Microwave-assisted synthesis of pyrazolo[3,4-b]pyridine- spirocycloalkanediones by three-component reaction of 5-aminopyrazole derivatives, paraformaldehyde and cyclic β-diketones

Article abstract of DOI:10.1016/j.tetlet.2010.07.009

New pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives were prepared via three-component reaction between 5-(4-R-benzylamino)pyrazoles, cyclic β-diketones and paraformaldehyde. The use of indandione as β-diketone resulted in the formation of two products, the pyrazolo[3,4-b]pyridine-5-spiroindanediones and 3-tert-butyl-1-phenylindeno[2,3- e]pyrazolo[3,4-b]pyridine. The structures of the pyrazolo[3,4-b]pyridine-5- spirocycloalkanedione were confirmed by single-crystal X-ray diffraction. This protocol provides a simple one-step synthetic methodology with the advantages of easy work-up, mild reaction conditions and environmentally benign.

Full text of DOI:10.1016/j.tetlet.2010.07.009

Tetrahedron Letters 51 (2010) 4717–4719
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted synthesis of pyrazolo[3,4-b]pyridine-
spirocycloalkanediones by three-component reaction of 5-aminopyrazole
derivatives, paraformaldehyde and cyclic b-diketones
b,
a
a
a
Jairo Quiroga a, , Jorge Trilleras , Dayana Pantoja , Rodrigo Abonía , Braulio Insuasty ,
*
*
Manuel Nogueras c, , Justo Cobo
c
*
a Grupo de Investigación de Compuestos Heterocíclicos, Department of Chemistry, Universidad del Valle, A. A. 25360, Cali, Colombia
b Grupo de Investigación en Compuestos Heterocíclicos, Programa de Química, Universidad del Atlántico, Km 7 vía Puerto Colombia, Barranquilla, Colombia
c Department of Inorganic and Organic Chemistry, Universidad de Jaén, 23071 Jaén, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
New pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives were prepared via three-component
reaction between 5-(4-R-benzylamino)pyrazoles, cyclic b-diketones and paraformaldehyde. The use of
indandione as b-diketone resulted in the formation of two products, the pyrazolo[3,4-b]pyridine-5-spir-
oindanediones and 3-tert-butyl-1-phenylindeno[2,3-e]pyrazolo[3,4-b]pyridine. The structures of the pyr-
azolo[3,4-b]pyridine-5-spirocycloalkanedione were confirmed by single-crystal X-ray diffraction. This
protocol provides a simple one-step synthetic methodology with the advantages of easy work-up, mild
reaction conditions and environmentally benign.
Received 8 June 2010
Revised 30 June 2010
Accepted 1 July 2010
Available online 7 July 2010
Keywords:
Microwave
Cyclic b-diketones
Solvent-free reaction
Multicomponent reaction
Annulation
Ó 2010 Elsevier Ltd. All rights reserved.
Spiro-compounds
Compounds with spiro skeletons not only constitute subunits in
numerous alkaloids, but are also templates for drug discovery and
have been used as scaffolds for combinatorial libraries.1–3 The syn-
thesis of spiro-compounds has been performed by conventional
methods and procedures based on the three-component one-pot
synthesis.4,5
On the other hand, microwave irradiation (MWI) is also emerg-
ing as a powerful tool for high-throughput organic synthesis. It has
been demonstrated that the use of microwave irradiation can dra-
matically shorten reaction times, increase product purities and
yields, and allow precise control of reaction parameters.6
In our interest in the development of synthetic strategies to
obtain functionalized heterocycles,7 we have concentrated much
of our recent efforts in the preparation of such bioactive nitro-
gen-containing heterocycles, and have already reported simple
and efficient procedures to reach interesting molecules such as
pyrazolo[3,4-b]pyridines with biological properties.8,9
potcondensationof5-aminopyrazolesderivatives1,10 formaldehyde
(2 as paraformaldehyde) and cyclic b-diketones 3 (Scheme 1).11
In a general experimental procedure equimolar amounts of start-
ing compounds 1 and 3 with an excess of formaldehyde (2 as para-
formadehyde 30 mol %) were exposed to MWI using a focused
microwave reactor (CEM Discover TM) at 200 °C with a maximum
power of 300 W for 25 min to give compounds 4–6 that were iso-
lated in good yields, after purification by simple crystallization of
H3C
H3C
CH3
CH3
CH
3O
H3C
4
O
3
3
O
2
5
Ar
2
N
N
+
+
N
H
6
N
1
1 N
N7
H
H
O
O
Ar
4-6
Herein, we wish to report a simple method for the synthesis of
pyrazolopyridine-5-spirocyclodiketones derivatives 4–6 via one-
O
O
O
O
O
R
R
O
O
O
R = H, CH3
* Corresponding authors. Fax: +57 2 33392440 (J.Q.); fax: +34 618907111 (M.N.).
E-mail addresses: jaiquir@univalle.edu.co (J. Quiroga), jorgetrilleras@mail.unia
tlantico.edu.co (J. Trilleras), mmontiel@ujaen.es (M. Nogueras)
.
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.009

4718
J. Quiroga et al. / Tetrahedron Letters 51 (2010) 4717–4719
the reaction mixture from ethanol. We have also carried out this
three-component reaction under conventional heating in refluxing
absolute ethanol and again spiro-compounds were isolated in good
yields. This three-component reaction can easily be carried out by
microwave irradiation or conventional heating in ethanol. In
both cases the reaction gave the same products 4–6. The only
difference between these two methods is that by MWI the reaction
times are much shorter than by refluxing ethanol, 25 min versus
24 h, respectively. The results are summarized in Table 1, entries
1–33.
A possible mechanism for the reported condensation is outlined
in Scheme 2. Presumably, the reaction starts with the formation of
Knoevenagel adduct intermediate A, which then suffers a Michael-
type addition reaction of the nucleophilic C-4 at 5-aminopyrazole 1
leading to the formation of intermediate B. Finally, the intermedi-
ate B undergoes cyclocondensation with another molecule of form-
aldehyde yielding 4–6.9a,12
2 + 3
HO
O
H3C
CH3
H3C
H3C
CH3
O
N
H3C
CH2=O
1
N
N
N
N
O
O
O
NH
-H2O
CH2
A
Ar
Ar
B
4-6
Scheme 2.
δ 8.45
δ 34.4
In the case of reaction with indandione, the formation of two
products was observed, and after separation by column chroma-
tography using chloroform as eluent, they were characterized by
spectroscopic and analytical data as pyrazolo[3,4-b]pyridine-5-
spiroindanediones 6 and 3-tert-butyl-1-phenylindeno[2,3-e]pyraz-
olo[3,4-b]pyridine 7 (Fig. 1).13
The formation of compound 7 occurred with the loss of a benzyl
fragment. We have previously reported the synthesis of analogues
to compound 7 via the three-component reaction between 5-ami-
no-3-methyl-1-phenylpyrazole, indandione and aromatic alde-
hydes.8d Compound 7 can be easily identified because of it is
high luminescence both in the solid and in the solution state. The
H3C
CH3
H3C
H
4
O
3
5
δ 156.7
6
2
N
1
N
7
N
10
9
HMBC correlations
8
δ 153.6
δ 164.1
Figure 1. Structural determination of compounds 7.
formation of compound 7 takes place in the reaction of indandione
with all 5-benzylaminopyrazoles 1a–m and isolated in 45%
yields.13
Table 1
One-pot condensation of 5-aminopyrazoles, formaldehyde and cyclic b-diketones—
synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives 4–6
A plausible rationalization may be advanced to explain the for-
mation of product 7. Presumably, after the intermediate B is
formed from Knoevenagel adduct A, it can be a competition be-
tween cyclocondensation reaction to render 6 and intramolecular
cyclocondensation with loss of benzyl alcohol that stabilizes the
product by aromatization yielding the lineal derivative 7. This ap-
proach with indandione represents a general method widely used
to close both carbocyclic and heterocyclic rings.
We have described multicomponent cyclocondensation reactions
(5-aminopyrazoles, cycloalkane-1,3-diones and paraformaldehyde)
as a method for spiroannulation of pyrazolo[3,4-b]pyridine deriva-
tives in the 5-position, forming four bonds in one-step. The reaction
proceeds by Knoevenagel condensation and selective cycloconden-
sation reaction obtaining spiro derivatives in good purity and yield,
showing that the synthetic route allows us to build blocks of 5-spi-
ropyrazolo[3,4-b]pyridine derivatives with a wide diversity in sub-
stituents. Spiro derivatives with an indandione substituent were
obtained in low yields due to the formation of a competitive pyraz-
olopyridine indeno-fused-derivative. This methodology is simple,
practical and is a regioselective alternative synthetic route to obtain
good yields spiro derivatives by conventional heating or by
microwave irradiation. The latter is much more efficient due to short
reaction times and easy work up.
Entry
Cyclic b-diketonea
Ar
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
4-H3CC6H4
4-F3CC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-H3COC6H4
C6H5
3,4,5-Tri-H3COC6H2
3,4-OCH2O–C6H3
4-O2NC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
84
73
O
72
66
69
77
75
55
68
70
O
4j
11
12
13
14
4-F3CC6H4
4-BrC6H4
4-H3COC6H4
5a
5b
5c
75
80
75
70
O
O
3,4-OCH2O-C6H3
5d
15
16
4-H3CC6H4
4-F3CC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-H3COC6H4
2,4-DiH3COC6H3
3,4,5-Tri-H3COC6H2
3,4-OCH2O–C6H3
5e
5f
5g
5h
5i
5j
5k
5l
75
85
O
O
17
18
19
20
21
22
23
85
85
77
75
85
71
70
H3C
CH3
5m
24
25
4-H3CC6H4
4-F3CC6H4
6a
6b
50
50
O
26
27
28
29
30
31
32
33
4-FC6H4
4-ClC6H4
4-BrC6H4
4-H3COC6H4
C6H5
3,4,5-Tri-H3COC6H2
3,4-OCH2O–C6H3
4-O2NC6H4
6c
6d
6e
6f
6g
6h
6i
51
59
54
55
52
52
20
56
References and notes
O
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Krasnov, K. A.; Kartsev, V. G. Russ. J. Org. Chem. 2005, 41(6), 901–906.
6j
a
Compounds 5a–d to pyrazolo[3,4-b]pyridine-5-spirocyclohexanedione deriva-
tives and 5e–m to 40,40-dimethyl-pyrazolo[3,4-b]pyridine-5-spirocyclohexanedione
derivatives.

J. Quiroga et al. / Tetrahedron Letters 51 (2010) 4717–4719
4719
4. (a) Rahimizadeh, M.; Shiri, A.; Bakavoli, M. Chin. Chem. Lett. 2007, 18, 689–693;
(b) Rolandsgard, M.; Baldawi, S.; Sirbu, D.; Bjørnstad, V.; Rømming, C.;
Undheim, K. Tetrahedron 2005, 61, 4129–4140; (c) Arya, K.; Dandia, A. J.
Fluorine Chem. 2007, 128, 224–231.
mp 224–226 °C. 1H NMR CDCl3 400 MHz rt d: 1.42 (s, 9H, CH3, t-Bu), 2.36 (s,
3H, CH3), 2.80 (m, 4H, C(30)H2 and C(40)H2), 2.94 (s, 2H, H-4), 3.22 (s, 2H, H-5),
3.94 (s, 2H, N7–CH2), 7.09 (d, 2H, Ho, aryl J = 8.3 Hz), 7.14 (d, 2H, Hm, aryl,
J = 8.2 Hz), 7.19 (t, 1H, Hp, J = 7.5 Hz), 7.36 (t, 2H, Hm, J = 7.9 Hz), 7.72 (d, 2H, Ho,
J = 8.0 Hz). 13C NMR CDCl3 100 MHz rt d: 21.1 (CH3), 24.3 (C-4), 29.3 (CH3, t-
Bu), 33.4 (Cq, t-Bu), 35.3 (C-30 and C-40), 51.1 (C-6), 55.2 (N7–CH2), 55.5 (C-
5. Marti, C.; Carrei, E. M. Eur. J. Org. Chem. 2003, 2209–2219.
6. (a) Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Buriol, L.; Machado, P. Chem.
Rev. 2009, 109, 4140–4182; (b) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43,
6250–6284.
7. (a) Quiroga, J.; Trilleras, J.; Insuasty, B.; Abonía, R.; Nogueras, M.; Cobo, J.
Tetrahedron Lett. 2008, 49, 2689–2691; (b) Quiroga, J.; Trilleras, J.; Insuasty, B.;
Abonía, R.; Nogueras, M.; Marchal, A.; Cobo, J. Tetrahedron Lett. 2008, 49, 3257–
3259; (c) Quiroga, J.; Insuasty, B.; Insuasty, H.; Abonía, R.; Ortíz, A. J.; Sánchez,
A.; Nogueras, M. J. Heterocycl. Chem. 2001, 38, 339–341; (d) Quiroga, J.;
Hormaza, A.; Insuasty, B.; Ortíz, A. J.; Sánchez, A.; Nogueras, M. J. Heterocycl.
Chem. 1998, 35, 231–233.
8. (a) Quiroga, J.; Cruz, S.; Insuasty, B.; Abonía, R.; Hernandez, P.; Bolaños, A.;
Moreno, R. J. Heterocycl. Chem. 1998, 35, 333–338; (b) Orlov, V. D.; Quiroga, J.;
Kolos, N. N. Khim. Geterosikl. Soedin. 1987, 1247–1251. CA: 88, 167373; (c)
Quiroga, J.; Portilla, J.; Serrano, H.; Abonía, R.; Insuasty, B.; Nogueras, M.; Cobo,
J. Tetrahedron Lett. 2007, 48, 1987–1990; (d) Quiroga, J.; Cobo, D.; Insuasty, B.;
Abonía, R.; Cruz, S.; Nogueras, M.; Cobo, J. J. Heterocycl. Chem. 2008, 45, 155–
159; (e) Quiroga, J.; Trilleras, J.; Sánchez, A. I.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Cobo, J. Lett. Org. Chem. 2009, 6, 381–383.
9. (a) Quiroga, J.; Cruz, S.; Insuasty, B.; Abonía, R.; Nogueras, M.; Cobo, J.
Tetrahedron Lett. 2006, 47, 27–30; (b) Low, J. N.; Cobo, J.; Mera, J.; Quiroga, J.;
Glidewell, C. Acta Crystallogr., Sect. C 2004, 60, 265–269; (c) Low, J. N.; Ferguson,
G.; Cobo, J.; Nogueras, M.; Cruz, S.; Quiroga, J.; Glidewell, C. Acta Crystallogr.,
Sect. C 2004, 60, 438–443.
5(10)), 99.2 (C-3a), 123.4 (Co), 126.6 (Cp), 128.0 (Co, aryl), 129.0 (Cm), 129.4 (Cm
,
aryl), 133.5 (Ci, aryl), 137.5 (Cp, aryl), 140.1 (Ci), 144.6 (C-7a), 157.4 (C-3), 213.4
(C@O). IR (KBr) cmꢁ1 2962 (CH st), 1713–1691 (C@O st). The mass spectrum
shows the following peaks: MS (70 eV) m/z (%) = 441 (M+, 100), 336 (29), 280
(86). HR-MS calcd for C28H31N3O2 441.2416, found 441.2419. Anal. Calcd for
C28H31N3O2: C, 74.08; H, 7.14; N, 9.26. Found: C, 73.96; H, 6.97; N, 9.37.
Data for 3-tert-butyl-1-phenyl-7-(4-methylbenzyl)-40,40-dimethyl-4,5,6,7-tetrahydro-
1H-pyrazolo[3,4-b]pyridine-5-spiro-10-cyclohexane-20,60-dione 5e. White crystalline
solid, 75%, mp 199–201 °C. 1H NMR CDCl3 400 MHz rt d: 0.86 (s, 3H, CH3), 1.06
(s, 3H, CH3), 1.41 (s, 9H, CH3, t-Bu), 2.33 (s, 3H, CH3), 2.45 (d, 2H, CH2
J = 14.0 Hz), 2.67 (d, 2H, CH2 J = 14.0 Hz), 3.15 (s, 2H, H-4), 3.35 (s, 2H, H-6),
3.82 (s, 2H, N7–CH2), 7.09–7.14 (m, 5H, Hp, 4H aryl), 7.29 (t, 2H, Hm, J = 7.5 Hz),
7.63 (d, 2H, Ho, J = 7.5 Hz). 13C NMR CDCl3 100 MHz rt d: 21.1 (CH3), 23.6 (C-4),
26.9 (CH3), 29.3 (CH3, t-Bu), 29.9 (CH3), 31.0 (C40), 33.3 (Cq, t-Bu), 51.9 (C30,
C50), 53.5 (C-6), 55.4 (N7–CH2), 64.3 (C-5(10)), 100.7 (C-3a), 123.4 (Co), 126.5
(Cp), 127.6 (Cm), 129.0 (Cm, aryl), 129.4 (Co, aryl), 133.5 (Cp, aryl), 137.4 (Ci, aryl),
140.2 (Ci), 144.0 (C-7a), 157.4 (C-3), 206.5 (C@O). IR (KBr) cmꢁ1 2961 (CH st),
1722–1690 (C@O st). The mass spectrum shows the following peaks: MS
(70 eV) m/z (%) = 483 (M+, 100), 378 (76), 322 (57), 276 (22), 252 (19). HR-MS
calcd for C31H37N3O2 483.2886, found 483.2894. Anal. Calcd for C31H37N3O2: C,
76.98; H, 7.71; N, 8.69. Found: C, 76.96; H, 7.69; N, 8.72.
Data for 3-tert-butyl-5-spiro-1-phenyl-7-(4-methylbenzyl)-1H-pyrazolo[3,4-
b]pyridine-4,5,6,7-tetrahydro-20-indan-10,30-dione 6a. After separating the
compound 7 in 45% yield. Pale yellow solid, 50%, mp 230–231 °C. 1H NMR
CDCl3 400 MHz rt d: 1.38 (s, 9H, CH3, t-Bu), 2.25 (s, 3H, CH3), 3.06 (s, 2H, H-4),
3.33 (s, 2H, H-5), 4.07 (s, 2H, N7–CH2), 7.00 (s, 4H, Ho, Hm, aryl), 7.17 (t, 1H, Hp,
J = 7.5 Hz), 7.33 (t, 2H, Hm, J = 7.9 Hz), 7.75 (d, 2H, Ho, J = 7.5 Hz), 7.84–7.86 (m,
2H, H-50, H-60), 7.96–7.98 (m, 2H, H-40, H-70). 13C NMR CDCl3 100 MHz rt d:
21.0 (CH3), 26.0 (C-4), 29.30 (CH3, t-Bu), 33.3 (Cq, t-Bu), 50.8 (C-5(20)), 50.9 (C-
6) 55.4 (N7–CH2), 98.7 (C-3a), 123.4 (C-40 and C-70), 123.6 (Co), 126.5 (Cp),
127.9 (Cm, aryl), 129.0 (Cm), 129.1 (Co, aryl), 133.9 (Ci, aryl), 135.8 (C-50 and C-
60), 136.9 (Cp, aryl), 140.4 (Ci), 141.0 (C-30 and C-10), 145.4 (C-7a), 157.4 (C-3),
202.1(C@O). IR (KBr) cmꢁ1 2963 (CH st), 1721–1700 (C@O st). The mass
spectrum shows the following peaks: MS (70 eV) m/z (%) = 489 (M+, 100), 328
(90), 384 (19). HR-MS calcd for C32H31N3O2 489.2416, found 489.2426. Anal.
Calcd for C32H31N3O2: C, 77.66; H, 6.27; N, 8.49. Found C, 77.21; H, 6.43; N,
8.67.
Data for 3-tert-butyl-1-phenyl-1H-indeno[2,3-e]pyrazolo[3,4-b]pyridine-5-one 7.
The product was separated by silica gel chromatography eluting with
chloroform. Yellow solid, 45%, mp 192–194 °C. 1H NMR CDCl3 400 MHz rt d:
1.56 (s, 9H, CH3, t-Bu), 7.33 (t, 1H, Hp, J = 7.3 Hz), 7.47 (t, 1H, H-7, J = 7.5 Hz),
7.54 (t, 2H, Hm, aryl, J = 7.5 Hz), 7.76 (d, 2H, Ho, J = 7.3 Hz), 7.62 (t, 1H, H-8,
J = 7.5 Hz), 7.97 (d, 1H, H-6, J = 7.5 Hz), 8.34 (d, 1H, H-9, J = 8.0 Hz), 8.45 (s, 2H,
H-4). 13C NMR CDCl3 100 MHz rt d: 29.9 (CH3), 34.4 (Cq, t-Bu), 114.5 (C-3a),
121.5 (C-9), 121.6 (C-6), 123.9 (Co), 126.2 (Cp), 127.7 (C-4), 129.0 (Cm), 131.4 (C-
7), 135.0 (C-8), 137.3 (C-5a), 139.2 (Ci), 143.1 (C-9a), 153.6 (C-10a), 156.7 (C3),
164.1 (C-9b), 190.9 (C@O). IR (KBr) cmꢁ1 2963 (CH st), 1715 (C@O st). The mass
spectrum shows the following peaks: MS (70 eV) m/z (%) = 353 (M+, 39), 339
(22), 338 (100). HR-MS calcd for C23H19N3O 353.1528, found 353.1529. Anal.
Calcd for C23H19N3O: C, 78.16; H, 5.42; N, 11.89. Found: C, 78.10; H, 5.48; N,
11.90.
10. Castillo, J. C.; Abonía, R.; Cobo, J.; Glidewell, C. Acta Crystallogr., Sect. C 2009, 65,
303–310.
11. (a) Trilleras, J.; Cruz, S.; Cobo, J.; Low, J. N.; Glidewell, C. Acta Crystallogr., Sect. C
2008, 64, 671–674; (b) Trilleras, J.; Quiroga, J.; Cobo, J.; Low, J. N.; Glidewell, C.
Acta Crystallogr., Sect. C 2008, 64, 665–670; (c) Cruz, S.; Trilleras, J.; Cobo, J.; Low, J.
N.; Glidewell, C. Acta Crystallogr., Sect. C 2008, C64, 637–642; (d) General procedure
to the synthesis of pyrazolopyridine–5–spiro derivatives 4, 5 and 6. Microwave
method: Microwave experiment was carried out using a focused microwave
reactor (CEM Discover TM). A mixture of amine (2 mmol), cyclic b-diketone
(2 mmol
of
5,5-dimethylcyclohexane-1,3-dione,
cyclohexane-1,3-dione,
cyclopentane-1,3-dione or indandione) and an excess of paraformaldehyde
(30 mol %) was exposed to microwave radiation for 25 min at 200 °C and a
maximum power of 300 W. The reaction mixture was dissolved in hot ethanol.
After cooling down to room temperature, the solid product was filtered and
washed with fresh ethanol and hexanes (2 ꢀ 5 mL) to afford a pure product.
Conventional method: A solution of amine (2 mmol), cyclic b-diketone (2 mmol of
5,5-dimethylcyclohexane-1,3-dione, cyclohexane-1,3-dione, cyclopentane-1,3-
dione or indandione) in ethanol (15 mL), was added to an excess of
paraformaldehyde (30 mol %) and the mixture was heated under reflux for
24 h. After cooling down to rt, the colourless precipitate was filtered off, washed
with ethanol (2 ꢀ 5 mL) and dried to afford the pure products. In the case of the
reaction between indandione and all 5-aminopyrazoles derivatives 1, the
compound 7 was obtained in a yield of 45% in each reaction after separating by
column chromatography using chloroform as the eluent.
12. Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J. Org. Chem. 2004, 4957–4980.
13. All new compounds gave satisfactory 400 MHz 1H NMR and 100 MHz 13C NMR
and IR spectral data.
Selected physical data.
Data for 3-tert-butyl-5-spiro-1-phenyl-7-(4-methylbenzyl)-1H-pyrazolo[3,4-
b]pyridine-4,5,6,7-tetrahydro-10-cyclopentano-2,5-dione 4a. White solid, 84%,