TBAF-Catalyzed Tandem Synthesis of Triazolo[4,5-c]quinolines at Ambient Temperature

Article abstract of DOI:10.1002/ejoc.202001280

A mild, efficient and metal-free synthetic method for 1H-[1,2,3]triazolo[4,5-c]quinolines has been developed via intermolecular [3+2] cycloaddition of β-(2-aminoaryl)-α,β-ynones and TMS-N₃, followed by intramolecular dehydration annulation sequential reactions. With 5 mmol-% of TBAF as catalyst, the reaction can smoothly proceed in DMF at ambient temperature to afford a wide range of functionalized 1H-[1,2,3]triazolo[4,5-c]quinolines in good to excellent yields.

Full text of DOI:10.1002/ejoc.202001280

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: TBAF-Catalyzed Tandem Synthesis of Triazolo[4,5-c]quinolines
at Ambient Temperature
Authors: Nan Sun, Han Yang, Kai Zheng, Liqun Jin, Baoxiang Hu,
Zhenlu Shen, and Xinquan Hu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001280
Link to VoR: https://doi.org/10.1002/ejoc.202001280
01/2020

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
TBAF-Catalyzed Tandem Synthesis of Triazolo[4,5-c]quinolines at
Ambient Temperature
Nan Sun,* Han Yang, Kai Zheng, Liqun Jin, Baoxiang Hu, Zhenlu Shen, and Xinquan Hu*
Prof. Dr. N. Sun, H. Yang, K. Zheng, Prof. Dr. L. Jin, B. Hu, Prof. Dr. Z. Shen, and Prof. Dr. X. Hu
College of Chemical Engineering
Zhejiang University of Technology
Hangzhou 310014, People’s Republic of China
E-mail: sunnan@zjut.edu.cn or xinquan@zjut.edu.cn
Supporting information for this article is given via a link at the end of the document.
Abstract: A mild, efficient and metal-free synthetic method for 1H-
Previous works for acessing 1,2,3-triazolo[4,5-c]quinolines:
[1,2,3]triazolo[4,5-c]quinolines
has
been
developed
via
A) Chen, 2013
N
N
O
HN
N
intermolecular [3+2] cycloaddition of β-(2-aminoaryl)-α,β-ynones and
TMS-N3, followed by intramolecular dehydration annulation
sequential reactions. With 5 mmol% of TBAF as catalyst, the
reaction can smoothly proceed in DMF at ambient temperature to
CuO(2.0 equiv.)
DMF, 110 oC, 24 h
+
NaN3
Ar
R
R
(2.0 equiv.)
Br
Ar
CuBr2(10 mol%)
L-proline (20 mol%)
Cs2CO3(4.0 equiv.)
air (oxidant)
B) Wu and Jia, 2018
afford
a
wide range of functionalized 1H-[1,2,3]triazolo[4,5-
O
O
+
+
NaN3
R
c]quinolines in good to excellent yields.
DMSO, 100 oC, 20 h
Ar
Br
(4.0 equiv.)
C) Wang, 2013
R2-N3
+
N
R2
R2
N
N
Pd(OAc)2 (5 mol%)
TBAI (3.0 equiv.)
N
N
N
Three steps
I
OH
Introduction
DMF, 90-120 o
8-10 h
C
+
I
NH
R1
R1
N
R1
NH2
Heterocycles play a center role in drug discovery and medicinal
chemistry.[1] Notably, about 80% of the currently global best-
selling pharmaceuticals are heterocyclic compounds.[2] 1,2,3-
Triazolo[4,5-c]quinoline is a kind of structurally novel tricyclic
fused heterocycle condensed by 1,2,3-triazole and quinoline
frameworks. Owing to the great medicinal value of both 1,2,3-
triazoles[3] and quinolines,[4] this class of heterocyclic
compounds are considered as promising candidates for the
generation of new chemical therapeutic agents. Up to date,
several related synthetic methods have been reported, which
include CuO-promoted tandem SNAr and cyclization of (E)-3-(2-
bromoaryl)-1-arylprop-2-en-1-ones and sodium azide (Scheme
1A),[5] CuBr-catalyzed and aerobic oxdative three-component
tandem reaction of 2-bromobenzaldehydes, aryl methyl ketones,
and sodium azide (Scheme 1B),[6] Pd(OAc)2-catalyzed
D) Tripathi, 2013; Elangovan, 2018
R3-N3
Tripathi
Pd/C, H2
MeOH, RT, 8-12h
:
R3
N
N
R3
Oxidative [3+2]
Cycloaddition
N
N
N
O
+
N
R2
R2
Elangovan
:
R1
R1
R1
O
Fe/AcOH,
110oC, 0.5 h
NO2
NO2
N
R2
E) This work:
O
N
N
HN
N
R2
TBAF (5 mol%)
DMF, RT, 8 h
TMS-N3
(1.1 equiv.)
+
R1
R1
R2
NH2
32 examples, up to 95% yield
Metal-free Mild reaction conditions Broad substrate scope High atom-/step-economy
Scheme 1. Synthetic strategies for 1,2,3-triazolo[4,5-c]quinolones.
intramolecular
cyclization
of
2-iodo-((1H-1,2,3-triazol-4-
chemistry and can be conveniently derived from simple
materials by a variety of methods.[11] Both the carbonyl group
and the polarized alkyne group render this class of compounds
highly reactive to undergo 1,4-conjugated addition, cycloaddition,
isomerization, carbonyl addition and many other transformations.
An early work reported by Marinelli’s group attracted our
attention.[12] In their extensive study on tandem synthesizing
quinoline derivatives from β-(2-aminoaryl)-α,β-ynones,[13] it was
found that an N-aryl substituted 1,2,3-triazolo[4,5-c]quinoline
yl)methyl)benzenamines followed by TBAI-mediated oxidation
(Scheme 1C),[7] and Pd/C-catalyzed[8] or Fe/AcOH-mediated[9]
intramolecular
reductive
cyclization
of
4-benzoyl-5-(2-
nitrophenyl)-1,2,3-triazoles (Scheme 1D). These methods made
considerable contributions for the access of 1,2,3-triazolo[4,5-
c]quinolines and their N-substituted derivatives, all of them,
however, relied on the use of transition metals as catalysts or
stoichiometric reductants. The removal of the residual transition
metals remaining in the final products as well as the cost would
be great challenges if these methods were practically applied in
pharmaceuticals production.[10] In addition, these methods were
also suffered from some other drawbacks such as harsh
reaction conditions, limited functional group tolerance, and poor
availability of special prefunctionalizated substrates. Therefore,
derivative,
4-(naphthalen-2-yl)-3-(4-nitrophenyl)-3H-[1,2,3]
triazolo [4,5-c]quinoline, can be obtained in 63% yield after
refluxing 3-(2-aminophenyl)-1-(naphthalen-1-yl)prop-2-yn-1-one
and 4-nitrophenylazide in 1,1,2,2-tetrachloroethane for 6 hours.
The reaction was assumed to proceed via the sequential 1,3-
dipolar cycloaddition of ynone and organic azide followed by
intramolecular dehydration annulation reactions. Unfortunately,
this method was demonstrated only by this special example.
Moreover, the reaction was carried out under rather harsh
conditions (~150 oC) with unsatisfied yield, most likely due to the
low reactivity of organic azides toward ynones. However, this
the development of
a new approach for diverse 1,2,3-
triazolo[4,5-c]quinoline compounds from readily available
substrates under mild and metal-free conditions remains highly
desirable.
α,β-Ynones are valuable synthons in modern synthetic organic
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
simple protocol inspired us to develop a more promising and
general approach for 1,2,3-triazolo[4,5-c]quinolines from β-(2-
aminoaryl)-α,β-ynones, envisaging that the cycloaddition
reaction between ynones and organic azides could be improved
by employing an alternative azide reagent. Trimethylsilyl azide
(TMS-N3) is a safe, powerful and commercially available azide
reagent widely used in the synthesis of diverse nitrogen-
containing molecules.[14] In analogy with organic azides, TMS-N3
can behave as a 1,3-dipole toward acetylenes, olefins and
nitriles to give corresponding triazoles and tetrazoles.[15]
Recently, Vaccaro and co-workers reported that such
cycloaddition reactions can be promoted by catalysis of
tetrabutylammonium fluoride (TBAF).[16] Herein, we presented
our findings that a broad range of functionalized 1H-[1,2,3]-
triazolo[4,5-c]quinolines can be delivered from β-(2-aminoaryl)-
α,β-ynones in good to excellent yields at ambient temperature
with TMS-N3 as an azidation source and TBAF as catalyst in
DMF (Scheme 1E).
