A C-H Oxidation/Two-Fold Cyclization Approach to Imidazopyridoindole Scaffold under Mild Oxidizing Conditions

Article abstract of DOI:10.1021/acs.joc.7b02448

An expeditious one-step synthesis of the imidazopyridoindole scaffold was achieved through the C-H oxidation/two-fold cyclization reaction of methyl ketone and tryptamine derivatives. Mild oxidizing conditions were employed to realize the efficient oxidation of C(sp³)-H bonds, while suppressing overoxidation of the intermediate and ensuring the cross-trapping of two in situ generated acylimine intermediates.

Full text of DOI:10.1021/acs.joc.7b02448

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Note
A C–H Oxidation/Two-fold Cyclization Approach to
Imidazopyridoindole Scaffold Under Mild Oxidizing Conditions
Jia-Chen Xiang, Zi-Xuan Wang, Yan Cheng, Jin-Tian Ma,
Miao Wang, Bo-Cheng Tang, Yan-Dong Wu, and An-Xin Wu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 24 Nov 2017
Downloaded from http://pubs.acs.org on November 24, 2017
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A C–H Oxidation/Two-fold Cyclization Approach to
Imidazopyridoindole Scaffold Under Mild Oxidizing
Conditions
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Jia-Chen Xiang, Zi-Xuan Wang, Yan Cheng, Jin-Tian Ma, Miao Wang, Bo-Cheng
Tang, Yan-Dong Wu and An-Xin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, Hubei, Wuhan 430079, P. R. China
Supporting Information Placeholder
TOC Graphic:
ABSTRACT: An expeditious one-step synthesis of the imidazopyridoindole scaffold was achieved
through the C–H oxidation/two-fold cyclization reaction of methyl ketone and tryptamine derivatives. Mild
3
oxidizing conditions were employed to realize the efficient oxidative of C(sp )–H bonds, while suppressing
overoxidation of the intermediate and ensuring the cross-trapping of two in situ generated acylimine
intermediates.
Imidazopyridoindole, which comprises a β-carboline system attached to an imidazole ring (Figure 1-a, i),
1
–5
is a privileged scaffold present in a variety of bioactive lead compounds. For example, compound ii has
1
been used as a hypnotic and sedative, while compound iii has shown anticonvulsive activity in the maximal
2
electroshock seizure test. Notably, compound iv, which was prepared via a four-step synthesis from
3
a
resin-bound dipeptides, is a bioavailable anti-Alzheimer agent that inhibits Ab25–35 neurotoxicity toward
3
b
the rat pheochromocytoma PC-12 cell line. Furthermore, Peganumine A (v), which contains an
imidaz-opyridoindole scaffold, has been shown to be an anticancer drug candidate exhibiting significant
4
cytotoxic effects. However, synthetic endeavors towards imidazopyridoindoles have been limited. A classic
1
,6
literature approach requires multi operation steps from commercially available materials tryptamine
7
(Figure 1-b). Based on the leading strategy of BIOS, we focused on the bond construction of
imidazopyridoindole in an attempt to develop an expeditious protocol for the synthesis of analogues of this
value-added scaffold.
In our reaction design, methyl ketone and tryptamine were employed to produce the target using a cascade
8
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coupling reaction driven by C–H oxidation, followed by two-fold cyclization sequences. The
cross-trapping of two in situ generated acylimine intermediates 2H-β-carboline-acylimine (T1) and
1
-imino-2-one derivative (T2) are considered as a key approach. However, T1 is unable to be trapped by
additional nitrogen donor, but could be rapidly transformed into fully aromatic β-carboline in high
1
1
temperature and high oxidizing conditions. As a result, the most challenging aspect of this synthesis was
1
2
the modulation of the reaction pathway through versatile reactive intermediates. We assumed that to
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regulate the oxidative environment and strike a balance between ensuring that C–H oxidation runs smoothly
and avoiding overoxidation of T1. Furthermore, the in situ trapping of T1 is rarely reported but a significant
way to develop new method for the synthesis of indole alkaloid-like skeletons. Herein, a successful
execution of our logic design is reported, providing an unprecedented one-pot one-stage synthesis of
imidazopyridoindoles (Figure 1-c).
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Figure 1. Representative Imidazopyridoindole Compounds and Related Synthetic Methods.
Our study commenced with the model reaction of acetophenone (1a) and tryptamine (2a) with 2.0 equiv
o
of NH Cl at 110 C. To realize C–H oxidation, 2.5 equiv of I and solvent DMSO, were used. TFA (1.0 equiv)
4
2
1
3
was also added to promote C–H oxidation and the Pictet–Spengler reaction. The major product was the
single cyclization product, β-carboline 3’. To our delight, a small amount (<10% yield) of
imidazopyridoindole 3a was obtained (Table 1, entry 1). However, the high temperature had led to the strong
o
oxidation environment generating 3’. A lower temperature (70 C) was attempted in the presence of
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additional oxidant oxone (0.2 equiv) to ensure C(sp )–H oxidation of acetophenone (1a). This resulted in a
significant improvement, with a 31% yield of 3a and supression of 3’ generation (entry 2). Next, different
nitrogen donors were investigated, of which ammonium molybdate gave the best result (85% of 3a and <10%
of 3’) (entries 3–7). Yields were not further improved when switching TFA with other acids, such as TFAA,
TfOH, HI, or Lewis acid Cu(NO ) •3H O (entries 8–11). Furthermore, a variety of oxidants were screened,
3
2
2
but failed to improve the yields (entries 12–15). Finally, we optimized the nitrogen donor dosage with the
results showing that 1/3 equiv of ammonium molybdate gave the best yield (entry 7).
(a)
Table 1. Reaction Optimization .
