New one-step synthesis of pyrazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]quinazoline derivatives via multicomponent reactions

Article abstract of DOI:10.1002/jhet.128

(Chemical Equation Presented) A series of pyrazolopyrimidine and pyrazoloquinozoline derivatives has been synthesized in one step by multicomponent reactions using, 5-aminopyrazole, p- substitutedbenzoylacetonitrile/dimedone and triethylorthoesters. pyraz

Full text of DOI:10.1002/jhet.128

708
New One-Step Synthesis of Pyrazolo[1,5-a]pyrimidine and
Pyrazolo[1,5-a]quinazoline Derivatives via
Multicomponent Reactions
Vol 46
Bhausaheb K. Ghotekar, Madhukar N. Jachak, and Raghunath B. Toche*
Organic Chemistry Research Center, Department of Chemistry, K.R.T. Arts, B.H. Commerce and
A.M. Science College, Gangapur Road, Nashik 422002, Maharashtra, India
*E-mail: bhausaheb.ghotekar@rediffmail.com
Received March 10, 2009
DOI 10.1002/jhet.128
Published online 13 July 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of pyrazolopyrimidine and pyrazoloquinozoline derivatives has been synthesized in one step
by multicomponent reactions using, 5-aminopyrazole, p-substitutedbenzoylacetonitrile/dimedone and
triethylorthoesters. pyrazolopyrimidine derivatives were also studied for their absorption and fluores-
cence maxima.
J. Heterocyclic Chem., 46, 708 (2009).
INTRODUCTION
On the other hand, multicomponent reactions
(MCRs) are of increasing importance in organic and
medicinal chemistry. MCR strategies offer significant
advantages over conventional linear type synthesis
[22–24]. As a part of our continued interest [25–27] in
the synthesis of novel heterocyclic compounds, we
have reported the synthesis of pyrazolo[3,4-b]pyri-
dines, pyrazolo[3,4-b]quinolines, pyrazolonaphthyri-
dines and pyrazolopyridopyrimidines by Friedlander
condensation of 5-aminopyrazole-4-carbaldehyde with
various reactive methylene compounds and the synthe-
sis of fused pyrimidines [28] by using 2-aminohetero-
cycles and cyclic b-formylesters in ammonium acetate
at 120ꢀC. We have also reported the study of fluores-
cence properties of benzo[h]quinolines and dipyrazolo-
pyridines [29,30]. In our recent communications
[31,32], we have reported the synthesis of chromenes,
quinolines, and pyrazolo[3,4-b]pyridines by multicom-
ponent reaction strategy. These literature reports and
increasing importance of multicomponent reactions in
organic chemistry encourage us to synthesize, pyra-
zolo[1,5-a]pyrimidine and pyrazolo[1,5-a] quinazoline
derivatives using multicomponent reactions and study
the photophysical properties of pyrazolopyrimidine
derivatives.
Heterocyclic ring systems that containing the pyrazole
ring fused to pyrimidine or quinazoline rings are interest-
ing classes of compounds both chemically and biologi-
cally. For example, pyrazolopyrimidines display signifi-
cant chemical properties [1–7]. In particular, pyra-
zolo[1,5-a]pyrimidines structural motif may be found in a
large number of pharmaceutical agents with a diverse
range of physiological activities, such as, antiepileptic
agents [8], anxiolytics [9], antidepressants [10], agents for
treatment of sleep disorders [11], and oncolytics [12,13].
Whereas, several naturally occurring and synthetic com-
pounds containing the quinazoline derivatives exhibit a
wide range of biological properties [14,15]. In recent
years an increasing interest has been focused on synthesis
of fluorescent compounds owing to their significant bio-
logical applications in the medicinal chemistry [16,17]. In
particular, these compounds have important applications
in the field of dyes [18] and are used in the security
papers [19]. In literature the synthesis of pyrazolo[1,5-
a]pyrimidines has been reported [20,21] by using Michael
addition reaction of 5-aminopyrazoles with enol ether of
reactive methylene compounds and triethylorthoesters.