Table 1. Optimizing the reaction conditionsa)
Yields (%)[b]
Catalyst
(x mol%)
Entry
Solvent
B1
54
52
20
23
27
19
14
88
93(90)
91
92
79
75
75
93
89
56
84
B1’
15
15
31
12
42
44
74(68)
4
1
THF
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
TBAF (5)
NH4F (5)
KF (5)
2
dioxane
toluene
EtOH
CH3CN
DCE
3
4
5
6
7
TCE
Results and Discussion
8
DMSO
DMF
We first selected our studies by choosing the reaction of 3-(2-
aminophenyl)-1-phenylprop-2-yn-1-one A1 and TMS-N3 (1.1
equiv.) as a template reaction to explore the feasibility of the
protocol (Table 1). In the initial attempt, the reaction was carried
out in THF with 5 mol% TBAF as catalyst. Excitingly, after stirred
at room temperature for 8 h, the starting material A1 was totally
9
2
10
11
12
13
14
15
16
17
18[c]
DMAc
NMP
DMF
5
3
5
consumed
and
the
desired
product
4-phenyl-1H-
[1,2,3]triazolo[4,5-c]quinolines (B1) was obtained in 54% yields,
along with 14% of 2-(5-phenylisoxazol-3-yl)aniline (B1’) as the
main by-product by HPLC analysis (entry 1, Table 1). Recently,
this competitive isoxazoles formation between α,β-ynones and
TMS-N3 via tandem hydroazidation/denitrogenation/cyclization
reactions has been disclosed by Reddy and co-workers, and its
chemo-selectivity was reported to be strongly solvent-
dependent.[17] To restrain this competitive side reaction as well
as improve the yield of B1, a wide range of organic solvents
were subsequently screened. The change of THF to either
dioxane, toluene, EtOH, CH3CN, DCM or TCE brought no
improvement in the reaction outcome (entries 2-7, Table 1).
However, on the other hand, the competitive by-product B1’ was
significantly depressed to less than 5%, and the target product
B1 was obtained in excellent yields when we switched to
aprotonic dipolar solvents, such as, DMSO, DMF, DMAc and
NMP (entries 8-11, Table 1). In particular, with DMF as reaction
medium, the isolated yield of B1 reached to 90% (entry 9, Table
1). After that, the catalytic activity of other F- source, such as
NH4F, KF and NaF, on this transformation was tested.
Unfortunately, all of them were far inferior to TBAF, which was
most likely ascribed to their insolubility in DMF (entries 12-14,
Table 1). Further optimization by varying the amount of TBAF
catalyst and reaction time did not provide better results (entries
15-18, Table 1). Finally, the optimal reaction conditions for this
transformation were obtained as follows: TBAF (5 mmol%) as
catalyst in DMF at room temperature for 8 h.
DMF
3
DMF
NaF (5)
2
DMF
TBAF (10)
TBAF (3)
-
2
DMF
2
DMF
4
DMF
TBAF (5)
2
[a] Reaction conditions: 3-(2-aminophenyl)-1-phenylprop-2-yn-1-one 1a (0.5
mmol), TMS-N3 (0.55 mmol), catalyst (0-10 mol%) and solvent (5 ml) at room
temperature (25-30 oC) for 8h. THF = tetrahydrofuran, DCE = dichloroethane,
TCE = trichloroethylene, DMF = N,N-dimethyl formamide, DMAc = N,N-
dimethyl acetamide, NMP = N-methyl-2-pyrrolidone. [b] Determined by HPLC
analyses, the yields were obtained with a standard curve method and the data
in parentheses were isolated yields. [c] Reacted at RT for 6 h.
with electron-donating group (Me and OMe) or moderated
electron-withdrawing group (F, Cl, Br and CF3) exhibited similar
reaction activity to the basic substrate A1 and corresponding
products (B2-B7) were obtained in excellent yields (91-95%)
under the identified reaction conditions. Whereas, for the
reaction of highly electron-withdrawing group (COOCH3, CN and
NO2) substituted phenyl ynone analogues A8-A10, a slight lower
yields (77-85%) were resulted, which was ascribed to their
reduced nucleophilicity of the carbonyl group affecting the
efficiency of this transformation (retarding the intramolecular
dehydration annulation to form quinoline cycle). Noteworthy,
most of these functionalized products can be further derived. It
seemed that the position of the substituents attached on the
phenyl ring had little influence on the reaction efficiency, since
no obvious difference in yield was observed for the reactions of
With the optimal conditions in hand, we started to evaluate the
substrate scope of this protocol. At first, the reaction scope with
respect to substituted phenyl on the carbonyl terminal of ynones
was investigated. As the results summarized in Table 2, a
variety of para-substituted phenyl ynones A2-A7 either attached
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
ortho- and mata-methyl substituted phenyl ynones (A11 and
A12) with its para-substituted analogue (A2). Furthermore,
ynones possessing multiple-substituted phenyl group (3-bromo-
5-methyl phenyl), fused aromatic group (naphthyl) or heteroaryl
group (furyl and thienyl) were employed and the desired
products B13-B16 were obtained in 87%, 79%, 78% and 75%
yields, respectively. In addition to aromatic ynones, alkyl ynones
also showed good compatibility with this transformation affording
the corresponding 4-alkyl 1H-[1,2,3]triazolo[4,5-c]quinolines
B17-B20 in good to excellent yields (75-84%). It is noteworthy to
point out that these type of products cannot be acquired by
previous reported methods.
Table 3. Substrate scope of β-(2-aminoaryl)-α,β-ynones with different
substituted 2-aminoaryls.[a, b]
Table 2. Substrate scope of β-(2-aminoaryl)-α,β-ynones with varying
substitutions at the carbonyl terminal.[a, b]
[a] Reaction conditions: A (0.5 mmol), TMS-N3 (0.55 mmol), TBAF (0.025
mmol) in DMF (5 mL) at room temperature for 8 h. [b] The data in
parentheses were isolated yields. [c] 69% of 3-(2-amino-5-cyanophenyl)-5-
phenylisoxazole was obtained. [d] 55% of 3-(2-amino-5-methoxycarbonyl-
phenyl)-5-phenylisoxazole was obtained. [e] 87% of 3-(2-amino-5-nitrophenyl)-
5-phenylisoxazole was obtained.
isoxazole (B26’) and 55% of 3-(2-amino-5-methoxycarbonyl-
phenyl)-5-phenyl isoxazole (B27’) were isolated. Furthermore,
when NO2 substituted 2-aminoaryl ynone was employed, the
reaction exclusively gave rise to 3-(2-amino-5-nitrophenyl)-5-
phenyl isoxazole (B28’) up to an 87% isolated yield. Finally, with
various alkyne and carbonyl terminal substituted ynones as
substrates, we efficiently synthesized a diversity of multi-
substituted 1H-[1,2,3]Triazolo[4,5-c]quinolines B29-B32.
To further demonstrate the practicability of the newly
developed method, two selected reactions on a gram scale (5
mmol of substrates) were carried out. Delightedly, no obvious
change in yields was found, which indicates that this reaction
can be scaled up (Scheme 2a). Considering that 1H-
[a] Reaction conditions: A (0.5 mmol), TMS-N3 (0.55 mmol), TBAF (0.025
mmol) in DMF (5 mL) at room temperature for 8 h. [b] The data in parentheses
were isolated yields.
[1,2,3]triazolo[4,5-c]quinolines
can
undergo
nucleophilic
substitution reaction with alkyl halides to form N2-alkylated
derivatives,[18] the one-pot alkylation without the isolation of
formed 1H-[1,2,3]triazolo[4,5-c]quinolines was carried out, too.
Firstly, 3-(2-aminophenyl)-1-phenylprop-2-yn-1-one (A1) reacted
with TMS-N3 under the previous standard reaction conditions to
generate 4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline (B1). Then
1.0 equiv. of benzyl bromide and 2.0 equiv. of K2CO3 was added.
After further heated at 80 oC for 4h, the desired 2-benzyl-4-
phenyl-2H-[1,2,3]triazolo[4,5-c]quinoline (C1) was isolated in
69% total yield in this one-pot procedure (Scheme 2b). Similarly,
with allyl bromide as an alkylating agent, 2-allyl-4-phenyl-2H-
[1,2,3]triazolo[4,5-c]quinoline (C2) was obtained in 65% total
yield (Scheme 2b).
Various substituted 2-aminoaryls at the alkyne terminal of
ynones were explored to further extend the substrate scope
(Table 3). The substrates attached with either electron-donating
group (alkyl and alkoxy) or moderate electron-withdrawing group
(Br and CF3) at 2-aminoaryl were high productive, and delivered
the corresponding cyclized products B21-B25 in good to
excellent yields (83-92%) under the identified reaction conditions.
