Simultaneous synthesis of pyrazolopyridines and pyrazolopyrimidinones under microwave irradiation

Article abstract of DOI:10.1080/00397910902883629

The direct reaction of o-aminopyrazocarbonitriles and carbonyl compounds to afford pyrazolopyrimidinones was discovered; hence, a simultaneous synthetic method for pyrazolopyridines and pyrazolopyrimidinones was achieved. Under microwave irradiation, bett

Full text of DOI:10.1080/00397910902883629

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Simultaneous Synthesis
of Pyrazolopyridines and
Pyrazolopyrimidinones Under
Microwave Irradiation
Li-Jun Zhang a , Da-Xin Shi b & Jia-Rong Li b
a School of Chemistry and Chemical Engineering,
Tianjin University of Technology, Tianjin, China
b School of Chemical Engineering and Environment,
Beijing Institute of Technology, Beijing, China
Version of record first published: 16 Oct 2009.
To cite this article: Li-Jun Zhang , Da-Xin Shi & Jia-Rong Li (2009): Simultaneous
Synthesis of Pyrazolopyridines and Pyrazolopyrimidinones Under Microwave
Irradiation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:22, 4010-4018
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Synthetic Communications1, 39: 4010–4018, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902883629
Simultaneous Synthesis of Pyrazolopyridines
and Pyrazolopyrimidinones Under
Microwave Irradiation
Li-Jun Zhang,1 Da-Xin Shi,2 and Jia-Rong Li2
1School of Chemistry and Chemical Engineering, Tianjin
University of Technology, Tianjin, China
2School of Chemical Engineering and Environment, Beijing
Institute of Technology, Beijing, China
Abstract: The direct reaction of o-aminopyrazocarbonitriles and carbonyl
compounds to afford pyrazolopyrimidinones was discovered; hence, a simulta-
neous synthetic method for pyrazolopyridines and pyrazolopyrimidinones was
achieved. Under microwave irradiation, better yields of products than those of
conventional method were given.
Keywords: Microwave irradiation, pyrazolopyridines, pyrazolopyrimidinones,
synthesis
Condensed polyazaheterocycles are an important ring system presenting
in a variety of natural products, pharmaceuticals, and agrochemicals.[1]
Compounds containing pyrazolopyrimidinone or pyrazolo-pyridine
skeletons are important heterocycles and exhibit a wide range of biologi-
cal and pharmaceutical activities, such as acting as a potent and selective
phosphodiesterase type-5 inhibitor and an A1-adenosine receptor.[2–10] In
literature,[11,12] the two skeletons of heterocycles are prepared separately
by different reactions; the direct synthesis of pyrazolopyrimidinones from
o-aminopyrazocarbonitriles and carbonyl compounds has never been
Received November 17, 2008.
Address correspondence to Li-Jun Zhang, School of Chemistry and Chemical
Engineering, Tianjin University of Technology, Tianjin 300191, China. E-mail:
cdlijun2002@126.com
4010

Pyrazolopyridines and Pyrazolopyrimidinones
4011
Scheme 1. Reaction
cyclohexanone.
of
3-amino-4-cyano-1-phenyl-1H-pyrazole
and
reported. Classically, when catalyzed by Lewis acids, pyrazolopyridines,
as exclusive products, were obtained via the reaction of o-aminopyrazo-
carbonitriles and carbonyl compounds; however, during our synthesis of
pyrazolopyridines by the condensation of o-aminopyrazocarbonitrile 1
and cyclohexanone 2a in the presence of zinc chloride, two different
skeletons of products, pyrazolopyridine 3a and pyrazolopyrimidinone
4a, were separated (Scheme 1). By utilizing Boitage microwave reactor,
greater product yields than those of conventional methods were afforded.
3-Amino-4-cyano-1-phenyl-1H-pyrazole (1), the starting material for
this work, was conveniently synthesized from the reaction of ethoxy-
methylenemalononitrile with phenyl hydrazine.[13] Then, the reaction of
compound 1 with excessive cyclohexanone, catalyzed by zinc chloride,
was carried out at the boiling point of cyclohexanone in an oil bath,
and 7 h later, two different skeletons of compounds, 3a and 4a, were
simultaneously obtained in poor yields (Scheme 1). On the basis of
spectral data and elemental analysis, the structure of 4a was assigned
as 1H-pyrazolo[3,4-b]-pyrimidin-4-one and the structure of 3a was
assigned as pyrazolopyridine, which was further confirmed by x-ray
diffraction of 3c (Fig. 1) The crystal structure of 3c has been determined
as monoclinic, with space group P21=c with lattice parameters
ꢀ
˚
˚
˚
a ¼ 13.694(13) A, b ¼ 6.888(6) A, c ¼ 16.929(16) A, b ¼ 112.417(12) ,
V ¼ 1476(2) A , Z ¼ 4, and Dcalc ¼ 1.252 Mg=m3. T ¼ 293(2) K, R indices
3
˚
(all data): R1 ¼ 0.0824, wR2 ¼ 0.1597. CCDC 635028.
Among all the parameters, the catalyst plays the most important role
in leading to different conversion products. Complying with Friedla¨nder
reaction,[14] only product 3a was afforded in 42% yield after pyrazole 1
reacted with 2a for 4 h in 1,2-dichloroethane and was catalyzed by AlCl3.
However, when the same reaction was carried out under ZnCl2, products

4012
L.-J. Zhang, D.-X. Shi, and J.-R. Li
Figure 1. Molecular structure of 3c, with the atom-labeling scheme. Displacement
ellipsoids are drawn at the 50% probability level.
3a and 4a were obtained in 37% and 21% yields, respectively. Other
catalysts such as p-PhSO3H, HCl, pyridine, and sodium carbonate failed
to give 4a in a separable yield. After screening a lot of catalysts, we found
that ZnCl2 was the best one in promoting the formation of 4a.
Because the optimization of reaction parameters failed to give accep-
table product yields, we adopted microwave irradiation to improve the
reaction; fortunately, better yields of both 3a and 4a were obtained
(Table 1).
To extend the reaction scope, several ketones were employed to react
with reactant 1, and in most cases, pyrazolopyrimidinones 4 were also
obtained. As shown in Table 1 for the formation of compound 4, ketones
with six-membered rings were better than others. When compound 1
reacted with cycloheptanone, the new conversion product 4c was
obtained in merely trace amounts. In the case of acetone, only one
direction of reactions occurred, and the product 4d with pyrazolo[3,
4-d]pyrimidinone skeleton was isolated in 65% yield.
Based on these observations, the possible mechanism for the
formation of compounds 4 is shown in Scheme 2. Intermediate 5
was produced by the addition of the amino group of o-aminopyrazo-
nitrile onto the carbonyl of cyclohexanone; then the hydroxyl group
of intermediate 5 attacked the nitrile moiety via Pinner reaction[15]
to afford an oxazine derivative 6, which was unstable in reaction sites
and quickly rearranged to the new conversion product 4a (Dimorth
rearrangement[16]).
In summary, we have developed a convenient, straightforward
method for the construction of the pyrazolopyrimidinone and

Pyrazolopyridines and Pyrazolopyrimidinones
4013
Table 1. Synthesis of pyrazolopyridines 3 and pyrazolopyrimidinones 4 catalyzed
by ZnCl2 under microwave irradiationa
Temperature
(ꢀC)
Yield
(%)b
Yield Total
(%)b yieldb (%)
Entry
1
2
Product
Product
150
130
150
110
130
43
42
46
29
89
71
43
65
81
2
3
4
5
43
Trace
65
Trace
28
53
aAll reactions were carried out at variable power in a Biotage microwave
reactor for 10 min using 1 (4 mmol), ZnCl2 (4.2 mmol), and 2 (3 mL).
bIsolated yield.
Scheme 2. Mechanism for the formation of 4.

4014
L.-J. Zhang, D.-X. Shi, and J.-R. Li
pyrazoloquinoline frameworks that involves the direct cyclization of
o-aminocyanopyrazoles with ketones in the presence of a Lewis acid
catalyst; thus, a new method to afford pyrazolopyrimidinones was dis-
covered. With microwave assistance, the reaction was completed quickly
and gave good yields of products. It may represent a potentially useful
route to otherwise laboriously accessible polyazaheterocycles. Further
work is under way.
EXPERIMENTAL
Melting points were determined using an XT4 microscope melting-point
apparatus and are uncorrected. Infrared (IR) spectra were recorded on a
Perkin-Elmer Fourier transform (FT)–IR spectrophotometer and were
run as KBr pellets. 1H and 13C NMR spectra were recorded at
400 MHz on a Bruker 400 spectrometer. Chemical shifts were reported
in d (ppm) relative to internal tetramethylsilane (TMS). Mass spectra
were recorded on a ZAB-HS mass spectrometer using electrospray ioni-
zation (ESI). Elemental analyses were within ꢁ0.4% of theoretical
values and were performed on an Elementar Vario EL instrument.
X-ray diffraction data were collected at 113(2) K on a Rigaku
MM-007 Rotating anode diffractometer equipped with Saturn 70
˚
CCD, using confocal Mo Ka radiation (k ¼ 0.71070 A), and the struc-
ture was solved by direct methods using the program SHELXS6.12.
Refinements were done by the full-matrix least-squares on F2 using
SHELXL6.12.
General Procedure
A solution of corresponding ketone (3 mL), o-aminopyrazocarbonitrile 1
(4 mmol), and anhydrous ZnCl2 (4.2 mmol) was added in a 5-mL tube,
which was sealed and put into the microwave reactor (‘‘Initiator,’’ man-
ufactured by Biotage, formerly Personal Chemistry). The time (10 min)
and different temperatures were set up (Table 1). (The power is variable
during the reaction stage). After the completion of the reaction as
indicated by thin-layer chromatography (TLC), the hot mixture was
quenched with water (10 mL) and neutralized to pH 10–12 with 20%
sodium hydroxide. The organic layer was dried over anhydrous
sodium sulfate and filtered, and the solvent was evaporated. The resulting
solid was isolated by column chromatography (200 to 300-mesh silica
gel, ethyl acetate–petroleum 1:2) to give pyrazolopyridines 3 and
pyrazolopyrimidinones 4.

Pyrazolopyridines and Pyrazolopyrimidinones
Data
4015
1-Phenyl-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-b]quinolin-4-amine (3a)
White crystal; mp 194–195ꢀC; IR (KBr) n (cmꢂ1): 3335 and 3230 (NH),
2937 and 2855 (CH aliph.), 1648, 1597, 1567, 1502, 1355, 1255, 1154; 1H
NMR (400 MHz, CDCl3, d ppm): 1.85–1.93 (m, 4 H, aliph-H), 2.49–2.52
(t, 2 H, aliph-H), 2.96–2.99 (t, 2 H, aliph-H), 4.59 (s, 2 H, NH2), 7.21–7.26
(t, 1 H, J ¼ 7.4 Hz, Ph-H), 7.45–7.49 (t, 2 H, J ¼ 7.5 Hz, Ph-H), 7.98 (s,
1 H, pyrazole-H), 8.30–8.32 (d, 2 H, J ¼ 7.6 Hz, Ph-H); 13C NMR
(100 MHz, CDCl3, d ppm): 22.84, 22.86, 22.91, 34.19, 105.47, 107.67,
120.80 (2C), 125.25, 128.90 (2C), 130.44, 140.10, 144.88, 150.04, 158.53;
MS-ESI (MHþ, 100%): 265.1. Anal. calcd. for C16H16N4: C, 72.70; H,
6.10; N, 21.20. Found: C, 72.41; H, 6.08; N, 21.47.
1-Phenyl-1,5,6,7-tetrahydrocyclopenta[b]pyrazolo[4,3-e]pyridin-
4-amine (3b)
White crystal; mp 188–189ꢀC; IR (KBr) n (cmꢂ1): 3397 and 3337 (NH),
2955 and 2838 (CH aliph.), 1659, 1591, 1576, 1505, 1363; 1H NMR
(400 MHz, CDCl3, d ppm): 2.15–2.22 (qt, 2 H, CH2), 2.73–2.77 (t, 2 H,
CH2), 3.03–3.07 (t, 2 H, CH2), 4.57 (br, 2 H, NH2), 7.22–7.24 (t,
J ¼ 7.4 Hz, 1 H, Ph-H), 7.45–7.49(t, J ¼ 7.7 Hz, 2 H, Ph-H), 7.99 (s, 1 H,
pyrazole-H), 8.22–8.24 (d, J ¼ 7.8 Hz, 2 H, Ph-H); 13C NMR (100 MHz,
CDCl3, d ppm): 23.12, 26.33, 34.97, 105.94, 112.54, 121.32 (2C),
125.56, 128.94 (2C), 130.55, 139.94, 142.74, 152.40, 167.80; MS-ESI
(MHþ, 100%): 251.15. Anal. calcd. for C15H14N4: C, 71.98; H, 5.64; N,
22.38. Found: C, 71.72; H, 5.66; N, 22.39.
1-Phenyl-1,5,6,7,8,9-hexahydrocyclopenta[b]pyrazolo[4,3-e]pyridin-
4-amine (3c)
White crystal; mp 194–195ꢀC; IR (KBr) n (cmꢂ1): 3482, 3350, 2922, 1638,
1594, 1501, 1358; 1H NMR (400 MHz, CDCl3, d ppm): 1.62–1.90 (m, 6 H,
C6H2, C7H2 and C8 H2), 2.66–2.69 (t, 2 H, C5H2), 3.08–3.01 (t, 2 H,
C9 H2), 4.60 (s, 2 H, NH2), 7.22–7.26 (t, J ¼ 7.4 Hz, 1 H), 7.46–7.50 (t, J ¼
7.5 Hz, 2 H), 7.98 (s, 1 H, pyrazole-H), 8.30–8.32 (d, J ¼ 7.6 Hz, 2 H); 13
C
NMR (100 MHz, CDCl3, d ppm): 25.40, 26.79, 27.56, 32.16, 39.81, 106.11,
113.24, 120.91 (2C), 125.37, 128.89 (2C), 130.61, 140.02, 143.69, 149.52,
165.25; MS-ESI (MHþ, 100%): 279.1. Anal. calcd. for C15H14N4: C,
73.35; H, 6.52; N, 20.13. Found: C, 73.17; H, 6.52; N, 19.99.

4016
L.-J. Zhang, D.-X. Shi, and J.-R. Li
5,6-Dimethyl-1H-Pyrazolo[3,4-b]pyridin-4-amine (3e)
White powder; mp 170–172ꢀC; IR (KBr) n (cmꢂ1): 3399, 3347, 1658,
1600, 1571, 1504, 1351, 1288; 1H NMR (400 MHz, CDCl3, d ppm):
2.16 (s, 3 H), 2.61 (s, 3 H), 4.60 (s, 2 H, NH2), 7.24–7.27 (t, 1 H,
J ¼ 7.4 Hz), 7.47–7.51 (t, J ¼ 7.5 Hz, 2 H), 8.0 (s, pyrazole-H), 8.31–8.33
(d, 2 H, J ¼ 7.6 Hz); 13C NMR (100 MHz, CDCl3, d ppm): 11.70, 24.44,
105.81, 106.31, 120.86 (2C), 125.37, 128.90 (2C), 130.34, 140.01, 144.84,
149.68, 157.98; MS-ESI (MHþ, 100%): 239.15. Anal. calcd. for
C14H14N4: C, 70.57; H, 5.92; N, 23.51. Found: C, 70.30; H, 5.88; 23.62.
10-Phenyl-spiro[Cyclohexane-1,60-[6H]pyrazolo[3,4-d]pyrimidin]-
40(50h)-one (4a)
White crystal; mp 164–166ꢀC; IR (KBr) n (cmꢂ1): 3204 (NH), 2952, 2936 (CH2),
1
1649, 1598, 1545, 1458, 1309, 1216; H NMR (400 MHz, CDCl3, d ppm):
1.21–1.93 (m, 10 H), 4.36 (s, 1 H, NH), 5.67 (s, 1 H, NH), 7.37–7.41 (t, 1 H,
J¼ 7.4 Hz), 7.50–7.54 (t, 2 H, J¼ 7.5 Hz), 7.59–7.62 (d, 2 H, J¼ 7.8 Hz), 7.90
(s, pyrazole-H); 13C NMR (100 MHz, CDCl3, d ppm): 22.10 (2C), 27.01,
37.41 (2C), 71.47, 122.23 (2C), 127.72, 129.79 (2C), 137.83, 137.97, 138.63,
147.02, 161.90; MS-ESI (MHþ, 100%): 283.1. Anal. calcd. for C16H18N4O: C,
68.06; H, 6.43; N, 19.84. Found: C, 67.98; H, 6.47; N, 20.13.
10-Phenyl-spiro[cyclopentane-1,60-[6H]pyrazolo[3,4-d]pyrimidin]-
40(50h)-one (4b)
White crystal; mp 161–163ꢀC; IR (KBr) n (cmꢂ1): 3378, 3229, 2957, 1650,
1578, 1500, 1382, 777; 1H NMR (400 MHz, CDCl3, d ppm): 1.78–2.0 (m,
4 H, 2CH2), 1.86–2.02 (m, 4 H, 2CH2), 4.43 (s, 1 H, NH), 6.15 (s, 1 H,
NH), 7.38–7.40 (t, 1 H, J ¼ 7.3 Hz, Ph-H), 7.48–7.53 (t, 2 H, J ¼ 7.4 Hz,
Ph-H), 7.59–7.61 (d, 2 H, J ¼ 7.5 Hz, Ph-H), 7.90 (s, 1 H, pyrazole-H);
13C NMR (400 MHz, CDCl3, d ppm): 22.23 (2C), 39.82 (2C), 80.14,
122.17, 122.19, 123.78, 127.62, 129.67, 129.74, 137.95, 138.54, 147.68,
162.72; MS-ESI (MHþ, 100%): 269.2. Anal. calcd. for C15H16N4O: C,
67.15; H, 6.01; N, 20.88. Found: C, 67.01; H, 5.99; N, 20.96.
6,6-Dimethyl-1-phenyl-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-
4(5H)-one (4d)
White crystal; mp 213–214ꢀC; IR (KBr) n(cmꢂ1): 3267, 3188, 1655, 1637,
1577, 1542, 1386; 1H NMR (400 MHz, CDCl3, d ppm): 1.61 (s, 6 H), 4.52

Pyrazolopyridines and Pyrazolopyrimidinones
4017
(s, 1 H, NH), 6.22 (s, 1 H, NH), 7.36–7.40 (t, 1 H, J ¼ 7.2 Hz), 7.49–7.53
(t, 2 H, J ¼ 7.6 Hz), 7.56–7.59 (d, 2 H, J ¼ 7.5 Hz), 7.89 (s, pyrazole-H);
13C NMR (100 MHz, CDCl3, d ppm): 29.24 (2C), 70.38, 99.99, 122.41
(2C), 127.71, 129.71 (2C), 137.85, 138.57, 147.35, 162.33; MS-ESI
(MHþ, 100%): 243.15. Anal. calcd. for C13H14N4O: C, 64.45; H, 5.82;
N, 23.13. Found: C, 64.20; H, 5.78; N, 23.21.
6-Ethyl-6-methyl-1-phenyl-6,7-dihydro-1H-
pyrazolo[3,4-d]pyrimidin-4(5h)-one (4e)
White crystal; mp 165–166ꢀC; IR (KBr) n(cmꢂ1): 3211, 2968, 2927, 2876,
2855, 1649, 1600, 1578, 1560, 1504, 1458, 1272; H NMR (400 MHz,
1
CDCl3, d ppm): 0.98–1.02 (t, 3 H, J ¼ 7.4 Hz), 1.55 (s, 3 H), 1.84–1.89 (q,
J ¼ 7.4 Hz), 4.51 (s, 1 H, NH), 6.29 (s, 1 H, NH), 7.36–7.40 (t, 1 H,
J ¼ 7.3 Hz), 7.49–7.53 (t, 2 H, J ¼ 7.4 Hz), 7.56–7.58 (d, 2 H, J ¼ 7.6 Hz),
7.87 (s, pyrazole-H); 13C NMR (100MHz, CDCl3, d ppm): 8.35, 27.07,
34.29, 73.08, 99.59, 122.45 (2C), 127.77, 129.78 (2C), 137.84, 138.59,
147.40, 162.55; MS-ESI (MHþ, 100%): 257.15. Anal. calcd. for
C14H16N4O: C, 65.61; H, 6.29; N, 21.86. Found: C, 65.40; H, 6.25; N, 22.08.
REFERENCES
1. Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Comprehensive Heterocyclic
Chemistry II; Pergamon: New York, 1996.
2. Dunn, P. J. Synthesis of commercial phosphodiesterase(V) inhibitors. Org.
Process Res. Dev. 2005, 9, 88–97.
3. Allerton, C. M. N.; Barber, C. G.; Beaumont, K. C.; Brown, D. G.; Cole, S.
M.; Ellis, D.; Lane, C. A. L.; Maw, G. N.; Mount, N. M.; Rawson, D. J.;
Robinson, C. M.; Street, S. D. A.; Summerhill, N. W. A novel series of potent
and selective PDE5 inhibitors with potential for high and dose-independent
oral bioavailability. J. Med. Chem. 2006, 49, 3581–3594.
4. Markwalder, J. A.; Arnone, M. R.; Benfield, P. A.; Boisclair, M.; Burton, C.
R.; Chang, C. H.; Cox, S. S.; Czerniak, P. M.; Dean, C. L.; Doleniak, D.;
Grafstrom, R.; Harrison, B. A.; Kaltenbach, R. F. III; Nugiel, D. A.; Rossi,
K. A.; Sherk, S. R.; Sisk, L. M.; Stouten, P.; Trainor, G. L.; Worland, P.;
Seitz, S. P. Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyr-
azolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases. J. Med.
Chem. 2004, 47, 5894–5911.
5. Bontems, R. J.; Anderson, J. D.; Smee, D. F.; Jin, A.; Alaghamandan, H. A.;
Sharma, B. S.; Jolley, W. B.; Robins, R. K.; Cottam, H. B. Guanosine ana-
logs: Synthesis of nucleosides of certain 3-substituted 6-aminopyrazolo[3,4-
d]pyrimidin-4(5 H)-ones as potential immunotherapeutic agents. J. Med.
Chem. 1990, 33, 2174–2178.

4018
L.-J. Zhang, D.-X. Shi, and J.-R. Li
6. Xia, Y.; Chackalamannil, S.; Czarniecki, M.; Tsai, H.; Vaccaro, H.; Cleven,
R.; Cook, J.; Fawzi, A.; Watkins, R.; Zhang, H. Synthesis and evaluation of
polycyclic pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP phospho-
diesterase inhibitors. J. Med. Chem. 1997, 40, 4372–4377.
7. Yu, G.; Mason, H. J.; Wu, X.; Wang, J.; Chong, S.; Dorough, G.; Henwood,
A.; Pongrac, R.; Seliger, L.; He, B.; Normandin, D.; Adam, L.; Krupinski, J.;
Macor, J. E. Substituted pyrazolopyridines as potent and selective PDE5
inhibitors: Potential agents for treatment of erectile dysfunction. J. Med.
Chem. 2001, 44, 1025–1027.
8. Dornow, A.; Siebrecht, M. Synthesen stickstoffhaltiger Heterocyclen, XXII:
¨
Uber die Synthese einiger Pyrazolo[3.4-b]pyridine. Chem. Ber. 2006, 93,
1106–1110.
9. Rawlings, D. A. Pyrazolo[3,4-c]pyridines as GSK-3 inhibitors. US patent
7105532, 2006.
10. Schenone, S.; Bruno, O.; Fossa, P.; Ranise, A.; Menozzi, G.; Mosti, L.;
Bondavalli, F.; Martini, C.; Trincavelli, L. Synthesis and biological data of
4-amino-1-(2-chloro-2-phenylethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic
acid ethyl esters, a new series of A1-adenosine receptor (A1AR) ligands.
Bioorg. Med. Chem. Lett. 2001, 11, 2529–2531.
11. Tominaga, Y.; Honkawa, Y.; Hara, M.; Hosomi, A. Heteroaromatization
with ketene dithioacetals, part I: Synthesis of some novel 5-amino-1-
(1,3,4-thiadiazol-2-yl) and 1-(1,3,4-thiadiazin-2-yl)pyrazole-4-carbonitriles.
J. Heterocycl. Chem. 1990, 27, 775–783.
12. Adams, N. D.; Schmidt, S. J.; Knight, S. D.; Dhanak, D. A novel synthesis
of substituted 4H-pyrazolo[3,4-d]pyrimidin-4-ones. Tetrahedron Lett. 2007,
48, 3983–3986.
13. Cheng, C. C.; Robins, R. K. Potential purine antagonists, VI: Synthesis of
1-alkyl- and 1-aryl-4-substituted pyrazolo[3,4-d]pyrimidines. J. Org. Chem.
1956, 21, 1240–1256.
14. Marttnez-Grau, A.; Marco, J. L. Friedlander reaction on 2-amino-3-cyano-
4 h-pyrans: Synthesis of derivatives of 4 H-pyran [2,3-b] quinoline, new
tacrine analogues. Bioorg. Med. Chem. Lett. 1997, 7, 3165–3170.
15. Pinner, A.; Klein, F. Umwandlung der Nitrile in Irnide. Ber. Dtsch. Chem.
Ges. 1877, 10, 1899.
16. Rozhkov, V. Y.; Batog, L. V.; Shevtsova, E. K.; Struchkova, M. I. Synthesis
and dimroth rearrangement of 3-amino-4-(5-amino-1H-1,2,3-triazol-1-
yl)-1,2,5-oxadiazoles. Mendeleev Commun. 2004, 14, 76–77.