Facile and efficient synthesis of indol-3-yl substituted pyran derivatives via one-pot multicomponent reactions under ultrasonic irradiation

Article abstract of DOI:10.1002/jhet.983

A series of polysubstituted indol-3-yl substituted pyran derivatives have been synthesized via one-pot multicomponent reactions of aldehydes, malononitrile with 3-cyanoacetyl indoles under ultrasonic irradiation. This method has the advantages of high yield, easy operation, short-reaction time, mild-reaction condition, and catalyst recyclability.

Full text of DOI:10.1002/jhet.983

Month 2013
Facile and Efficient Synthesis of Indol‐3‐yl Substituted Pyran
Derivatives via One‐Pot Multicomponent Reactions under
Ultrasonic Irradiation
*
Tao Chen, Xiao‐Ping Xu, and Shun‐Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123
People’s Republic of China
*
E-mail: chemjsj@suda.edu.cn
Received February 24, 2011
DOI 10.1002/jhet.983
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
A series of polysubstituted indol‐3‐yl substituted pyran derivatives have been synthesized via one‐pot
multicomponent reactions of aldehydes, malononitrile with 3‐cyanoacetyl indoles under ultrasonic irradia-
tion. This method has the advantages of high yield, easy operation, short‐reaction time, mild‐reaction condi-
tion, and catalyst recyclability.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
economy, convergence, ease of execution, and access to
complex molecules has been recognized in the past decade
[16]. Also, ultrasound irradiation has been considered as a
clean and useful protocol in organic synthesis during the
last three decades. Compared with traditional methods,
the procedure is more convenient. Moreover, a large num-
ber of organic reactions can be carried out in higher yield,
shorter reaction time, or milder conditions under ultrasonic
irradiation [17].
Because of the potent and diverse biological activities of
indoles and 4H‐pyrans, guided by the observation that the
presence of two or more different heterocyclic moieties in
a single molecule often enhances the biocidal profile re-
markably and out of our interest in the multicomponent
synthesis and in continuation of our work on the synthesis
of indole derivatives [18]. Herein, we report the synthesis
of various indol‐3‐yl substituted pyran derivatives via a
facile, efficient, one‐pot, atom‐economical, and three‐com-
ponent reaction under ultrasonic irradiation in much
shorter time compared with the reported literatures [19].
Indoles substituted with heterocyclic rings at the 3‐posi-
tion are featured in a wide variety of pharmacologically
and biologically active compounds especially with antican-
cer, antitumor, hypoglycemic, anti‐inflammatory, analge-
sic, and antipyretic activities [1] (Fig. 1). For instance,
nortopsentins A–C exhibit in vitro cytotoxicity against
P388 cells [2]; meridianins A–E show cytotoxicity toward
murine tumor cell lines and have potent inhibition against
several protein kinases [3]. Thus, synthetic methods and
the structure decoration of indole derivatives have received
an increasing attention in recent years.
Polysubstituted 4H‐pyran derivatives occupy a special
place in organic and medicinal chemistry because these
compounds show various biological properties, such as an-
ticoagulant, anticancer, antioxidant, spasmolytic, diuretic,
and antianaphylactic activities. A great many of 2‐amino‐
4H‐pyran derivatives are employed as photoactive materi-
als, cosmetics, and pigments [4–11]. With all these fasci-
nating applications, much research has been devoted to
the development of directed synthetic routes to suitable
4H‐pyran units, as well as effective functionalized strate-
gies [12–15].
RESULTS AND DISCUSSION
Multicomponent reactions (MCRs) are powerful tools in
preparing libraries to screen for biologically active com-
pounds and potent drug candidates. A wide range of
advantages offered by MCRs, such as high degree of atom
In our initial study, the reaction of 4‐bromobenzalde-
hyde 1{1} (0.5 mmol), malononitrile 2{1} (0.5 mmol),
and 3‐(5‐bromo‐1H‐indol‐3‐yl)‐3‐oxopropanenitrile 3{1}
© 2013 HeteroCorporation

T. Chen, X.-P. Xu, and S.-J. Ji
Vol 50
Table 1
Optimization of catalysts and solvents in the synthesis of 4{1, 1, 1}.
Catalyst
(mol %)
Yieldb
(%)
Entrya
Solvent
Time (min)
1
2
3
4
5
6
7
8
none
p‐TsOH (20%)
FeCl3 (20%)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
DMF
DMSO
H2O
EtOH
EtOH
EtOH
EtOH
180
180
180
180
180
60
60
60
60
60
60
60
60
60
60
15
15
15
0
0
0
Figure 1. Representatives of important indol‐3‐yl substituted
heterocycles.
Bi(NO3)3 (20%)
0
CANc(20%)
Trace
35
80
53
60
90
37
78
62
70
18
91
77
61
49
NaOH (20%)
Et3N (20%)
DBUd(20%)
DABCOe(20%)
Piperidine (20%)
K2CO3 (20%)
Piperidine (20%)
Piperidine (20%)
Piperidine (20%)
Piperidine (20%)
Piperidine (20%)
Piperidine (15%)
Piperidine (10%)
Piperidine (5%)
(0.5 mmol) was chosen as a model reaction (Scheme 1) to
establish the feasibility of the strategy and optimize the re-
action conditions. The results are summarized in Table 1.
The reaction was first carried out in ethanol in the ab-
sence of any catalyst at room temperature. However, after
3 h, product 4{1, 1, 1} was not obtained, even if the reac-
tion was catalyzed by p‐TsOH, Bi(NO3)3 or FeCl3 (Table
1, entries 1–4). Ceric ammonium nitrate could catalyze this
reaction to lead to the desired product, but, in trace amount
(Table 1 entry 5). To our delight, 35% of the target com-
pound 4{1, 1, 1} was obtained when NaOH was used as
catalyst (Table 1, entry 6). Encouraged by this success, as
seen in Table 1, entries 7–11, a variety of bases, such as
Et3N, 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, 1,4‐diazabicy-
clo[2.2.2]octane, piperidine, and K2CO3 were screened in
model reaction, and the yield was up to 90% when the re-
action was catalyzed by piperidine in EtOH (Table 1, entry
10). Afterward, various solvents were examined for this re-
action. When the reaction solvent was changed from aceto-
nitrile to N,N-Dimethylformamide (DMF) or Dimethyl
sulfoxide (DMSO), the compound 4{1, 1, 1} was produced
in moderate yields (Table 1, entries 12–14). When H2O
was used as the reaction solvent, the desired product was
obtained in a much lower yield (Table 1, entry 15). Finally,
it was found that EtOH was the most suitable solvent
for this reaction. In recent years, microwaves [18(i),(j)]
and ultrasonic irradiation [18(a),(c),(e)] were always
adopted to synthesize many indole‐containing compounds
in our group, because under these circumstances, the
reactions were often greatly accelerated. So the ultrasonic
irradiation was applied to improve the rate for the model
reaction. It was found that the reaction time was sharply
decreased from 60 to 15 min, as is seen from Table 1,
9
10
11
12
13
14
15
16f
17f
18f
19f
15
aAll reactions were carried out at room temperature.