However, for the substrates with high electron-withdrawing
groups, the reaction tended to form isoxazoles instead of 1H-
[1,2,3]triazolo[4,5-c]quinolines. For instance, when COOCH3-
and CN-substituted 2-aminoaryl ynones were subjected to the
standard conditions, the expected products B26 and B27 were
obtained only in 27% and 34% yields, respectively. On the
contrary, about 69% of 3-(2-amino-5-cyanophenyl)-5-phenyl
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
General Information: All chemicals and organic solvents were
commercially available and directly used without further purification. All
proton and 13C nuclear magnetic resonance (NMR) spectra were
recorded on a Bruker AVANCE III 500 MHz or a Bruker Magnet System
400/600 MHz spectrometer in deuterated solvents with tetramethylsilane
(TMS) as internal standard. High resolution mass spectra were recorded
in the EI mode on Waters GCT Premier TOF mass spectrometer with an
Agilent 6890 gas chromatography using a DB-XLB column (30 m x 0.25
mm (i.d.), 0.25 μ) or ESI mode on an Agilent 6210 LC/TOF mass
spectrometer. Melting points (uncorrected) were determined on a BUCHI
M-565 apparatus. High performance liquid chromatography (HPLC)
analyses were performed on Shimadzu LC-20ADXR using a Insertsil
ODS-3 column (4.6 mm
x 250 mm x 5 μm). Flash column
chromatography was performed on silica gel (200-300 mesh) with
petroleum ether/ethyl acetate as eluents.
General procedure for the synthesis of 1H-[1,2,3]triazolo[4,5-
c]quinolones: To a 15 mL of Young tube were added β-(2-aminoaryl)-
α,β-ynones A (0.5 mmol), TMS-N3 (0.55 mmol), TBAF (0.025 mmol,
1mol/L in THF) and DMF (5 mL). The resulting mixture was stirred at
room temperature (25-30 oC) for 8 h. Upon completion, the crude
reaction mixture was poured into saturated brine (10.0 mL) and extracted
with ethyl acetate (3 × 5 mL). The extractions were combined, dried over
anhydrous Na2SO4, filtrated and removed the solvent under reduced
pressure. The residual was purified by flash chromatography on silica to
afford the desired products.
Scheme 2. Gram-scale reactions and one-pot derivation to synthesize N2-
alkyl substituted 1,2,3-triazolo[4,5-c]quinolines
19]
On the basis of the reported works[16b,
and our
experimental results, a plausible mechanism is proposed in
Scheme 3. Initially, under the catalysis of TBAF, ynone A1 and
TMS-N3 proceeded [3+2] cycloaddition to form triazole D,
followed by subsequent intermolecular dehydration annulation to
afford the correponding N-TMS substituted triazole-quinoline E.
The N-Si bond of E was instable and tended to occur
protonation with the in-situ releasing H2O molecule, and finally
furnished the target product B1.
4-Phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline B1 (CAS No.: 1537188-84-
3): Flash column chromatography eluent (petroleum ether/ethyl acetate =
[6]
o
5:1); 90% yield (110 mg); white solid; m.p. 216.2 C (lit. m.p.: 219-221
oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.97 (br, 1H), 8.86 (s, 1H), 8.43
(d, J = 8.0 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 7.90-7.85 (m, 1H), 7.82-7.77
(m, 1H), 7.68-7.63 (m, 2H), 7.63-7.59 (m, 1H). 13C NMR (DMSO-d6, 125
MHz): δ = 149.5, 144.1, 136.5, 130.5, 129.8, 129.7, 129.3, 128.6, 127.4,
122.7, 115.3. IR (KBr): ν = 3460.1, 3064.3, 2794.5, 2688.3, 1576.8,
1519.6, 1458.3, 1417.5, 1327.6, 1241.8, 1135.5, 972.1, 955.7, 763.7,
698.3 cm-1. HRMS (+ESI): m/z calculated for C15H11N4 [M+H]+, 247.0978,
found 247.0989.
4-(p-Tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B2 (CAS No.: 1537188-
85-4): Flash column chromatography eluent (petroleum ether/ethyl
[6]
o
acetate = 5:1); 91% yield (118 mg); yellowish solid; m.p. 218.1 C (lit.
m.p.: 210-212 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.93 (br, 1H),
8.79 (s, 2H), 8.41 (d, J = 8.1 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.88-7.83
Scheme 3. Plausible reaction mechanism
(m, 1H), 7.79-7.74 (m, 1H), 7.45 (d, J = 8.1 Hz, 2H), 2.44 (s, 3H). 13
C
NMR (DMSO-d6, 125 MHz): δ = 149. 4, 144.1, 140.3, 133.8, 129.8, 129.6,
129.2, 129.2, 127.2, 122.7, 115.2, 21.1. IR (KBr): ν = 3442.1, 3084.7,
2917.4, 2651.5, 1634.1, 1609.5, 1527.8, 1511.5, 1356.2, 1209.1, 1180.5,
984.3, 829.0, 763.7 730.9 cm-1. HRMS (+ESI): m/z calculated for
C16H13N4 [M+H]+, 261.1140, found 261.1161.
Conclusion
In conclusion, we demonstrated an effcient and promising
protocol for the tandem synthesis of 1H-[1,2,3]triazolo[4,5-
c]quinolines from β-(2-aminoaryl)-α,β-ynones and TMS-N3. With
TBAF as catalyst and DMF as reaction medium, the reaction
smoothly proceeded with high selectivity under ambient
conditions. Salient features of this protocol included metal-free,
mild reaction conditions, broad substrate scope, and high atom-
/step-economy, which made it a more practical alternative to the
existing methods. Moreover, this protocol also enabled further
derivation for N2-substituted 1,2,3-triazolo[4,5-c]quinolines in
one-pot. Further studies related to biological activity of the
synthesized 1,2,3-triazolo[4,5-c]quinoline derivatives are in
progress in our laboratory.
4-(4-Methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B3 (CAS No.:
1417697-01-8): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 91% yield (126 mg); white solid; m.p. 208.7 oC
[5]
(lit. m.p.: 206-208 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.84 (br,
1H), 8.87 (d, J = 8.3 Hz, 2H), 8.38 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.5 Hz,
1H), 7.86-7.78 (m, 1H), 7.76-7.68 (m, 1H), 7.19 (d, J = 9.0 Hz, 2H), 3.88
(s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ = 161.3, 149.1, 144.2, 137.1,
131.3, 130.9, 129.7, 129.5, 129.0, 126.9, 122.7, 114.0, 113.8, 55.3. IR
(KBr): ν = 3389.0, 3082.6, 2920.2, 2759.6, 1637.6, 1601.4, 1503.3,
1458.1, 1362.0, 1254.0, 1173.9, 1030.8, 983.7, 835.9, 765.4 cm-1. HRMS
(+ESI): m/z calculated for C16H13N4O [M+H]+, 277.1089, found 277.1105.
4-(4-Fluorophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B4 (CAS No.:
1537188-87-6): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 93% yield (123 mg); white solid; m.p. 246.9 oC
Experimental Section
[6]
(lit. m.p.: 234-236 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.97 (br,
1H), 8.95 (s, 2H), 8.42 (d, J = 7.9 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.90-
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
7.85 (m, 1H), 7.82-7.76 (m, 1H), 7.52-7.45 (m, 2H). 13C NMR (DMSO-d6,
4-(4-Nitrophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B10 (CAS No.:
1537188-91-2): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:2); 78% yield (113 mg); white solid; m.p. 263.5 oC
1
125 MHz): δ = 163.6 (d, J = 247.7 Hz, JCF), 148.3, 144.0, 137.4, 132.9
4
3
(d, J = 2.4 Hz, JCF), 131.5 (d, J = 8.8 Hz, JCF), 129.8, 129.7, 127.4,
122.7, 115.6 (d, J = 21.5 Hz, 2JCF). IR (KBr): ν = 3482.0, 3044.8, 2936.7,
2827.4, 1638.1, 1603.1, 1503.3, 1356.3, 1233.6, 1158.8, 1085.1, 996.7,
842.4, 764.6, 664.4 cm-1. HRMS (+ESI): m/z calculated for C15H10N4F
[M+H]+, 265.0889, found 265.0903.
[5]
(lit. m.p.: 256-258 oC); 1H NMR (DMSO-d6, 600 MHz): δ = 9.10 (s, 2H),
8.47 (d, J = 8.2Hz, 2H), 8.43 (d, J = 7.8Hz, 1H), 8.28 (d, J = 8.7Hz, 1H),
7.93-7.81 (m, 2H). 13C NMR (DMSO-d6, 150 MHz): δ = 148.2, 146.7,
143.7, 142.0, 137.1, 130.1, 129.9, 128.2, 123.6, 122.7, 115.5. IR (KBr): ν
= 3386.5, 3088.8, 2924.8, 2840.5, 1640.3, 1607.1, 1571.9, 1500.5,
1452.7, 1339.0, 1294.9, 1099.1, 914.3, 831.2, 693.9 cm-1. HRMS (+ESI):
m/z calculated for C16H9N5O2 [M+H]+, 292.0756, found 292.0760.
