Meglumine promoted one-pot, four-component synthesis of pyranopyrazole derivatives

Article abstract of DOI:10.1016/j.tet.2013.09.082

Meglumine, a bio-based chemical, was demonstrated to be a highly efficient and reusable catalyst for the synthesis of a series of pyranopyrazole derivatives via a one-pot, four-component reaction of carbonyl compound or isatin, hydrazine hydrate, malononi

Full text of DOI:10.1016/j.tet.2013.09.082

Accepted Manuscript
Meglumine promoted one-pot, four-component synthesis of pyranopyrazole
derivatives
Rui-Yun Guo, Zhi-Min An, Li-Ping Mo, Shu-Tao Yang, Hong-Xia Liu, Shu-Xia Wang,
Zhan-Hui Zhang
PII:
S0040-4020(13)01504-4
10.1016/j.tet.2013.09.082
TET 24857
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 August 2013
Revised Date: 17 September 2013
Accepted Date: 27 September 2013
Please cite this article as: Guo R-Y, An Z-M, Mo L-P, Yang S-T, Liu H-X, Wang S-X, Zhang Z-H,
Meglumine promoted one-pot, four-component synthesis of pyranopyrazole derivatives, Tetrahedron
(2013), doi: 10.1016/j.tet.2013.09.082.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Meglumine promoted one-pot, four-component
synthesis of pyranopyrazole derivatives
Rui-Yun Guo, Zhi-Min An, Li-Ping Mo, Shu-Tao Yang, Hong-Xia Liu, Shu-Xia Wang, Zhan-Hui Zhang*
College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024, China

ACCEPTED MANUSCRIPT
Tetrahedron
1
Meglumine promoted one-pot, four-component synthesis of
pyranopyrazole derivatives
Rui-Yun Guo, Zhi-Min An, Li-Ping Mo, Shu-Tao Yang, Hong-Xia Liu, Shu-Xia Wang, Zhan-
Hui Zhang*
College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024, China
ABSTRACT—Meglumine, a bio-based chemical, was demonstrated to be a highly efficient and reusable catalyst for the synthesis of a
series of pyranopyrazole derivatives via a one-pot, four-component reaction of carbonyl compound or isatin, hydrazine hydrate,
malononitrile, and β-keto ester in EtOH-H2O. The catalyst was found to work extremely for aldehydes, ketones or isatins at room
temperature to give the corresponding dihydroprano[2,3-c]pyrazole or spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives in high yields.
The salient features of this new methodology are broad substrate scope, room temperature reaction conditions, short reaction times, high
yields, easy work-up process, reusability of catalyst and the absence of hazardous organic solvents. All rights reserved.
Keywords:
Pyranopyrazoles
Multicomponent reaction
One-pot synthesis
Meglumine
biodegradable material
group, primary and secondary hydroxyl groups and that
1. Introduction
can activate the nucleophilic as well as electrophilic
components of the reactions by hydrogen bonding and
donation of lone pair of electrons, respectively. Thus,
such organic molecule may constitute alternative catalyst
for the development of sustainable chemistry.
Meanwhile, multicomponent reactions (MCRs) are
known as a powerful tool for the construction of novel
and structurally complex molecules in a single pot
ensuring high atom-economy, good overall yields and
high selectivity, lower costs, shorter reaction times,
minimizing waste, labor, energy, and avoidance of
expensive purification processes. It has been established
that MCRs are generally much more environmentally
friendly, and offer rapid access to large compound
libraries with diverse functionalities.9
Potential biological activities and widespread
synthetic utilities of pyranopyrazoles have led to their
identification as a class of heterocyclic compounds
which has created considerable interest in the
pharmaceutical industry and in the diversified field of
organic synthesis.10 As a result, several strategies have
been developed for the synthesis of pyranopyrazoles
Following the increasing demand of “green
chemistry”, the search for more environmentally benign
forms of catalysis has received overwhelming attention,
and one of the leading contestant for environmentally
acceptable alternatives is biodegradable materials.
Although some
biodegradable materials such as
chitosan,1 gluconic acid,2 cellulose sulfuric acid,3
xanthan sulfuric acid,4 starch sulfuric acid,5 sulfuric acid-
modified PEG (PEG-OSO3H),6 and eggshell7 have been
proposed as catalysts in some organic transformations.
However, the number of available bio-based catalysts is
far from abundant at this stage. Recently, Gu et al.
introduced meglumine and gluconic acid aqueous
solution as a promoting medium and catalyst for the
multicomponent reaction of β-ketosulfones and
formaldehyde.8 Meglumine is an amino sugar derived
from sorbitol with molecular formula C7H17NO5. In
particular, the low toxicity of meglumine allows its use
in the formulation of pharmaceuticals as an excipient and
in conjunction with iodinated compounds in contrast
media such as diatrizoate meglumine and iodipamide
meglumine. Meglumine possesses environmentally
benign properties such as bio-degradablity and
physiological inertness. Additionally, meglumine is
inexpensive, non-corrosive, stabile to air and moisture
and readily available in the market. It contains an amino
_____________
through
a
two-component11 or three-component
reaction.12 Recently, Prasanna et al. have developed a
four-component domino reaction from hydrazines, β-
dicarbonyl compounds, nitriles in the presence of L-
proline for the synthesis of densely functionalized 4H-
pyrano[2,3-c]pyrazoles.13 Zonouz and co-workers
reported an efficient four-component reaction of
dimethyl acetylenedicarboxylate, hydrazinehydrate,
malononitrile, and aromatic aldehydes for the synthesis
* Corresponding author. fax: +86 311 80787431.
E-mail address: zhanhui@mail.nankai.edu.cn (Z.-H. Zhang)

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Tetrahedron
2
Table 1
of 2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates in
water.14 One-pot, four-component syntheses of diverse
pyranopyrazoles has also been accomplished and
consists of condensation of aldehydes, ethyl acetoacetate,
malononitrile and hydrazines. In this context, some
catalysts have been used to promote these condensations
such as Amberlyst A21,15 triethylamine,16 hexadecyl
dimethyl benzyl ammonium chloride (HDBAC),17 L-
proline,18 per-6-amino-β-cyclodextrin,19 γ-alumina,20
basic ionic liquids,21 or piperidine.22 Although these
methods are quite satisfactory, some of them suffer from
the absence of green chemistry, and have been associated
with several shortcomings such as the use of volatile and
hazardous organic solvents, low yields, extended
reaction time, high temperature, and tedious procedure
for the preparation of catalysts. Thus, the development of
general, economically and environmentally benign
synthetic methodologies for these heterocycles is highly
desirable.
The combination of multicomponent reactions, an
environmentally benign form of catalyst and a green
solvent has become a promising frontier field of research
in organic, medicinal and combinatorial chemistry.23
Considering the above subjects and continuing our
efforts on the development of new catalyst and
environmental benign synthetic methodologies,24 we
report here on the first example of meglumine-catalyzed
one-pot, four-component reaction of carbonyl compound,
hydrazine hydrate, malononitrile, and β-keto ester for the
synthesis of pyranopyrazole derivatives in ethanol-water
mixture at room temperature (Scheme 1).
Influence of different catalysts on the reaction of benzaldehyde, hydrazine
hydrate, malononitrile and ethyl acetoacetatea
Entry
1
2
3
4
5
6
7
8
9
10
11
12
Catalyst
No
K2CO3
CH3COONa
CH3COONH4
Al2O3
CeO2
ZnO
CuO
MgO
Time (min)
Yield (%)
5
60
60
60
60
60
60
60
60
60
60
60
15
41
29
35
26
31
28
26
21
22
66
95
Et3N
L-Proline
Meglumine
a
Experimental conditions: benzaldehyde (1 mmol), hydrazine hydrate (1
mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol), catalyst (10
mol%), EtOH-H2O (9:1, 2 ml).
With regard to the choice of solvents, we carried out
the above reaction in various solvents. As shown in
Table 2, when the reaction was performed under solvent-
free conditions, low yield of target product was obtained.
To find the best solvent for this transfortion, the present
four-component reaction was screened in H2O, PEG 400,
i
THF, PrOH, MeOH, EtOH and ethanol-water mixture.
Among all these solvents, ethanol-water mixture (9:1)
was found to be the best one and afforded the highest
yield (Table 2, entry 9). Therefore, aqueous ethanol was
selected as the solvent system for the subsequent
reaction. Then the amount of the catalyst was evaluated
in the model reaction at room temperature in EtOH-H2O
(9:1). The results showed that 10 mol% of catalyst was
the best choice for the completing the reaction and the
use of excessive catalyst had no impact either on the rate
Scheme 1. Synthesis of pyranopyrazole derivatives.
2. Results and discussion
of the reaction or on the product yield.
Table 2
Optimization of reaction conditionsa
Catalyst loading
Initially, we selected benzaldehyde (1 mmol),
hydrazine hydrate (1 mmol), malononitrile (1 mmol),
ethyl acetoacetate (1 mmol) as model substrates to
establish optimum reaction conditions. When the
reaction was attempted without a catalyst, it was found
that only a low yield of product was obtained even after
1 h (Table 1, entry 1). This result suggests that a
catalyst plays a critical role in this reaction. A
number of catalysts such as K2CO3, CH3COONa,
CH3COONH4, Al2O3, CeO2, ZnO, CuO, MgO, Et3N, and
L-proline were examined to promote this transformation
at room temperature. In comparison with these catalyst,
meglumine proved to be the most efficient one which
gave higher yield (95%) with 15 min (Table 1, entry 12).
Entry
Solvent
Time (min) Yield (%)
(mol%)
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
5
no
H2O
60
60
60
60
60
60
15
15
10
30
62
76
81
88
92
90
95
93
94
93, 92, 90
PEG 400
THF
iPrOH
MeOH
EtOH
EtOH: H2O (9:1)
9
10
EtOH: H2O (9:1)
15
10
15
10
10
EtOH: H2O (9:1)
EtOH: H2O (9:1)
EtOH: H2O (9:1)
15
15
15
11b
12c
a
Experimental conditions: benzaldehyde (1 mmol), hydrazine hydrate (1
mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol), solvent (2
ml). b 50 mmol scale. c Catalyst was reused three times.
In addition, in order to demonstrate practical

ACCEPTED MANUSCRIPT
Tetrahedron
3
usefulness of the present method, the model reaction was
carried out in a scale of 50 mmol. As expected, the
desired product could be obtained through
recrystalization with 94% yield in 15 min. In this
protocol, the product was separated from the reaction
mixture by simple filtration, as it is not soluble in water
and ethanol, while meglumine and the starting materials
are soluble. The possibility of recycling the catalyst was
examined in the model reaction. As shown in Table 2,
meglumine can be reused three times without significant
decrease in catalytic activity, the yields ranged from 93%
to 90%.
Encouraged by the efficiency of the reaction protocol
described above, the scope and specificity of this
protocol were further investigated. Firstly, a broad range
of structurally diverse aldehydes were treated with
hydrazine hydrate, malononitrile, and ethyl acetoacetate
and the results are depicted in Table 3. As evident from
Table 3, all reactions proceeded efficiently and the
desired products were obtained in high to excellent
yields in relatively short times without formation of any
by-products. The nature of the functional group on the
aromatic ring of the aldehyde exerted a slightly influence
on the reaction time. A decrease of the reaction rate was
observed with arylaldehyde carrying an electron-
donating group in comparison to the unsubstituted
benzaldehyde. The reaction was also sensitive to the
steric environment of the aromatic aldehyde, and longer
Having been inspired by these results, we have
scrutinized the reactions of various of ketones. An
extensive literature survey reveals that there are
relatively fewer methods to synthesize pyranopyrazole
derivatives from ketones due to the low reactivity of
ketones as compared to aldehydes. Without any
optimization, we were pleased to find that cyclic ketones
such as cyclopenyanone, cyclohexanone and as well as
alkyl-alkyl ketones, and aryl-alkyl ketones also
underwent this one-pot conversion to afford the
respective ketone-derived dihydroprano[2,3-c]pyrazoles
in high yields under these conditions, albeit with a
prolonged reaction time.
Istain is a privilieged lead molecule for designing
potential pharmacological agents, and its derivatives
have been shown to possess a broad spectrum of
bioactivity. These interesting properties promoted us to
widen the applicability of this procedure with isatins.
Recently, Shestopalov and co-workers reported one-pot,
two-step reaction of istain, hydrazine hydrate,
malononitrile, and β-keto ester for synthesis of
spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives in
the presence of Et3N in refluxing EtOH.16 Pleasantly, we
found that one-step preparation of spiro[indoline-3,4'-
pyrano[2,3-c]pyrazole] derivatives (7) could be
accomplished using various isatins having electron-
neutral, electron-deficient, and electron-rich substituents
on the aryl ring under above optimized conditions (Table
4).
reaction times were required for
benzaldehyde
containing substituens at 2-position (Table 3, entries 2, 7,
12, 15 and 19). Heteroatomatic aldehydes, such as furan-
2-carbaldehyde, thiophene-2-carbaldehyde, pyridine-4-
carbaldehyde readily participated in this transformation,
affording the potentially bio-important pyranopyrazoles
in high yields (Table 3, entries 24-26). Furthermore, 1-
naphthaldehyde was found to be a good substrate, and
the target compound was obtained in 89% yield.
It is pertinent to note that aliphatic aldehydes are not
appropriate starting materials in many reported
procedures due to form unwanted byproducts via various
side reactions such as aldo condensation and the
Cannizzaro reaction. Fortunately, this meglumine-
catalyzed transformation is not limited to aliphatic
aldehydes and gave the pyranopyrazole product in high
yields (Table 3, entries 28 and 29). Additionally, when
the ethyl acetoacetate was switched to ethyl
propionylacetate under above conditions, it exhibited
analogous behavior to ethyl acetoacetate (Table 3,
entries 30-32).
To explore the scope of this reaction to form new
spiroheterocyclic compounds, we investigated the use of
acenaphtylene-1,2-dione (8) as a substrate to react with
hydrazine hydrate, malononitrile, ethyl acetoacetate
under the optimized conditions. As expected the reaction
proceeded well to afford spiro[acenaphthylene-1,4'-
pyrano[2,3-c]pyrazole] derivative (9) in 35 min with
90% yield (Scheme 2). These successful results clearly
indicate that the present catalytic approach is extendable
to a wide variety of substrates.
Scheme 2. Synthesis of spiro[acenaphthylene-1,4'-pyrano[2,3-c]pyrazole]

ACCEPTED MANUSCRIPT
Tetrahedron
4
Table 3
Synthesis of dihydroprano[2,3-c]pyrazole 5 from carbonyl compounds
Entry
1
Carbonyl compounds
R3
Product
5a
Time (min)
15
30
20
18
17
20
25
17
22
20
20
16
10
11
22
12
15
17
13
10
7
Yield (%)a
95
90
91
92
93
91
89
90
91
90
91
92
91
92
90
92
95
92
92
93
94
94
93
90
92
90
89
85
86
90
90
92
m.p. (oC)
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
243-244 (244-245)21a
249-250 (251-252)21a
210-212 (211-213)21a
175-176
PhCHO
2
5b
5c
2-OCH3C6H4CHO
4-OCH3C6H4CHO
4-CH3(CH2)2OC6H4CHO
4-CH3(CH2)4OC6H4CHO
2-OMe-5-CHMe2C6H3CHO
2,3,4-(OMe)3C6H2CHO
3-CH3C6H4CHO
3
4
5d
5e
5
240-242
6
5f
163-164
7
5g
223-225
170-171 (170-172)19
8
5h
5i
9
223-225
4-C(CH3)3C6H4CHO
4-SCH3C6H4CHO
4-OHC6H4CHO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
5j
219-220
5k
5l
223-224 (224-226)21a
261-262 (260-261)25
242-243 (245-246)25
244-245 (245-246)21a
245-246 (246-247)21a
230-231 (231-232)16
234-235 (233-234)21a
229-230
2-FC6H4CHO
5m
5n
5o
3-FC6H4CHO
4-FC6H4CHO
2-ClC6H4CHO
5p
5q
5r
3-ClC6H4CHO
4-ClC6H4CHO
2,4-Cl2C6H3CHO
2-NO2C6H4CHO
5s
243-244 (241-244)21a
248-249 (251-252)21a
201-202
5t
4-NO2C6H4CHO
5u
5v
3-CF3C6H4CHO
8
243-244 (244-245)26
4-CF3C6H4CHO
5w
5x
20
17
12
23
30
60
20
15
23
20
206-207
4-((4-Nitrobenzyl)oxy)benzaldehyde
Furan-2-carbaldehyde
Thiophene-2-carbaldehyde
Pyridine-4-carbaldehyde
1-Naphthaldehyde
Decanal
230-231 (232-234)21a
224-226 (221-223)27
216-217 (214-215)15
223-224 (226-228)21a
145-146
5y
5z
5aa
5ab
5ac
5ad
5ae
5af
170-171 (172-173)19
Cyclohexanecarbaldehyde
PhCHO
216-217
Et
193-195
4-OCH3C6H4CHO
Et
218-220
4-ClC6H4CHO
O
33
34
35
36
37
Me
Me
Me
Me
Me
5ag
5ah
5ai
60
92
90
91
92
90
176-177 (175)28
540
540
540
540
161-162
165-166 (164-165)15
148-149 (147-148)15
196-197
5aj
5ak

ACCEPTED MANUSCRIPT
Tetrahedron
5
O
38
39
Me
Me
5al
480
480
86
85
178-179 (177-178)15
184-185 (183-184)15
5am
40
41
Me
Me
5an
5ao
360
300
87
88
183-184 (181-182)15
220-221
a Isolated yield.
Table 4.
Synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] 7 from isatins
Entry
R
Product
7a
Time (min)
Yield (%)a
m.p. (oC)
1
2
3
4
5
6
35
40
27
30
27
25
92
85
90
92
93
93
286-287 (285-286)29
282-283 (279-281)29
275-276 (274-275)29
298-299 (297-298)29
283-284(282-283)29
273-274(270-271)30
H
7b
Me
F
7c
7d
Cl
7e
Br
NO2
7f
a Isolated yield.
Subsequent experiment showed that the formation of
ylidenemalononitrile via Knoevenagel condensation of
acetophenone and malononitrile was slower than istain in
the presence of meglumine, which might be the part
reason for longer time requirement for four-component
reaction of ketones, hydrazine hydrate, malononitrile,
and β-keto ester.
On the basis of the above results and previous
studies,19
plausible mechanism can reasonably
a
proposed for the synthesis of pyranopyrazole 5a from
benzaldehyde, hydrazine hydrate, malononitrile and
ethyl acetoacetate (Scheme 3). We think that the
presence of the amino group in the structure of
meglumine plays a major role in its promoting activity
for the formation of ylidenemalononitrile (I) from
Knoevenagel condensation of benzaldehyde and
malononitrile. The 3-methyl-1H-pyrazol-5(4H)-one (I)
was formed from the condensation of ethyl acetoacetate
and hydrazine, which would be converted to its
corresponding enolate form II in the presence of
meglumine. Subsequent Michael-type addition of II to
the intermediate I to produce intermediated IV, which
underwent intramolecular cyclization by the nucleophilic
addition of enolate oxygen to nitrile group to generate
intermediate V. Finally, the tautomerization of
intermediate V gave dihydropyrano[2,3-c]pyrazole 5a.
Scheme 3. Plausible mechanism for synthesis of pyrrole derivatives.

ACCEPTED MANUSCRIPT
Tetrahedron
6
4.2
Typical
procedure
for
synthesis
of
Finally, in order to show the efficiency of the
proposed method, meglumine was compared with other
catalysts reported earlier for the synthesis of 5a. As
demonstrated in Table 5, the use of meglumine leads to
an improved protocol in terms of compatibility with
environment, reaction time, and yield when compared
with other catalyst.
dihydropyrano[2,3-c]pyrazoles
Meglumine (10 mol%) was added to a mixture of
carbonyl compound (1, 1 mmol), hydrazine hydrate (2, 1
mmol), malononitrile (3, 1 mmol), and β-keto ester (4, 1
mmol) in EtOH-H2O (9:1, 2 ml). The resulting mixture was
stirred at room temperature. After completion of the
reaction (monitored by TLC), the precipitated product was
filtered and washed with aqueous ethanol (5 ml). The crude
product was purified by recrystallization from ethanol to
afford the desired product. In order to recover the catalyst,
the filtrate was dried under reduced pressure and recovered
catalyst was washed with diethyl ether (2 ml) twice and
reused after drying.
Table 5 Comparison of our results with previously reported methods
Catalyst
Reaction conditions
Time (min) Yield (%)
Entry
Amberlyst A21 (50 mg) EtOH, rt
25
15
45
9015
6516
7317
9018a
9018a
8020
8821a
1
2
3
4
5
6
7
Et3N (20 mol%)
EtOH, reflux
EtOH, reflux
HDBAC (30 mol%)
L-Proline (10 mol%)
L-Proline (10 mol%)
γ-Alumina (30 mol%)
[Bmim]BF4, 50 oC 10
H2O, reflux
H2O, reflux
10
50
10
4.3 Characterization data
[bmim]OH (20 mol%) 50-60 oC
Piperidine (5 mol%)
H2O, rt
10
8322
8
9
4.3.1
6-Amino-3-methyl-4-(4-propoxy-phenyl)-1,4-
Meglumine (10 mol%) EtOH: H2O (9:1), rt 15
95
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5d). White
solid; IR (KBr): 3473, 3236, 2189, 1641, 1597, 1491, 1402,
1255, 1055, 981, 746 cm-1; 1H NMR (DMSO-d6, 500 MHz)
δ 0.97 (t, J = 7.5 Hz, 3H, CH3), 1.67-1.74 (m, 2H, CH2),
1.78 (s, 3H, CH3), 3.88 (t, J = 6.5 Hz, 2H, CH2), 4.52 (s, 1H,
CH), 6.82 (s, 2H, NH2), 6.85 (d, J = 8.5 Hz, 2H, HAr), 7.05
(d, J = 8.0 Hz, 2H, HAr), 12.1 (s, 1H, NH) ppm; 13C NMR
(DMSO-d6, 125 MHz) δ 10.2, 10.9, 22.3, 35.9, 58.0, 69.3,
98.4, 114.7, 121.3, 128.9, 136.0, 136.8, 155.2, 157.9, 161.1
ppm; Anal. Calcd for C17H18N4O2: C, 65.79; H, 5.85; N,
18.05. Found: C, 65.61; H, 5.62; N, 17.90.
3. Conclusion
In summary, we have developed a highly efficient
and greener approach for the one-pot, four-component
synthesis of pyranopyrazole derivatives using
meglumine as an inexpensive, biodegradable and reused
catalyst. This method was found not only to applied to
aromatic, heteroaromatic, and aliphatic aldehydes, but
also to be useful for synthesis of ketone-derived
dihydroprano[2,3-c]pyrazole and spiro[indoline-3,4'-
pyrano[2,3-c]pyrazole] derivatives. The merits for the
presented methodology are its efficient, generality, wide
scope of substrates, high yield, short reaction time,
simplicity, no elevated temperature, ease of product
isolation, cleaner reaction profile, evasion of hazardous
catalysts or solvents, and agreement with the green
chemistry protocols, which make it a useful and
attractive process for the synthesis of pyranopyrazoles.
4.3.2
6-Amino-3-methyl-4-(4-pentyloxy-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5e). White
solid; IR (KBr): 3444, 3238, 2195, 1637, 1600, 1491, 1394,
1236, 1055, 869, 756 cm-1; 1H NMR (DMSO-d6, 500 MHz)
δ 0.89 (t, J = 6.5 Hz, 3H, CH3), 1.32-1.41 (m, 4H, 2CH2),
1.68-1.71 (m, 2H, CH2), 1.78 (s, 3H, CH3), 3.92 (t, J = 6.0
Hz, 2H, CH2), 4.52 (s, 1H, CH), 6.82 (s, 2H, NH2), 6.84 (d,
J = 8.0 Hz, 2H, HAr), 7.05 (d, J = 8.0 Hz, 2H, HAr), 12.1 (s,
1H, NH) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 10.2,
14.4, 22.4, 28.2, 28.9, 35.9, 58.0, 67.8, 98.4, 114.7, 121.3,
128.9, 136.0, 136.8, 155.2, 157.9, 161.1 ppm; Anal. Calcd
for C19H22N4O2: C, 67.44; H, 6.55; N, 16.56. Found: C,
67.62; H, 6.73; N, 16.38.
4. Experimental
4.1 General information
All solvents and chemicals were obtained commercially
and were used as received. All known compounds were
identified by comparison of their melting points and H
4.3.3 6-Amino-3-methyl-4-(5-isopropyl-2-methoxy-phenyl)-
1
1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5f).
NMR data with those in the authentic samples. Melting
points were determined using an X-4 apparatus and are
uncorrected. IR spectra were taken as KBrdiscs with a
Bruker-TENSOR 27 spectrometer. NMR spectra were
recorded on a Bruker DRX-500 spectrometer at 500 MHz
(1H) and 125 MHz (13C) using DMSO-d6 as the solvent with
TMS as internal standard. Elemental analyses were
obtained on a Vario EL III CHNOS elemental analyzer.
White solid; IR (KBr): 3375, 3173, 2195, 1647, 1602, 1487,
1396, 1249, 1105, 870 cm-1; 1H NMR (DMSO-d6, 500 MHz)
δ 1.11 (d, J = 7.0 Hz, 6H, 2CH3), 1.78 (s, 3H, CH3), 2.73-
2.79 (m, 1H, CH), 3.73 (s, 3H, OCH3), 4.91 (s, 1H, CH),
6.78 (s, 2H, NH2), 6.83 (d, J = 1.5 Hz, 1H, HAr), 6.91 (d, J
= 8.5 Hz, 1H, HAr), 7.07 (dd, J = 8.5 Hz, J = 2.0 Hz, 1H,
HAr), 12.0 (s, 1H, NH) ppm; 13C NMR (DMSO-d6, 125
MHz) δ 10.0, 24.5, 24.6, 33.0, 56.1, 56.7, 98.3, 111.8, 121.4,
125.6, 127.0, 132.0, 135.5, 140.9, 155.1, 155.6, 161.9 ppm;
Anal. Calcd for C18H20N4O2: C, 66.65; H, 6.21; N, 17.27.
Found: C, 66.83; H, 6.05; N, 12.46.
4.3.4 6-Amino-3-methyl-4-(2,3,4-trimethoxy-phenyl)-1,4-

ACCEPTED MANUSCRIPT
Tetrahedron
7
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5g). White
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5s). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.80 (s, 3H, CH3),
5.12 (s, 1H, CH), 7.08 (s, 2H, NH2), 7.35 (d, J = 8.0 Hz, 1H,
HAr), 7.53 (t, J = 7.0 Hz, 1H, HAr), 7.70 (t, J = 7.5 Hz, 1H,
HAr), 7.88 (d, J = 8.0 Hz, 1H, HAr), 12.2 (s, 1H, NH) ppm.
1
solid; IR (KBr): 3392, 3306, 3173, 2187, 1641, 1600, 1491,
1
1392, 1101, 898 cm-1; H NMR (DMSO-d6, 500 MHz) δ
1.78 (s, 3H, CH3), 3.66 (s, 3H, OCH3), 3.73 (s, 3H, OCH3),
3.76 (s, 3H, OCH3), 4.72 (s, 1H, CH), 6.71-6.76 (m, 2H,
HAr), 6.79 (s, 2H, NH2), 12.0 (s, 1H, NH) ppm; 13C NMR
(DMSO-d6, 125 MHz) δ 9.91, 31.0, 56.1, 57.3, 60.7, 61.3,
98.5, 108.4, 121.5, 123.8, 130.1, 135.6, 141.9, 151.6, 152.6,
155.4, 161.5 ppm; Anal. Calcd for C17H18N4O4: C, 59.64; H,
5.30; N, 16.37. Found: C, 59.80; H, 5.56; N, 16.53.
4.3.11 6-Amino-3-methyl-4-(3-trifluoromethyl-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5u). White
solid; IR (KBr): 3481, 3238, 2191, 1637, 1597, 1491, 1404,
1
1122, 1057, 794 cm-1; H NMR (DMSO, 500 MHz) δ 1.78
(s, 3H, CH3), 4.80 (s, 1H, CH), 7.00 (s, 2H, NH2), 7.47 (d, J
= 7.0 Hz, 1H, HAr), 7.53 (s, 1H, HAr), 7.56-7.63 (m, 2H,
HAr), 12.2 (s, 1H, NH) ppm; 13C NMR (DMSO, 125 MHz)
4.3.5
6-Amino-3-methyl-4-(4-tert-butyl-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5i). White
3
solid; IR (KBr): 3493, 3244, 2195, 1633, 1597, 1491, 1398,
δ 10.1, 36.3, 56.8, 97.4, 121.0, 124.1 (q, JFC = 3.8 Hz),
1055, 761 cm-1; H NMR (DMSO-d6, 500 MHz) δ 1.26 (s,
1
124.2 (q, 3JFC = 3.6 Hz), 124.8 (q, 1JFC = 270.3 Hz), 129.5 (q,
2JFC = 31.4 Hz), 130.3, 132.2, 136.3, 146.3, 151.2, 161.5
ppm; Anal. Calcd for C15H11F3N4O: C, 56.25; H, 3.46; N,
17.49. Found: C, 56.41; H, 3.28; N, 17.65.
9H, 3CH3), 1.79 (s, 3H, CH3), 4.55 (s, 1H, CH), 6.86 (s, 2H,
NH2), 7.07 (d, J = 8.0 Hz, 2H, HAr), 7.33 (d, J = 7.5 Hz,
2H, HAr), 12.1 (s, 1H, NH) ppm; 13C NMR (DMSO-d6, 125
MHz) δ 10.3, 31.6, 34.6, 36.2, 57.7, 98.3, 121.4, 125.6,
127.5, 135.9, 141.9, 149.3, 155.2, 161.4 ppm; Anal. Calcd
for C18H20N4O: C, 70.11; H, 6.54; N, 18.17. Found: C,
69.89; H, 6.38; N, 17.90.
4.3.12 6-Amino-3-methyl-4-[3-(4-nitro-benzyloxy)-phenyl]-
1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5w).
White solid; IR (KBr): 3462, 3331, 2185, 1633, 1606, 1508,
1
1398, 1267, 1107 cm-1; H NMR (DMSO-d6, 500 MHz) δ
4.3.6 6-Amino-3-methyl-4-(4-methylsulfanyl-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5j). White
solid; IR (KBr): 3483, 3254, 2191, 1641, 1608, 1492, 1390,
1.78 (s, 3H, CH3), 4.55 (s, 1H, CH), 5.25 (s, 2H, CH2), 6.84
(s, 2H, NH2), 6.97 (d, J = 8.5 Hz, 2H, HAr), 7.09 (d, J = 8.5
Hz, 2H, HAr), 7.72 (d, J = 8.5 Hz, 2H, HAr), 8.25 (d, J =
8.5 Hz, 2H, HAr), 12.1 (s, 1H, NH) ppm; 13C NMR
(DMSO-d6, 125 MHz) δ 10.2, 35.9, 57.9, 68.5, 98.3, 115.1,
121.3, 124.1, 128.7, 129.1, 136.0, 137.6, 145.6, 147.5,
155.2, 157.2, 161.2 ppm; Anal. Calcd for C21H17N5O4: C,
62.53; H, 4.25; N, 17.36. Found: C, 62.38; H, 4.42; N,
17.18.
1053, 796 cm-1; H NMR (DMSO-d6, 500 MHz) δ 1.79 (s,
1
3H, CH3), 2.45 (s, 3H, SCH3), 4.56 (s, 1H, CH), 6.88 (s, 2H,
NH2), 7.10 (d, J = 8.0 Hz, 2H, HAr), 7.19 (d, J = 8.0 Hz,
2H, HAr), 12.1 (s, 1H, NH) ppm; 13C NMR (DMSO, 125
MHz) δ 10.2, 15.1, 36.1, 57.6, 97.8, 121.3, 126.4, 128.6,
136.1, 136.7, 141.6, 155.2, 161.3 ppm; Anal. Calcd for
C15H14N4OS: C, 60.38; H, 4.73; N, 18.78. Found: C, 60.10;
H, 4.56; N, 18.90.
4.3.13
6-Amino-4-(furan-2-yl)-3-methyl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5x). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.97 (s, 3H, CH3),
4.77 (s, 1H, CH), 6.17 (d, J = 3.0 Hz, 1H, HAr), 6.37 (t, J =
2.0 Hz, 1H, HAr), 6.96 (s, 2H, NH2), 7.53 (d, J = 1.0 Hz,
1H, HAr), 12.2 (s, 1H, NH) ppm.
4.3.7
6-Amino-4-(2-fluorophenyl)-3-methyl-1,4-
1
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5l). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.78 (s, 3H, CH3),
4.63 (s, 1H, CH), 6.91 (s, 2H, NH2), 7.14 (t, J = 9.0 Hz, 2H,
HAr), 7.19-7.22 (m, 2H, HAr), 12.1 (s, 1H, NH) ppm.
1
4.3.14
6-Amino-3-methyl-4-(thiophen-2-yl)-1,4-
4.3.8
6-Amino-4-(2-chlorophenyl)-3-methyl-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5y). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.95 (s, 3H, CH3),
5.03 (s, 1H, CH), 6.96-6.99 (m, 3H, HAr, NH2), 7.04 (d, J =
3.0 Hz, 1H, HAr), 7.41 (d, J = 5.0 Hz, 1H, HAr), 12.2 (s,
1H, NH) ppm.
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5o). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.76 (s, 3H, CH3),
5.06 (s, 1H, CH), 6.96 (s, 2H, NH2), 7.17 (d, J = 7.0 Hz, 1H,
HAr), 7.24-7.27 (m, 1H, HAr), 7.31 (t, J = 7.5 Hz, 1H,
HAr), 7.41 (d, J = 8.0 Hz, 1H, HAr), 12.1 (s, 1H, NH) ppm.
1
1
4.3.15
6-Amino-3-methyl-4-(pyridin-4-yl)-1,4-
4.3.9
6-Amino-3-methyl-4-(2,4-dichloro-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5r). White
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5z). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.82 (s, 3H, CH3),
4.66 (s, 1H, CH), 7.04 (s, 2H, NH2), 7.19 (d, J = 6.0 Hz, 2H,
HAr), 8.52 (d, J = 5.0 Hz, 2H, HAr), 12.2 (s, 1H, NH) ppm.
1
solid; IR (KBr): 3481, 3252, 2187, 1643, 1593, 1492, 1410,
1058, 871 cm-1; H NMR (DMSO-d6, 500 MHz) δ 1.77 (s,
1
3H, CH3), 5.06 (s, 1H, CH), 7.02 (s, 2H, NH2), 7.21 (d, J =
7.0 Hz, 1H, HAr), 7.40 (d, J = 8.0 Hz, 1H, HAr), 7.59 (s,
1H, HAr), 12.2 (s, 1H, NH) ppm; 13C NMR (DMSO-d6, 125
MHz) δ 10.0, 33.6, 55.7, 96.8, 120.7, 128.5, 129.3, 132.6,
133.3, 135.9, 140.6, 155.4, 161.8 ppm; Anal. Calcd for
C14H10Cl2N4O: C, 52.36; H, 3.14; N, 17.45. Found: C,
52.53; H, 2.88; N, 17.62.
4.3.16 6-Amino-3-methyl-4-octyl-1,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (5ab). White solid; IR (KBr):
3471, 3257, 2187, 1643, 1404, 1051, 723 cm-1; H NMR
1
(DMSO-d6, 500 MHz) δ 0.83 (t, J = 7.0 Hz, 3H, CH3), 0.96-
0.98 (m, 1H, CH), 1.16-1.25 (m, 11H, CH2), 1.54-1.60 (m,
2H, CH2), 2.14 (s, 3H, CH3), 3.55 (t, J = 4.0 Hz, 1H, CH),
6.77 (s, 2H, NH2), 12.0 (s, 1H, NH) ppm; 13C NMR
4.3.10
6-Amino-3-methyl-4-(2-nitrophenyl)-1,4-

ACCEPTED MANUSCRIPT
Tetrahedron
8
(DMSO-d6, 125 MHz) δ 10.6, 14.4, 22.5, 24.2, 29.1, 29.4,
21.86.
29.5, 30.1, 31.7, 35.3, 55.6, 97.3, 121.5, 135.3, 156.1, 162.3
ppm; Anal. Calcd for C16H24N4O: C, 66.64; H, 8.39; N,
19.43. Found: C, 66.81; H, 8.20; N, 19.62.
4.3.22
6-Amino-3,4-dimethyl-4-(4-nitro-phenyl)-1,4-
dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile (5ao). White
solid; IR (KBr): 3439, 2980, 2185, 1645, 1516, 1349, 1026,
1
4.3.17 6-Amino-3-ethyl-4-phenyl-1,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (5ad). White solid; IR (KBr):
3423, 3171, 2185, 1651, 1608, 1489, 1402, 1043, 871 cm-1;
1H NMR (DMSO-d6, 500 MHz) δ 0.76 (t, J = 7.5 Hz, 3H,
CH3), 2.12-2.19 (m, 2H, CH2), 4.60 (s, 1H, CH), 6.87 (s, 2H,
NH2), 7.16 (d, J = 7.5 Hz, 2H, HAr), 7.22 (t, J = 7.0 Hz, 1H,
HAr), 7.31 (t, J = 7.0 Hz, 1H, HAr), 12.1 (s, 1H, NH) ppm;
13C NMR (DMSO-d6, 125 MHz) δ 12.9, 18.3, 36.8, 57.9,
97.4, 121.3, 127.2, 127.9, 128.9, 141.6, 145.3, 155.2, 161.2
ppm; Anal. Calcd for C15H14N4O: C, 67.65; H, 5.30; N,
21.04. Found: C, 67.83; H, 5.15; N, 20.86.
763 cm-1; H NMR (DMSO-d6, 500 MHz) δ 1.79 (s, 3H,
CH3), 1.81 (s, 3H, CH3), 6.97 (s, 2H, NH2), 7.52 (d, J = 9.0
Hz, 2H, HAr), 8.18 (d, J = 9.0 Hz, 2H, HAr), 12.2 (s, 1H,
NH) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 10.6, 27.4,
38.4, 63.9, 102.0, 120.1, 123.9, 128.4, 135.9, 146.2, 154.3,
155.3, 160.7 ppm; Anal. Calcd for C15H14N4O: C, 67.65; H,
5.30; N, 21.04. Found: C, 67.48; H, 5.52; N, 20.86.
4.3.23 6'-Amino-3'-methyl-2-oxo-1'H-spiro[indoline-3,4'-
pyrano[2,3-c]pyrazole]-5'-carbonitrile (7a). White solid;
1H NMR (DMSO-d6, 500 MHz) δ 1.52 (s, 3H, CH3), 6.90 (d,
J = 7.5 Hz, 1H, HAr), 6.98-7.04 (m, 2H, HAr), 7.22-7.25
(m, 3H, HAr, NH2), 10.6 (s, 1H, NH), 12.3 (s, 1H, NH)
ppm.
4.3.18
6-Amino-3-ethyl-4-(4-methyl-phenyl)-1,4-
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5ae). White
solid; IR (KBr): 3234, 3119, 2189, 1639, 1489, 1406, 1033,
1
752 cm-1; H NMR (DMSO-d6, 500 MHz) δ 0.80 (t, J = 7.5
4.3.24
6'-Amino-3',5-dimethyl-2-oxo-1'H-spiro[indoline-
Hz, 3H, CH3), 2.11-2.18 (m, 2H, CH2), 3.72 (s, 3H, CH3),
4.55 (s, 1H, CH), 6.81 (s, 2H, NH2), 6.86 (d, J = 8.5 Hz, 2H,
HAr), 7.07 (d, J = 8.0 Hz, 2H, HAr), 12.1 (s, 1H, NH) ppm;
13C NMR (DMSO-d6, 125 MHz) δ 13.0, 18.3, 36.0, 55.5,
58.3, 97.6, 114.2, 121.3, 129.0, 137.3, 141.6, 155.2, 158.5,
161.0 ppm; Anal. Calcd for C16H16N4O2: C, 64.85; H, 5.44;
N, 18.91. Found: C, 65.02; H, 5.26; N, 19.09.
3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile (7b). White
solid; H NMR (DMSO-d6, 500 MHz) δ 1.54 (s, 3H, CH3),
2.22 (s, 3H, CH3), 6.78-6.84 (m, 2H, HAr), 7.04 (d, J = 7.0
Hz, 1H, HAr), 7.20 (s, 2H, NH2), 10.5 (s, 1H, NH), 12.3 (s,
1H, NH) ppm.
1
4.3.25 6'-amino-5-fluoro-3'-methyl-2-oxo-1,2-dihydro-1'H-
spiro[indole-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile
(7c). White solid; IR (KBr): 3410, 3346, 3221, 2187, 1707,
4.3.19
6-Amino-3-ethyl-4-(4-chloro-phenyl)-1,4-
1
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5af). White
solid; IR (KBr): 3485, 3232, 2187, 1641, 1593, 1491, 1408,
1062, 750 cm-1; 1H NMR (DMSO-d6, 500 MHz) δ 0.80 (t, J
= 7.0 Hz, 3H, CH3), 2.13-2.18 (m, 2H, CH2), 4.65 (s, 1H,
CH), 6.92 (s, 2H, NH2), 7.19 (d, J = 8.0 Hz, 2H, HAr), 7.37
(d, J = 8.0 Hz, 2H, HAr), 12.2 (s, 1H, NH) ppm; 13C NMR
(DMSO-d6, 125 MHz) δ 12.9, 18.3, 36.1, 57.4, 97.0, 121.1,
128.9 129.9, 131.7, 141.7, 144.4, 155.1, 161.2 ppm; Anal.
Calcd for C15H13ClN4O: C, 59.91; H, 4.36; N, 18.63. Found:
C, 60.10; H, 4.52; N, 18.80.
1581, 1500, 1485, 1408, 1301, 1057, 792 cm-1; H NMR
(DMSO-d6, 500 MHz) δ 1.57 (s, 3H, CH3), 6.89-6.91 (m,
1H, HAr), 6.98 (d, J = 8.0 Hz, 1H, HAr), 7.08 (t, J = 8.5 Hz,
1H, HAr), 7.28 (s, 2H, NH2), 10.6 (s, 1H, NH), 12.3 (s, 1H,
NH) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 9.5, 48.3,
3
2
55.1, 95.3, 111.1 (d, JCF = 7.6 Hz), 112.7 (d, JCF = 24.5
2
3
Hz), 115.8 (d, JCF = 23.6 Hz), 119.1, 134.9 (d, JCF = 9.0
Hz), 135.2, 138.2, 155.7, 159.0 (d, JCF = 236.8 Hz), 162.9
1
ppm; Anal. Calcd for C15H10FN5O2: C, 57.88; H, 3.24; N,
22.50. Found: C, 57.70; H, 3.52; N, 22.35.
4.3.20
6'-Amino-3'-methyl-1'H-spiro[cyclobutane-1,4'-
4.3.26
6'-Amino-5-chloro-3'-methyl-2-oxo-1'H-
pyrano[2,3-c]pyrazole]-5'-carbonitrile (5ah). White solid;
spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile
(7d). White solid; 1H NMR (DMSO-d6, 500 MHz) δ 1.61 (s,
3H, CH3), 6.96 (d, J = 8.0 Hz, 1H, HAr), 7.08 (d, J = 2.0 Hz,
1H, HAr), 7.33-7.35 (m, 3H, HAr, NH2), 10.8 (s, 1H, NH),
12.4 (s, 1H, NH) ppm.
IR (KBr): 3342, 3107, 2189, 1649, 1390, 995 cm-1; H
1
NMR (DMSO-d6, 500 MHz) δ 1.93-2.00 (m, 2H, CH2),
2.37-2.45 (m, 7H, CH2, CH3), 6.71 (s, 2H, NH2), 12.1 (s,
1H, NH) ppm; 13C NMR (DMSO-d6, 125 MHz) δ 11.0, 13.9,
35.3, 37.3, 63.5, 102.6, 121.0, 135.4, 154.2, 159.8 ppm;
Anal. Calcd for C11H12N4O: C, 61.10; H, 5.59; N, 25.91.
Found: C, 60.91; H, 5.78; N, 26.06.
4.3.27
6'-amino-3'-methyl-2-oxo-2H,2'H-
spiro[acenaphthylene-1,4'-pyrano[2,3-c]pyrazole]-5'-
carbonitrile (9). Light yellow solid, mp: 245-246 °C (lit.31
mp: 246 oC); IR (KBr): 3416, 3300, 2189, 1701, 1608, 1406
4.3.21 6'-Amino-3',4-dimethyl-1'H-spiro[cyclohexane-1,4'-
pyrano[2,3-c]pyrazole]-5'-carbonitrile (5ak). White solid;
IR (KBr): 3471, 3244, 2179, 1629, 1491, 1406, 1053, 717
cm-1; 1H NMR (DMSO-d6, 500 MHz) δ 0.93 (d, J = 6.0 Hz,
3H, CH3), 1.46-1.52 (m, 2H, CH2), 1.73 (d, J = 10.0 Hz, 2H,
CH2), 1.83-1.90 (m, 4H, 2CH2), 2.23 (s, 3H, CH3), 6.58 (s,
2H, NH2), 12.0 (s, 1H, NH) ppm; 13C NMR (DMSO-d6, 125
MHz) δ 12.0, 22.9, 30.7, 31.7, 32.8, 60.8, 103.8, 124.6,
134.6, 154.8, 162.1 ppm; Anal. Calcd for C14H18N4O: C,
65.09; H, 7.02; N, 21.69. Found: C, 64.90; H, 6.95; N,
1
cm-1; H NMR (DMSO-d6, 500 MHz) δ 1.06 (s, 3H, CH3),
7.31 (s, 2H, NH2), 7.45 (d, J = 7.0 Hz, 1H, HAr), 7.77 (t, J
= 7.5 Hz, 1H, HAr), 7.91 (t, J = 8.0 Hz, 1H, HAr), 8.05 (d,
J = 7.0 Hz, 2H, HAr), 8.40 (d, J = 8.0 Hz, 1H, HAr), 12.20
(s, 1H, NH) ppm; Anal. Calcd for C19H12N4O2: C, 69.51; H,
3.68; N, 17.06. Found: C, 69.70; H, 3.85; N, 16.88.

ACCEPTED MANUSCRIPT
Tetrahedron
9
Acknowledgement
Ding, T. L.; Zhang, H.; Cao, W. G. Tetrahedron 2013, 69,
6121-6128; (f) Chen, S. F.; Li, L.; Zhao, H. Y.; Li, B. G.
Tetrahedron 2013, 69, 6223-6229; (g) Liu, Y. P.; Liu, J. M.;
Wang, X.; Cheng, T. M.; Li, R. T. Tetrahedron 2013, 69,
5242-5247; (h) Sun, J.; Zhang, L. L.; Yan, C. G. Tetrahedron
2013, 69, 5451-5459; (i) Tu, X. C.; Fan, W.; Jiang, B.; Wang,
The project was financially supported by the National
Natural Science Foundation of China (Nos. 21272053,
21072042 and 20872025), Nature Science Foundation of
Hebei Province (B2011205031) and the Training
Programs of Innovation and Entrepreneurship for
Undergraduates of Hebei Province (201310094021).
S. L.; Tu, S. J. Tetrahedron 2013, 69, 6100-6107.
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Chem. Lett. 2013, 23, 2714-2717; (b) Kupcewicz, B.;
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