Chitosan: An efficient promoter for the synthesis of 2-aminopyrimidine-5- carbonitrile derivatives in solvent free conditions

Article abstract of DOI:10.1039/c4nj00199k

Reusable chitosan without any post-modification, with active -NH ₂ and -OH groups, was found to be a highly efficient and renewable heterogeneous catalyst for the rapid and convenient synthesis of 2-aminopyrimidine-5-carbonitrile derivatives from guanidines, aldehydes and cyanoketones, under mild reaction conditions at 85 °C in good yields. Undoubtedly this methodology gives a facile and straightforward pathway to construct 2-aminopyrimidine-5-carbonitrile derivatives in an eco-friendly fashion.

Full text of DOI:10.1039/c4nj00199k

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PAPER
Chitosan: An efficient promoter for the synthesis of 2-aminopyrimidine-
5-carbonitrile derivatives in solvent free conditions
I. R. Siddiqui*, Pragati Rai, Rahila and Anushree Srivastava
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Reusable chitosan–without any post-modification with active –NH2 and -OH group was found to be a
highly efficient and renewable heterogeneous catalyst for the rapid and convenient synthesis of 2-
aminopyrimidine-5-carbonitrile from guanidines, aldehydes and cyanoketones under mild reaction
conditions at 85°C in good yield. Undoubtedly this methodology disclose facile and straightforward
10 pathway to construct 2-aminopyrimidine-5-carbonitrile in eco-friendly fashion.
electron12. The use of such a basic support can provide a strategy
having advantages of easy handling of the catalyst, easy
separation of the product and avoiding the use of alkali or organic
50 bases. Hence, chitosan as a natural poly-glucosamine can be
utilized without any post-modification, as a mild bifunctional
heterogeneous catalyst in organic process.
Introduction
Research oriented towards ‘sustainable chemistry’ evoke
increasing interest in recent years resulting in new
environmentally benign procedures which include solvent-free
15 syntheses, multicomponent reactions, use of reusable and
biodegradable heterogeneous catalysts to save resources and
Pyrimidine and their derivatives a type of important N-
containing heteroaromatic scaffolds, exhibit a wide range of
55 biological activities13. Especially 2-amino-substituted pyrimidine
has frequently been studied during the recent decades because of
their pharmacological potential covering wide spectrum of
energy1,2
.
Organic solvents are major contributor to
environmental pollution. In order to eliminate organic solvent
from the chemical conversion, an important aspect of green
20 chemistry pertains to removal of volatile organic solvents or their
replacement by non-hazardous solvents. In this context the best
reaction medium is ‘no medium’ and therefore solvent free
condition is preferable choice3. Now solvent free MCR
(Multicomponent reaction) will be one of the most apt
25 approaches, which will meet the requirement of green chemistry4.
Furthermore, the use of heterogeneous catalysts has become
highly desirable in recent year because they incorporate many
green chemistry principles5. As a consequence the absence of
organic solvent in heterogeneous catalyst is the best situation for
30 achieving a more efficient and eco-friendly process6.
Recently, chitosan has been identified as important and
effective catalyst in various organic reactions because of its
positive attributes such as non-toxicity, biodegradability,
reusability, physiological inertness, stability to air and moisture7.
35 Literature survey shows that a wide range of applications have
been reported for chitosan in different fields such as medicine,
drug delivery, organic synthesis, chemical industries, agriculture,
and water treatment8. Being hydrophilic and possessing basic
moieties, chitosan has been used as heterogeneous basic catalyst
40 for organic transformation9,10. Chitosan is linear polyamine and
second most abundant naturally available polymer in world after
cellulose which is obtain from chitin by treatment with alkali. It
contains higher concentration of NH2 group and hydroxyl group
possible applications14,15
inestimable synthetic precursors in
.
Moreover, this moiety constitutes
variety of organic
a
60 conversions and in coordination chemistry16. This prominent
moiety exhibit protein kinase inhibitory activity, with the bcr-Abl
kinase inhibitor Imatinib the first drug of this family to enter
clinical trials17. Numerous elegant protocols for the synthesis of
this scaffold, involving various types of catalysts have been
65 reported. Despite these advances, there are still some potential
limitations including unsatisfactory yield, long reaction time,
limited substrate tolerance, use of expensive catalyst, toxic
organic solvents and cumbersome experimental procedure18.
These necessitate the development of a more efficient, convenient
70 and eco-friendly methodology for the synthesis of this
aesthetically appealing molecular architecture.
The Biginelli MCR is one of the most prominent approaches
that enable rapid access to diverse pharmacologically active
library of pyrimidine derivatives19. Whereas the use of urea and
75 thiourea20 as reactive component in the Biginelli reaction
reported, similar conversion that employs guanidine derivatives
are less reported21.
Result and Discussion
In view of above consideration and on the basis of our
and show insolubility in vast majority of common solvents 80 progressive endeavours in exploring green protocol for the
45 including water11. It can activate the nucleophilic and eletrophilic
components of the reaction by hydrogen bonding and lone pair of
synthesis of heterocyclic frameworks22, herein we wish to
uncover
a
more practical and expedient synthesis of 2-
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aminopyrimidine derivatives by using aldehyde (1) guanidine (2), 40 of catalyst afforded the desired product with moderate yield
and cyanoketone (3) under solvent free condition at 85°C in the
presence of chitosan without any post modification (Scheme 1).
(Table 2 Entries 2, 3) while using the 25 mol% of catalyst there
was no appreciable increase in the yield of product (Table 2,
Entry 4) was observed. Finally we noticed that 20 mol% of
chitosan was the most appropriate amount of catalyst for
45 achieving the desired conversion (Table 2, Entry 5).
Ph
O
CN
NC
R3
Chitosan/85oC
N
R2
Ph
H
1
Solvent -free
3h
N
N
NH
O
R3
3
R1
R2
Table 2 Effect of amount of catalyst on the synthesis of 4aa
4a
H2N
N
2
R1
Scheme 1 Three component synthesis of 2-aminopryrimidens-5-
5 carbonitriles and their derivatives
Entry
Catalyst
(mol%)
5
10
15
25
20
Time
(h)
5.5
4.0
3.5
3
Yield(%)b
1
2
3
4
5
54
77
83
89
89
The synthetic protocol is efficient, convergent and allows easy
placement of a various types of substituent around the periphery
of the heterocyclic ring system. Our careful literature survey
revealed that there is no report on the use of chitosan as a catalyst
10 in the synthesis of 2-aminopyrimidine derivatives using
guanidine under solvent free condition.
In our preliminary experiments, we have investigated the
optimized conditions regarding the catalyst, solvent and
temperature. For this Benzaldehyde (1a) Guanidine (2a), and
15 benzoacetonitrile (3a) were selected as test substrates. In order to
find the optimum reaction condition, equimolar amounts of the
test substrates were stirred in the absence of catalyst, no desired
product was observed (Table 1, Entry 1). But when reaction was
carried out in the presence of DBU in ethanol, the reaction took
20 long time for completion of reaction with low yield of product
(Table 1, Entry 2).
3
aReaction condition : Guanidine (1mmol), Benzaldehyde (1mmol),
cyanoketone (1mmol), catalyst, solvent free condition, T=85°C.
bYield of isolated product.
During solvent optimization, the reaction was carried out in
different solvents such as EtOH, MeOH and DCM with chitosan,
but no superior results were obtained (Table 3, Entries 1, 2, 3).
50 Whereas when reaction was carried out in aqueous medium,
reaction again took longer time (Table 3, Entry 4).
Table 3 Effect of various solvent and temperature on the model reaction
4aa
Entry
solvent
Temp
(°C)
85
85
85
85
85
95
65
Time
(h)
5
Yield
(%)b
77
61
59
55
89
89
70
Table 1 Screening of catalyst for the synthesis of 4aa
1
2
3
4
5
6
7
8
EtOH
MeOH
DCM
Yieldb
(%)
-
9
Entry
Catalyst
(20 mol%)
-
Time
(h)
10
10
10
10
6
7
6
5
10
12
3
3
4.5
10
water
1
2
3
4
5
6
7
8
solvent free
solvent free
solvent free
Solvent free
DBU
45
53
59
63
67
64
77
P2O5.SiO2
HClO4.SiO2
Na2CO3
K2CO3
Piperidine
Chitosan
r.t.
12
aReaction condition : Guanidine (1mmol), Benzaldehyde (1mmol),
cyanoketone (1mmol), catalyst (20 mol%), solvent free condition,
T=85°C, in solvent 4mL at reflux.
aReaction condition : Guanidine (1mmol), Benzaldehyde (1mmol),
cyanoketone (1mmol), catalyst (20 mol%), solvent (EtOH), T=85°C
bYield of isolated product.
bYield of isolated product.
