Convenient ultrasound-promoted regioselective synthesis of fused 6-amino-3-methyl-4-aryl-1h-pyrazolo[3,4-B]pyridine-5-carbonitrile

Article abstract of DOI:10.1080/00397911.2010.502990

A multicomponent, catalyst-free reaction for the synthesis of fused 6-amino-3- methyl-4-aryl-1H-pyrazolo [3,4-b] pyridine-5-carbonitrile from 3-amino-5-methylpyrazole, malononitrile, and substituted aldehydes under ultrasound irradiation in short reaction times (8-10 min) with good yields (85-98%) is reported. Copyright

Full text of DOI:10.1080/00397911.2010.502990

Synthetic Communications1, 41: 2323–2330, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.502990
CONVENIENT ULTRASOUND-PROMOTED
REGIOSELECTIVE SYNTHESIS OF FUSED 6-AMINO-3-
METHYL-4-ARYL-1H-PYRAZOLO[3,4-b]PYRIDINE-5-
CARBONITRILE
Leila Zare, Nosrat O. Mahmoodi, Asieh Yahyazadeh, and
Manouchehr Mamaghani
Department of Chemistry, Faculty of Sciences, University of Guilan,
Rasht, Iran
GRAPHICAL ABSTRACT
Abstract A multicomponent, catalyst-free reaction for the synthesis of fused 6-amino-3-
methyl-4-aryl-1H-pyrazolo [3,4-b] pyridine-5-carbonitrile from 3-amino-5-methylpyrazole,
malononitrile, and substituted aldehydes under ultrasound irradiation in short reaction times
(8–10 min) with good yields (85–98%) is reported.
Keywords 3-Amino-5-methylpyrazole; fused 6-amino-3-methyl-4-aryl-1H-pyrazolo
[3,4-b] pyridine-5-carbonitrile; malononitrile; multicomponent
INTRODUCTION
Pyrazolopyridines have received much attention in recent years. Pharmaceutical
research of this kind of compound has been reported, such as a potent cyclin depen-
dent kinase 1 (CDK1) inhibitor,[1] HIV reverse transcriptase inhibitors,[2] CCR1
antagonists,[3] protein kinase inhibitors,[4] and inhibitors of cGMP degradation,
together with several herbicidal and fungicidal activities.[5] Some derivatives exhibit
potential antimalarial[6] and antiviral properties.[7,8] Others show intense fluorescence
in the blue-green region and have been considered for applications as fluorescence
Received February 6, 2010.
Address correspondence to Nosrat O. Mahmoodi, Department of Chemistry, Faculty of Sciences,
University of Guilan, P. O. Box 1914, Rasht, Iran. E-mail: mahmoodi@guilan.ac.ir, nosmahmoodi@
gmail.com
2323

2324
L. ZARE ET AL.
standards and luminophores in organic light-emitting diodes.[9] Numerous methods
for the synthesis of pyrazolopyridines in the past 20 years have been reported with
respect to their different structures.[10]
The main disadvantages of most of these procedures are harsh reaction
conditions, tedious workups, poor yields, long reaction times, multistep reactions,
use of large quantities of volatile organic solvents, and poor regioselectivity. There-
fore, development of an efficient and versatile method is still required.
Green chemistry has become a major driving force for organic chemists to
develop environmentally benign routes for the preparation of organic compounds
of synthetic and biological values. For example, the possibility of performing
reactions under ultrasounic irradiation to enhance the reaction efficiency from both
economical and ecological points of view has remarkable synthetic value and
received great attention.[11]
RESULTS AND DISCUSSION
Recent developments in pyrazolopyridines chemistry and our continued interest
in the development of efficient and environmentally friendly procedures for the
synthesis of pharmaceutical compounds[12–16] triggered us to describe here an efficient
method for the regioselective synthesis of new derivatives of pyrazolopyridines.
Multicomponent reactions of 3-amino-5-methylpyrazole, aldehydes, and CH-acid
compounds, forming different condensation products depending on the specific
conditions, have recently attracted the interest of many chemists.[17]
In this report, we have devised an efficient one-pot, three-component reaction
for the synthesis of novel fused derivatives of pyrazolopyridines (4a–j) from alde-
hydes (1a–j), malononitrile 2, and 3-amino-5-methylpyrazole 3 under ultrasounic
irradiation (Scheme 1).
Equimolar amounts of reactants 1 (Table 1, entries 6–10, 0.5 eq.), 2, and 3 in
ethanol were placed into a Pyrex open vessel and irradiated at 60 ꢀC by ultrasound
(45 kHz) to produce the desired pyrazolopyridine derivatives (4a–j) in 8–10 min with
85–98% yields (Table 1). A control reaction on substrates in refluxing ethanol, using
the same ratio of the reactants, furnished the related pyrazolopyridines in lower
yields and in much longer reaction times (5–6 h) (Table 1).
It is important to point out that when 3-amino-5-methylpyrazole 3, malononi-
trile 2, and substituted benzaldehyde 1 were irradiated for just 4–5 min, in all cases the
Scheme 1. Synthesis of pyrazolopyridine derivatives (4a–j).