The title compounds could be synthesized in one pot in
which the synthesis of enol ether is not required.
C
V
2009 HeteroCorporation

July 2009
New One-Step Synthesis of Pyrazolo[1,5-a]pyrimidine and Pyrazolo[1,5-a]quinazoline
Derivatives via MultiComponent Reactions
709
Scheme 1
RESULTS AND DISCUSSION
167, 131, 133, 134. Mass Spectrum of 4a showed char-
acteristic peaks for Mþ and Mþ2 at 279 and 281 m/z,
due to presence of chlorine. The elemental analysis
obtained is in agreement with molecular formula. Analo-
gously, the cyclocondensation of 5-amino-1H-pyrazole-
4-carbonitrile 1, p-substituted benzoylacetonitriles 2 and
triethylorthoesters 3 by refluxing in ethanol in the pres-
ence of catalytic amount of hydrochloric acid for 2 h,
afforded compounds 5 in good yield. The structure of
5a was confirmed by IR, 1H-NMR, 13C-NMR, mass
spectroscopy and elemental analysis for example the IR
spectrum of 5a showed the bands at 1621 and 2231
cmꢁ1 for C¼¼O and CN stretching respectively and two
The cyclocondensation of 5-amino-1H-pyrazole-4-car-
bonitrile 1, p-substituted benzoylacetonitriles 2 and trie-
thylorthoesters 3 by refluxing in toluene containing cata-
lytic amount of triethylamine for 2 h, afforded com-
pounds 4 in good yield. The structure of 4a was con-
firmed by IR, 1H-NMR, 13C-NMR, mass spectroscopy
and elemental analysis for example the IR spectrum of
4a showed bands at 2237 cmꢁ1 for CN stretching. The
1H-NMR of compound 4a showed a multiplets at d
7.85–7.89 for four aromatic protons and the two singlets
at d 8.87 and d 9.16 corresponding to C2H and C5H aro-
matic protons. The 13C-NMR spectrum of this com-
pound exhibits a peaks of tertiary carbons at d 128, 129,
138, 161 and of quaternary carbons at d 66, 106, 117,
bands for NH2 groups were appears at 3328–3425 cmꢁ1
.
The 1H-NMR of compound 5a showed a multiplet
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

710
B. K. Ghotekar, M. N. Jachak, and R. B. Toche
Vol 46
The 1H-NMR of compound 7a showed a singlet at d
1.25 for six methyl protons, singlet at d 2.65 and d 3.40
for four methylene protons, a singlet at 8.49 and 9.18
corresponding to C2H and C5H protons respectively.
Further this structure was confirmed by 13C-NMR which
is in agreement with the structure proposed. Similarly,
the structures of compound 7b and 7c were confirmed.
After synthesis of all these compounds, it was noted
that the pyrazolo[1,5-a]pyrimidine derivatives showed
good fluorescence properties. So, we further studied the
photophysical properties of pyrazolopyrimidine deriva-
tives 4 and 5. It was observed that compounds 4 showed
UV absorption in the range 267–296 nm and fluores-
cence maxima in the range of 304–332 nm. While the
compounds 5 showed slightly better absorption and
emission values. From Table 1. It is evident that the
incorporation of amino group at C7 position in com-
pounds 5 markedly increases the absorption and emis-
sion properties compared with aryl group at C7 position
in compounds 4. The compound 5d showed good
absorption and emission spectra as shown in Figure 1.
The reactions reported here represent new synthetic
methods toward synthesis of novel pyrazolopyrimidine
and pyrazoloquinozoline derivatives with simple workup
and clean products in single step.
Table 1
The absorbance, emission kmax, and quantum yield of
pyrazolopyrimidines (4a-f and 5a-f).
Absorbance
kmax (nm)
Emission
kmax (nm)
Quantum
yield (UF)
Compd.
(4a)
(4b)
(4c)
(4d)
(4e)
(4f)
(5a)
(5b)
(5c)
(5d)
(5e)
(5f)
293
280
296
279
267
284
336
342
345
360
338
350
322
316
332
306
304
312
393
398
400
414
402
407
0.110
0.109
0.111
0.108
0.107
0.112
0.113
0.114
0.116
0.117
0.103
0.104
between d 7.71 and 7.97 for four aromatic protons and
the two singlets at d 6.84 and d 8.63 for C2H and C5H
aromatic protons. The two broad singlets appeared at d
7.01 and d 8.48 corresponding to NH2 protons. The NH2
protons are splits in to two broad singlets due to forma-
tion of hydrogen bonding between hydrogen atom of
NH2 group and oxygen atom of C¼¼O group. The 13C-
NMR spectrum of this compound exhibits a peaks of
tertiary carbons at d 129, 131, 138, 160, and of quater-
nary carbons at d 68, 115, 133, 138, 168. The cyanide
and carbonyl carbon appears at d 126 and 196. The
mass spectrum of a showed Mþ and Mþ2 at 297 and
299 m/z. The elemental analysis obtained is in agree-
ment with the molecular formula. Similarly, the struc-
tures of bromo-derivatives 4d and 5d were confirmed. It
was observed that, the cyclocondensation of intermedi-
ate Y with ACOCH2A fragment of substrate 2 should
give product 4 but cyclocondensation of Y with
ACH2CNA fragment of substrate 2 should give product
5 [21,33].
EXPERIMENTAL
Melting points were determined on a Gallenkamp Melting
Point Apparatus, Mod. MFB-595 in open capillary tubes and
are uncorrected. The 1H and 13C-NMR spectra were recorded
on a Varian XL-300 spectrometer (300 MHz). Chemical shifts
are reported in ppm from internal tetramethylsilane standard
and are given d-units. The solvents for NMR spectra was
duteriochloroform unless otherwise stated. Infrared spectra
were taken on Shimadzu IR-408, a Shimadzu FTIR instrument
in potassium bromide pellets unless otherwise stated. UV
Spectra were recorded on a Shimadzu UV-1601 UV–visible
It was interesting to note that the cyclocondensaton
reaction in presence of basic medium at pH 9–10 led 7-
(4-aryl)pyrazolo[1,5-a] pyrimidine-3,6-dicarbonitriles 4,
where the cyclization on carbonyl carbon takes place,
whereas the similar cyclocondensation reaction when
carried out in presence of acidic medium at pH 3-4 gave
7-amino-6-(4-aroyl)pyrazolo[1,5-a]pyrimidine-3-carboni-
triles 5 in which the cyclization on nitrile carbon takes
place [21,33]. The synthesis of pyrazolo[1,5-a]quinazo-
lines 7 were also achieved in one step, by the cyclocon-
densation of 5-aminopyrazole 1, dimedone 6 and trie-
thyorthoesters 3 by refluxing in toluene for 3 h furnished
the compound 7 in 75–80% yield. The structure of 7a
1
was confirmed by IR, H-NMR, 13C-NMR and elemen-
tal analysis for example the IR spectrum of 7a showed
bands at 2215, 1687 cmꢁ1 for CN and carbonyl groups.
Figure 1. The absorption (dotted line) and emission spectra of com-
pound 5d.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
New One-Step Synthesis of Pyrazolo[1,5-a]pyrimidine and Pyrazolo[1,5-a]quinazoline
Derivatives via MultiComponent Reactions
711
Spectrophotometer. High-resolution mass spectra were obtained
with a Mat 112 Varian Mat Bremen (70 eV) mass spectrometer.
Compounds for UV scan were dissolved in methanol. Fluores-
cence spectra were recorded using RF-5301 PC Spectrofluoro-
photometer. Compounds for fluorescence measurements were
dissolved in methanol. UV and fluorescence scans were recorded
from 200 to 500 nm. Elemental analyses were performed on a
Hosli CH-Analyzer and are within ꢂ0.3 of the theoretical per-
centage. Solutions were concentrated in a rotary evaporator
under reduced pressure. All reactions were monitored by thin
layer chromatography, carried out on 0.2-mm silica gel 60 F254
(Merk) plates using UV light (254 and 366 nm) for detection.
Common reagents-grade chemicals are either commercially
available and were used without further purification or prepared
by standard literature procedures.
General procedure for the synthesis of 7-(4-aryl) pyrazo-
lo[1,5-a]pyrimidine-3,6-dicarbonitrile (4). A mixture of 5-
aminopyrazole 1 (1.08 g, 10 mmole), aroylacetonitriles 2 (10
mmole), and triethylorthoesters 3 (10 mmole) in toluene (20
mL) containing catalytic amount of triethylamine (0.5 mL)
was refluxed for 2–3 h. The completion of reaction was moni-
tored by thin layer chromatography (TLC). Then the excess of
solvent was removed under reduced pressure. The solid
obtained was stirred in ethanol (10 mL), filtered, washed with
ethanol, dried and recrystallized from suitable solvent fur-
nished compounds 4 in good yield.
7-(4-Chlorophenyl)pyrazolo[1,5-a]pyrimidine-3,6-dicarb-
onitrile (4a). This compound was obtained as colorless prism
(ethanol), 2.15 g (77%), mp 223–224ꢀC; IR: (Potassium bro-
mide): 2237, 1654, 1606, 1590, 1525, 1486, 1264, 1065, 1012,
827, 637 cmꢁ1; 1H-NMR: (CDCl3) d 7.85–7.89 (m, 4H,
ArAH), 8.87 (s, 1H, ArAH), 9.16 (s, 1H, ArAH); 13C-NMR:
(CDCl3) d 66, 106, 117, 119, 128, 129, 131, 133, 134, 138,
161, 167. MS: (70 eV) m/z (%) 281 (90) (Mþ2), 279 (100)
(Mþ), 271 (80), 258 (65), 244 (70), 233 (80), 207 (10), 181
(20), 153 (40), 122 (30), 93 (50), 78 (70), 63 (80), 44 (40).
Anal. Calcd for C14H6ClN5: C, 60.12; H, 2.16; N, 25.04.
Found: C, 60.29; H, 2.45; N, 25.33.
(ethanol), 2.78 g (86%), mp 246–248ꢀC; IR: (Potassium bro-
mide): 2239, 1656, 1610, 1587, 1521, 1482, 1262, 1068,
1
1018, 828, 639 cmꢁ1; H-NMR: (CDCl3) d 7.85 (d, 2H, J ¼
8.5 Hz, ArAH), 7.89 (d, 2H, J ¼ 8.4 Hz, ArAH), 8.85 (s,
1H, ArAH), 9.12 (s, 1H, ArAH); 13C-NMR: (CDCl3) d 67,
108, 118, 121, 125, 127, 131, 134, 136, 140, 163, 168. MS:
(70 eV) m/z (%) 326 (90) (Mþ2), 324 (100) (Mþ), 323 (80),
322 (60), 298 (10), 271 (10), 258 (10), 244 (20), 233 (10),
207 (10), 183 (20), 181 (10), 153 (40), 122 (60), 102 (70), 91
(60), 75 (80), 63 (70), 44 (60). Anal. Calcd for C14H6BrN5:
C, 51.88; H, 1.87; N, 21.61. Found: C, 51.54; H, 1.62; N,
21.41.
7-(4-Bromorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine-
3,6-dicarbonitrile (4e). This compound was obtained as yel-
low prism (ethanol/DMF), 2.77 g (82%), mp 142–143ꢀC; IR:
(Potassium bromide): 2243, 1611, 1592, 1485, 1460, 1383,
1
1097, 1016, 830, 641 cmꢁ1; H-NMR: (CDCl3) d 2.83 (s, 3H,
CH3), 7.76 (d, 2H, J ¼ 8.7 Hz, ArAH), 7.86 (d, 2H, J ¼ 8.7 Hz,
ArAH), 8.85 (s, 1H, ArAH). Anal. Calcd for C15H8BrN5: C,
53.28; H, 2.38; N, 20.71. Found: C, 53.51; H, 2.49; N, 20.39.
7-(4-Bromophenyl)-5-ethylpyrazolo[1,5-a]pyrimidine-3,6-di-
carbonitrile (4f). This compound was obtained as yellow
prism (ethanol/DMF), 2.67 g (76%), mp 194–196ꢀC; IR: (Po-
tassium bromide): 2234, 1622, 1587, 1491, 1461, 1382, 1093,
1016, 836, 646 cmꢁ1
;
1H-NMR: (CDCl3) d 1.40 (t, 3H, J ¼
7.2 Hz, CH3), 3.18 (q, 2H, J ¼ 7.2 Hz, CH2), 7.83 (d, 2H, J ¼
8.7 Hz, ArAH), 7.94 (d, 2H, J ¼ 8.4 Hz, ArAH), 8.91 (s, 1H,
ArAH). Anal. Calcd for C16H10BrN5: C, 54.56; H, 2.86; N,
19.89. Found: C, 54.29; H, 2.66; N, 19.65.
General procedure for the synthesis of 7-Amino-6-(4-
aroyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (5). A mix-
ture of 5-aminopyrazole 1 (1.08 g, 10 mmole), aroylacetoni-
triles 2 (10 mmole) and triethylorthoesters 3 (10 mmole) in
absolute ethanol (20 mL) containing catalytic amount of hy-
drochloric acid (0.1N, 0.5 mL) was refluxed for 2–3 h. The
completion of reaction was monitored by thin layer chroma-
tography (TLC). The solid obtained on cooling was filtered,
washed with ethanol, dried, and recrystallized from suitable
solvent furnished compounds 5 in good yield.
7-(4-Chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine-3,6-
dicarbonitrile (4b). This compound was obtained as yellow
prism (ethanol/DMF), 2.58 g (88 %), mp 228–230ꢀC; IR: (Po-
tassium bromide): 2246, 1615, 1596, 1489, 1464, 1381, 1098,
7-Amino-6-(4-chlorobenzoyl)pyrazolo[1,5-a]pyrimidine-3-
carbonitrile (5a). This compound was obtained as colorless
prism (DMF), 2.64 g (89%), mp 273–274ꢀC; IR: (Potassium
bromide): 3425, 3328, 2887, 2874, 2554, 2231, 1660, 1621,
1499, 1368, 1313, 1200, 1076, 1011, 899, 821, 726, 627.
1
1018, 832, 643 cmꢁ1; H-NMR: (CDCl3) d 2.81 (s, 3H, CH3),
7.74 (d, 2H, J ¼ 8.7 Hz, ArAH), 7.84 (d, 2H, J ¼ 8.7 Hz,
ArAH), 8.89 (s, 1H, ArAH). Anal. Calcd for C15H8ClN5: C,
61.34; H, 2.75; N, 23.84. Found: C, 61.13; H, 2.45; N, 23.61.
7-(4-Chlorophenyl)-5-ethylpyrazolo[1,5-a]pyrimidine-3,6-
dicarbonitrile (4c). This compound was obtained as colorless
prism (ethanol/DMF), 2.43 g (79%), mp 174–175ꢀC; IR: (Po-
tassium bromide): 2233, 1622, 1587, 1492, 1463, 1385, 1094,
1
cmꢁ1; H-NMR: (CDCl3) d 6.84 (s, 1H, ArAH), 7.01 (bs, 1H,
NH), 7.71 (d, 2H, J ¼ 8.4 Hz, ArAH), 7.97 (d, 2H, J ¼ 8.4
Hz, ArAH), 8.48 (bs, 1H, NH), 8.63 (s, 1H, ArAH); 13C-
NMR: (CDCl3) d 68, 115, 126, 129, 131, 133, 138, 160, 164,
168, 169, 196. MS: (70 eV) m/z (%) 299 (70) (Mþ2), 297
(90) (Mþ), 275 (80), 243 (65), 236 (70), 233 (80), 205 (10),
173 (100), 151 (40), 119 (30), 91 (50), 74 (70), 61 (80), 42
(40). Anal. Calcd for C14H8ClN5O: C, 56.48; H, 2.71; N,
23.52. Found: C, 56.29; H, 2.45; N, 23.33.
1021, 838, 642 cmꢁ1
;
1H-NMR: (CDCl3) d 1.41 (t, 3H, J ¼
7.2 Hz, CH3), 3.19 (q, 2H, J ¼ 7.2 Hz, CH2), 7.83 (d, 2H, J ¼
8.7 Hz, ArAH), 7.95 (d, 2H, J ¼ 8.4 Hz, ArAH), 8.91 (s, 1H,
ArAH); MS: (70 eV) m/z (%) 309 (40) (Mþ2), 307 (100)
(Mþ), 280 (40), 272 (80), 252 (20), 245 (30), 229 (10), 218
(10), 187 (30), 179 (20), 161 (50), 152 (30), 126 (30), 113
(10), 111 (40), 88 (10), 75 (60), 63 (50), 51 (55), 40 (40).
Anal. Calcd for C16H10ClN5: C, 62.45; H, 3.28; N, 22.76.
Found: C, 62.67; H, 3.53; N, 22.55.
7-Amino-6-(4-chlorobenzoyl)-5-methylpyrazolo[1,5-a] pyri-
midine-3-carbonitrile (5b). This compound was obtained as
colorless prism (DMF), 2.43 g (78%), mp 275–277ꢀC; IR: (Po-
tassium bromide): 3427, 3330, 3086, 2888, 2524, 2235, 1660,
1623, 1400, 1367, 1310, 1200, 1069, 1011, 890, 820, 726,
626. cmꢁ1 1H-NMR: (CDCl3) d 2.35 (s, 3H, CH3), 5.29 (bs,
;
7-(4-Bromophenyl)pyrazolo[1,5-a]pyrimidine-3,6-dicarb
onitrile (4d). This compound was obtained as colorless prism
2H, NH2), 7.60 (s 1H, ArAH), 7.62 (d, 2H, J ¼ 8.7 Hz,
ArAH), 7.70 (d, 2H, J ¼ 8.7 Hz, ArAH). Anal. Calcd for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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B. K. Ghotekar, M. N. Jachak, and R. B. Toche
Vol 46
C15H10Cl N5O: C, 57.79; H, 3.23; N, 22.47. Found: C, 57.63;
H, 3.41; N, 22.61.
(s, 6H, 2CH3), 2.65 (s, 2H, CH2), 3.40 (s, 2H, CH2), 8.49 (s,
1H, ArAH), 9.18 (s, 1H, ArAH); 13C-NMR: 28, 32, 37, 50,
85, 111, 115, 149, 150, 151, 153, 193. Anal. Calcd for
C13H12N4O: C, 64.99; H, 5.03; N, 23.32. Found: C, 65.29; H,
5.16; N, 23.56.
7-Amino-6-(4-chlorobenzoyl)-5-ethylpyrazolo[1,5-a]pyri-
midine-3-carbonitrile (5c). This compound was obtained as
colorless prism (DMF), 2.47 g (76%), mp 271–272ꢀC; IR: (Po-
tassium bromide): 3430, 3320, 3086, 2920, 2877, 2530, 2231,
1620, 1622, 1401, 1369, 1310, 1200, 1069, 1011, 890, 830,
5,8,8-Trimethyl-6-oxo-6,7,8,9-tetrhydropyrazolo[1,5-a] quin-
azoline-3-carbonitrile (7b). This compound was obtained as
colorless prism (ethanol), 2.13 g (84%), mp 186–187ꢀC; IR:
(Potassium bromide): 2217, 1689, 1610, 1539, 1369, 1312,
1
710, 636. cmꢁ1; H-NMR: (CDCl3) d 1.24 (t, 3H, J ¼ 7.2 Hz,
CH3), 2.55 (q, 2H, J ¼ 7.2 Hz, CH2), 5.62 (bs, 2H, NH2), 7.89
(d, 2H, J ¼ 8.7 Hz, ArAH), 7.98 (d, 2H, J ¼ 8.4 Hz, ArAH),
8.96 (s, 1H, ArAH). Anal. Calcd for C16H12ClN5O: C, 58.99;
H, 3.71; N, 21.50. Found: C, 58.76; H, 3.53; N, 21.69.
1264, 1177, 1098, 802, 684 cmꢁ1 1H-NMR: (CDCl3) d 1.23
;
(s, 6H, 2CH3), 2.63 (s, 2H, CH2), 2.79 (s, 3H, CH3), 3.38 (s,
2H, CH2), 8.47 (s, 1H, ArAH), 9.17 (s, 1H, ArAH). Anal.
Calcd for C14H14N4O: C, 66.13; H, 5.55; N, 22.03. Found: C,
65.97; H, 5.31; N, 22.41.
7-Amino-6-(4-bromobenzoyl)pyrazolo[1,5-a]pyrimidine-3-
carbonitrile (5d). This compound was obtained as colorless
prism (DMF), 2.87 g (84%), mp 289–290ꢀC; IR: (Potassium
bromide): 3426, 3329, 2889, 2877, 2559, 2232, 1661, 1623,
1496, 1363, 1310, 1201, 1077, 1012, 890, 823, 722, 628.
5-Ethyl-8,8-dimethyl-6-oxo-6,7,8,9-tetrhydropyrazolo[1,5-a]
quinazoline-3-carbonitrile (7c). This compound was obtained
as colorless prism (ethanol), 2.38 g (89%), mp 205–206ꢀC; IR:
(Potassium bromide): 2216, 1688, 1610, 1538, 1366, 131 0,
1
cmꢁ1; H-NMR: (CDCl3) d 6.86 (s, 1H, ArAH), 7.12 (bs, 1H,
1266, 1176, 1098, 801, 685 cmꢁ1 1H-NMR: (CDCl3) d 1.27
;
NH), 7.77 (d, 2H, J ¼ 8.2 Hz, ArAH), 7.95 (d, 2H, J ¼ 8.2
Hz, ArAH), 8.52 (bs, 1H, NH), 8.65 (s, 1H, ArAH); 13C-
NMR: (CDCl3) d 65, 120, 122, 123, 124, 128, 130, 133, 134,
165, 166, 192. MS: (70 eV) m/z (%) 344 (20) (Mþ2), 342
(90) (Mþ), 339 (30), 326 (10), 315 (60), 307 (10), 288 (10),
275 (10), 145 (25), 235 (20), 218 (60), 196 (65), 182 (45), 157
(10), 151 (05), 127 (20), 116 (15), 109 (100), 97 (60), 63 (40).
Anal. Calcd for C14H8BrN5O: C, 49.14; H, 2.36; N, 20.47.
Found: C, 49.29; H, 2.48; N, 20.28.
(s, 6H, 2CH3), 1.43 (t, 3H, J ¼ 7.2 Hz, CH3), 2.66 (s, 2H,
CH2), 3.19 (q, 2H, J ¼ 7.1 Hz, CH2), 3.41 (s, 2H, CH2), 8.50
(s, 1H, ArAH). Anal. Calcd for C15H16N4O: C, 67.15; H, 6.01;
N, 20.88. Found: C, 67.29; H, 6.16; N, 20.56.
Acknowledgment. The authors thank University Grant Com-
mission (UGC), New Delhi, India for financial support and Prof.
D. D. Dhavale, Department of Chemistry, University of Pune,
Pune, India for his valuable cooperation for the measurement of
fluorescence spectra and useful discussion.
7-Amino-6-(4-bromobenzoyl)-5-methylpyrazolo[1,5-a]py-
rimidine-3-carbonitrile (5e). This compound was obtained
as colorless prism (DMF), 2.77 g (78%), mp 292–293ꢀC; IR:
(Potassium bromide): 3429, 3331, 3089, 2890, 2221, 1660,
1619, 1400, 1369, 1315, 1200, 1069, 1013, 892, 823, 729,
628. cmꢁ1 1H-NMR: (CDCl3) d 2.37 (s, 3H, CH3), 5.21 (bs,
;
2H, NH2), 7.63 (s 1H, ArAH), 7.65 (d, 2H, J ¼ 8.7 Hz,
ArAH), 7.73 (d, 2H, J ¼ 8.7 Hz, ArAH). Anal. Calcd for
C15H10BrN5O: C, 50.58; H, 2.83; N, 19.66. Found: C, 50.73;
H, 2.68; N, 19.53.
REFERENCES AND NOTES
[1] Taylor, E.; Mc Killop, A. The Chemistry of Cyclic Enami-
nonitriles and o-Aminonitriles in Advanced Organic Chemistry; Wiley:
New York, 1970; p 415.
7-Amino-(4-bromobenzoyl)-5-ethylpyrazolo[1,5-a]pyrimi-
dine-3-carbonitrile (5f). This compound was obtained as col-
orless prism (DMF), 2.73 g (74%), mp 277–278ꢀC; IR: (Potas-
sium bromide): 3433, 3316, 3086, 2921, 2879, 2530, 2233,
1620, 1623, 1401, 1363, 1319, 1200, 1069, 1011, 895, 830,
[2] Taylor, E.; Loeffler, R. J Am Chem Soc 1960, 82, 3147.
[3] Baraldi, P.; Cacciari, B.; Romagnoli, R.; Spalluto, G.;
Klotz, K.; Leung, E.; Varani, K.; Gessi, S.; Merighi S.; Borea, P. J
Med Chem 1999, 42, 4473.
1
712, 630 cmꢁ1; H-NMR: (CDCl3) d 1.21 (t, 3H, J ¼ 7.2 Hz,
[4] Robins, R. J Am Chem Soc 1956, 78, 784.
[5] Cheng C.; Robins, R. J Org Chem 1956, 21, 1240.
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[8] (a) Tomeufcik, A.; Albright, J.; Dusza, J. US Pat.
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CH3), 2.59 (q, 2H, J ¼ 7.2 Hz, CH2), 5.62 (bs, 2H, NH2), 7.85
(d, 2H, J ¼ 8.7 Hz, ArAH), 7.93 (d, 2H, J ¼ 8.4 Hz, ArAH),
8.91 (s, 1H, ArAH). Anal. Calcd for C16H12BrN5O: C, 51.91;
H, 3.27; N, 18.92. Found: C, 51.77; H, 3.41; N, 18.73.
General procedure for the synthesis of 8,8-Dimethyl-6-
oxo-6,7,8,9-tetrhydropyrazolo[1,5-a]quinazoline-3-carbo-nit-
rile (7). A mixture of 5-aminopyrazole 1 (1.08 g, 10 mmole),
dimedone 2 (10 mmole) and triethylorthoesters 3 (10 mmole)
was refluxed in toluene for about 3 h. Completion of reaction
was monitored by thin layer chromatography (TLC). The
excess of solvent was removed under reduced pressure. The
solid obtained was stirred in ethanol (20 mL), filtered, washed
with ethanol, dried, and recrystallized from suitable solvent
furnished compounds 7 in good yield.
[9] (a) Chen, Y. Jpn. Pat. 2,000,502,723; (b) Chen, Y. Chem
Abstr 1998, 17, 20490s; (c) Dusza, J.; Albright, J.; Tomcufcik, A. US
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Abstr 1996, 13, 168011c.
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8,8-Dimethyl-6-oxo-6,7,8,9-tetrhydropyrazolo[1,5-a]quin-
azoline-3-carbonitrile (7a). This compound was obtained as
colorless prism (ethanol), 1.96 g (82%), mp 162–163ꢀC; IR:
(Potassium bromide): 2215, 1687, 1609, 1537, 1367, 1310,
1261, 1175, 1096, 801, 683 cmꢁ1 1H-NMR: (CDCl3) d 1.25
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
New One-Step Synthesis of Pyrazolo[1,5-a]pyrimidine and Pyrazolo[1,5-a]quinazoline
Derivatives via MultiComponent Reactions
713
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet