One-Pot Cascade Reactions Leading to Pyrido[2′,1′:2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinolines under Bimetallic Relay Catalysis with Air as the Oxidant

Article abstract of DOI:10.1021/acs.joc.6b00996

In this paper, we report an efficient one-pot synthesis of 1,2,3-triazole/quinoline-fused imidazo[1,2-a]pyridines starting from 2-(2-bromophenyl)imidazo[1,2-a]pyridines, alkynes, and sodium azide. This novel method involves a one-pot bimetallic relay-catalyzed cascade process combining azide-alkyne cycloaddition, C-N coupling between 1,2,3-triazole and aryl bromide, and intramolecular cross dehydrogenative C-C coupling between 1,2,3-triazole and imidazo[1,2-a]pyridine. Notable features of this protocol include simple starting materials, sustainable oxidants, reduced synthetic steps, and high efficiency.

Full text of DOI:10.1021/acs.joc.6b00996

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Article
One-pot Cascade Reactions Leading to
Pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinolines
under Bimetallic Relay Catalysis with Air as the Oxidant
Ze Wang, Bin Li, Xinying Zhang, and Xuesen Fan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00996 • Publication Date (Web): 28 Jun 2016
Downloaded from http://pubs.acs.org on June 30, 2016
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One-pot Cascade Reactions Leading to Pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo-
[1,5-a]quinolines under Bimetallic Relay Catalysis with Air as the Oxidant
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Ze Wang, Bin Li, Xinying Zhang, and Xuesen Fan*
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School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Henan
Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical
Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan
453007, China. E-mail: xuesen.fan@htu.cn
Abstract: In this paper, we report an efficient one-pot synthesis of 1,2,3-triazole/quinoline fused
imidazo[1,2-a]pyridines starting from 2-(2-bromophenyl)imidazo[1,2-a]pyridines, alkynes and
sodium azide. This novel method involves a one-pot bimetallic relay catalyzed cascade process
combining azide−alkyne cycloaddition, C−N coupling between 1,2,3-triazole and aryl bromide,
and intramolecular cross dehydrogenative C−C coupling between 1,2,3-triazole and imidazo-
[1,2-a]pyridine. Notable features of this protocol include simple starting materials, sustainable
oxidant, reduced synthetic steps, and high efficiency.
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INTRODUCTION
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The 1,2,3-triazole scaffold plays an important role in medicinal arena as numerous molecules
bearing this framework are endowed with HIV protease inhibiting, anticancer, antituberculosis,
antifungal, or antibacterial activities.1-2 Owing to its stability toward metabolic degradation and
capability of hydrogen bonding, 1,2,3-triazole is also an ideal connecting unit in drug design.2 In
a further aspect, 1,2,3-triazole derivatives are frequently used as substrates in organic synthesis3
and material science.4 Therefore, the search for highly efficient methods for the preparation of
1,2,3-triazole derivatives has remained as a hot topic in the past several decades.5
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On the other hand, imidazo[1,2-a]pyridine constitutes a valuable skeleton of antiviral,
antimicrobial, antitumor, and neuroactive pharmaceuticals.6 As a result, continuing pursue for
efficient and sustainable strategies for the preparation and derivation of imidazo[1,2-a]pyridine
has been implemented.7 In this regard, Kumar et al. recently reported a novel protocol for the
preparation of 1,2,3-triazole/quinoline-fused imidazo[1,2-a]pyridines via copper-catalyzed
cascade reactions of 3-bromo-2-(2-bromophenyl)imidazo[1,2-a]pyridines with alkynes and
sodium azide (Scheme 1, eq. 1).8 While this elegant synthetic method is straightforward and
reliable, its use of substrates bearing a bromonated imidazo[1,2-a]pyridine scaffold is arguably
undesirable in terms of atom economy and environmental aspects as it requires an additional
bromonation step to prepare the substrates, and also results in more by-products.
The formation of C−C bond from two simple C−H bonds is highly appreciable as it does not
require substrate prefunctionalisation, and holds advantages such as reduced reaction steps, low
costs and less wastes.9 Inspired by the sustainable and environmental benign nature of cross
dehydrogenative coupling (CDC),10 and as part of our continuing interest in imidazo-
[1,2-a]pyridine derivatives,11 we envisioned a one pot synthesis of pyrido[2',1':2,3]imidazo-
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[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4) from 2-(2-bromophenyl)imidazo[1,2-a]pyridine (1),
alkyne (2) and sodium azide (3) via a cascade process combining azide-alkyne cycloaddition,
C−N coupling and cross dehydrogenative C−C coupling as shown in Scheme 1, eq. 2.
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Scheme 1. Different routes leading to 1,2,3-triazole/quinoline-fused imidazo[1,2-a]pyridine.
RESULTS AND DISCUSSIONS
To evaluate the feasibility of our proposed synthetic pathway, 2-(2-bromophenyl)imidazo-
[1,2-a]pyridine (1a), ethynylbenzene (2a) and sodium azide (3) were chosen as model substrates,
and they were initially treated with CuCl2·2H2O and K2CO3 in DMF at 80 ºC for 6 h.8 From this
reaction, 2-(2-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyl)imidazo[1,2-a]pyridine (I), the proposed
intermediate for the formation of 4 as shown in Scheme 1, was obtained in 60% yield (Table 1,
entry 1). To improve the efficiency, different copper salts were tried (entries 2-5). Among them,
CuI was the most efficient. Following studies on the effect of various bases showed that Na2CO3,
Cs2CO3, K3PO4·3H2O and DBU were less efficient than K2CO3 in promoting this reaction
(entries 5-9). When DMSO, 1-methyl-2-pyrrolidinone (NMP), ethanol or CH3CN was used as
the reaction medium, the yield of I decreased compared with DMF (entries 5, 10-13). Raising
the reaction temperature, to our delight, improved the yield of I obviously (entries 5, 14-16).