4-(4-Chlorophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B5 (CAS No.:
1537188-88-7): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 93% yield (131 mg); white solid; m.p. 251.9 oC
[6]
(lit. m.p.: 252-254 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.90 (br,
4-(3-Methylphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
B11:
Flash
1H), 8.85 (d, J = 8.4 Hz, 2H), 8.35 (d, J = 7.9 Hz, 1H), 8.18 (d, J = 8.3 Hz,
column chromatography eluent (petroleum ether/ethyl acetate = 5:1);
93% yield (121 mg); orange solid; m.p. 197.6 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 16.02 (br, 1H), 8.65 (s, 2H), 8.42 (d, J = 8.1 Hz, 1H), 8.25
(d, J = 8.2 Hz, 1H), 7.89-7.83 (m, 1H), 7.80-7.75 (m, 1H), 7.55-7.50 m,
1H), 7.41 (d, J = 7.4 Hz, 1H ), 2.48 (s, 3H). 13C NMR (DMSO-d6, 125
MHz): δ = 149.5, 144.1, 137.7, 136.5, 131.1, 129.7, 129.7, 129.6, 128.5,
127.3, 126.6, 122.7, 21.2. IR (KBr): ν = 3510.0, 3150.1, 2937.6, 2864.0,
1630.0, 1585.0, 1515.6, 1446.1, 1343.9, 1209.1, 1074.2, 984.3, 771.9,
735.1, 694.2 cm-1. HRMS (+ESI): m/z calculated for C16H13N4 [M+H]+,
261.1140, found 261.1160.
1H), 7.84-7.79 (m, 1H), 7.77-7.72 (m, 1H), 7.66 (d, J = 8.7 Hz, 2H). 13
C
NMR (DMSO-d6, 125 MHz): δ = 148.0, 143.9, 135.4, 135.2, 130.8, 129.8,
129.7, 128.7, 127.6, 122.7, 115.3. IR (KBr): ν = 3444.2, 3135.1, 2932.5,
2870.6, 1646.3, 1593.5, 1491.8, 1460.7, 1354.9, 1236.7, 1090.0, 997.0,
837.1, 760.9 664.0 cm-1. HRMS (+ESI): m/z calculated for C15H10ClN4
[M+H]+, 281.0589, found 281.0596.
4-(4-Bromophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B6 (CAS No.:
1537188-89-8): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 95% yield (155 mg); white Solid; m.p. 252.4 oC
[6]
(lit. m.p.: 247-249 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 17.00 (br,
4-(2-Methylphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
B12:
Flash
1H), 8.84 (d, J = 5.5 Hz, 2H), 8.43 (d, J = 8.1 Hz, 1H), 8.26 (d, J = 8.1 Hz,
1H), 7.91-7.85 (m, 3H), 7.84-7.78 (m, 1H). 13C NMR (DMSO-d6, 125
MHz): δ = 148.2, 144.0, 135.5, 131.7, 131.1, 129.9, 129.8, 127.7, 124.4,
122.8, 115.5. IR (KBr): ν = 3372.9, 3091.2, 2920.1, 2855.6, 2663.1,
1638.1, 1585.0, 1486.9, 1421.9, 1356.0, 1209.0, 1070.2, 984.3, 834.3,
761.6 cm-1. HRMS (+ESI): m/z calculated for C15H10BrN4 [M+H]+,
325.0083, found 325.0094.
column chromatography eluent (petroleum ether/ethyl acetate = 5:1);
o
90% yield (117 mg); white solid; m.p. 225.4 C; 1H NMR (DMSO-d6, 500
MHz): δ = 16.68 (br, 1H), 8.45 (d, J = 7.8 Hz, 1H), 8.20 (d, J = 8.4 Hz,
1H), 7.86-7.81 (m, 1H), 7.80-7.75 (m, 1H), 7.70 (d, J = 7.4 Hz, 1H), 7.47-
7.36 (m, 3H), 2.34 (s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ = 152.9,
144.1, 136.6, 136.6, 130.7, 130.5, 129.6, 129.2, 127.6, 125.6, 122.7,
115.3, 20.2. IR (KBr): ν = 3248.1, 2921.2, 2627.0, 2553.5, 2492.2, 1642.2,
1564.6, 1523.7, 1462.4, 1360.3, 1230.0, 1200.9, 976.2, 767.7, 730.9 cm-
1. HRMS (+ESI): m/z calculated for C16H13N4 [M+H]+, 261.1135, found
261.1145.
4-(4-(Trifluoromethyl)phenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
B7:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 91% yield (143 mg); yellowish solid; m.p. 224.2 oC; 1H NMR
(DMSO-d6, 500 MHz): δ = 17.05 (br, 1H), 9.06 (d, J = 6.8 Hz, 2H), 8.45 (d,
J = 7.6 Hz, 1H), 8.30 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 8.3 Hz, 1H), 7.93-
7.88 (m, 1H), 7.86-7.82 (m, 1H). 13C NMR (DMSO-d6, 125 MHz): δ =
4-(3-Bromo-5-methylphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B13:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 87% yield (148 mg); white solid; m.p. 281.0 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 16.91 (br, 1H), 8.81 (s, 1H), 8.64 (s, 1H), 8.38 (d, J = 7.8
Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 7.87-7.83 (m, 1H), 7.79-7.76 (m, 1H),
7.60 (s, 1H) , 2.47 (s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ = 147.6,
143.8, 140.6, 138.5, 133.5, 129.9, 129.8, 128.8, 128.6, 127.7, 122.7,
121.7, 20.9. IR (KBr): ν = 3442.1, 3052.8, 2923.7, 2550.3, 1637.2, 1590.8,
1498.6, 1454.5, 1296.0, 1216.2, 1171.2, 1096.1, 959.9, 775.9, 747.4 cm-
1. HRMS (+ESI): m/z calculated for C16H12N4Br [M+H]+, 339.0245, found
339.0256.
2
147.7, 143.9, 140.1, 137.2, 130.2 (q, J = 31.9 Hz, JCF), 129.9, 129.9,
3
1
129.8, 128.0, 125.5 (q, J = 3.8 Hz, JCF), 124.2 (q, J = 272.3 Hz, JCF),
122.7. IR (KBr): ν = 3374.8, 3088.7, 2766.0, 2659.7, 1634.1, 1564.6,
1523.7, 1425.7, 1319.4, 1164.1, 1127.4, 1057.9, 980.3, 853.6, 767.8 cm-
1. HRMS (+ESI): m/z calculated for C16H10F3N4 [M+H]+, 315.0852, found
315.0864.
4-(4-Methoxycarbonylphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline B8:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:2); 77% yield (117 mg); yellowish solid; m.p. 249.7 oC; 1H NMR
(DMSO-d6, 500 MHz): δ = 16.97 (br, 1H), 8.95 (d, J = 6.8 Hz, 2H), 8.40 (d,
J = 6.3 Hz, 1H), 8.24 (d, J = 7.4 Hz, 1H), 8.20-8.14 (m, 2H), 7.89-7.83 (m,
1H), 7.82-7.76 (m, 1H), 3.91 (s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ =
166.0 148.1, 144.0, 140.6, 137.2, 130.9, 129.9, 129.9, 129.4, 127.9,
122.8, 115.5, 52.3. IR (KBr): ν = 3203.5, 3020.7, 2953.6, 2845.3, 1687.2,
1607.8, 1491.1, 1442.0, 1323.5, 1286.7, 1200.3, 1114.1, 948.3, 775.2,
726.9 cm-1. HRMS (+ESI): m/z calculated for C17H13N4O2 [M+H]+,
305.1033, found 305.1040.
4-(Naphthalen-1-yl)-1H-[1,2,3]triazolo[4,5-c]quinoline B14 (CAS No.:
2251704-60-4): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 79% yield (117 mg); orange solid; m.p. 227.2
[6]
o
oC (lit. mp: 235-237 C); 1H NMR (DMSO-d6, 500 MHz): δ = 16.93 (br,
1H), 8.51 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.08
(d, J = 8.2 Hz, 2H), 8.01 (d, J = 7.3 Hz, 1H), 7.92-7.82 (m, 2H), 7.76-7.71
(m, 1H), 7.60-7.56 (m, 1H), 7.51-7.45 (m, 1H). 13C NMR (DMSO-d6, 125
MHz): δ = 144.2, 134.1, 133.5, 132.9, 131.0, 130.7, 129.7, 128.6, 128.3,
127.7, 127.5, 126.6, 126.2, 126.1, 125.7, 125.5, 125.2, 124.9, 122.9. IR
(KBr): ν = 3446.5, 3102.7, 2973.4, 2755.3, 1627.4, 1600.2, 1595.1,
1510.0, 1458.5, 1394.4, 1259.1, 1164.3, 957.7, 779.0, 732.2 cm-1. HRMS
(+ESI): m/z calculated for C19H13N4 [M+H]+, 297.1135, found 297.1138.