SYNTHESIS OF PYRAZOLOPYRIDINE
Table 1. Comparative studies of pyrazolopyridines synthesized under thermal and ultrasonic irradiation
Thermal Ultrasound irradiation
2325
Entry
Aldehydes
Time (h)
Yielda (%)
Time (min)
Yielda (%)
a
b
c
4-NO2 C6H4CHO
3-NO2 C6H4CHO
2-NO2 C6H4CHO
4-Cl C6H4CHO
4-Br C6H4CHO
6
50
52
61
56
54
10
8.5
8
85
89
92
85
88
5.5
5
d
e
5
8.5
8
5
f
6
62
65
9
95
96
g
5.5
8.5
h
i
5.5
5
63
62
59
8
8.5
10
95
98
98
j
5
aIsolated yields.
bIdentified by spectroscopic analysis (IR, 1H NMR) and elemental analysis.
Scheme 2. Mechanism of formation of 4a–j via intermediates 6 and 7.

2326
L. ZARE ET AL.
Scheme 3. Synthesis of bispyrazolopyridines (4f–j).
reaction led to the formation of the stable intermediates 7, which in one case were
isolated and characterized. For this reason, we assume that the formation of 4
proceeds by a Michael-type addition from the free ring carbon atom in 3-amino-5-
methylpyrazole 3 to the activated double bond of the compound 5 (formed in situ
by a Knovenagel condensation between malononitrile 2 and substituted benzal-
dehyde 1), which subsequently cyclizes the previously form Michael adduct 6 to give
7 (Scheme 2). When compound 7 is continuously irradiated (an additional 4–5 min),
it yields pyrazolopyridine 4a–j.
Interestingly, this multicomponent reaction also afforded an efficient protocol
for the synthesis of bispyrazolopyridines 4f–j in good yields and short reaction times.
All of compounds summarized in Table 1 were characterized by spectroscopic
1
methods [infrared (IR) and H NMR] and elemental analysis. In the other efforts,
when 37% formaldehyde was used instead of substituted benzaldehyde with refluxing
the reaction mixture for 9 h or under ultrasounic irradiation, no product was observed.
CONCLUSION
In conclusion, this one-pot, three component protocol under ultrasound
irradiation provides a regioselective, fast, and practical method for the preparation
of fused pyrazolo[3,4-b]pyridine carbonitriles from 5-amino-3-methylpyrazole, malo-
nonitrile, and various aryl aldehydes in short reaction times and in excellent yields,
which pave the way for assessment of pharmacological activities of these novel
pyrazolopyridine derivatives. The simplicity, high atom economy, easy excecution,
east workup, and productivity, together with the use of inexpensive material and
environmentally friendly procedure, are the remarkable features of this procedure.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus. For the
ultrasounic reactions, ultrasound apparatus Astra 3D (9.5 L, 45 kHz frequency,

SYNTHESIS OF PYRAZOLOPYRIDINE
2327
input power with heating 305 W, number of transducers 2) from TECNO-GAZ was
1
used. IR spectra were determined on a Shimadzo IR-470 spectrometer. H NMR
spectra were recorded on a 500-MHz Bruker DRX-500 in dimethylsulfoxide
(DMSO-d6) as solvent and tetramethylsilane (TMS) as an internal standard. Chemi-
cals were purchased from Merck and Fluka. Elemental analyses were done on a
Carlo-Erba EA1110 CNNO-S analyser and agreed with the calculated values. All
solvents used were dried and distilled according to standard procedures.
General Procedure
Thermal condition. A solution of 5-amino-3-methylpyrazole 3 (1 mmol),
malononitrile 2 (1 mmol), and aldehyde 1 (1 mmol) (Table 1, entries 1f–j, 0.5 mmol)
in EtOH (10 mL) were refluxed for the required reaction time. After completion of
the reaction, the amount of solvent was reduced to a minimum under vacuum, to
afford 4a–j as crystalline products in 50–65% yields (Table 1).
Ultrasounic irradiation. A solution of 5-amino-3-methylpyrazole
3
(1 mmol), malononitrile 2 (1 mmol), and aldehyde 1 (1 mmol) (Table 1, entries
1f–j, 0.5 mmol) in EtOH (10 mL) were placed into a Pyrex open vessel and irradiated
in a water bath under silent conditions by ultrasound (45 kHz) at 60 ꢀC for the
required reaction times (Table 1). When the irradiation was stopped, the amount
of solvent was reduced to a minimum under vacuum to afford 4a–j as crystalline
products in 85–98% yields (Table 1).
Selected Data
6-Amino-4,7-dihydro-3-methyl-4-(4-nitrophenyl)-1H-pyrazolo[3,4-b]
pyridine-5-carbonitrile 7a. Off-white solid; mp 310–312 ꢀC; FT-IR (KBr, cmꢁ1):
1
3420, 3300, 2200, 1645, 1600, 1560, 1340, 1265. H NMR (DMSO, 500 MHz): 2.5
(s, 3H), 6.4 (s, 1H), 7.53 (d, J ¼ 7.2 Hz, 2H), 7.84 (d, J ¼ 7.2 Hz, 2H), 8.50 (s, br,
1H). Anal. calcd. for C14H12N6O2: C, 56.75; H, 4.08; N, 28.36. Found: C, 56.60;
H, 3.82; N, 28.42.
6-Amino-3-methyl-4-(3-nitrophenyl)-1H-pyrazolo[3,4-b]pyridine-5-
carbonitrile 4b. Off-white solid; mp 285–287 ꢀC; FT-IR (KBr, cmꢁ1): 3369, 3313,
3236, 3099, 2925, 2187, 1600, 1517, 1352. 1H NMR (DMSO, 500 MHz): 2.04
(s, 3H), 7.42 (t, J ¼ 7.9 Hz, 1H), 7.63 (d, J ¼ 7.7 Hz, 1H), 8.01 (dd, J ¼ 8.1 Hz,
1.32 Hz, 1H), 8.14 (t, J ¼ 1.86 Hz, 1H), 8.65 (s, 1H). Anal. calcd. for C14H10N6O2:
C, 57.14; H, 3.43; N, 28.56. Found: C, 57.25; H, 3.52; N, 28.93.
6-Amino-3-methyl-4-(2-nitrophenyl)-1H-pyrazolo[3,4-b]pyridine-5-
carbonitrile 4c. Brown solid; mp 290–292 ꢀC; FT-IR (KBr, cmꢁ1): 3404, 3132,
1
2935, 2202, 1623, 1585, 1496, 1434. H NMR (DMSO, 500 MHz): 2.46 (s, 3H),
7.48 (t, J ¼ 6.0 Hz, 1H), 7.63 (d, J ¼ 8.4 Hz, 1H), 7.81 (t, J ¼ 7.2 Hz, 1H), 7.85 (d,
J ¼ 8.2 Hz, 1H). Anal. calcd. for C14H10N6O2: C, 57.14; H, 3.43; N, 28.56. Found:
C, 57.36; H, 3.25; N, 28.65.
6-Amino-4-(4-chlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-
carbonitrile 4d. Off-white solid; mp 268–270 ꢀC; FT-IR (KBr, cmꢁ1); 3433, 3311,

2328
L. ZARE ET AL.
3234, 3172, 2925, 2212, 1580, 1554, 1087. 1H NMR (DMSO, 500 MHz): 2.4 (s, 3H),
7.59 (d, J ¼ 8.5 Hz, 2H), 7.81 (d, J ¼ 8.5 Hz, 2H), 8.82 (s, br, 2H). Anal. calcd. for
C14H10ClN5: C, 59.27; H, 3.55; N, 24.68. Found: C, 59.55; H, 3.59; N, 24.73.
6-Amino-4-(4-bromophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-
carbonitrile 4e. Off-white solid; mp 278–280 ꢀC; FT-IR (KBr, cmꢁ1): 3600, 3100,
1
2900, 2200, 1600, 1590, 1460, 1100. H NMR (DMSO, 500 MHz): 2.45 (s, 3H),
8.04 (d, J ¼ 7.78 Hz, 2H), 8.37 (d, J ¼ 7.78 Hz, 2H), 8.92 (s, br, 2H). Anal. calcd.
for C14H10BrN5: C, 51.24; H, 3.07; N, 21.34. Found: C, 51.55; H, 3.24; N, 21.53.
4,4’-((Butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(6-amino-3-methyl-
1H-pyrazolo[3,4-b]pyridine-5-carbonitrile) 4f. Yellow solid; mp 210–212 ꢀC;
FT-IR (KBr, cmꢁ1): 3458, 3037, 2946, 2219, 1589, 1483, 1452, 1255. 1H NMR
(DMSO, 500 MHz): 2.0 (s, br, 4H), 2.43 (s, br, 6H), 4.22 (s, br, 4H), 7.07 (s, br,
2H), 7.24 (s, br, 2H), 7.67 (s, br, 2H), 7.98 (s, br, 2H), 8.4 (s, br, 2H). Anal. calcd.
for C32H28N10O2: C, 65.74; H, 4.83; N, 23.96. Found: C, 65.54; H, 4.64; N, 23.59.
4,4’-((Pentane-1,5-diylbis(oxy))bis(2,1-phenylene))bis(6-amino-3-methyl-
1H-pyrazolo[3,4-b]pyridine-5-carbonitrile) 4g. Light brown solid; mp 204–
1
206 ꢀC; FT-IR (KBr, cmꢁ1): 3434, 3230, 2937, 2194, 1639, 1602, 1242. H NMR
(DMSO, 500 MHz): 1.4 (s, br, 2H), 2.0 (s, br, 4H), 2.5 (s, 3H), 4.20 (s, br, 4H),
7.14 (s, br, 2H), 7.23 (d, J ¼ 7.5 Hz, 2H), 7.66 (s, br, 3H),7.97 (d, J ¼ 6.30 Hz, 2H),
8.41(s, br, 1H). Anal. calcd. for C33H30N10O2: C, 66.21; H, 5.05; N, 23.40. Found:
C, 66.24; H, 5.33; N, 23.48.
4,4’-((Hexane-1,6-diylbis(oxy))bis(2,1-phenylene))bis(6-amino-3-methyl-
1H-pyrazolo[3,4-b]pyridine-5-carbonitrile) 4h. Yellow solid; mp 166–168 ꢀC;
FT-IR (KBr, cmꢁ1): 3471, 3458, 3035, 2945, 2219, 1591, 1573, 1454, 1257. 1H
NMR (DMSO, 500 MHz): 1.5 (s, br, 2H), 2.0 (s, br, 2H), 2.5 (s, 3H), 4.14 (s, br,
2H), 7.06 (s, br, 1H), 7.13 (s, br, 1H), 7.66 (s, br, 1H), 7.98 (s, br, 1H), 8.43 (s, br,
1H). Anal. calcd. for C34H32N10O2: C, 66.65; H, 5.26; N, 22.86. Found: C, 66.10;
H, 5.91; N, 22.74.
4,4’-((Butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(6-amino-3-methyl-
1H-pyrazolo[3,4-b]pyridine-5-carbonitrile) 4i. Yellow solid; mp 200–202 ꢀC;
1
FT-IR (KBr, cmꢁ1): 3473, 3039, 2943, 2200, 1589, 1452, 1253. H NMR (DMSO,
500 MHz): 1.9 (s, br, 2H), 2.45 (s, 3H), 4.2 (s, br, 2H), 7.18 (d, J ¼ 8.04 Hz, 2H),
7.96 (d, J ¼ 8.04 Hz, 2H), 8.38 (s, 1H). Anal. calcd. for C32H28N10O2: C, 65.74; H,
4.83; N, 23.96. Found: C, 65.36; H, 4.95; N, 23.69.
4,4’-(((1,4-Phenylenebis(methylene))bis(oxy))bis(2,1-phenylene))bis(6-
amino-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile) 4j. Yellow solid;
mp 230–232 ꢀC; FT-IR (KBr, cmꢁ1): 3446, 3029, 2936, 2225, 1593, 1483, 1456,
1299, 1244. 1H NMR (DMSO, 500 MHz): 2.5 (s, 3H), 5.3 (s, 2H), 7.17
(t, J ¼ 7.56 Hz, 1H), 7.31 (d, J ¼ 8.5 Hz, 1H), 7.57 (s, 2H), 7.66 (t, J ¼ 7.81 Hz,
1H), 8.01 (d, J ¼ 7.78 Hz, 1H), 8.5 (s, 1H). Anal. calcd. for C36H28N10O2: C,
68.34; H, 4.46; N, 22.14. Found: C, 68.62; H, 4.55; N, 22.07.

SYNTHESIS OF PYRAZOLOPYRIDINE
2329
ACKNOWLEDGMENT
We thank the Research Committee of University of Guilan for the partial
support given to this study.
REFERENCES
1. Huang, S.; Lin, R.; Yu, Y.; Lu, Y.; Connolly, P. J.; Chiu, G.; Li, S.; Emanuel, S. L.;
Middleton, S. A. Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-
b]pyridine, a potent cyclin dependent kinase 1 (CDK1) inhibitor. Bioorg. Med. Chem.
Lett. 2007, 17, 1243.
2. Saggar, S. A.; Sisko, J. T.; Tucker, T. J.; Tynebor, R. M.; Su, D. S.; Anthony, N. J. U. S.
Patent Appl. 2007,021,442, 2007.
3. Zhang, P.; Pennell, A. M. K.; Wright, J. J. K.; Chen, W.; Leleti, M. R.; Li, Y.; Li, L.;
Xu, Y. PCT Int. Appl. WO 2007002293, 2007.
4. Chiu, G.; Li, S.; Connolly, P. J.; Middleton, S. A.; Emanuel, S. L.; Huang, S.; Lin, R.;
Lu, Y. PCT Int. Appl. WO 2006130673, 2006.
5. Feurer, A.; Luithle, J.; Wirtz, S.; Koenig, G.; Stasch, J.; Stahl, E.; Schreiber, R.; Wunder,
F.; Lang, D. PCT Int. Appl. WO 2004009589, 2004.
6. Stein, R. G., Biel, J. H., Singh, T. Antimalarials: 4-Substituted 1H-pyrazolo[3,4-b]
quinolines. J. Med. Chem. 1970, 13, 153.
7. Crenshaw, R. R., Luke, G. M., Smirnoff, P. Interferon inducing activities of derivatives of
1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazolo[3,4-b]quinoline and related
compounds. J. Med. Chem. 1976, 19, 262.
8. Crenshaw, R., Luke, G. M., Smirnoff, P. Canadian Patent 10,32,538. Chem. Abstr. 1978,
89, 179995r.
9. Kendre, D. B.; Toche, R. B.; Jachak, M. N. Synthesis of novel dipyrazolo[3,4-b:3,4-d]
pyridines and study of their fluorescence behavior. Tetrahedron 2007, 63, 11000.
10. (a) Chen, T.; He, H. Huaxue Tongbao 2005, 68, w040=1; (b) Diaz-Ortiz, A.; De la Hoz, A.;
Langa, F. Microwave irradiation in solvent-free conditions: An eco-friendly methodology
to prepare indazoles, pyrazolopyridines, and bipyrazoles by cycloaddition reactions.
Green Chem. 2000, 2, 165; (c) Krygowski, T. M.; Anulewicz, R.; Cyranski, M. K.;
Puchala, A.; Rasala, D. Separation of the energetic and geometric contribution to the
romaticity, part IX: Aromaticity of pyrazoles in dependence on the kind of substitution.
Tetrahedron 1998, 54, 12295.
11. (a) Peng, K.; Chen, F.; She, X.; Yang, C.; Cui, Y.; Pan, X. Selective oxidation of benzylic or
allylic hydroxyl group of sec-1,2-diols. Tetrahedron Lett. 2005, 46, 1217; (b) Zhou, W.-J.; Ji,
S.-J.; Shen, Z.-L. An efficient synthesis of ferrocenyl substituted 3-cyanopyridine deriva-
tives under ultrasound irradiation. J. Organomet. Chem. 2006, 691, 1356; (c) Ji, S. J.; Shen,
Z. L.; Gu, D. G.; Huang, X. Y. Ultrasound-promoted alkynylation of ethynylbenzene to
ketones under solvent-free condition. Ultrason. Sonochem. 2005, 12, 161; (d) Ji, S. J., Wang,
S. Y. An expeditious synthesis of b-indolylketones catalyzed by p-toluenesulfonic acid
(PTSA) using ultrasonic irradiation. Ultrason. Sonochem. 2005, 12, 339; (e) Ji, S. J.; Wang,
S. Y. Ultrasound-accelerated Michael addition of indole to a, b-unsaturated ketones cat-
alyzed by ceric ammonium nitrate (CAN). Synlet. 2003, 13, 2074; (f) Wang, S. Y.; Ji, S.
J.; Loh, T. P. The Michael addition of indole to a, b-unsaturated ketones catalyzed by iod-
ine at room temperature. Synlett 2003, 15, 2377; (g) Luche, J. L. Synthetic Organic Sono-
chemistry; Plenum Press: New York, 1998; (h) Khosropour, A. R. Ultrasound-promoted
greener synthesis of 2,4,5-trisubstituted imidazoles catalyzed by Zr(acac)4 under ambient
conditions. Ultrason. Sonochem. 2008, 15, 659.