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[
N]
oxidant temp. 3a (3’)
acid
entry
1
(b)
(2.0)
(1.0)
(0.2)
(°C )
(%)
<10
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NH Cl
TFA
-
110
4
(
77)
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NH Cl
TFA
TFA
TFA
TFA
TFA
oxone
oxone
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70
70
70
70
31 (43)
trace
4
NH OAc
4
NH H O
oxone
oxone
oxone
trace
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•
2
NH PF
54 (27)
trace
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NH Al(SO )
4
4 2
ammonium
molybdate
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7
TFA
oxone
70
(<10)
(1/3)
(c)
8
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AM (1/3)
TFAA
TfOH
oxone
oxone
oxone
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70
70
trace
67
AM (1/3)
AM (1/3)
(
d)
1
0
HI
Cu(NO3)2
trace
11
AM (1/3)
oxone
H O
70
trace
·
3H O
2
1
2
AM (1/3)
AM (1/3)
AM (1/3)
AM (1/3)
TFA
TFA
TFA
TFA
70
70
70
70
trace
49
2
2
13
Na S O
2 2 4
1
1
4
5
K S O
4
66
2
2
TBHP
21
(a)
Reaction conditions: 1a (2.0 mmol), 2a (1.0 mmol), acid, oxidant and I
2
(2.5 mmol) were added in DMSO (3.0 mL)
(b)
(c)
and stirred for 10 h. Reactions were carried out in a pressure vessel. Isolated yields. AM = ammonium molybdate
(d)
(
4 6 7 2 2
(NH ) Mo O24•4H O). Using hydriodic acid, 57 wt.% solution in H O. TFA = trifluoroacetic acid. Oxone = potassium
peroxomonosulfate. TFAA = trifluoroacetic anhydride. TBHP = t-butyl hydroperoxide.
With optimal conditions in hand, we tested the reaction scope using various substituted methyl ketones and
tryptamine derivatives (Scheme 1). Aryl methyl ketones bearing electron-donating groups (4-Me, 4-OEt)
gave good yields (3b, 79%; 3c, 90%). However, when bearing more than one electron-donating substituents
(
3,4-OCH O, 3,4,5-OCH ), desired imidazopyridoindoles 3d and 3e were furnished in relative low yields
2 3
(
66% and 37%, respectively). Aromatic ketones bearing halogen substituents, such as 4–F, 4–Cl, and 4–Br,
afforded the corresponding products in moderate yields (3f, 72%; 3g, 39%; 3h, 70%), allowing further
modifications. When electron-withdrawing substituents were employed, desired products bearing 4-CF3,
4
-SO Me, and 4-Ph groups were readily prepared (3i, 61%; 3j, 68%; 3k, 85%). Sterically hindered
2
substituents 2-naphthyl methyl ketone and 1-naphthyl methyl ketone were also transformed into products
with moderate yields (3l, 37%; 3m, 51%) under these conditions. We investigated using unsaturated methyl
ketones to further expand the scope. (E)-4-phenylbut-3-en-2-one afforded imidazopyridoindole 3n smoothly
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in 83% yield. Fatty chain substrate α-ionone was also applicable, producing 3o in 55% yield. These results
determined that sensitive groups were tolerated under these mild conditions. However, this reaction still has
limitations in substrate scope. For example, simple ketone such as propan-2-one could not transform into
desired product. Ethyl acetate, N-phenylacetamide and 4-phenylbut-3-yn-2-one are also failed to afford the
corresponding imidazopyridoindole derivatives. Next, we investigated tryptamine substrate scope.
Tryptamines bearing electron-donating groups (5-Me, 5-OMe, and 7-Me) afforded 3p–3r in moderate yields
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(55–76%). Sensitive halogens groups were also tolerated (3s, 71%; 3t, 64%). Therefore, the electronic nature
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of the tryptamine substrates had little influence on the reactivity. To our delight, serotonin, which is a
privileged scaffold in bioactivity studies, afforded 3u in 45% yield. Furthermore, N-Me tryptamine
congeners were well tolerated, furnishing desired product 3v in reasonable yield (72%), for which the
structure was unambiguously confirmed by X-ray crystallography (please see Supporting information Fig.
S2 and Table S1). Natural tryptophan could not be converted to imidazopyridoindole targets. Instead, a little
trace of β-carboline-imidazo was obtained through decarboxylative oxidation (3w, <5%).
Scheme 1. Scope of Imidazopyridoindole Synthesis.
Next, we investigated the mechanism experimentally. The reaction of 1a under standard conditions without
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adding TFA or oxone, the yield of 3a decreased sharply (Scheme 2-A, entries 2 and 3). When react at room
temperature or replace DMSO to DMF, the transformation did not occur (Scheme 2-A, entries 4 and 5).
These results determined that, acid, oxidant, proper heating temperature and DMSO are all necessary. Next,
we conducted 1a in a similar condition without adding tryptamine and nitrogen donor, oxidation product M1
and its hydrate isomer M1’ could be isolated with or without TFA and oxone. However, when reacted at
room temperature, M1 and M1’ could only be detected with the addition of TFA and oxone which
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determined that TFA and oxone could promote C(sp )-H oxidation approach in low temperature (Scheme
2
-B). Using commercially available M1’ or prepared 2-iodo-1-phenylethanone (1aa) with tryptamine (2:1
mole ratio) under standard conditions with 0.5 equiv of I , 3a could be afforded in 87% and 82% yield,
2
respectively (Scheme 2-C) which determined M1 and 1aa are key intermediates. To the same reaction
without adding nitrogen donor, 2H-β-carboline-acylimine T1 could be isolated in 32% yield (Scheme 2-D).
Conducted M1’ and ammonium molybdate (6: 1 mole ratio) in DMSO-d6 for 20 min afford
2-imino-1-phenylethanone T2 (Scheme 2-E, please see Supporting information Fig. S1). According to these
results, we suggested that T1 and T2 are both key intermediates. Reaction of T1, ammonium molybdate and
phenylglyoxal hydrated species (M1’) or 1-(4-ethoxyphenyl)-2,2-dihydroxyethanone (M2’) gave desired
products 3a or asymmetric product 3x in 84% and 61% yield, respectively (Scheme 2-F), the by-product is
also 3’. These results proved our hypothesis that the reaction pathway involving a cross-trapping of two in
situ generated acylimine intermediates T1 and T2.
