found 528.2198.
5-bromo-1H-indole-3-carbaldehyde (15 mmol), anhydrous potassium
carbonate (33 mmol), halogenated hydrocarbon (C2H5Br or PhCH2Cl,18
mmol) or ethyl acrylate (18 mmol), tributyl benzyl ammonium chloride
(0.2 g) and 2 5mL acetonitrile were added to a two-necked flask. The
mixture was stirred at reflux for a certain time (TLC tracking reaction),
then acetonitrile was evaporated, and then water was dripped to dissolve
potassium carbonate, and filtered. The filter cakes were recrystallized
with absolute ethanol to give compounds of M1–M3, pale yellow crystal
M1 (1-ethyl-5-bromo-1H-indole-3-carbaldehyde) with yield 96%, red
crystal M2 (1-benzyl-5-bromo-1H-indole-3-carbaldehyde) with yield 95%
and pale yellow crystal M3 {ethyl 3-(5-bromo-3-formyl-1H-indol-1-
y)propanoate} with yield 92%.
4-(3-(1H-Benzo[d]imidazol-2-yl)-1-benzyl-1H-indol-5-yl)-N,N-
diphenylaniline 1f. White powder, m.p.232.1–232.3 °C , yield 88.4%.1H
NMR (300 MHz, DMSO-d6)δ: 12.54 (s, 1H), 8.74 (s, 1H), 8.27 (s, 1H),
7.71–7.61 (m, 4H), 7.51 (d, J = 8.2 Hz, 2H), 7.39–7.26 (m, 9H), 7.18–
7.01 (m, 10H), 5.57 (s, 2H); 13C NMR (75 MHz, DMSO-d6)δ: 149.35,
147.71, 146.43, 144.67, 137.99,136.61, 136.36, 134.66, 133.52, 130.45,
130.02, 129.21, 128.54, 128.16, 127.82, 126.65, 124.62, 124.22, 123.38,
122.18, 121.98, 121.46, 119.78, 118.48, 111.63, 107.30, 50.03; IR(KBr)ν:
3060, 2980, 1626, 1587, 1515, 1493, 745 cm-1; HRMS (ESI): m/z[M - H]+
calcd for C40H30N4 565.2398, found 565.2402.
Synthesis of compounds 1
The synthesis of compounds 1a–1m was carried out according to the
previously published synthetic procedures[7c]. The coarse product was
concentrated under vacuum and recrystallized with EtOAc to obtain the
yellow or white powders products, respectively, with moderate low to high
yields.
4-(1-Benzyl-3-(5-methyl-1H-benzo[d]imidazol-2-yl)-1H-indol-5-yl)-
N,N-diphenylaniline 1g. White powder, m.p. 190.7–191.3 °C , yield
86.5%. 1H NMR (300 MHz, DMSO-d6)δ: 12.48 (s, 1H), 8.70 (d, J = 1.7 Hz,
1H), 8.23 (s, 1H), 7.66 (dd, J = 8.6, 6.2 Hz, 3H), 7.51 (dd, J = 8.6, 1.8 Hz,
1H), 7.43 (s, 1H), 7.38-7.31 (m, 10H), 7.15–7.04 (m, 8H), 6.96 (dd, J =
8.3, 1.6 Hz, 1H), 5.57 (s, 2H), 2.42 (s, 3H); 13C NMR (75 MHz, DMSO-
d6)δ: 149.51, 147.71, 146.41, 138.03, 136.62, 136.33, 133.43, 130.03,
129.21, 128.53, 128.14, 127.80, 126.63, 124.61, 124.22, 123.38, 111.59,
107.43, 50.01, 21.81; IR(KBr)ν: 3060, 3031, 1632, 1590, 1515, 1492, 753
cm-1; HRMS (ESI): m/z[M - H]+ calcd for C41H32N4 579.2554, found
579.2554.