4-(4-Cyanophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
B9:
Flash
column chromatography eluent (petroleum ether/ethyl acetate = 5:2);
o
1
85% yield (115 mg); white solid; m.p. 263.5 C; H NMR (DMSO-d6, 500
MHz): δ = 16.79 (br, 1H), 8.93 (d, J = 8.4 Hz, 2H), 8.34 (d, J = 8.0 Hz,
1H), 8.17 (d, J = 8.6 Hz, 1H), 8.02 (d, J = 8.5 Hz, 2H), 7.85-7.80 (m, 1H),
7.79-7.73 (m, 1H). 13C NMR (DMSO-d6, 125 MHz): δ = 147.2, 143.8,
140.3, 137.1, 132.5, 129.9, 129.6, 128.1, 122.7, 118.7, 115.4, 112.6. IR
(KBr): ν = 3480.2, 3198.9, 2922.8, 2864.3, 2185.6, 1617.8, 1563.9,
1492.1, 1322.1, 1286.7, 1202.7, 1161.8, 1008.3, 852.2, 749.8 cm-1.
HRMS (+ESI): m/z calculated for C16H10N5 [M+H]+, 272.0936, found
272.0951.
4-(Furan-2-yl)-1H-[1,2,3]triazolo[4,5-c]quinoline B15: Flash column
chromatography eluent (petroleum ether/ethyl acetate = 5:1); 78% yield
o
1
(92 mg); brown solid; m.p. 281.9 C; H NMR (DMSO-d6, 500 MHz): δ =
16.94 (br, 1H), 8.38 (s, 1H), 8.19 (d, J = 8.3 Hz, 1H), 8.09 (s, 1H), 8.05 (s,
1H), 7.87-7.81 (m, 1H), 7.78-7.72 (m, 1H), 6.88-6.83 (m, 1H). 13C NMR
(DMSO-d6, 125 MHz): δ = 150.0, 146.0, 144.2, 129.9, 129.4, 127.3,
122.7, 112.7. IR (KBr): ν = 3395.4, 3150.1, 2924.1, 2856.5, 1608.3,
1556.9, 1445.9, 1389.9, 1255.0, 1156.8, 1040.0, 1004.1, 916.8, 844.9,
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
741.1 cm-1. HRMS (+ESI): m/z calculated for C13H9N4O [M+H]+, 236.0698,
found 236.0705.
13C NMR (DMSO-d6, 125 MHz): δ = 149.3, 144.3, 139.6, 137.3, 136.6,
134.2, 130.4, 129.2, 129.1, 129.0, 128.5, 122.3, 112.2, 21.3. IR (KBr): ν =
3476.5, 3019.3, 2868.1, 2823.2, 1638.1, 1560.5, 1519.6, 1486.9, 1458.3,
1343.9, 1254.0, 1090.6, 996.6, 771.8, 686.0 cm-1. HRMS (+ESI): m/z
calculated for C16H13N4 [M+H]+, 261.1135, found 261.1142.
4-(Thiophen-2-yl)-1H-[1,2,3]triazolo[4,5-c]quinoline B16 (CAS No.:
2251704-61-5): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 75% yield (95 mg); yellowish solid; m.p. 285.3
[6]
oC (lit. m.p.: 279-281 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.92 (br,
7-Methoxy-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline B22: Flash
1H), 8.82 (d, J = 2.42 Hz, 1H), 8.34 (d, J = 7.8 Hz, 1H), 8.11 (d, J = 8.1
Hz, 1H), 7.88 (d, J = 5.0 Hz, 1H), 7.82-7.77 (m, 1H), 7.73-7.68 (m, 1H),
7.38-7.33 (m, 1H). 13C NMR (DMSO-d6, 125 MHz): δ = 145.1, 144.1,
141.5, 135.9, 131.5, 130.8, 129. 9, 129.1, 128.8, 127.1, 122.8, 115.2. IR
(KBr): ν = 3472.9, 3080.7, 2958.0, 2786.4, 1625.9, 1580.9, 1564.6,
1531.9, 1450.2, 1360.3, 1205.0, 1045.6, 976.2, 759.6, 714.6 cm-1. HRMS
(+ESI): m/z calculated for C13H9N4S [M+H]+, 253.0542, found 253.0543.
column chromatography eluent (petroleum ether/ethyl acetate = 5:1);
o
84% yield (116 mg); yellowish solid; m.p. 254.9 C; 1H NMR (DMSO-d6,
500 MHz): δ = 16.75 (br, 1H), 8.87 (d, J = 2.9 Hz, 2H), 8.27 (d, J = 8.6 Hz,
1H), 7.67 (d, J = 2.5 Hz 1H), 7.66-7.62 (m, 2H), 7.61-7.57 (m, 1H), 7.40
(d, J = 8.8 Hz, 1H), 3.96 (s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ =
160.5, 149.0, 146.0, 136.9, 136.6, 136.3, 130.4, 129.3, 128.6, 123.8,
118.4, 109.8, 55.5. IR (KBr): ν = 3466.5, 3019.5, 2827.2, 1638.1, 1597.3,
1487.0, 1458.3, 1343.9, 1262.2, 1196.8, 1155.9, 1082.4, 996.6, 845.4,
720.8 cm-1. HRMS (+ESI): m/z calculated for C16H13N4O [M+H]+,
277.1089, found 277.1091.
4-Ethyl-1H-[1,2,3]triazolo[4,5-c]quinoline
B17:
Flash
column
chromatography eluent (petroleum ether/ethyl acetate = 10:1); 81% yield
(80 mg); light yellowish solid; m.p. 236.5 oC; 1H NMR (DMSO-d6, 500
MHz): δ = 16.70 (br, 1H), 8.37 (d, J = 7.9 Hz, 1H), 8.12 (d, J = 8.3 Hz,
1H), 7.882-7.77 (m, 1H), 7.75-7.70 (m, 1H), 3.34 (q, J = 7.6 Hz, 4H), 1.46
(t, J = 7.5 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz): δ = 156.3, 143.9,
136.6, 129.1, 128.9, 126.8, 122.6, 115.7, 27.7, 12.2. IR (KBr): ν = 3435.2,
3088.0, 2974.3, 2796.2, 1639.2, 1605.5, 1529.2, 1421.6, 1368.4, 1205.1,
1074.2, 1017.6, 988.4, 861.8, 763.7 cm-1. HRMS (+ESI): m/z calculated
for C11H11N4 [M+H]+, 199.0978, found 199.0983.
4-Phenyl-1H-[1,3]dioxolo[4,5-g][1,2,3]triazolo[4,5-c]quinoline
B23
(CAS No.: 2251704-67-1): Flash column chromatography eluent
(petroleum ether/ethyl acetate = 5:1); 87% yield (126 mg); yellowish
[6]
solid; m.p. 268.8 oC (lit. m.p.: 267-269 oC); 1H NMR (DMSO-d6, 500
MHz): δ = 16.63 (br, 1H), 8.79 (s, 2H), 7.70 (s,1H), 7.64-7.60 (m, 3H),
7.58-7.54 (m, 1H), 6.26 (s, 2H). 13C NMR (DMSO-d6, 125 MHz): δ =
150.1, 147.8, 146.7, 141.4, 136.6, 135.8, 130.1, 128.9, 128.6, 107.2,
102.4, 99.2. IR (KBr): ν = 3450.2, 3035.6, 2868.1, 2827.2, 2670.1, 1646.3,
1495.1, 1462.4, 1348.0, 1262.2, 1033.4, 984.3, 939.4, 861.7, 720.4 cm-1.
HRMS (+ESI): m/z calculated for C16H11N4O2 [M+H]+, 291.0882, found
291.0887.
4-Pentyl-1H-[1,2,3]triazolo[4,5-c]quinoline
B18:
Flash
column
chromatography eluent (petroleum ether/ethyl acetate = 10:1); 84% yield
o
1
(101 mg); yellowish solid; m.p. 181.4 C; H NMR (DMSO-d6, 500 MHz):
δ = 16.57 (br, 1H), 8.35 (d, J = 7.7 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1H),
7.78-7.72 (m, 1H), 7.71-7.65 (m, 1H), 3.27 (t, J = 7.7 Hz, 2H), 1.87-1.94
(m, 2H), 1.26-1.38 (m, 4H), 0.82 (t, J = 6.97 Hz, 3H). 13C NMR (DMSO-d6,
125 MHz): δ = 155.7, 143.9, 136.9, 129.1, 128.9, 126.7, 122.6, 115.7,
34.4, 31.2, 27.5, 21.9, 13.8. IR (KBr): ν = 3450.5, 3020.5, 2953.8, 2854.8,
1661.8, 1593.2, 1552.4, 1502.1, 1464.5, 1433.2, 1356.9, 1185.2, 755.5,
708.7, 624.5 cm-1. HRMS (+ESI): m/z calculated for C14H17N4 [M+H]+,
240.1375, found 240.1382.
7-Bromo-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline
B24:
Flash
column chromatography eluent (petroleum ether/ethyl acetate = 5:1);
o
83% yield (135 mg); yellowish solid; m.p. 279.2 C; 1H NMR (DMSO-d6,
500 MHz): δ = 16.93 (br, 1H), 8.77 (s, 1H), 8.33 (d, J = 1.9 Hz, 1H), 8.25
(d, J = 8.6 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.65-7.60 (m, 3H). 13C NMR
(DMSO-d6, 125 MHz): δ = 150.6, 144.8, 136.0, 132.8, 131.6, 130.8,
130.2, 129.4, 129.2, 128.6, 128.5, 124.5, 122.6. IR (KBr): ν = 3442.5,
3007.0, 2925.3, 2810.9, 1634.1, 1552.3, 1507.4, 1486.9, 1343.9, 1241.8,
1086.5, 992.5, 869.9, 763.7, 681.9 cm-1. HRMS (+ESI): m/z calculated
for C15H10N4Br [M+H]+, 325.0089, found 325.0090.
4-Cyclopropyl-1H-[1,2,3]triazolo[4,5-c]quinoline B19: Flash column
chromatography eluent (petroleum ether/ethyl acetate = 10:1); 75% yield
(79 mg); yellowish solid; m.p. 180.9 oC; 1H NMR (DMSO-d6, 500 MHz): δ
= 16.69 (br, 1H), 8.31 (d, J = 7.9 Hz, 1H), 7.98 (d, J = 8.7 Hz, 1H), 7.75-
7.69 (m, 1H), 7.67-7.60 (m, 1H), 2.95-2.87 (m, 1H), 1.41 (s, 2H), 1.26-
1.91 (m, 2H). 13C NMR (DMSO-d6, 125 MHz): δ = 157.0, 144.1, 129.3,
128.6, 126.2, 122.7, 115.1, 99.6, 14.3, 10.8. IR (KBr): ν = 3567.1, 3002.1,
2655.4, 1661.6, 1615.8, 1589.3, 1468.1, 1423.0, 1346.7, 1170.0, 1074.1,
987.1, 919.9, 766.8, 707.9 cm-1. HRMS (+ESI): m/z calculated for
C12H11N4 [M+H]+, 211.0984, found 211.1004.
4-Phenyl-8-(trifluoromethyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
B25:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 83% yield (130 mg); white solid; m.p. 275.2 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 16.95 (br, 1H), 8.79 (s, 2H), 8.69 (s, 1H), 8.29 (d, J = 8.8
Hz, 1H), 8.02 (d, J = 8.8 Hz, 1 H), 7.65-7.59 (m, 3H). 13C NMR (DMSO-d6,
125 MHz): δ = 151.6, 145.3, 137.3, 135.8, 131.0, 130.8, 129.5, 128.5,
2
3
126.7 (q, J = 32.5 Hz, JCF), 125.1 (q, J = 3.1 Hz, JCF), 124.5 (q, J =
271.7 Hz, 1JCF), 120.5, 120.4, 114.8. IR (KBr): ν = 3446.5, 3072.4, 2757.8,
2688.3, 1618.1, 1593.2, 1450.2, 1331.7, 1294.9, 1160.1, 1127.4, 1061.9,
980.3, 837.2, 767.7 cm-1. HRMS (+ESI): m/z calculated for C16H10N4F3
[M+H]+, 315.0858, found 315.0868.
4-Cyclohexyl-1H-[1,2,3]triazolo[4,5-c]quinoline B20: Flash column
chromatography eluent (petroleum ether/ethyl acetate = 10:1); 80% yield
o
1
(101 mg); yellowish solid; m.p. 207.3 C; H NMR (DMSO-d6, 500 MHz):
δ = 16.46 (br, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H),
7.77-7.71 (m, 1H), 7.70-7.64 (m, 1H), 3.50 (t, J = 11.3 Hz, 1H), 2.02 (t, J
= 11.1 Hz, 2H), 1.80-1.92 (m, 4H), 1.73 (d, J = 12.5 Hz, 1H), 1.40-1.52
(m, 2H), 1.25-1.36 (m, 1H). 13C NMR (DMSO-d6, 125 MHz): δ = 159.1,
143.9, 129.1, 128.8, 128.1, 126.7, 125.2, 122.5, 115.6, 43.1, 31.0, 25.9,
25.7. IR (KBr): ν = 3480.0, 2925.3, 2851.8, 1658.6, 1585.0, 1507.4,
1458.3, 1421.6, 1356.2, 1188.6, 1002.2, 980.3, 755.5, 686.0, 637.0 cm-1.
HRMS (+ESI): m/z calculated for C15H17N4 [M+H]+, 254.1453, found
253.1455.
4-Phenyl-8-cyano-1H-[1,2,3]triazolo[4,5-c]quinoline
B26:
Flash
column chromatography eluent (petroleum ether/ethyl acetate = 5:1);
27% yield (37 mg); yellowish solid; m.p. 276.3 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 17.05 (br, 1H), 8.82-8.77 (m, 2H), 8.75 (d, J = 1.6 Hz, 1H),
8.26 (d, J = 8.8 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.66-7.62 (m, 3H). 13
C
NMR (DMSO-d6, 125 MHz): δ = 152.3, 145.4, 137.3, 135.8, 131.3, 131.2,
130.8, 129.6, 128.7, 128.4, 118.5, 115.7, 109.1. IR (KBr): ν = 3447.8,
3064.4, 2937.2, 2870.3, 2223.4, 1640.7, 1604.5, 1499.6, 1324.7, 1230.9,
1169.2, 1025.2, 913.6, 829.8, 693.8 cm-1. HRMS (+ESI): m/z calculated
for C16H10N5 [M+H]+, 272.0936, found 272.0939.
7-Methyl-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline B21 (CAS No.:
2251704-64-8): Flash column chromatography eluent (petroleum
ether/ethyl acetate = 5:1); 92% yield (120 mg); white solid; m.p. 253.6 oC
4-Phenyl-8-methoxycarbonyl-1H-[1,2,3]triazolo[4,5-c]quinoline B27:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 34% yield (52 mg); brown solid; m.p. 278.5 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 16.97 (br, 1H), 8.97 (d, J = 7.1 Hz, 1H), 8.83 (s, 2H), 8.21
[6]
(lit. m.p.: 245-247 oC); 1H NMR (DMSO-d6, 500 MHz): δ = 16.77 (br,
1H), 8.82 (d, J = 5.6 Hz, 2H), 8.21 (d, J = 8.2 Hz, 1H), 7.97 (s, 1H), 7.65-
7.60 (m, 2H), 7.60-7.55 (m, 1H), 7.52 (d, J = 8.2 Hz, 1H), 2.52 (s, 3H).
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
(d, J = 6.2 Hz, 2H), 7.69-7.60 (m, 1H), 3.94 (s, 3H). 13C NMR (DMSO-d6,
125 MHz): δ = 165.6, 151.6, 146.2, 141.5, 136.0, 131.0, 130.0, 129.5,
129.0, 128.7, 127.5, 125.0, 52.5. IR (KBr): ν = 3476.2, 3141.9, 3060.2,
3027.5, 1687.2, 1642.2, 1515.6, 1446.1, 1352.1, 1290.8, 1192.7, 1025.2,
988.4, 718.7, 686.0 cm-1. HRMS (+ESI): m/z calculated for C17H13N4O2
[M+H]+, 305.1039, found 305.1044.
2-Benzyl-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline C1: Flash column
chromatography eluent (petroleum ether/ethyl acetate = 20:1); 69% yield
(116 mg); white solid; m.p. 101.0 oC; 1H NMR (CDCl3, 600 MHz): δ =
8.74 (d, J = 7.8 Hz, 2H), 8.46 (d, J = 7.7 Hz, 1H), 8.26 (d, J = 8.8 Hz, 1H),
8.75 (t, J = 7.6 Hz, 1H), 7.67-7.52 (m, 4H), 7.48 (d, J = 7.6 Hz, 2H), 7.40-
7.32 (m, 3H), 6.00 (s, 2H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 151.2,
146.1, 144.7, 138.6, 137.2, 134, 7, 130.5, 130.4, 129.5, 129.1, 128.8,
128.7, 128.4, 127.4, 126.0, 122. 7, 119.3, 60.6 ppm. IR (KBr): ν = 3062.2,
2934.1, 1622.7, 1568.0, 1517.2, 1492.7, 1449.5, 1368.9, 1327.9, 1236.0,
1177.0, 951.7, 770.7, 737.2, 693.2 cm-1. HRMS (+ESI): m/z calculated
for C22H17N4 [M+H]+, 337.1453, found 337.1459.