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Scheme 2. Control Experiments.
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Based on the above results and related reports, a mechanism is proposed in Scheme 3. Initially, the
3
combination of I , DMSO, TFA and oxone enabled oxidation of C (sp )–H in methyl ketones in a relative
2
low temperature gave phenylglyoxal M1. The Pictet–Spengler reaction of M1 and tryptamine then afforded
the 4H-β-carboline intermediate which is unstable. It could transform into 2H-β-carboline-acylimine T1
quickly. As a minor pathway, T1 could undergo overoxidation to generate β-carboline 3’ as a byproduct.
However, under our mild oxidizing conditions, T1 could be trapped by acylimine intermediates T2 which
generated in situ through the condensation of a nitrogen donor with another M1. Cyclization and proton
transformation realize imidazole formation, affording the desired product, imidazopyridoindole 3.
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Scheme 3. Possible Reaction Mechanism.
In conclusion, we report the straightforward synthesis of value-added imidazopyridoindole scaffolds from
simple materials. Mild oxidizing reaction conditions were chosen to generate 2H-β-carboline-acylimine,
which could be trapped by subsequent cross-trapping without overoxidation. Using this approach, a wide
library of imidazopyridoindoles with diverse substitution diversity can be readily prepared. The trapping
strategy of 2H-β-carboline-acylimine intermediate will also give inspirations to prepare other indole
alkaloid-like targets.
Experimental Section
General
All substrates and reagents were commercially available and used without further purification. TLC analysis
was performed using pre-coated glass plates. Column chromatography was performed using alkaline
aluminum oxide (200–300 mesh). IR spectra were recorded on a Perkin-Elmer PE-983 infrared spectrometer
–1 1
as KBr pellets with absorption in cm . H spectra were recorded in CDCl or DMSO-d on 600 MHz NMR
3
6
spectrometers and resonances (δ) are given in parts per million relative to tetramethylsilane. Data are
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reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet q =
1
3
quadruple), coupling constants (Hz) and integration. C spectra were recorded in CDCl or DMSO-d on 150
3
6
MHz. NMR spectrometers and resonances (δ) are given in ppm. HRMS were obtained on a Bruker 7-tesla
FT-ICR MS equipped with an electrospray source. The X-ray crystal structure determinations were obtained
on a Bruker SMART APEX CCD system. Melting points were determined using XT-4 apparatus.
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General procedure for the synthesis
A mixture of acetophenone 1a (2.0 mmol), tryptamine 2a (1.0 mmol), (NH ) Mo O •4H O (ammonium
4
6
7
24
2
molybdate) (0.33 mmol), trifluoroacetic acid (1.0 mmol), I (2.5 mmol), potassium peroxomonosulfate (0.2
2
o
mmol) and DMSO (3.0 mL) were added in a pressure vessel, then stirred at 70 C for 10 h. Then added 50
mL water and 30 mL saturated brine solution to the mixture and extracted with EtOAc 3 times (3 × 50 mL).
The extract was washed with 10% Na S O solution, dried over anhydrous Na SO and concentrated under
2
2
3
2
4
reduced pressure. The crude product was purified by column chromatography (eluent: petroleum ether
EtOAc=7/1) to afford the product 3a as yellow crystalline solid (330 mg, 85%).
/
Analytical Data for Compounds 3
phenyl(1-phenyl-6,11-dihydro-5H-imidazo [1',5':1,2]pyrido[3,4-b]indol-3-yl)methanone: (3a)
Yellow crystalline solid; 330 mg, 85% yield. mp = 214-215 ℃; IR (KBr) νmax: 1630, 1426, 1259,
−1 1
1
002, 907, 771, 676, cm ; H NMR (600 MHz, CDCl ) δ 8.44 – 8.29 (m, 3H), 7.79 (d, J = 7.2 Hz, 2H),
3
7.56 – 7.50 (m, 2H), 7.49 – 7.43 (m, 4H), 7.41 – 7.36 (m, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.20 – 7.16 (m,
13
1
H), 7.15 – 7.10 (m, 1H), 4.83 (t, J = 7.2 Hz, 2H), 3.20 (t, J = 7.2 Hz, 2H). C NMR (150 MHz,
CDCl ) δ 183.5, 142.4, 137.3, 136.7, 136.6, 134.4, 132.6, 131.0, 129.0, 128.13, 128.0, 127.7, 125.8,
3
+
1
24.8, 123.3, 120.4, 118.6, 111.4, 110.4, 103.7, 44.3, 20.7. HRMS (ESI) m/z calcd for C H N O
26 20 3
+
(
M+H) 390.1601, found 390.1605.
p-tolyl(1-(p-tolyl)-6,11-dihydro-5H-imidazo [1',5':1,2]pyrido[3,4-b]indol-3-yl)methanone: (3b)
Yellow crystalline solid; 327 mg, 79% yield. mp = 152-154 ℃; IR (KBr) νmax: 1623, 1603, 1438,
−1
1
1
2
328, 1261, 1177, 961, 906, 742 cm ; H NMR (600 MHz, CDCl ) δ 8.34 (s, 1H), 8.29 (d, J = 7.8 Hz,
3
H), 7.69 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 7.8 Hz, 1H), 7.31 – 7.23 (m, 5H), 7.20 – 7.17 (m, 1H), 7.16 –
13
7.12 (m, 1H), 4.83 (t, J = 7.2 Hz, 2H), 3.22 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.40 (s, 3H). C NMR
150 MHz, CDCl ) δ 183.3, 143.5, 142.6, 138.0, 136.8, 136.6, 134.8, 131.6, 131.2, 129.8, 128.7, 127.6,
(
3
1
25.9, 125.0, 124.4, 123.1, 120.4, 118.6, 111.4, 110.1, 44.3, 21.7, 21.3, 20.8. HRMS (ESI) m/z calcd
+
+
for C H N O (M+H) 418.1914, found 418.1910.