Finally, it was found that reaction period shorter than 6 h gave lower yield (entry 15 vs 17). In
summary of the optimization study, I could be obtained in 92% yield through treatment of 1a,
2a and 3 with CuI and K2CO3 in DMF at 120 ºC under air for 6 h (entry 15).
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Table 1. Optimization Study for the Formation of intermediate I a
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Entry
1
Catalyst
CuCl2·2H2O
CuCl2
Cu(OAc)2
CuCl
CuI
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
K3PO4·3H2O
DBU
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
NMP
ethanol
CH3CN
DMF
DMF
DMF
DMF
t/h T/ºC Yield (%)b
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4
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CuI
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CuI
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CuI
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CuI
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CuI
K2CO3
K2CO3
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K2CO3
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K2CO3
K2CO3
K2CO3
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CuI
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CuI
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CuI
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CuI
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CuI
CuI
CuI
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), 3 (0.6 mmol), catalyst (0.05
mmol), base (0.6 mmol), solvent (3 mL), air. b Isolated yields.
With the highly efficient formation of the key intermediate I, we moved forward to study the
one pot preparation of 1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4a). Thus, the mixture of 1a, 2a and 3 was treated with CuI and K2CO3 in DMF at 120 ºC for 6
h. Then, Pd(OAc)2 and Cu(OAc)2 were added, and the resulting mixture was stirred at 120 ºC
for 7 h. From this reaction, 4a was successfully obtained albeit in low yield (Table 2, entry 1).
To improve the efficiency, optimizations were carried out by varying the reaction parameters.
As a first aspect, inspired by the fact that protonic acids have been frequently used as effective
additives for metal-catalyzed C−H functionalizations,12 we tried acetic acid as an additive for
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this transformation. To our delight, addition of AcOH could indeed improve the reaction (entry
2). Gratifyingly, increases in the loading of AcOH till to 3 equiv provided a substantial increase
in the yield of 4a (entries 3-5). Although PivOH has proven to be superior to other organic acids
in previous cases of C−H functionalization,12c replacing AcOH with PivOH did not lead any
improvement in the efficiency of this reaction (entry 4 vs 6). In following studies, acetic acid
was selected as the additive of choice due to lower cost. Furthermore, to check the effect of
different catalysts, PdCl2, Pd2(dba)3, and Pd(PPh3)2Cl2 were tried, and they were found to be less
effective than Pd(OAc)2 in promoting this reaction (entries 4, 7-9). Other oxidant such as
Cu(OTf)2 was found to be inferior to Cu(OAc)2 (entry 10 vs 4). When the reaction was run
under O2 or air in the absence of Cu(OAc)2, its efficiency diminished (entries 11-12). On the
other hand, when it was run under air but in the presence of 10 mol% of Cu(OAc)2, the yield of
4a was comparable with those obtained by using stoichiometric amount of Cu(OAc)2 (entry 13
vs 4). In another control experiment, the reaction was run under N2 in the presence of 10 mol%
of Cu(OAc)2. Under this circumstance, only trace amount of 4a was formed (entry 14). These
results indicated that air could act as the terminal oxidant for this CDC reaction. Arguably, this
is an interesting and promising finding as in most of the previous CDC reactions stoichiometric
or even excess amount of oxidants such as Cu(OAc)2, AgOAc, PhI(OAc)2, BQ etc. were
needed.7 Compared with those oxidants, air is obviously more advantageous, and thus offers
attractive industrial prospects in terms of green and sustainable chemistry. Temperature also
showed some effect on the yield of 4a, and the optimum temperature turned out to be 120 ºC
(entries 13, 15-17). Finally, it was found that doubling the amount of CuI to 20 mol%, the yield
of 2a was only 46% (entry 18), indicating that addition of Cu(II) is crucial for the CDC process.
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Table 2. Optimization Study for the Formation of 4aa
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Entry
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Catalyst
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Oxidant (equiv) Additive (equiv) T/ºC Yield (%)b
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Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
Cu(OAc)2 (1)
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trace
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AcOH (1)
AcOH (2)
AcOH (3)
AcOH (4)
PivOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (3)
3
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Pd2(dba)3
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Pd(PPh3)2Cl2 Cu(OAc)2 (1)
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14c
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18d
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Cu(OTf)2 (1)
O2
Cu(OAc)2 (0.1)
Cu(OAc)2 (0.1)
Cu(OAc)2 (0.1)
Cu(OAc)2 (0.1)
Cu(OAc)2 (0.1)
100
130
120
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), 3 (0.6 mmol), CuI (0.05 mmol),
K2CO3 (0.6 mmol), DMF (3 mL), air, 120 ºC, 6 h; then Pd catalyst (0.025 mmol), oxidant,
additive, air, 7 h. b Isolated yields. c Under N2. d 0.1 mmol of CuI were used.
Once the optimization had been performed, we next evaluated a series of substrates to
determine the influence of steric and electronic parameters on the efficiency of this cascade
transformation. Firstly, with 1a and 3 as model substrates, the scope of alkynes (2) was explored.
The results listed in Table 3 indicated that ethynylbenzenes bearing different substituents on the
phenyl ring took part in this cascade process smoothly to give 4a-4i in reasonably good yields.
Meanwhile, various functional groups such as fluoro, bromo, methyl, methoxy and
trifluoromethyl were well tolerable, and the electronic and steric nature of the substituents did
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not show obvious effect on the yield of 4. Moreover, 2-ethynylthiophene could also participate
in this cascade process to give the corresponding product 4j in moderate yield. Interestingly, in
addition to aryl substituted alkynes, dec-1-yne and prop-2-ynylbenzene were found to be also
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suitable substrates for this transformation to afford 4k and 4l.
