Design, Multicomponent Synthesis and Characterization of Diversely Substituted Pyrazolo[1,5-a] Pyrimidine Derivatives

Article abstract of DOI:10.1002/jhet.2496

The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide in the presence of base in isopropyl alcohol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the novel synthetic methodology for the fused pyrazolopyrimidines.

Full text of DOI:10.1002/jhet.2496

Month 2015
Design, Multicomponent Synthesis and Characterization of Diversely
Substituted Pyrazolo[1,5-a] Pyrimidine Derivatives
*
Satish M. Ghelani and Yogesh T. Naliapara
Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India
*
E-mail: naliaparachem@yahoo.co.in
Additional Supporting Information may be found in the online version of this article.
Received November 23, 2014
DOI 10.1002/jhet.2496
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated
that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to
explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and
5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide in the presence of base in isopropyl alco-
hol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the
novel synthetic methodology for the fused pyrazolopyrimidines.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
attracted considerable interest because of their biological ac-
tivity. For instance, this heterocyclic system is found as pu-
rine analogues and has useful properties as antimetabolites
in purine biochemical reactions [2]. Several compounds of
this class display interesting antitrypanosomal [3] and
antischistosomal activities [4]. They are used as HMG-
CoA reductaseinhibitors [5], COX-2 selective inhibitors
[6], 30,50-cyclic-AMP phosphodiesteraseinhibitors [7],
Biaryls and heterobiaryls have attracted significant atten-
tion from the scientific community because of their relevance
in medicinal chemistry. Heterobiaryls frequently can be ob-
served in numerous bioactive small molecules, and in partic-
ular, heterobiaryls fused with various heterocycles, such as
pyrazole, pyridine, and pyrimidine, have been used as key
pharmacophores [1]. Pyrazolo[1,5-a]pyrimidines have
© 2015 HeteroCorporation

S. M. Ghelani and Y. T. Naliapara
Vol 000
CRF1 antagonists [8a–d], selective peripheral benzodiaze-
pine receptor ligands [9a–c], potassium channel [10]
and histamine-3 receptor ligands [11], and antianxiety
agents [12].
Figure 2. Substituted 3-(arylsulfonyl)pyrazolo[1,5-a] pyrimidines.
Some pyrazolopyrimidines serve as efficient sedative–
hypnotic and anxiolytic drugs like zaleplon (Sonata,
hypnotic) [13], indiplon (hypnotic) [14], and ocinaplon
(anxiolytic) [15], fasiplon (anxiolytic) [16] (Fig. 1); these
drugs are related to the class of nonbenzodiazepines, and
their therapeutic effect is because of allosteric enhance-
ment of the action of the inhibitory neurotransmitter
GABA at the GABAA receptor [13,14]. These examples
emphasize the importance of pyrazol-fused heterobiaryls,
as well as pyrazolopyridines, as key pharmacophores in
bioactive small molecules.
Pyrazolopyrimidines have multiple pharmacological ac-
tivities including hypnotic [17,18], anti-inflammatory
[19,20], anti-tumor, antimycobacterial [21–23], antidia-
betic, antiphlogistic agents, antidepressants, analgesics
[24,25], and anti-viral [26]. Several diverse biological ac-
tivities have been reported for pyrazolopyrimidine ring
systems which are described as below.
Ivashchenko et al. [27] reported that substituted
3-(arylsulfonyl)pyrazolo[1,5-a] pyrimidines (Fig. 2) are
claimed as antagonists of serotonin 5-HT6 receptors for
treating and preventing pathol states and diseases of the
central nervous system in humans and warm-blooded ani-
mals, the pathogenesis of which is caused by disorder in
the serotonin 5-HT6 receptor activation.
Alexandre V. Ivachtchenko et al. [28] have described
structure activity relationships for a series of novel 2-
substituted 3-benzenesulfonyl-5,6-dimethyl-pyrazolo[1,5-
a]pyrimidines. In spite of a wide, four orders of magnitude,
SAR range (Ki varied from 260 pM to 2.96mM), no sig-
nificant correlation of 5-HT6R antagonistic potency was
observed with major physiochemical characteristics, such
as molecular weight, surface polar area, cLogP, or number
of rotatable bonds. Statistically significant trend was only
observed for size of substitute group, which was not
enough to explain the deep SAR trend. Besides with the
substitute group size, another factor that presumably plays
a role in defining the compound potencies is a relative po-
sition of the heterocycle and sulfophenyl moieties. Among
all synthesized derivatives, (3 benzenesulfonyl-5,7-dimethyl-
pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine (Fig. 3) is the
most potent (Ki ¼ 260 pM) and extremely selective, 5000
to >50,000-fold relative to 55 therapeutic targets, antago-
nist of the 5-HT6 receptor.
RESULTS AND DISCUSSION
Scheme: synthesis of novel substituted pyrazolo[1,5-a]
pyrimidine derivatives.
Preparation of the target
compounds was initiated by the reaction of ethylcynoacetate
(1) with cyclohexyl amines (2) in toluene at reflux
temperature to afford the cyanoacetamides (3) in 90%
yields. This product undergoes reaction with carbon
disulfide in the presence of base in DMF followed by
methylation to afford corresponding 2-cyano-3,3-
bis(methylthio)-N-cyclohexylacrylamide (4). Which on
reaction with hydrazine hydrate undergoes cyclization to
form 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-
carboxamide (5) (Scheme 1).
Various acetoactanilide[AAA] (8a–j) (Scheme 2) were
synthesized by reacting substituted amine (7a–j) with
ethylacetoacetate (6) in toluene in the presence of catalytic
amount of KOH at reflux temperature for 15–20h.
The resulting various acetoactanilide[AAA] (8a–j) were
reacted with an appropriate aldehyde (9a–c) and 5-amino-N-
cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide (5)
in the presence of NaHCO3 and methanol as a solvent to
Figure 3. (3-Benzenesulfonyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-
yl)-methyl-amine.
Figure 1. Pyrazolopyrimidines serving as efficient sedative–hypnotic and anxiolytic drugs.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
A Simple Approach to Synthesis of Pyrazolopyrimidine Derivatives Using Various
Acetoacetanilide
Scheme 1. 5-Amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide (5).
afford highly substituted pyrazolo[1,5-a]pyrimidines (CBH,
BBH, NBH) in low yield (Tables 1 and 2). To optimize the
reaction condition for the synthesis of compound CBH-01,
various solvents and various bases were utilized. As a result,
we found the reaction of (9a), an acetoacetamide (8a) with
(5) was faster and afforded the pyrazolo[1,5-a]pyrimidine
CBH-01 in good yield in the presence of K2CO3 as a base
and isopropyl alcohol (Scheme 3).
REACTION MECHANISM
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. M. Ghelani and Y. T. Naliapara
Vol 000
Scheme 2. Various acetoactanilide[AAA] (8a–j).
The progress of reaction was monitored by thin layer
chromatography. The reaction mixture was cooled to room
temperature, and the solid product was filtered, washed with
toluene to afford 90% yield.
White solid; mp 70–72°C; IR (KBr): 3412, 3310, 2925,
2264, 1413, 810cmÀ1; 1H NMR(400MHz, DMSO): δppm
1.33–1.39 (m, 4H, 2 × CH2), 1.63–1.66 (m, 2H, CH2),
1.77–1.94 (m, 4H, 2 × CH2), 3.34 (s, 2H, ―CH2), 3.82
(m, 1H, ―CH), 7.99–8.01 (s, 1H, ―NH―); 13C NMR
(400 MHz, DMSO): δppm 23.8, 24.7, 31.3, 48.2, 124.7,
169.6; MS (m/z): 166 (M+); Anal. Calcd. for C9H14N2O:
C, 65.03; H, 8.49; N, 16.85; O, 9.63; Found: C, 65.12;
H, 8.52; N, 16.80; O, 9.54.
Table 1
Reaction of (9a), (8a), and (5) with various solvents in the presence of base.
Entry
Solvent
Base
Time (h) Yield (%)
1
2
3
4
5
6
7
8
Methanol
Ethanol
NaHCO3
NaHCO3
Isopropyl alcohol NaHCO3
20
18
16
15
10
14
13
10
10
8
65
68
70
58
60
70
72
78
75
68
75
80
94
82
78
65
Synthesis of 2-cyano-N-cyclohexyl-3,3-bis(methylthio)
acrylamide (4). A 100-mL conical flask equipped with
Dioxane
DMF
Methanol
Ethanol
NaHCO3
NaHCO3
Na2CO3
Na2CO3
magnetic stirrer and septum was charged with a solution
of 2-cyano-N-cyclohexylacetamide (3), (0.01 M) in DMF
(10 mL). Dry K2CO3 (0.01 M) was added, and the
mixture was stirred at room temperature for 2h. CS2
(0.03 M) was added, and the mixture was stirred for an
additional 2h at room temperature. Then, methyl iodide
(0.02 M) was added at 0–5°C and the mixture was stirred
for 4 h at room temperature. The progress of the reaction
was monitored by thin layer chromatography. After
completion of the reaction, it was poured into 50-mL
cold water. The precipitated crude product was purified
by filtration followed by crystallization from EtOH.
Isopropyl alcohol Na2CO3
9
Dioxane
DMF
Methanol
Ethanol
Na2CO3
Na2CO3
K2CO3
K2CO3
10
11
12
12
14
15
16
10
10
8
8
7
Isopropyl alcohol K2CO3
Dioxane
DMF
AcOH
K2CO3
K2CO3
CH3COONa
8
CONCLUSIONS
Crimson white solid; mp 138–142°C; IR (KBr): 3427,
1
3315, 2922, 2272, 1620, 1593, 1472, 835 cmÀ1; H NMR
The heterocyclizations of various acetoactanilide, an ap-
propriate aldehyde with 5-aminopyrazole derivative, were
studied in details, and the influence of the reaction param-
eters and the aminoazole structure on the direction of the
reaction was established. We found that the reaction of var-
ious acetoactanilide (8a–j), an appropriate aldehyde with
5-aminopyrazole derivative (5), was faster and afforded
the pyrazolo[1,5-a]pyrimidine [CBH, BBH, NBH] in
good yield in the presence of K2CO3 as a base and isopro-
pyl alcohol. The results of the study described above have
led to the development of a simple approach for synthesis
of pyrazolo[1,5-a]pyrimidines, substances that potentially
interesting biological and medicinal properties. Among
all the derivatives, the electron donating group present on
aromatic ring has more yield as compared to electron with-
drawing group. Compounds (Table 2, Entry 01, 02, 11, 12,
14, 15, 21, 22, 25, 26) are with excellent yields because
electron donating group present on aromatic ring.
(400 MHz, DMSO): δppm 1.35–1.41 (m, 4H, 2 × CH2),
1.65–1.68 (m, 2H, CH2), 1.79–1.96 (m, 4H, 2 × CH2),
3.12 (s, 6H, 2 × CH3), 3.85 (m, 1H, ―CH), 7.98–8.02 (s,
1H, ―NH―); 13C NMR(400 MHz, DMSO): δppm 15.8,
23.8, 24.7, 31.3, 48.6, 77.7, 114.8, 157.9, 176.4; MS (m/z):
270 (M+); Anal. Calcd. for C12H18N2OS2: C, 53.30; H,
6.71; N, 10.36; O,5.92; S, 23.72; Found: C, 53.36; H, 6.76;
N, 10.32; O,5.87; S, 23.68.
Synthesis of 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-
4-carboxamide (5). A 100-mL conical flask equipped with
magnetic stirrer and septum was charged 2-cyano-N-
cyclohexyl-3,3-bis(methylthio)acrylamide (4) (0.1M) in
isopropyl alcohol (100mL) and hydrazine hydrate (0.1M).
The reaction mixture was heated to reflux for 2h. After
completion of the reaction, it was poured into 50-mL cold
water. The precipitated crude product was purified by
filtration followed by crystallization from EtOH.
Yellowish white solid; mp 182–184°C; IR (KBr): 3408,
3318, 3030, 2920, 2827, 1624, 1593, 1417, 1240, 885, and
EXPERIMENTAL
1
827cmÀ1; H NMR(400MHz, DMSO): δppm 1.26–1.31
Synthesis of 2-cyano-N-cyclohexylacetamide (3).
In a
(m, 4H, 2×CH2), 1.57–1.60 (m, 2H, CH2), 1.71–1.87 (m,
4H, 2×CH2), 2.52 (s, 3H, ―SCH3), 3.83 (m, 1H, ―CH),
7.70–7.74 (s, 2H, ―NH2), 7.98–8.04 (s, 1H, ―NH―),
12.58–12.62 (s, 1H, ―NH―); 13C NMR(400MHz,
DMSO): δppm 12.7, 24.75, 25.65, 32.32, 50.72, 97.38,
250-mL round bottom flask equipped with a magnetic
stirrer, and thermometer was placed ethyl 2-cyanoacetate
(0.25M), cyclohexyl amine (0.25M), and toluene (100mL).
The reaction mixture was heated up to 110–120°C for 8h.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
A Simple Approach to Synthesis of Pyrazolopyrimidine Derivatives Using Various
Acetoacetanilide
Table 2
Synthesis of novel substituted and fused pyrazolo[1,5-a]pyrimidine derivatives.
Sr. no.
Compound
-R1
-R2
4-CH3
Mole. formula
Time (h)
Yield (%)
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
CBH-01
CBH-02
CBH-03
CBH-04
CBH-05
CBH-06
CBH-07
CBH-08
CBH-09
CBH-10
BBH-01
BBH-02
BBH-03
BBH-04
BBH-05
BBH-06
BBH-07
BBH-08
BBH-09
BBH-10
NBH-01
NBH-02
NBH-03
NBH-04
NBH-05
NBH-06
NBH-07
NBH-08
NBH-09
NBH-10
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
3-Br
-H
C29H32ClN5O2S
C28H29Cl2N5O2S
C28H29Cl2N5O2S
C28H29ClFN5O2S
C28H29BrClN5O2S
C29H32ClN5O3S
C30H34ClN5O4S
C28H29ClN6O4S
C28H29ClN6O4S
C28H29ClN6O4S
C29H32BrN5O2S
C28H29BrClN5O2S
C28H29BrClN5O2S
C28H29BrFN5O2S
C28H29Br2N5O2S
C29H32BrN5O3S
C30H34BrN5O4S
C28H29BrN6O4S
C28H29BrN6O4S
C28H29BrN6O4S
C29H33N5O2S
C28H30ClN5O2S
C28H30ClN5O2S
C28H30FN5O2S
C28H30BrN5O2S
C29H33N5O3S
C30H35N5O4S
C28H30N6O4S
C28H30N6O4S
C28H30N6O4S
8.0
7.5
7.5
7.0
7.0
9.0
8.0
8.5
8.0
7.0
7.5
7.0
7.5
8.5
8.0
8.5
8.5
7.5
7.0
7.5
8.0
8.5
7.5
8.0
8.5
8.0
8.5
8.5
7.5
7.0
94
92
90
88
92
95
90
89
93
87
95
94
92
97
94
90
88
92
87
90
93
96
90
87
97
94
90
88
92
87
3-Cl
4-Cl
4-F
4-Br
4-OCH3
2,4-di-OCH3
4-NO2
2-NO2
3-NO2
4-CH3
3-Cl
4-Cl
4-F
4-Br
4-OCH3
2,4-di-OCH3
4-NO2
2-NO2
3-NO2
4-CH3
3-Cl
-H
-H
-H
-H
-H
-H
-H
-H
4-Cl
4-F
4-Br
4-OCH3
2,4-di-OCH3
4-NO2
2-NO2
3-NO2
-H
Scheme 3. Pyrazolo[1,5-a]pyrimidine CBH-01.
149.25, 153.10, 167.28; MS (m/z): 254 (M+); Anal. Calcd.
for C11H18N4OS: C, 51.94; H, 7.13; N, 22.03; O, 6.29; S,
12.61; Found: C, 51.98; H, 7.16; N, 21.98; O, 6.24; S, 12.59.
General synthesis of acetoacetanilide derivatives [AAA]
(8a–j). A mixture containing the primary amine (7a–j)
(0.01 M), ethylacetoacetate (6) (0.01 M), and catalytic
amount of sodium or potassium hydroxide lie (10%) in
toluene (50 mL) was refluxed at 110°C for 12–15h. The
reaction was monitored by TLC. After completion of
reaction, the solvent was removed under vacuo, and the
residue was crystallized from methanol.
potassium carbonate (0.006 M),an appropriate aldehyde
(9a–c), and acetoactanilide (8a–j) (0.003M) in isopropyl
alcohol (10 mL) was heated to reflux for 7–10h. The
progress of reaction mixture was monitored by TLC.
After completion of reaction, the mixture was cooled to
room temperature, and solid residue was filtered and
washed with 10mL of isopropyl alcohol followed by
50ml of water. The product was crystallized from MeOH
to give [01 to 30] in 87–97% yield.
Spectroscopic data for the synthesized compounds [01 to 30].
7-(4-Chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(p-tolyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
[CBH-01]. White solid; mp 240–242°C; IR (KBr): 3402,
General synthesis of substituted and fused pyrazolopyrimidines
[01 to 30].
A mixture of 5-amino-N-cyclohexyl-3-
3306, 3036, 2922, 2852, 1686, 1620, 1593 and 1516,
(methylthio)-1H-pyrazole-4-carboxamide (5) (0.003 M),
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S. M. Ghelani and Y. T. Naliapara
Vol 000
1413, 1238, 835 and 810cmÀ1
;
1H NMR(400 MHz,
(KBr): 3430, 3133, 3051, 2922, 1651, 1516, 1483, 1232,
1166, 954, 883, 780, 743, 698 cmÀ1; MS (m/z): 613 (M+);
Anal. Calcd. for C28H29BrClN5O2S: C, 54.68; H, 4.75;
Br,12.99; Cl, 5.76; N,11.39; O, 5.20; S, 5.21; Found: C,
54.60; H, 4.71; Br,12.90; Cl, 5.71; N,11.38; O, 5.28; S, 5.19.
7-(4-Chlorophenyl)-N3-cyclohexyl-N6-(4-methoxyphenyl)-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
DMSO): δppm 1.23–1.29 (m, 4H, 2 × CH2), 1.53–1.56 (m,
2H, CH2), 1.67–1.84 (m, 4H, 2×CH2), 2.23 (s, 3H,
―CH3), 2.42 (s, 3H, ―CH3), 2.50 (s, 3H, ―SCH3), 3.79
(m, 1H, ―CH), 6.47 (s, 1H, ―CH), 6.99–7.01 (s, 1H,
3
―NH―), 7.05–7.07 (dd, 2H, Ar―H, J=8.4Hz), 7.17–
7.20 (dd, 2H, Ar―H, 3J=8.8Hz), 7.36–7.42 (m, 4H,
Ar―H, 3J = 8.8 Hz and 3J =8.4 Hz), 8.80 (s, 1H, ―CONH),
9.70 (s, 1H, ―CONH―Ar); 13C NMR(400MHz, DMSO):
δppm 15.90, 17.40, 20.39, 24.15, 59.18, 96.89, 97.84,
103.91, 119.64, 128.54, 128.61, 128.93, 132.47, 135.50,
136.38, 141.37, 143.68, 161.50, 164.53; MS (m/z): 549
(M+); Anal. Calcd. for C29H32ClN5O2S: C, 63.32; H, 5.86;
Cl,6.44; N, 12.73; O,5.82; S, 5.83; Found: C, 63.30; H,
dicarboxamide[CBH-06].
Yellow solid; mp 218–222°C;
IR (KBr): 3421, 3122, 3088, 2922, 1651, 1516, 1483,
1232, 1166, 954, 883, 780, 743, 698 cmÀ1; MS (m/z): 565
(M+); Anal. Calcd. for C29H32ClN5O3S: C, 61.53; H,
5.70; Cl,6.26; N, 12.37; O, 8.48; S, 5.66; Found: 61.50;
H, 5.75; Cl,6.20; N, 12.34; O, 8.46; S, 5.62.
7-(4-Chlorophenyl)-N3-cyclohexyl-N6-(2,4-dimethoxyphenyl)-
5-methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-
5.88; Cl, 6.38; N, 12.67; O, 5.80; S, 5.73.
3,6-dicarboxamide[CBH-07].
Creamish solid; mp 228–
N6-(3-chlorophenyl)-7-(4-chlorophenyl)-N3-cyclohexyl-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[CBH-02]. Creamish solid; mp 226–228°C;
232°C; IR (KBr): 3422, 3127, 3085, 2942, 1628, 1483,
1237, 1158, 883, 780, 743 cmÀ1; MS (m/z): 595 (M+);
Anal. Calcd. for C30H34ClN5O4S: C, 60.44; H, 5.75; Cl,
5.95; N, 11.75; O, 10.74; S, 5.38; Found: C, 60.40; H,
IR (KBr): 3329, 3242, 3030, 2929, 2852, 1690, 1591,
1525, 1421, 1238, 840, 779, and 675cmÀ1 1H NMR
;
5.71; Cl, 5.90; N, 11.78; O, 10.74; S, 5.29.
(400MHz, DMSO):δppm 1.23–1.33 (m, 4H, 2×CH2),
1.52–1.55 (m, 2H, CH2), 1.66–1.84 (m, 4H, 2×CH2), 2.27
(s, 3H, ―CH3), 2.40 (s, 3H, ―SCH3), 3.79–3.81 (m, 1H,
―CH), 6.51 (s, 1H, ―CH), 6.99–7.01 (s, 1H, ―NH―),
7-(4-Chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(4-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[CBH-08]. Creamish solid; mp 236–238°C;
IR (KBr): 3430, 3133, 3051, 2922, 1651, 1516, 1483, 1232,
1166, 954, 883, 780, 743, 698cmÀ1; MS (m/z): 580 (M+);
Anal. Calcd. for C28H29ClN6O4S: C, 57.87; H, 5.03; Cl,
6.10; N, 14.46; O, 11.01; S, 5.52; Found: C, 57.80; H,
3
4
7.06–7.08 (dt, 1H, Ar―H, J=8.4Hz, J=2.0Hz), 7.19–
7.22 (dd, 2H, Ar―H, 3J=8.4Hz), 7.27–7.31 (t, 1H,
Ar―H, 3J=8.0Hz), 7.36–7.39 (dd, 2H, Ar―H,
3J=8.4Hz), 7.44–7.46 (dt, 1H, Ar―H, 3J=7.4Hz,
5.01; Cl, 6.17; N, 14.53; O, 11.07; S, 5.47.
4J=2.0Hz), 7.75–7.76 (t, 1H, Ar―H, J=2.0Hz), 8.91 (s,
4
7-(4-Chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(2-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[CBH-09]. White solid; mp 230–234°C;
1H, ―CONH―), 9.96 (s, 1H, ―CONH―Ar); 13C NMR
(400MHz, DMSO): δppm 15.90, 17.52, 24.15, 25.13,
32.22, 47.12, 59.04, 97.06, 103.41, 117.84, 118.95,
122.96, 128.59, 130.25, 132.66, 132.94, 136.53, 139.89,
140.41, 141.24, 143.58, 161.33, 165.01; MS (m/z): 569
(M+); Anal. Calcd. for C28H29Cl2N5O2S: C, 58.94; H,
5.12; Cl,12.43; N, 12.28; O,5.61; S, 5.62; Found: C, 58.91;
IR (KBr): 3198, 3157, 3042, 2942, 2832, 1734, 1668,
1654, 1257, 832, 806, 742 cmÀ1; MS (m/z): 580 (M+);
Anal. Calcd. for C28H29ClN6O4S: C, 57.87; H, 5.03; Cl,
6.10; N, 14.46; O, 11.01; S, 5.52; Found: C, 57.84; H,
5.01; Cl, 6.14; N, 14.52; O, 11.01; S, 5.48.
7-(4-Chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(3-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[CBH-10]. White solid; mp 220–222°C;
H, 5.08; Cl,12.48; N, 12.21; O,5.57; S, 5.59.
N6,7-bis(4-chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide[CBH-
03]. White solid; mp 216–220°C; IR (KBr): 3323, 3026,
IR (KBr): 3198, 3157, 3042, 2942, 2832, 1734, 1668,
1654, 1257, 832, 806, 742 cmÀ1; MS (m/z): 580 (M+);
Anal. Calcd. for C28H29ClN6O4S: C, 57.87; H, 5.03; Cl,
6.10; N, 14.46; O, 11.01; S, 5.52; Found: C, 57.88; H,
2908, 2856, 1674, 1630, 1563, 1473, 1246, 927, 843, 798,
732, cmÀ1; MS (m/z): 569 (M+); Anal. Calcd. for
C28H29Cl2N5O2S: C, 58.94; H, 5.12; Cl,12.43; N, 12.28;
O,5.61; S, 5.62; Found: C, 58.90; H, 5.10; Cl,12.45; N,
5.01; Cl, 6.14; N, 14.40; O, 11.01; S, 5.47.
7-(3-Bromophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(p-tolyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
12.29; O,5.58; S, 5.60.
7-(4-Chlorophenyl)-N3-cyclohexyl-N6-(4-fluorophenyl)-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide [CBH-04]. Creamish solid; mp 224–226°C;
[BBH-01].
Creamish solid; mp 218–222°C; IR (KBr):
3483, 3242, 3162, 3068, 2902, 1675, 1584,1425, 1332,
1066, 954, 820, 750cmÀ1; MS (m/z): 593 (M+); Anal.