bIsolated yield.
cCAN = ceric ammonium nitrate.
dDBU = 1,8‐diazabicyclo[5.4.0]undec‐7‐ene.
eDABCO = 1,4‐diazabicyclo[2.2.2]octane.
fThe reaction was carried out under ultrasonic irradiation.
entry 16. We also evaluated the amount of piperidine
required for this reaction. The results from Table 1 (entries
16–19) show that 20 mol % piperidine is necessary to
complete the reaction in excellent yield 91% under ultra-
sonic irradiation within 15 min at room temperature. Under
ultrasonic irradiation in EtOH, the reaction yield would
obviously decrease along with cutting down the loading
of the catalyst.
With this result in hand, we went on to study the scope of
the methodology (Scheme 2). Using the optimized reaction
conditions, a variety of structurally diverse aryl aldehydes
1{1–8} and 3‐(1H‐indol‐3‐yl)‐3‐oxopropanenitriles 3{1–5}
were investigated (Fig. 4). The results can be represented
as in Table 2. As shown in Table 2, when aromatic aldehydes
with electron‐withdrawing groups (such as nitro and halide
groups) 1{1–5} reacted with malononitrile 2{1} and 3‐
(1H‐indol‐3‐yl)‐3‐oxopropanenitriles both with electron‐
withdrawing and electron‐donating groups 3{1–5}, the
corresponding products were obtained smoothly; when alde-
Scheme 1
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013
Facile and Efficient Synthesis of Indol-3-yl Substituted Pyran Derivatives via One-Pot
Multicomponent Reactions under Ultrasonic Irradiation
Figure 2. Diversity of reagents.
was increased to 50°C. The yields of the expected products
were very poor as the aldehydes with electron‐donating
group 1{8–9} were used as substrates.
hydes changed to benzaldehyde and 2‐naphthaldehyde, the
reaction time was prolonged to 60–90 min, and the yield
was reduced to 74–79%, while the reaction temperature
Apart from the mild conditions of the process and its
good results, the simplicity of product isolation and the
possibility to recover and recycle the piperidine as catalyst
offer a significant advantage. Because piperidine is soluble
in the reaction medium (ethanol) and the desired products
are less soluble in ethanol, the products can be directly sep-
arated by filtering after the reaction is completed. The fil-
trate containing piperidine can directly be recovered and
recycled. Studies using 1{1}, 2{1}, and 3{1} as model
substrates showed that the recovered reaction solution
could be successively recycled in subsequent reactions
without any noticeable decrease of yields for four runs
(Fig. 3).
Table 2
Synthesis of indol‐3‐yl substituted pyran derivatives 4.
Entry
Time (min)
Yielda (%)
4{1, 1, 1}
4{1, 1, 2}
4{1, 1, 3}
4{1, 1, 4}
4{1, 1, 5}
4{2, 1, 1}
4{2, 1, 2}
4{2, 1, 3}
4{2, 1, 4}
4{2, 1, 5}
4{3, 1, 1}
4{3, 1, 2}
4{3, 1, 3}
4{3, 1, 4}
4{3, 1, 5}
4{4, 1, 3}
4{4, 1, 4}
4{5, 1, 1}
4{5, 1, 3}
4{5, 1, 4}
4{5, 1, 5}
4{6, 1, 1}b
4{6, 1, 4}b
4{7, 1, 4}b
4{8, 1, 4}b
4{9, 1, 4}bb
15
10
8
6
6
13
11
9
5
5
91
90
89
92
94
85
86
85
89
91
85
87
85
89
92
82
85
83
81
84
87
74
79
76
Trace
Trace
17
12
12
8
9
13
10
18
15
10
10
90
60
60
90
90
aIsolated yield.
Figure 3. Catalyst recycle. Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.
bThe reaction was carried out at 50°C.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

T. Chen, X.-P. Xu, and S.-J. Ji
Vol 50
ScShcehmeme e3.3SuSpuppopsoesdedreraecatciotinonmmecehcahnainsimsm.
Given a number of commercially available aromatic
aldehydes and 3‐(1H‐indol‐3‐yl)‐3‐oxopropanenitriles, the
present method should be applicable to synthesis of librar-
ies with high diversity. We expect this method to find ex-
tensive application in the field of combinatorial
chemistry, diversity‐oriented synthesis, and drug
discovery.
According to the experimental observation, compound 5
was formed from Knoevenagel condensation of aromatic
aldehydes and malononitrile, which was faster than Knoe-
venagel condensation of aromatic aldehydes and 3‐(1H‐
indol‐3‐yl)‐3‐oxopropanenitriles in the earlier optimized
condition. Although the detailed mechanism of the above
reaction remains to be fully clarified, compound 4 could
be produced from the intermediate 5 via Michael addition
with the tautomer of 3‐cyanoacetyl indole 6 followed by
intramolecular cyclization (Scheme 3). In this work, the
products were characterized by melting point, IR, NMR,
and combustion analysis. Furthermore, the structure of 4
{1, 1, 1} was established by X‐ray crystallographic analy-
sis. Its structure is shown in Figure 4, and its crystallo-
graphic data are shown in Table 3.
Table 3
Crystallographic data of compound 4{1, 1, 1}.