Table 3. Studies on the scope of alkynes (2) a,b
4a, 69%
4e, 68%
4i, 67%
4b, 68%
4f, 74%
4j, 68%
4c, 72%
4g, 71%
4k, 69%
4d, 66%
4h, 62%
4l, 63%
a Conditions: 1a (0.5 mmol), 2 (0.6 mmol), 3 (0.6 mmol), CuI (0.05 mmol), K2CO3 (0.6 mmol),
DMF (3 mL), air, 120 ºC, 6 h; then Pd(OAc)2 (0.025 mmol), Cu(OAc)2 (0.05 mmol), AcOH
(1.5 mmol), air, 120 ºC, 7 h. b Isolated yields.
Next, with 2a and 3 as model substrates, diversely substituted 2-(2-bromophenyl)imidazo-
[1,2-a]pyridines (1) were explored, and the results were included in Table 4. First, 1 with either
electron-donating or electron-withdrawing group(s) on its 2-phenyl moiety reacted smoothly
with 2a and 3 to give 4m-4r in good yields. No obvious electronic effect was observed. Second,
1 having a methyl, methoxy, chloro, or trifluoromethyl group on its imidazo[1,2-a]pyridine unit
were tried, and they were all suitable for this cascade process to give products 4s-4w in an
efficient manner. Finally, 1 bearing substituents attached on both the 2-phenyl and the
imidazo[1,2-a]pyridine units took part in this reaction smoothly to afford 4x-4ab.
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Table 4. Studies on the scope of 2-(2-bromophenyl)imidazo[1,2-a]pyridines (1) a,b
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4m, 65%
4q, 71%
4u, 70%
4y, 61%
4n, 72%
4r, 62%
4v, 71%
4z, 70%
4o, 68%
4s, 70%
4w, 75%
4aa, 66%
4p, 64%
4t, 58%
4x, 66%
4ab, 65%
a Conditions: 1 (0.5 mmol), 2a (0.6 mmol), 3 (0.6 mmol), CuI (0.05 mmol), K2CO3 (0.6 mmol),
DMF (3 mL), air, 120 ºC, 6 h; then Pd(OAc)2 (0.025 mmol), Cu(OAc)2 (0.05 mmol), AcOH (1.5
mmol), air, 120 ºC, 7 h. b Isolated yields.
Based on the above results and previous reports,8,9,13 it is supposed that the formation of 4a
should firstly involve a CuI-catalyzed azide−alkyne cycloaddition of 2a with 3 to afford
intermediate A, which then undergoes a copper-hydrogen exchange to give intermediate B
(Scheme 2). Arylation of B with 1a through a C−N coupling results in the formation of the key
intermediate I. In the second phase of this cascade process, aromatic palladation of I through
cleavage of the C−H1 bond affords intermediate C. Subsequently, palladation of C by the
cleavage of the C−H2 bond affords a seven-membered palladacycle intermediate D. Finally,
reductive elimination occurs with D to generate 4a together with Pd(0), which is re-oxidized
into the Pd(II) species by Cu(OAc)2(cat.)/air. While the precise role played by the carboxylic
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acid additive is still unclear at this stage, it is postulated that it might have contributed to
neutralize the resulting mixture of the first phase and stabilize the Pd complex formed in the
second phase of this cascade procedure. Meanwhile, an alternative pathway, in which the
Cu-catalyzed azidation14 may occur in the initial step for the subsequent click reaction with
alkynes, could not be eliminated at this stage.
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Scheme 2. Plausible mechanism for the formation of 4a
CONCLUSION
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In conclusion, we have discovered an efficient one-pot approach for the synthesis of
1,2,3-triazole/quinoline-fused imidazo[1,2-a]pyridines via bimetallic relay catalyzed cascade
reactions of simple and readily available starting materials featured with a CDC of two C−H
bonds by using air as a sustainable oxidant. With this method, a series of diversely substituted
fused heterocycles were successfully constructed. Given its straightforward and sustainable
nature, and the importance of 1,2,3-triazole- and imidazo[1,2-a]pyridine-related heterocycles,
this new synthetic strategy is expected to find wide applications in both heterocyclic and
medicinal chemistry.
EXPERIMENTAL SECTION
General Methods. Unless otherwise noted, all the commercial reagents were used without
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further purification. 2-(2-Bromophenyl)imidazo[1,2-a]pyridines (1) were synthesized through
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condensation of the corresponding 2-aminopyridines with 2-bromophenacyl bromides.15
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1
Melting points were recorded with a micro melting point apparatus and uncorrected. The H
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NMR spectra were recorded at 400 MHz. The 13C NMR spectra were recorded at 100 MHz.
Chemical shifts (in ppm) were referenced to tetramethylsilane in CDCl3 or TFA-d1. Multiplicity
was indicated as follows: s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of
doublets), etc. Coupling constants were given in hertz. High-resolution mass spectra (HRMS)
were obtained via an ESI mode by using a MicrOTOF mass spectrometer. The conversion of
starting materials was monitored by thin layer chromatography (TLC) using silica gel plates
(silica gel 60 F254 0.25 mm), and components were visualized by observation under UV light
(254 and 365 nm).
Typical procedure for the synthesis of 4a and spectroscopic data of 4a-4ab
To a flask containing 2-(2-bromophenyl)imidazo[1,2-a]pyridine (1a, 137 mg, 0.5 mmol),
phenylacetylene (2a, 61 mg, 0.6 mmol) and sodium azide (3, 39 mg, 0.6 mmol) in DMF (3 mL)
were added CuI (10 mg, 0.05 mmol) and K2CO3 (83 mg, 0.6 mmol). The mixture was then
stirred at 120 ºC for 6 h. Upon cooling to ambient temperature, Pd(OAc)2 (6 mg, 0.025 mmol),
Cu(OAc)2 (9 mg, 0.05 mmol) and AcOH (88 µL, 1.5 mmol) were added. The resulting mixture
was stirred at 120 ºC for 7 h. Then, it was quenched with saturated NH4Cl (10 mL), and
extracted with EtOAc (6 mL × 3). The combined organic phases were dried over anhydrous
Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography
on silica gel with petroleum ether/ethyl acetate (1:1) as eluent to give 4a in 69% yield. Other
1,2,3-triazole/quinoline-fused imidazo[1,2-a]pyridine derivatives 4b-4ab were obtained in a
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Phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4a)：Eluent: petroleum
ether/ethyl acetate (1:1); white solid (116 mg, 69%), mp 248-250 °C (lit.8 248-250 °C); 1H NMR
(400 MHz, TFA-d1) δ 6.99 (t, J = 6.8 Hz, 1H), 7.39 (d, J = 6.8 Hz, 1H), 7.46 (t, J = 7.2 Hz, 4H),
7.60 (t, J = 6.8 Hz, 1H), 7.83-7.93 (m, 4H), 8.38 (d, J = 7.6 Hz, 1H), 8.72 (d, J = 7.2 Hz, 1H);
13C NMR (100 MHz, TFA-d1) δ 109.7, 109.8, 112.6, 113.5, 115.4, 117.8, 118.0, 118.2, 118.8,
123.8, 129.4, 130.7, 132.1, 133.2, 134.2, 137.8, 142.0. MS: 336 [M+H]+.
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1-(4-Fluorophenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4b):
Eluent: petroleum ether/ethyl acetate (1:1); white solid (120 mg, 68%), mp 267-269 °C (lit.8
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268-270 °C); H NMR (400 MHz, CDCl3) δ 6.76 (td, J1 = 7.2 Hz, J2 = 0.8 Hz, 1H), 7.30-7.34
(m, 2H), 7.40-7.44 (m, 1H), 7.57 (d, J = 6.8 Hz, 1H), 7.71 (td, J1 = 6.8 Hz, J2 = 2.0 Hz, 2H),
7.74-7.78 (m, 1H), 7.80-7.88 (m, 2H), 8.69 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 8.92 (d, J = 8.0
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Hz, 1H); C NMR (100 MHz, CDCl3) δ 112.8, 115.6 (d, JC-F = 21.4 Hz), 117.1, 118.0, 118.9,
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122.5, 124.1, 127.4, 127.7, 127.9, 128.1 (d, JC-F = 3.2 Hz), 129.8, 131.4, 133.1 (d, JC-F = 7.9
Hz), 136.5, 140.0, 148.1, 163.5 (d, 1JC-F = 248.5 Hz). MS: 354 [M+H]+.
1-(p-Tolyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4c):
Eluent:
1
petroleum ether/ethyl acetate (1:1); white solid (126 mg, 72%), mp 265-267 °C; H NMR (400
MHz, CDCl3) δ 2.54 (s, 3H), 6.68 (td, J1 = 7.2 Hz, J2 = 0.8 Hz, 1H), 7.34-7.41 (m, 3H), 7.59 (d,
J = 8.0 Hz, 3H), 7.68-7.73 (m, 1H), 7.76-7.81 (m, 2H), 8.62 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H),
8.87 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.6, 112.5, 113.0, 117.0, 117.7, 118.8,
122.3, 123.9, 127.2, 127.5, 128.3, 129.0, 129.1, 129.6, 131.2, 131.4, 137.7, 139.3, 139.7, 148.0.
HRMS calcd for C22H15N5Na: 372.1220 [M+Na]+, found: 372.1202.
1-(4-(Trifluoromethyl)phenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4d): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (133 mg, 66%), mp 307-308 °C;
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1H NMR (400 MHz, CDCl3) δ 6.77 (td, J1 = 6.8 Hz, J2 = 0.8 Hz, 1H), 7.41-7.45 (m, 1H), 7.53 (d,
J = 6.8 Hz, 1H), 7.72-7.76 (m, 1H), 7.78-7.83 (m, 1H), 7.84-7.90 (m, 5H), 8.64 (dd, J1 = 8.0 Hz,
J2 = 0.8 Hz, 1H), 8.87 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 112.5, 112.9, 117.1,
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118.0, 118.8, 122.3, 123.8 (q, JC-F = 233.4 Hz), 124.0, 125.4 (q, JC-F = 4.0 Hz), 127.5, 127.8,
127.9, 129.9, 131.1, 131.3, 131.4, 135.7, 136.1, 140.3, 148.2. HRMS calcd for C22H13F3N5:
404.1118 [M+H]+, found: 404.1104.
1-(4-Bromophenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4e):
1
Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (141 mg, 68%), mp 273-274 °C; H
NMR (400 MHz, CDCl3) δ 6.80 (t, J = 6.8 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.58-7.62 (m,
3H), 7.71-7.76 (m, 3H), 7.78-7.85 (m, 2H), 8.64 (d, J = 8.0 Hz, 1H), 8.86 (d, J = 8.4 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 112.7, 112.8, 117.0, 117.9, 118.8, 122.2, 123.7, 124.0, 127.4,
127.7, 128.0, 129.8, 130.9, 131.3, 131.7, 132.7, 136.4, 140.1, 148.1. HRMS calcd for
C21H12BrN5Na: 436.0168 [M+Na]+, found: 436.0158.
1-(4-Methoxyphenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4f):
Eluent: petroleum ether/ethyl acetate (1:1); white solid (135 mg, 74%), mp 228-230 °C (lit.8
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231-232 °C); H NMR (400 MHz, CDCl3) δ 3.97 (s, 3H), 6.72 (t, J = 6.8 Hz, 1H), 7.12 (d, J =
8.4 Hz, 2H), 7.38 (t, J = 8.0 Hz, 1H), 7.62-7.65 (m, 3H), 7.73 (t, J = 7.6 Hz, 1H), 7.78-7.84 (m,
13
2H), 8.66 (d, J = 7.2 Hz, 1H), 8.91 (d, J = 8.0 Hz, 1H); C NMR (100 MHz, CDCl3) δ 55.6,
112.7, 113.1, 113.8, 117.1, 117.8, 118.9, 122.4, 124.0, 124.2, 127.2, 127.5, 128.2, 129.6, 131.5,
132.6, 137.4, 139.7, 148.0, 160.5. MS: 366 [M+H]+.