8-Bromo-6-methyl-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinolone B29:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 62% yield (105 mg); yellowish solid; m.p. 275.9 oC; 1H NMR
(DMSO-d6, 500 MHz): δ = 16.75 (br, 1H), 8.81 (d, J = 4.9 Hz, 2H), 8.29 (s,
1H), 8.74 (s, 1H), 7.64-7.57 (m, 3H), 2.75 (s, 3H). 13C NMR (DMSO-d6,
125 MHz): δ = 148.1, 141.2, 140.3, 136.5, 132.5, 130.6, 129.2, 128.6,
122.6, 119.7, 116.1, 18.0. IR (KBr): ν = 3433.5, 3064.6, 2917.0, 2847.9,
1631.8, 1573.8, 1516.0, 1491.5, 1350.2, 1184.4, 1076.2, 967.5, 862.9,
770.7, 687.9 cm-1. HRMS (+ESI): m/z calculated for C16H12N4Br [M+H]+,
339.0245, found 339.0250.
1-Allyl-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline C2: Flash column
chromatography eluent (petroleum ether/ethyl acetate = 20:1); 65% yield
(93 mg); yellowish oil; 1H NMR (CDCl3, 600 MHz): δ = 8.73 (d, J = 8.0 Hz,
2H), 8.46 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 7.7 Hz, 1H), 7.75 (t, J = 6.9 Hz,
1H), 7.65 (t, J = 7.0 Hz, 1H), 7.60 (t, J = 7.2 Hz, 2H), 7.54 (t, J = 7.5 Hz,
1H), 6.32-6.24 (m, 1H), 5.46-5.40 (m, 4H) ppm. 13C NMR (CDCl3, 150
MHz): δ = 151.2, 145.9, 144.7, 138.4, 137.1, 131.1, 130.5, 130.4, 129.5,
129.3, 128.7, 127.4, 122.6, 120.4, 119.2, 59.2 ppm. IR (KBr): ν = 3057.2,
2926.8, 1620.5, 1566.4, 1515.6, 1493.8, 1448.2, 1362.7, 1323.4, 1235.7,
1182.4, 951.4, 769.7, 728.4, 692.1 cm-1. HRMS (+ESI): m/z calculated
for C18H15N4 [M+H]+, 287.1297, found 287.1330.
7-Methyl-4-(4-methylphenyl)-1H-[1,2,3]triazolo[4,5-c]quinolone B30:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 93% yield (128 mg); white solid; m.p. 225.3 oC; 1H NMR (DMSO-d6,
500 MHz): δ = 16.77 (br, 1H), 8.75 (d, J = 6.6 Hz, 2H), 8.24 (d, J = 8.4 Hz,
1H), 7.99 (s, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.1 Hz, 2H), 2.54
(s, 3H), 2.42 (s, 3H). 13C NMR (DMSO-d6, 125 MHz): δ = 149.3, 144.3,
140.2, 139.5, 137.1, 133.9, 129.2, 129.1, 129.0, 128.8, 122.3, 21.3, 21.0.
IR (KBr): ν = 3468.8, 3145.9, 3019.3, 2835.4, 1642.2, 1605.3, 1503.3,
1458.3, 1348.1, 1213.2, 1180.5, 1090.5, 996.6, 820.9, 792.3 cm-1. HRMS
(+ESI): m/z calculated for C17H15N4 [M+H]+, 275.1297, found 275.1313.
Acknowledgements
This work was supported by the National Natural Science
Foundations of China (21972125). We also thank the support
from “Zhejiang Key Laboratory of Green Pesticides and Cleaner
Production Technology of Zhejiang Province” of Zhejiang
University of Technology.
4-Pentyl-8-(trifluoromethyl)-1H-[1,2,3]triazolo[4,5-c]quinolone B31:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
o
1
5:1); 62% yield (96 mg); white solid; m.p. 236.1 C; H NMR (DMSO-d6,
500 MHz): δ = 16.69 (br, 1H), 8.66 (s, 1H), 8.20 (d, J = 8.9 Hz, 1H), 7.97
(d, J = 8.5 Hz, 1H), 3.25 (t, J = 7.6 Hz, 2H), 1.94-1.84 (m, 2H), 1.39-1.27
(m, 4H), 0.83 (t, J = 7.0 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz): δ =
Keywords: 1H-[1,2,3-triazolo[4,5-c]quinolines • β-(2-aminoaryl)-
α,β-ynones • TMS-N3 • TBAF-catalyzed tandem reaction •
ambient temperature reaction
2
158.6, 145.4, 136.6, 130.3, 126.5 (q, J = 32.29 Hz, JCF), 124.8 (q, J =
3
1
2.81 Hz, JCF), 124.1 (q, J = 274.58 Hz, JCF), 120.5, 120.4, 115.3, 34.5,
31.2, 27.3, 21.9, 13.8. IR (KBr): ν = 3460.6, 3043.8, 2958.0, 2851.7,
1620.5, 1593.2, 1503.3, 1466.5, 1331.7, 1282.6, 1172.3, 1135.5, 1066.1,
837.2, 714.5 cm-1. HRMS (+ESI): m/z calculated for C15H16N4F3 [M+H]+,
309.1327, found 309.1330.
[1]
a) P. Das, M. D. Delost, M. H. Qureshi, D. T. Smith, J. T. Njardarson, J.
Med. Chem. 2019, 62, 4265-4311; b) A. P. Taylor, R. P. Robinson, Y.
M. Fobian, D. C. Blakemore, L. H. Jones, O. Fadeyi, Org. Biomol.
Chem. 2016, 14, 6611-6637; c) R. D. Taylor, M. MacCoss, A. D. G.
Lawson, J. Med. Chem. 2014, 57, 5845-5859.
7-Bromo-4-(thiophen-2-yl)-1H-[1,2,3]triazolo[4,5-c]quinolone
B32:
Flash column chromatography eluent (petroleum ether/ethyl acetate =
5:1); 79% yield (131 mg); yellowish solid; m.p. 303.4 oC; 1H NMR
(DMSO-d6, 500 MHz): δ = 16.84 (br, 1H), 8.76 (s, 1H), 8.23-8.14 (m, 2H),
7.90 (d, J = 4.8 Hz, 1H), 7.83-7.77 (m, 1H), 77.37-7.31 (m, 1H). 13C NMR
(DMSO-d6, 125 MHz): δ = 146.1, 144.9, 141.0, 136.5, 135.9, 132.0,
131.5, 130.9, 129.8, 128.9, 124.5, 122.7, 114.2. IR (KBr): ν = 3458.0,
3084.7, 2998.8, 2823.2, 1638.1, 1531.9, 1503.3, 1433.8, 1352.1, 1233.6,
1057.9, 992.5, 841.3, 784.1, 714.6 cm-1. HRMS (+ESI): m/z calculated
for C13H8N4SBr [M+H]+, 330.9653, found 330.9656.
[2]
[3]
“Best-selling” is defined herein based on surveys conducted by the
Njardarson
group
in
2018,
Lists
available
from
http://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster.
a) K. Bozorov, J. Zhao, H. A. Aisa, Bioorg. Med. Chem. 2019, 27, 3511-
3531; b) E. Bonandi, M. S. Christodoulou, G. Fumagalli, D. Perdicchia,
G. Rastelli, D. Passarella, Drug Discov. Today 2017, 22, 1572-1581; c)
D. Dheer, V. Singh, R. Shankar, Bioorg. Chem. 2017, 71, 30-54.
a) N. Chokkar, S. Kalra, M. Chauhan, R. Kumar, Mini-Rev. Med. Chem.
2019, 19, 510-526; b) X.-F. Shang, S. L. Morris-Natschke, Y.-Q. Liu, X.
Guo, X.-S. Xu, M. Goto, J.-C. Li, G.-Z. Yang, K.-H. Lee, Med. Res. Rev.
2018, 38, 775-828; c) R. Musiol, Expert Opin. Drug Dis. 2017, 12, 583-
597.
[4]
One-pot procedure for the synthesis of N2-alkyl substituted 4-
phenyl-1H-[1,2,3]triazolo[4,5-c]quinolines (C1 and C2): To a 15 mL of
Young tube were added β-(2-aminoaryl)-α,β-ynones (0.5 mmol), TMS-N3
(0.55 mmol), TBAF (0.025 mmol, 1mol/L in THF) and DMF (5 mL). The
resulting mixture was stirred at room temperature for 8 h to get 4-phenyl-
1H-[1,2,3]triazolo[4,5-c]quinolines (B1). Then, benzyl bromide or allyl
bromide (0.5 mmol) and K2CO3 (1.0 mmol) were added. The reaction
temperature was raised to 80 oC in an oil bath and stirred for another 4 h
(monitored by TLC). After completion of the reaction, the crude reaction
mixture was cooled to room temperature, poured into brine (10 mL) and
extracted with ethyl acetate (3 × 5 mL). The extractions were combined,
dried over anhydrous Na2SO4, filtrated and removed the solvent under
reduced pressure. The residual was purified by flash chromatography on
silica to afford the desired products C1 and C2.
[5]
[6]
[7]
[8]
[9]
K. Li, J. Chen, J. Li, Y. Chen, J. Qu, X. Guo, C. Chen, B. Chen, Eur. J.
Org. Chem. 2013, 6246-6248.
C. Xu, S.-F. Jiang, Y.-D. Wu, F.-C. Jia, A.-X. Wu, J. Org. Chem. 2018,
83, 14802-14810.
C.-Y. Chen, C.-H. Yang, W.-P. Hu, J. Kishore Vandavasi, M.-I. Chung,
J.-J. Wang, RSC Adv. 2013, 3, 2710-2719.
K. Upadhyaya, A. Ajay, R. Mahar, R. Pandey, B. Kumar, S. K. Shukla,
R. P. Tripathi, Tetrahedron 2013, 69, 8547-8558.
D. Gangaprasad, J. P. Raj, K. Karthikeyan, R. Rengasamy, J.
Elangovan, Adv. Synth. Catal. 2018, 360, 4485-4490.
[10] a) C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219-9280; b) C. E.
Garrett, K. Prasad, Adv. Synth. Catal. 2004, 346, 889-900.
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
[11] a) Z.-Y. Wang, K.-K. Wang, R. Chen, H. Liu, K. Chen, Eur. J. Org.
Chem. 2020, 2456-2474; b) C. Najera, L. K. Sydnes, M. Yus, Chem.
Rev. 2019, 119, 11110-11244; c) Y. Li, J. Yu, Y. Bi, G. Yan, D. Huang,
Adv. Synth. Catal. 2019, 361, 4839-4881; d) R. E. Whittaker, A.
Dermenci, G. Dong, Synthesis 2016, 48, 161-183.
[12] A. Arcadi, F. Marinelli, E. Rossi, Tetrahedron 1999, 55, 13233-13250.
[13] a) V. Marsicano, M. Chiarini, F. Marinelli, A. Arcadi, Adv. Synth. Catal.
2019, 361, 2365-2370; b) N. D. Rode, A. Arcadi, A. Di Nicola, F.
Marinelli, V. Michelet, Org. Lett. 2018, 20, 5103-5106; c) N. D. Rode, I.
Abdalghani, A. Arcadi, M. Aschi, M. Chiarini, F. Marinelli, J. Org. Chem.
2018, 83, 6354-6362; d) N. D. Rode, M. Aschi, M. Chiarini, L. Del
Vecchio, F. Marinelli, A. Arcadi, Adv. Synth. Catal. 2018, 360, 3672-
3676; e) N. D. Rode, A. Arcadi, M. Chiarini, F. Marinelli, G. Portalone,
Adv. Synth. Catal. 2017, 359, 3371-3377; f) N. D. Rode, A. Arcadi, M.
Chiarini, F. Marinelli, Synthesis 2017, 49, 2501-2512; g) G. Abbiati, A.
Arcadi, F. Marinelli, E. Rossi, Synthesis 2014, 46, 687-721; h) G.
Abbiati, A. Arcadi, F. Marinelli, E. Rossi, Eur. J. Org. Chem. 2003,
1423-1427; i) E. Rossi, G. Abbiati, A. Arcadi, F. Marinelli, Tetrahedron
Lett. 2001, 42, 3705-3708.
[14] For reviews: a) X. R. Song, Y. F. Qiu, X. Y. Liu, Y. M. Liang, Org.
Biomol. Chem. 2016, 14, 11317-11331; b) M. Jafarzadeh, Synlett 2007,
2144-2145; c) S. Brase, C. Gil, K. Knepper, V. Zimmermann, Angew.
Chem. Int. Ed. 2005, 44, 5188-5240; For selected recent examples: d)
Z. Xie, F. Zhou, K. Ding, Adv. Synth. Catal. 2020, 362, 3442-3446; e)
M.-M. Xu, W.-B. Cao, X.-P. Xu, S.-J. Ji, Chem. Commun. 2018, 54,
12602-12605; f) H. Peng, Z. Yuan, P. Chen, G. Liu, Chin. J. Chem.
2017, 35, 876-880; g) D. Mahesh, V. Satheesh, S. V. Kumar, T.
Punniyamurthy, Org. Lett. 2017, 19, 6554-6557; h) Z. Xie, J. Deng, Z.
Qiu, J. Li, Q. Zhu, Chem. Commun. 2016, 52, 6467-6470; i) J.
Dhineshkumar, K. R. Prabhu, Eur. J. Org. Chem. 2016, 447-452; j) N.
Khatun, A. Modi, W. Ali, B. K. Patel, J. Org. Chem. 2015, 80, 9662-
9670; k) Z. Liu, J. Liu, L. Zhang, P. Liao, J. Song, X. Bi, Angew. Chem.
Int. Ed. 2014, 53, 5305-5309; l) J. Peng, M. Chen, Z. Xie, S. Luo, Q.
Zhu, Org. Chem. Front. 2014, 1, 777-781; m) Z. Liu, P. Liao, X. Bi, Org.
Lett. 2014, 16, 3668-3671; n) T. Shen, T. Wang, C. Qin, N. Jiao, Angew.
Chem. Int. Ed. 2013, 52, 6677-6680; o) C. Qin, W. Zhou, F. Chen, Y.
Ou, N. Jiao, Angew. Chem. Int. Ed. 2011, 50, 12595-12599.
[15] a) D. M. Stout, T. Takaya, A. I. Meyers, J. Org. Chem. 1975, 40, 563-
569; b) S. S. Washburne, W. R. Peterson, Jr., J. Organometal. Chem.
1970, 21, 427-430; c) E. Ettenhuber, K. Ruehlmann, Chem. Ber. 1968,
101, 743-750; d) L. Birkofer, P. Wegner, Chem. Ber. 1966, 99, 2512-
2517.
[16] a) D. Amantini, F. Fringuelli, O. Piermatti, F. Pizzo, E. Zunino, L.
Vaccaro, J. Org. Chem. 2005, 70, 6526-6529; b) G. D'Ambrosio, F.
Fringuelli, F. Pizzo, L. Vaccaro, Green Chem. 2005, 7, 874-877; c) D.
Amantini, R. Beleggia, F. Fringuelli, F. Pizzo, L. Vaccaro, J. Org. Chem.
2004, 69, 2896-2898.
[17] G. R. Kumar, Y. K. Kumar, M. S. Reddy, Chem. Commun. 2016, 52,
6589-6592.
[18] a) J. Li, Y. Zhang, D. Wang, W. Wang, T. Gao, L. Wang, J. Li, G.
Huang, B. Chen, Synlett 2010, 1617-1622; b) Y. Chen, Y. Liu, J. L.
Petersen, X. Shi, Chem. Commun. 2008, 44, 3254-3256.
[19] a) A. A. Taherpour, K. Kheradinand, J. Heterocycl. Chem. 2009, 46,
131-133; b) M. J. Schulz, S. J. Coats, D. J. Hlasta, Org. Lett. 2004, 6,
3265-3268.
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001280
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
Heterocycle Synthesis:
O
N
N
HN
N
R2
TBAF (5 mol%)
DMF, RT, 8 h
TMS-N3
+
R1
R1
(1.1 equiv.)
R2
NH2
32 examples, up to 95% yield
 Metal-free  Mild reaction conditions  Broad substrate scope  High atom-/step-economy
An efficient and metal-free approach for 1H-[1,2,3]triazolo[4,5-c]quinolines have been developed based on tandem TBAF-catalyzed
intermolecular azide-alkyne [3+2] cycloaddition of β-(2-aminoaryl)-α,β-ynones and TMS-N3, and intramolecular dehydration
annulation reactions. This transformation can smoothly proceed at ambient temperature to provide a broad range of functionalized
1H-[1,2,3]triazolo[4,5-c]quinolines in up to 95% yield for 32 examples.
9
This article is protected by copyright. All rights reserved.