When reaction was performed in solvent free condition we
55 observed that the yield of product increased dramatically in short
time period (Table 3, Entry 5). In addition, we studied the
influence of temperature on the reaction time and percentage
yield. All results were demonstrated in Table 3. Table 3 displays
that 85°C was optimum temperature for maximum conversion.
60 Increasing the temperature above 85°C neither improved the yield
nor decreased the reaction time (Table 3, Entry 6). Whereas,
reducing the temperature is detrimental to the reaction resulting
in lower yields (Table 3, Entry 7). When reaction was carried out
at room temperature very low yield of product was obtained
65 (Table 3, Entry 8).
Next a series of catalytic cycles were run to explore the
constancy of the catalyst activity for the synthesis of 2-
aminopyrimidine-carbonitrile derivatives. After completion of
reaction, the product was extracted with ethylacetate. The catalyst
70 left after extraction was used for the subsequent cycles. The result
showed that there is no appreciable loss in yield up to five times
Replacing DBU with other catalyst such as P2O5.SiO2 and
HClO4.SiO2 again resulted in low yield and took longer reaction
25 time (Table 1, Entries 3 and 4). Fate of the conversion in the
presence of other basic catalysts such as Na2CO3, K2CO3 and
piperidine were also investigated but we did not find any
appreciable improvement in the reaction time and yield of
product (Table 1, Entries 5, 6 and 7). In order to develop an easy
30 and eco-friendly procedure for the synthesis of this prominent
motif, we planned our strategy to exploit chitosan as catalyst.
Reaction went smoothly and resulted in the formation of
desirable products (4a) in good yield within short time period
(5h) as monitored by TLC. With chitosan as good activator in
35 hand, we next intended to investigate the reaction by using
different amount of chitosan.
For this, we first examined the synthesis of 4a in the presence of
5 mol% chitosan. After 5.5h, the desired product 4a was formed
in low amount (Table 2, Entry 1). Further using 10 and 15 mol%
2
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New Journal of Chemistry
25
without significant decrease of its catalytic activity (Table 4,
Cyanoketones 3
Entries 1-5).
O
O
Table 4 Reusability of catalyst for the synthesis of 4aa
CN
CN
Entry
Time
(h)
3
Yieldb
(%)
89
MeO
b
a
1
2
3
4
5
3
89
84
82
82
30 Figure 1 Diversity elements employed during library synthesis of 2
aminopyrimidine-5-carbonitrile derivatives
3.5
3.5
3.5
H
O
O
aReaction condition: Reaction progress monitored by TLC.
bIsolated yield.
OH
O
O
n
NH2
H
Chitosan
H
Ph
R3
H
1
Next, to explore the diversity of this methodology, various
cyanoketones, aldehydes and guanidines were used for the
construction of library of 2-aminopyrimidine-5-carbonotrile. The
corresponding functionalized pyrimidines were obtained in good
yield. All results are concluded in Table 5.
Ph
N
CN
NC
R3
5
3
O
R2
N
4
N
R1
H2
N
R1
N
O
OH
R3
N
O
R2
Table 5 Scope of substrates for the synthesis of compound 4
n
NH
H
N
HO
NC
H
R2
N
H2
N
Ph
CN
R1
N
O
Entry Aldehydes Guanidine Cyanoketone Producta Yieldb
HN
2
R3
R1
(1)
a
(2)
a
(3)
(4)
4a
4b
4c
4d
4e
4f
4g
4h
4i
R2
H
N
R3
O
NC
1
2
3
4
5
6
7
8
9
a
a
a
a
a
a
a
a
b
a
a
a
89
89
89
83
85
85
89
89
82
89
50
87
Ph
b
c
d
a
e
f
a
g
a
h
b
a
a
a
b
b
b
c
c
d
e
c
IV
CN
OH
NH
R2
Ph
N
N
R3
R1
II
III
10
11
12
4j
4k
4l
Scheme 2 Plausible mechanism for the synthesis of 2-aminopyrimidine-
35 5-carbonitrile
aReaction condition: Guanidines (1mmol), Aldehydes (1mmol),
Cyanoketones ( 1mmol), Solvent free condition.