1-(m-Tolyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4g):
Eluent:
petroleum ether/ethyl acetate (1:1); pale yellow solid (124 mg, 71%), mp 216-217 °C (lit.8
1
218-219 °C); H NMR (400 MHz, CDCl3) δ: 2.48 (s, 3H), 6.65 (t, J = 6.8 Hz, 1H), 7.34 (t, J =
8.0, 1H), 7.41 (d, J = 4.0 Hz, 1H), 7.46 (t, J = 7.6, 2H), 7.53 (d, J = 5.6 Hz, 2H), 7.67 (t, J = 8.0,
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1H), 7.75 (t, J = 8.8, 2H), 8.58 (d, J = 7.6 Hz, 1H), 8.83 (d, J = 8.4 Hz, 1H); C NMR (100
MHz, CDCl3) δ 21.5, 112.4, 112.9, 117.0, 117.6, 118.8, 122.3, 123.9, 127.1, 127.5, 128.3, 128.4,
129.5, 130.0, 131.4, 131.8, 131.9, 137.8, 138.2, 139.7, 147.9. MS: 350 [M+H]+.
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1-(3-Fluorophenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4h):
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Eluent: petroleum ether/ethyl acetate (1:1); white solid (109 mg, 62%), mp 270-272 °C; H
NMR (400 MHz, CDCl3) δ 6.74 (t, J = 6.8 Hz, 1H), 7.33 (t, J = 8.0, 1H), 7.40 (t, J = 8.0 Hz, 1H),
7.46 (d, J = 7.6, 1H), 7.51 (d, J = 9.6 Hz, 1H), 7.57 (d, J = 7.2, 2H), 7.74 (t, J = 7.6, 1H),
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7.79-7.85 (m, 2H), 8.65 (d, J = 7.6 Hz, 1H), 8.88 (d, J = 8.4 Hz, 1H); C NMR (100 MHz,
CDCl3) δ 112.6, 112.8, 116.3 (d, 2JC-F = 20.7 Hz), 117.1, 117.9, 118.2 (d, 2JC-F = 21.4 Hz), 118.8,
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122.4, 124.0, 127.1 (d, JC-F = 2.4 Hz), 127.4, 127.7, 127.9, 129.8, 130.0 (d, JC-F = 8.7 Hz),
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131.4, 134.1 (d, JC-F = 8.0 Hz), 136.3, 140.1, 148.1, 162.5 (d, JC-F = 247.8 Hz). HRMS calcd
for C21H13FN5: 354.1150 [M+H]+, found: 354.1138.
1-(2-Fluorophenyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4i): Eluent:
petroleum ether/ethyl acetate (1:1); yellow solid (118 mg, 67%), mp 246-248 °C; 1H NMR (400
MHz, CDCl3) δ 6.73 (t, J = 6.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.39-7.46 (m, 2H), 7.62 (d, J
= 6.4 Hz, 1H), 7.67 (d, J = 6.0 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.81-7.91 (m, 3H), 8.71 (d, J =
13
7.6 Hz, 1H), 8.94 (d, J = 8.0 Hz, 1H); C NMR (100 MHz, CDCl3) δ 112.8, 113.2, 115.8 (d,
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2JC-F = 21.1 Hz), 117.2, 118.0, 119.0, 120.5 (d, JC-F = 14.6 Hz), 123.8, 124.1, 124.7 (d, JC-F
=
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3.6 Hz), 127.4 (d, JC-F = 9.5 Hz), 127.7, 129.7, 130.9, 131.5, 131.7 (d, JC-F = 7.3 Hz), 133.1,
133.2, 140.1, 148.3, 160.7 (d, 1JC-F = 246.5 Hz). HRMS calcd for C21H13FN5: 354.1150 [M+H] +,
found: 354.1141.
1-(Thiophen-2-yl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4j): Eluent:
petroleum ether/ethyl acetate (1:1); pale yellow solid (116 mg, 68%), mp 252-254 °C; 1H NMR
(400 MHz, TFA-d1) δ 7.23 (t, J = 6.8 Hz, 1H), 7.30 (s, 1H), 7.56 (d, J = 6.0 Hz, 2H), 7.80 (d, J=
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3.2 Hz, 1H), 7.95-8.00 (m, 1H), 8.02-8.09 (m, 3H), 8.51 (d, J = 8.0 Hz, 1H), 8.91 (s, 1H); C
NMR (100 MHz, TFA-d1) δ 111.1, 111.6, 112.3, 112.5, 112.9, 113.5, 114.4, 115.4, 116.3, 116.7,
117.2, 119.2, 128.3, 129.8, 131.6, 132.6, 134.5, 137.9, 142.4. HRMS calcd for C19H11N5SNa:
364.0627 [M+Na]+, found: 364.0620.
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1-Octylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4k): Eluent: petroleum
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ether/ethyl acetate (1:1); yellow solid (128 mg, 69%), mp 121-122 °C; H NMR (400 MHz,
CDCl3) δ 0.85 (t, J = 6.8 Hz, 3H), 1.25-1.37 (m, 8H), 1.45-1.52 (m, 2H), 1.82-1.90 (m, 2H),
3.28 (t, J = 8.0 Hz, 2H), 6.93 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.31-7.35 (m, 1H), 7.53-7.57 (m,
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1H), 7.60-7.67 (m, 2H), 8.38 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 8.58-8.60 (m, 2H); C NMR
(100 MHz, CDCl3) δ 14.1, 22.6, 28.3, 29.2, 29.3, 29.4, 31.5, 31.8, 113.2, 113.4, 116.6, 118.1,
118.3, 122.0, 123.6, 125.5, 127.0, 127.2, 129.2, 131.2, 136.9, 138.6, 147.3. HRMS calcd for
C23H25N5Na: 394.2002 [M+Na]+, found: 394.1983.
