Synthesis of spiro[benzopyrazolonaphthyridine-indoline]-diones and spiro[chromenopyrazolopyridine-indoline]-diones by one-pot, three-component methods in water

Article abstract of DOI:10.1016/j.tet.2009.09.009

The synthesis of spiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,3′-indoline]-2′,6(5H)-diones and spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,3′-indoline]-2′,6(6aH,10H)-diones via a one-pot, three-component reaction of 4-hydroxycoumarin or 4-hydroxy-

Full text of DOI:10.1016/j.tet.2009.09.009

Tetrahedron 65 (2009) 9316–9321
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of spiro[benzopyrazolonaphthyridine-indoline]-diones
and spiro[chromenopyrazolopyridine-indoline]-diones
by one-pot, three-component methods in water
*
Somayeh Ahadi, Ramin Ghahremanzadeh, Peiman Mirzaei, Ayoob Bazgir
Department of Chemistry, Shahid Beheshti University G.C., PO Box 19396-4716, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
The synthesis of spiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-diones and
spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-20,6(6aH,10H)-diones via a one-pot, three-
component reaction of 4-hydroxycoumarin or 4-hydroxy-1-methylquinolin-2(1H)-one, isatins and 1H-
pyrazol-5-amines in water is reported.
Article history:
Received 8 April 2009
Received in revised form 19 August 2009
Accepted 3 September 2009
Available online 9 September 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
4-Hydroxy-1-methylquinolin-2(1H)-one
Coumarin
Isatin
Pyrazole
Spirooxindole
1. Introduction
moiety in numerous biologically active compounds,18–20 among
them such prominent drug molecules as Celecoxib and Pyr-
The development of organic reactions in water has become
highly desirable in recent years to meet environmental consider-
ations.1,2 The use of water as a sole medium for organic reactions
would greatly contribute to the expansion of environmentally
friendly processes. In this context, in recent years, much attention
has been focused on organic reactions in water.
Multi-component reactions (MCRs), due to their productivity,
simple procedures, convergence and facile execution, are one of the
best tools in combinatorial chemistry.3 Therefore, the design of novel
MCRs has attracted great attention from research groups working in
areas such as drug discovery, organic synthesis and materials science.
As a result, the number of new MCRs in water has grown rapidly.4–8
Indole and indoline fragments are important moieties of a large
number of natural products and medicinal agents,9 and some
indolines, spiro-annulated with heterocycles in the 3-position, have
shown high biological activity.10,11 The spirooxindole system is the
core structure of many pharmacological agents and natural alka-
loids.12,13 Therefore, a number of methods have been reported for
the preparation of spirooxindole fused heterocycles.14–17
azofurine. On the other hand, benzonaphthyridine derivatives are
compounds of current interest due to their diverse biological
activities.21 These compounds can also be considered as ‘aza-
analogues’ of phenanthridine derivatives, which are widely studied
in the field of medicinal chemistry.22
Chromenes are an important group of compounds; they widely
exist in plants, including edible vegetables and fruits.23 Synthetic
analogues were developed over the years, some of them displaying
remarkable effects as pharmaceuticals,24,25 including antifungal26
and antimicrobial activity.27 Similarly, pyrazolopyridines are very
interesting compounds and have received considerable attention as
a result of their biological activity and structural relationship to in-
doles.28–31
As part of our continuing efforts on the development of new
routes for the synthesis of biologically active heterocyclic com-
pounds,32–39 we have already reported some procedures for the
synthesis of spiropyrimidoquinoline’pyrrolopyrimidines, spiroin-
doline-pyridodipyrimidines, spiroindoline-xanthen-triones and
spirodibenzoxanthene-indoline-pentaones by the condensation
reaction between amino-uraciles, dimedone or 2-hydroxynaph-
thalene-1,4-dione and isatins.40–43 Herein, we report a simple and
clean synthesis of spiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyr-
idine-7,30-indoline]-20,6(5H)-diones and spiro[chromeno[4,3-b]-
pyrazolo[4,3-e]pyridine-7,30-indoline]-20,6(6aH,10H)-diones in
water.
Heterocycles containing the pyrazole ring are important targets
in synthetic and medicinal chemistry because this fragment is a key
* Corresponding author. Fax: þ98 21 2403041.
E-mail address: a_bazgir@sbu.ac.ir (A. Bazgir).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.009

S. Ahadi et al. / Tetrahedron 65 (2009) 9316–9321
9317
2. Results and discussion
The elucidation of the structure of 4 using NMR spectroscopic
data is discussed with 4a as an example. The 1H NMR spectrum of
The one-pot, three-component condensation reaction of 4-
hydroxy-1-methylquinolin-2(1H)-one 1, various isatins 2 and 1H-
pyrazol-5-amines 3 in the presence of catalytic p-TSA proceeded
rapidly in refluxing water and were complete after 24 h to afford
10,11-dihydrospiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-
indoline]-20,6(5H)-diones 4, in good yields (Scheme 1).
compound 4a exhibited one singlet at
a multiplet at
¼6.49–8.05 for the aromatic hydrogens and two
singlets at 9.77 and 9.91 for the two NH groups. The generated
d
¼3.44 for the methyl group,
d
d
spirocyclic carbon was assigned through 13C NMR and DEPT exper-
iments at 50.7 ppm. The 13C NMR and DEPTspectrum of 4a confirms
the presence of one methyl group, ten quaternary carbons in the
aromatic or alkenic region and two carbonyl groups. The mass
spectrum shows the expected molecular ion peak.
Ar
H
N
The results were good in terms of yields and product purity in
the presence of p-TSA, while without p-TSA the yields of products
were trace even after 30 h.
To the best of our knowledge, this new procedure provides the
first example of an efficient and three-component method for the
synthesis of spiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-
indoline]-20,6(5H)-diones. This method, based on three-component
p-TSA-catalyzed reaction in water, is the most simple and conve-
nient and would be applicable for the synthesis of different types of
spirobenzopyrazolonaphthyridine-indolines.
We have not established an exact mechanism for the formation
of spirobenzopyrazolonaphthyridine-indolines 4, however, a rea-
sonable possibility is shown in Scheme 2.
To further explore the potential of this protocol for spiro-hetero-
cycle synthesis, we investigated reaction of acenaphthylene-1,2-
N
OH
N
O
Ph
X
H2O (Reflux)
Ph
+
+
O
N
NMe
H2N
X
N
Ar
p-TSA
24h
N
N
O
O
O
R
Me
N
R
1
2
3
4
Product
R
X
Ar
Yield (%)a
4
a
b
c
d
e
f
g
h
i
H
Me
Et
Br
Br
H
H
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
79
78
70
85
83
72
80
68
77
73
65
67
H
Me
Et
H
Et
H
H
Br
NO2
Br
NO2
NO2
H
Me
H
4-NO2 - C6H4
4-NO2 - C6H4
4-NO2 - C6H4
4-NO2 - C6H4
j
k
l
O
O
H
OH
Ph
O
O
aIsolated yields
Ph
H2O (Reflux)
+
N
+
NMe
NH2
N
Ph
p-TSA
24 h
N
Scheme 1. Synthesis of spirobenzopyrazolonaphthyridine-indolines 4.
N
O
N
H
N
Me
Ph
1
5
3
6
73%
O
Scheme 3.
X
O
N
2
R
Ph
OH
Ar
N
H
N
OH
OH
O
O
Ph
N
N
Ph
NH2
X
H2O (Reflux)
N
Ar
O
O
+
O
+
N
O
N
1
H2N
3
O
N
p-TSA
24h
Me
N
X
N
R
O
O
Ar
H+
H+
N
R
7
2
3
8
RN
RN
X
HO
X
O
Ph
N
Ar
N
OH
H
N
OH
O
N
N
Ar
NH2
Me
Ph
O
X
O
9
O
H+
H+
3
N
1
R
RN
X
Product 8
R
X
Ar
Yield (%)a
72
O
O
Ph
a
H
Me
Et
H
H
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
NMe
N
N
70
69
75
68
84
88
86
80
70
84
b
c
d
e
f
O
NH2
RN
Ar
H
NO2
NO2
Br
Et
H
X
O
Me
H
Br
g
h
i
Ph
N
O
H
4-NO2- C6H4
4-NO2- C6H4
4-NO2- C6H4
4-NO2- C6H4
NMe
HO
N
H
Me
H
H
N
Br
j
Ar
H
NO2
k
- H2O
Product 4
aIsolated yields
Scheme 4. Synthesis of spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
diones 8.
Scheme 2.

9318
S. Ahadi et al. / Tetrahedron 65 (2009) 9316–9321
dione 5 instead of isatin 2 and obtained 50-methyl-80,100-diphenyl-
100,110-dihydro-2H-spiro[acenaphthylene-1,70-benzo[h]pyrazolo[3,4-b]-
[1,6]naphthyridine]-2,60(50H)-dione 6 in 73% yield (Scheme 3).
After completion, the reaction mixture was filtered and the pre-
cipitate washed with water (10 mL) and EtOH (10 mL) to afford the
pure product 4a as cream powder (0.41 g, 79%). Mp 290 ꢀC (dec); IR
(KBr) (nmax, cmꢁ1): 3363, 3198, 1725, 1632; 1H NMR (300 MHz,
DMSO-d6) dH¼3.44 (3H, s, CH3), 6.49–8.05 (18H, m, H-Ar), 9.77 (1H,
s, NH), 9.91 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.4
(NCH3), 50.7 (Cspiro), 101.6 (C), 109.3 (CH), 114.0 (C), 115.1 (CH), 121.5
(CH), 121.8 (CH), 123.0 (CH), 123.6 (CH), 124.3 (CH), 127.4 (CH), 127.7
(CH), 128.0 (CH), 128.2 (CH), 129.1 (CH), 130.0 (CH), 131.6 (CH), 133.2
(C), 138.4 (C), 138.5 (C), 139.1 (C), 139.2 (C), 142.8 (C), 143.4 (C), 149.6
(C), 159.9 (CO), 179.6 (CO). MS (EI, 70 eV) m/z: 521 (Mþ). Anal. Calcd
for C33H23N5O2: C, 75.99; H, 4.44; N, 13.43%. Found: C, 75.78; H,
4.50; N, 13.49%.
When we introduced 4-hydroxycoumarin 7 into the described
three-component condensation reaction instead of the 4-hydroxy-
1-methylquinolin-2(1H)-one 1, it was interesting that the desired
products of 9 were not detected at all, while spiro[chromeno[4,3-
b]pyrazolo[4,3-e]pyridine-7,30-indoline]-20,6(6aH,10H)-diones
8
were obtained in good yields under the same reaction conditions
(Scheme 4).
As expected, when the isatin 2 was replaced by acenaphthylene-
1,2-dione 5, 11a0-hydroxy-80,100-diphenyl-110,11a0-dihydro-2H,60H-
spiro[acenaphthylene-1,70-chromeno[3,4-e]pyrazolo[3,4-b]pyridine]-
2,60(6a0H, 100H)-dione 10 was obtained under the same reaction
conditions (Scheme 5).
4.2.1. 10,5-Dimethyl-8,10-diphenyl-10,11-dihydrospiro[benzo[h]pyr-
azolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-dione
(4b). Light brown powder (0.42 g, 78%); mp 300 ꢀC dec; IR (KBr)
(
nmax, cmꢁ1): 3419, 3055,1723, 1610; 1H NMR (300 MHz, DMSO-d6):
O
O
OH
O
Ph
O
O
dH¼2.83 (3H, s, CH3), 3.35 (3H, s, CH3), 6.67–8.02 (18H, m, H-Ar),
9.75 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼27.0 (NCH3), 49.0
(NCH3), 49.4 (Cspiro), 95.9 (C), 97.4 (C), 109.1 (CH), 123.8 (CH), 124.3
(CH), 127.0 (CH), 127.2 (CH), 127.6 (CH), 127.7 (CH), 127.9 (CH), 128.8
(CH), 128.9 (CH), 129.6 (CH), 129.6 (CH), 132.2 (C), 134.7 (C), 135.2
(C), 138.7 (C), 139.0 (C), 142.7 (C), 145.9 (C), 146.6 (C), 150.4 (CO),
177.9 (CO). MS (EI, 70 eV) m/z: 535 (Mþ). Anal. Calcd for
C34H25N5O2. C, 76.24; H, 4.70; N, 13.08. Found: C, 76.13; H, 4.75; N,
13.01%.
Ph
H2O (Reflux)
+
N
+
O
NH2
N
Ph
p-TSA
24 h
N
O
N
H
N
Ph
OH
10
1
5
3
70%
Scheme 5.
The nature of products 4, 6, 8 and 10 as 1:1:1 adducts was ap-
parent from their mass spectra, which displayed, in each case, the
molecular ion peak at appropriate m/z values. Compounds 4, 6, 8 and
10 are stable solids whose structures are fully supported by IR,1H and
13C NMR spectroscopies, mass spectrometry and elemental analysis.
4.2.2. 10-Ethyl-5-methyl-8,10-diphenyl-10,11-dihydrospiro[benzo[h]-
pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-dione
(4c). Yellow powder (0.38 g, 70%); mp 270 ꢀC dec; IR (KBr) (nmax
,
cmꢁ1): 3399, 3055, 1704, 1637; 1H NMR (300 MHz, DMSO-d6):
dH¼0.77 (3H, t, CH3, 3JHH¼6.6 Hz), 3.12–3.38 (2H, m, CH2), 3.42 (3H,
s, CH3), 6.55–8.06 (18H, m, H-Ar), 9.84 (1H, s, NH). 13C NMR
(75 MHz, DMSO-d6): dC¼12.0 (CH3), 29.5 (NCH3), 34.4 (CH2), 50.1
(Cspiro), 101.5 (C), 107.3 (CH), 108.2 (CH), 114.0 (C), 115.1 (CH), 121.8
(CH), 122.1 (CH), 123.0 (CH), 123.6 (CH), 124.3 (CH), 127.4 (CH), 127.8
(CH), 128.3 (CH), 129.0 (CH), 130.0 (CH), 131.7 (CH), 133.2 (C), 137.7
(C), 138.6 (C), 139.1 (C), 142.9 (C), 143.8 (C), 149.6 (C), 160.0 (CO),
177.5 (CO). MS (EI, 70 eV) m/z: 549 (Mþ). Anal. Calcd for
C35H27N5O2. C, 76.48; H, 4.95; N, 12.74. Found: C, 76.39; H, 4.91; N,
12.69%.
3. Conclusion
In conclusion, we have described a facile, one-pot and three-
component method for the synthesis of spiro[benzo[h]pyr-
azolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-diones and
spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-diones
in water. Prominent among the advantages of this new method are
novelty, operational simplicity, good yields and easy work-up pro-
cedures employed.
4. Experimental
4.1. General
4.2.3. 50-Bromo-5-methyl-8,10-diphenyl-10,11-dihydrospiro[benzo-
[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-dione
(4d). White powder (0.51 g, 85%); mp 288 ꢀC dec; IR (KBr) (nmax
,
cmꢁ1): 3429, 3311, 1719, 1627; 1H NMR (300 MHz, DMSO-d6):
dH¼3.49 (3H, s, CH3), 6.41–8.06 (17H, m, H-Ar), 9.92 (1H, s, NH),
10.08 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.5 (NCH3),
50.9 (Cspiro), 101.0 (C), 106.7 (CH), 111.2 (C), 113.0 (CH), 113.9 (C),
115.2 (CH), 123.2 (CH), 126.3 (CH), 127.5 (CH), 127.8 (CH), 128.4
(CH), 129.1 (CH), 129.9 (CH), 130.6 (CH), 131.8 (CH), 133.0 (C), 138.6
(C), 139.1 (C), 139.2 (C), 140.6 (C), 142.6 (C), 143.1 (C), 149.6 (C),
160.0 (CO), 179.3 (CO). MS (EI, 70 eV) m/z: 601 (Mþ), 599 (Mþ).
Anal. Calcd for C33H22BrN5O2. C, 66.01; H, 3.69; N, 11.66. Found: C,
66.17; H, 3.60; N, 11.60%.
Melting points were measured on an Electrothermal 9100 ap-
paratus. Mass spectra were recorded on a FINNIGAN-MAT 8430
mass spectrometer operating at an ionization potential of 70 eV. 1H,
13C NMR and DEPT spectra were recorded on a BRUKER DRX-300
AVANCE spectrometer at 300.13 and 75.47 MHz, respectively. 1H
and 13C NMR spectra were obtained on solutions in CD3SOCD3
using TMS as internal standard. IR spectra were recorded using an
FTIR apparatus. Elemental analyses were performed using
a Heracus CHN-O-Rapid analyzer.
The chemicals used in this work were obtained from Fluka and
Merck and were used without purification.
4.2.4. 50-Bromo-10,5-dimethyl-8,10-diphenyl-10,11-dihydrospiro[benzo-
[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-dione
4.2. 5-Methyl-8,10-diphenyl-10,11-dihydrospiro [benzo[h]-
pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-
dione (4a)
(4e). Cream powder (0.51 g, 83%); mp 293 ꢀC dec; IR (KBr) (nmax
,
cmꢁ1): 3260, 3070, 1713, 1643; 1H NMR (300 MHz, DMSO-d6):
dH¼2.67 (3H, s, CH3), 3.43 (3H, s, CH3), 6.56–8.08 (17H, m, H-Ar),
9.92 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼26.1 (CH3), 29.5
(NCH3), 50.2 (Cspiro), 101.0 (C), 106.3 (CH), 109.9 (C), 113.9 (C), 115.3
(CH), 121.9 (CH), 123.2 (CH), 124.4 (CH), 126.0 (CH), 127.5 (CH), 127.8
(CH),128.4 (CH), 129.0 (CH), 129.9 (CH), 130.8 (CH), 131.9 (CH), 132.8
A mixture of 4-hydroxy-1-methylquinolin-2(1H)-one (0.18 g,
1 mmol), isatin (0.15 g, 1 mmol), 1,3-diphenyl-1H-pyrazol-5-amine
(0.24 g, 1 mmol) and p-TSA (0.1 g) in refluxing water (5 mL) was
stirred for 24 h (the progress of the reaction was monitored by TLC).

S. Ahadi et al. / Tetrahedron 65 (2009) 9316–9321
9319
(C), 138.5 (C), 139.1 (C), 139.2 (C), 139.5 (C), 143.3 (C), 143.5 (C), 149.5
(C), 160.0 (CO), 177.6 (CO). MS (EI, 70 eV) m/z: 615 (Mþ), 613 (Mþ).
Anal. Calcd for C34H24BrN5O2. C, 66.46; H, 3.94; N, 11.40. Found: C,
66.54; H, 3.98; N, 11.48%.
8.5 (17H, m, H-Ar), 10.04 (1H, s, NH). MS (EI, 70 eV) m/z: 580 (Mþ).
Anal. Calcd for C34H24N6O4. C, 70.34; H, 4.17; N, 14.47. Found: C,
70.19; H, 4.11; N, 14.40%.
Due to very low solubility of the product 4c, we cannot report
the 13C NMR data for this product.
4.2.5. 50-Bromo-10-ethyl-5-methyl-8,10-diphenyl-10,11-dihydrospiro-
[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-
dione (4f). Cream powder (0.45 g, 72%); mp >300 ꢀC dec; IR (KBr)
4.2.10. 50-Bromo-5-methyl-10-(4-nitrophenyl)-8-phenyl-10,11-dihy-
drospiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-
20,6(5H)-dione (4k). Yellow powder (0.42 g, 65%); mp >300 ꢀC dec;
IR (KBr) (nmax, cmꢁ1): 3424, 3193, 1712, 1647; 1H NMR (300 MHz,
DMSO-d6): dH¼3.45 (3H, s, CH3), 6.42–8.51 (16H, m, H-Ar), 10.03
(1H, s, NH), 10.15 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.5
(NCH3), 50.8 (Cspiro), 102.0 (C), 107.0 (CH), 111.2 (CH), 113.1 (CH),
113.8 (C), 115.2 (CH), 123.3 (CH), 124.5 (CH), 125.6 (C), 126.4 (CH),
127.9 (CH), 128.7 (CH), 129.0 (CH), 130.8 (CH), 131.9 (CH), 132.4 (C),
139.2 (C), 139.5 (C), 140.3 (C), 142.6 (C), 143.0 (C), 144.1 (C), 145.6 (C),
151.2 (C), 159.9 (CO), 179.1 (CO). MS (EI, 70 eV) m/z: 646 (Mþ), 646
(Mþ). Anal. Calcd for C33H21BrN6O4. C, 61.41; H, 3.28; N, 13.02.
Found: C, 61.49; H, 3.22; N, 13.11%.
(
nmax, cmꢁ1): 3214, 3072, 1694, 1638; 1H NMR (300 MHz, DMSO-d6):
dH¼0.78 (3H, t, CH3, 3JHH¼6 Hz), 3.08–3.35 (2H, m, CH2), 3.42 (3H, s,
CH3), 6.61–8.07 (17H, m, H-Ar), 9.89 (1H, s, NH). 13C NMR (75 MHz,
DMSO-d6): dC¼11.9 (CH3), 29.6 (NCH3), 34.5 (CH2), 50.2 (Cspiro),100.8
(C), 106.5 (CH), 110.1 (C), 113.7 (CH), 113.9 (C), 115.2 (CH), 121.9 (CH),
123.2 (CH), 124.4 (CH), 126.3 (CH), 127.5 (CH), 127.9 (CH), 128.4 (CH),
129.0 (CH), 129.9 (CH),130.8 (C), 131.8 (CH),133.1 (C), 138.6 (C), 139.1
(C), 139.2 (C), 139.9 (C),143.1 (C), 149.4 (C), 160.0 (CO),177.2 (CO). MS
(EI, 70 eV) m/z: 629 (Mþ), 627 (Mþ). Anal. Calcd for C35H26BrN5O2. C,
66.88; H, 4.17; N, 11.14. Found: C, 66.75; H, 4.11; N, 11.20%.
4.2.6. 5-Methyl-50-nitro-8,10-diphenyl-10,11-dihydrospiro[benzo[h]pyr-
azolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-dione
4.2.11. 5-Methyl-50-nitro-10-(4-nitrophenyl)-8-phenyl-10,11-dihy-
drospiro[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-
20,6(5H)-dione (4l). Yellow powder (0.40 g, 65%); mp >300 ꢀC dec; IR
(KBr) (nmax, cmꢁ1): 3394, 3203,1717,1637; 1H NMR (300 MHz, DMSO-
d6): dH¼3.45 (3H, s, CH3), 6.61–8.51 (16H, m, H-Ar), 10.1 (1H, s, NH),
10.73 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.6 (NCH3), 50.5
(Cspiro), 101.6 (C), 106.4 (CH), 109.2 (CH), 113.8 (C), 119.1 (CH), 122.1
(CH), 123.4 (CH), 124.5 (CH), 125.6 (C), 128.0 (CH), 128.8 (CH), 129.0
(CH), 132.1 (CH), 132.2 (CH), 138.6 (C), 139.2 (C), 139.6 (C), 142.3 (C),
143.4 (C), 144.1 (C), 145.7 (C), 149.7 (C),151.2 (C),160.0 (C),166.7 (CO),
180.1 (CO). MS(EI, 70 eV)m/z: 611 (Mþ). Anal. Calcd for C33H21N7O6. C,
64.81; H, 3.46; N, 16.03. Found: C, 64.92; H, 3.42; N, 15.97%.
(4g). Yellow powder (0.45 g, 80%); mp 275 ꢀC dec; IR (KBr) (nmax
,
cmꢁ1): 3409, 3224, 1744, 1626; 1H NMR (300 MHz, DMSO-d6):
dH¼3.46 (3H, s, CH3), 6.61–8.09 (17H, m, H-Ar), 9.97 (1H, s, NH),10.70
(1H, s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.5 (NCH3), 50.6
(Cspiro), 100.5 (C), 106.1 (CH), 113.9 (C), 115.3 (CH), 122.0 (CH), 123.3
(CH), 123.6 (CH), 124.4 (CH), 125.6 (CH), 127.6 (CH), 127.9 (CH), 128.5
(CH),129.1 (CH), 129.5 (CH), 130.0 (CH),132.0 (C),132.8 (C),138.6 (C),
139.0 (C),139.2 (C),142.3 (C),143.5 (C),149.6 (C),149.8 (C),160.1 (CO),
180.3 (CO). MS (EI, 70 eV) m/z: 566 (Mþ). Anal. Calcd for C33H22N6O4.
C, 69.96; H, 3.91; N, 14.83. Found: C, 69.88; H, 3.87; N, 14.76%.
4.2.7. 10-Ethyl-5-methyl-50-nitro-8,10-diphenyl-10,11-dihydrospiro-
[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-
dione (4h). Yellow powder (0.40 g, 68%); mp 266 ꢀC dec; IR (KBr)
4.3. 50-Methyl-80,100-diphenyl-100,110-dihydro-2H-
spiro[acenaphthylene-1,70-benzo[h]pyrazol[3,4-b]-
[1,6]naphthyridine]-2,60(50H)-dione (6)
(
nmax, cmꢁ1): 3255, 3070, 1714, 1638; 1H NMR (300 MHz, DMSO-
3
d6): dH¼. 0.86 (3H, t, CH3, JHH¼9 Hz), 3.18–3.52 (5H, m, CH2 and
CH3), 6.65–8.16 (17H, m, H-Ar), 10.03 (1H, s, NH). 13C NMR (75 MHz,
DMSO-d6): dC¼11.9 (CH3), 29.6 (NCH3), 35.3 (CH2), 50.0 (Cspiro),
100.3 (C), 106.0 (CH), 108.1 (CH), 113.8 (C), 115.4 (CH), 118.8 (CH),
122.0 (CH), 123.3 (CH), 124.5 (CH), 125.7 (CH), 127.6 (CH), 128.0
(CH), 129.0 (CH), 130.0 (CH), 132.0 (CH), 132.8 (C), 138.4 (C), 138.7
(C), 139.0 (C), 139.2 (C), 142.7 (C), 143.5 (C), 149.4 (C), 149.8 (C), 160.1
(CO), 178.4 (CO). MS (EI, 70 eV) m/z: 594 (Mþ). Anal. Calcd for
C35H26N6O4. C, 70.70; H, 4.41; N, 14.13. Found: C, 70.79; H, 4.47; N,
14.05%.
Cream powder (0.41 g, 73%); mp 210 ꢀC dec; IR (KBr) (nmax
,
cmꢁ1): 3260, 3073, 1714, 1643; 1H NMR (300 MHz, DMSO-d6):
dH¼3.02 (3H, s, CH3), 6.6 (20H, m, H-Ar), 8.77 (1H, s, NH). 13C NMR
(75 MHz, DMSO-d6): dC¼28.4 (CH3), 63.0 (Cspiro), 97.6 (CH),111.4 (C),
111.7 (CH), 114.6 (C), 120.7 (CH), 121.0 (CH), 121.4 (C), 122.8 (CH),
123.3 (CH), 125.8 (CH), 126.6 (CH), 128.8 (CH), 129.1 (CH), 129.5
(CH), 131.2 (C), 131.4 (CH), 135.1 (C), 135.4 (CH), 140.4 (C), 141.8 (C),
142.0 (C), 144.5 (C), 153.1 (C), 158.7 (CO), 159.1 (CO). MS (EI, 70 eV)
m/z: 556 (Mþ). Anal. Calcd for C37H24N4O2. C, 79.84; H, 4.35; N,
10.07. Found: C, 79.71; H, 4.39; N, 10.02%.
4.2.8. 5-Methyl-10-(4-nitrophenyl)-8-phenyl-10,11-dihydrospiro-
[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-
20,6(5H)-dione (4i). Yellow powder (0.44 g, 77%); mp >300 ꢀC dec;
IR (KBr) (nmax, cmꢁ1): 3414, 3168, 1698, 1643; 1H NMR (300 MHz,
DMSO-d6): dH¼3.44 (3H, s, CH3), 6.47–8.50 (17H, m, H-Ar), 9.97 (1H,
s, NH). 13C NMR (75 MHz, DMSO-d6): dC¼29.4 (NCH3), 50.6 (Cspiro),
102.7 (C), 107.8 (CH), 109.4 (CH), 113.9 (C), 115.1 (CH), 121.6 (CH),
121.9 (CH), 123.1 (CH), 123.7 (CH), 124.4 (CH), 125.6 (C), 127.8 (CH),
128.1 (CH), 128.6 (CH), 129.0 (CH), 131.8 (CH), 132.6 (C), 138.1 (C),
139.1 (C), 139.4 (C), 142.7 (C), 143.3 (C), 144.2 (C), 145.5 (C), 151.4 (C),
159.8 (CO), 179.4 (CO). MS (EI, 70 eV) m/z: 566 (Mþ). Anal. Calcd for
C33H22N6O4. C, 69.96; H, 3.91; N, 14.83. Found: C, 69.82; H, 3.84; N,
14.77%.
4.4. Typical procedure for the preparation of 11a-hydroxy-
8,10-diphenyl-11,11a-dihydro-6H-spiro[chromeno[4,3-
b]pyrazolo[4,3-e]pyridine-7,30-indoline]-20,6(6aH,10H)-
dione (8a)
A mixture of 4-hydroxycoumarin (0.16 g, 1 mmol), isatin (0.15 g,
1 mmol), 1,3-diphenyl-1H-pyrazol-5-amine (0.24 g, 1 mmol) and p-
TSA (0.1 g) in refluxing water (5 mL) was stirred for 24 h (TLC). After
completion, the reaction mixture was filtered and the precipitate
washed with water (10 mL) and recrystallization from ethanol to
afford the pure product 8a as white powder (0.38 g, 72%). Mp
280 ꢀC (dec); IR (KBr) (nmax, cmꢁ1): 3409, 3157, 3070, 1726, 1647; 1H
NMR (300 MHz, DMSO-d6) dH¼6.07 (1H, s, CH), 6.43–7.97 (18H, m,
H-Ar), 10.66 (1H, s, NH), 11.22 (1H, s, NH), 11.31 (1H, br s, OH). 13C
NMR (75 MHz, DMSO-d6): dC¼48.5 (Cspiro), 57.3 (CH), 102.6 (C),
109.8 (CH), 118.0 (CH), 119.7 (CH), 121.7 (CH), 122.1 (C), 123.7 (CH),
123.9 (CH), 127.8 (CH), 128.0 (CH), 128.2 (CH), 129.0 (CH), 129.8
(CH), 131.7 (CH), 132.5 (C), 136.8 (CH), 138.2 (C), 140.9 (C), 144.2 (C),
4.2.9. 10,5-Dimethyl-10-(4-nitrophenyl)-8-phenyl-10,11-dihydrospiro-
[benzo[h]pyrazolo[3,4-b][1,6]naphthyridine-7,30-indoline]-20,6(5H)-
dione (4j). Yellow powder (0.42 g, 73%); mp >300 ꢀC dec; IR (KBr)
(
nmax, cmꢁ1): 3162, 3070, 1685, 1643; 1H NMR (300 MHz, DMSO-
d6): dH¼2.65 (3H, s, CH3)¼2.65 (3H, s, CH3), 3.42 (3H, s, CH3), 6.58–

9320
S. Ahadi et al. / Tetrahedron 65 (2009) 9316–9321
148.7 (C), 160.6 (C), 168.3 (C), 178.2 (CO), 199.2 (CO). MS (EI, 70 eV)
m/z: 526 (Mþ). Anal. Calcd for C32H22N4O4: C, 72.99; H, 4.21; N,
10.64%. Found: C, 72.80; H, 4.17; N, 10.58%.
118.1 (CH), 119.8 (CH), 122.1 (C), 123.6 (CH), 127.1 (CH), 127.8 (CH),
128.0 (CH), 129.8 (CH), 130.4 (CH), 131.7 (CH), 132.5 (C), 136.8 (CH),
138.1 (C),140.6 (C),143.5 (C),148.7 (C),160.5 (C),168.1 (C),177.8 (CO),
199.0 (CO). MS (EI, 70 eV) m/z: 606 (Mþ), 604 (Mþ). Anal. Calcd for
C32H21BrN4O4: C, 63.48; H, 3.50; N, 9.25%. Found: C, 63.34; H, 3.56; N,
9.17%.
4.4.1. 11a-Hydroxy-10-methyl-8,10-diphenyl-11,11a-dihydro-6H-spiro-
[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8b). White powder (0.38 g, 70%); mp 289 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3352, 1716, 1637; 1H NMR (300 MHz,
DMSO-d6): dH¼3.28 (3H, s, CH3), 6.10 (1H, s, CH), 6.51–7.92 (18H, m,
H-Ar), 11.23 (1H, s, NH), 11.29 (1H, br s, OH). 13C NMR (75 MHz,
DMSO-d6): dC¼26.8 (CH3), 47.9 (Cspiro), 57.6 (CH), 102.3 (C), 108.7
(CH), 118.0 (CH), 119.7 (CH), 122.2 (CH), 122.4 (C), 123.5 (CH), 123.7
(CH), 127.5 (CH), 127.8 (CH), 128.0 (CH), 128.3 (CH), 129.1 (CH), 129.8
(CH), 131.7 (CH), 132.4 (C), 136.7 (CH), 138.1 (C), 140.9 (C), 145.6 (C),
148.7 (C), 160.5 (C), 168.2 (C), 176.3 (CO), 198.8 (CO). MS (EI, 70 eV)
m/z (%): 540 (Mþ). MS (EI, 70 eV) m/z: 526 (Mþ). Anal. Calcd for
C33H24N4O4: C, 73.32; H, 4.48; N, 10.36%. Found: C, 73.17; H, 4.53; N,
10.44%.
4.4.6. 50-Bromo-11a-hydroxy-10-methyl-8,10-diphenyl-11,11a-dihy-
dro-6H-spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8g). White powder (0.54 g, 88%); mp 270 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3024, 1730, 1678; 1H NMR (300 MHz,
DMSO-d6): dH¼3.27 (3H, s, CH3), 6.12 (1H, s, CH), 6.68–7.89 (17H, m,
H-Ar), 11.17 (1H, s, NH), 11.30 (1H, s, OH). 13C NMR (75 MHz, DMSO-
d6): dC¼26.9 (CH3), 47.8 (Cspiro), 57.5 (CH), 101.8 (C), 110.7 (CH), 114.1
(C), 118.0 (CH), 119.6 (CH), 119.7 (CH), 122.1 (C), 123.6 (CH), 126.8
(CH), 128.0 (CH), 128.9 (CH), 129.5 (CH), 129.8 (CH), 131.3 (CH), 131.6
(CH), 132.3 (C), 136.4 (CH), 136.8 (C), 138.1 (C), 140.7 (C), 144.9 (C),
148.7 (C), 160.4 (C), 168.0 (C), 176.0 (CO), 198.5 (CO). MS (EI, 70 eV)
m/z: 620 (Mþ), 618 (Mþ). Anal. Calcd for C33H23BrN4O4: C, 63.98; H,
3.74; N, 9.04%. Found: C, 64.09; H, 3.70; N, 9.10%.
4.4.2. 10-Ethyl-11a-hydroxy-8,10-diphenyl-11,11a-dihydro-6H-spiro-
[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8c). Yellow powder (0.38 g, 69%); mp 287 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3229, 1726, 1678; 1H NMR (300 MHz,
DMSO-d6): dH¼1.30 (3H, t, J¼6.2 Hz, CH3), 3.87 (2H, m, CH2), 6.09
(1H, s, CH), 6.50–7.94 (18H, m, H-Ar), 11.26 (1H, s, NH), 11.29 (1H, br
s, OH). MS (EI, 70 eV) m/z (%): 554 (Mþ). MS (EI, 70 eV) m/z: 526
(Mþ). Anal. Calcd for C34H26N4O4: C, 73.63; H, 4.73; N, 10.10%.
Found: C, 73.70; H, 4.77; N, 10.16%.
4.4.7. 11a-Hydroxy-10-(4-nitrophenyl)-8-phenyl-11,11a-dihydro-6H-
spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8h). Brown powder (0.49 g, 86%); mp 285 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3413, 3193, 1730, 1724; 1H NMR
(300 MHz, DMSO-d6): dH¼6.12 (1H, s, CH), 6.44–8.45 (17H, m, H-
Ar), 10.68 (1H, s, NH), 11.27 (1H, s, NH), 11.46 (1H, s, OH). 13C NMR
(75 MHz, DMSO-d6): dC¼48.3 (Cspiro), 57.1 (CH), 104.0 (C), 109.9
(CH), 118.0 (CH), 119.8 (CH), 121.8 (CH), 122.0 (C), 123.7 (CH), 125.5
(CH), 127.9 (CH), 128.0 (CH), 128.1 (CH), 129.1 (CH), 131.6 (CH), 131.9
(C), 136.9 (CH), 141.5 (C), 143.1 (C), 144.2 (C), 146.0 (C), 150.2 (C),
160.5 (C), 168.4 (C), 178.0 (CO), 198.9 (CO). MS (EI, 70 eV) m/z: 571
(Mþ). Anal. Calcd for C32H21N5O6: C, 67.25; H, 3.70; N, 12.25%.
Found: C, 67.35; H, 3.76; N, 12.34%.
Due to very low solubility of the product 4c, we cannot report
the 13C NMR data for this product.
4.4.3. 11a-Hydroxy-50-nitro-8,10-diphenyl-11,11a-dihydro-6H-spi-
ro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8d). Cream powder (0.43 g, 75%); mp 234 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3347, 1734, 1611; 1H NMR (300 MHz,
DMSO-d6): dH¼6.30 (1H, s, CH), 6.87–7.89 (17H, m, H-Ar), 11.15 (1H,
s, NH), 11.32 (1H, s, NH), 11.40 (1H, br s, OH). 13C NMR (75 MHz,
DMSO-d6): dC¼48.1 (Cspiro), 57.6 (CH), 101.6 (C), 110.0 (CH), 118.0
(CH), 119.7 (CH), 120.4 (CH), 122.2 (C), 123.7 (CH), 126.4 (CH), 127.9
(CH), 128.1 (CH), 128.2 (CH), 129.1 (CH), 129.8 (CH), 131.7 (CH), 132.5
(C), 136.9 (CH), 138.1 (C), 140.7 (C), 142.0 (C), 148.7 (C), 150.8 (C),
160.4 (C), 167.9 (C), 178.7 (CO), 198.8 (CO). MS (EI, 70 eV) m/z: 571
(Mþ). Anal. Calcd for C32H21N5O6: C, 67.25; H, 3.70; N, 12.25%.
Found: C, 67.39; H, 3.63; N, 12.17%.
4.4.8. 11a-Hydroxy-10-methyl-10-(4-nitrophenyl)-8-phenyl-11,11a-
dihydro-6H-spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indo-
line]-20,6(6aH,10H)-dione (8i). Brown powder (0.47 g, 80%); mp
276 ꢀC (dec); IR (KBr) (nmax, cmꢁ1): 3625, 3183, 1728, 1685, 1642; 1H
NMR (300 MHz, DMSO-d6): dH¼3.28 (3H, s, CH3), 6.15 (1H, s, CH),
6.50–8.48 (17H, m, H-Ar),11.2 (1H, s, NH),11.54 (1H, s, OH). 13C NMR
(75 MHz, DMSO-d6): dC¼26.8 (CH3), 47.8 (Cspiro), 57.4 (CH), 103.7
(C), 108.8 (CH), 118.0 (CH), 119.7 (CH), 122.1 (C), 122.4 (CH), 123.5
(CH), 123.7 (CH), 125.5 (C), 127.1 (CH), 127.9 (CH), 128.0 (CH), 128.1
(CH), 128.2 (CH), 129.3 (CH), 131.6 (CH), 131.8 (C), 141.6 (C), 143.1 (C),
145.6 (C), 146.1 (C), 150.2 (C), 160.5 (C), 168.4 (C), 176.2 (CO), 198.5
(CO). MS (EI, 70 eV) m/z: 585 (Mþ). Anal. Calcd for C33H23N5O6: C,
67.69; H, 3.96; N, 11.96%. Found: C, 67.69; H, 4.04; N, 11.89%.
4.4.4. 10-Ethyl-11a-hydroxy-50-nitro-8,10-diphenyl-11,11a-dihydro-
6H-spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8e). Cream powder (0.41 g, 68%); mp 224 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3445, 3394, 3234, 1725, 1673; 1H NMR
(300 MHz, DMSO-d6): dH¼1.36 (3H, br s, CH3), 3.94 (2H, br s, CH2),
6.34 (1H, s, CH), 6.83–7.90 (17H, m, H-Ar),11.14 (1H, s, NH),11.39 (1H,
s, OH). 13C NMR (75 MHz, DMSO-d6): dC¼12.4 (CH3), 35.3 (CH3), 47.5
(Cspiro), 57.8 (CH), 101.2 (C), 109.1 (CH), 118.0 (CH), 119.8 (CH), 120.2
(CH), 122.1 (C), 123.7 (CH), 126.4 (CH), 127.9 (CH), 128.1 (CH), 128.2
(CH),128.3 (CH),129.8 (CH),131.7 (CH),132.4 (C),136.9 (CH),138.1 (C),
140.8 (C),142.3 (C), 148.7 (C),150.8 (C),160.4 (C),167.8 (C),176.6 (CO),
198.7 (CO). MS (EI, 70 eV) m/z: 599 (Mþ). Anal. Calcd for C34H25N5O6:
C, 72.99; H, 4.21; N, 10.64%. Found: C, 72.78; H, 4.26; N, 10.58%.
4.4.9. 50-Bromo-11a-hydroxy-10-(4-nitrophenyl)-8-phenyl-11,11a-
dihydro-6H-spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indo-
line]-20,6(6aH,10H)-dione (8j). Brown powder (0.55 g, 70%); mp
285 ꢀC (dec); IR (KBr) (nmax, cmꢁ1): 3394, 3219, 1740, 1688, 1638; 1H
NMR (300 MHz, DMSO-d6): dH¼6.18 (1H, s, CH), 6.64–8.45 (16H, m,
H-Ar), 10.89 (1H, s, NH), 11.24 (1H, s, NH), 11.53 (1H, br s, OH). 13C
NMR (75 MHz, DMSO-d6): dC¼48.4 (Cspiro), 57.2 (CH),103.6 (C),111.8
(CH), 113.4 (C), 118.1 (CH), 119.8 (CH), 122.1 (C), 123.7 (CH), 125.5
(CH), 127.2 (C), 127.9 (CH), 128.1 (CH), 128.3 (CH), 130.1 (CH), 131.6
(CH), 131.8 (CH), 131.9 (C), 136.9 (CH), 141.3 (C), 143.1 (C), 143.6 (C),
146.1 (C), 150.3 (C), 160.5 (C), 168.3 (C), 177.7 (CO), 198.6 (CO). MS
(EI, 70 eV) m/z: 651 (Mþ), 649 (Mþ). Anal. Calcd for C32H20BrN5O6:
C, 59.09; H, 3.10; N, 10.77%. Found: C, 59.19; H, 3.14; N, 10.71%.
4.4.5. 50-Bromo-11a-hydroxy-8,10-diphenyl-11,11a-dihydro-6H-spiro-
[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indoline]-
20,6(6aH,10H)-dione (8f). Cream powder (0.51 g, 84%); mp 260 ꢀC
(dec); IR (KBr) (nmax, cmꢁ1): 3347, 3260, 3065, 1719, 1638; 1H NMR
(300 MHz, DMSO-d6): dH¼6.10 (1H, s, CH), 6.63–7.92 (17H, m, H-Ar),
10.79 (1H, s, NH), 11.24 (2H, br s, OH and NH). 13C NMR (75 MHz,
DMSO-d6): dC¼48.4 (Cspiro), 57.3 (CH), 102.2 (C), 111.7 (CH), 113.3 (C),
4.4.10. 11a-Hydroxy-50-nitro-10-(4-nitrophenyl)-8-phenyl-11,11a-di-
hydro-6H-spiro[chromeno[4,3-b]pyrazolo[4,3-e]pyridine-7,30-indo-
line]-20,6(6aH,10H)-dione (8k). Brown powder (0.52 g, 84%); mp

S. Ahadi et al. / Tetrahedron 65 (2009) 9316–9321
9321
287 ꢀC (dec); IR (KBr) (nmax, cmꢁ1): 3383, 3224,1744, 1690, 1628; 1H
NMR (300 MHz, DMSO-d6): dH¼6.14 (1H, s, CH), 6.65–8.43 (16H, m,
H-Ar), 10.88 (1H, s, NH), 11.25 (1H, s, NH), 11.56 (1H, br s, OH). 13C
NMR (75 MHz, DMSO-d6): dC¼48.1 (Cspiro), 57.5 (CH), 102.9 (C),
110.2 (CH), 118.1 (CH), 119.8 (CH), 120.4 (CH), 122.2 (C), 123.7 (CH),
125.5 (CH), 126.5 (CH),128.1 (CH),128.3 (CH),128.8 (CH), 131.6 (CH),
131.9 (C), 136.9 (CH), 141.4 (C), 142.1 (C), 143.0 (C), 146.2 (C), 150.2
(C), 150.8 (C), 160.4 (C), 168.1 (C), 178.7 (CO), 198.5 (CO). MS (EI,
70 eV) m/z: 616 (Mþ). Anal. Calcd for C32H20N6O8: C, 62.34; H, 3.27;
N, 13.63%. Found: C, 62.23; H, 3.22; N, 13.54%.
10. Da-Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc. 2001, 12, 273.
11. Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-BadySh, M. Bioorg. Med.
Chem. 2006, 12, 2483.
12. Kang, T.-H.; Matsumoto, K.; Murakami, Y.; Takayama, H.; Kitajima, M.; Aimi, N.;
Watanabe, H. Eur. J. Pharmacol. 2002, 444, 39.
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4.5. 11a0-Hydroxy-80,100-diphenyl-110,11a0-dihydro-2H,60H-
spiro[acenaphthylene-1,70-chromeno[3,4-e]pyrazolo[3,4-b]-
pyridine]-2,60(6a0H,100H)-dione (10)
Whit powder (0.39 g, 70%); mp 241 ꢀC dec; IR (KBr) (nmax, cmꢁ1):
3316, 3044,1721, 1632; 1H NMR (300 MHz, DMSO-d6): dH¼6.31 (1H,
s, CH), 6.33–8.16 (20H, m, H-Ar), 10.98 (1H, s, NH), 11.37 (1H, s, OH).
13C NMR (75 MHz, DMSO-d6): dC¼52.8 (Cspiro), 59.18 (CH), 103.4 (C),
118.0 (CH), 119.8 (CH), 121.0 (CH), 122.0 (C), 122.2 (CH), 123.6 (CH),
125.1 (CH), 127.2 (CH), 127.7 (CH), 128.0 (CH), 128.7 (CH), 129.1 (CH),
129.8 (CH), 130.5 (C), 131.7 (CH), 132.3 (C), 132.8 (C), 136.8 (CH),
137.5 (C), 138.1 (C), 140.5 (C), 142.5 (C), 149.1 (C), 160.4 (C), 168.5 (C),
198.6 (CO), 202.8 (CO). MS (EI, 70 eV) m/z: 561 (Mþ). Anal. Calcd for
C36H23N3O4. C, 76.99; H, 4.13; N, 7.48. Found: C, 76.90; H, 4.17; N,
7.41%.
Acknowledgements
31. Fujikama, Y.; Suzuki, M.; Iwasaki, H.; Sakashita, M.; Kitahara, M. European
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8790.
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University, G.C.
33. Sayyafi, M.; Seyyedhamzeh, M.; Khavasi, H. R.; Bazgir, A. Tetrahedron 2008, 64,
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