28
24
3
(4-ethoxyphenyl)(1-(4-ethoxyphenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)metha
none: (3c)
Yellow crystalline solid; 429 mg, 90% yield. mp = 217-218 ℃; IR (KBr) νmax: 1618, 1598, 1444, ,
−1
1
1
7
333, 1253, 1169, 1044 cm ; H NMR (600 MHz, CDCl ) δ 8.51 (s, 1H), 8.36 (d, J = 8.4 Hz, 2H),
3
.69 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 7.8 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.16-7.10 (m, 2H), 6.96 (d,
J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 4.77 (t, J = 7.2 Hz, 2H), 4.03-3.97 (m, 4H), 3.17 (t, J = 7.2
13
Hz, 2H), 1.40 (t, J = 7.2 Hz, 3H), 1.36 (t, J = 7.2 Hz, 3H). C NMR (150 MHz, CDCl ) δ 181.9, 162.7,
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2
2
2
2
2
2
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58.8, 142.5, 136.6, 136.3, 133.3, 129.9, 129.0, 126.6, 125.8, 125.2, 123.9, 122.9, 120.2, 118.4, 114.8,
+
+
1
13.6, 111.4, 109.7, 63.5, 63.4, 44.2, 20.7, 14.7. HRMS (ESI) m/z calcd for C H N O (M+H)
30 28 3 3
478.2125, found 478.2137.
benzo[d][1,3]dioxol-5-yl(1-(benzo[d][1,3]dioxol-5-yl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]i
ndol-3-yl)methanone: (3d)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Yellow crystalline solid; 315 mg, 66% yield. mp = 242-243 ℃; IR (KBr) νmax: 1620, 1479, 1256,
−
1 1
1
7
027, 1005 cm ; H NMR (600 MHz, CDCl ) δ 8.31 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H),
3
.58 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.27 (d, J = 6.6 Hz, 2H), 7.24 – 7.21 (m,
1H), 7.19 – 7.14 (m, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 6.08-6.05 (m, 4H), 4.86 (t,
13
J = 7.2 Hz, 2H), 3.25 (t, J = 7.2 Hz, 2H). C NMR (150 MHz, DMSO-d ) δ 180.5, 151.4, 147.7, 147.2,
6
1
47.1, 141.9, 137.6, 135.6, 131.3, 127.9, 127.6, 125.5, 124.7, 124.2, 122.5, 121.2, 119.7, 118.5, 112.5,
+
110.3, 110.0, 108.9, 107.9, 102.0, 101.2, 79.2, 44.2, 20.2. HRMS (ESI) m/z calcd for C H N O
5
28
20
3
+
(
M+H) 478.1397, found 478.1399.
(3,4,5-trimethoxyphenyl)(1-(3,4,5-trimethoxyphenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]i
ndol-3-yl)methanone: (3e)
Yellow crystalline solid; 209 mg, 37% yield. mp = 261-264 ℃; IR (KBr) νmax: 1631, 1576, 1465,
−1 1
1
7
6
451, 1336, 1326, 1127, 1003, 767 cm ; H NMR (600 MHz, DMSO-d ) δ 11.09 (s, 1H), 7.90 (s, 2H),
6
.58 (d, J = 7.8 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.20 – 7.10 (m, 3H), 7.10 – 7.04 (m, 1H), 4.78 (t, J =
13
.0 Hz, 2H), 3.89 (s, 6H), 3.81-3.79 (m, 9H), 3.75 (s, 3H), 3.21 (t, J = 6.0 Hz, 2H). C NMR (150
MHz, DMSO-d ) δ 180.7, 153.3, 152.3, 141.8, 137.7, 137.1, 135.7, 132.0, 129.1, 125.4, 124.7, 122.8,
6
119.8, 118.6, 112.4, 110.9, 108.5, 104.0, 603, 60.1, 55.9, 55.5, 44.4, 20.2. HRMS (ESI) m/z calcd for
+
+
C H N O (M+H) 570.2235, found 570.2233.
32
32
3
7
(4-fluorophenyl)(1-(4-fluorophenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)methan
one:(3f)
Yellow crystalline solid; 307 mg, 72% yield. mp = 243-245 ℃; IR (KBr) νmax: 1666, 1632, 1598,
−1 1
1
437, 1223, 1154, 907cm ; H NMR (600 MHz, CDCl ) δ 8.51 – 8.39 (m, 2H), 8.20 (s, 1H), 7.81 –
3
7.72 (m, 2H), 7.58 (d, J = 7.8 Hz, 1H), 7.32 (d, J = 7.2 Hz, 1H), 7.25-7.13 (m, 6H), 4.87 (t, J = 7.2 Hz,
13
2
1
H), 3.26 (t, J = 7.2 Hz, 2H). C NMR (150 MHz, CDCl ) δ 181.9, 166.5, 161.9, 142.3, 136.7, 135.8,
3
33.7, 133.7, 133.6, 133.6, 130.5, 129.6, 129.5, 125.8, 124.8, 124.6, 123.6, 120.6, 118.8, 116.3, 116.1,
+
+
115.3, 115.1, 111.5, 110.8, 44.5, 20.8. HRMS (ESI) m/z calcd for C H F N O (M+H) 426.1412,
26
18
2
3
found 426.1415.
(4-chlorophenyl)(1-(4-chlorophenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)metha
none: (3g)
Orange crystalline solid; 187 mg, 39% yield. mp = 286-287 ℃; IR (KBr) νmax: 1635, 1586, 1438,
−1
1
1
284, 1089, 960, 741 cm ; H NMR (600 MHz, DMSO-d ) δ 10.95 (s, 1H), 8.30 (d, J = 7.8 Hz, 2H),
6
7.79 (d, J = 7.2 Hz, 2H), 7.66 – 7.50 (m, 5H), 7.44 (d, J = 7.8 Hz, 1H), 7.19 – 7.12 (m, 1H), 7.10 – 7.04
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(
m, 1H), 4.74 (t, J = 7.2 Hz, 2H), 3.20 (t, J = 7.2 Hz, 2H). C NMR (150 MHz, DMSO-d ) δ 181.4,
6
1
41.9, 137.8, 135.9, 134.8, 132.6, 132.5, 132.4, 129.1, 129.0, 128.3, 125.5, 125.4, 124.3, 122.8, 119.8,
+
+
118.7, 112.5, 111.1, 44.2, 20.3. HRMS (ESI) m/z calcd for C H Cl N ONa (M+Na) 480.0641,
26
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2
3
found 480.0636.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
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2
2
3
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3
3
4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
4-bromophenyl)(1-(4-bromophenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)metha
none: (3h)
Orange powder solid; 381 mg, 70% yield. mp = 277-278 ℃; IR (KBr) νmax: 1636, 1440, 1259, 903,
−1 1
831, 740 cm ; H NMR (600 MHz, CDCl ) δ 8.28 (d, J = 7.8 Hz, 2H), 8.20 (s, 1H), 7.70 (d, J = 7.8 Hz,
3
2
1
H), 7.66 (d, J = 7.2 Hz, 2H), 7.62 (d, J = 7.8 Hz, 2H), 7.59 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 7.8 Hz,
13
H), 7.24 (s, 1H), 7.20 – 7.16 (m, 1H), 4.89 (t, J = 6.6 Hz, 2H), 3.27 (t, J = 6.6 Hz, 2H). C NMR (150
MHz, CDCl ) δ 182.3, 142.4, 136.8, 136.1, 135.7, 133.3, 132.6, 132.4, 131.4, 129.3, 128.1, 125.8,
3
1
25.2, 124.4, 123.8, 122.4, 120.7, 118.9, 111.6, 111.2, 44.5, 20.8. HRMS (ESI) m/z calcd for
+
+
C H Br N O (M+H) 545.98111, found 545.98114.
26
18
2
3
(
4-(trifluoromethyl)phenyl)(1-(4-(trifluoromethyl)phenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,
4-b]indol-3-yl)methanone: (3i)
Yellow crystalline solid; 322 mg, 61% yield. mp = 228-230 ℃; IR (KBr) νmax: 1643, 1620, 1326,
−1 1
1119, 1108, 1066, cm ; H NMR (600 MHz, CDCl ) δ 8.47 (d, J = 7.8 Hz, 2H), 8.20 (s, 1H), 7.94 (d, J
3
=
7.8 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 7.8 Hz, 1H), 7.36 (d, J =
8
.4 Hz, 1H), 7.28-7.25 (m, 1H), 7.20 (t, J = 7.2 Hz, 1H), 4.91 (t, J = 7.2 Hz, 2H), 3.29 (t, J = 7.2 Hz,
13
2H). C NMR (150 MHz, CDCl ) δ 182.4, 142.4, 140.2, 137.9, 136.9, 135.5, 134.0, 133.7, 131.2,
3
1
1
5
30.3, 130.0, 129.9, 127.8, 126.2, 126.0, 125.7, 125.0, 124.8, 124.6, 124.0, 123.1, 122.8, 120.9, 119.0,
+
+
11.8, 111.6, 103.9, 44.5, 20.8 HRMS (ESI) m/z calcd for C H F N O (M+H) 526.1349, found
28
18
6
3
26.1347.
(
4-(methylsulfonyl)phenyl)(1-(4-(methylsulfonyl)phenyl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4
b]indol-3-yl)methanone: (3j)
-
Orange crystalline solid; 386 mg, 68% yield. mp = 237-240 ℃; IR (KBr) νmax: 1637, 1441, 1330,
−1
1
1
295, 1151, 780 cm ; H NMR (600 MHz, DMSO-d ) δ 11.12 (s, 1H), 8.43 (d, J = 7.8 Hz, 2H), 8.17
6
(
d, J = 7.8 Hz, 1H), 8.11 (d, J = 7.8 Hz, 2H), 8.04 (s, 3H), 7.62 (d, J = 7.8 Hz, 1H), 7.45 (d, J = 7.8 Hz,
1H), 7.21 – 7.15 (m, 1H), 7.12 – 7.05 (m, 1H), 4.79 (t, J = 6.6 Hz, 2H), 3.32 (s, 3H), 3.28 (s, 3H), 3.24
1
3
(
d, J = 6.6 Hz, 2H). C NMR (150 MHz, DMSO-d ) δ 181.9, 143.7, 142.1, 141.4, 139.6, 138.6, 138.0,
6
1
34.6, 131.4, 130.2, 128.0, 127.8, 127.4, 126.7, 126.6, 125.5, 124.0, 123.2, 120.0, 118.9, 112.6, 111.9,
+
+
4
4.2, 43.7, 43.3, 20.2. HRMS (ESI) m/z calcd for C H N O S Na (M+H) 568.0971, found
28 23 3 5 2
568.1000.
[
1,1'-biphenyl]-4-yl(1-([1,1'-biphenyl]-4-yl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)
methanone: (3k)
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6
Yellow crystalline solid; 461 mg, 85% yield. mp = 185-186 ℃; IR (KBr) νmax: 1631, 1600, 1440,
−1 1
1
264, 909, 747, 694 cm ; H NMR (600 MHz, CDCl ) δ 8.54 (s, 1H), 8.38 (d, J = 7.8 Hz, 2H), 7.83 (d,
3
J = 7.8 Hz, 2H), 7.63 (d, J = 7.8 Hz, 2H), 7.53 (t, J = 7.8 Hz, 7H), 7.42 – 7.38 (m, 2H), 7.35 (t, J = 7.2
Hz, 3H), 7.31 – 7.27 (m, 1H), 7.20 (d, J = 7.8 Hz, 1H), 7.16 (t, J = 7.3 Hz, 1H), 7.14 – 7.10 (m, 1H),
13
4
.68 (t, J = 6.6 Hz, 2H), 3.08 (t, J = 6.6 Hz, 2H). C NMR (150 MHz, CDCl ) δ 182.9, 145.2, 142.7,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
140.7, 140.3, 140.1, 136.8, 136.4, 136.1, 133.3, 131.6, 128.8, 128.1, 127.7, 127.5, 127.3, 126.9, 126.6,
+
1
25.8, 124.9, 123.3, 120.4, 118.7, 111.6, 110.6, 44.3, 20.7. HRMS (ESI) m/z calcd for C H N O
38 28 3
+
(
M+H) 542.2227, found 542.2214.
naphthalen-2-yl(1-(naphthalen-2-yl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)metha
none: (3l)
Yellow crystalline solid; 181 mg, 37% yield. mp = 198-200 ℃; IR (KBr) νmax: 1688, 1629, 1441,
−1 1
1021, 783cm ; H NMR (600 MHz,CDCl ) δ 8.45 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 6.6 Hz, 1H), 8.11 (d,
3
J = 8.4 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.92 (dd, J = 16.4, 8.2 Hz, 2H), 7.87 (d, J = 8.0 Hz, 1H), 7.72
–
7.67 (m, 2H), 7.57 (d, J = 7.2 Hz, 3H), 7.54 – 7.49 (m, 3H), 7.44 – 7.40 (m, 1H), 7.16 – 7.11 (m, 2H),
13
7
.09 (d, J = 7.8 Hz, 1H), 5.15 (d, J = 6.6 Hz, 2H), 3.38 (t, J = 7.2 Hz, 2H). C NMR (150 MHz, CDCl )
3
δ 186.73, 143.46, 136.70, 135.54, 135.51, 135.27, 134.11, 133.85, 132.19, 131.88, 131.29, 130.61,
1
1
29.29, 128.43, 128.38, 127.71, 127.17, 126.90, 126.66, 126.35, 126.07, 125.88, 125.77, 125.58,
25.40, 124.56, 124.33, 123.33, 120.44, 118.78, 111.39, 110.27, 77.21, 77.00, 76.79, 44.57, 20.93.
+
+
HRMS (ESI) m/z calcd for C H N O (M+H) 490.19139, found 490.19138.
3
4
24
3
naphthalen-1-yl(1-(naphthalen-1-yl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)metha
none: (3m)
Yellow crystalline solid; 250 mg, 51% yield. mp = 111-112 ℃; IR (KBr) νmax: 1629, 1590, 1463,
−1
1
1
331, 1251, 903, 783, 775, 727 cm ; H NMR (600 MHz, DMSO-d ) δ 10.41 (s, 1H), 8.28 (d, J = 8.4
6
Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 8.01-7.96 (m, 4H), 7.64-7.56 (m, 6H), 7.51
– 7.47 (m, 1H), 7.36 – 7.32 (m, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.12 – 7.08 (m, 1H), 7.08 – 7.04 (m, 1H),
13
5
1
.06 (t, J = 6.6 Hz, 2H), 3.35 (t, J = 6.6 Hz, 2H). C NMR (150 MHz, DMSO-d ) δ 186.4, 142.8, 137.7,
6
36.2, 135.3, 133.8, 133.1, 131.6, 131.2, 130.7, 130.5, 129.1, 128.6, 128.4, 128.1, 127.6, 127.1, 127.1,
126.2, 126.1, 125.9, 125.9, 125.5, 124.6, 124.3, 122.6, 119.6, 118.6, 112.4, 110.2, 44.2, 20.3. HRMS
+
+
(
ESI) m/z calcd for C H N O (M+H) 490. 19139, found 490.1938.
34 24 3
(E)-3-phenyl-1-(1-((E)-styryl)-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)prop-2-en-1-o
ne: (3n)
Yellow powder; 366 mg, 83% yield. mp = 234-247 ℃; IR (KBr) νmax: 1644, 1633, 1599, 1574, 1447,
−1 1
1
260, 1040, 802 cm ; H NMR (600 MHz, CDCl ) δ 8.57 (s, 1H), 8.16 (d, J = 16.2 Hz, 1H), 7.84 (d, J
3
= 16.2 Hz, 1H), 7.71-7.70 (m, 2H), 7.61 (s, 1H), 7.60 – 7.57 (m, 2H), 7.46 (s, 1H), 7.42-7.40 (m, 3H),
7
.38 (s, 1H), 7.32 – 7.27 (m, 2H), 7.25 (t, J = 6.6 Hz, 2H), 7.21-7.18 (m, 2H), 4.87 (t, J = 7.2 Hz, 2H),
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.18 (t, J = 7.2 Hz, 2H). C NMR (150 MHz, CDCl ) δ 180.1, 143.4, 143.3, 137.7, 137.0, 135.0, 134.7,
3
30.7, 130.4, 128.8, 128.7, 127.9, 126.7, 126.5, 126.1, 125.1, 123.6, 123.2, 120.8, 119.0, 118.5, 111.6,
+
+
111.3, 44.0, 20.8. HRMS (ESI) m/z calcd for C H N O (M+H) 442.1914, found 442.1915.
30
24
3
(
E)-3-(2,6,6-trimethylcyclohex-2-en-1-yl)-1-(1-((E)-2-(2,6,6-trimethylcyclohex-2-en-1-yl)vinyl)-6,11-dih
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)prop-2-en-1-one: (3o)
−1
Yellow oil; 293 mg, 55% yield. IR (KBr) νmax: 1632.43, cm ; IR (KBr) νmax: 1653, 1447, 1420,
−1
1
1
283, 1095, 1025, 801 cm ; H NMR (600 MHz, CDCl ) δ 8.55 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.44
3
(
d, J = 15.0 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.97
(dd, J = 15.6, 10.2 Hz, 1H), 6.57 (d, J = 15.0 Hz, 1H), 6.41 (dd, J = 15.6, 10.2 Hz, 1H), 5.56 (s, 1H),
5
2
.46 (s, 1H), 4.91 (s, 1H), 4.83 (d, J = 4.2 Hz, 1H), 3.17 (t, J = 7.2 Hz, 2H), 2.43 (d, J = 10.2 Hz, 1H),
.32 (d, J = 9.6 Hz, 1H), 2.08 (s, 2H), 2.04 (s, 2H), 1.72 (s, 3H), 1.58 (s, 3H), 1.24-1.22 (m, 2H), 0.96
1
3
(s, 3H), 0.93 (s, 6H), 0.87 (s, 3H). C NMR (150 MHz, CDCl ) δ 180.1, 149.4, 142.8, 137.3, 135.0,
3
1
5
34.3, 133.5, 132.1, 127.5, 125.9, 125.4, 125.1, 123.2, 122.2, 121.5, 120.4, 118.7, 111.4, 110.3, 55.1,
4.3, 43.9, 32.5, 32.1, 31.2, 31.1, 28.0, 27.7, 26.8, 26.6, 23.0, 22.8, 22.8, 20.8. HRMS (ESI) m/z calcd
+
+
for C H N O (M+H) 534.3479, found 534.3478.
36 44
3
(
8-methyl-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
3p)
(
Yellow crystalline solid; 221 mg, 55% yield. mp = 236-238 ℃; IR (KBr) νmax: 1727, 1627, 1449,
−1
1
1
276, 1025, 798 cm ; H NMR (600 MHz, CDCl ) δ 8.43 (d, J = 7.8 Hz, 2H), 8.31 (s, 1H), 7.84 (d, J
3
=
7.8 Hz, 2H), 7.59 (t, J = 7.2 Hz, 1H), 7.55 – 7.47 (m, 4H), 7.44 (t, J = 7.2 Hz, 1H), 7.39 (s, 1H), 7.19
(d, J = 8.4 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 4.87 (t, J = 7.2 Hz, 2H), 3.23 (t, J = 7.2 Hz, 2H), 2.50 (s,
13
3
1
H). C NMR (150 MHz, CDCl ) δ 183.7, 142.5, 137.5, 135.0, 134.6, 132.7, 131.1, 129.9, 129.2, 128.2,
3
28.1, 1280, 128.0, 127.8, 126.1, 125.1, 124.9, 118.4, 111.1, 110.1, 44.5, 21.5, 20.8. HRMS (ESI) m/z
+
+
calcd for C H N O (M+H) 404.1757, found 404.1758.
27 22
3
(
8-methoxy-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
3q)
(
Yellow crystalline solid; 264 mg, 63% yield. mp = 171-174 ℃; IR (KBr) νmax: 1627, 1450, 1428,
−1 1
1
1
414, 1325, 1288, 1176, 924, 697 cm ; H NMR (600 MHz, CDCl ) δ 8.39 (d, J = 6.6 Hz, 2H), 8.19 (s,
3
H), 7.81 (d, J = 6.6 Hz, 2H), 7.56 (s, 1H), 7.49-7.41 (m, 4H), 7.43 (d, J = 6.6 Hz, 1H), 7.18 (d, J = 8.4
Hz, 1H), 6.98 (s, 1H), 6.87 (d, J = 7.2 Hz, 1H), 4.95 – 4.82 (m, 2H), 3.87 (s, 3H), 3.29 – 3.16 (m, 2H).
13
C NMR (150 MHz, CDCl ) δ 183.5, 154.5, 142.4, 137.4, 136.7, 134.4, 132.6, 131.7, 131.0, 129.0,
3
1
28.1, 127.9, 127.7, 126.2, 125.4 124.9, 113.6, 112.2, 110.1, 100.0, 55.7, 44.3, 20.7. HRMS (ESI) m/z
+
+
calcd for C H N O (M+H) 420.1707, found 420.1709.
2
7
22
3
2
(
10-methyl-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
3r)
(
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Yellow powder; 306 mg, 76% yield. mp = 126-127 ℃; IR (KBr) νmax:1634, 1451, 1433, 1261, 1022,
−1 1
8
02, 680, cm ; H NMR (600 MHz, CDCl ) δ 8.38 (d, J = 7.8 Hz, 2H), 8.19 (s, 1H), 7.83 (d, J = 7.2
3
Hz, 2H), 7.53 – 7.36 (m, 7H), 7.04 (t, J = 6.6 Hz, 1H), 6.98 (d, J = 6.6 Hz, 1H), 4.81 (t, J = 6.6 Hz, 2H),
13
3
1
.16 (t, J = 6.6 Hz, 2H), 2.34 (s, 3H). C NMR (150 MHz, CDCl ) δ 183.4, 142.4, 137.3, 136.6, 136.1
3
34.5, 132.6, 130.9, 128.9, 128.2, 127.9, 127.6, 125.3, 124.9, 124.4, 123.8, 120.6, 120.3, 116.4, 110.9,
+
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
44.3, 20.8, 16.3. HRMS (ESI) m/z calcd for C H N O (M+H) 404.1757, found 404.1759.
27 22 3
(8-chloro-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone: (3s)
Yellow crystalline solid; 300 mg, 71% yield. mp = 232-233 ℃; IR (KBr) νmax: 1637, 1277, 1049,
−1
1
1
025, 1005, 674 cm ; H NMR (600 MHz, DMSO-d ) δ 11.09 (s, 1H), 8.28 (d, J = 6.6 Hz, 2H), 7.80
6
(
d, J = 6.6 Hz, 2H), 7.66 (s, 2H), 7.58 – 7.49 (m, 4H), 7.45 (d, J = 7.8 Hz, 2H), 7.13 (d, J = 7.8 Hz, 1H),
1
3
4.74-4.72 (m, 2H), 3.20-3.19 (m, 2H). C NMR (150 MHz, CDCl ) δ 183.45, 142.49, 137.15, 137.02,
3
1
34.99, 134.13, 132.66, 130.89, 129.02, 128.12, 127.89, 127.62, 126.77, 126.11, 125.90, 124.20,
+
+
1
23.22, 117.94, 112.51, 109.62, 44.18, 20.52. HRMS (ESI) m/z calcd for C H ClN O (M+H)
26 19 3
424.12112, found 424.12112.
(
8-bromo-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]
3t)
pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
(
Yellow crystalline solid; 298 mg, 64% yield. mp = 214-217 ℃; IR (KBr) νmax: 1626, 1449, 1431,
−1
1
1
275, 962, 789, 687 cm ; H NMR (600 MHz, CDCl ) δ 8.39 (s, 1H), 8.36 (d, J = 7.8 Hz, 2H), 7.78 (d,
3
J = 7.8 Hz, 2H), 7.67 (s, 1H), 7.57 – 7.54 (m, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.46 (t, J = 7.2 Hz, 2H),
7.43 – 7.40 (m, 1H), 7.25 (d, J = 9.0 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 4.85 (t, J = 7.2 Hz, 2H), 3.18 (t,
1
3
J = 7.2 Hz, 2H). C NMR (150 MHz, CDCl ) δ 183.7, 142.7, 137.2, 135.2, 134.3, 132.8, 131. 0, 129.2,
3
1
28.3, 128.0, 127.8, 127.6, 126.0, 124.2, 121.3, 113.6, 112.8, 109.6, 44.3, 20.6. HRMS (ESI) m/z calcd
+
+
for C H BrN O (M+H) 468.0706, found 468.0707.
26 19
3
(
8-hydroxy-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
3u)
(
Yellow crystalline solid; 182 mg, 45% yield. mp = 243-245 ℃; IR (KBr) νmax: 1634, 1451, 1432,
−1
1
1
7
293, 1046, 976, 695 cm ; H NMR (600 MHz, DMSO-d ) δ 10.91 (s, 1H), 9.42 (s, 1H), 8.28 (d, J =
6
.2 Hz, 2H), 7.78 (d, J = 7.2 Hz, 2H), 7.65 (d, J = 6.6 Hz, 1H), 7.62 – 7.46 (m, 4H), 7.43 (d, J = 6.6 Hz,
13
1H), 6.85 (d, J = 8.4 Hz, 1H), 4.76-4.74 (m, 2H), 3.50-3.48 (m, 2H). C NMR (150MHz, DMSO-d ) δ
6
1
82.9, 146.9, 142.0, 137.3, 136.2, 133.8, 132.8, 130.7, 129.0, 128.1, 127.8, 127.4, 125.9, 124.5, 123.6,
+
1
13.6, 111.8, 109.6, 108.9, 44.2, 21.5. HRMS (ESI) m/z calcd for C H N O + (M+H) 406.15500,
26
20
3
2
found 406.15503.
(11-methyl-1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)(phenyl)methanone:
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8
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(
3v)
Yellow crystalline solid; 290 mg, 72% yield. mp = 161-164 ℃; IR (KBr) νmax: 1631, 1453, 1434,
−
1 1
1
267, 902, 742, 731, 695, cm ; H NMR (600 MHz, DMSO-d ) δ 8.31 (d, J = 7.8 Hz, 2H), 7.67 (d, J =
6
7.8 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2H), 7.58 (t, J = 7.2 Hz, 2H), 7.51 (t, J = 7.2 Hz, 2H), 7.45 (d, J = 7.8
Hz, 2H), 7.25 (t, J = 7.8 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 4.71 (t, J = 6.0 Hz, 2H), 3.20 (t, J = 6.0 Hz,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
2
1
H), 3.18 (s, 3H). C NMR (150 MHz, DMSO-d ) δ 182.8, 142.4, 139.5, 137.2, 136.6, 134.9, 132.9,
6
30.7, 128.7, 128.4, 128.2, 128.1, 125.7, 124.3, 122.8, 120.2, 119.0, 111.8, 110.7, 44.1, 33.5, 20.9.
+
+
HRMS (ESI) m/z calcd for C H N O (M+H) 404.1757, found 404.1759.
2
7
22
3
(4-ethoxyphenyl)(1-phenyl-6,11-dihydro-5H-imidazo[1',5':1,2]pyrido[3,4-b]indol-3-yl)methanone: (3x)
1
Yellow crystalline solid; 262 mg, 61% yield. mp = 190-192 ℃; H NMR (600 MHz, DMSO-d ) δ
6
1
0.87 (s, 1H), 8.35 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 7.2 Hz, 2H), 7.58 – 7.47 (m, 3H), 7.46-7.42 (m,
2H), 7.14 (t, J = 7.2 Hz, 1H), 7.05 (t, J = 10.2 Hz, 3H), 4.69 (s, 2H), 4.10 (d, J = 6.6 Hz, 2H), 3.17 (s,
13
2
1
H), 1.35 (t, J = 6.6 Hz, 3H). C NMR (150 MHz, DMSO-d ) δ 181.2, 162.5, 142.4, 137.7, 135.6,
6
34.0, 133.2, 129.6, 129.0, 127.7, 127.3, 125.6, 124.8, 124.4, 122.6, 119.7, 118.5, 113.9, 112.6, 110.5,
+
2
+
63.6, 44.1, 20.3, 14.6. HRMS (ESI) m/z calcd for C H N O (M+H) 434.18630, found 434.18631.
28
24
3
ASSOCIATED CONTENT
Supporting Information
1
13
Crystallographic data and copies of the H and C NMR spectra are involved. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
E-mail: chwuax@mail.ccnu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China (Grant Nos. 21472056 and 21602070)
and the Fundamental Research Funds for the Central Universities (CCNU15ZX002 and CCNU16A05002)
for financial support. This work was also supported by the 111 Project B17019. We acknowledge an
Excellent Doctoral Dissertation Cultivation Grant from Central China Normal University (2015YBYB089).
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