1-Benzylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4l):
Eluent:
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petroleum ether/ethyl acetate (1:1); white solid (110 mg, 63%), mp 238-239 °C; H NMR (400
MHz, TFA-d1) δ 5.04 (s, 2H), 7.06 (d, J = 6.8 Hz, 2H), 7.16-7.21 (m, 3H), 7.36-7.40 (m, 1H),
7.94-8.01 (m, 2H), 8.04 (d, J = 3.2 Hz, 2H), 8.48 (d, J = 8.0 Hz, 1H), 8.78 (d, J = 8.4 Hz, 1H),
8.95 (d, J = 6.8 Hz, 1H); 13C NMR (100 MHz, TFA-d1) δ 109.8, 112.1, 112.6, 112.8, 113.5,
115.4, 117.9, 118.1, 118.2, 119.2, 123.8, 127.4, 128.4, 128.7, 129.7, 132.2, 132.3, 134.3, 138.1,
142.1. HRMS calcd for C22H15N5Na: 372.1220 [M+Na]+, found: 372.1236.
6-Fluoro-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4m):
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Eluent: petroleum ether/ethyl acetate (1:1); brown solid (115 mg, 65%), mp 260-262 °C; H
NMR (400 MHz, CDCl3) δ 6.65 (t, J = 6.8 Hz, 1H), 7.33-7.42 (m, 2H), 7.46 (d, J = 6.8 Hz, 1H),
7.61 (s, 3H), 7.69 (d, J = 5.6 Hz, 2H), 7.74 (d, J = 8.8 Hz, 1H), 8.48 (d, J = 9.6 Hz, 1H), 8.54 (t,
J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 103.9 (d, 2JC-F = 27.0 Hz), 112.3, 112.6, 115.2,
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116.0 (d, JC-F = 23.8 Hz), 117.6, 122.6, 126.1 (d, JC-F = 8.7 Hz), 127.4, 128.1, 128.5, 129.5,
131.3, 131.7, 132.1 (d, 3JC-F = 10.4 Hz), 137.6, 139.5, 148.0, 163.0 (d, 1JC-F = 248.5 Hz). HRMS
calcd for C21H13FN5: 354.1150 [M+H]+, found: 354.1136.
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6-Chloro-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4n): Eluent:
petroleum ether/ethyl acetate (1:1); yellow solid (133 mg, 72%), mp 274-276 °C; 1H NMR (400
MHz, CDCl3) δ 6.68 (t, J = 6.8 Hz, 1H), 7.40 (t, J = 8.4 Hz, 1H), 7.49 (d, J = 6.8 Hz, 1H),
7.61-7.66 (m, 4H), 7.70-7.71 (m, 2H), 7.79 (d, J = 8.8 Hz, 1H), 8.53 (d, J = 8.4 Hz, 1H), 8.86 (d,
J = 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 112.8, 112.9, 117.1, 117.3, 117.8, 122.6, 125.3,
127.5, 128.1, 128.2, 128.5, 129.5, 131.3, 131.67, 131.71, 135.7, 137.7, 139.3, 148.1. HRMS
calcd for C21H12ClN5Na: 392.0673 [M+Na] +, found: 392.0660.
6-Methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4o): Eluent:
petroleum ether/ethyl acetate (1:1); pale yellow solid (119 mg, 68%), mp 215-217 °C; 1H NMR
(400 MHz, CDCl3) δ 2.61 (s, 3H), 6.59 (td, J1 = 7.2 Hz, J2 = 0.8 Hz, 1H), 7.27-7.31 (m, 1H),
7.41-7.46 (m, 2H), 7.58 (dd, J1 = 5.2 Hz, J2 = 2.0 Hz, 3H), 7.68-7.71 (m, 3H), 8.36 (d, J = 8.0
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Hz, 1H), 8.58 (s, 1H); C NMR (100 MHz, CDCl3) δ 22.1, 112.3, 116.2, 116.8, 117.5, 122.3,
123.6, 127.0, 128.1, 128.4, 128.9, 129.3, 131.2, 131.3, 132.0, 135.2, 137.4, 139.8, 140.3, 147.8.
HRMS calcd for C22H15N5Na: 372.1220 [M+Na] +, found: 372.1186.
7-Methoxy-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4p):
1
Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (117 mg, 64%), mp 225-226 °C; H
NMR (400 MHz, CDCl3) δ 4.04 (s, 3H), 6.67 (t, J = 6.8 Hz, 1H), 7.33-7.39 (m, 2H), 7.52 (d, J =
7.2 Hz, 2H), 7.59-7.60 (m, 3H), 7.69-7.71 (m, 2H), 7.81 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 2.8 Hz,
13
1H), 7.78 (d, J = 9.2 Hz, 1H); C NMR (100 MHz, CDCl3) δ 56.0, 104.4, 112.5, 113.3, 117.7,
118.7, 119.3, 120.1, 121.6, 125.8, 127.3, 128.2, 128.4, 129.3, 131.3, 132.1, 137.5, 139.6, 147.9,
159.0. HRMS calcd for C22H16N5O: 366.1349 [M+H] +, found: 366.1361.
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(4q): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (143 mg, 71%), mp 283-284 °C;
1H NMR (400 MHz, CDCl3) δ 6.73 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.42-7.46 (m, 1H), 7.55 (d,
J = 7.2 Hz, 1H), 7.62-7.66 (m, 3H), 7.71-7.73 (m, 2H), 7.88 (d, J = 8.8 Hz, 1H), 8.05 (dd, J1 =
8.8 Hz, J2 = 1.6 Hz, 1H), 9.04 (s, 1H), 9.07 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
113.1, 113.6, 117.98, 118.03, 119.0, 122.0 (q, 3JC-F = 4.0 Hz), 124.0 (q, 1JC-F = 227.8 Hz), 126.1
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(q, JC-F = 4.0 Hz), 127.8, 128.2, 128.6, 129.6, 129.7, 129.9, 131.3, 131.5, 133.0, 138.0, 139.3,
148.4. HRMS calcd for C22H13F3N5: 404.1118 [M+H]+, found: 404.1132.
8-Phenyl-[1,3]dioxolo[4,5-g]pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4r): Eluent: petroleum ether/ethyl acetate (1:1); pale brown solid (118 mg, 62%), mp
224-226 °C; 1H NMR (400 MHz, CDCl3) δ 6.24 (s, 2H), 6.67 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H),
7.37 (td, J1 = 6.8 Hz, J2 = 0.8 Hz, 1H), 7.53 (d, J = 7.2 Hz, 1H), 7.60 (dd, J1 = 5.2 Hz, J2 = 1.6
Hz, 3H), 7.70-7.72 (m, 2H), 7.79 (d, J = 9.2 Hz, 1H), 7.97 (s, 1H), 8.32 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 97.6, 101.9, 102.4, 112.1, 112.3, 113.9, 117.5, 122.0, 127.2, 127.3, 128.3, 128.4,
129.3, 131.3, 132.1, 137.2, 140.1, 147.9, 148.1, 149.9. HRMS calcd for C22H13N5O2Na:
402.0961 [M+Na]+, found: 402.0966.
12-Methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4s):
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Eluent: petroleum ether/ethyl acetate (1:1); white solid (122 mg, 70%), mp 224-226 °C; H
NMR (400 MHz, CDCl3) δ 2.01 (s, 3H), 7.20-7.27 (m, 2H), 7.59-7.65 (m, 3H), 7.70-7.77 (m,
4H), 7.81 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 8.69 (dd, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 8.94 (d, J=
8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 18.0, 112.7, 116.9, 117.1, 119.1, 122.4, 122.9,
124.0, 126.1, 127.6, 128.3, 129.3, 129.5, 130.4, 131.4, 131.7, 132.2, 137.5, 139.7, 147.1. HRMS
calcd for C22H16N5: 350.1400 [M+H]+, found: 350.1385.
1-Phenyl-12-(trifluoromethyl)pyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
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(4t): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (117 mg, 58%), mp 271-272 °C;
1H NMR (400 MHz, TFA-d1) δ 7.57 (t, J = 7.6 Hz, 2H), 7.65 (d, J = 6.8 Hz, 2H), 7.73 (d, J =
7.6 Hz, 1H), 7.96 (s, 1H), 8.00 (d, J = 7.6 Hz, 1H), 8.03-8.10 (m, 2H), 8.30 (d, J = 9.2 Hz, 1H),
8.66 (d, J = 7.6 Hz, 1H), 8.83 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, TFA-d1) δ 112.8, 113.8,
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114.3, 118.2, 120.8 (q, JC-F = 180.8 Hz), 121,3, 123.5, 124.5, 124.8 (q, JC-F = 16.0 Hz), 128.7
(q, 3JC-F = 2.9 Hz), 130.0, 130.9, 131.0, 131.9, 132.6, 133.5, 134.0, 134.9, 135.9, 142.9. HRMS
calcd for C22H13F3N5: 404.1118 [M+H]+, found: 404.1122.
12-Chloro-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4u):
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Eluent: petroleum ether/ethyl acetate (1:1); brown solid (129 mg, 70%), mp 245-247 °C; H
NMR (400 MHz, CDCl3) δ 7.32 (dd, J1 = 9.6 Hz, J2 = 1.6 Hz, 1H), 7.40 (s, 1H), 7.62-7.68 (m,
3H), 7.70-7.75 (m, 4H), 7.82 (t, J = 7.6 Hz, 1H), 8.63 (d, J = 8.0 Hz, 1H), 8.91 (d, J = 8.0 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 113.2, 117.2, 117.9, 118.7, 120.8, 122.3, 124.1, 126.1,
127.7, 128.5, 128.6, 129.8, 129.9, 131.5, 131.55, 131.57, 138.0, 140.4, 146.2. HRMS calcd for
C21H13ClN5: 370.0854 [M+H]+, found: 370.0853.
11-Methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4v):
Eluent: petroleum ether/ethyl acetate (1:1); pale yellow solid (124 mg, 71%), mp 275-276 °C
(lit.8 273-274 °C); 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 6.35 (d, J = 6.8 Hz, 1H), 7.22(d,
J = 6.8 Hz, 1H), 7.32 (s, 1H), 7.56-7.62 (m, 4H), 7.66-7.70 (m, 3H), 8.42 (d, J = 8.0 Hz, 1H),
8.73 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 21.5, 112.3, 115.0, 115.7, 116.8, 118.6,
122.3, 123.7, 127.1, 127.3, 128.4, 129.20, 129.23, 131.0, 131.3, 132.0, 137.1, 138.6, 139.5,
148.2. MS: 350 [M+H]+.
11-Methoxy-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4w):
Eluent: petroleum ether/ethyl acetate (1:1); pale brown solid (137 mg, 75%), mp 260-261 °C; 1H
NMR (400 MHz, CDCl3) δ 3.92 (s, 3H), 6.35 (dd, J1 = 7.6 Hz, J2 = 2.4 Hz, 1H), 7.08 (d, J = 2.4
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Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.58-7.61(m, 3H), 7.70-7.73 (m, 2H), 7.75 (d, J = 7.6 Hz, 1H),
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7.78-7.82 (m, 1H), 8.64 (d, J = 7.6 Hz, 1H), 8.93 (d, J = 8.4 Hz, 1H); C NMR (100 MHz,
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CDCl3) δ 55.8, 94.8, 107.6, 112.4, 117.1, 118.8, 122.5, 123.9, 127.5, 128.4, 128.5, 129.3, 131.15,
131.21, 132.1, 136.9, 140.1, 150.2, 159.6. HRMS calcd for C22H15N5ONa: 388.1169 [M+Na]+,
found: 388.1158.
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11-Methoxy-7-methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinolin
e (4x): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (125 mg, 66%), mp 234-236 °C;
1H NMR (400 MHz, CDCl3) δ 2.67 (s, 3H), 3.89 (s, 3H), 6.33 (dd, J1 = 7.6 Hz, J2 = 2.8 Hz, 1H),
7.08 (d, J = 2.4 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.58-7.60 (m, 3H),
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7.69-7.72 (m, 2H), 8.48 (d, J = 8.0 Hz, 1H), 8.72 (s, 1H); C NMR (100 MHz, CDCl3) δ 22.0,
55.7, 94.8, 107.3, 111.9, 116.4, 116.9, 122.6, 123.6, 128.4, 128.5, 128.9, 129.3, 131.16, 131.21,
132.2, 136.8, 140.1, 140.3, 150.2, 159.4. HRMS calcd for C23H18N5O: 380.1506 [M+H]+, found:
380.1499.
7-Methoxy-11-methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinolin
e (4y): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (116 mg, 61%), mp 217-218 °C;
1H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H), 4.03 (s, 3H), 6.48 (dd, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H),
7.31-7.36 (m, 2H), 7.51 (s, 1H), 7.57-7.58 (m, 1H), 7.59 (d, J = 2.0 Hz, 2H), 7.69-7.71 (m, 2H),
13
7.92 (d, J = 2.8 Hz, 1H), 8.74 (d, J = 9.6 Hz, 1H); C NMR (100 MHz, CDCl3) δ 21.6, 56.0,
104.3, 112.9, 115.2, 116.0, 118.6, 119.1, 120.1, 121.7, 125.7, 127.3, 128.4, 129.2, 131.3, 132.2,
137.1, 138.7, 139.6, 148.3, 158.9. HRMS calcd for C23H17N5ONa: 402.1325 [M+Na]+, found:
402.1309.
7-Chloro-11-methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4z): Eluent: petroleum ether/ethyl acetate (1:1); pale yellow solid (134 mg, 70%), mp 230-
232 °C; 1H NMR (400 MHz, CDCl3) δ 1.94 (s, 3H), 7.10 (s, 1H), 7.16 (dd, J1 = 6.0 Hz, J2 = 0.8
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Hz, 1H), 7.54 (t, J = 5.2 Hz, 2H), 7.58 (d, J = 5.2 Hz, 1H), 7.62-7.64 (m, 3H), 7.66 (dd, J1 = 6.0
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Hz, J2 = 1.6 Hz, 1H), 8.58 (d, J = 1.2 Hz, 1H), 8.78 (d, J = 6.0 Hz, 1H); C NMR (100 MHz,
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CDCl3) δ 18.0, 113.3, 117.0, 118.7, 120.4, 122.7, 122.8, 123.6, 126.1, 128.3, 129.5, 129.67,
129.70, 130.7, 131.7, 132.0, 133.7, 137.6, 138.7, 147.2. HRMS calcd for C22H14ClN5Na:
406.0830 [M+Na]+, found: 406.0828.
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7-Fluoro-12-methyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline
(4aa): Eluent: petroleum ether/ethyl acetate (1:1); yellow solid (121 mg, 66%), mp 197-199 °C;
1H NMR (400 MHz, CDCl3) δ 1.94 (s, 3H), 7.10 (s, 1H), 7.16 (dd, J1 = 8.8 Hz, J2 = 1.2 Hz, 1H),
7.41-7.46 (m, 1H), 7.52-7.59 (m, 3H), 7.62 (d, J = 1.6 Hz, 2H), 7.64-7.65 (m, 1H), 8.23 (dd, J1 =
8.8 Hz, J2 = 2.8 Hz, 1H), 8.83-8.86 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 18.0, 109.6 (d, 2JC-F
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3
= 24.6 Hz), 113.2, 117.0, 117.5 (d, JC-F = 24.6 Hz), 119.4 (d, JC-F = 8.7 Hz), 120.9 (d, JC-F
=
9.6 Hz), 122.5, 122.7, 126.1, 127.8, 128.3, 129.4, 130.6, 131.7, 132.1, 137.6, 138.9, 147.1,
161.6 (d, 1JC-F = 246.1 Hz). HRMS calcd for C22H15FN5: 368.1306 [M+H]+, found: 368.1309.
6,12-Dimethyl-1-phenylpyrido[2',1':2,3]imidazo[4,5-c][1,2,3]triazolo[1,5-a]quinoline (4ab):
Eluent: petroleum ether/ethyl acetate (1:1); pale yellow solid (118 mg, 65%), mp 252-254 °C;
1H NMR (400 MHz, CDCl3) δ 1.97 (s, 3H), 2.64 (s, 3H), 7.11 (s, 1H), 7.13-7.16 (m, 1H), 7.49
(d, J = 7.6 Hz, 1H), 7.58-7.64 (m, 4H), 7.70-7.72 (m, 2H), 8.43 (d, J = 8.0 Hz, 1H), 8.65 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 18.0, 22.0, 112.1, 116.4, 116.6, 116.9, 122.1, 122.8, 123.6, 126.0,
128.2, 128.9, 129.2, 130.1, 131.2, 131.7, 132.3, 137.3, 139.7, 140.1, 146.9. HRMS calcd for
C23H17N5Na: 386.1376 [M+Na]+, found: 386.1377.
Acknowledgments. We are grateful to the National Natural Science Foundation of China
(NSFC) (grant numbers 21272058, 21572047), Program for Innovative Research Team in
Science and Technology in Universities of Henan Province (15IRTSTHN003), Program for
Science and Technology Innovation Talents in Universities of Henan Province (15HASTIT005),
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and PCSIRT (IRT 1061) for financial support.
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Supporting Information. Copies of 1H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
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