Reaction with substrate having electron rich and electron poor
group at R3 and Ph sites furnished the corresponding product in
high yield. No obvious electronic and steric effects of reactant
were observed. Using best reaction condition, we carried out the
40 reaction of guanidine and cyanoketone with aliphatic aldehyde. In
this case, slightly lower yield was obtained in comparison to the
aromatic aldehydes. The structures of all compounds were
confirmed with the help of elemental and spectral (1HNMR,
13CNMR and MS) studies. On the basis of above results, a
45 plausible mechanism for the formation of 2-aminopyrimidine-5-
carbonitrile derivatives can be tentatively rationalized which is
depicted in Scheme 2. Presumably this transformation is triggered
by hydroxyl group of chitosan which activate carbonyl group of
aldehyde (1) which undergoes condensation with guanidine (2)
50 leading to the formation of intermediate (II). Formation of III is
facilitated by amine group present on the surface of chitosan.
Final step involve addition between intermediate II and III to
form new intermediate (IV) which undergoes intramolecular
cyclisation followed by aromatization to produce desired product
55 in good yield.
bIsolated Yield.
10
Aldehydes 1
CHO
CHO
CHO
CHO
OMe
N
d
c
a
OH
b
15
CHO
CHO
CHO
CHO
Cl
OMe
g
F
e
h
f
Guanidines 2
NH
b
NH
NH
20
H
H
H
H2N
N
H2N
N
H2N
N
Et
a
c
Ph
Me
NH
d
NH
Conclusions
H
Me
H2N
N
H
H2N
N
In summary, we have disclosed a convenient and efficient multi-
component synthesis for the 2-aminopyrimidine carbonitrile
e
Me
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65 5.
2-(Dimethylamino)-4,6-diphenylpyrimidine-5-carbonitrile
mp
framework by the reaction of guanidine, aldehyde and
cyanoketone in the presence of chitosan in solvent free condition.
In this experimentally simple process two new bonds are formed
in a single operation with all reactant efficiently utilized.
Moreover the amine and cyano substituent in the 2- and 5-
position of pyrimidine core are quite reactive; this makes this
motif good candidate as precursors for further conversion to meet
the need for various useful purposes. The pyrimidine formation is
accomplished through the ability of chitosan to function dually as
10 base and dehydrating agent in this transformation. The short
reaction time, excellent yield and more importantly the
recyclability without losing catalytic activity makes this protocol
a good alternative to previously reported methodologies. This
solvent-free strategy accords with the developing of the current
15 organic synthesis trend toward cleaner and greener organic
processes because of the pressing environmental and energy
problems.
236C; white solid; 1HNMR (CDCl3, 400MHz) δ (ppm) 7.90 (m, 4H), 7.54
(m, 6H), 3.51 (s, 6H); 13CNMR (CDCl3, 100MHz) δ (ppm) 168.8, 136.8,
129.6, 129.0, 128.5, 127.5, 117.1, 97.1, 37.0; HRMS-ESI m/z calcd. For
C19H16N4 [M +] 301.15, found 301.17.
5
70 6.
2-(Dimethylamino)-4-(4-fluorophenyl)-6-phenylpyrimidine-5-
carbonitrile ; mp 241°C; white solid; 1HNMR (CDCl3, 400 MHz) δ
(ppm) 8.10−8.08 (m, 2H), 7.98−7.93 (m, 2H), 7.59−7.52 (m, 3H),
7.39−7.34 (m, 2H), 3.39 (s, 6H); 13CNMR (CDCl3, 100MHz) δ (ppm)
171.2, 168.7, 160.6, 137.1, 136.6, 131.0, 131.0, 129.1, 127.9, 119.0,115.1,
75 116.0, 91.3, 36.3; HRMS-ESI m/z calcd. for C19H15N4F[M+] 319.14,
found 319.11.
7.
4-(3-Chlorophenyl)-2-(dimethylamino)-6-phenylpyrimidine-5-
carbonitrile; mp 181°C; white solid; 1HNMR (CDCl3, 400 MHz) δ
(ppm) 7.99−7.87 (m, 4H),7.68−7.52 (m, 5H), 3.35 (s, 6H); 13CNMR
80 (CDCl3, 100 MHz) δ(ppm) 171.1, 168.7, 161.5, 137.1, 137.4, 132.6,
132.5, 131.2,130.9, 129.2, 129.0, 128.4, 128.1, 119.3, 91.3, 38.3; HRMS-
ESI m/z calcd. for C19H15ClN4 [M +] 335,11, found 335.09.
8. 4,6-Diphenyl-2-(phenylamino)pyrimidine-5-carbonitrile mp 167°C;
white solid; 1H NMR (CDCl3, 400 MHz) δ (ppm) 8.14−8.12 (m, 4H),
85 7.77 (m, 3H), 7.59−7.55 (m, 6H), 7.39 (t J = 7.5 Hz, 2H), 7.15 (t J = 7.5
Hz, 1H); 13CNMR (CDCl3, 100 MHz) δ (ppm) 169.1, 158.9, 138.6, 136.3,
132.2, 129.9, 128.6, 128.5, 124.8, 119.9, 118.5, 94.0; HRMS-ESI m/z
calcd for C23H16N4 [M +] 349.15, found 349.17.
4. Experimental
4.1 Material and methods
9.
4,6-Bis(4-methoxyphenyl)-2-(phenylamino)pyrimidine-5-
90 carbonitrile; mp 215°C; white solid; 1HNMR (CDCl3, 400 MHz) δ
(ppm) 11.51 (bs, 1H), 7.99 (d J =8.7 Hz, 4H), 7.80 (d J = 7.6 Hz, 2H),
7.29 (m, 2H), 7.09 (d J =8.7 Hz, 4H), 7.14 (t J = 7.6 Hz, 1H), 3.81 (s, 6H);
13CNMR (CDCl3, 100 MHz) δ (ppm) 168.7, 162.8, 157.0, 139.3, 131.0,
128.4, 123.3, 121.3, 118.0, 114.1, 92.8, 55.9; HRMS-ESI m/z calcd. for
95 C25H20N4O2 [M +] 409.17, found 409.15.
20 All chemical were reagent grade purchased from Aldrich and Alfa Aesar
and were used without purification. NMR spectra were recorded on a
BRUKER AVANCE II-400FT Spectrometer (400 for 1HNMR, 100MHz
for 13C) using CDCl3 as solvent and TMS as an internal reference. ESI-
MS were recorded on a Quattro II (ESI) spectrometer.
25
10.
2-(Ethylamino)-4,6-diphenylpyrimidine-5-carbonitrile; white
4.2 General Procedure for the synthesis of 2,4,6-Substituted
Pyrimidine-5-carbonitriles. Guanidine (1mmol) and chitosan (20 mol%)
were added to an equimolecular mixture of the α cyanoketone(1.0 mmol)
and the corresponding aldehyde in solvent free condition, and the mixture
30 was stirred at 85 °C until the starting materials had been consumed (3h).
The mixture was cooled to room temperature to give an oily residue.
After completion of reaction the product was extracted by using ethyl
acetate and the catalyst was recovered by simple decantation and reused.
After seperation of catalyst, the solvent was evaporated under reduced
35 pressure. The oily residue was precipitated by the addition of MeOH and
the isolated solid was purified by column chromatography.
1
solid mp 188°C ; H NMR (CDCl3, 400 MHz) δ (ppm) 8.12−7.89 (m,
4H), 7.49−7.24 (m, 6H), 5.80 (t, 1H, J = 4.63), 3.69 (m, 2H, CH2), 1.28
(t, 3H, J = 7.2, CH3); 13CNMR (CDCl3, 100MHz) δ (ppm) 171.1, 160.7,
100 136.4, 131.1, 127.9, 128.6, 117.5, 92.7, 28.9; HRMS m/z calcd. For
C19H16N4 [M+] 300.37, found 300.35.
11. 2-Amino-4-cyclohexyl-6-phenylpyrimidine-5-carbonitrile mp
190°C; white solid; H NMR (CDCl3, 400 MHz) δ (ppm) 7.91−7.88 (m,
2H), 7.49−7.22 (m, 3H), 5.59 (s, 2H), 3.12−2.95 (m, 1H), 1.76−1.21 (m,
105 10H); 13CNMR (CDCl3, 100 MHz) δ (ppm) 181.4, 162.4, 136.2, 172.3,
169.9, 131.9,128.7, 118.2, 93.7, 44.9, 31.9, 27.8, 25.3; HRMS-ESI m/z
calcd. for C17H18N4 [M +] 279.17, found 279.13.
1
1.
2-(Methylamino)-4,6-diphenylpyrimidine-5-carbonitrile
mp
12.
4-(4-Hydroxyphenyl)-6-phenyl-2-(phenylamino)-pyrimidine-5-
1
219°C; white solid; H NMR (CDCl3, 400 MHz) δ (ppm) 8.09−7.84 (m,
4H), 7.59−7.54 (m, 6H), 5.91 (bs, 1H), 3.09 (d J = 5.1 Hz, 3H); 13C NMR
40 (CDCl3, 100 MHz) δ (ppm) 171.8, 160.7, 136.3, 131.1, 128.9, 128.6,
118.5, 92.7, 30.1; HRMS-ESI m/z calcd. for C18H14N4 [M +] 287.13,
found 287.15.
carbonitrile mp 284°C; white solid; 1H NMR (CDCl3, 400 MHz) δ (ppm)
110 10.61 (m,1H), 10.42 (s, 1H), 7.96−7.89 (m, 4H), 7.85−7.81 (d J = 7.6 Hz,
2H), 7.61−7.59 (m, 3H), 7.44 (m, 2H), 7.07−7.01 (m,1H), 6.89 (d J = 7.6
Hz, 2H); 13CNMR (CDCl3, 100 MHz) δ (ppm) 172.7, 168.7, 161.6, 159.2,
139.1, 137.6, 130.1, 130.1,129.0, 128.6, 128.0, 127.9, 123.2, 120.4, 118.8,
114.4, 93.2; HRMS-ESI m/z calcd. for C23H16N4O [M +] 365.16, found
115 365.13.
2.
4-(4-Hydroxyphenyl)-2-(methylamino)-6-phenylpyrimidine-5-
carbonitrile mp >300°C white solid; 1HNMR (CDCl3, 400 MHz) δ (ppm)
45 10.19 (bs, 1H,OH), 8.35 (bs, 1H, −NH), 7.90−7.81 (m, 4H), 7.53−7.50
(m, 3H), 6.89−6.84 (m, 2H), 2.93 (d J = 3.8 Hz, 3H); 13CNMR (CDCl3,
100 MHz) δ (ppm) 170.4, 169.6, 161.5, 160.5, 137.0,130.9, 129.0, 128.4,
127.9, 127.1, 119.3, 116.2, 89.9, 28.7; HRMS-ESI m/z calcd. for
C18H14N4O [M +] 303.12, found 303.10.
Acknowledgements
We gratefully acknowledge the financial support from the Council of
Scientific and Industrial Research and University Grant Commission.
Authors gratefully acknowledge the SAIF, Punjab University,
120 Chandigarh, for providing all the spectroscopic data.
50 3.
4-(2-Methoxyphenyl)-2-(methylamino)-6-phenylpyrimidine-5-
carbonitrile mp 225°C ; white solid; 1HNMR (CDCl3 400 MHz) δ (ppm)
8.35−8.33 (m, 1H), 7.92−7.89 (m, 1H), 7.85−7.80 (m, 1H), 7.57−7.37 (m,
5H), 7.30−7.21 (d J = 4.1 Hz, 1H), 7.20−7.14 (m, 1H), 3.89 (s, 3H), 2.92
(d J = 4.7 Hz, 3H); 13C NMR (CDCl3, 100MHz) δ (ppm) 170.1, 169.7,
55 162.5, 156.2, 136.7, 131.8, 131.0, 130.2, 128.9, 128.8, 126.3, 120.6,
118.2, 112.9, 93.3, 54.7, 31.1; HRMS-ESI m/z calcd. for C19H16N4O
[M +] 317.15, found 317.13.
Notes and references
Laboratory of Green Synthesis, Department of Chemistry, University of
Allahabad, Allahabad-211002, India,
E-mail: dr.irsiddiqui@gmail.com
4.
2-(Methylamino)-6-phenyl-4-(pyridin-3-yl)pyrimidine-5-
carbonitrile white solid; 221°C 1HNMR (CDCl3, 400 MHz) δ (ppm)
60 9.13−9.01 (bs, 1H),8.75−8.69 (m, 1H), 8.41 (m, 1H), 8.35−8.21 (m, 1H),
7.94−7.89 (m, 2H), 7.60−7.54 (m, 4H), 2.97 (d J = 4.7 Hz, 3H); 13CNMR
(CDCl3, 100 MHz) δ (ppm) 187.6, 171.3, 167.9,160.6, 152.7, 149.4,
136.4, 132.7, 130.2, 129.9, 123.5, 118.9,112.3, 91.3, 28.7; HRMS-ESI
m/z calcd. For C17H13N5 [M+] 288.13, Found 288.11
125
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