Empirical formula
Formula weight
Temperature
C21H12N4Br2O
496.15
223(2) K
Wavelength
0.71075A
Crystal system
Space group
triclinic
P ‐1
Unit‐cell dimensions
a = 9.4650(3) Å; α = 64.471(8)°
b = 11.3668(3) Å; β =69.884(9)°
c = 12.8881(4) Å; γ = 69.542(9) °
Volume
1141.25(6) Å3
Z
2
Density (calculated) Mg/m3
Absorption coefficient mm−1
F(000)
1.657
3.584
568
Crystal size
0.45 × 0.30 × 0.15 mm3
Theta range for data collection 3.17–27.48°
Limiting indices
−11 ≤ h ≤ 12, −14 ≤ k ≤ 10,
−16 ≤ l ≤ 16
Reflections collected
10490/5133 [R(int) = 0.0291]
5133/0/304
1.010
R1 = 0.0373, wR2 = 0.0791
R1 = 0.0580, wR2 = 0.0854
0.382 and −0.616 e.Å−3
Data/restraints/parameters
Goodness‐of‐fit on F2
Final R indices [I > 2•(I)]
R indices (all data)
Largest diff. peak and hole
Figure 4. Compound 4{1, 1, 1} crystal structure.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013
Facile and Efficient Synthesis of Indol-3-yl Substituted Pyran Derivatives via One-Pot
Multicomponent Reactions under Ultrasonic Irradiation
129.5, 124.5, 122.7, 121.6, 121.0, 121.0, 119.2, 118.9, 112.4,
105.4, 83.5, 55.5, 39.2. Anal. calcd for C21H13BrN4O: C, 60.45;
CONCLUSION
In summary, we have demonstrated a simple, atom‐eco-
nomical, and efficient approach for the synthesis of indol‐
3‐yl substituted pyran derivatives via one‐pot, three‐com-
ponent reactions using readily available starting materials.
This method incorporates both indole and pyran moieties
into a single molecule. In view of the presence of either
functionality, these compounds may suppose to demon-
strate improvement in biological activities. Prominent
among the advantages of this new method are novelty,
high yields, easy operation, mild reaction condition, and
catalyst recyclability. Further reactivity studies and syn-
thetic applications of this methodology are in progress in
our laboratory.
H, 3.14; N, 13.43. Found: C, 60.47; H, 3.28; N, 13.45.
2‐ Amino‐ 4‐ (4‐ bromophenyl)‐ 6‐(2‐ phenyl‐1H‐indol‐3‐yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{1, 1, 3}). Solid; M.p. 206–208°
C. IR (potassium bromide): ν 3445.1, 3396.3, 3312.5, 3186.5,
2201.6, 1681.4, 1599.8, 1486.1, 1451.0, 1396.5, 1217.5,
1133.6, 1010.9, 927.6, 752.6 cm−1 1H‐NMR (400 MHz,
.
DMSO‐d6) (δ, ppm): 12.13 (s, 1H, NH), 7.66 (d, 2H, J = 8.4
Hz, ArH), 7.58 (d, 2H, J = 7.2 Hz, ArH), 7.38–7.54 (m, 5H,
ArH), 7.32 (d, J = 8.4 Hz, 2H, ArH), 7.22–7.26 (m, 3H, NH2 +
ArH), 7.17 (t, J = 7.6 Hz, 1H, ArH), 4.48 (s, 1H, CH). 13C‐
NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.3, 155.1, 141.6,
139.5, 135.7, 131.9, 130.9, 130.1, 129.0, 128.8, 127.5, 127.0,
122.9, 121.0, 120.9, 119.2, 119.1, 116.6, 112.0, 102.3, 92.3,
54.9. Anal. calcd for C27H17BrN4O: C, 65.73; H, 3.47; N,
11.36. Found: C, 65.89; H, 3.55; N, 11.36.
2‐Amino‐4‐(4‐bromophenyl)‐6‐ (1‐ methyl‐ 1H‐ indol‐ 3‐ yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{1, 1, 4}). Solid; M.p. 236–238°
C. IR (potassium bromide): ν 3346.6, 3335.7, 3058.1, 2933.7,
2197.0, 1672.6, 1614.5, 1587.7, 1528.1, 1474.5, 1404.5,
EXPERIMENTAL
Melting points were uncorrected. IR spectra were recorded on
a Varian F‐1000 spectrometer in KBr with absorptions in cm−1
.
1364.7, 1121.4, 738.1 cm−1 1H‐NMR (400 MHz, DMSO‐d6)
.
1H‐NMR spectra were determined on a Varian‐300 or 400 MHz
spectrometer in DMSO‐d6 solution. J values are in Hz. Chemical
shifts are expressed in ppm downfield from internal standard
Tetramethylsilane (TMS). Combustion analysis was performed
with Carlo‐Erba EA1110CHNO‐S elemental analyzer. X‐ray
crystallographic analysis was performed with a Rigaku Mercury
CCD/AFC diffractometer.
(δ, ppm): 8.15 (s, 1H, ArH), 7.97 (d, 1H, J = 8.0 Hz, ArH),
7.63 (d, 2H, J = 8.4 Hz, ArH), 7.56 (d, 1H, J = 8.4 Hz, ArH),
7.29–7.35 (m, 5H, NH2 + ArH), 7.19–7.23 (m, 1H, ArH), 4.48
(s, 1H, CH), 3.88 (s, 3H, CH3). 13C‐NMR (100 MHz, DMSO‐
d6) (δ, ppm): 158.7, 155.4, 142.5, 136.5, 132.9, 131.8, 129.9,
124.9, 122.8, 121.8, 121.3, 120.9, 119.1, 118.7, 110.6, 104.3,
83.3, 55.4, 39.2, 33.2. Anal. calcd for C22H15BrN4O: C, 61.27;
H, 3.51; N, 12.99. Found: C, 61.45; H, 3.77; N, 13.05.
General procedure for the synthesis of 4 is represented as follows.
A
mixture of benzaldehyde 1 (0.5 mmol), malononitrile 2 (0.5 mmol),
and 3‐(1H‐indol‐3‐yl)‐3‐oxopropanenitrile 3 (0.5 mmol) in 3 mL
EtOH was placed in a round bottom flask. The reaction was carried
out at room temperature under ultrasonic irradiation for some min-
utes (the progress was monitored by TLC). Ultrasonication was
performed in a KQ‐250E ultrasonic cleaner with a frequency of
40 KHz and a normal power of 250 W. After the completion, the re-
action mixture was filtered. Then the precipitate was washed with
water (5 mL) and ethanol (2 mL) to afford the pure 4.
2‐Amino‐4‐(4‐bromophenyl)‐ 6‐ (7‐ methyl‐1H‐ indol‐ 3‐ yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{1, 1, 5}). Solid; M.p. 250–252°
C. IR (potassium bromide): ν 3467.3, 3204.5, 3054.5, 2200.8,
1615.2, 1521.9, 1444.3, 1360.7, 1160.9, 1009.4, 737.5 cm−1
.