2-(1-Ethyl-5-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole 1a. Yellow
powder, m.p. > 320 °C (lit[7c], > 320 °C ), yield 92.3%. 1H NMR (300 MHz,
DMSO-d6)δ: 12.48 (s, 1H), 8.75 (s, 1H), 8.23 (s, 1H), 7.81–7.62 (m, 4H),
7.53 (dd, J = 17.0, 9.4 Hz, 4H), 7.37 (t, J = 7.2 Hz, 1H), 7.19–7.10 (m,
2H), 4.38 (q, J = 6.7 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz,
DMSO-d6) δ: 149.53, 144.68, 142.15, 136.17, 134.64, 133.75, 129.59,
129.34, 127.49, 127.04, 127.00, 126.57, 122.15, 120.12, 118.38, 111.29,
110.81, 106.83, 41.39, 15.81; IR (KBr) ν: 3056, 2975, 1625, 1576, 1507,
1453, 1119, 741 cm-1; HRMS (ESI): m/z [M + H]+ calcd for C23H19N3
338.1652, found 338.1654.
2-(1-Benzyl-5-(4-(diphenylamino)phenyl)-1H-indol-3-yl)-1H-
benzo[d]imidazole-5-carbonitrile 1h. White powder, m.p. 198.0–
198.7 °C, yield 86.3%. 1H NMR (300 MHz, DMSO-d6) δ: 13.06 (s, 1H),
8.71 (s, 1H), 8.36 (d, J = 12.9 Hz, 1H), 8.10–7.98 (m, 1H), 7.66 (dd, J =
14.7, 8.6 Hz, 4H), 7.57–7.49 (m, 2H), 7.42–7.27 (m, 9H), 7.12–7.06 (m,
8H), 5.58 (s, 2H); 13C NMR (75 MHz, DMSO-d6)δ: 149.66, 147.64,
146.52, 136.35, 136.23, 130.03, 129.24, 128.52, 128.26, 127.81, 124.45,
124.26, 123.45, 56.54, 18.93; IR(KBr)ν: 3062, 3032, 2221, 1625, 1588,
1515, 1476, 754 cm-1; HRMS (ESI): m/z[M - H]+ calcd for C41H29N5
590.2350, found 590.2355.
2-(1-Ethyl-5-(p-tolyl)-1H-indol-3-yl)-1H-benzo[d]imidazole 1b. White
powder, m.p. > 320 °C (lit[7c], > 320 °C ), yield 90.2%. 1H NMR (300 MHz,
DMSO-d6)δ: 12.35 (s, 1H), 8.73 (d, J = 1.7 Hz, 1H), 8.19 (s, 1H), 7.76–
7.65 (m, 3H), 7.59–7.42 (m, 4H), 7.41–7.31 (m, 2H), 6.97 (dd, J = 8.1,
1.5 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 2.43 (s, 3H), 1.48 (t, J = 7.2 Hz,
3H); 13C NMR (75 MHz, DMSO-d6) δ: 149.22, 142.15, 136.14, 133.65,
129.34, 127.46, 127.02, 126.55, 123.00, 122.10, 120.14, 41.36, 21.81,
15.8. IR (KBr) ν: 3055, 2976, 1629, 1574, 1508, 1450, 1119, 752 cm-1;
HRMS (ESI): m/z [M + H]+ calcd for C24H21N3 352.1808, found 352.1809.
Synthesis of compounds 2
Here the synthesis of 2a {3-(3-(1H-Benzo[d]imidazol-2-yl)-5-phenyl-1H-
indol-1-yl)-N-(3,4,5-trimethoxyphenyl)propanamide } is used to illustrate
the general procedure for preparation of compounds 2.
2-(1-Ethyl-5-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole-5-
carbonitrile 1c. White powder, m.p. 281.3–281.8 °C , yield 87.6%.1H
NMR (300 MHz, DMSO-d6)δ: 13.03 (s, 1H), 8.73 (s, 1H), 8.37–7.98 (m,
2H), 7.73 (d, J = 6.8 Hz, 4H), 7.54 (dt, J = 13.6, 8.6 Hz, 4H), 7.39 (d, J =
7.1 Hz, 1H), 4.37 (q, J = 7.0 Hz, 2H), 1.49 (t, J = 6.9 Hz, 3H); 13C NMR
(75 MHz, DMSO-d6)δ: 142.01, 136.26, 134.21, 129.35, 127.51, 127.14,
126.51, 122.44, 119.97, 111.51, 105.79, 56.50, 41.54, 19.00, 15.73;
IR(KBr)ν: 3055, 2978, 2220, 1630, 1580, 1507, 1456,1118, 753 cm-1;
HRMS (ESI): m/z[M + H]+ calcd for C24H18N4363.1604, found363.1606.
Ester compound 1i (2 mmol) was added to a solution of NaOH (80 mmol)
in 40 mL ethonal/H2O (1:1) and stirred at refiux for 24 h, then 10% HCl
was added to the reaction mixture until PH to 2–3 following lots of
flocculation, and filtered. The filter cake was recrystallized with absolute
ethanol to give the corresponding acid.
3,4,5-Trimethoxyaniline (1.2 mmol) was added to a stirred solution of
EDC·HCl (1.2 mmol), HOBt (1.2 mmol) and the above corresponding
acid (1.0 mmol) in 15 mL DMF. At room temperature, the stirred mixture
reacted for 24 h, then solvent evaporated and get residue which
extracted with EtOAc (3 × 20 mL). Used anhydrous MgSO4 to dry the
combined organic phase, then concentrated under vacuum, the solid
residue was purified by recrystalliation with EtOAc to give the target
product 2a with total yield of 76.2%.
2-(1-Benzyl-5-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole 1d. White
powder, m.p. 281.5–282.4 °C (lit[7c],281.6–282.1 °C), yield 90.1%. 1H
NMR (300 MHz, DMSO-d6)δ: 12.54 (s, 1H), 8.77 (s,1H), 8.28 (s, 1H),
7.79–7.62 (m, 4H), 7.61–7.41 (m, 5H), 7.39–7.32 (m, 5H), 7.22–7.09 (m,
2H), 5.59 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ: 149.33, 142.08,
138.01, 136.56, 133.97, 130.54, 129.34, 129.22, 128.16, 127.78, 127.52,
127.08, 122.43, 120.19, 111.67, 107.36, 50.03; IR(KBr) ν: 3057, 2976,
1625, 1579, 1507, 1452,1086, 753 cm-1 HRMS (ESI): m/z[M + H]+ calcd
for C28H21N3 400.1808, found 400.1810
3-(3-(1H-Benzo[d]imidazol-2-yl)-5-phenyl-1H-indol-1-yl)-N-(3,4,5-
trimethoxyphenyl)propanamide 2a. White powder, m.p. 137.2–
137.5 °C, yield 76.2%. 1H NMR (300 MHz, DMSO-d6)δ: 12.58 (s, 1H),
9.92 (d, J = 8.4 Hz, 1H), 8.72 (s, 1H), 8.21 (s, 1H), 7.81–7.58 (m, 4H),
7.46 (t, J = 14.5 Hz, 4H), 7.23–7.04 (m, 3H), 6.89 (d, J = 8.5 Hz, 2H),
4.63 (d, J = 6.6 Hz,2H), 3.69 (s, 6H), 3.58 (s, 3H), 2.90 (d, J = 6.6 Hz,
2-(5-(4-(Diphenylamino)phenyl)-1-ethyl-1H-indol-3-yl)-1H-
benzo[d]imidazole-5-carbonitrile 1e. White powder, m.p. 213.8–
214.2 °C , yield 91.8%. 1H NMR (300 MHz, DMSO-d6)δ: 13.02 (s, 1H),
8.69 (s, 1H), 8.32–7.98 (m,2H), 7.78–7.64 (m, 4H), 7.56 (d, J = 3 Hz, 2H),
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