2330
L. ZARE ET AL.
12. Belletire, J. L.; Mahmoodi, N. O. Direct butyrolactone production using tin hydride.
Tetrahedron Lett. 1989, 30, 4363.
13. Belletire, J. L.; Mahmoodi, N. O. Dianion-based methodology for the preparation of
2,3-disubstitutrd butyrolactones. Synth. Commun. 1989, 19, 3371.
14. Mahmoodi, N. O.; Jazayri, M. Direct synthesis of c-butyrolactones via c-phenyl subti-
tuted butyric acids–mediated benzyl radical cyclization. Synth. Commun. 2001, 31, 1467.
15. Mahmoodi, N. O.; Salehpour, M. Direct synthesis of c-substituted phthalides via
ortho-aryl benzoic acid–mediated benzyl radical cyclization. J. Heterocycl. Chem. 2003,
40, 875.
16. Mahmoodi, N. O.; Salehpour, M. Direct synthesis of c-substituted phthalides by cycliza-
tion of benzyl radicals generated from o-(arylmethyl)benzoic acids. Russ. J. Org. Chem.
2003, 39, 1760.
17. (a) Shi, C.-L.; Shi, D.-Q.; Kim, S. H.; Huang, Z.-B.; Ji, S.-B.; Ji, M. A novel and efficient
one-pot synthesis of furo[30,40:5,6]pyrido[2,3-c]pyrazole derivatives using organocatalysts.
Tetrahedron 2008, 64, 2425; (b) Quiroga, J.; Portilla, J.; Serrano, H.; Abonia, R.; Insuasty,
B.; Nogueras, M.; Cobo, J. Regioselective synthesis of fused benzopyrazolo[3,4-b]quino-
lines under solvent-free conditions. Tetrahedron Lett. 2007, 48, 1987; (c) Insuasty, H.;
Estrada, M.; Cortes, E.; Quiroga, J.; Insuasty, B.; Abonia, R.; Nogueras, M.; Cobo, J.
Regioselective synthesis of novel 4-aryl-2-ethylthio-7-methyl pyrazolo[1,5-a]-[1,3,5]-
triazines. Tetrahedron Lett. 2006, 47, 5441; (d) Quiroga, J.; Insuasty, B.; Hormaza, A.;
Saitz, C.; Jullian, C. Synthesis of 4-aryl-4,7,8,9-tetrahydro-6H-pyrazolo[3,4-b]quinolin-5-
ones. J. Heterocycl. Chem. 1998, 35, 575.