1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.01 (s, 1H, NH),
8.10 (d, 1H, J = 3.2 Hz, ArH), 7.70 (d, 1H, J = 7.6 Hz, ArH),
7.63 (d, 2H, J = 8.0 Hz, ArH), 7.32–7.35 (m, 4H, NH2 + ArH),
7.03–7.10 (m, 2H, ArH), 4.48 (s, 1H, CH), 2.50 (s, 1H, CH3).
13C‐NMR (100 MHz, DMSO‐d6) (δ, ppm): 158.8, 156.0, 142.5,
135.5, 131.9, 130.0, 129.1, 124.3, 123.2, 121.5, 121.2, 121.0,
119.2, 118.9, 105.8, 83.6, 55.4, 39.2, 16.8. Anal. calcd for
C22H15BrN4O: C, 61.27; H, 3.51; N, 12.99. Found: C, 61.54;
H, 3.73; N, 13.14.
2‐Amino‐6‐ (5‐ bromo‐1H‐ indol‐3‐ yl)‐ 4‐ (4‐ bromophenyl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{1, 1, 1}). Solid; M.p. 243–245°
C. IR (potassium bromide): ν 3462.9, 3357.9, 3224.2, 3079.1,
3027.6, 2935.9, 2201.4, 1659.7, 1608.4, 1517.4, 1400.8,
1360.7, 1147.3, 811.2 cm−1 1H‐NMR (400 MHz, DMSO‐d6)
.
2‐Amino‐6‐(5‐bromo‐1H‐indol‐3‐yl)‐4‐(4‐ nitrophenyl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{2, 1, 1}). Solid; M.p. 256–258°C.
IR (potassium bromide): ν 3481.0, 3379.7, 3294.3, 3072.6,
2194.9, 1658.9, 1613.9, 1514.6, 1452.7, 1351.2, 1148.0, 804.2,
(δ, ppm): 12.15 (s, 1H, NH), 8.16 (d, 1H, J = 3.2 Hz, ArH),
8.02 (d, 1H, J = 1.6 Hz, ArH), 7.63 (d, 2H, J = 8.4 Hz, ArH),
7.48 (d, 1H, J = 8.4 Hz, ArH), 7.43 (s, 2H, NH2), 7.33–7.37
(m, 3H, ArH), 4.49 (s, 1H, CH). 13C‐NMR (100 MHz, DMSO‐
d6) (δ, ppm): 158.7, 155.2, 142.3, 134.8, 131.8, 130.7, 130.1,
126.1, 125.5, 123.3, 121.0, 119.2, 118.6, 114.3, 113.9, 105.0,
84.6, 55.3. Anal. calcd for C21H12Br2N4O: C, 50.84; H, 2.44;
N, 11.29. Found: C, 50.94; H, 2.61; N, 11.38.
703.3 cm−1 1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.19
.
(d, 1H, J = 2.4 Hz, NH), 8.31 (d, 2H, J = 8.8 Hz, ArH), 8.20
(d, 1H, J = 3.2 Hz, ArH), 8.06 (d, 1H, J = 1.6 Hz, ArH), 7.70
(d, 2H, J = 8.8 Hz, ArH), 7.56 (s, 2H, NH2), 7.49 (d, 1H, J =
8.4 Hz, ArH), 7.36–7.39 (m, 1H, ArH), 4.72 (s, 1H, CH). 13C‐
NMR (100 MHz, DMSO‐d6) (δ, ppm): 158.9, 155.8, 150.2,
147.1, 134.8, 131.0, 129.3, 126.1, 125.6, 124.2, 123.4, 119.1,
118.5, 114.4, 114.1, 105.0, 83.7, 54.7, 39.4. Anal. calcd for
C21H12BrN5O3: C, 54.56; H, 2.62; N, 15.15. Found: C, 55.54;
H, 2.71; N, 15.13.
2‐Amino‐4‐(4‐bromophenyl)‐6‐(1H‐ indol‐ 3‐ yl)‐ 4H‐ pyran‐
3,5‐dicarbonitrile (4{1, 1, 2}). Solid; M.p. 202–204°C. IR
(potassium bromide): ν 3457.0, 3306.5, 3256.6, 3209.9, 3055.6,
2200.9, 1615.6, 1586.7, 1522.0, 1488.6, 1430.8, 1410.2, 877.0,
737.6 cm−1 1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.00
.
(s, 1H, NH), 8.14–8.15 (m, 1H, ArH), 7.94–7.96 (m, 1H, ArH),
7.63 (d, 2H, J = 8.4 Hz, ArH), 7.51 (d, 1H, J = 8.0 Hz, ArH),
7.32–7.36 (m, 4H, NH2 + ArH), 7.22–7.26 (m, 1H, ArH), 7.15–
7.19 (m, 1H, ArH), 4.49 (s, 1H, CH). 13C‐NMR (100 MHz,
DMSO‐d6) (δ, ppm): 158.8, 156.0, 142.5, 136.0, 131.9, 130.0,
2‐Amino‐6‐(1H‐indol‐3‐yl)‐4‐(4‐nitrophenyl)‐4H‐pyran‐3,5‐
dicarbonitrile (4{2, 1, 2}). Solid; M.p. 238–240°C. IR
(potassium bromide): ν 3456.0, 3351.8, 3277.8, 2202.7, 1668.2,
1
1615.0, 1513.9, 1406.9, 1351.9, 1191.1, 922.3, 740.6 cm−1. H‐
NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.04 (s, 1H, NH), 8.31
Journal of Heterocyclic Chemistry
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T. Chen, X.-P. Xu, and S.-J. Ji
Vol 50
(d, 1H, J = 8.4 Hz, ArH), 8.17 (d, 1H, J = 2.4 Hz, ArH), 7.98 (d,
2H, J = 8.0 Hz, ArH) 7.67 (d, 2H, J = 8.4 Hz, ArH), 7.52 (d, 1H, J
= 7.6 Hz, ArH), 7.46 (s, 2H, NH2), 7.25 (t, 1H, J = 7.6 Hz, ArH),
7.18 (t, 1H, J = 7.6 Hz, ArH), 4.72 (s, 1H, CH). 13C‐NMR (75
MHz, DMSO‐d6) (δ, ppm): 158.9, 156.4, 150.3, 147.1, 136.0,
129.7, 129.2, 124.5, 124.3, 122.8, 121.7, 121.1, 119.0, 118.7,
112.4, 105.2, 82.6, 54.8, 39.3. Anal. calcd for C21H13N5O3: C,
65.79; H, 3.42; N, 18.27. Found: C, 65.63; H, 3.47; N, 18.19.
2‐Amino‐4‐(4‐nitrophenyl)‐6‐(2‐phenyl‐1H‐indol‐3‐ yl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{2, 1, 3}). Solid; M.p. 222–224°C.
IR (potassium bromide): ν 3441.3, 3371.8, 3308.7, 3182.3,
2198.4, 1677.9, 1594.7, 1518.1, 1396.7, 1348.5, 1130.8, 746.6,
2‐ Amino‐ 4‐ (2,4‐ dichlorophenyl)‐ 6‐ (1H‐ indol‐ 3‐ yl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{3, 1, 2}). Solid; M.p. 258–260°C.
IR (potassium bromide): ν 3467.1, 3295.9, 3214.7, 2203.6,
1676.0, 1588.7, 1495.1, 1470.1, 1433.8, 1046.1, 740.7, 706.2
1
cm−1. H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.01 (s, 1H,
NH), 8.14 (d, 1H, J = 3.2 Hz, ArH), 7.95 (d, 1H, J = 8.0 Hz,
ArH), 7.69 (s, 1H, ArH), 7.50–7.54 (m, 3H, ArH), 7.41 (s, 2H,
NH2), 7.22–7.26 (m, 1H, ArH), 7.17 (t, 1H, J = 7.6 Hz, ArH),
4.94 (s, 1H, CH). 13C‐NMR (100 MHz, DMSO‐d6) (δ, ppm):
159.1, 156.6, 138.5, 136.0, 133.5, 133.3, 132.5, 129.5, 128.4,
124.5, 122.7, 121.6, 121.1, 118.9, 118.6, 112.4, 105.3, 81.9,
54.1, 37.2. Anal. calcd for C21H12Cl2N4O: C, 61.93; H, 2.97;
N, 13.76. Found: C, 62.18; H, 3.10; N, 13.71.
697.7 cm−1 1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.14
.
(s, 1H, NH), 8.33 (d, 2H, J = 8.4 Hz, ArH), 7.66 (d, 2H, J =
8.8 Hz, ArH), 7.55–7.59 (m, 3H, ArH), 7.49 (d, 1H, J = 8.0 Hz,
ArH), 7.38–7.45 (m, 5H, NH2 + ArH), 7.23–7.27 (m, 1H, ArH),
7.16–7.20 (m, 1H, ArH), 4.70 (s, 1H, CH). 13C‐NMR (75 MHz,
DMSO‐d6) (δ, ppm): 159.5, 155.8, 149.4, 147.2, 139.9, 135.8,
130.9, 129.4, 129.0, 128.9, 127.7, 127.0, 124.3, 123.0, 121.0,
119.3, 119.1, 116.5, 112.1, 102.1, 91.4, 54.3. Anal. calcd for
C27H17N5O3: C, 70.58; H, 3.73; N, 15.24. Found: C, 70.59; H,
3.94; N, 15.29.
2‐Amino‐4‐(2,4‐dichlorophenyl)‐6‐(2‐phenyl‐1H‐indol‐3‐yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{3, 1, 3}). Solid; M.p. 208–210°
C. IR (potassium bromide): ν 3450.5, 3306.9, 3265.3, 3183.8,
2201.5, 1677.7, 1583.4, 1392.4, 1215.2, 1125.0, 748.4 cm−1
.
1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.15 (s, 1H, NH),
7.40–7.68 (m, 10H, ArH), 7.30 (s, 2H, NH2), 7.24 (t, 1H, J =
7.6 Hz, ArH), 7.17 (t, 1H, J = 7.6 Hz, ArH), 4.95 (s, 1H, CH).
13C‐NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.6, 155.9, 139.6,
137.8, 135.7, 133.4, 133.3, 132.6, 130.9, 129.5, 129.0, 128.9,
128.4, 127.7, 127.0, 122.9, 120.9, 119.3, 118.9, 116.3, 112.0,
102.1, 90.6, 53.8, 37.2. Anal. calcd for C27H16Cl2N4O: C,
67.09; H, 3.34; N, 11.59. Found: C, 67.36; H, 3.50; N, 11.71.
2‐Amino‐4‐(2,4‐dichlorophenyl)‐6‐(1‐methyl‐1H‐indol‐3‐yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{3, 1, 4}). Solid; M.p. 262–264°C.
IR (potassium bromide): ν 3474.4, 3339.8, 3312.5, 3122.9, 2197.1,
1672.8, 1617.5, 1523.7, 1475.1, 1402.4, 1365.1, 856.6, 735.0 cm−1.
1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 8.16 (s, 1H, ArH), 7.97
(d, 1H, J = 8.0 Hz, ArH), 7.69 (d, 1H, J = 1.2 Hz, ArH), 7.49–7.57
(m, 3H, ArH), 7.41 (s, 2H, NH2), 7.31 (t, 1H, J = 7.6 Hz, ArH),
7.22 (t, 1H, J = 7.6 Hz, ArH), 4.93 (s, 1H, CH), 3.88 (s, 3H, CH3).
13C‐NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.0, 156.1, 138.4,
136.5, 133.5, 133.3, 133.0, 132.4, 129.5, 128.3, 124.9, 122.8,
121.8, 121.3, 118.9, 118.5, 110.7, 104.2, 81.7, 54.0, 37.2, 33.2.
Anal. calcd for C22H14Cl2N4O: C, 62.72; H, 3.35; N, 13.30. Found:
C, 62.91; H, 3.60; N, 13.49.
2‐Amino‐6‐(1‐methyl‐1H‐indol‐3‐yl)‐4‐(4‐ nitrophenyl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{2, 1, 4}). Solid; M.p. 232–234°C.
IR (potassium bromide): ν 3447.8, 3336.9, 3308.5, 3217.5,
3056.6, 2199.3, 1676.9, 1622.0, 1518.2, 1474.9, 1403.8,
1347.5, 1122.2, 736.2 cm−1 1H‐NMR (400 MHz, DMSO‐d6)
.
(δ, ppm): 8.30 (d, 2H, J = 8.4 Hz, ArH), 8.18 (s, 1H, ArH),
8.00 (d, 1H, J = 8.0 Hz, ArH), 7.66 (d, 2H, J = 8.4 Hz, ArH),
7.57 (d, 1H, J = 8.4 Hz, ArH), 7.46 (s, 2H, NH2), 7.30–7.33
(m, 1H, ArH), 7.22 (t, 1H, J = 7.6 Hz, ArH), 4.71 (s, 1H, CH),
3.88 (s, 3H, CH3). 13C‐NMR (100 MHz, DMSO‐d6) (δ, ppm):
158.9, 155.9, 150.3, 147.1, 136.5, 133.1, 129.1, 124.9, 124.2,
122.8, 121.9, 121.4, 119.0, 118.6, 110.7, 104.2, 82.4, 54.8,
39.4, 33.3. Anal. calcd for C22H15N5O3: C, 66.49; H, 3.80; N,
17.62. Found: C, 66.61; H, 3.85; N, 17.57.
2‐Amino‐6‐(7‐methyl‐1H‐indol‐3‐yl)‐4‐(4‐ nitrophenyl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{2, 1, 5}). Solid; M.p. 250–252°C.
IR (potassium bromide): ν 3440.6, 3299.5, 3208.4, 3056.0,
2203.7, 1681.4, 1621.1, 1595.5, 1518.3, 1406.1, 1350.0,
2‐Amino‐4‐(2,4‐dichlorophenyl)‐6‐(7‐methyl‐1H‐indol‐3‐yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{3, 1, 5}). Solid; M.p. 266–268°C.
IR (potassium bromide): ν 3473.2, 3283.2, 3205.4, 2202.8, 1672.7,
1616.3, 1521.2, 1405.9, 1362.4, 1159.7, 824.7 cm−1. 1H‐NMR (400
MHz, DMSO‐d6) (δ, ppm): 12.02 (s, 1H, NH), 8.10 (d, 1H, J = 3.2
Hz, ArH), 7.77 (d, 1H, J = 8.4 Hz, ArH), 7.69 (s, 1H, ArH), 7.50–
7.55 (m, 2H, ArH), 7.40 (s, 2H, NH2), 7.03–7.10 (m, 2H, ArH),
4.94 (s, 1H, CH), 2.50 (s, 3H, CH3). 13C‐NMR (75 MHz, DMSO‐
d6) (δ, ppm): 159.1, 156.6, 138.4, 135.5, 133.5, 133.3, 132.5,
129.5, 129.1, 128.3, 124.3, 123.2, 121.5, 121.2, 119.1, 118.9,
118.5, 105.7, 82.0, 54.0, 37.1, 16.7. Anal. calcd for C22H14Cl2N4O:
C, 62.72; H, 3.35; N, 13.30. Found: C, 62.83; H, 3.46; N, 13.55.
2‐Amino‐4‐(3‐nitrophenyl)‐6‐(2‐phenyl‐1H‐indol‐3‐ yl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{4, 1, 3}). Solid; M.p. 230–232°C.
IR (potassium bromide): ν 3442.5, 3317.5, 2193.0, 1671.8,
1164.1, 1011.2, 724.8 cm−1 1H‐NMR (400 MHz, DMSO‐d6)
.
(δ, ppm): 12.04 (s, 1H, NH), 8.31 (d, 2H, J = 8.8 Hz, ArH),
8.12 (d, 1H, J = 3.2 Hz, ArH), 7.78 (d, 1H, J = 7.6 Hz, ArH),
7.66 (d, 2H, J = 8.8 Hz, ArH), 7.44 (s, 2H, NH2), 7.04–7.10
(m, 2H, ArH), 4.71 (s, 1H, CH), 2.50 (s, 1H, CH3). 13C‐NMR
(75 MHz, DMSO‐d6) (δ, ppm): 158.9, 156.5, 150.3, 147.1,
135.5, 129.3, 129.2, 124.3, 123.3, 121.6, 121.3, 119.2, 119.0,
118.8, 105.7, 82.7, 54.8, 39.4, 16.7. Anal. calcd for
C22H15N5O3: C, 66.49; H, 3.80; N, 17.62. Found: C, 66.70; H,
3.97; N, 17.85.
2‐Amino‐6‐(5‐bromo‐1H‐indol‐3‐yl)‐4‐(2,4‐dichlorophenyl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{3, 1, 1}). Solid; M.p. 298–300°C.
IR (KBr): ν 3483.0, 3215.4, 3083.8, 2201.5, 1672.5, 1587.8, 1519.0,
1361.1, 1402.3, 1102.8, 887.0, 825.6 cm−1. 1H‐NMR (400 MHz,
DMSO‐d6) (δ, ppm): 12.17 (d, 2H, J = 2.0 Hz, NH), 8.17 (d, 1H,
J = 3.2 Hz, ArH), 8.03 (d, 1H, J = 1.6 Hz, ArH), 7.69 (d, 1H, J = 1.6
Hz, ArH), 7.47–7.57 (m, 5H, NH2 + ArH), 7.35–7.38 (m, 1H, ArH),
4.95 (s, 1H, CH). 13C‐NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.1,
155.9, 138.3, 134.8, 133.5, 133.4, 132.6, 130.8, 129.4, 128.4, 126.1,
125.5, 123.3, 118.9, 118.3, 114.4, 114.0, 105.0, 83.0, 53.9, 37.0.
Anal. calcd for C21H11BrCl2N4O: C, 51.88; H, 2.28; N, 11.52.
Found: C, 52.07; H, 2.41; N, 11.53.
1
1601.0, 1528.2, 1452.5, 1401.1, 1138.8, 741.5 cm−1. H‐NMR
(400 MHz, DMSO‐d6) (δ, ppm): 12.16 (s, 1H, NH), 8.25 (d,
1H, J = 8.0 Hz, ArH), 8.21 (s, 1H, ArH), 7.88 (d, 1H, J = 7.2
Hz, ArH), 7.80 (t, 1H, J = 8.0 Hz, ArH), 7.57 (s, 3H, ArH),
7.50 (d, 1H, J = 8.0 Hz, ArH), 7.38–7.40 (m, 5H, NH2 + ArH),
7.24–7.27 (m, 1H, ArH), 7.16–7.20 (m, 1H, ArH), 4.77 (s, 1H,
CH). 13C‐NMR (100 MHz, DMSO‐d6) (δ, ppm): 159.6, 155.7,
148.2, 144.4, 139.8, 135.8, 134.7, 131.0, 130.8, 128.9, 128.8,
127.6, 127.0, 123.0, 122.3, 121.0, 119.2, 119.1, 116.6, 112.1,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013
Facile and Efficient Synthesis of Indol-3-yl Substituted Pyran Derivatives via One-Pot
Multicomponent Reactions under Ultrasonic Irradiation
102.2, 91.6, 54.5. Anal. calcd for C27H17N5O3: C, 70.58; H, 3.73;
N, 15.24. Found: C, 70.65; H, 3.84; N, 15.33.
3H, NH2 + ArH), 7.03–7.09 (m, 2H, ArH), 4.92 (s, 1H, CH),
2.50 (s, 3H, CH3). 13C‐NMR (75 MHz, DMSO‐d6) (δ, ppm):
159.0, 156.4, 141.0, 135.5, 133.3, 131.2, 129.9, 129.0, 128.8,
124.3, 123.2, 122.7, 121.5, 121.2, 119.1, 118.9, 118.6, 105.8,
82.7, 54.7, 39.7, 16.7. Anal. calcd for C22H15BrN4O: C, 61.27;
H, 3.51; N, 12.99. Found: C, 61.53; H, 3.79; N, 13.17.
2‐Amino‐6‐(1‐methyl‐1H‐indol‐3‐yl)‐4‐(3‐ nitrophenyl)‐ 4H‐
pyran‐3,5‐dicarbonitrile (4{4, 1, 4}). Solid; M.p. 238–240°C.
IR (potassium bromide): ν 3439.8, 3346.1, 3123.0, 2933.6,
2194.3, 1671.6, 1621.7, 1588.3, 1530.6, 1408.1, 1349.8,
1307.4, 1155.0, 742.5 cm−1
.
1H‐NMR (400 MHz, DMSO‐d6)
2‐Amino‐6‐(5‐bromo‐1H‐ indol‐3‐ yl)‐ 4‐ phenyl‐ 4H‐ pyran‐
3,5‐dicarbonitrile (4{6, 1, 1}). Solid; M.p. 238–240°C. IR
(potassium bromide): ν 3397.4, 3390.8, 3290.5, 3115.4, 2201.4,
(δ, ppm): 8.19–8.24 (m, 3H, ArH), 8.00 (d, 1H, J = 8.0 Hz,
ArH), 7.88 (d, 1H, J = 7.6 Hz, ArH), 7.77 (t, 1H, J = 8.0 Hz,
ArH), 7.57 (d, 1H, J = 8.0 Hz, ArH), 7.48 (m, 2H, NH2), 7.30–
7.34 (m, 1H, ArH), 7.23 (t, 1H, J = 7.6 Hz, ArH), 4.77 (s, 1H,
CH), 3.88 (s, 3H, CH3). 13C‐NMR (100 MHz, DMSO‐d6) (δ,
ppm): 159., 156.0, 148.2, 145.3, 136.6, 134.6, 133.1, 130.7,
124.9, 122.9, 122.8, 122.2, 122.0, 121.4, 119.1, 118.7, 110.7,
104.3, 82.6, 54.9, 39.2, 33.3. Anal. calcd for C22H15N5O3: C,
66.49; H, 3.80; N, 17.62. Found: C, 66.55; H, 3.94; N, 17.88.
2‐Amino‐6‐(5‐ bromo‐1H‐ indol‐ 3‐ yl)‐ 4‐ (2‐ bromophenyl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{5, 1, 1}). Solid; M.p. 294–296°
C. IR (potassium bromide): ν 3449.9, 3202.6, 2192.1, 1665.0,
1
1669.3, 1530.7, 1392.7, 1363.0, 1256.4, 899.1, 799.0 cm−1. H‐
NMR (400 MHz, DMSO‐d6) (δ, ppm): 12.14 (s, 1H, NH), 8.15
(d, 1H, J = 3.2 Hz, ArH), 8.01 (d, 1H, J = 1.2 Hz, ArH), 7.32–
7.49 (m, 9H, NH2 + ArH), 4.43 (s, 1H, CH). 13C‐NMR (75
MHz, DMSO‐d6) (δ, ppm): 158.7, 155.0, 142.9, 134.7, 130.6,
128.9, 127.7, 126.1, 125.5, 123.2, 119.3, 118.7, 114.3, 113.9,
105.1, 85.3, 55.8. Anal. calcd for C21H13BrN4O: C, 60.45; H,
3.14; N, 13.43. Found: C, 60.44; H, 3.19; N, 13.53.
2‐Amino‐6‐(1‐methyl‐1H‐ indol‐3‐ yl)‐ 4‐ phenyl‐4H‐ pyran‐
3,5‐dicarbonitrile (4{6, 1, 4}). Solid; M.p. 242–244°C. IR
(potassium bromide): ν 3479.0, 3343.5, 3130.2, 2855.9, 2203.5,
1
1625.5, 1518.5, 1465.8, 1359.8, 1157.0, 805.3 cm−1. H‐NMR
1
(400 MHz, DMSO‐d6) (δ, ppm): 12.16 (s, 1H, NH), 8.16 (s,
1H, J = 2.8 Hz, ArH), 8.03 (s, 1H, ArH), 7.67 (d, 1H, J = 8.0
Hz, ArH), 7.45–7.49 (m, 5H, NH2 + ArH), 7.36 (d, 1H, J = 8.8
Hz, ArH), 7.27–7.31 (m, 1H, ArH), 4.92 (s, 1H, CH). 13C‐
NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.0, 155.7, 140.9,
134.8, 133.3, 131.4, 130.7, 129.9, 128.8, 126.1, 125.5, 123.3,
122.8, 119.0, 118.4, 114.4, 113.9, 105.1, 83.8, 54.6. Anal. calcd
for C21H12Br2N4O: C, 50.84; H, 2.44; N, 11.29. Found: C,
50.88; H, 2.59; N, 11.40.
1672.3, 1608.0, 1525.3, 1388.5, 1112.9, 744.2, 708.0 cm−1. H‐
NMR (400 MHz, DMSO‐d6) (δ, ppm): 8.15 (s, 1H, ArH), 7.97
(d, 1H, J = 8.0 Hz, ArH), 7.56 (d, 1H, J = 8.0 Hz, ArH), 7.41–
7.45 (m, 2H, ArH), 7.30–7.35 (m, 6H, NH2 + ArH), 7.21 (t, 1H, J
= 7.6 Hz, ArH), 4.42 (s, 1H, CH), 3.87 (s, 3H, CH3). 13C‐NMR
(75 MHz, DMSO‐d6) (δ, ppm): 158.7, 155.3, 143.1, 136.5, 132.8,
128.9, 127.7, 127.6, 124.9, 122.7, 121.8, 121.3, 119.3, 118.9,
110.7, 104.4, 84.0, 55.9, 33.2. Anal. calcd for C22H16N4O: C,
74.98; H, 4.58; N, 15.90. Found: C, 74.99; H, 4.71; N, 16.03.
2‐Amino‐6‐(1‐ methyl‐1H‐ indol‐3‐yl)‐ 4‐ (naphthalen‐2‐ yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{7, 1, 4}). Solid; M.p. 244–246°
C. IR (potassium bromide): ν 3478.4, 3318.2, 3120.3, 3024.9,
2195.7, 1676.6, 1588.1, 1525.0, 1360.7, 1239.0, 1120.7, 736.9
2‐Amino‐4‐(2‐bromophenyl)‐ 6‐ (2‐ phenyl‐ 1H‐ indol‐3‐ yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{5, 1, 3}). Solid; M.p. 220–222°
C. IR (potassium bromide): ν 3447.2, 3378.4, 3314.5, 3184.1,
1
2201.0, 1672.7, 1394.0, 1126.7, 1023.9, 744.2 cm−1. H‐NMR
(400 MHz, DMSO‐d6) (δ, ppm): 12.14 (s, 1H, NH), 7.65 (d,
3H, J = 7.6 Hz, ArH), 7.38–7.58 (m, 7H, ArH), 7.22–7.32 (m,
4H, NH2 + ArH), 7.17 (t, 1H, J = 7.6 Hz, ArH), 4.95 (s, 1H,
CH). 13C‐NMR (75 MHz, DMSO‐d6) (δ, ppm): 159.5, 155.6,
140.4, 139.5, 135.7, 133.2, 131.2, 130.9, 130.0, 129.0, 128.8,
127.6, 127.0, 122.9, 122.7, 120.8, 119.3, 119.0, 116.4, 112.0,
102.2, 91.3, 54.5. Anal. calcd for C27H17BrN4O: C, 65.73; H,
3.47; N, 11.36. Found: C, 65.93; H, 3.63; N, 11.49.
cm−1 1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 8.16 (s, 1H,
.
ArH), 7.93–8.01 (m, 4H, ArH), 7.87 (s, 1H, ArH), 7.48–7.58
(m, 4H, ArH), 7.30–7.36 (m, 3H, NH2 + ArH), 7.20–7.24 (m,
1H, ArH), 4.62 (s, 1H, CH), 3.87 (s, 3H, CH3). 13C‐NMR (75
MHz, DMSO‐d6) (δ, ppm): 158.7, 155.3, 140.4, 136.5, 132.9,
132.6, 129.0, 127.9, 127.6, 126.6, 126.3, 126.3, 125.5, 124.9,
122.8, 121.8, 121.3, 119.3, 118.9, 110.7, 104.4, 83.8, 55.8,
33.2. Anal. calcd for C26H18N4O: C, 77.59; H, 4.51; N, 13.92.
Found: C, 77.32; H, 4.62; N, 13.88.
2‐Amino‐4‐(2‐bromophenyl)‐6‐(1‐ methyl‐ 1H‐ indol‐ 3‐ yl) ‐
4H‐pyran‐3,5‐dicarbonitrile (4{5, 1, 4}). Solid; M.p. 250–252°
C. IR (potassium bromide): ν 3459.4, 3299.8, 3175.1, 2202.9,
Acknowledgments. The work was partially supported by the
National Natural Science Foundation of China (Nos. 20672079,
20910102041, 21042007), Natural Science Foundation of
Jiangsu Province (No. BK 2006048), Nature Science Key Basic
Research of Jiangsu Province for Higher Education (No. 10KJB
150016), the Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20060285001), and Key
Project in Science and Technology Innovation Cultivation
Program of Soochow University.
1672.3, 1594.1, 1531.4, 1465.0, 1367.6, 1238.1, 747.1 cm−1
.
1H‐NMR (400 MHz, DMSO‐d6) (δ, ppm): 8.15 (s, 1H, ArH),
7.97 (d, 1H, J = 8.0 Hz, ArH), 7.67 (d, 1H, J = 8.0 Hz, ArH),
7.57 (d, 1H, J = 8.0 Hz, ArH), 7.43–7.49 (m, 2H, ArH), 7.27–
7.36 (m, 4H, NH2 + ArH), 7.22 (t, 1H, J = 7.6 Hz, ArH), 4.92
(s, 1H, CH), 3.88 (s, 3H, CH3). 13C‐NMR (75 MHz, DMSO‐d6)
(δ, ppm): 158.9, 155.9, 141.0, 136.5, 133.3, 132.9, 131.2,
129.9, 128.7, 124.9, 122.8, 122.7, 121.8, 121.3, 118.9, 118.5,
110.7, 104.3, 82.4, 54.7, 39.7, 33.2. Anal. calcd for
C22H15BrN4O: C, 61.27; H, 3.51; N, 12.99. Found: C, 61.45;
H, 3.80; N, 13.10.
REFERENCES AND NOTES
2‐Amino‐4‐(2‐ bromophenyl)‐ 6‐ (7‐ methyl‐1H‐ indol‐3‐ yl)‐
4H‐pyran‐3,5‐dicarbonitrile (4{5, 1, 5}). Solid; M.p. 218–220°
C. IR (KBr): ν 3473.3, 3260.3, 3054.0, 2881.2, 2195.9, 1667.9,
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Journal of Heterocyclic Chemistry
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Vol 50
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Featured Compounds
2{1}
1{1}
3{1}
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1
1{2}
1{3}
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1{4}
1{5}
1{6}
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FC-1

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1{7}
1{8}
1{9}
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3
3{2}
3{3}
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3{4}
3{5}
4{1,1,1}
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FC-2

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4{1,1,2}
4{1,1,3}
4{1,1,4}
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4{1,1,5}
4{2,1,1}
4{2,1,2}
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4{2,1,3}
4{2,1,4}
4{2,1,5}
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FC-3

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4{3,1,1}
4{3,1,2}
4{3,1,3}
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4{3,1,4}
4{3,1,5}
4{4,1,3}
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4{4,1,4}
4{5,1,1}
4{5,1,3}
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FC-4

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4{5,1,4}
4{5,1,5}
4{6,1,1}
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4{6,1,4}
4{7,1,4}
4{8,1,4}
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4{9,1,4}
4
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FC-5