Calcd. for C29H32BrN5O2S: C, 58.58; H, 5.42; Br, 13.44;
N, 11.78; O, 5.38; S, 5.39; Found: C, 58.55; H, 5.40; Br,
IR (KBr): 3379, 3024, 2902, 1651, 1516,1483, 1332, 1166,
954, 852, 822, 748, 709cmÀ1; MS (m/z): 553 (M+); Anal.
Calcd. for C28H29ClFN5O2S: C, 60.70; H, 5.28; Cl,6.40;
F, 3.43; N, 12.64; O, 5.78; S, 5.79; Found: C, 60.60; H,
13.41; N, 11.74; O, 5.42; S, 5.28.
7-(3-Bromophenyl)-N6-(3-chlorophenyl)-N3-cyclohexyl-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-
3,6-dicarboxamide[BBH-02]. White solid; mp 238–234°C;
5.24; Cl,6.36; F, 3.40; N, 12.61; O, 5.76; S, 5.69.
N6-(4-bromophenyl)-7-(4-chlorophenyl)-N3-cyclohexyl-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[CBH-05]. White solid; mp 240–242°C; IR
IR (KBr): 3483, 3242, 3162, 3068, 2902, 1675, 1584,1425,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
A Simple Approach to Synthesis of Pyrazolopyrimidine Derivatives Using Various
Acetoacetanilide
7-(3-Bromophenyl)-N3-cyclohexyl-N6-(4-methoxyphenyl)-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[BBH-06]. White solid; mp 236–240°C; IR
(KBr): 3503, 3450, 3206, 3068, 2908, 1628, 1548,1420,
1342, 1066, 825, 754cmÀ1; MS (m/z): 609 (M+); Anal.
Calcd. for C29H32BrN5O3S: C, 57.05; H, 5.28; Br, 13.09;
N, 11.47; O, 7.86; S, 5.25; Found: C, 57.09; H, 5.26; Br,
1332, 1066, 954, 820, 750cmÀ1; MS (m/z): 613 (M+); Anal.
Calcd. for C28H29BrClN5O2S: C, 54.68; H, 4.75; Br, 12.99;
Cl, 5.76; N, 11.39; O, 5.20; S, 5.21; Found: C, 54.66; H,
4.77; Br, 12.99; Cl, 5.72; N, 11.48; O, 5.28; S, 5.17.
7-(3-Bromophenyl)-N6-(4-chlorophenyl)-N3-cyclohexyl-5-methyl-
2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[BBH-03]. Creamish solid; mp 248–252°C;
IR (KBr): 3389, 3273, 3052, 2926, 2850, 1685, 1589, 1516,
13.07; N, 11.42; O, 7.86; S, 5.21.
7-(3-Bromophenyl)-N3-cyclohexyl-N6-(2,4-dimethoxyphenyl)-
5-methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-
1438, 817, 765, and 690cmÀ1
;
1H NMR(400 MHz,
DMSO): δppm 1.24–1.34 (m, 4H, 2 ×CH2), 1.53–1.56
(m, 2H, CH2), 1.67–1.84 (m, 4H, 2× CH2), 2.22 (s, 3H,
―CH3), 2.40 (s, 3H, ―SCH3), 3.79–3.81 (m, 1H, ―CH),
6.48 (s, 1H, ―CH), 7.01–1.03 (s, 1H, ―NH―), 7.18–
7.20 (dt, 1H, Ar―H, 3J= 8.8 Hz), 7.26–7.33 (m, 4H,
Ar―H, 3J = 8.8 Hz, 4J =2.4 Hz), 7.44–7.47 (dt, 1H,
Ar―H, 4J = 2.4 Hz), 7.55–7.59 (dd, 2H, Ar―H,
3J =8.8 Hz), 8.91 δppm (s, 1H, ―CONH―), 9.92 δppm
(s, 1H, ―CONH―Ar); 13C NMR(400 MHz, DMSO):
δppm 15.91, 17.53, 24.16, 25.13, 32.23, 59.18, 97.11,
103.31, 121.15, 121.75, 125.95, 126.96, 128.48, 129.33,
130.81, 136.40, 137.83, 141.21, 143.48, 143.70, 161.30,
164.77; MS (m/z): 615 (M+); Anal. Calcd. for
C28H29BrClN5O2S: C, 54.68; H, 4.75; Br, 12.99; Cl, 5.76;
N, 11.39; O, 5.20; S, 5.21; Found: C, 54.60; H, 4.71; Br,
3,6-dicarboxamide[BBH-07].
Creamish solid; mp 252–
256°C; IR (KBr): 3457, 3345, 3147, 3038, 2952, 1615,
1539,1422, 1336, 1076, 828, 745 cmÀ1; MS (m/z): 639
(M+); Anal. Calcd. for C30H34BrN5O4S: C, 56.25; H,
5.35; Br, 12.47; N, 10.93; O, 9.99; S, 5.01; Found: C,
56.29; H, 5.34; Br, 12.49; N, 10.98; O, 9.99; S, 5.00.
7-(3-Bromophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(4-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[BBH-08].
White solid; mp 258–260°C;
IR (KBr): 3457, 3345, 3147, 3038, 2952, 1615,
1539,1422, 1336, 1076, 828, 745 cmÀ1; MS (m/z): 624
(M+); Anal. Calcd. for C28H29BrN6O4S: C, 53.76; H,
4.67; Br, 12.77; N, 13.43; O, 10.23; S, 5.13; Found: C,
53.71; H, 4.61; Br, 12.79; N, 13.49; O, 10.28; S, 5.10.
7-(3-Bromophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(2-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[BBH-09]. Creamish solid; mp 230–232°C;
IR (KBr): 3448, 3250, 3130, 2948, 2902, 1651, 1516,
1483, 1332, 1166, 850, 772, 705cmÀ1; MS (m/z): 624
(M+); Anal. Calcd. for C28H29BrN6O4S: C, 53.76; H, 4.67;
Br, 12.77; N, 13.43; O, 10.23; S, 5.13; Found: C, 53.70; H,
13.09; Cl, 5.66; N, 11.38; O, 5.28; S, 5.17.
7-(3-Bromophenyl)-N3-cyclohexyl-N6-(4-fluorophenyl)-5-methyl-
2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[BBH-04]. Creamish solid; mp 222–226°C;
IR (KBr): 3284, 3032, 2928, 2852, 1680, 1589, 1514, 823,
1
781, and 686 cmÀ1; H NMR(400 MHz, DMSO): δppm
1.17–1.33 (m, 4H, 2 × CH2), 1.52–1.55 (m, 2H, CH2),
1.66–1.84 (m, 4H, 2 × CH2), 2.27 (s, 3H, ―CH3), 2.42 (s,
3H, ―SCH3), 3.80–3.81 (m, 1H, ―CH), 6.48 (s, 1H,
―CH), 7.01–7.03 (s, 1H, ―NH―), 7.08–7.15 (dd, 2H,
Ar―H, 3J= 8.4 Hz), 7.20–7.22 (dt, 1H, Ar―H,
4.61; Br, 12.72; N, 13.41; O, 10.28; S, 5.10.
7-(3-Bromophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
N6-(3-nitrophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide [BBH-10]. Creamish solid; mp 262–266°C;
IR (KBr): 3328, 3248, 3057, 2964, 2926, 1651, 1516, 1483,
1328, 1158, 850, 772cmÀ1; MS (m/z): 624 (M+); Anal.
Calcd. for C28H29BrN6O4S: C, 53.76; H, 4.67; Br, 12.77;
N, 13.43; O, 10.23; S, 5.13; Found: C, 53.70; H, 4.69; Br,
3
4J =2.4 Hz), 7.25–7.30 (t, 1H, Ar―H, J= 8.0 Hz), 7.34–
7.35 (t, 1H, Ar―H, 4J= 2.4 Hz), 7.41–7.49 (dt, 1H,
3
Ar―H, J= 8.4Hz), 7.52–7.57 (dd, 2H, Ar―H), 8.89 (s,
12.79; N, 13.45; O, 10.28; S, 5.11.
1H, ―CONH―), 9.86 (s, 1H, ―CONH―Ar); 13C NMR
(400 MHz, DMSO): δppm 15.94, 17.51, 24.15, 25.13,
32.21, 47.13, 59.23, 97.04, 103.44, 115.02, 115.24,
121.43, 121.50, 121.75, 125.98, 129.36, 130.77, 130.94,
135.22, 135.98, 141.30, 143.48, 143.66, 156.92, 161.33,
164.62; MS (m/z): 599 (M+); Anal. Calcd. for
C28H29BrFN5O2S: C, 56.19; H, 4.88; Br, 13.35; F, 3.17;
N, 11.70; O, 5.35; S, 5.36; Found: C, 56.25; H, 4.86; Br,
N3-cyclohexyl-5-methyl-2-(methylthio)-7-phenyl-N6-(p-tolyl)-
4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide[NBH-
01]. White solid; mp 244–248°C; IR (KBr): 3450, 3058,
3012, 2933, 2852, 1672, 1660, 1352, 833, 732, 748,
709 cmÀ1; MS (m/z): 515 (M+); Anal. Calcd. for
C29H33N5O2S: C, 67.55; H, 6.45; N, 13.58; O, 6.21; S,
6.22; Found: C, 67.52; H, 6.44; N, 13.58; O, 6.20; S,
6.27.
N6-(3-chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
13.31; F, 3.11; N, 11.68; O, 5.30; S, 5.32.
7-(3-Bromophenyl)-N6-(4-bromophenyl)-N3-cyclohexyl-5-
methyl-2-(methylthio)-4,7-dihydropyrazolo[1,5-a]pyrimidine-
[NBH-02].
Creamish solid; mp 260–262°C; IR (KBr):
3352, 3289, 3040, 2931, 2852, 1682, 1589, 1525, 1423,
846, 777, and 700cmÀ1 1H NMR(400MHz, DMSO):
3,6-dicarboxamide[BBH-05].
White solid; mp 208–212°C;
IR (KBr): 3483, 3242, 3162, 3068, 2902, 1675, 1584,1425,
1332, 1066, 954, 820, 750 cmÀ1; MS (m/z): 657 (M+); Anal.
Calcd. for C28H29Br2N5O2S: C, 51.00; H, 4.43; Br, 24.23;
N, 10.62; O, 4.85; S, 4.86; Found: C, 51.10; H, 4.39; Br,
24.28; N, 10.68; O, 4.88; S, 4.80.
;
δppm 1.24–1.34 (m, 4H, 2× CH2), 1.53–1.56 (m, 2H,
CH2), 1.67–1.85 (m, 4H, 2× CH2), 2.26 (s, 3H, ―CH3),
2.40 (s, 3H, ―SCH3), 3.80–3.81 (m, 1H, ―CH), 6.51 (s,
1H, ―CH), 7.00–7.02 (s, 1H, ―NH―), 7.06–7.08 (dt, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. M. Ghelani and Y. T. Naliapara
Vol 000
N3-cyclohexyl-N6-(2,4-dimethoxyphenyl)-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
3
4
Ar―H, J=8.4Hz), 7.16–7.18 (t, 1H, Ar―H, J=2.4Hz),
7.22–7.32 (m, 5H, Ar―H), 7.44–7.46 (dt, 1H, Ar―H,
4
[NBH-07].
Creamish solid; mp 238–242°C; IR (KBr):
3J=8.8Hz), 7.74–7.75 (t, 1H, Ar―H, J=2.4Hz), 8.85 (s,
3445, 3247, 3038, 2952, 1628, 1539,1422, 1336, 1257,
838, 745 cmÀ1; MS (m/z): 561 (M+); Anal. Calcd. for
C30H35N5O4S: C, 64.15; H, 6.28; N, 12.47; O, 11.39; S,
5.71; Found: C, 64.20; H, 6.26; N, 12.44; O, 11.35; S, 5.69.
N3-cyclohexyl-5-methyl-2-(methylthio)-N6-(4-nitrophenyl)-7-phenyl-
4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide[NBH-
08]. Creamish solid; mp 230–234°C; IR (KBr): 3258,
3158, 3038, 2948, 1645, 1558,1426, 1358, 1216, 835,
745,708cmÀ1; MS (m/z): 546 (M+); Anal. Calcd. for
C28H30N6O4S: C, 61.52; H, 5.53; N, 15.37; O, 11.71; S,
5.87; Found: C, 61.53; H, 5.50; N, 15.34; O, 11.79; S, 5.79.
N3-cyclohexyl-5-methyl-2-(methylthio)-N6-(2-nitrophenyl)-7-
phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
[NBH-09]. White solid; mp 266–268°C; IR (KBr): 3450,
3058, 3012, 2933, 2852, 1672, 1660, 1352, 833, 732,
748, 709cmÀ1; MS (m/z): 546 (M+); Anal. Calcd. for
C28H30N6O4S: C, 61.52; H, 5.53; N, 15.37; O, 11.71; S,
5.87; Found: C, 61.50; H, 5.51; N, 15.31; O, 11.80; S, 5.80.
N3-cyclohexyl-5-methyl-2-(methylthio)-N6-(3-nitrophenyl)-7-
phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
1H, ―CONH―), 9.95 (s, 1H, ―CONH―Ar); 13C NMR
(400 MHz, DMSO): δppm 15.96, 17.48, 24.14, 25.13,
32.21, 47.09, 59.67, 97.00, 103.86, 117.83, 118.91, 122.89,
126.59, 127.98, 128.57, 130.26, 132.90, 136.31, 140.50,
141.02, 141.35, 143.32, 161.40, 165.13; MS (m/z): 535
(M+); Anal. Calcd. for C28H30ClN5O2S: C, 62.73; H, 5.64;
Cl, 6.61; N, 13.06; O, 5.97; S, 5.98; Found: C, 62.63; H,
5.60; Cl, 6.65; N, 13.01; O, 5.92; S, 5.96.
N6-(4-Chlorophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
[NBH-03]. Creamish solid; mp 258-262°C; IR (KBr):
3445, 3247, 3038, 2952, 1628, 1539,1422, 1336, 1257,
838, 745 cmÀ1; MS (m/z): 535 (M+); Anal. Calcd. for
C28H30ClN5O2S: C, 62.73; H, 5.64; Cl, 6.61; N, 13.06;
O, 5.97; S, 5.98; Found: C, 62.70; H, 5.61; Cl, 6.61; N,
13.07; O, 5.99; S, 5.99.
N3-Cyclohexyl-N6-(4-fluorophenyl)-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[NBH-04]. Creamish solid; mp 256–258°C;
IR (KBr): 3335, 3037, 2924, 2850, 1682, 1591, 1525,
[NBH-10].
Creamish solid; mp 270–274°C; IR (KBr):
1446, 827, 775, and 704cmÀ1
;
1H NMR(400 MHz,
3422, 3205, 3169, 2964, 2856, 1658, 1522, 1425, 1084,
838, 736cmÀ1; MS (m/z): 546 (M+); Anal. Calcd. for
C28H30N6O4S: C, 61.52; H, 5.53; N, 15.37; O, 11.71; S,
5.87; Found: C, 61.50; H, 5.51; N, 15.43; O, 11.75; S, 5.81.
DMSO): δppm 1.24–1.34 (m, 4H, 2 ×CH2), 1.52–1.55
(m, 2H, CH2), 1.67–1.85 (m, 4H, 2 × CH2), 2.30 (s, 3H,
―CH3), 2.40 (s, 3H, ―SCH3), 3.81–3.82 (m, 1H,
―CH), 6.51 (s, 1H, ―CH), 7.00–7.02 (s, 1H, ―NH―),
7.08–7.12 (dd, 2H, Ar―H, 3J= 8.2 Hz), 7.17–7.19 (dd,
2H, Ar―H, 3J= 8.0 Hz), 7.22–7.26 (m, 1H, Ar―H),
7.29–7.32 (dd, 2H, Ar―H, 3J= 8.0 Hz), 7.55–7.58 (dd,
REFERENCES AND NOTES
3
2H, Ar―H, J= 8.2 Hz), 8.80 (s, 1H, ―CONH―), 9.85
[1] PCT Int. Appl., WO 2007076092 A2 20070705, 2007.
[2] (a) Alexander, J. O.; Wheeler, G. R.; Hill, P. D.; Morris, M. P.
Biochem Pharmacol 1966, 15, 881; (b) Elion, G. B.; Callahan, S.; Nathan,
H.; Bieher, S.; Rundles, R. W.; Hitchings, G. H. Biochem Pharmacol
1963, 12, 85; (c) Earl, R. A.; Pugmire, R. J.; Revanker, G. R.; Townsend,
L. B. J Org Chem 1975, 40, 1822.
(s, 1H, ―CONH―Ar); 13C NMR(400 MHz, DMSO):
δppm 16.01, 17.43, 24.14, 25.14, 32.25, 47.08, 59.78,
96.87, 104.15, 114.98, 115.20, 121.33, 121.41, 126.61,
127.93, 128.53, 135.35, 135.55, 141.04, 141.52, 143.22,
156.85, 159.23, 161.45, 164.76; MS (m/z): 519 (M+);
Anal. Calcd. for C28H30FN5O2S: C, 64.72; H, 5.82; F,
3.66; N, 13.48; O, 6.16; S, 6.17; Found: C, 64.70; H,
[3] Novinson, T.; Bhooshan, B.; Okabe, T.; Revankar, G. R.;
Wilson, H. R. J Med Chem 1976, 19, 512.
[4] Senga, K.; Novinson, T.; Wilson, H. R. J Med Chem 1981, 24, 610.
[5] Suzuki, M.; Iwasaki, H.; Fujikawa, Y.; Sakashita, M.;
Kitahara, M.; Sakoda, R. Bioorg Med Chem Lett 2001, 11, 1285.
[6] Almansa, C. A.; Alberto, F.; Cavalcanti, F. L.; Gomez, L. A.;
Miralles, A.; Merlos, M.; Garcia-Rafanell, J.; Forn, J. J Med Chem 2001,
44, 350.
5.87; F, 3.61; N, 13.45; O, 6.23; S, 6.11.
N6-(4-Bromophenyl)-N3-cyclohexyl-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-
dicarboxamide[NBH-05]. White solid; mp 238–240°C; IR
[7] Novinson, T.; Hanson, R.; Dimmitt, M. K.; Simmon, L. N.;
Robins, R. K.; O’Brien, D. E. J Med Chem 1974, 17, 645.
[8] (a) Chen, C.; Wilcoxen, K. M.; Huang, C. Q.; Xie, Y.-F.;
McCarthy, J. R.; Webb, T. R.; Zhu, Y.-F.; Saunders, J.; Liu, X.-J.; Chen,
T.-K.; Bozigian, H.; Grigoriadis, D. E. J Med Chem 2004, 47, 4787; (b)
Huang, C. Q.; Wilcoxen, K. M.; Grigoriadis, D. E.; McCarthy, J. R.;
Chen, C. Bioorg Med Chem Lett 2004, 14, 3943; (c) Chen, C.; Wilcoxen,
K. M.; Huang, C. Q.; McCarthy, J. R.; Chen, T.; Grigoriadis, D. E. Bioorg
Med Chem Lett 2004, 14, 3669; (d) Wustrow, D. J.; Capiris, T.; Rubin,
R.; Knobelsdorf, A.; Akunne, H.; Davis, M. D.; MacKenzie, R.; Pugsley,
T. A.; Zoski, K. T.; Heffner, T. G.; Wise, L. D. Bioorg Med Chem Lett
1998, 8, 2067.
[9] (a) Selleri, S.; Gratteri, P.; Costagli, C.; Bonaccini, C.;
Costanzo, A.; Melani, F.; Guerrini, G.; Ciciani, G.; Costa, B.; Spinetti, F.;
Martini, C.; Bruni, F. Bioorg Med Chem 2005, 13, 4821; (b) Selleri, S.;
Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Costa, B.;
Martini, C. Bioorg Med Chem 2001, 9, 2661; (c) Selleri, S.; Bruni, F.;
(KBr): 3450, 3058, 3012, 2933, 2852, 1672, 1660, 1352,
833, 732, 748, 709cmÀ1; MS (m/z): 579 (M+); Anal.
Calcd. for C28H30BrN5O2S: C, 57.93; H, 5.21; Br, 13.76;
N, 12.06; O, 5.51; S, 5.52; Found: C, 57.95; H, 5.20; Br,
13.72; N, 12.04; O, 5.50; S, 5.48.
N3-cyclohexyl-N6-(4-methoxyphenyl)-5-methyl-2-(methylthio)-
7-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarboxamide
[NBH-06]. Creamish solid; mp 266–270°C; IR (KBr):
3422, 3205, 3169, 2964, 2856, 1658, 1522, 1425,
1084, 838, 736cmÀ1; MS (m/z): 531 (M+); Anal.
Calcd. for C29H33N5O3S: C, 65.51; H, 6.26; N, 13.17;
O, 9.03; S, 6.03; Found: C, 65.59; H, 6.21; N, 13.19;
O, 9.09; S, 6.05.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
A Simple Approach to Synthesis of Pyrazolopyrimidine Derivatives Using Various
Acetoacetanilide
[17] Ghozlan, S. S.; Abdelrazek, F. M.; Mohamed, M. H.; Azmy,
K. E. J Heterocycl Chem 2010, 47, 1379.
Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Costa, B.; Martini, C.
Bioorg Med Chem 1999, 7, 2705.
[18] Frizzo, C. P.; Martins, M. P.; Marzari, M. B.; Campos, P. T.;
Claramunt, R. M.; García, M. A.; Sanz, D.; Alkorta, A.; Elguero, J.
J Heterocycl Chem 2010, 47, 1259.
[19] Ghotekar, B. K.; Jachak, M. N.; Toche, R. B. J Heterocycl
Chem 2009, 46, 708.
[20] Rote, R. V.; Shelar, D. P.; Patil, S. R.; Jachak, M. N.
J Heterocycl Chem 2014, 51, 815.
[21] Shamroukh, A. H.; Rashad, A. E.; Ali, H. S.; Abdel-Megeid,
F. E. J Heterocycl Chem 2013, 50, 758.
[22] Hosseinnia, R.; Mamaghani, M.; Shirini, F.; Tabatabaeian, K.
J Heterocycl Chem 2014, 51, 363.
[23] Hussein, A. M. J Heterocycl Chem 2012, 49, 446.
[24] Masevicius, V.; Juskenas, R.; Tumkevicius, S. J Heterocycl
Chem 2012, 49, 315.
[10] Drizin, I.; Holladay, M. W.; Yi, L.; Zhang, H. Q.;
Gopalakrishnan, S.; Gopalakrishnan, M.; Whiteaker, K. L.; Buckner, S. A.;
Sullivan, J. P.; Carroll, W. A. Bioorg Med Chem Lett 2002, 12, 1481.
[11] Altenbach, R. J.; Black, L. A.; Chang, S.; Cowart, M. D.;
Faghih, R.; Gfesser, G. A.; Ku, Y.; Liu, H.; Lukin, K. A.; Nersesian, D. L.;
Pu, Y.; Curtis, M. P. U.S. Patent Appl. 256,309, 2005; Chem Abstr 2005,
144, 36332.
[12] Kirkpatrick, W. E.; Okabe, T.; Hillyard, I. W.; Robin, R. K.;
Dren, A. T. J Med Chem 1977, 20, 386.
[13] George, C. F. P. Lancet 2001, 358, 1623.
[14] (a) Sullivan, S. K.; Petroski, R. E.; Verge, G.; Gross, R. S.;
Foster, A. C.; Grigoriadis, D. E. J Pharmacol Exp Ther 2004, 311, 537;
(b) Wegner, F.; Deuther-Conrad, W.; Scheunemann, M.; Brust, P.;
Fischer, S.; Hiller, A.; Diekers, M.; Strecker, K.; Wohlfarth, K.; Allgaier, C.;
[25] Mustazza, C.; Rosaria, M.; Giudice, D.; Borioni, A.; Gatta, F.
J Heterocycl Chem 2001, 38, 1119.
[26] Baraldi, P. G.; Fruttarolo, F.; Tabrizi, M. A.; Romagnoli, R.;
Preti, D.; Ongini, E.; El-Kashef, H.; Carrión, M. D.; Borea, P. A.
J Heterocycl Chem 2007, 44, 355.
[27] Alexandrovich, I. A.; Vasilievich, I. A.; Filippovich, S. N.
PCT Int. Appl., 2009093206.
[28] Ivachtchenko, A. V.; Golovina, E. S.; Kadieva, M. G.;
Koryakova, A. G.; Mitkin, O. D.; Tkachenko, S. E.; Kysil, V. M.; Okun, I.
Eur J Med Chem 2011, 46, 1189.
Steinbach, J.; Hoepping, A. Eur
J Pharmacol 2008, 580, 1; (c)
Hoepping, A.; Diekers, M.; Deuther-Conrad, W.; Scheunemann, M.;
Fischer, S.; Hiller, A.; Wegner, F.; Steinbach, J.; Brus, P. Bioorg
Med Chem 2008, 16, 1184.
[15] (a) Lippa, A.; Czobor, P.; Stark, J.; Beer, B.; Kostakis, E.;
Gravielle, M.; Bandyopadhyay, S.; Russek, S. J.; Gibbs, T. T.; Farb, D. H.;
Skolnick, P. Proc Natl Acad Sci U S A 2005, 102, 7380; (b) Mirza, N. R.;
Rodgers, R. J.; Mathiasen, L. S. J Pharmacol Exp Ther 2006, 316, 1291.
[16] Tully, W. R.; Gardner, C. R.; Gillespie, R. J.; Westwood, R.
J Med Chem 1991, 34, 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet