A strategy to access fused triazoloquinoline and related nucleoside analogues

Article abstract of DOI:10.1016/j.tet.2013.07.088

Fused triazoloquinolines have been prepared starting from (E)-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd-C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N¹-glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.

Full text of DOI:10.1016/j.tet.2013.07.088

Tetrahedron 69 (2013) 8547e8558
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A strategy to access fused triazoloquinoline and related nucleoside
analogues
,
c
Kapil Upadhyaya b, Arya Ajay b, Rohit Mahar c, Renu Pandeyc, Brijesh Kumar a
,
,
,b,
*
Sanjeev K. Shukla a c, Rama Pati Tripathi a
a Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow 226001, India
b Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226001, India
c Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow 226001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Fused triazoloquinolines have been prepared starting from (E)-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-
ones and sugar or benzyl azides in a sequential [3þ2] cycloaddition reaction, followed by one pot
PdeC assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N1-glycosyl
substituents as unnatural nucleosides have inherent potential to generate a library of compounds for
bioevaluations.
Received 1 January 2013
Received in revised form 23 July 2013
Accepted 30 July 2013
Available online 3 August 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cycloaddition
Reductive cyclization
Triazoloquinolines
Unnatural nucleoside
1. Introduction
At the intersection of heterocyclic and carbohydrate chemistry,
synthesis of carbohydrate coupled heterocycles as unnatural nu-
Benzofused aza-heterocycles are a class of compounds endowed
with numerous pharmacological properties and considered as
‘privileged structures’ in medicinal chemistry.1 Among these het-
cleoside analogues is an interesting concept in medicinal and bio-
organic chemistry. Modifications in the N-heterocycle or sugar
moieties in nucleosides have led to the evolution of unnatural
nucleosides or related analogues, which circumvent the problem of
enzymatic degradations of nucleosides.12 Nucleoside analogues
with modified bases have gained importance in organic synthesis13
due to interesting biological activities14 and they are known to
modulate the properties of DNA to expand the genetic code and
creation of a semisynthetic organism.15 Further such nucleosides,
have found applications in DNA probe technology with fluorescent
properties,16 study of DNA damages17 and as antisense approach
and efficiently act as antiviral agents against VZV and HIV.18
There are several reports to access these triazoloquinolines,
however the methods for directly fused triazoloquinolines are
erocycles, quinoline derivatives with planar
p-electron deficient
ring systems are ubiquitous in nature2 and encountered in several
compounds having great pharmaceutical significance.3 The 1,2,3-
triazole unit, a peptide bond surrogate4 has wide application in
medicinal chemistry5 as well as in fine chemical industry.6 Func-
tionalized 1,2,3-triazoles constitute one of the common fragments
in biologically active compounds and this has resulted in a wealth
of synthetic methodologies for their preparation and incorporation
in more complex structures. Moreover, functionalized (benzo/het-
ero-fused) quinoline analogues are of great interest in synthetic
and in medicinal chemistry.7 In this context 1,2,3-triazoles fused
with quinolines (triazoloquinolines), are particularly interesting
due to their wide range of biological properties, such as antiviral,8
antimicrobial,9 RNA-dependent RNA polymerase inhibitor10 and
anticonvoluscent11 activity.
rare.19 Functional-group tolerance during
a chemical trans-
formation has high significance in organic synthesis and more
particularly in carbohydrate chemistry and the reactions that fol-
low these criterions allow the design of simpler synthetic routes
exempted by the protecting-group operations. In this perspective,
reductive cyclization reactions are key to many organic trans-
formations leading to several important bioactive natural products,
and clinically useful molecules, such as indoles,20 2(1H)-inda-
zoles,21 quinolines,22 4(1H)-quinolones,23 quinazolines,24 benz-
imidazoles,25 benzotriazoles26 and several others.27
* Corresponding author. Tel.: þ91 0522 2612412 418x4462, þ91 0522 2612412
418x4311; fax: þ91 (522) 2623405, þ91 (522) 2623938, þ91 (522) 2629504; e-mail
address: rpt.cdri@gmail.com (R.P. Tripathi).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.088

8548
K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
Recently we have been involved in azido sugar chemistry to
operative catalysis. The anomeric glycosyl azides are more reactive
as compared to the primary azides and therefore less selective and
provide unidentified side products (TLC). p-TSA may form the ion
pair with the reactive anomeric sugar azide, resulting in its less
reactivity and enhanced selectivity to offer better yield of the de-
sired product.
Similarly, galactopyranosyl azide (2e) on reaction with prope-
none 1j resulted in the desired N1-galactosyl triazolyl methanone
(3u) in 50% yield (entry 8, Table 1). Structures of these triazolyl
methanones were established on the basis of their analytical data.
The stereochemical integrity of compound 3t and 3u was main-
tained during the transformation and none of the isomerization
was observed during the course of the reaction (SD).
access new chemotherapeutic agents for different applications.
Initially heterocyclic molecules coupled with sugar moiety, were
prepared by azideealkenone cycloaddition chemistry.28 Herein we
report a simple and mild protocol for facile transformation of (E)-3-
(2-nitrophenyl)-1-aryl-prop-2-en-1-ones into tricyclic heterocyclic
fused triazoloquinolines, involving [3þ2] cycloaddition of benzyl/
sugar azides followed by one pot sequential PdeC mediated re-
ductive cyclization and aromatization. To the best of our knowledge
this is the first report for the synthesis of triazoloquinoline using
reductive cyclization in the designed triazolyl methanones.
2. Result and discussion
With the above ortho-nitrophenyl substituted triazolyl meth-
anones (3aeu) in our hands, we were ready to perform the key
reductive cyclization for the concomitant construction of tri-
azoloquinoline (4aeg) and unnatural nucleoside analogues (4heu)
respectively, in good yields. Although the repertoire of reductive
cyclization reactions is colossal, however the methodologies that
could be advantageous in terms of selectivity, availability, afford-
ability of starting materials, operational simplicity, functional-
group tolerance and environmental sustainability is a matter of
great interest. Therefore, to maintain the efficiency of the protocol
the reductive cyclization reaction was separately optimized on two
different substrates; (i) ortho-nitrophenyl triazolyl methanone de-
rived from benzyl azide, and (ii) ortho-nitrophenyl triazolyl meth-
Our synthetic strategy for tricyclic triazoloquinolines was in-
spired by the unique versatility of ortho-nitroaryl substituted pro-
penones (chalcones), which serve as substrates during dipolar
cycloaddition with diverse azides. Reductive cyclization of the
resulting ortho-nitrophenyl substituted triazolyl methanones has
yielded the fused triazoloquinolines. These nucleoside analogues
have stereochemical diversity in the monosaccharide used and the
stereochemistry of these monosaccharides is conserved through-
out the synthetic maneuver.
The strategy begins with the synthesis of readily accessible or-
tho-nitrophenyl substituted propenones (1aej).29 The starting
benzyl azide (2a) and sugar azides, 5-azido-5-deoxy-1,2-O-iso-
anone derived from 5-azido-5-deoxy-1,2-O-isoproylidene-a-D-
xylofuranose, and results are summarized in Table 2.
proylidene-
isopropylidene-
-glucopyranosyl azide (2d) and 2,3,4,6-tetra-O-acetyl-
actopyranosyl azide (2e) were prepared from the benzyl bromide
and respective monosaccharides, -xylose, -glucose and -galac-
a
-D
-xylofuranose (2b), 6-azido-6-deoxy-1,2:3,4-di-O-
-galactopyranose (2c), 2,3,4,6-tetra-O-acetyl-
-gal-
a-
D
b-
The reaction pattern with the N1-benzyl- and N1-xylofuranosyl
triazolyl methanones (3g and 3j) for reductive cyclization is al-
most similar. With Fe powder (3 equiv)/NH4Cl as catalytic system,
a mixture of cyclized products (4g and 4j) and reduced uncyclized
amine products (4g0 and 4j0) were formed (entries 3 and 8, Table
2). PdeC/HCOONH4 also provides the same results as Fe powder
(3 equiv)/NH4Cl catalytic system (entries 4 and 9, Table 2). The
uncyclized amine product could not be cyclized under above re-
action condition even for a prolonged reaction time. Furthermore,
increase in catalyst loading also does not affect the course of
reaction. SnCl2$2H2O (10 equiv) as catalyst gave exclusively only
the uncyclized reduced products (entries 1 and 6, Table 2) in
quantitative yields. Reaction under ultrasonic vibrations also did
not affect the cyclization and only uncyclized amines were ob-
tained (entries 1 and 6, Table 2). Formation of uncyclized product
in the above reductions may be explained in terms protonation of
the substrates (intermediate amine) with the acids generated
during reaction and further cyclization would be difficult to
achieve with the protonated amine substrate. However, applying
H2 pressure in presence of PdeC, no such acid is generated and
only the cyclized product is obtained (entry 5, Table 2). Thus
among all the catalytic systems screened, PdeC/H2 under pres-
sure in MeOH was found to be the best one with excellent yield of
the cyclized product.
D
b-D
D
D
D
tose by the procedure already reported in the literature.30 The
primary azides (2aec) on 1e3 dipolar cycloaddition reaction31 with
different propenones (1aei) at 100 ꢀC in presence of 20 mol % of
tetrabutylammonium hydrogensulphate (TBAHS) as catalyst in di-
methyl formamide (DMF) separately led to the formation of dif-
ferently substituted triazolyl methanones (3aes) in good yields
(65e97%) (Scheme 1).
Scheme 1. Synthesis of ortho-nitrophenyl substituted triazolyl methanone (3aes).
However, the above cycloaddition reaction with anomeric gly-
cosyl azides 2d and 2e under same reaction condition was very
sluggish and resulted in only 20e25% yield of the desired products
3t and 3u, respectively. Therefore, to improve the yield of the
products with these anomeric azides, the procedure was rein-
vestigated with different catalytic systems and results are sum-
marized in Table 1.
Among all the reaction conditions optimized, 20 mol % of tet-
rabutylammonium hydrogensulphate (TBAHS) as catalyst with
10 mol % p-toluene sulphonic acid (p-TSA), proved to be the most
efficient condition for cycloaddition reaction between propenone
1i and glucosyl azide 2d (entry 6, Table 1) with 55% yield of desired
product 3t. The precise role of p-TSA in this reaction is not clearly
established however, it is presumed to work on the concept of co-
With the above optimized reaction condition for reductive cy-
clization, first we explored our methodology for differently
substituted aromatic heterocyclic systems (3aeg), where the
methodology hold promise and desired products (4aeg) were ob-
tained in very good yields (87e98%, Table 3). The electronic factor
does not play any significant role in reductive cyclization. Further,
to see the steric effect, a comparison of the reductive cyclization
with 2-, 3-, 4-, Me/OMe substituted substrates in acetophenone
ring (3beg) was also carried out, without any significant change in
the yield of the products with little alteration in time was noted
(Table 3). The scope of reaction is well illustrated with variously
substituted triazolyl methanones (Table 3).
Next we explored the possibility of preparing unnatural homo-
nucleoside analogues. For this purpose, we set out a model reaction

K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
8549
Table 1
Optimization of cycloaddition reaction for glycosyl (anomeric azide) and synthesized molecules (3t, u)
Entry
1
Substrate
Product
Catalytic systema (mol %)
TBAHS (20)
Time (h)
24
Yield (%)
25b
2
3
4
5
6
7
1iþ2d
1iþ2d
1iþ2d
1iþ2d
1iþ2d
1iþ2d
3t
3t
3t
3t
3t
3t
TBAHS (20)þAlCl3 (10)
TBAHS (20)þSnCl4 (10)
TBAHS (20)þCuI (10)
TBAHS (20)þTBAB (10)
TBAHS (20)þp-TSA (10)
p-TSA (20)
16
16
18
16
18
24
15c
15c
35b
25b
55
20b
8
TBAHS (20)þp-TSA (10)
18
50
a
All the reactions were performed in anhydrous DMF as solvent.
Reaction picture was consistent and incomplete even after several hours.
Reaction was very sluggish and incomplete after several hours.
b
c
Table 2
Optimization of reductive cyclization of different substrates under different catalytic conditions
Entry
Substrate
Catalyst
Solvent
Temp (ꢀC)
Time (h)
Yield (%) 4g
or 4j/4g0 or 4j0
1
2
3
4
5
6
7
8
3g
3g
3g
3g
3g
3j
3j
3j
3j
3j
SnCl2$2H2O (10 equiv)
SnCl2$2H2O (10 equiv)a
Fe powder (3 equiv)/NH4Cl
PdeC/HCOONH4
PdeC/H2
SnCl2$2H2O (10 equiv)
aSnCl2$2H2O (10 equiv)
Fe powder (3 equiv)/NH4Cl
PdeC/HCOONH4
PdeC/H2
EtOH
EtOH
EtOH/H2O
MeOH
MeOH
EtOH
80
30
80
30
30
80
30
80
25
25
25
25
2
2
14
19
8
2
2
16
12
8
e/90
e/93
65/22b
50/20b
92/e
e/67
e/71
60/25
63/5b
83/e
72/e
73/e
EtOH
EtOH/H2O
MeOH
MeOH
EtOH
9
10
11
12
3j
3j
PdeC/H2
PdeC/H2
8
9
EtOAc
a
Reaction was carried out under sonication.
Reaction was incomplete even for a prolonged reaction time.
b
to validate our hypothesis and gratifyingly the starting carbohy-
drate derived substrate (3j) was efficiently transformed in to the
desired triazoloquinoline (4j) in promising yield without any side
reaction or incomplete conversion (entry10, Table 2). With this
encouraging result, we have extended the scope of the methodol-
ogy with different carbohydrate derived triazoles (3hes) to obtain
the respective N1-glycosyl triazoloquinolines (4he4s) as homo-
nucleoside analogues in promising yields (80e96%).
Further extension of the scope of the methodology for unnatural
nucleoside analogues was also investigated with the anomeric
carbon linked ortho-nitrophenyl substituted triazolyl methanone
(3t). The latter was successfully transformed into respective tri-
azoloquinoline glycoside (4t), under the above optimized reaction
condition. The desired product 4t was formed in moderate yield
(50%) along with the deacetylated nucleoside analogue (4t0, yield
10%) during reductive cyclization with PdeC/H2 (Scheme 2).

8550
K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
Table 3
Synthesized triazoloquinolines (4aes)
Scheme 2. Synthesis of unnatural nucleoside (4t).
Entry
Compd no.
R
R1
Time (h)
Yielda (%)
orientation (all equatorial). It was further supported by NOE cor-
relations of H-10 to H-30, H-20 to H-40 and H-10 to H-50. Similarly in
4t0 the coupling constant for anomeric proton H-10 (d, J¼9.66 Hz)
suggests trans relationship (equatorial) (SD).
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
H
Bn
Bn
Bn
Bn
Bn
Bn
Bn
10
13
12
10
14
13
11
94
87
91
98
87
90
97
2-Me
3-Me
4-Me
2-OMe
3-OMe
4-OMe
In light of above observation we were keen to synthesize the
deacetylated nucleoside analogue 4u in one pot. For this purpose,
we reinvestigated our protocol with substrate 3u and reaction was
run for extended period of time to form the directly deacetylated
triazoloquinoline (4u) in one pot (Scheme 3). To our pleasant sur-
prise the complete deprotection was observed under reaction
condition with improved yield of the desired product (4u, 61%)
((debromination was also observed when reaction was carried out
for very long time or >10 h) (see ESMS of debrominated product in
Supplementary data)).
4g
O
O
O
O
O
8
4h
4i
3-Me
12
11
12
14
11
11
89
90
92
86
91
85
O
HO
HO
HO
HO
O
9
4-Me
O
O
10
11
12
13
4j
4-OMe
2,4-Dichloro
4-Fluoro
H
O
O
4k
4l
O
O
O
O
O
HO
O
Scheme 3. Synthesis of unnatural nucleoside (4u).
O
O
4m
O
The structure of unnatural nucleosides was established on the
basis of their analytical data, further to confirm the structure;
several 2D NMR experiments were also carried out, which estab-
lished the complete correlation of synthesized molecules (SD).
O
O
O
14
15
16
17
18
4n
4o
4p
4q
4r
2-Me
14
13
11
13
12
11
80
81
96
84
87
93
O
O
O
O
O
O
O
3. Conclusion
O
O
O
3-Me
O
In conclusion, we have developed a mild, convenient and
compatible strategy for the modular construction of functionalized
tricyclic triazoloquinoline and related unnatural nucleoside ana-
logues. First time we demonstrate the application of the reductive
cyclization as valuable tool for such one-pot multistep trans-
formation. From the synthetic point of view, this conversion rep-
resents a simple approach, a task that otherwise requires several
synthetic steps. The scope and functional-group tolerance of the
reaction is also well illustrated with a wide range of substrate,
however, more optimization with the anomeric sugar azide is still
needed, which is currently underway in our group.
O
O
O
4-Me
O
O
O
O
2-OMe
3-OMe
4-OMe
O
O
O
O
O
4. Experimental section
4.1. General chemistry
O
O
O
19
4s
O
Commercially available reagent grade chemicals were used as
received. Reactions were monitored by TLC on E. Merck Kieselgel 60
F254, with detection by UV light, spraying a 5% H2SO4 ethanolic so-
lution and applying heat. Column chromatography was performed
on silica gel (60e120 and 100e200 mesh E. Merck). IR spectra were
recorded as thin films or in KBr solution with a Perkin Elmer Spec-
trum RX-1 (4000e450 cmꢁ1) spectrophotometer. 1H and 13C NMR
spectra were recorded on Bruker 200, 300 and 400 MHz spec-
trometer in CDCl3 or DMSO-d6. Chemical shift values are reported in
a
Isolated yield.
The configuration of the glucose sugar moiety in 4t was estab-
lished on the basis of NMR spectrum using the chemical shift,
splitting pattern and coupling constants. Coupling constants of H-10
(d, J¼9.40 Hz), H-20 (t, J¼9.60 Hz), H-30 (t, J¼9.60 Hz) and H-40 (t,
J¼9.86 Hz) indicated that H-10, H-20, H-30, H-40 were in the trans

K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
8551
parts per million relative to TMS (tetramethylsilane) as internal
reference, unless otherwise stated; s (singlet), d (doublet), t (triplet),
m (multiplet) and br (broad); J in hertz. HRMS were performed using
Quattro II (Micromass). Optical rotation was recorded on Autopol III,
S. No. 301, manufactured by Rudolph Research Analytical, USA.
3-(2-nitrophenyl)prop-2-en-1-one 1d (0.83 g, 3.12 mmol), benzyl
azide 2a (0.50 g, 3.76 mmol) and TBAHS (0.25 g, 0.75 mmol), in DMF
(5 mL) at 100 ꢀC for 12 h. Purification by column chromatography
using 60e120 mesh silica gel (10% ethyl acetate/hexane), yielded
the titled compound 3d (1.45 g, 97%) as yellow solid; mp
136e138 ꢀC, Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2921,
4.2. General procedure for the preparation of triazolyl
methanone (3aes)
1645, 1530, 1351 cmꢁ1
;
dH (300 MHz, CDCl3): 8.31 (2H, d, J¼8.01 Hz,
ArH), 8.26 (1H, d, J¼7.89 Hz, ArH), 7.69e7.56 (2H, m, ArH),
7.29e7.23 (5H, m, ArH), 7.07e7.01 (3H, m, ArH), 5.62 (1H, d,
J¼15.00 Hz, CH2), 5.32 (1H, d, J¼15.03 Hz, CH2), 2.44 (3H, s, CH3); dC
(75 MHz, CDCl3): 184.9, 148.2, 144.3, 143.8, 138.3, 133.9, 133.7, 133.0,
132.0, 130.9, 128.9, 128.8, 128.6, 127.9, 125.0, 122.9, 52.8, 21.7; HRMS
(ESI): MHþ, found 399.1443. C23H19N4O3 requires 399.1452.
4.2.1. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](phenyl)
methanone (3a). (E)-1-(2-Phenyl)-3-(2-nitrophenyl)prop-2-en-1-
one 1a (0.79 g, 3.12 mmol) and benzyl azide 2a (0.50 g,
3.76 mmol) were reacted in presence of 20 mol % TBAHS (0.25 g,
0.75 mmol) as catalyst in DMF (5 mL) at 100 ꢀC for 12 h. After
completion of the reaction (TLC), the mixture was diluted with
water and extracted with ethyl acetate. The organic layer was
washed with water to remove DMF and then dried over sodium
sulfate (Na2SO4) and evaporated under reduced pressure to get the
crude mass, which upon purification by column chromatography
using 60e120 mesh silica gel (10% ethyl acetate/hexane), yielded the
titled compound 3a (1.37 g, 95%) as yellow solid; mp 112e114 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2921, 1646, 1530,
4.2.5. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](2-methox-
yphenyl)methanone (3e). It was obtained by the reaction of (E)-1-
(2-methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1e (0.88 g,
3.12 mmol), benzyl azide 2a (0.50 g, 3.76 mmol) and TBAHS (0.25 g,
0.75 mmol), in DMF (5 mL) at 100 ꢀC for 14 h. Purification by col-
umn chromatography using 60e120 mesh silica gel (10% ethyl ac-
etate/hexane), yielded the titled compound 3e (1.37 g, 88%) as
white solid; mp 96e98 ꢀC; Rf¼0.50 (ethyl acetate/hexane,1:3); nmax
1349 cmꢁ1
;
dH (300 MHz, CDCl3): 8.41 (2H, d, J¼7.32 Hz, ArH), 8.28
(KBr) 2925, 1651, 1529, 1345, 1214 cmꢁ1
; dH (300 MHz, CDCl3): 8.17
(1H, d, J¼8.04 Hz, ArH), 7.72e7.66 (1H, m, ArH), 7.65e7.58 (2H, m,
ArH), 7.53e7.48 (2H, m, ArH), 7.33e7.26 (3H, m, ArH), 7.10e7.03 (3H,
m, ArH), 5.64 (1H, d, J¼15.03 Hz, CH2), 5.36 (1H, d, J¼15.00 Hz, CH2);
dC (75 MHz, CDCl3): 185.2, 148.3, 144.2, 138.5, 136.5, 133.7, 133.1,
132.0,130.9,130.8,128.8,128.7,128.1,128.0,125.0,123.0, 52.8; HRMS
(ESI): MHþ, found 385.1288. C22H17N4O3 requires 385.1295.
(1H, dd, J1¼8.07 Hz, J2¼1.20 Hz, ArH), 7.62e7.50 (2H, m, ArH),
7.49e7.46 (1H, dd, J1¼7.56 Hz, J2¼1.59 Hz, ArH), 7.42e7.36 (1H, m,
ArH), 7.22e7.15 (3H, m, ArH), 7.05 (1H, dd, J1¼7.35 Hz, J2¼1.41 Hz,
ArH), 6.98e6.93 (3H, m, ArH), 6.90 (1H, d, J¼8.34 Hz, ArH), 5.59 (1H,
d, J¼15.06 Hz, CH2), 5.24 (1H, d, J¼15.09 Hz, CH2), 3.73 (3H, s,
OCH3); dC (75 MHz, CDCl3): 187.8, 158.2, 148.0, 145.1, 136.5, 133.9,
133.0, 132.6, 132.5, 130.8, 130.3, 128.7, 128.5, 128.2, 127.8, 125.0,
122.5, 120.2, 111.6, 55.6, 52.8; HRMS (ESI): MNaþ, found 437.1213.
C23H18N4O4Na requires 437.1220.
4.2.2. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](o-tolyl)
methanone (3b). It was obtained by the reaction of (E)-1-(o-tolyl)-
3-(2-nitrophenyl)prop-2-en-1-one 1b (0.83 g, 3.12 mmol), benzyl
azide 2a (0.50 g, 3.76 mmol) and TBAHS (0.25 g, 0.75 mmol), in DMF
(5 mL) at 100 ꢀC for 15 h. Purification by column chromatography
using 60e120 mesh silica gel (10% ethyl acetate/hexane), yielded
the titled compound 3b (1.34 g, 90%) as light yellow solid; mp
122e124 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2923,
4.2.6. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](3-
methoxyphenyl)methanone (3f). It was obtained by the reaction of
(E)-1-(3-methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one
1f
(0.88 g, 3.12 mmol), benzyl azide 2a (0.50 g, 3.76 mmol) and TBAHS
(0.25 g, 0.75 mmol), in DMF (5 mL) at 100 ꢀC for 13 h. Purification by
column chromatography using 60e120 mesh silica gel (10% ethyl
acetate/hexane), yielded the titled compound 3f (1.15 g, 90%) as
yellow solid; mp 88e90 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4);
1649, 1528, 1347 cmꢁ1
;
dH (300 MHz, CDCl3): 8.27 (1H, d, J¼7.77 Hz,
ArH), 7.79 (1H, d, J¼7.62 Hz, ArH), 7.72e7.62 (2H, m, ArH), 7.43e7.38
(1H, m, ArH), 7.32e7.18 (5H, m, ArH), 7.14 (1H, d, J¼7.29 Hz, ArH),
7.03 (2H, d, J¼7.14 Hz, ArH), 5.62 (1H, d, J¼15.03 Hz, CH2), 5.36e5.31
(1H, d, J¼15.03 Hz, CH2), 2.38 (3H, s, CH3); dC (75 MHz, CDCl3):
189.6, 148.0, 144.8, 137.9, 137.7, 137.0, 133.6, 133.2, 132.1, 131.1, 131.0,
130.5, 128.8, 128.7, 127.9, 125.2, 125.1, 122.6, 52.9, 20.3; HRMS (ESI):
MHþ, found 399.1445. C23H19N4O3 requires 399.1452.
nmax (KBr) 2929, 1650, 1531, 1351, 1218 cmꢁ1
; dH (300 MHz, CDCl3):
8.30 (1H, d, J¼7.26, ArH), 8.15 (1H, d, J¼6.99, ArH), 7.89 (1H, s, ArH),
7.73e7.68 (1H, m, ArH), 7.65e7.60 (1H, m, ArH), 7.42 (1H, t, J¼6.87,
ArH), 7.31e7.29 (3H, m, ArH), 7.17e7.14 (1H, m, ArH), 7.07 (3H, br,
ArH), 5.67 (1H, d, J¼14.91, CH2), 5.34 (1H, d, J¼15.06, CH2), 3.90 (3H,
s, OCH3); dC (75 MHz, CDCl3): 184.9, 159.4, 148.3, 144.3, 138.5, 137.6,
133.7, 132.9, 132.0, 130.8, 129.1, 128.8, 128.6, 128.0, 125.0, 123.9,
123.0, 120.4, 114.1, 55.2, 52.8; HRMS (ESI): MNaþ, found 437.1211.
C23H18N4O4Na requires 437.1220.
4.2.3. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](m-tolyl)
methanone (3c). It was obtained by the reaction of (E)-1-(m-tolyl)-
3-(2-nitrophenyl)prop-2-en-1-one 1c (0.83 g, 3.12 mmol), benzyl
azide 2a (0.50 g, 3.76 mmol) and TBAHS (0.25 g, 0.75 mmol), in DMF
(5 mL) at 100 ꢀC for 14 h. Purification by column chromatography
using 60e120 mesh silica gel (10% ethyl acetate/hexane), yielded
the titled compound 3c (1.32 g, 88%) as yellow solid; mp
152e155 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2928,
4.2.7. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](4-methox-
yphenyl)methanone (3g). It was obtained by the reaction of (E)-1-
(4-Methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1g (0.88 g,
3.12 mmol), benzyl azide 2a (0.50 g, 3.76 mmol) and TBAHS (0.25 g,
0.75 mmol), in DMF (5 mL) at 100 ꢀC for 12 h. Purification by col-
umn chromatography using 60e120 mesh silica gel (10% ethyl ac-
etate/hexane), yielded the titled compound 3g (1.42 g, 91%) as
yellow solid; mp 94e96 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4);
1650, 1531, 1345 cmꢁ1
;
dH (300 MHz, CDCl3): 8.22 (1H, d, J¼8.1 Hz,
ArH), 8.17 (1H, d, J¼6.21 Hz, ArH), 8.11 (1H, s, ArH), 7.66e7.53 (2H,
m, ArH), 7.35e7.32 (2H, m, ArH), 7.24e7.20 (3H, m, ArH), 7.02e6.98
(3H, m, ArH), 5.59 (1H, d, J¼15.00 Hz, CH2), 5.28 (1H, d, J¼15.03 Hz,
CH2), 2.41 (3H, s, CH3); dC (75 MHz, CDCl3): 185.5, 148.3, 144.3,
138.4,137.7,136.5,133.9,133.7,133.0,132.0,131.1,130.8,128.8,128.6,
128.1, 128.0, 125.0, 123.0, 52.8, 21.4; HRMS (ESI): MHþ, found
399.1447. C23H19N4O3 requires 399.1452.
nmax (KBr) 2928, 1644, 1529, 1349, 1262 cmꢁ1
; dH (300 MHz, CDCl3):
8.26 (1H, d, J¼7.92 Hz, ArH), 8.11 (1H, d, J¼7.56 Hz, ArH), 7.84 (1H, s,
ArH), 7.69e7.57 (2H, m, ArH), 7.38 (1H, t, J¼7.92 Hz, ArH), 7.28e7.23
(3H, m, ArH), 7.13e7.11 (1H, m, ArH), 7.05e7.01 (3H, m, ArH), 5.62
(1H, d, J¼14.97 Hz, CH2), 5.31 (1H, d, J¼15.00 Hz, CH2), 3.85 (3H, s,
OCH3); dC (75 MHz, CDCl3): 184.9, 159.5, 148.3, 144.3, 137.7, 133.7,
133.0, 132.1, 130.9, 129.1, 128.8, 128.6, 128.0, 125.0, 123.8, 120.3,
4.2.4. [1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](p-tolyl)
methanone (3d). It was obtained by the reaction of (E)-1-(p-tolyl)-

8552
K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
114.2, 55.2, 52.8; HRMS (ESI): MHþ, found 415.1394 C23H19N4O4
requires 415.1401.
methanone (3k). It was obtained by the reaction of (E)-1-(2,4-
dichlorophenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1h (1.49 g,
4.60 mmol), 5-azido-5-deoxy-1,2-O-isopropylidene-a-D-xylofur-
4.2.8. [1-(5-Deoxy-1,2-O-isopropylidene-
a
-
D
-xylofuranos-5-yl)-5-(2-
anose (1.00 g, 4.60 mmol) 2b and TBAHS (0.31 g, 0.92 mmol), in
DMF (10 mL) at 100 ꢀC for 17 h. The crude product was purified by
column chromatography using 60e120 mesh silica gel (20% ethyl
acetate/hexane), yielded the titled compound 3k (1.61 g, 65%) as
yellow solid; mp 82e84 ꢀC, Rf¼0.50 (ethyl acetate/hexane, 1:2);
nitrophenyl)-1H-1,2,3-triazol-4-yl](m-tolyl)methanone (3h). It was
obtained by the reaction of (E)-1-(m-tolyl)-3-(2-nitrophenyl)prop-
2-en-1-one 1c (1.49 g, 4.60 mmol), 5-azido-5-deoxy-1,2-O-iso-
propylidene-a-D-xylofuranose 2b (1.00 g, 4.60 mmol) and TBAHS
(0.31 g, 0.92 mmol), in DMF (10 mL) at 100 ꢀC for 17 h. The crude
product was purified by column chromatography using
60e120 mesh silica gel (20% ethyl acetate/hexane), yielded the titled
compound 3h (1.47 g, 66%) as yellow solid; mp 76e78 ꢀC; Rf¼0.50
½
a 3D0
1074 cmꢁ1
ꢂ
ꢁ37 (c 0.1, CHCl3); nmax (KBr) 3436, 2929, 1641, 1531, 1348,
;
dH (300 MHz, CDCl3): 8.35e8.29 (1H, m, ArH), 7.83e7.76
(2H, m, ArH), 7.54e7.44 (3H, m, ArH), 7.34e7.25 (1H, m, ArH),
5.82e5.78 (1H, m, H-10), 4.65e4.58 (1H, m, CH2), 4.54e4.46 (1H, m,
CH2), 4.27e4.17 (3H, m, H-20, H-40 and H-30), 1.37 (3H, s, C(CH3)2),
1.26 (3H, s, C(CH3)2); dC (75 MHz, CDCl3):184.5, 148.7, 137.5, 135.6,
133.8, 133.1, 132.5, 131.7, 131.6, 131.1, 130.2, 128.2, 126.8, 125.6, 112.0,
105.0, 85.0, 78.9, 78.1, 74.4, 46.0, 26.8, 26.3; HRMS (ESI): MHþ,
found 535.0778. C23H21Cl2N4O7 requires 535.0782.
(ethyl acetate/hexane,1:2); ½a D30
ꢂ
ꢁ58 (c 0.1, CHCl3); nmax (KBr) 3432,
2929,1646,1531,1347,1071 cmꢁ1
;
dH (300 MHz, CDCl3): 8.29 (1H, br,
ArH), 8.08e8.05 (2H, m, ArH), 7.74 (2H, br, ArH), 7.47e7.27 (3H, m,
ArH), 5.86 (1H, br, H-10), 5.28 (1H, s, OH), 4.73 (1H, br, CH2),
4.55e4.52 (2H, m, CH2 and H-20), 4.37e4.26 (2H, m, H-40 and H-30),
2.39 (3H, s, CH3),1.26 (6H, s, 2ꢃ C(CH3)2); dC (75 MHz, CDCl3): 185.9,
148.6,143.5, 139.5, 138.1, 136.3, 134.2, 133.7, 132.6, 131.6, 131.5, 131.0,
128.0, 125.2, 122.2, 112.2, 105.0, 85.1, 78.2, 74.5, 46.0, 26.3, 21.3, 14.4;
HRMS (ESI): MHþ, found 481.1713. C24H25N4O7 requires 481.1718.
Note: (For numbering of the proton see the Supplementary
data).
4.2.12. [1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-5-
(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](4-fluorophenyl)methanone
(3l). It was obtained by the reaction of (E)-1-(4-fluorophenyl)-3-(2-
nitrophenyl)prop-2-en-1-one 1i (1.26 g, 4.64 mmol), 5-azido-5-
deoxy-1,2-O-isopropylidene-
a-
D-xylofuranose
2b
(1.00
g,
4.60 mmol) and TBAHS (0.31 g, 0.92 mmol), in DMF (10 mL) at
100 ꢀC for 15 h. The crude product was purified by column chro-
matography using 60e120 mesh silica gel (20% ethyl acetate/hex-
ane), yielded the titled compound 3l (1.57 g, 71%) as white solid;
4.2.9. [1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-5-(2-
nitrophenyl)-1H-1,2,3-triazol-4-yl](p-tolyl)methanone (3i). It was
obtained by the reaction of (E)-1-(p-tolyl)-3-(2-nitrophenyl)prop-
2-en-1-one 1d (1.49 g, 4.60 mmol), 5-azido-5-deoxy-1,2-O-iso-
mp 86e88 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:2); ½a 3D0
ꢂ
ꢁ68 (c 0.1,
propylidene-
a
-
D
-xylofuranose 2b (1.00 g, 4.60 mmol) and TBAHS
CHCl3); nmax (KBr) 3432, 2927, 1646, 1533, 1347, 1078 cmꢁ1
; dH
(0.31 g, 0.92 mmol), in DMF (10 mL) at 100 ꢀC for 16 h. The crude
product was purified by column chromatography using
60e120 mesh silica gel (20% ethyl acetate/hexane), yielded the ti-
tled compound 3i (1.51 g, 68%) as yellow solid; mp 78e80 ꢀC;
(300 MHz, CDCl3): 8.42e8.36 (2H, m, ArH), 7.80e7.73 (2H, m, ArH),
7.49 (1H, dd, J1¼7.17 Hz, J2¼1.92 Hz, ArH), 7.39e7.36 (1H, m, ArH),
7.17e7.11 (2H, m, ArH), 5.90 (1H, m, H-100), 4.76e4.70 (1H, m, CH2),
4.58e4.53 (1H, m, CH2), 4.36 (1H, s, H-20), 4.32e4.27 (2H, m, H-40
and H-30), 1.30 (3H, s, C(CH3)2), 1.27 (3H, s, C(CH3)2); dC (75 MHz,
Rf¼0.50 (ethyl acetate/hexane, 1:2); ½a D30
ꢂ
ꢁ66 (c 0.1, CHCl3); nmax
1
(KBr) 3435, 2926, 1642, 1530, 1350, 1074 cmꢁ1
;
dH (300 MHz,
CDCl3): 184.0, 164.6 (d, JCF¼247.00 Hz), 148.7, 143.7, 139.8, 133.9,
3
CDCl3): 8.33e8.30 (1H, m, ArH), 8.27e8.20 (2H, m, ArH), 7.78e7.71
(2H, m, ArH), 7.25e7.23 (3H, m, ArH), 5.84e5.81 (1H, m, H-10),
4.65e4.59 (1H, m, CH2), 4.54e4.50 (1H, m, CH2), 4.31e4.23 (3H, m,
H-20, H-40 and H-300), 2.42 (3H, s, CH3), 1.36 (3H, s, C(CH3)2), 1.28
(3H, s, C(CH3)2); dC (75 MHz, CDCl3): 184.5, 143.8, 139.1, 133.4, 132.3,
131.3, 131.2, 130.9, 128.9, 125.4, 125.2, 122.5, 112.0, 105.1, 85.0, 46.1,
26.8, 26.2, 21.7; HRMS (ESI): MHþ, found 481.1717. C24H25N4O7 re-
quires 481.1718.
133.5, 132.4, 131.6 (d, JCF¼7.50 Hz), 125.2, 122.1, 115.3 (d,
2JCF¼22.50 Hz), 112.2, 105.0, 85.2, 78.9, 74.5, 46.5, 26.8, 26.2; HRMS
(ESI): MHþ, found 485.1461. C23H22FN4O7 requires 485.1467.
4.2.13. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](phenyl)meth-
anone (3m). It was obtained by the reaction of (E)-1-phenyl-3-(2-
nitrophenyl)prop-2-en-1-one 1a (0.89 g, 3.50 mmol), 6-azido-6-
deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose 2c (1.00 g,
4.2.10. [1-(5-Deoxy-1,2-O-isopropylidene-
a
-
D
-xylofuranos-5-yl)-5-
3.50 mmol) and TBAHS (0.24 g, 0.70 mmol), in DMF (10 mL) at
100 ꢀC for 13 h. The crude product was purified by column chro-
matography using 60e120 mesh silica gel (15% ethyl acetate/hex-
ane), yielded the titled compound 3m (1.39 g, 74%) as yellow solid;
(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](4-methoxyphenyl)methanone
(3j). It was obtained by the reaction of (E)-1-(4-methoxyphenyl)-3-
(2-nitrophenyl)prop-2-en-1-one 1g (1.32 g, 4.60 mmol), 5-azido-5-
deoxy-1,2-O-isopropylidene-
a
-D
-xylofuranose
2b
(1.00
g,
mp 62e64 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:7); ½a 3D0
ꢂ
þ105 (c 0.1,
4.60 mmol) and TBAHS (0.31 g, 0.92 mmol), in DMF (10 mL) at
100 ꢀC for 15 h. The crude product was purified by column chro-
matography using 60e120 mesh silica gel (20% ethyl acetate/hex-
ane), yielded the titled compound 3j (1.67 g, 72%) as yellow solid;
CHCl3); nmax (KBr) 2929, 1648, 1531, 1346, 1077 cmꢁ1
; dH (300 MHz,
CDCl3): 8.34e8.31 (3H, m, ArH), 7.75e7.69 (2H, m, ArH), 7.57e7.52
(2H, m, ArH), 7.50e7.46 (2H, m, ArH), 5.44 (1H, d, J¼4.68 Hz, H-10),
4.65e4.61 (2H, m, CH2), 4.46e4.44 (1H, m, H-30), 4.33e4.31 (1H, m,
H-20), 4.25e4.20 (2H, m, H-40 and H-500), 1.31e1.23 (9H, m, 3ꢃ
C(CH3)2), 1.16 (3H, s, C(CH3)2); dC (75 MHz, CDCl3): 186.0, 148.6,
139.9, 136.6, 133.1, 133.1, 133.0, 130.9, 130.7, 128.2, 128.2, 124.8,
122.8, 109.7, 109.4, 70.9, 70.8, 70.4, 67.0, 48.1, 26.0, 25.7, 25.0, 24.3;
HRMS (ESI): MHþ, found 537.1971. C27H29N4O8 requires 537.1980.
mp 68e70 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:2); ½a 3D0
ꢂ
ꢁ61 (c 0.1,
CHCl3); nmax (KBr) 3438, 2928, 1645, 1533, 1351, 1077 cmꢁ1
;
dH
(300 MHz, CDCl3): 8.36e8.23 (3H, m, ArH), 7.73e7.68 (2H, m, ArH),
7.45e7.34 (1H, m, ArH), 6.92e6.90 (2H, m, ArH), 5.82e5.81 (1H, m,
H-10), 4.70e4.63 (1H, m, CH2), 4.57e4.48 (2H, m, CH2 and H-20),
4.34e4.18 (2H, m, H-40 and H-30), 3.87 (3H, s, OCH3), 1.36 (3H, s,
C(CH3)2), 1.27 (3H, s, C(CH3)2); dC (75 MHz, CDCl3): 183.6, 163.9,
149.1, 143.7, 139.1, 133.4, 133.2, 132.5, 131.3, 125.3, 122.5, 113.5, 111.9,
105.0, 85.2, 79.0, 74.4, 55.2, 45.8, 26.9, 26.2; HRMS (ESI): MHþ,
found 497.1658. C24H25N4O8 requires 497.1667.
4.2.14. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](o-tolyl)meth-
anone (3n). It was obtained by the reaction of (E)-1-(o-tolyl)-3-(2-
nitrophenyl)prop-2-en-1-one 1b (0.94 g, 3.50 mmol), 6-azido-6-
deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose (1.00 g,
4.2.11. [1-(5-Deoxy-1,2-O-isopropylidene-
(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](2,4-dichlorophenyl)
a
-
D
-xylofuranos-5-yl)-5-
3.50 mmol) and TBAHS (0.24 g, 0.70 mmol), in DMF (10 mL) at
100 ꢀC for 16 h. The crude product was purified by column

K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
8553
chromatography using 60e120 mesh silica gel (15% ethyl acetate/
hexane), yielded the titled compound 3n (1.35 g, 70%) as yellow
hexane, 3:7); ½a D30
ꢂ
þ88 (c 0.1, CHCl3); nmax (KBr) 2926, 1646, 1533,
dH (300 MHz, CDCl3): 8.07 (1H, d, J¼8.49 Hz, ArH),
1343, 1076 cmꢁ1
;
solid; mp 82e84 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:7); ½a 3D0
ꢂ
7.80e7.79 (1H, m, ArH), 7.65e7.59 (2H, m, ArH), 7.50e7.49 (1H, m,
ArH), 7.38e7.35 (2H, m, ArH), 7.13e7.11 (1H, m, ArH), 5.46 (1H, d,
J¼4.89 Hz, H-10), 4.61e4.58 (2H, m, CH2), 4.29e4.18 (4H, m, H-300, H-
20, H-40 and H-50), 3.79 (3H, s, OCH3), 1.34e1.31 (12H, m, 4ꢃ
C(CH3)2); dC (75 MHz, CDCl3): 183.2, 157.4, 148.3, 141.2, 132.3, 130.9,
130.6, 130.3, 130.2, 129.2, 128.8, 127.9, 124.7, 120.4, 119.9, 111.5,
109.6, 108.6, 71.5, 71.0, 66.5, 57.1, 42.3, 26.0, 25.9, 24.9, 24.3; HRMS
(ESI): MHþ, found 567.2089. C28H31N4O9 requires 567.2086.
þ65 (c 0.1, CHCl3); nmax (KBr) 2928, 1646, 1530, 1344, 1071 cmꢁ1
; dH
(300 MHz, CDCl3): 8.30 (1H, d, J¼8.16 Hz, ArH), 7.74e7.69 (3H, m,
ArH), 7.57e7.54 (1H, m, ArH), 7.51e7.49 (1H, m, ArH), 7.26e7.19 (2H,
m, ArH), 5.41 (1H, d, J¼4.59 Hz, H-10), 4.61e4.57 (2H, m, CH2),
4.37e4.35 (1H, m, H-30), 4.30e4.27 (2H, m, H-20 and H-40), 4.19 (1H,
m, H-50), 2.34 (3H, s, CH3),1.32e1.25 (9H, m, 3ꢃ C(CH3)2),1.15 (3H, s,
C(CH3)2); dC (75 MHz, CDCl3):189.9, 148.7, 137.8, 133.2, 132.8, 130.9,
130.4, 129.7, 129.2, 128.3, 127.5, 125.1, 124.9, 122.7, 109.6, 109.3, 71.5,
70.9, 70.4, 67.0, 48.0, 26.1, 25.7, 25.0, 24.3, 20.3; HRMS (ESI): MHþ,
found 551.2130. C28H31N4O8 requires 551.2136.
4.2.18. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](3-methoxy-
phenyl)methanone (3r). It was obtained by the reaction of (E)-1-(3-
methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1e (0.99 g,
4.2.15. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](m-tolyl)meth-
anone (3o). It was obtained by the reaction of (E)-1-(m-tolyl)-3-(2-
nitrophenyl)prop-2-en-1-one 1c (0.94 g, 3.50 mmol), 6-azido-6-
3.50 mmol), 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranose 2c (1.00 g, 3.50 mmol) and TBAHS (0.24 g,
0.70 mmol), in DMF (10 mL) at 100 ꢀC for 15 h. The crude product
was purified by column chromatography using 60e120 mesh silica
gel (15% ethyl acetate/hexane), yielded the titled compound 3r
(1.46 g, 74%) as yellow solid; mp 60e62 ꢀC; R f¼0.50 (ethyl acetate/
deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose 2c (1.00 g,
3.50 mmol) and TBAHS (0.24 g, 0.70 mmol), in DMF (10 mL) at
100 ꢀC for 15 h. The crude product was purified by column chro-
matography using 60e120 mesh silica gel (15% ethyl acetate/hex-
ane), yielded the titled compound 3o (1.39 g, 72%) as yellow solid;
a 30
hexane, 3:7); ½ ꢂD þ128 (c 0.1, CHCl3); nmax (KBr) 2928, 1643, 1531,
1341, 1073 cmꢁ1
;
dH (300 MHz, CDCl3): 8.32 (1H, dd, J1¼7.56 Hz,
mp 84e86 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:7); ½a 3D0
ꢂ
þ84 (c 0.1,
J2¼1.41 Hz, ArH), 8.09 (1H, d, 7.86 Hz, ArH), 7.82e7.78 (1H, m, ArH),
7.74e7.69 (2H, m, ArH), 7.53 (1H, d, 2.22 Hz, ArH), 7.39e7.37 (1H, m,
ArH), 7.12e7.09 (1H, m, ArH), 5.41 (1H, d, J¼4.74 Hz, H-100),
4.62e4.59 (2H, m, CH2), 4.43e4.41 (1H, m, H-30), 4.30e4.27 (1H, m,
H-20), 4.22e4.19 (2H, m, H-40 and H-50), 3.83 (3H, s, OCH3), 1.30 (3H,
s, C(CH3)2), 1.28 (3H, s, C(CH3)2), 1.22 (3H, s, C(CH3)2), 1.15 (3H, s,
C(CH3)2); dC (75 MHz, CDCl3): 185.5, 159.6, 149.2, 143.5, 140.0, 138.0,
133.2, 130.8, 129.1, 125.2, 124.8, 123.0, 120.3, 114.1, 109.6, 109.4, 70.9,
70.8, 70.4, 67.0, 55.3, 48.1, 26.0, 25.7, 25.0, 24.3; HRMS (ESI): MHþ,
found 567.2089. C28H31N4O9 requires 567.2086.
CHCl3); nmax (KBr), 2924, 1642, 1534, 1343, 1073 cmꢁ1
; dH (300 MHz,
CDCl3): 8.31 (1H, d, J¼7.74 Hz, ArH), 8.18e8.12 (1H, m, ArH), 8.09
(1H, s, ArH), 7.76e7.66 (2H, m, ArH), 7.53 (1H, d, J¼7.74 Hz, ArH),
7.38e7.34 (2H, m, ArH), 5.42 (1H, d, J¼3.72 Hz, H-10), 4.66e4.57
(2H, m, CH2), 4.43e4.39 (1H, m, H-300), 4.30e4.29 (1H, m, H-20),
4.22e4.17 (2H, m, H-40 and H-500), 2.41 (3H, s, CH3), 1.30e1.22 (12H,
m, 4ꢃ C(CH3)2); dC (75 MHz, CDCl3): 184.5, 148.7, 143.4, 139.7, 137.5,
136.7, 133.7, 133.1, 132.8, 132.0, 131.1, 130.6, 128.2, 128.0, 124.8, 123.1,
109.5, 109.3, 70.8, 70.8, 67.0, 48.0, 26.1, 25.7, 25.0, 24.3, 21.4; HRMS
(ESI): MHþ, found 551.2128. C28H31N4O8 requires 551.2136.
4.2.19. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
4.2.16. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-
a
-
D
-galactopyr-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](4-methoxy-
phenyl)methanone (3s). It was obtained by the reaction of (E)-1-(4-
methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1g (0.99 g,
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](p-tolyl)meth-
anone (3p). It was obtained by the reaction of (E)-1-(p-tolyl)-3-(2-
nitrophenyl)prop-2-en-1-one 1d (0.94 g, 3.5 mmol), 6-azido-6-
3.50 mmol), 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-
deoxy-1,2:3,4-di-O-isopropylidene-
a
-
D
-galactopyranose 2c (1.00 g,
galactopyranose 2c (1.00 g, 3.50 mmol) and TBAHS (0.24 g,
0.70 mmol), in DMF (10 mL) at 100 ꢀC for 13 h. The crude product
was purified by column chromatography using 60e120 mesh silica
gel (15% ethyl acetate/hexane), yielded the titled compound 3s
(1.44 g, 73%) as yellow solid; mp 54e56 ꢀC; Rf¼0.50 (ethyl acetate/
3.50 mmol) and TBAHS (0.24 g, 0.70 mmol), in DMF (10 mL) at
100 ꢀC for 14 h. The crude product was purified by column chro-
matography using 60e120 mesh silica gel (15% ethyl acetate/hex-
ane), yielded the titled compound 3p (1.45 g, 75%) as yellow solid;
mp 56e59 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:7); ½a 3D0
ꢂ
þ66 (c 0.1,
hexane, 3:7); ½a D30
ꢂ
þ94 (c 0.1, CHCl3); nmax (KBr) 2926, 1642, 1530,
dH (300 MHz, CDCl3): 8.32 (1H, d, J¼7.50 Hz, ArH),
CHCl3); nmax (KBr) 2928, 1644, 1531, 1344, 1075 cmꢁ1
;
dH (300 MHz,
1343, 1071 cmꢁ1
;
CDCl3): 8.30e8.25 (3H, m, ArH), 7.75e7.65 (2H, m, ArH), 7.53 (1H,
dd, J1¼7.26 Hz, J2¼1.86 Hz, ArH), 7.25e7.24 (2H, m, ArH), 5.41 (1H, d,
J¼5.10 Hz, H-100), 4.65e4.58 (2H, m, CH2), 4.42e4.36 (1H, m, H-30),
4.29e4.27 (1H, m, H-20), 4.21e4.18 (2H, m, H-40 and H-50), 2.41 (3H,
s, CH3), 1.30e1.21 (12H, m, 4ꢃ C(CH3)2); dC (75 MHz, CDCl3): 185.1,
148.7, 143.6, 139.6, 134.2, 133.1, 132.8, 130.9, 130.7, 128.9, 128.8,
125.2, 124.7,123.1,109.6, 109.3, 70.8, 70.4, 67.0, 48.0, 26.0, 25.7, 25.0,
24.3, 21.7; HRMS (ESI): MNaþ, found 573.1965. C28H30N4O8Na re-
quires 573.1956.
8.10 (1H, d, J¼7.86 Hz, ArH), 7.79 (1H, m, ArH), 7.73e7.69 (2H, m,
ArH), 7.53 (1H, d, J¼7.47 Hz, ArH), 7.39e7.34 (2H, m, ArH), 5.40 (1H,
d, J¼4.71 Hz, H-10), 4.61e4.58 (2H, m, CH2), 4.42e4.36 (1H, m, H-30),
4.28e4.15 (3H, m, H-20, H-40 and H-50), 3.84 (3H, s, OCH3), 1.30e1.21
(12H, m, 4ꢃ C(CH3)2); dC (75 MHz, CDCl3): 184.5, 163.9, 149.0, 143.5,
139.5, 133.6, 133.0, 132.1, 131.3, 129.6, 125.1, 123.1, 113.7, 109.7, 109.4,
70.9, 70.8, 70.4, 67.0, 55.4, 48.1, 26.0, 25.7, 25.0, 24.3; HRMS (ESI):
MHþ, found 567.2090. C28H31N4O9 requires 567.2086.
4.2.20. [1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-
4.2.17. [1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-
a
-
D
-galactopyr-
nitrophenyl)-1H-1,2,3-triazol-4-yl](4-fluorophenyl)methanone
(3t). It was obtained by the reaction of (E)-1-(4-fluorophenyl)-3-
(2-nitrophenyl)prop-2-en-1-one 1i (0.72 g, 2.68 mmol), 2,3,4,6-
anos-6-yl)-5-(2-nitrophenyl)-1H-1,2,3-triazol-4-yl](2-methoxyp-
henyl)methanone (3q). It was obtained by the reaction of (E)-1-(2-
methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one 1e (0.99 g,
tetra-O-acetyl-b-D-glucopyranosyl azide 2d (1.00 g, 2.68 mmol),
3.50 mmol), 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-
a
-
D
-
TBAHS (0.18 g, 0.53 mmol) and p-TSA (0.05 g, 0.27 mmol), in DMF
(10 mL) at 100 ꢀC for 18 h. The crude product was purified by col-
umn chromatography using 60e120 mesh silica gel (25% ethyl ac-
etate/hexane), yielded the titled compound 3t (0.94 g, 55%) as
yellow solid; mp 65e68 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:2);
galactopyranose 2c (1.00 g, 3.50 mmol) and TBAHS (0.24 g,
0.70 mmol), in DMF (10 mL) at 100 ꢀC for 15 h. The crude product
was purified by column chromatography using 60e120 mesh silica
gel (15% ethyl acetate/hexane), yielded the titled compound 3q
(1.38 g, 70%) as yellow solid; mp 58e60 ꢀC; Rf¼0.50 (ethyl acetate/
½
a 3D0
ꢂ
þ62 (c 0.1, CHCl3); nmax (KBr) 2925, 1651, 1530, 1338,

8554
K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
1070 cmꢁ1
;
dH (300 MHz, CDCl3): 8.13 (1H, d, J¼6.75 Hz, ArH), 7.85
0.50 mmol). The purification of crude product by column chro-
matography using 60e120 mesh silica gel (10% ethyl acetate/hex-
ane), yielded the titled compound 4c (0.16 g, 91%) as white solid;
mp 128e130 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr),
(1H, t, J¼6.75 Hz, ArH), 7.68e7.66 (3H, m, ArH), 7.13e7.01 (3H, m,
ArH), 5.26e5.10 (3H, m, H-10, H-20 and H-30), 5.05e4.98 (1H, m, H-
400), 4.29e4.08 (3H, m, H-50 and CH2), 2.03e1.97 (12H, m, 4ꢃ
eCOCH3); dC (75 MHz, CDCl3): 188.7, 170.5, 170.1, 170.0, 169.3, 163.3
(d, 1JCF¼250.32 Hz), 148.1, 135.2, 133.3, 132.6 (d, 3JCF¼7.95 Hz), 131.1,
2927, 1518, 765 cmꢁ1
; dH (300 MHz, CDCl3): 8.72e8.67 (2H, m, ArH),
8.33 (1H, d, J¼8.19 Hz, ArH), 8.02 (1H, d, J¼7.92 Hz, ArH), 7.73 (1H, t,
J¼7.20 Hz, ArH), 7.54e7.46 (2H, m, ArH), 7.39e7.28 (4H, m, ArH),
7.20e7.18 (2H, m, ArH), 6.27 (2H, s, CH2), 2.58 (3H, s, CH3); dC
(75 MHz, CDCl3): 151.5, 145.5, 139.9, 138.0, 136.5, 134.4, 134.2, 131.2,
130.9, 130.3, 129.4, 129.2, 128.4, 127.3, 126.7, 126.3, 121.6, 114.6, 53.7,
21.7; HRMS (ESI): MHþ, found 351.1606. C23H19N4 requires
351.1604.
2
130.7, 130.1, 130.0, 124.5, 115.1 (d, JCF¼22.50 Hz), 83.6, 73.9, 73.0,
72.6, 68.4, 62.1, 20.7, 20.7, 20.5, 20.5; HRMS (ESI): MHþ, found
643.1678. C29H28FN4O12 requires 643.1682.
4.2.21. [1-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-5-(2-
nitrophenyl)-1H-1,2,3-triazol-4-yl](4-bromophenyl)methanone
(3u). It was obtained by the reaction of (E)-1-(4-Bromophenyl)-3-
(2-nitrophenyl)prop-2-en-1-one 1j (0.89 g, 2.68 mmol), 2,3,4,6-
4.3.3. 1-Benzyl-4-(p-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4d). It
was obtained by the reductive cyclization of 3d (0.20 g, 0.50 mmol).
The purification of crude product by column chromatography using
60e120 mesh silica gel (10% ethyl acetate/hexane), yielded the ti-
tled compound 4d (0.17 g, 98%) as white solid; mp 182e184 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2926, 1519,
tetra-O-acetyl-b-D-galactopyranosyl azide 2e (1.00 g, 2.68 mmol),
TBAHS (0.18 g, 0.53 mmol) and p-TSA (0.05 g, 0.27 mmol), in DMF
(10 mL) at 100 ꢀC for 18 h. The crude product was purified by col-
umn chromatography using 60e120 mesh silica gel (25% ethyl ac-
etate/hexane), yielded the titled compound 3u (0.94 g, 50%) as
yellow solid; mp 78e80 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 3:2);
771 cmꢁ1
;
dH (300 MHz, CDCl3): 8.85 (2H, d, J¼7.77 Hz, ArH), 8.28
½
a 3D0
1074 cmꢁ1
ꢂ
þ71 (c 0.1, CHCl3); nmax (KBr) 2926, 1653, 1533, 1341,
(1H, d, J¼8.16 Hz, ArH), 7.98 (1H, d, J¼7.92 Hz, ArH), 7.69 (1H, t,
J¼7.20 Hz, ArH), 7.44e7.41 (3H, m, ArH), 7.33e7.30 (3H, m, ArH),
7.18e7.16 (2H, m, ArH), 6.23 (2H, s, CH2), 2.51 (3H, s, CH3); dC
(75 MHz, CDCl3): 151.1, 145.5, 140.4, 139.8, 134.5, 134.1, 133.9, 130.7,
129.9, 129.2, 129.2, 128.4, 126.5, 126.3, 121.5, 114.5, 53.6, 21.6; HRMS
(ESI): MHþ, found 351.1613. C23H19N4 requires 351.1604.
;
dH (300 MHz, CDCl3): 7.71e7.66 (4H, m, ArH), 7.53e7.48
(3H, m, ArH), 7.13 (1H, br, ArH), 5.43e5.27 (2H, m, H-10 and H-20),
5.10 (1H, m, H-30), 4.91e4.88 (1H, m, H-40), 4.18e4.00 (3H, m, H-50
and CH2), 2.09e1.97 (12H, m, 4ꢃ eCOCH3); dC (50 MHz,
CDCl3):184.0, 170.0, 169.7, 168.9, 168.7, 148.8, 143.9, 139.9, 134.9,
133.2, 132.2, 131.6, 128.8, 125.2, 121.8, 84.7, 75.0, 72.5, 69.6, 67.4,
61.5, 20.5, 20.4, 20.1; HRMS (ESI): MHþ, found 703.0876.
C29H28BrN4O12 requires 703.0882.
4.3.4. 1-Benzyl-4-(2-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quino-
line (4e). It was obtained by the reductive cyclization of 3e (0.20 g,
0.48 mmol). The purification of crude product by column chro-
matography using 60e120 mesh silica gel (10% ethyl acetate/hex-
ane), yielded the titled compound 4e (0.15 g, 87%) as white solid;
mp 174e177 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr)
4.3. General procedure for the preparation of 1-benzyl-4-
phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline (4a)
A mixture of triazolyl methanone 3a (0.20 g, 0.52 mmol) and 5%
palladium on charcoal (0.10 g) in dry methanol (10 mL) was stirred
under a hydrogen atmosphere at room temperature for 10 h. The
reaction mixture was filtered through Celite and the solvent evap-
orated under vacuum to give the crude product, which was purified
by column chromatography using 60e120 mesh silica gel (10% ethyl
acetate/hexane), yielded the title compound 4a (0.16 g, 94%) as
white solid; mp 72e74 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax
2928, 1521, 1218, 768 cmꢁ1
; dH (400 MHz, CDCl3): 8.32 (1H, d,
J¼8.32 Hz, ArH), 8.03 (1H, d, J¼8.20 Hz, ArH), 7.72e7.66 (2H, m,
ArH), 7.51e7.47 (2H, m, ArH), 7.34e7.27 (3H, m, ArH), 7.19e7.18 (2H,
m, ArH), 7.14e7.10 (2H, m, ArH), 6.22 (2H, s, CH2), 3.83 (3H, s,
OCH3); dC (100 MHz, CDCl3): 158.1, 153.2, 146.1, 141.0, 134.8, 133.5,
131.5, 131.3, 131.2, 129.5, 129.5, 128.6, 127.1, 126.8, 126.7, 122.0, 121.1,
115.2, 112.0, 56.0, 53.9; HRMS (ESI): MHþ, found 367.1554.
C23H19N4O requires 367.1553.
(KBr) 2926, 1519 cmꢁ1
; dH (300 MHz, CDCl3): 8.87e8.84 (2H, m,
ArH), 8.31 (1H, d, J¼8.25 Hz, ArH), 8.03 (1H, d, J¼7.68 Hz, ArH),
7.74e7.68 (1H, m, ArH), 7.64e7.55 (3H, m, ArH), 7.51e7.46 (1H, m,
ArH), 7.35e7.27 (3H, m, ArH), 7.18e7.15 (2H, m, ArH), 6.25 (2H, s,
CH2); dC (75 MHz, CDCl3): 151.4, 145.5, 139.9, 136.6, 134.4, 134.3,
130.8,130.4,129.9,129.6,129.2,128.6,128.5,127.0,126.4,121.7,114.7,
53.8; HRMS (ESI): MHþ, found 337.1441. C22H17N4 requires 337.1448.
4.3.5. 1-Benzyl-4-(3-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quino-
line (4f). It was obtained by the reductive cyclization of 3f (0.20 g,
0.48 mmol). The purification of crude product by column chro-
matography using 60e120 mesh silica gel (10% ethyl acetate/hex-
ane), yielded the titled compound 4f (0.16 g, 90%) as white solid;
mp 146e148 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr)
2927, 1518, 1219, 762 cmꢁ1
; dH (400 MHz, CDCl3): 8.52 (1H, d,
4.3.1. 1-Benzyl-4-(o-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4b). It
was obtained by the reductive cyclization of 3b (0.20 g, 0.50 mmol).
The purification of crude product by column chromatography using
60e120 mesh silica gel (10% ethyl acetate/hexane), yielded the ti-
tled compound 4b (0.15 g, 87%) as white solid; mp 140e142 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr) 2926, 1521,
J¼7.56 Hz, ArH), 8.44 (1H, s, ArH), 8.27 (1H, d, J¼8.24 Hz, ArH), 7.97
(1H, d, J¼8.08 Hz, ArH), 7.70e7.66 (1H, m, ArH), 7.51e7.43 (2H, m,
ArH), 7.30e7.28 (3H, m, ArH), 7.16e7.14 (2H, m, ArH), 7.09 (1H, d,
J¼8.16 Hz, ArH), 6.21 (2H, s, CH2), 3.97 (3H, s, OCH3); dC (100 MHz,
CDCl3): 159.8, 151.0, 145.4, 139.9, 137.8, 134.4, 134.2, 130.9, 129.4,
129.4, 129.2, 128.4, 126.8, 126.3, 122.6, 121.5, 117.0, 114.6, 114.3, 55.3,
53.7; HRMS (ESI): MHþ, found 367.1553. C23H19N4O requires
367.1553.
769 cmꢁ1
;
dH (300 MHz, CDCl3): 8.35 (1H, d, J¼8.10 Hz, ArH), 8.11
(1H, d, J¼8.10 Hz, ArH), 7.83e7.74 (2H, m, ArH), 7.57 (1H, t,
J¼7.77 Hz, ArH), 7.43 (3H, s, ArH), 7.37e7.35 (3H, m, ArH), 7.25e7.23
(2H, m, ArH), 6.28 (2H, s, CH2), 2.50 (3H, s, CH3); dC (100 MHz,
CDCl3): 154.8, 145.5, 140.5, 137.1, 136.2, 134.4, 133.6, 131.0, 130.9,
130.8, 129.5, 129.3, 129.2, 128.5, 127.0, 126.4, 125.7, 121.7, 114.6, 53.7,
20.6; HRMS (ESI): MHþ, found 351.1607. C23H19N4 requires
351.1604.
4.3.6. 1-Benzyl-4-(4-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quino-
line (4g). It was obtained by the reductive cyclization of 3g (0.20 g,
0.48 mmol). The purification of crude product by column chro-
matography using 60e120 mesh silica gel (10% ethyl acetate/hex-
ane), yielded the titled compound 4g (0.17 g, 97%) as white solid;
mp 134e136 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:4); nmax (KBr),
4.3.2. 1-Benzyl-4-(m-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
2926, 1519, 1217, 772 cmꢁ1
;
dH (300 MHz, CDCl3): 8.57 (1H, d,
(4c). It was obtained by the reductive cyclization of 3c (0.20 g,
J¼7.62 Hz, ArH), 8.49 (1H, s, ArH), 8.34 (1H, d, J¼8.28 Hz, ArH), 8.05

K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
8555
(1H, d, J¼8.07 Hz, ArH), 7.74 (1H, t, J¼7.14 Hz, ArH), 7.56e7.49 (2H,
m, ArH), 7.35e7.33 (3H, m, ArH), 7.21e7.19 (2H, m, ArH), 7.13 (1H, d,
J¼6.66 Hz, ArH), 6.28 (2H, s, CH2), 4.01 (3H, s, OCH3); dC (75 MHz,
CDCl3): 159.9, 151.0, 145.5, 139.9, 137.9, 134.5, 131.0, 129.5, 129.2,
128.5, 126.9, 126.3, 122.6, 121.5, 117.1, 114.8, 114.4, 55.3, 53.8; HRMS
(ESI): MHþ, found 367.1553. C23H19N4O requires 367.1553.
105.0, 85.6, 79.4, 74.1, 49.8, 27.0, 26.5, 21.7; HRMS (ESI): MHþ, found
433.1864. C24H25N4O4 requires 433.1870.
4.3.9. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-4-(p-
tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4i). It was obtained by the
reductive cyclization of 3i (0.20 g, 0.42 mmol). The purification of
crude product by column chromatography using 60e120 mesh
silica gel (25% ethyl acetate/hexane), yielded the titled compound
4i (0.18 g, 90%) as white solid; mp 232e234 ꢀC; Rf¼0.50 (ethyl ac-
4.3.7. [1-Benzyl-5-(2-aminophenyl)-1H-1,2,3-triazol-4-yl](4-
methoxyphenyl)methanone (4g0). (A) With SnCl2$2H2O: To a stirred
solution of 3g (0.10 g, 0.24 mmol) in ethanol (5 mL), SnCl2$2H2O
(0.54 g, 2.40 mmol) was added. The reaction mixture was stirred
at 80 ꢀC for 2 h. After completion of reaction (TLC), it was neu-
tralized with sodium bicarbonate. After neutralization, it was fil-
tered through Celite and the solvent evaporated under vacuum to
give the crude product, which was diluted with water and
extracted with ethyl acetate. The organic layer was collected, dried
over sodium sulfate (Na2SO4) and evaporated under reduced
pressure to get the crude mass, which upon purification by column
chromatography using 60e120 mesh silica gel (15% ethyl acetate/
hexane), yielded the titled compound 4g0 (0.08 g, 90%) as white
solid.
etate/hexane, 2:3); ½a D30
ꢁ44 (c 0.1, DMSO); nmax (KBr) 3461, 2927,
ꢂ
1218, 770 cmꢁ1
;
dH (300 MHz, DMSO-d6): 8.76 (2H, d, J¼8.16 Hz,
ArH), 8.59 (1H, d, J¼8.19 Hz, ArH), 8.27 (1H, d, J¼8.13 Hz, ArH), 7.88
(1H, t, J¼7.53 Hz, ArH), 7.76 (1H, t, J¼7.71 Hz, ArH), 7.45 (2H, d,
J¼8.19 Hz, ArH), 5.88e5.86 (2H, m, H-100 and OH), 5.42e5.29 (2H, m,
CH2), 4.72e4.70 (1H, m, H-40), 4.56 (1H, d, J¼3.54 Hz, H-20),
4.35e4.33 (1H, m, H-30), 2.44 (3H, s, CH3), 1.22 (3H, s, C(CH3)2), 1.19
(3H, s, C(CH3)2); dC (75 MHz, CDCl3): 150.1, 145.1, 140.8, 139.0, 134.8,
133.9, 130.4, 130.3, 129.8, 129.6, 127.5, 123.1, 115.1, 111.3, 104.9, 85.6,
79.4, 74.0, 49.7, 27.0, 26.4, 21.5; HRMS (ESI): MHþ, found 433.1863.
C24H25N4O4 requires 433.1870.
(B) With SnCl2$2H2O under ultrasonic irradiation: Above pro-
cedure was repeated under ultrasonic irradiation at 30 ꢀC, yielded
the titled compound 4g0 (0.09 g, 93%) as white solid.
4.3.10. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-4-
(4-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4j). It was
obtained by the reductive cyclization of 3j (0.20 g, 0.40 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (25% ethyl acetate/hexane), yielded the ti-
tled compound 4j (0.17 g, 92%) as white solid; mp 242e244 ꢀC;
(C) With Iron powder and ammonium chloride: Iron powder
(0.04 g, 0.72 mmol) and ammonium chloride (0.008 g, 0.140 mmol)
was added to a stirred solution of 3g (0.10 g, 0.24 mmol) in a mix-
ture of ethanol (5 mL) and water (0.5 mL). The reaction mixture was
stirred at 80 ꢀC for 14 h. After completion of reaction (TLC), it was
filtered through Celite and the solvent evaporated under reduced
pressure to give the crude product, which was purified by column
chromatography using 60e120 mesh silica gel (15% ethyl acetate/
hexane), yielded the titled compound 4g0 (0.02 g, 22%) as white
solid.
Rf¼0.50 (ethyl acetate/hexane, 2:3); ½a D30
ꢁ56 (c 0.1, DMSO); nmax
ꢂ
(KBr) 3462, 2927, 1219, 771 cmꢁ1
; dH (300 MHz, DMSO-d6): 8.84
(2H, d, J¼8.88 Hz, ArH), 8.54 (1H, d, J¼8.16 Hz, ArH), 8.21 (1H, d,
J¼8.16 Hz, ArH), 7.83 (1H, t, J¼7.72 Hz, ArH), 7.71 (1H, t, J¼7.84 Hz,
ArH), 7.18 (2H, d, J¼8.92 Hz, ArH), 5.88 (1H, d, J¼3.56 Hz, H-10), 5.87
(1H, d, J¼4.92 Hz, OH), 5.38e5.24 (2H, m, CH2), 4.71e4.68 (1H, m,
H-400), 4.56 (1H, d, J¼3.60 Hz, H-200), 4.35 (1H, dd, J1¼4.60, J2¼3.00,
H-300) 3.87 (3H, s, OCH3), 1.21 (3H, s, C(CH3)2), 1.18 (3H, s, C(CH3)2);
dC (50 MHz, CDCl3): 161.2, 149.2, 144.7, 138.4, 134.3, 130.9, 129.8,
129.8, 128.7, 126.7, 122.5, 114.5, 114.0, 110.8, 104.4, 85.1, 78.9, 73.5,
55.3, 49.2, 26.5, 25.9; HRMS (ESI): MHþ, found 449.1820.
C24H25N4O5 requires 449.1819.
(D) With PdeC and ammonium formate: Ammonium formate
(0.08 g, 1.20 mmol) was added to a stirred solution of 3g (0.10 g,
0.24 mmol) in dry methanol. The reaction mixture was stirred at
30 ꢀC for 19 h. After completion of reaction (TLC), it was filtered
through Celite and the solvent evaporated under reduced pressure
to give the crude product, which was purified by column chroma-
tography using 60e120 mesh silica gel (15% ethyl acetate/hexane),
yielded the titled compound 4g0 (0.019 g, 20%) as white solid; mp
146e148 ꢀC; Rf¼0.45 (ethyl acetate/hexane, 1:4); nmax (KBr) 3432,
4.3.11. [1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-5-
(2-aminophenyl)-1H-1,2,3-triazol-4-yl](4-methoxyphenyl)meth-
anone (4j0). (A) With SnCl2$2H2O: To a stirring solution of 3j
(0.10 g, 0.20 mmol) in ethanol (5 mL), SnCl2$2H2O (0.45 g,
2.00 mmol) was added. The reaction mixture was stirred at 80 ꢀC
for 2 h. After completion of reaction (TLC), it was neutralized
with sodium bicarbonate. After neutralization, it was filtered
through Celite and the solvent evaporated under vacuum to give
the crude product, which was diluted with water and extracted
with ethyl acetate. The organic layer was collected, dried over
sodium sulfate (Na2SO4) and evaporated under reduced pressure
to get the crude mass, which upon purification by column
chromatography using 60e120 mesh silica gel (15% ethyl acetate/
hexane), yielded the titled compound 4j0 (0.06 g, 67%) as white
solid.
2926, 1647, 1216, 768 cmꢁ1
; dH (300 MHz, CDCl3): 7.94 (1H, d,
J¼7.62 Hz, ArH), 7.41e7.32 (4H, m, ArH), 7.24 (1H, d, J¼6.48 Hz,
ArH), 7.17e7.06 (4H, m, ArH), 6.87 (1H, t, J¼7.26 Hz, ArH), 6.67 (1H,
t, J¼7.23 Hz, ArH), 6.26 (2H, s, CH2), 3.94 (3H, s, CH3); dC (75 MHz,
CDCl3): 184.5, 159.4, 141.2, 140.8, 130.5, 130.0, 129.4, 129.2, 128.8,
126.5, 126.4, 123.8, 122.6, 122.4, 116.9, 116.1, 115.0, 55.5, 54.1; HRMS
(ESI): MHþ, found 385.1654. C23H21N4O2 requires 385.1659.
4.3.8. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-4-(m-
tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4h). It was obtained by the
reductive cyclization of 3h (0.20 g, 0.42 mmol). The purification of
crude product by column chromatography using 60e120 mesh
silica gel (25% ethyl acetate/hexane), yielded the titled compound
4h (0.16 g, 89%) as white solid; mp 228e232 ꢀC; Rf¼0.50 (ethyl
(B) With SnCl2$2H2O under ultrasonic irradiation: Above pro-
cedure was repeated under ultrasonic irradiation at 30 ꢀC, yielded
the titled compound 4j0 (0.07 g, 71%) as white solid.
acetate/hexane, 2:3); ½a D30
ꢁ46 (c 0.1, DMSO); nmax (KBr) 3463,
ꢂ
2926, 1217, 763 cmꢁ1
;
dH ( 300 MHz, DMSO-d6): 8.67e8.64 (3H, m,
(C) With Iron powder and ammonium chloride: To a stirred so-
lution of 3j (0.100 g, 0.200 mmol) in a mixture of ethanol (5 mL) and
water (0.5 mL), iron powder (0.034 g, 0.600 mmol) and ammonium
chloride (0.006 g, 0.120 mmol) were added. The reaction mixture
was stirred at 80 ꢀC for 16 h. After completion of reaction (TLC), it
was filtered through Celite and the solvent evaporated under re-
duced pressure to give the crude product, which was purified by
column chromatography using 60e120 mesh silica gel (15% ethyl
ArH), 8.35 (1H, d, J¼8.13 Hz, ArH), 7.94 (1H, t, J¼7.80 Hz ArH), 7.83
(1H, t, J¼7.98 Hz, ArH), 7.57 (1H, t, J¼7.56 Hz, ArH), 7.47 (1H, d,
J¼7.47 Hz, ArH), 5.92e5.91 (2H, m, H-10 and OH), 5.47e5.31 (2H, m,
CH2), 4.77e4.72 (1H, m, H-40), 4.59 (1H, d, J¼3.60 Hz, H-20),
4.39e4.36 (1H, m, H-30), 2.53 (3H, s, CH3), 1.26 (3H, s, C(CH3)2), 1.23
(3H, s, C(CH3)2); dC (75 MHz, CDCl3): 150.4, 145.2, 139.1, 138.2, 136.7,
134.9, 131.6, 130.6, 130.4, 130.2, 129.0, 127.7, 127.3, 123.2, 115.3, 111.4,

8556
K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
acetate/hexane), yielded the titled compound 4j0 (0.024 g, 25%) as
white solid.
J¼4.89 Hz, H-10), 5.34 (2H, d, J¼6.69 Hz, CH2), 4.75e4.71 (1H, dd,
J1¼7.89 Hz, J2¼2.37 Hz, H-30), 4.61 (1H, t, J¼6.60 Hz, H-20),
4.42e4.39 (1H, dd, J1¼7.89 Hz, J2¼1.53 Hz, H-40), 4.37e4.35 (1H, m,
H-50), 1.70 (3H, s, C(CH3)2), 1.45 (3H, s, C(CH3)2), 1.31 (3H, s,
C(CH3)2), 1.26 (3H, s, C(CH3)2); dC (75 MHz, CDCl3): 151.5, 145.7,
139.4, 136.8, 135.1, 130.8, 130.3, 129.9, 129.5, 128.6, 126.6, 122.1,
115.2, 109.9, 109.0, 70.8, 70.4, 67.4, 50.1, 26.1, 25.8, 24.7, 24.4; HRMS
(ESI): MHþ, found 489.2123. C27H29N4O5 requires 489.2132.
(D) With PdeC and ammonium formate: To a stirred solution of 3j
(0.100 g, 0.200 mmol) in dry methanol, ammonium formate(0.076 g,
1.000 mmol) was added. The reaction mixture was stirred at 25 ꢀC
for 12 h. After completion of reaction (TLC), it was filtered through
Celite and the solvent evaporated under reduced pressure to give
the crude product, which was purified by column chromatography
using 60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the
titled compound 4j0 (0.005 g, 5%) as white solid; mp 187e189 ꢀC;
4.3.15. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-
Rf¼0.45 (ethyl acetate/hexane, 2:3); ½a D30
ꢁ26 (c 0.1, CHCl3); nmax
ꢂ
6-yl)-4-(o-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4n). It was ob-
tained by the reductive cyclization of 3n (0.20 g, 0.36 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the titled
compound 4n (0.14 g, 80%) as white solid; mp 58e60 ꢀC; Rf¼0.50
(KBr) 3431, 2926,1219, 771 cmꢁ1
; dH (300 MHz, CDCl3): 8.88 (1H, br,
ArH), 8.47 (1H, br, ArH), 8.26e8.24 (2H, m, ArH), 7.74e7.69 (2H, m,
ArH), 7.07 (2H, br, ArH), 5.90 (1H, br, H-10), 5.15 (2H, br, CH2), 4.77
(1H, br, H-40), 4.48 (1H, br, H-20), 4.07 (1H, br, H-30), 3.85 (3H, s,
OCH3),1.36 (3H, s, C(CH3)2),1.24 (3H, s, C(CH3)2); dC (75 MHz, CDCl3):
184.3,161.7,140.7,139.8,133.2,130.8,129.2,128.1,123.0,121.9,120.6,
115.1,113.7, 112.2,105.2, 85.6, 79.7, 74.3, 55.6, 49.3, 26.9, 26.3; HRMS
(ESI): MHþ, found 467.1917. C24H27N4O6 requires 467.1925.
(ethyl acetate/hexane,1:3); ½a D30
ꢁ99 (c 0.1, CHCl3); nmax (KBr) 2928,
ꢂ
1212, 762 cmꢁ1
;
dH (300 MHz, CDCl3): 8.59 (1H, d, J¼8.01 Hz, ArH),
8.38 (1H, d, J¼8.19 Hz, ArH), 7.84e7.81 (2H, m, ArH), 7.73e7.68 (1H,
m, ArH), 7.43 (3H, br, ArH), 5.46 (1H, d, J¼4.92 Hz, H-10), 5.31e5.27
(2H, m, CH2), 4.72 (1H, dd, J1¼7.89 Hz, J2¼2.37 Hz, H-30), 4.60 (1H, t,
J¼6.03 Hz, H-20), 4.39e4.32 (2H, m, H-40 and H-50), 2.50 (3H, s, CH3),
1.69 (3H, s, C(CH3)2), 1.44 (3H, s, C(CH3)2), 1.33 (3H, s, C(CH3)2), 1.30
(3H, s, C(CH3)2); dC (75 MHz, CDCl3): 154.8, 145.6, 139.9, 137.2, 136.3,
134.4, 130.9, 129.3, 129.2, 126.6, 125.6, 122.1, 115.1, 109.8, 108.8, 70.9,
70.4, 67.4, 50.1, 29.7, 26.2, 25.8, 24.8, 24.4, 20.7; HRMS (ESI): MHþ,
found 503.2294. C28H31N4O5 requires 503.2289.
4.3.12. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-4-
(2,4-dichlorophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4k). It was
obtained by the reductive cyclization of 3k (0.20 g, 0.42 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (25% ethyl acetate/hexane) as eluent, yielded
the titled compound 4k (0.16 g, 86%) as white solid; mp 224e226 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 2:3); ½a D30
ꢁ2 (c 0.1, DMSO); nmax
ꢂ
4.3.16. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-
(KBr) 3462, 2928, 1218, 768 cmꢁ1
;
dH (300 MHz, DMSO-d6þCDCl3):
6-yl)-4-(m-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4o). It was ob-
tained by the reductive cyclization of 3o (0.20 g, 0.36 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the titled
compound 4o (0.15 g, 81%) as white solid; mp 52e54 ꢀC; Rf¼0.50
8.69 (1H, d, J¼7.89 Hz, ArH), 8.32 (1H, d, J¼7.86 Hz, ArH), 7.88e7.83
(1H, m, ArH), 7.80e7.71 (2H, m, ArH), 7.63e7.58 (1H, m, ArH), 7.50
(1H, d, J¼7.86 Hz, ArH), 5.94 (1H, br, H-10), 5.35e5.33 (2H, m, CH2),
4.82 (1H, br, H-40), 4.59 (1H, br, H-20), 4.34 (1H, s, H-30), 1.36 (3H, s,
C(CH3)2),1.27 (3H, s, C(CH3)2); dC (75 MHz, CDCl3): 145.1,139.3,135.5,
134.2,134.0,132.8,130.5,129.8,129.5,127.5,126.9,122.5,115.4,111.4,
104.8, 85.4, 79.8, 74.0, 49.4, 26.6, 26.1; HRMS (ESI): MHþ, found
487.0928. C23H21Cl2N4O4 requires 487.0934.
(ethyl acetate/hexane, 1:3); ½a D30
ꢁ106 (c 0.1, CHCl3); nmax (KBr)
ꢂ
2926,1217,1070, 771 cmꢁ1
; dH (300 MHz, CDCl3): 8.66e8.62 (2H, m,
ArH), 8.47 (1H, d, J¼8.13 Hz, ArH), 8.33 (1H, d, J¼8.25 Hz, ArH), 7.76
(1H, t, J¼7.95 Hz, ArH), 7.59 (1H, t, J¼7.83 Hz, ArH), 7.46 (1H, t,
J¼7.62 Hz, ArH), 7.33 (1H, d, J¼7.47 Hz, ArH), 5.40 (1H, d, J¼4.95 Hz,
H-10), 5.27e5.21 (2H, m, CH2), 4.65 (1H, dd, J1¼7.89 Hz, J2¼2.31 Hz,
H-300), 4.55 (1H, t, J¼7.11 Hz, H-20), 4.31e4.25 (2H, m, H-40 and H-500),
2.53 (3H, s, CH3), 1.62 (3H, s, C(CH3)2), 1.37 (3H, s, C(CH3)2), 1.25 (6H,
s, 2ꢃ C(CH3)2); dC (75 MHz, CDCl3): 151.6, 145.7, 139.4, 137.8, 136.6,
134.9,131.1,130.9,130.4,129.3,128.4,127.4,126.4,122.0,115.1,109.8,
108.8, 70.8, 70.8, 70.4, 67.2, 50.0, 29.7, 26.1, 25.8, 24.8, 24.4, 21.7;
HRMS (ESI): MHþ, found 503.2293. C28H31N4O5 requires 503.2289.
4.3.13. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-4-
(4-fluorophenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4l). It was ob-
tained by the reductive cyclization of 3l (0.20 g, 0.41 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (25% ethyl acetate/hexane), yielded the titled
compound 4l (0.16 g, 91%) as white solid; mp 214e217 ꢀC; Rf¼0.50
(ethyl acetate/hexane, 2:3); ½a D30
ꢁ39 (c 0.1, DMSO); nmax (KBr) 3462,
ꢂ
2928, 1218, 768 cmꢁ1
; dH (400 MHz, DMSO-d6): 8.91e8.87 (2H, m,
ArH), 8.61 (1H, d, J¼8.16 Hz, ArH), 8.27 (1H, d, J¼8.24 Hz, ArH), 7.89
(1H, t, J¼7.40 Hz, ArH), 7.78 (1H, t, J¼7.60, ArH), 7.47 (2H, t, J¼8.80 Hz,
ArH), 6.21 (1H, br, OH), 5.86 (1H, d, J¼3.40 Hz, H-10), 5.42 (1H, dd,
J1¼14.92 Hz, J2¼3.72 Hz, CH2), 5.33e5.27 (1H, m, CH2), 4.69e4.67
(1H, m, H-40), 4.56 (1H, d, J¼3.44 Hz, H-20), 4.35 (1H, d, J¼1.88 Hz, H-
300), 1.20 (3H, s, C(CH3)2), 1.18 (3H, s, C(CH3)2); dC (100 MHz, CDCl3):
162.4 (d, 1JCF¼252.00 Hz), 148.4, 144.5, 138.4, 134.5, 132.7, 131.6 (d,
4.3.17. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-
6-yl)-4-(p-tolyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4p). It was ob-
tained by the reductive cyclization of 3p (0.20 g, 0.36 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the ti-
tled compound 4p (0.17 g, 96%) as white solid; mp 84e87 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 1:3); ½ ꢂD ꢁ105 (c 0.1, CHCl3); nmax
a 30
2
3JCF¼10.00 Hz), 130.0, 127.3, 122.7, 115.7, (d, JCF¼20.00 Hz), 114.7,
(KBr) 2927, 1216, 1069, 770 cmꢁ1
; dH (300 MHz, CDCl3): 8.82 (2H, d,
110.8,104.5, 85.1, 79.1, 73.5, 49.4, 26.5, 26.0; HRMS (ESI): MHþ, found
437.1626. C23H22FN4O4 requires 437.1620.
J¼8.07 Hz, ArH), 8.56 (1H, d, J¼8.22 Hz, ArH), 8.40 (1H, d, J¼8.28 Hz,
ArH), 7.84 (1H, t, J¼7.47 Hz, ArH), 7.67 (1H, t, J¼7.65 Hz, ArH), 7.48
(2H, d, J¼8.01 Hz, ArH), 5.49 (1H, d, J¼4.89 Hz, H-100), 5.34 (2H, d,
J¼6.66 Hz, CH2), 4.75 (1H, dd, J1¼7.86 Hz, J2¼2.10 Hz, H-30), 4.62
(1H, t, J¼6.18 Hz, H-20), 4.42e4.36 (2H, m, H-40 and H-50), 2.53 (3H,
s, CH3), 1.71 (3H, s, C(CH3)2), 1.46 (3H, s, C(CH3)2), 1.32 (3H, s,
C(CH3)2), 1.27 (3H, s, C(CH3)2); dC (75 MHz, CDCl3): 151.4, 145.7,
140.5, 139.4, 135.0, 134.0, 130.7, 129.8, 129.4, 126.4, 122.1, 115.1,
109.9, 108.9, 70.8, 70.4, 67.4, 50.1, 26.1, 25.8, 24.8, 24.4, 21.5; HRMS
(ESI): MHþ, found 503.2293. C28H31N4O5 requires 503.2289.
4.3.14. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-
6-yl)-4-phenyl-1H-[1,2,3]triazolo[4,5-c]quinoline (4m). It was ob-
tained by the reductive cyclization of 3m (0.20 g, 0.35 mmol). The
purification of crude product by column chromatography using
60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the ti-
tled compound 4m (0.15 g, 85%) as white solid; mp 68e70 ꢀC;
Rf¼0.50 (ethyl acetate/hexane, 1:3); ½a D30
ꢁ184 (c 0.1, CHCl3); nmax
ꢂ
(KBr) 2925, 1212, 1070, 761 cmꢁ1
; dH (300 MHz, CDCl3): 8.89e8.86
4.3.18. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-
6-yl)-4-(2-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline
a-D-galactopyranos-
(2H, m, ArH), 8.57 (1H, d, J¼8.07 Hz, ArH), 8.42 (1H, d, J¼8.04 Hz,
ArH), 7.87e7.82 (1H, m, ArH), 7.71e7.59 (4H, m, ArH), 5.47 (1H, d,

K. Upadhyaya et al. / Tetrahedron 69 (2013) 8547e8558
8557
(4q). It was obtained by the reductive cyclization of 3q (0.20 g,
0.35 mmol). The purification of crude product by column chroma-
tography using 60e120 mesh silica gel (15% ethyl acetate/hexane),
yielded the titled compound 4q (0.15 g, 84%) as white solid; mp
DMSO-d6): 8.88e8.84 (2H, m, ArH), 8.61 (1H, d, J¼8.31 Hz, ArH),
8.35 (1H, d, J¼8.35 Hz, ArH), 7.99 (1H, t, J¼7.60 Hz, ArH), 7.92 (1H, t,
J¼7.60 Hz, ArH), 7.48 (2H, m, ArH), 7.24 (1H, d, J¼9.40 Hz, H-10), 6.07
(1H, t, J¼9.60 Hz, H-20), 5.82 (1H, t, J¼9.60 Hz, H-30), 5.34 (1H, t,
J¼9.86 Hz, H-40), 4.81e4.78 (1H, m, H-50), 4.27 (1H, dd, J1¼12.58 Hz,
J2¼5.72 Hz, H-6a0), 4.13 (1H, dd, J1¼12.58, J2¼1.52, H-6b0), 2.09 (3H,
s, eCOCH3), 2.00 (3H, s, eCOCH3), 1.92 (3H, s, eCOCH3), 1.75 (3H, s,
eCOCH3); dC (75 MHz, DMSO-d6): 170.4, 169.9, 169.4, 168.6, 162.2
(d, 1JCF¼246.00 Hz),149.2, 145.2, 137.9,136.1, 132.0 (d, 3JCF¼8.58 Hz),
78e80 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:3); ½a 3D0
ꢁ92 (c 0.1,
ꢂ
CHCl3); nmax (KBr) 2929, 1218,1071, 764 cmꢁ1
; dH (300 MHz, CDCl3):
8.51 (1H, d, J¼8.13 Hz, ArH), 8.35 (1H, d, J¼8.25 Hz, ArH), 7.77 (1H, t,
J¼7.29 Hz, ArH), 7.68e7.61 (2H, m, ArH), 7.49e7.44 (1H, m, ArH),
7.14e7.07 (2H, m, ArH), 5.42 (1H, d, J¼4.92 Hz, H-10), 5.30e5.14 (2H,
m, CH2), 4.65e4.62 (1H, dd, J1¼7.89 Hz, J2¼2.28 Hz, H-30), 4.54 (1H, t,
J¼6.18 Hz, H-20), 4.31e4.27 (2H, m, H-40 and H-50), 3.80 (3H, s, OCH3),
1.63 (3H, s, C(CH3)2), 1.37 (3H, s, C(CH3)2), 1.27 (3H, s, C(CH3)2), 1.22
(3H, s, C(CH3)2); dC (75 MHz, CDCl3): 157.9, 152.8, 145.9, 140.1, 134.0,
131.3,130.9,130.8,129.2,126.6,122.1,120.8,115.4,111.8,109.8,108.8,
70.8, 70.4, 67.4, 55.7, 55.0, 26.1, 25.9, 24.8, 24.4; HRMS (ESI): MHþ,
found 519.2243. C28H31N4O6 requires 519.2238.
2
131.1, 130.3, 128.2, 123.5, 115.7(d, JCF¼21.55 Hz), 114.0, 84.0, 73.6,
72.7, 69.1, 67.6, 61.6, 20.5, 20.2, 19.9; HRMS (ESI): MHþ, found
595.1845. C29H28FN4O9 requires 595.1835.
4.4.1. 1-(b-D-Glucopyranosyl)-4-(4-fluorophenyl)-1H-[1,2,3]triazolo
[4,5-c]quinoline (4t0). It was obtained by the reductive cyclization
of 3t (0.20 g, 0.31 mmol). The purification of crude product by
column chromatography using 60e120 mesh silica gel (2% meth-
anol/chloroform), yielded the titled compound 4t0 (0.01 g, 10%) as
white solid; mp 203e205 ꢀC; Rf¼0.50 (methanol/chloroform, 1:24);
4.3.19. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-
6-yl)-4-(3-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4r). It
was obtained by the reductive cyclization of 3r (0.20 g, 0.35 mmol).
The purification of crude product by column chromatography using
60e120 mesh silica gel (15% ethyl acetate/hexane), yielded the ti-
tled compound 4r (0.16 g, 87%) as white solid; mp 72e74 ꢀC;
½
a 3D0
771 cmꢁ1
ꢂ
þ32 (c 0.1, MeOH); nmax (KBr) 3463, 2926, 1218, 1070,
;
dH (300 MHz, DMSO-d6): 8.98e8.93 (2H, m, ArH), 8.75
(1H, d, J¼7.80 Hz, ArH), 8.37 (1H, d, J¼7.80 Hz, ArH), 7.98 (1H, t,
J¼7.41 Hz, ArH), 7.85 (1H, t, J¼7.41 Hz, ArH), 7.55 (2H, t, J¼8.91 Hz,
ArH), 6.42 (1H, d, J¼9.66 Hz, H-10), 5.48 (3H, br, 3ꢃ OH), 4.78 (1H,
br, OH), 4.32e4.26 (1H, m, H-200), 3.92e3.80 (2H, m, H-30 and H-40),
3.70e3.59 (3H, m, H-50 and CH2); dC (75 MHz, DMSO-d6): 162.9 (d,
1JCF¼247.32 Hz), 149.5, 146.0, 139.0, 135.5, 133.1, 132.3(2C) (d,
3JCF¼7.50 Hz), 130.8, 128.2, 116.1(2C) (d, 2JCF¼22.50 Hz), 114.8, 80.5,
77.4, 71.4(2C), 69.9, 61.0; HRMS (ESI): MHþ, found 427.1409.
C21H20FN4O5 requires 427.1412.
Rf¼0.50 (ethyl acetate/hexane, 1:3); ½a D30
ꢁ113 (c 0.1, CHCl3); nmax
ꢂ
(KBr) 2926, 1217, 1070, 771 cmꢁ1
; dH (300 MHz, CDCl3): 8.54e8.50
(2H, m, ArH), 8.47e8.46 (1H, m, ArH), 8.39 (1H, d, J¼8.22 Hz, ArH),
7.84e7.79 (1H, m, ArH), 7.66 (1H, t, J¼7.26 Hz, ArH), 7.53 (1H, t,
J¼8.01 Hz, ArH), 7.14 (1H, dd, J1¼8.19 Hz, J2¼2.49 Hz, ArH), 5.46 (1H,
d, J¼4.95 Hz, H-10), 5.36e5.23 (2H, m, CH2), 4.71 (1H, dd, J1¼7.89 Hz,
J2¼2.40 Hz, H-30), 4.60e4.56 (1H, m, H-20), 4.38e4.32 (2H, m, ArH,
H-40 and H-50), 4.02 (3H, s, OCH3), 1.68 (3H, s, C(CH3)2), 1.43 (3H, s,
C(CH3)2), 1.30 (3H, s, C(CH3)2), 1.25 (3H, s, C(CH3)2); dC (75 MHz,
CDCl3): 159.8, 151.1, 145.6, 139.4, 138.0, 135.0, 131.0, 129.4, 129.3,
126.5, 122.7, 122.0, 117.0, 115.2, 114.3, 109.8, 108.8, 70.8, 70.8, 70.4,
67.3, 55.3, 50.0, 26.1, 25.8, 24.8, 24.4; HRMS (ESI): MHþ, found
519.2241. C28H31N4O6 requires 519.2238.
4.4.2. 1-(b-D-Galactopyranosyl)-4-(4-bromophenyl)-1H-[1,2,3]tri-
azolo[4,5-c]quinoline (4u). It was obtained by the reductive cycli-
zation of 3u (0.20 g, 0.28 mmol). The purification of crude product
by column chromatography using 60e120 mesh silica gel (2%
methanol/chloroform), yielded the titled compound 4u (0.08 g,
61%) as white solid; mp 193e195 ꢀC; Rf¼0.50 (methanol/chloro-
4.3.20. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-
a-
D
-galactopyranos-
form, 1:24); ½a 3D0
ꢂ
þ64 (c 0.1, MeOH); nmax (KBr) 3461, 2927, 1217,
6-yl)-4-(4-methoxyphenyl)-1H-[1,2,3]triazolo[4,5-c]quinoline (4s). It
was obtained by the reductive cyclization of 3s (0.20 g, 0.35 mmol).
The purification of crude product by column chromatography using
60e120 mesh silica gel with 15% ethyl acetate/hexane as eluent,
yielded the titled compound 4s (0.17 g, 93%) as white solid; mp
1071, 773 cmꢁ1
; dH (300 MHz, DMSO-d6): 9.15 (1H, br, ArH), 8.83
(2H, d, J¼8.07 Hz, ArH), 8.32 (1H, d, J¼8.07 Hz, ArH), 7.89e7.87 (2H,
m, ArH), 7.75e7.64 (2H, m, ArH), 6.31 (1H, d, J¼9.18 Hz, H-100), 5.39
(2H, br, 2ꢃ OH), 4.87 (1H, br, OH), 4.45 (1H, br, OH), 4.07e4.00 (2H,
m, H-20, H-30), 3.78 (4H, m, H-40, H-50, CH2); dC (75 MHz, DMSO-d6):
156.7, 148.7, 145.5, 139.4, 135.8, 132.2, 131.8, 130.7, 130.3, 129.9,
129.1, 128.1, 124.9, 115.1, 79.3, 74.0, 68.9, 68.2, 60.9; HRMS (ESI):
MHþ, found 487.0607. C21H20BrN4O5 requires 487.0612.
80e82 ꢀC; Rf¼0.50 (ethyl acetate/hexane, 1:3); ½a 3D0
ꢂ
ꢁ96 (c 0.1,
CHCl3); nmax (KBr) 2926, 1218, 1069, 771 cmꢁ1
; dH (300 MHz,
CDCl3): 8.93 (2H, d, J¼8.46 Hz, ArH), 8.45 (1H, d, J¼7.35 Hz, ArH),
8.30 (1H, d, J¼7.92 Hz, ArH), 7.75 (1H, t, J¼6.99 Hz, ArH), 7.60e7.58
(1H, m, ArH), 7.12 (2H, d, J¼8.46 Hz, ArH), 5.44 (1H, d, J¼4.32 Hz, H-
100), 5.25e5.18 (2H, m, CH2), 4.67 (1H, d, J¼6.54 Hz, H-30), 4.55 (1H,
br, H-20), 4.33e4.30 (2H, m, H-40 and H-50), 3.93 (3H, s, OCH3), 1.64
(3H, s, C(CH3)2), 1.39 (3H, s, C(CH3)2), 1.27 (3H, s, C(CH3)2), 1.22 (3H,
s, C(CH3)2); dC (75 MHz, CDCl3): 161.5, 150.7, 145.7, 139.2, 134.8,
131.5, 130.6, 129.5, 129.2, 126.0, 121.9, 114.9, 113.8, 109.7, 108.8, 70.8,
70.8, 70.4, 67.2, 55.2, 50.0, 26.1, 25.8, 24.7, 24.3; HRMS (ESI): MHþ,
found 519.2248. C28H31N4O6 requires 519.2238.
Acknowledgements
K.U., A.A. and R.M. are thankful to CSIR and UGC, New Delhi
respectively for fellowships. R.P.T. thank DRDO and CSIR (SPLENDID
Project) New Delhi for financial supports. We thank SAIF division,
CSIR-CDRI for the analytical facilities. This is CDRI communication
No: 8506.
Supplementary data
4.4. General procedure for the preparation of 1-(2,3,4,6-tetra-
O-acetyl-b-D-glucopyranosyl)-4-(4-fluorophenyl)-1H-[1,2,3]
triazolo[4,5-c]quinoline (4t)
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.088.
It was obtained by the reductive cyclization of 3t (0.20 g,
0.31 mmol). The purification of crude product by column chroma-
tography using 60e120 mesh silica gel (25% ethyl acetate/hexane),
yielded the titled compound 4t (0.09 g, 50%) as white solid; mp
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