Chemoselective Azidation of o-Alkynylaldehydes over [3 + 2] Cycloaddition and Subsequent Staudinger Reaction: Access to Benzonaphthyridines/Naphthyridines

Article abstract of DOI:10.1021/acs.joc.7b01016

An efficient tandem approach for the chemoselective synthesis of functionalized azido-pyranoquinolines and azido-iodo-pyranoquinolines via electrophilic cyclization of o-alkynylaldehydes in the presence of sodium azide under mild reaction conditions is described. Mechanistic studies confirm the formation of azido-pyranoquinolines through nucleophilic attack of azide on pyrilium intermediate over [3 + 2] cycloaddition of the azide on the alkyne. The synthesized azido-pyranoquinolines were transformed into benzonaphthyridines via Staudinger reaction. The mechanistic pathway was supported by deuterium labeling experiment and X-ray crystallographic studies.

Full text of DOI:10.1021/acs.joc.7b01016

Subscriber access provided by Binghamton University | Libraries
Article
Chemoselective Azidation of o-Alkynylaldehydes over
[3+2] Cycloaddition and Subsequent Staudinger Reaction:
An Access to Benzonaphthyridines/Naphthyridines
Pradeep Kumar, Trapti Aggarwal, and Akhilesh K. Verma
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 24 May 2017
Downloaded from http://pubs.acs.org on May 24, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
Chemoselective Azidation of o-Alkynylaldehydes
over [3+2] Cycloaddition and Subsequent Staudinger
Reaction: An Access to
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Benzonaphthyridines/Naphthyridines
Pradeep Kumar, Trapti Aggarwal and Akhilesh K. Verma*
Synthetic Organic Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi–110007, India
Email: averma@acbr.du.ac.in
ABSTRACT: An efficient tandem approach for the chemoselective synthesis of functionalized azido-
pyranoquinolines and azido-iodo-pyranoquinolines via electrophilic cyclization of o-alkynylaldehydes
in presence of sodium azide under mild reaction conditions has been described. The Mechanistic studies
confirm the formation of azido-pyranoquinolines through nucleophilic attack of azide on pyrilium
intermediate over [3+2] cycloaddition of azide on alkyne. The synthesized azido-pyranoquinolines were
transformed into benzonaphthyridines via Staudinger reaction. The mechanistic pathway was supported
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 34
1
2
3
by deuterium labeling experiment and X-Ray crystallographic studies.
4
5
6
INTRODUCTION
7
8
9
In recent time, new perspectives have been developed for organic azides, and their synthesis has
gained considerable attention due to their versatile use as an intermediate for the construction of N-
containing molecules.1 Synthetic utility of azides has been explicitly demonstrated by their
implementation in azide−alkyne Huisgen cycloaddition2a and Staudinger ligation2b for chemical biology
and drug discovery. Moreover, the incorporation of azide moiety in lead organic compounds accelerates
their biological activities.3 Despite an ample of azidation reactions,4 strategy for selective azidation at
carbonyl center remains challenging. Triazoles formation via [3+2] cycloaddition of azide with alkynes5
and alkynyl aldehydes6 has been well established (Scheme 1, i-ii). Electrophilic cyclization using metal-
catalysts and nucleophiles has emerged as an efficient tool for the construction of heterocycles (Scheme
1, iii).7 Although, implication of azide as an external nucleophile in the cyclization of o-
alkynylaldehydes remains elusive.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Notably, the napthyridines core is associated with a wide range of biological activities including
anticancer,8a anti-HIV-1,8b antimicrobial,8c and adrenoceptor blocking activities.8d Naphthyridines are
also known to use as luminescence materials because of their structural properties.8e Previously,
naphthyridine9 derivatives were synthesized using metal-catalyzed tandem cyclization.10a Recently,
Singh10b and our group10c have described the synthesis of benzonapthyridines using Pd-catalyzed
arylation and cyclization, respectively (Scheme 1, iv). Owing to the pharmacological importance and in
continuation of our ongoing research,11 herein we have developed a facile chemoselective strategy for
the synthesis of pyranoquinolines and benzonaphthyridines. We initiated our reaction with readily
accessible o-alkynylaldehydes and sodium azide via electrophilic cyclization followed by concomitant
Staudinger Reaction to afford the substituted napthyridines (Scheme 1, v).
2
ACS Paragon Plus Environment

Page 3 of 34
The Journal of Organic Chemistry
1
2
3
Scheme 1. Previous Reports V/s Present Work.
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
RESULTS AND DISCUSSION
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
We begin our preliminary observations with 2-(phenylethynyl)quinoline-3-carbaldehyde 1a along with
NaN3 by using our previously reported conditions11b i.e. 10 mol % of AgNO3 as a catalyst in H2O at 80
°C; however, no progress in the reaction was observed after 1 h (Table 1, entry 1). Other solvents like
DCE and toluene (entries 2 and 3) failed to provide the desired product. When MeOH was used as a
solvent at 70 °C, it acts as strong nucleophile and formed 1-methoxy-3-phenyl-1H-isochromene
exclusively in 70% yield instead of product 2a (entry 4); however, MeCN failed to provide desired
product with AgNO3 (entry 5). The reaction with other silver salts like AgTFA and AgOAc (10 mol %)
in MeCN afforded the desired product 2a in lower yield (entries 6 and 7). Use of AgOTf afforded the
desired product 2a in 76% yield in 6 h (entry 8). The yield of product remained same when the reaction
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 34
1
2
3
4
5
6
7
8
was run for 4 h (entry 9). Longer reaction time afforded the product in slightly lower yield (entry 10).
While 5 mol % of AgOTf provided the product 2a in 56% yield (entry 11). Use of TMSN3 as azide
source gave product 2a in diminished yield (entry 12), whereas TsN3 found incompatible for the
reaction (entry 13). When the amount of NaN3 was decreased to 0.5 mmol, the product 2a was obtained
in 58% yield (entry 14). Other metal salts such as cobalt (II), copper (II), palladium (II), gold (I) and
gold (III) with different counter ions were found inadequate (entry 12 –19). When the reaction was
performed in the absence of catalyst and solvent, the desired product 2a was not obtained in 24 h (entry
20). After screening various solvent and catalyst, it was found that the solvent and choice of silver salts
was crucial for the formation of desired azido products.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table1. Optimization of Reaction Conditionsa
Entry
Catalyst (mol %)
Solvent
temp( oC)/
time (h)
80/1
2a
yield (%)b
NR
111b
2
AgNO3(10)
AgNO3(10)
AgNO3(10)
AgNO3(10)
AgNO3(10)
AgTFA (10)
AgOAc (10)
AgOTf (10)
AgOTf (10)
H2O
DCE
80/6
80/6
70/6
70/6
70/6
70/6
70/6
70/4
NR
NR
NRc
NR
46
3
Toluene
MeOH
MeCN
MeCN
MeCN
MeCN
MeCN
4
5
6
7
35
8
76
9
76
4
ACS Paragon Plus Environment

Page 5 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
10
11
12
13
14
15
16
17
18
19
20
AgOTf (10)
AgOTf (5)
AgOTf (10)
AgOTf (10)
AgOTf (1o)
COCl2 (10)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
70/12
70/4
70/4
70/4
70/24
70/6
70/6
70/6
70/6
70/6
70/24
72
56
68d
NRe
58 f
26
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
CuOAc (10)
PdCl2 (10)
AuCl (10)
AuCl3 (10)
-
MeCN
MeCN
MeCN
MeCN
-
31
20
35
28
NR
aReactions were carried out using 1a (0.5 mmol), NaN3 (1.0 mmol.) in 2.0 mL of solvents. Isolated
b
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
c
yield. Isochromene was obtained in 70% yield. d Using TMSN3 (1.0 mmol). e Using TsN3 (1.0 mmol). f
0.5 mmol of NaN3 was used.
With optimal reaction condition, we next extended the scope of the reaction by utilizing a variety of
substituted o-alkynylaldehyde having an electron-releasing, electron-withdrawing, hetero-aromatic and
aliphatic group (Table 2). When phenyl substituted substrate 1a was reacted under standard condition,
76% yield of desired product 2a was obtained. Electron-releasing groups like -Me, -Et and -OMe at a
distal end of the phenyl ring of alkyne afforded the corresponding products 2b–e in 74–84% yields,
however, 2-(o-tolylethynyl)quinoline-3-carbaldehyde 1f provided the desired product 2f in slightly
lower yield which might be due to the steric congestion. The substrate 1g bearing an electron-
withdrawing -CF3 group on para-position of the phenyl ring provided the products 2g in 67% yield;
whereas, thienyl substituted o-alkynylaldehyde 1h provided the desired product 2h in 72% yield. The
reaction was successful with substrates having aliphatic alkynes 1i and terminal alkyne 1j. Further, the
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 34
1
2
3
4
5
6
7
8
optimal protocol was utilized for substrates having 6-methyl and 6-methoxy-substituted alkynyl
quinoline-3-carbaldehydes 1k–w having a variety of electron-rich and electron-poor alkynes; the
corresponding products 2k–w were obtained in 65-84% yields. The reaction was also compatible with
substrate 2-((3,5-dimethoxyphenyl)ethynyl)-6-methoxy quinoline-3-carbaldehyde 1x and afforded the
desired product 2x in 82% yield. The formations of desired azido-pyranoquinolines were confirmed by
the spectroscopic studies and X-ray crystallographic data of product 2b.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Synthesis of Azidopyranoquinolinesa,b
entry
1
o-alkynylaldehyde (1)
product (2)
yield (%)
76
1a
1b
2a
2b
2
3
4
5
80
80
84
74
1c
1d
1e
2c
2d
2e
6
ACS Paragon Plus Environment

Page 7 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
6
7
64
1f
2f
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
67
72
1g
2g
8
9
1h
1i
2h
2i
65
10
11
60
80
1j
2j
1k
2k
1l
12
13
82
83
2l
1m
2m
1n
14
78
2n
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 34
1
2
3
1o
4
5
6
7
8
9
15
16
70
68
2o
2p
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1p
1q
1r
1s
1t
17
18
19
20
75
81
65
84
2q
2r
2s
2t
1u
1v
21
22
87
72
2u
2v
8
ACS Paragon Plus Environment

Page 9 of 34
The Journal of Organic Chemistry
1
2
3
1w
1x
4
5
6
7
8
9
10
11
12
13
14
15
16
17
23
24
79
82
2w
2x
aReactions were carried out using optimal reaction conditions (Table 1 entry 11). yield. Reaction
b
c
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
completed in 18 h. dReaction completed in 24 h
After obtaining successful results with metal-catalyzed cyclization, we next explored iodine-
induced ring closure for the synthesis of substituted azido-iodo-pyranoquinolines 3a–f from
corresponding o-alkynyl aldehydes (Scheme 2). The reaction was preceded through the iodonium
intermediate 1’ which subsequently cyclized through 6-endo dig cyclization in the presence of sodium
azide and molecular iodine afforded the desired product 3. The phenyl and electron-rich substituted
arenes afforded the substituted azido-Iodo products 3a-e in 76-90% yield. The alkyl substituted 1y was
well tolerated and provided the product 3f in moderate yield.
Scheme 2. Synthesis of Azido-Iodo-pyrano quinolines
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 34
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Next, we extended the utility of synthesized azido-pyranoquinolines/azido-iodopyrano
quinolines via Staudinger reaction12 (Table 3). When substrates 2 or 3 were treated with PPh3 in MeOH
at room temperature, interestingly we obtained benzonapthyridines 4 exclusively instead of amino-
pyranoquinolines 5/ iodo-benzonapthyridines 4’. We have successfully explored the Staudinger reaction
for the construction of biologically important functionalized benzonaphthyridines 4a-j in good to
excellent yield. The reaction proceeded smoothly with various electron-donating as well as electron-
deficient substrates. The substrate 3f having aliphatic substitution provided the targeted
benzonapthyridine 4j in 88% yield.
Table 3. Synthesis of Benzo-naphthyridines via Staudinger Reaction.a
Substrate 2/ 3
Yield %
Entry
Product 4
1
90
2a
4a
10
ACS Paragon Plus Environment

Page 11 of 34
The Journal of Organic Chemistry
1
2
3
88
4
5
6
7
8
9
2
3
2b
4b
4c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
84/ 82
2d/3b
4
5
6
90
90
87
2h
2k
3c
4d
4e
4f
7
87
2l
4g
8
9
90/ 89
92
2r
2v
4h
4i
10
88
3f
4j
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 34
1
2
3
4
aReactions were carried out using 2/ 3 (0.5mmol), PPh3 (1.2 equiv.) in 2.0 mL of MeOH at rt for 15
mins. b Using 3 as substrate.
5
6
7
8
9
The scope of chemoselective azidation was next investigated with alkynyl-nicotinaldehyde 1z and 1aa
for the synthesis of napthyridines 6. The reaction proceeded well and provided the desired 1,6 and 2,6
napthyridines 6a and 6b via electrophilic iodocyclization followed by Staudinger reaction in good yields
(Scheme 3).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Synthesis of 1,6 and 2,6-Naphthyridines from Azido-iodo-pyranopyridines
Further, we performed the deuterium labeling studies of azido-substrate 2l by using MeOD as a
solvent, which showed that the deuterium was incorporated at the C-4 position in the
benzonaphthyridine 4f-D1 (Scheme 4). This result supports the involvement of tautomerization
step (v-vi) as described in the plausible mechanism (Scheme 7) for the synthesis of
benzonapthyridine.
Scheme 4. Deuterium Labeling Studies
Based on the above observations, we proposed a mechanistic pathway for the reaction as
described in scheme 5.
It includes two steps; the first step involves the formation of
azidopyranoquinolines 2 and the second step shows the direct conversion of azidopyrano quinolines 2
12
ACS Paragon Plus Environment

Page 13 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
into benzonaphthyridines 4. The first step of mechanistic cycle initiated by the coordination of silver
metal to alkyne triple bond,13 which triggers the attack of carbonyl oxygen to form oxonium ion via
electrophilic cyclization i. Consequently, nucleophilic attack of azide followed by demetallation
afforded the azidated product 2.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 5. Proposed Reaction Mechanism
Next, the synthesis of benzonapthyridine was demonstrated in step 2 via formation of aza-ylide
species12 iii by using triphenylphosphine, which subsequently from unstable intermediate iv in the
presence of MeOD. The instability and presence of nitrogen lone pair trigger the opening of pyran ring
which immediately tautomerizes to give species vi.14 Rapid intramolecular cyclization of species vi
followed by aromatization leads to the generation of desired product 4.
Scheme 6. Reaction of an Alkyne with Azide.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 34
1
2
3
4
5
6
7
8
9
It was interesting to note that when the reaction was performed with substrate 1l in DMSO at 120 °C
under the metal-free condition the triazole substituted aldehyde 7 was formed exclusively in 74% yields
instead of azido-pyranoquinolines 2l (Scheme 6). This was probably due to the preferential [3+2]
cycloaddition over alkyne activation in the absence of a metal catalyst.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 7. Synthesis of Trizolopyranoquinolines.
Next, we demonstrated the synthetic utility of the azidopyranoquinolines for the synthesis of trizolo
pyranoquinolines via [3+2] cycloaddition (Scheme 7). The analogs of these compounds have been used
to tag azide installation within the virus particles,15a nucleic acids15b and proteins from complex tissue
lysates15c with virtually no background labeling. The trizolo-pyranoquinolines 8a-c was synthesized in
96 to 98% yield using CuSO4.5H2O as a catalyst.
CONCLUSION
In summary, we have demonstrated chemoselective azidation of o-alkynyl aldehydes via 6-endo dig
electrophilic cyclization over [3+2] cycloaddition reaction using the silver catalyst as well as
14
ACS Paragon Plus Environment

Page 15 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
inexpensive iodine. Further, the synthesized azido-pyranoquinolines were elucidated under Staudinger
reaction condition for the generation of benznaphthyridines and napthyridines via breaking of C-O bond
and successive intramolecular N-C bond formation. In contrary, the metal-free condition afforded the
trizolopyranoquinolines through [3+2] cycloaddition reaction. The deuterium incorporation in
benzonaphthyridines confirmed the proposed mechanistic pathway. This chemistry is general and
expected to find application in a variety of organic synthesis.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
EXPERIMENTAL SECTION
The starting material 2-alkynylaldehydes required for synthesis were prepared by using our reported
methodology. The structure and purity of known starting materials were confirmed by comparison of
their physical and spectral data (1H NMR and 13C NMR) with those reported in literature.17
1
Characterization. H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in
CDCl3/DMSO-d6. Chemical shifts for protons and carbons are reported in ppm from tetramethylsilane
and are referenced to the carbon resonance of the solvent. Data are reported as follows: chemical shift,
multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd =
doublet of doublet), coupling constants in Hertz and integration. High-resolution mass spectra were
recorded on electrospray mass spectrometer. Crystal structure analysis was accomplished on single
needles X-ray diffractometer. TLC analysis was performed on commercially prepared 60 F254 silica gel
plates and visualized by either UV irradiation or by staining with I2. All purchased chemicals were used
as received. All melting points are uncorrected. All the HRMS are measured by Q-TOF B.05.01
(B5125).
General Procedure for the Synthesis of Azidopyranoquinolines (2a-x).
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 34
1
2
3
4
5
6
7
8
In an oven-dried reaction vial, 2-alkynyl-quinoline3-carbaldehyde (0.5 mmol) was dissolved in
acetonitrile (2 mL), then NaN3 (1.0 mmol) was added. Then, AgOTf (10 mol %) was added to the
reaction mixture. The resulting reaction mixture was heated at 70 °C for 4_24 h. Progression of the
reaction was monitored by TLC while noticing complete consumption of 2-alkynyl-quinoline3-
carbaldehyde, the reaction was cool to room temperature. The reaction mixture was diluted water (15
mL) and washed with aqueous saturated brine solution, and then extracted with EtOAc. The combined
organic layers were dried over Na2SO4, concentrated, and purified by column chromatography (:
hexane: ethylacetate :: 90:10) to afford the corresponding product. All compounds were crystallized in
DCM-Hexane.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-phenyl-1H-pyrano[4,3-b]quinoline (2a). The product was obtained as light yellow crystals,
(114.0 mg, 76% yield), mp 102–104 °C,1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.3 Hz, 1H), 7.93 (s,
1H), 7.81–7.77 (m, 2H), 7.73 (d, J = 8.3 Hz, 1H), 7.67–7.63 (m, 1H), 7.44–7.35 (m, 4H), 6.89 (s, 1H),
13
6.72 (s, 1H). C NMR (100 MHz, CDCl3) δ 156.2, 149.11, 149.06, 133.0, 132.6, 130.7, 130.3, 128.8,
128.7, 128.0, 126.9, 126.1, 125.6, 120.8, 102.8, 88.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C18H12N4O 301.1089; found 301.1088.
1-Azido-3-(p-tolyl)-1H-pyrano[4,3-b]quinoline (2b). The product was obtained as pale white
needles, (122.46 mg, 78% yield), mp 120–122 °C,1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.3 Hz,
1H), 7.96 (s, 1H), 7.78–7.68 (m, 4H), 7.48–7.44 (m, 1H), 7.24 (d, J = 7.6 Hz, 2H), 6.90 (s, 1H), 6.75 (s,
1H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 156.4, 149.3, 149.1, 140.7, 132.5, 130.6, 130.2,
129.4, 128.7, 128.0, 126.8, 126.0, 125.6, 120.8, 102.1, 88.3, 21.4; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C19H14N4O 315.1246; found 315.1238.
1-Azido-3-(4-ethylphenyl)-1H-pyrano[4,3-b]quinolines (2c). The product was obtained as pale yellow
crystals, (131.20 mg, 80% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.3 Hz,
1H), 7.95 (s, 1H), 7.75–7.72 (m, 3H), 7.68–7.64 (m, 1H), 7.44–7.41 7.43 (m, 1H), 7.23 (d, J = 7.6 Hz,
16
ACS Paragon Plus Environment

Page 17 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
2H), 6.87 (s, 1H), 6.73 (s, 1H), 2.64 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 156.4, 149.3, 149.1, 147.0, 132.5, 130.7, 130.4, 128.8, 128.3, 128.0, 126.8, 126.0, 125.7,
120.8, 102.1, 88.3, 28.8, 15.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H16N4O 329.1402; found
329.1402.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-(4-methoxyphenyl)-1H-pyrano[4,3-b]quinolines (2d). The product was obtained as light
brown needles, (138.60 mg, 84% yield), mp 150–152 °C,1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.6
Hz, 1H), 7.93 (s, 1H), 7.76–7.73 (m, 3H), 7.67–7.63 (m, 1H), 7.44–7.40 (m, 1H), 6.92 (dd, J = 8.7 and
1.8 Hz, 2H), 6.79 (s, 1H), 6.71 (s, 1H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 157.6, 155.0,
146.9, 145.1, 133.1, 131.3, 130.2, 130.1, 128.7, 127.9, 125.5, 123.3, 121.0, 105.7, 102.8, 88.3, 55.6;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H14N4O2 331.1195; found 331.1189.
1-Azido-3-(3-methoxyphenyl)-1H-pyrano[4,3-b]quinolines (2e). The product was obtained as yellow
crystals, (122.10 mg, 74% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.3 Hz,
1H), 8.00 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.74–7.69 (m, 1H), 7.50–7.44 (m, 2H), 7.35–7.33 (m, 2H),
6.98 (dd, J = 8.3 and 2.2 Hz, 1H), 6.94 (s, 1H), 6.78 (s, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 159.8, 155.6, 148.3, 147.6, 136.2, 134.5, 133.0, 131.9, 128.5, 126.9, 120.8, 118.2, 116.4, 110.6,
103.2, 88.4, 55.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H14N4O2 331.1195; found 331.1203.
1-Azido-3-(o-tolyl)-1H-pyrano[4,3-b]quinolines (2f). The product was obtained as light yellow
needles (100.48 mg, 64% yield), mp 115–117 °C,1H NMR (400 MHz, CDCl3) δ 8.04–8.00 (m, 2H),
7.77 (d, J = 7.6 Hz, 1H), 7.71–7.67 (m, 1H), 7.50–7.44 (m, 2H), 7.31–7.26 (m, 1H), 7.22 (d, J = 6.8
13
Hz, 2H), 6.70 (s, 1H), 6.54 (s, 1H), 2.51 (s, 3H); C NMR (100 MHz, CDCl3) δ 158.5, 150.2, 149.0,
141.0, 132.6, 131.1, 130.7, 129.8, 129.7, 129.6, 129.3, 128.1, 126.1, 125.9, 125.8, 121.2, 106.8, 88.7,
20.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H14N4O 315.1246; found 315.1238.
1-Azido-3-(4-(trifluoromethyl)phenyl)-1H-pyrano[4,3-b]quinoline (2g). The product was obtained as
light yellow needles, (125.0 mg, 67% yield), mp 160–162 °C,1H NMR (400 MHz, CDCl3) δ 7.98 (d, J
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 34
1
2
3
4
= 8.3 Hz, 1H), 7.95 (s, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 8.3 Hz, 1H), 7.69–7.58 (m, 3H),
13
7.46–7.42 (m, 1H), 6.96 (s, 1H), 6.73 (s, 1H). C NMR (100 MHz, CDCl3) δ 154.4, 149.1, 148.5,
5
6
7
136.3, 132.8, 130.9, 128.9, 128.0, 127.0, 126.5, 125.7 (q, J = 3.8 Hz, 1C), 120.8, 104.6, 88.4; HRMS
8
9
(ESI-TOF) m/z: [M + H]+ Calcd for C19H11F3N4O 369.0963; found 369.0962.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-(thiophen-3-yl)-1H-pyrano[4,3-b]quinoline (2h). The product was obtained as pale yellow
crystals, (110.16 mg, 72% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.3 Hz,
1H), 7.96 (s, 1H), 7.80–7.76 (m, 2H), 7.72–7.68 (m, 1H), 7.48–7.47 (m, 1H), 7.45–7.42 (m, 1H), 7.38–
13
7.36 (m, 1H), 6.78 (s, 1H), 6.72 (s, 1H); C NMR (100 MHz, CDCl3) δ 152.6, 149.1, 135.5, 132.6,
130.7, 128.8, 128.0, 126.8, 126.0, 124.9, 124.6, 120.8, 102.6, 88.2; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C16H10N4OS 307.0654; found 307.0648.
1-Azido-3-cyclohexyl-1H-pyrano[4,3-b]quinolines (2i). The product was obtained as light orange
crystals, (99.45 mg, 65% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz,
1H), 7.86 (s, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.64–7.61 (m, 1H), 7.41–7.37 (m, 1H), 6.51 (s, 1H), 6.12 (s,
1H), 2.25–2.19 (m, 1H), 1.98–1.93 (m, 2H), 1.79–1.76 (m, 2H), 1.37–1.26 (m, 6H); 13C NMR (100
MHz, CDCl3) δ 165.9, 149.2, 148.8, 132.6, 130.5, 128.6, 127.9, 126.7, 125.7, 120.4, 101.5, 88.0, 42.4,
30.4, 26.0, 25.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H18N4O 307.1559; found 307.1565.
1-Azido-1H-pyrano[4,3-b]quinoline (2j). The product was obtained as light yellow crystals, (67.20 mg,
60% yield), mp 122–124 °C, 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.3 Hz, 1H), 7.91 (s, 1H), 7.74
(d, J = 8.3 Hz, 1H), 7.68–7.64 (m, 1H), 7.46–7.42 (m, 1H), 6.94 (d, J = 6.1 Hz, 1H), 6.55 (s, 1H), 6.29
13
(d, J = 6.1 Hz, 1H); C NMR (100 MHz, CDCl3) δ 148.6, 133.1, 130.7, 128.9, 128.0, 127.0, 126.3,
107.6, 87.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C12H8N4O 225.0776; found 225.0784.
1-Azido-8-methyl-3-phenyl-1H-pyrano[4,3-b]quinoline (2k). The product was obtained as dark yellow
crystals, (125.60 mg, 80% yield), mp 130–132 °C,1H NMR (400 MHz, CDCl3) δ 7.89–7.86 (m, 2H),
18
ACS Paragon Plus Environment

Page 19 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
7.81–7.78 (m, 2H), 7.51–7.48 (m, 2H), 7.41–7.35 (m, 3H), 6.88 (s, 1H), 6.71 (s, 1H), 2.46 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 155.7, 148.3, 147.7, 136.2, 133.1, 133.0, 131.9, 130.2, 128.7, 128.5, 127.0,
125.6, 120.8, 102.9, 88.4, 21.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H14N4O 315.1246;
found 315.1238.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-(4-ethylphenyl)-8-methoxy-1H-pyrano[4,3-b]quinoline (2l). The product was obtained as
white crystals, (140.22 mg, 82% yield), mp 158–160 °C,1H NMR (400 MHz, CDCl3) δ 7.86 (d, J =
9.1 Hz, 1H), 7.82 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.48–7.47 (m, 2H), 7.21 (d, J = 7.6 Hz, 2H), 6.83
13
(s, 1H), 6.68 (s, 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.45 (s, 3H), 1.19 (t, J = 7.6 Hz, 3H); C NMR (100
MHz, CDCl3) δ 155.9, 148.5, 147.6, 146.8, 136.0, 132.9, 131.9, 130.5, 128.4, 128.2, 126.9, 126.8,
125.6, 120.8, 102.2, 88.3, 28.8, 21.5, 15.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18N4O
343.1559; found 343.1573.
1-Azido-3-(4-(tert-butyl)phenyl)-8-methyl-1H-pyrano[4,3-b]quinolines (2m). The product was obtained
as light yellow needles, (153.55 mg, 83% yield), mp 168–170 °C,1H NMR (400 MHz, CDCl3) δ 7.93–
7.89 (m, 2H), 7.78 (d, J = 9.1 Hz, 2H), 7.55–7.53 (m, 2H), 7.47 (d, J = 8.3 Hz, 2H), 6.90 (s, 1H), 6.75
13
(s, 1H), 2.51 (s, 3H), 1.33 (s, 9H); C NMR (100 MHz, CDCl3) δ 155.9, 153.7, 148.5, 147.6, 136.0,
132.9, 131.9, 128.4, 126.9, 125.7, 125.4, 120.8, 102.2, 88.4, 22.6, 21.5, 14.1; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C23H22N4O 371.1872; found 371.1869.
1-Azido-3-(3-methoxyphenyl)-8-methyl-1H-pyrano[4,3-b]quinoline (2n). The product was obtained as
light yellow crystals, (134.16 mg, 78% yield), mp 138–140 °C,1H NMR (400 MHz, CDCl3) δ 7.90–
7.88 (m, 4H), 7.65 (d, J = 8.4 Hz, 2H), 7.53–7.51 (m, 2H), 6.96 (s, 1H), 6.75 (s, 1H), 3.90 (s, 3H), 2.48
13
(s, 3H); C NMR (100 MHz, CDCl3) δ 159.8, 155.6, 148.3, 147.6, 136.2, 134.5, 133.0, 131.9, 129.7,
128.5, 126.9, 120.8, 118.2, 116.4, 110.6, 103.2, 88.4, 55.2, 21.5; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C20H16N4O2 345.1352; found 345.1352.
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 34
1
2
3
4
5
6
7
8
1-Azido-8-methyl-3-(4-(trifluoromethoxy)phenyl)-1H-pyrano[4,3-b]quinolines (2o). The product was
obtained as yellow crystals, (139.30 mg, 70% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ
7.89–7.87 (m, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.52–7.50 (m, 2H), 7.23 (d, J = 8.3 Hz, 2H), 6.87 (s, 1H),
6.72 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.2, 150.3, 147.8, 147.5, 136.4, 133.1,
132.0, 131.6, 128.4, 127.1, 126.9, 121.6, 120.9, 120.5, 119.1, 103.3, 88.3, 21.5; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C20H13F3N4O2 399.1069; found 399.1077.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-8-methyl-3-(4-(trifluoromethyl)phenyl)-1H-pyrano[4,3-b]quinolines (2p). The product was
obtained as pale yellow crystals, (129.88 mg, 68% yield), mp 170–172 °C,1H NMR (400 MHz, CDCl3)
δ 7.90–7.88 (m, 4H), 7.65 (d, J = 8.3 Hz, 2H), 7.53 –7.51 (m, 2H), 6.96 (s, 1H), 6.75 (s, 1H), 2.48 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 153.9, 147.7, 147.6, 136.6, 136.4, 133.2, 132.1, 128.6, 127.1,
127.0, 125.7 (q, J = 3.8 Hz, 1C), 120.7, 104.6, 88.4, 21.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C20H13F3N4O 383.1120; found 383.1132.
1-Azido-8-methyl-3-(thiophen-3-yl)-1H-pyrano[4,3-b]quinoline (2q). The product was obtained as pale
white crystals, (120.0 mg, 75% yield), mp 135–137 °C,1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.3
Hz, 1H), 7.89 (s, 1H), 7.797–7.790 (m, 1H), 7.55–7.53 (m, 2H), 7.44–7.43 (m, 1H), 7.39–7.37 (m, 1H),
6.78 (s, 1H), 6.72 (s, 1H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.2, 148.2, 147.5, 136.1,
135.6, 133.0, 132.0, 128.3, 126.9, 126.7, 124.9, 124.5, 120.7, 102.5, 88.2, 21.5; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C17H12N4OS 321.0810; found 321.0808.
1-Azido-8-methoxy-3-phenyl-1H-pyrano[4,3-b]quinolines (2r). The product was obtained as yellow
crystals, (133.78 mg, 81% yield), mp 95–97 °C,1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 9.1 Hz, 1H),
7.88 (s, 1H). 7.84 (dd, J = 8.3 and 2.2 Hz, 2H), 7.46–7.41 (m, 3H), 7.37 (dd, J = 9.1 and 2.2 Hz, 1H),
7.07–7.06 (m, 1H), 6.92 (s, 1H), 6.75 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.6,
155.0, 146.9, 145.1, 133.1, 131.3, 130.2, 130.1, 128.7, 127.9, 125.5, 123.3, 121.0, 105.7, 102.8, 88.3,
20
ACS Paragon Plus Environment

Page 21 of 34
The Journal of Organic Chemistry
1
2
3
55.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H14N4O2 331.1195; found 331.1189.
4
5
6
7
8
1-Azido-8-methoxy-3-(o-tolyl)-1H-pyrano[4,3-b]quinoline) (2s). The product was obtained as yellow
needles, (111.8 mg, 65% yield), mp 98–100 °C,1H NMR (400 MHz, CDCl3) δ 7.90–7.87 (m, 2H),
7.52–7.49 (m, 2H), 7.40–7.38 (m, 1H), 7.32–7.28 (m, 2H), 6.93–6.90 (m, 2H), 6.72 (s, 1H), 3.81 (s,
3H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 155.6, 148.3, 147.6, 136.2, 134.5, 133.0,
131.9, 129.7, 128.5, 126.9, 120.8, 118.2, 116.4, 110.6, 103.2, 88.4, 55.2, 21.5; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C20H16N4O2 345.1352; found 345.1352.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-(4-ethylphenyl)-8-methoxy-1H-pyrano[4,3-b]quinolines (2t). The product was obtained as
light yellow crystals, (150.36 mg, 84% yield), mp 106–108 °C,1H NMR (400 MHz, CDCl3) δ 7.89 (d, J
= 9.1 Hz, 1H), 7.83 (s, 1H), 7.70 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 9.1 Hz, 1H), 7.22 (d, J = 8.3 Hz, 2H),
7.01 (s, 1H), 6.84 (s, 1H), 6.69 (s, 1H), 3.86 (s, 3H), 2.63 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 157.5, 155.4, 147.0, 146.8, 131.4, 130.5, 130.0, 128.2, 127.8, 125.6,
123.3, 121.0, 105.8, 101.9, 88.3, 55.6, 28.8, 15.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C21H18N4O2 359.1508; found 359.1506.
1-Azido-8-methoxy-3-(4-methoxyphenyl)-1H-pyrano[4,3-b] quinolines (2u). The product was obtained
as light yellow crystals, (156.6 mg, 87% yield), mp 115–117 °C,1H NMR (400 MHz, CDCl3) δ 7.89 (d,
J = 9.1 Hz, 1H), 7.83 (s, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.31 (dd, J = 9.1 and 2.2 Hz, 1H), 7.01 (d, J =
13
3.0 Hz, 1H), 6.90 (d, J = 9.1 Hz, 2H), 6.79 (s, 1H), 6.68 (s, 1H), 3.85 (s, 3H), 3.79 (s, 3H); C NMR
(100 MHz, CDCl3) δ 161.1, 157.4, 155.2, 147.2, 132.2, 131.3, 129.9, 127.7, 127.2, 125.6, 123.3, 121.0,
114.1, 105.8, 100.9, 88.3, 55.6, 55.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H16N4O3
361.1301; found 361.1292.
1-Azido-8-methoxy-3-(4-(trifluoromethyl)phenyl)-1H-pyrano[4,3-b]quinolone (2v). The product was
obtained as pale white crystals, (143.2 mg, 72% yield), mp 118–120 °C,1H NMR (400 MHz, CDCl3) δ
7.95–7.93 (m, 2H), 7.91–7.89 (m, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.39 (dd, J = 9.1 and 3.0 Hz, 1H), 7.07
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 34
1
2
3
4
5
6
7
(d, J = 2.2 Hz, 1H), 6.98 (s, 1H), 6.76 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.9,
153.3, 146.2, 145.2, 136.5, 131.3, 130.4, 128.1, 125.6 (q, J = 3.8 Hz, 1C), 123.6, 121.0, 105.7, 104.6,
88.4, 55.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H13F3N4O2 399.1069; found 399.1077.
8
9
1-Azido-8-methoxy-3-(thiophen-3-yl)-1H-pyrano[4,3-b]quinolines (2w).The product was obtained as
light yellow needles, (132.7 mg, 79% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 7.87 (d, J
= 9.1 Hz, 1H), 7.81 (s, 1H), 7.71 (s, 1H), 7.37–7.36 (m, 1H), 7.32–7.30 (m, 2H), 7.01 (d, J = 2.2 Hz,
1H), 6.70 (s, 1H), 6.65 (s, 1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.5, 151.6, 146.8, 145.0,
135.6, 131.3, 130.1, 127.8, 126.7, 124.8, 124.2, 123.3, 121.0, 105.8, 102.5, 88.2, 55.6; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C17H12N4O2S 337.0759; found 337.0753.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-3-(3,5-dimethoxyphenyl)-8-methoxy-1H-pyrano[4,3-b]quinolines (2x). The product was
obtained as light yellow crystals, (159.89 mg, 82% yield), mp 102 –104 °C,1H NMR (400 MHz,
CDCl3) δ 7.95 (d, J = 9.1 Hz, 1H), 7.90 (s, 1H), 7.40 (dd, J = 9.1 and 2.7 Hz, 1H), 7.08 (d, J = 2.2 Hz,
1H), 7.01 (d, J = 2.2 Hz, 2H), 6.92 (s, 1H), 6.76 (s, 1H), 6.55–6.54 (m, 1H), 3.93 (s, 3H), 3.85 (s, 6H);
13C NMR (100 MHz, CDCl3) δ 160.9, 157.6, 154.8, 146.7, 145.1, 135.0, 131.3, 130.2, 127.9, 123.4,
121.1, 105.7, 103.4, 103.3, 102.7, 88.3, 55.6, 55.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C21H18N4O4 391.1406; found 391.1403.
General Procedure for the synthesis of Azido-iodo-pyranoquinolines (3a-h).
In an oven-dried reaction vial, 2-alkynyl-quinoline3-carbaldehyde (0.5 mmol) was taken in acetonitrile
(2 mL), then NaN3 (2.0 equiv), K2CO3 (2.5 equiv) and molecular iodine (2.5 equiv) were added. The
resulting reaction mixture was heated at 70 °C for 0.5 h. Progression of the reaction was monitored by
TLC, while noticing complete consumption of 2-alkynyl-quinoline3-carbaldehyde, reaction was cool to
room temperature. The solution was washed with saturated solution of Na2S2O3 and then extracted with
EtOAc. The combined organic layers were dried over Na2SO4, concentrated, and purified by column
22
ACS Paragon Plus Environment

Page 23 of 34
The Journal of Organic Chemistry
1
2
3
chromatography (hexane: ethylacetate:: 98:2) to afford the corresponding product.
4
5
6
7
8
1-Azido-4-iodo-3-phenyl-1H-pyrano[4,3-b]quinoline (3a). The product was crystallised in DCM/
hexane and obtained as light yellow crystals, (180.62 mg, 85% yield), mp 140–142 °C,1H NMR (400
MHz, CDCl3) δ 8.14 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.78 (d, J = 8.3 Hz 1H), 7.72–7.68 (m, 3H), 7.50–
7.46 (m, 1H), 7.42–7.40 (m, 3H), 6.64 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 157.3, 148.9, 147.4,
135.8, 132.5, 130.7, 130.3, 130.2, 129.6, 128.0, 127.6, 127.3, 126.9, 120.2, 88.4, 78.4; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C18H11IN4O 427.0056; found 427.0029.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-Azido-4-iodo-3-(4-methoxyphenyl)-1H-pyrano[4,3-b]quinoline (3b). The product was crystallised in
DCM/ hexane and obtained as light yellow crystals, (205.20 mg, 90% yield), mp 140–142 °C,1H NMR
(400 MHz, CDCl3) δ 8.21 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.79–7.74 (m, 3H),
13
7.55–7.51 (m, 1H), 6.98 (d, J = 8.3 Hz, 2H), 6.68 (s, 1H), 3.87 (s, 3H); C NMR (100 MHz, CDCl3) δ
161.1, 157.0, 148.9, 147.8, 132.3, 132.1, 130.7, 129.5, 127.9, 127.6, 127.2, 126.7, 120.3, 113.3, 88.3,
77.3, 55.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H13IN4O2 457.0161; found 457.0158.
1-Azido-4-iodo-8-methyl-3-(p-tolyl)-1H-pyrano[4,3-b]quinoline (3c). The product was crystallised in
DCM/ hexane and obtained as light yellow crystals, (197.49 mg, 87% yield), mp 140–142 °C,1H NMR
(400 MHz, CDCl3) δ 8.02 (d, J = 9.16 Hz, 1H), 7.75 (s, 1H), 7.60 (d, J = 8.3 Hz 2H), 7.51–7.49 (m,
13
2H), 7.20 (d, J = 7.6 Hz, 2H), 6.58 (s, 1H), 2.45 (s, 3H), 2.4 (s, 3H); C NMR (100 MHz, CDCl3) δ
156.8, 147.5, 146.7, 140.5, 136.9, 132.95, 132.89, 131.7, 130.1, 129.2, 128.6, 127.2, 126.4, 120.1, 88.4,
78.0, 21.6, 21.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H15IN4O 454.0369; found 455.0365.
1-Azido-4-iodo-3-(4-methoxyphenyl)-8-methyl-1H-pyrano[4,3-b] quinoline (3d). The product was
crystallised in DCM/ hexane and obtained as light yellow crystals, (220.90 mg, 88% yield), mp 140–
142 °C,1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 9.16 Hz, 1H), 7.77 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H),
13
7.53–7.51 (m, 2H), 6.91 (d, J = 8.3 Hz, 2H), 6.59 (s, 1H), 3.80 (s, 3H), 2.47 (s, 3H); C NMR (100
MHz, CDCl3) δ 161.0, 156.5, 147.5, 147.0, 136.8, 133.0, 132.0, 131.7, 129.2, 127.9, 127.2, 126.5,
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 34
1
2
3
4
120.2, 113.2, 88.4, 76.7, 55.4, 21.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H15IN4O2
471.0318; found 471.0310.
5
6
7
8
9
1-Azido-4-iodo-8-methoxy-3-phenyl-1H-pyrano[4,3-b]quinoline (3e). The product was crystallised in
DCM/ hexane and obtained as light yellow crystals, (173.28 mg, 76% yield), mp 140–142 °C,1H NMR
(400 MHz, CDCl3) δ 8.03 (d, J = 9.1 Hz, 1H), 7.74 (s, 1H), 7.70–7.68 (m, 2H), 7.39–7.38 (m, 3H), 7.33
(dd, 9.5 and 3.0 Hz, 1H), 7.02–7.01 (m, 1H), 6.58 (s, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
158.1, 156.1, 145.2, 145.0, 135.8, 131.1, 131.0, 130.2, 130.1, 128.4, 127.9, 123.4, 120.4, 105.1, 88.4,
78.5, 55.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H13IN4O2 457.0161; found 457.0158.
1-Azido-4-iodo-8-methoxy-3-phenethyl-1H-pyrano[4,3-b]quinoline (3f). The product was crystallised in
DCM/ hexane and obtained as light yellow crystals, (164.56 mg, 68% yield), mp 140–142 °C,1H NMR
(400 MHz, CDCl3) δ 7.96 (d, J = 9.1 Hz, 1H), 7.64 (s, 1H), 7.28 (dd, 9.1 and 3.0 Hz, 1H), 7.23–7.22
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(m, 4H), 7.15–7.13 (m, 1H), 6.96–6.95 (m, 1H), 6.38 (s, 1H), 381 (s, 3H), 3.08 – 2.92 (m, 4H); C
NMR (100 MHz, CDCl3) δ 159.2, 157.8, 144.8, 144.3, 140.3, 130.93, 130.86, 128.5, 128.4, 128.1,
126.3, 123.2, 119.9, 105.2, 88.0, 78.9, 55.5, 39.7, 32.9, 29.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C21H17IN4O2 485.0474; found 485.0467.
1-Azido-4-iodo-3-phenyl-1H-pyrano[4,3-c]pyridine (3g). The product was crystallised in DCM/ hexane
1
and obtained as light yellow crystals, (142.50 mg, 76% yield), mp 140–142 °C, H NMR (400 MHz,
CDCl3) δ 8.75–8.73 (m, 1H), 7.75 (d, 9.1 Hz, 2H), 7.51 (d, 6.8 Hz, 1H), 7.28–7.25 (m, 1H), 6.98 (d, 8.3
13
Hz, 2H), 6.57 (s, 1H); C NMR (100 MHz, CDCl3) δ 161.0, 155.4, 151.2, 148.5, 132.6, 132.0, 127.4,
122.5, 120.8, 113.3, 88.2, 75.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H9IN4O 376.9899;
found 376.9908.
5-Azido-7-(4-(tert-butyl)phenyl)-8-iodo-5H-pyrano[4,3-b]pyridine (3h). The product was crystallised in
DCM/ hexane and obtained as light yellow crystals, (155.52 mg, 72% yield), mp 140–142 °C,1H NMR
(400 MHz, CDCl3) δ 8.74–8.72 (m, 1H), 7.73–7.70 (m, 2H), 7.51–7.47 (m, 3H), 7.26–7.24 (m, 1H),
24
ACS Paragon Plus Environment

Page 25 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
6.55 (s, 1H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 155.8, 153.6, 151.2, 148.3, 132.6, 132.4,
130.0, 124.9, 122.6, 120.8, 88.2, 76.2, 34.9, 31.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C18H17IN4O 433.0525; found 433.0540.
8
9
General Procedure for the Synthesis of 3-phenylbenzo[b][1,6]naphthyridine (4a-j).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The 3-substituted Benzonaphthyridines were prepared from azido-pyrano[4,3-b]quinoline 2 (0.50
mmol) in 2ml of methanol in reaction vial. Then 1.2 equiv of PPh3 was added to the reaction mixture
and stirred for 0.5 h. The solid compound was precipitate and settles down. The completion of reaction
was monitored by TLC and after completion the precipitate was filtered under vacuum and washed with
hexane. Then, the final compound were crystallizes from chloroform.
3-Phenylbenzo[b][1,6]naphthyridine (4a). The product was obtained as yellow crystals, (115.20 mg,
90% yield), mp 190–192 °C,1H NMR (400 MHz, CDCl3) δ 9.53 (s, 1H), 8.89 (s, 1H), 8.36 (s, 1H),
8.18–8.16 (m, 3H), 8.00 (d, J = 8.3 Hz, 1H), 7.84–7.81 (m, 1H), 7.69–7.66 (m, 1H), 7.55–7.51 (m, 1H),
7.41–7.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 154.7, 138.8, 137.3, 133.4, 133.3 132.6, 130.5,
130.4, 129.2, 129.03, 128.9, 128.5, 128.4, 127.2, 126.4, 121.1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C18H12N2 257.1079; found 257.1076.
3-(p-tolyl)Benzo[b][1,6]naphthyridine (4b). The product was obtained as light yellow crystals, (118.80
mg, 88% yield), mp 195–197 °C,1H NMR (400 MHz, CDCl3) 9.59 (s, 1H), 8.96 (s, 1H), 8.41 (s, 1H),
8.24 (d, J = 8.3 Hz, 1H), 8.15 (d, J = 7.6 Hz, 2H), 8.08 (d, J = 8.3 Hz, 1H), 77.50–7.46 (m, 1H), 7.62–
7.58 (m, 1H), 7.36 (d, J = 7.6 Hz, 2H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.7, 150.8, 150.3,
139.3, 137.3, 136.1, 135.2, 133.3, 132.5, 130.4, 129.7, 129.0, 128.6, 127.1, 126.3, 115.9, 22.6; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C19H14N2 271.1235; found 271.1235.
3-(4-Methoxyphenyl)benzo[b][1,6]naphthyridine (4c). The product was obtained as pale yellow
crystals, (120.12 mg, 84% yield), mp 188–190 °C,1H NMR (400 MHz, CDCl3) δ 9.56 (s, 1H), 8.92 (s,
1H), 8.34 (s, 1H), 8.23–8.19 (m, 3H), 8.05 (d, J = 8.3 Hz, 1H), 7.90–7.86 (m, 1H), 7.60–7.56 (m, 1H),
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 34
1
2
3
4
5
6
7
7.07 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.7, 154.6, 153.6, 152.1, 150.5,
137.3, 133.3, 132.5, 131.4, 130.5, 129.3, 129.0, 128.5, 126.1, 120.9, 114.3, 55.4; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C19H14N2O 287.1184; found 287.1179.
8
9
3-(Thiophen-3-yl)benzo[b][1,6]naphthyridine (4d). The product was obtained as pale white crystals,
(115.28 mg, 88% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 9.53 (s, 1H), 8.93 (s, 1H), 8.29
(s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.20–8.19 (m, 1H), 8.06 (d, J = 8.3 Hz, 1H), 7.91–7.87 (m, 1H), 7.82–
7.80 (m, 1H), 7.61–7.58 (m, 1H), 7.48–7.46 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 154.9, 152.1,
150.4, 150.0, 141.7, 137.4, 132.7, 129.3, 129.1, 126.9, 126.8, 126.3, 126.0, 124.8, 121.1, 115.6; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C16H10N2S 263.0643; found 263.0635.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8-Methyl-3-phenylbenzo[b][1,6]naphthyridine (4e). The product was obtained as yellow crystals,
(121.50 mg, 90% yield), mp 220–222 °C,1H NMR (400 MHz, CDCl3) δ 9.50 (s, 1H), 8.77 (s, 1H), 8.35
(s, 1H), 8.17–8.15 (m, 2H), 8.08 (d, J = 9.1 Hz, 1H), 7.74 (s, 1H), 7.68–7.65 (m, 1H), 7.49–7.45 (m,
2H), 7.40–7.37 (m, 1H), 2.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.6, 153.5, 151.0, 149.9, 139.0,
136.4, 136.0, 135.6, 129.1, 129.0, 128.9, 127.2, 127.0, 121.3, 116.7, 21.8; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C19H14N2 271.1235; found 271.1235.
8-Methyl-3-(p-tolyl)benzo[b][1,6]naphthyridine (4f). The product was obtained as yellow crystals,
(123.54 mg, 87% yield), mp 202–204 °C,1H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 8.80 (s, 1H), 8.38
(s, 1H), 8.14–8.12 (m, 3H), 7.78 (s, 1H), 7.48–7.45 (m, 1H), 7.34 (d, J = 7.6 Hz, 2H), 2.59 (s, 3H), 2.44
13
(s, 3H); C NMR (100 MHz, CDCl3) δ 154.5, 150.9, 149.8, 139.2, 136.3, 136.1, 135.6, 132.1, 132.0,
129.7, 128.9, 128.5, 128.4, 127.1, 121.2, 115.9, 21.7, 21.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C20H16N2 285.1392; found 285.1385.
3-(4-Ethylphenyl)-8-methylbenzo[b][1,6]naphthyridine (4g). The product was obtained as light yellow
crystals, (129.63 mg, 87% yield), mp 190–192 °C,1H NMR (400 MHz, CDCl3) δ 9.49 (s, 1H), 8.76 (s,
26
ACS Paragon Plus Environment

Page 27 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
1H), 8.33 (s, 1H), 8.10–8.06 (m, 3H), 7.74 (s, 1H), 7.66 (dd, J = 8.3 and 1.5 Hz, 1H), 7.31 (d , J = 8.3
Hz, 2H), 2.76 (q , J = 7.6 Hz, 2H), 2.53 (s, 3H). 1.24 (t , J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 154.6, 150.0, 148.6, 145.5, 143.2, 136.4, 136.3, 136.1, 135.6, 129.0, 128.5, 127.2, 127.1, 127.0, 118.9,
116.0, 28.7, 21.8, 15.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18N2 299.1548; found
299.1541.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8-Methyl-3-(p-tolyl)benzo[b][1,6]naphthyridine (4h). The product was obtained as light yellow crystals,
(128.70 mg, 90% yield), mp 98–100°C,1H NMR (400 MHz, CDCl3) δ 9.55 (s, 1H), 8.79 (s, 1H), 8.42 (s,
1H), 8.22 (d , J = 7.6 Hz, 2H), 8.14 (d , J = 9.1 Hz, 1H), 7.60–7.53 (m, 3H), 7.46 (d , J = 6.8 Hz, 1H),
7.22 (d , J = 2.3 Hz, 1H), 3.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.9, 154.0, 153.0, 149.3, 148.8,
138.9, 134.5, 130.8, 128.9, 128.07, 127.96, 127.1, 121.4, 116.9, 103.7, 55.6; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C19H14N2O 287.1184; found 287.1179.
8-Methoxy-3-(4-(trifluoromethyl)phenyl)benzo[b][1,6]naphthyridine (4i). The product was obtained as
pale white crystals, (162.84 mg, 92% yield), mp 140–142 °C,1H NMR (400 MHz, CDCl3) δ 9.48 (s,
1H), 8.72 (s, 1H), 8.38 (s, 1H), 8.26 (d, J = 8.3 Hz, 2H), 8.08 (d, J = 9.1 Hz, 1H), 7.72 (d, J = 8.3 Hz,
13
2H), 7.53 (dd, J = 9.5 and 2.3 Hz, 1H), 7.15 (d, J = 3.0 Hz, 1H), 3.94 (s, 3H); C NMR (100 MHz,
CDCl3) δ 157.8, 154.2, 151.2, 149.4, 148.5, 142.3, 134.5, 130.9, 128.4, 128.2, 127.3, 125.8 (q, J = 3.8
Hz, 1C), 122.2, 121.7, 117.7, 103.6, 55.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H13F3N2O
355.1058; found 355.1047.
8-Methoxy-3-phenethylbenzo[b][1,6]naphthyridine (4j). The product was obtained as light yellow
crystals, (138.1 mg, 88% yield), mp 195–197 °C,1H NMR (400 MHz, CDCl3) δ 9.37 (s, 1H), 8.68 (s,
1H), 8.03 (d, J = 9.9 Hz, 1H), 7.69 (s, 1H), 7.49 (dd, J = 9.5 and 3.0 Hz, 1H), 7.21 – 7.19 (m, 5H), 7.13
(d, J = 3.0 Hz, 1H), 3.93 (s, 3H), 3.28 – 3.25(m, 2H), 315 – 3.11(m, 2H); 13C NMR (100 MHz, CDCl3)
δ 157.3, 156.7, 153.8, 148.9, 148.4, 141.4, 134.7, 132.9, 130.6, 129.7, 129.6, 127.9, 127.8, 125.9, 120.7,
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 34
1
2
3
4
118.7, 103.7, 55.7, 33.9, 35.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18N2O 315.1497; found
315.1489.
5
6
7
8
General Procedure for the Synthesis of 4g-D1
9
The 3-(4-Ethylphenyl)-8-methylbenzo[b][1,6]naphthyridine(4g-D1) was prepared from azido-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
pyrano[4,3-b]quinoline 3l (0.50 mmol) in 2ml of deuterated methanol MeOD in reaction vial. Then 1.2
equiv of PPh3 was added to the reaction mixture and stirred for 0.5 h. The solid compound was
precipitate and settles down. After completion of the reaction, the precipitate was filtered under vacuum
and washed with hexane. Then, the final compound was crystallizes from chloroform.
3-(4-Ethylphenyl)-8-methylbenzo[b][1,6]naphthyridine (4g-D1). The product was obtained as yellow
crystals, (112.12 mg, 75% yield), mp 192–194 °C,1H NMR (400 MHz, CDCl3) δ 9.56–9.55 (m, 1H),
8.83 (s, 1H), 8.17–8.12 (m, 3H), 7.80 (s, 1H), 7.75–7.72 (m, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.26 (s, 1H),
2.74 (q , J = 7.6 Hz, 2H), 2.60 (s, 3H), 1.30 (dt , J = 7.6 and 2.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
154.5, 151.2, 151.0, 145.5, 136.6, 136.34, 136.26, 135.6, 129.0, 128.5, 127.4, 127.14, 127.08, 127.0,
119.6, 28.7, 21.8, 15.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17DN2 300.1611; found
300.1611.
General Procedure for the Synthesis of Naphthyridines from azido-iodo-pyranopyridines (6a-b).
The 3-substituted naphthyridines were prepared from azido-pyranopyridine 3 (0.50 mmol) in 2ml of
methanol in reaction vial. Then 1.2 equiv of PPh3 was added to the reaction mixture and stirred for 0.5
h. The solid compound was precipitate and settles down. The completion of reaction was monitored by
TLC and after completion the precipitate was filtered under vacuum and washed with hexane. Then, the
final compound were crystallizes from chloroform.
3-Phenyl-2,6-naphthyridine (6a). The product was obtained as light yellow crystals, (82.40 mg, 80%
yield), mp 195–197 °C,1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 8.69 (s, 1H), 8.03 (d, J = 9.1Hz,
1H), 7.69 (s, 1H), 7.49(dd, J = 9.5 and 2.2 Hz, 1H), 7.20 – 7.19 (m, 3H), 7.14 – 7.13 (m, 1H), 7.12 –
28
ACS Paragon Plus Environment

Page 29 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
13
7.10 (m, 1H); C NMR (100 MHz, CDCl3) δ 157.3, 153.8, 144.5, 141.5, 134.6, 130.8, 128.5, 128.4,
127.83, 127.78, 126.0, 122.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H10N2 207.0922; found
207.0933.
8
9
7-(4-(tert-Butyl)phenyl)-1,6-naphthyridine (6b). The product was obtained as yellow crystals (102.18
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
mg, 78%), mp 165–170 °C; H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 9.05–9.04 (m, 1H), 8.31 (s,
1H), 8.24 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.45–7.42 (m, 1H),
1.36 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 155.0, 154.8, 152.5, 152.3, 151.2, 135.8, 135.4, 126.8,
125.8, 122.4, 121.8, 117.1, 34.6, 31.2; HRMS (EI-TOF) m/z: [M]+ Calcd for C18H18N2 262.1470; found
262.1470.
General Procedure for the Synthesis of 1H-1, 2, 3-triazolyl Aldehydes 7.
1H-1,2,3-triazolyl aldehydes 7 was prepared by using 0.5 mmol of 1l and 1.0 mmol of NaN3in 2ml of
DMSO in an oven dried vial and stir the reaction at 120 °C for 24 h. Progression of the reaction was
monitored by TLC, while noticing complete consumption of substrate, reaction was cool to room
temperature and after completion reaction mixture was diluted with H2O and extracted with ethyl
acetate (15ml x 3) and dried over NaSO4. The compound was purified by column chromatography in
10% ethyl acetate/ hexane.
2-(5-(4-ethylphenyl)-1H-1,2,3-triazol-4-yl)-6-methylquinoline-3-carbaldehyde (7). The product was
1
crystallised in DCM/ hexane and obtained as yellow solid, (126.54 mg, 74% yield), H NMR (400
MHz, CDCl3) δ 9.97 (s, 1H), 8.70 (s, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.74 (s, 1H), 7.68 (d, J = 9.1 Hz,
1H), 7.44 (d, J = 8.3 Hz, 2H), 7.07 (d, J = 7.6 Hz, 2H), 2.61–2.55 (m, 5H), 1.17 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 150.1, 148.1, 145.2, 138.5, 137.5, 135.3, 129.0, 128.22, 128.16, 128.07,
128.0, 127.2, 127.0, 126.1, 28.6, 21.6, 15.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18N4O
343.1559; found 343.1529.
29
ACS Paragon Plus Environment