A modified, economical and efficient synthesis of variably substituted pyrazolo[4,3-d]pyrimidin-7-ones

Article abstract of DOI:10.1002/jhet.5570420608

1-Methyl-3-propyl-1H-pyrazole-5-carboxylic acid (3) was exclusively brominated at the 4-position by bromine in the dark. Brominated product 8 was then converted into 1-methyl-3-propyl-1H-pyrazole-5-carboxamide 9 by successive treatment with thionyl chloride and ammonium hydroxide. Carboxamide 9 was treated with various aroyl amides under microwave (MW) irradiation to afford 4-aroylamino-1-methyl-3-propyl-1H-pyrazole-5-carboxamides 10-22 and 5-aryl-1-methyl-3-propyl-1,6-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-ones 23-35. The 1H-pyrazole-5-carboxamides 10-22 were also converted to pyrimidinones 23-35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excellent yields in very short time.

Full text of DOI:10.1002/jhet.5570420608

Sep-Oct 2005
1085
A Modified, Economical and Efficient Synthesis of
Variably Substituted Pyrazolo[4,3-d]pyrimidin-7-ones
a
a
Khalid Mohammed Khan* , Ghulam Murtaza Maharvi , Muhammad Iqbal
a
a
b
Choudhary , Atta-ur-Rahman , and Shahnaz Perveen
a
International Center for Chemical Sciences, H.E.J. Research Institute of Chemistry, University of
Karachi, Karachi-75270, Pakistan
(Fax: +92-21-4819018-19; e-mail: hassaan2@super.net.pk)
b
PCSIR Laboratories Complex, Off University Road, Karachi-75280, Pakistan
Received December 16, 2004
1-Methyl-3-propyl-1H-pyrazole-5-carboxylic acid (3) was exclusively brominated at the 4-position by
bromine in the dark. Brominated product 8 was then converted into 1-methyl-3-propyl-1H-pyrazole-5-car-
boxamide 9 by successive treatment with thionyl chloride and ammonium hydroxide. Carboxamide 9 was
treated with various aroyl amides under microwave (MW) irradiation to afford 4-aroylamino-1-methyl-3-
propyl-1H-pyrazole-5-carboxamides 10-22 and 5-aryl-1-methyl-3-propyl-1,6-dihydro-1H-pyrazolo[4,3-
d]pyrimidin-7-ones 23-35. The 1H-pyrazole-5-carboxamides 10-22 were also converted to pyrimidinones
23-35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excel-
lent yields in very short time.
J. Heterocyclic Chem., 42, 1085 (2005).
Depending upon the identity of the starting material, the
reaction proceeded over 3 h at 200-220 °C and provided
1H-pyrazolo[3,4-b]quinolines 2 with up to 70% yield
along with difficult purification of the products [21].
Introduction.
In 1986 Richard Gedye and co-workers first described
the utilization and advantages of microwave irradiation for
organic synthesis [1,2]. The advantages of using
microwave irradiation (MW) technology high-speed syn-
thesis of organic molecules has grown quickly with publi-
cations growing from ~200 in 1995 to ~1000 in 2001 [3].
In addition, an unusually large number of review articles
and commentaries (~60) have been published on this sub-
ject covering various aspects of microwave-assisted
synthesis.
Scheme 1
Solvent free reactions [4,5] provide ease to synthetic
transformations; this cuts down the hazards of high-pres-
sure development and allows to conduct the reaction on
large scale. Conventional heating has certain drawbacks
due to poor thermal conductivity in solid support synthe-
sis. Nevertheless microwave activation has uniformity of
temperatures throughout the solid support reactions [6,7].
Alkylxanthines possess a variety of biological properties
like prototype antagonists for adenosine receptors. Many
of their physiological functions such as changes in conduc-
tance in the heart, CNS stimulators, and effects of the lung
and trachea have been described to their ability to block
AMPA receptors and antagonize endogenous adenosine
[22]. The pyrazolo[4,3-d]pyrimidines is the only class of
compounds that has been reported to have adenosine
receptor affinity [23]. Pyrazolo[4,3-d]pyrimidin-7-ones are
Nucleophilic aromatic substitution S Ar reactions are of
N
importance due to their use in industrial chemistry includ-
ing the synthesis of N-alkyl aminoheterocycles [8], bioac-
tive diarylethers [9] and N,N-disubstituted-5-aminothio-
phene-2-carboxaldehyde [9-10]. S Ar reactions are also
N
used to functionalize the pyrrole nucleus [11,12] and in the
preparation of quinoxalinedione [13], which are AMPA
receptor antagonists, as well as in synthesis of labeled 2'-
deoxyinosine and 2'-deoxyadenosine [14]. Various cata-
potent adenosine A receptors [24] and serve as intermedi-
ates for the synthesis of sildenafil (Viagra ) [25] and its
analogues which are potent inhibitors of the phosphodi-
esterase type 5 (PDE5) [26].
1

lysts [8,9,15-20] are used to carry out S Ar reactions
Previously, the synthesis of pyrazolo[4,3-d]pyrimidin-7-
ones was reported in six steps [25a,25b] from 1-methyl-3-
propyl-5-pyrazole-carboxylic acid (3 [25a,27-29]), which
involves nitration, acid chloride formation, amidation,
reduction of nitro- group, N-benzoylation followed by ring
closure to afford 5-(2-ethoxyphenyl)-1-methyl-3-propyl-
N
involving invariably higher temperature, toxic metal ions,
excess of reagents and are not environmental friendly.
Earlier, Hennig et al. reported the aromatic nucleophilic
substitution (S Ar) reaction of aniline with 4-aroyl-5-
N
chloro-1,3-disubstituted pyrazoles 1 (Scheme 1).

1086
K. M. Khan, G. M. Maharvi, M. I. Choudhary, A.-ur-Rahman, and S. Perveen
Vol. 42
1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (35),
(Scheme 2).
ent pyrazolo[4,3-d]pyrimidin-7-ones using MW irradia-
tion. In order to generalize our newly developed methodol-
Scheme 2
ogy, we have prepared a variety of variably substituted 5-
aroyl-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-
d]pyrimidin-7-ones 23-35. It is established, that by using
new emerging MW-assisted synthetic methodology for the
conversion of bromo-1-methyl-3-propyl-5-pyrazolecar-
Our research group is involved in methods development
in organic synthesis to produce known as well as new
bioactive molecules for the investigation of their unknown
biological effects [30]. Herein, we want to report an eco-
nomical and efficient method for the preparation of differ-
Scheme 3

Sep-Oct 2005
Efficient Synthesis of Variably Substituted Pyrazolo[4,3-d]pyrimidin-7-ones
1087
tion (S Ar) reaction on the activated C-4 position of 4-
bromo-1-methyl-3-propyl-5-pyrazolecarboxamide (9) by
boxamide (9) into pyrazolo[4,3-d]pyrimidin-7-ones 23-
35, reactions take place in shorter time to afford products
in high yields under mild conditions.
N
the NH group of various aroylamides led to the products
2
identified as compounds 10-22 and compounds 23-35 as
the key products. The reactions were performed on basic
alumina (5-7 min, MW) in dry media to trap the HBr
formed. On the other hand, the same reactions under con-
ventional heating by using potassium t-butoxide in t-
butanol, yielded either no products or only traces of com-
pounds 10-22 (Scheme 3).
Results and Discussion.
In our case, the synthetic procedure reported in the liter-
ature [25a,25b] was significantly modified and improved
by the applications of microwave heating. Our modified
synthesis (Scheme 3) starts with the bromination at acti-
vated 4-position to give the corresponding 4-bromo-1-
methyl-3-propyl-5-pyrazolecarboxylic acid (8) (see
Experimental), which was then converted into the respec-
tive acid chloride in refluxing thionyl chloride and into the
respective amide 9 upon treating of the chloride with aque-
ous ammonium hydroxide at room temperature. The
microwave (MW) assisted nucleophilic aromatic substitu-
The reaction proceeding through the transition states
TS-2 and TS-1 (Scheme 3) yielded compounds 10-22 (17-
25%) and 23-35 (58-76%) along with some unidentified
side products (Scheme 4). Compounds 10-22 were easily
converted to their corresponding pyrazolo[4,3-d]pyrim-
Scheme
4

1088
K. M. Khan, G. M. Maharvi, M. I. Choudhary, A.-ur-Rahman, and S. Perveen
Vol. 42
idin-7-ones 23-35 under the same MW irradiation reaction
protocol for 1-2 min following transition state TS-3
(Scheme 3), or by conventional heating in 98-100% yields
(Scheme-5).
These high-energy transition states (TS) can be achieved
under microwave irradiation by acquiring the certain
vibrational levels of the molecules, by exciting them
through a speedy MW heating, which can not be obtained
sufficiently by the conventional heating even after 60 h.
The formation of intermediates 10-22 provides an addi-
tional evidence for the hypothetical pathway to afford the
compounds 23-35. Compounds 10-22 were isolated by sil-
analysis. These side products may be due to decomposition
of target compounds 23-35, while prolonged heating (> 7
min) results in the complete decomposition of the prod-
ucts. The transformation of compounds 10-22 into com-
pounds 23-35 was achieved by both MW and conventional
heating (Scheme 5) through transition TS (TS-3) as shown
in Scheme 3.
To the best of our knowledge, this is the first report on
the synthesis of pyrazolo[4,3-d]pyrimidin-7-ones using
microwave irradiation.
Conclusion.
Reaction of 4-bromo-1-methyl-3-propyl-5-pyrazolecar-
boxamide (9) with various aroylamides provides a facile
route for pyrazolo[4,3-d]pyrimidin-7-ones 23-35, particu-
larly, when microwave irradiation is used as a source of
energy. This method provides a convenient, efficient, eco-
nomical, time saving, and high yielding synthesis of 5-sub-
stituted-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-
d]pyrimidin-7-one derivatives 23-35, which otherwise
would be available with difficulty using a classical method
[25a]. This method is also advantageous for the synthesis
ica gel column chromatography (CH Cl :EtOAc, 1:1)
along with some other unidentified minor side products;
the key products and were characterized by spectroscopic
2
2
Scheme 5

of sildenafil (Viagra ), its analogs as PDE5 inhibitors, and
various other AMPA receptor antagonists in higher yields
and shorter time.
EXPERIMENTAL
General.
M.p.'s were obtained in open capillaries, Büchi 434 apparatus;
1
uncorrected. H-NMR spectra were acquired using a Bruker appa-
ratus operating at 300 and 500 MHz in ppm (δ) relative to SiMe
4
(= 0 ppm) as internal standard. IR spectra were acquired using a
JASCO IR-A-302. EI-MS spectra were obtained using a
Finnigan-MAT-311A apparatus; m/z (rel %). Microwave-assisted
reactions were performed using 900 W, 2,450 MHz (LG Domestic
Microwave Appliance) oven. CHN analysis was performed by
Mr. Munawar Rasheed on a Carlo Erba Strumentazion-Mod-1106
Italy. TLC: Kieselgel (60-254 mesh, E. Merck); chromatograms
were visualized by iodine vapour; ultraviolet light (uv) at 254 and
365 nm; Ceric sulphate solution followed by heating and
Dragendroff's reagent. Column chromatography: silica gel (70-
230 mesh and 230-400 mesh, E. Merck) using commercial grade
solvents. Diethyl oxalate, dimethyl sulfate, bromine, and 2-pen-
tanone were purchased from E. Merck. The solvents used in reac-
tions were of analytical reagent grade (E. Merck) and dried before
use, whenever necessary by using standard protocols.
4-Bromo-1-methyl-3-propyl-1H-pyrazole-5-carboxylic acid (8).
To a solution of 3 (0.168 g, 1 mmol) and K CO (0.414 g, 3
2
3
mmol) in CH Cl (20 mL) at r.t., was added Br (3 mmol) in the
2
2
2
dark. After 6 h at r.t., the reaction was quenched with 1 M
Na S O (30 mL), extracted with CH Cl (3 x 25 mL), the
2
2
3
2
2
extract dried (Na SO ) and evaporated under reduced pressure to
2
4
dryness. The residue was chromatographed (CH Cl :AcOEt, 1:1)
2
2
to give the title compound as brown amorphous powder 0.148 g,
(Yield 88%); mp 112-113°; R = 0.46 (AcOEt: CH Cl , 6:4); ir.
f
2
2

Sep-Oct 2005
Efficient Synthesis of Variably Substituted Pyrazolo[4,3-d]pyrimidin-7-ones
1089
(potassium bromide): ν
2933, 2873 (O-H, C-H br. str. over-
4-Benzoylamino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide
(10) [31].
max
lapped), 1709 (C=O), 1465 (C=C str.), 1534 (CH bend.), 1390,
2
-1
1
1362 (CH bend.), 1240 (C-N str.), 610 (C-Br str.) cm ; H nmr
3
This compound was obtained as a white powder; Yield 18%;
(MeOD-d , 300 MHz): δ 0.98 (t, J = 7.2 Hz, 3H, CH -CH -CH ),
4
2
2
3
mp 169-170 °C; R = 0.51 (AcOEt: CH Cl , 7:3); ir. (potassium
f
2
2
1.67 (m, 2H, CH -CH -CH ), 2.81 (dd, J = 7.2 Hz, 7.8 Hz, 2H,
2
2
3
-1
bromide): ν
3399, 3335, 3306 (NH), 1677, 1647 (C=O) cm ;
max
+
CH -CH -CH ), 3.92 (s, 3H, N1-CH ); EIMS: m/z 249 (M , 18),
2
2
3
3
1
H nmr (CDCl , 400 MHz): δ 0.98 (t, J = 7.4 Hz, 3H,
3
247 (20), 233 (18), 203 (60), 191 (8), 189 (10), 168 (100), 154
(10), 141 (14), 124 (30), 97 (11), 44 (5%).
CH CH CH ), 1.58-1.69 (m, 2H, CH CH CH ), 2.55 (dd, 2H, J
2
2
3
2
2
3
= 7.7 Hz, J = 7.3 Hz, CH CH CH ), 4.09 (s, 3H, NCH ), 5.53 (br
2
2
3
3
Anal. Calcd. for C H BrN O : C, 38.89; H, 4.49; N, 11.34.
8
11
2 2
s, 2H, CONH ), 7.48-7.69 (m, 5H, Ar-H), 7.89 (br s, 1H,
2
Found: C, 38.92; H, 4.47; N, 11.33.
+
CONH); EIMS: m/z 286 (M , 15), 181 (3), 149 (100), 121 (82),
4-Bromo-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (9).
93 (21), 65 (23%).
Anal. Calcd. for C H N O : C, 62.92; H, 6.34; N, 19.57.
Found: C, 62.90; H, 6.35; N, 19.57.
15 18
4 2
Compound 8 (0.247 g, 1 mmol) was refluxed with thionyl
chloride (15 mL) for 2 h (oil bath). Excess of thionyl chloride
was distilled under reduce pressure and the crude acid chloride
4-[(2-Nitrobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (11) [25a,25b,32].
was added slowly to a cooled (≈ 0 °C) aqueous NH OH (20 mL,
4
25%). Stirring the reaction mixture for 2 h at room temperature.
Cold water (50 mL) was then added and the precipitated solid
product 7 was collected by suction filtration, and dried to obtain
This compound was obtained as yellow crystals; Yield 21%;
mp 187-188 °C; R = 0.44 (AcOEt); ir. (potassium bromide):
f
ν
3400, 3329, 3300 (NH), 1679, 1645 (C=O), 1588, 1365
max
light yellow powder 0.21 g (Yield 85%). mp 133-134°; R = 0.42
f
-1
1
(NO ) cm ; H nmr (CDCl , 400 MHz): δ 0.93 (t, J = 7.2 Hz,
2
3
(AcOEt: CH Cl , 7:3); ir. (potassium bromide): ν 3400
2
2
max
3H, CH CH CH ), 1.57-1.70 (m, 2H, CH CH CH ), 2.54 (dd,
2
2
3
2
2
3
(amide-NH ), 2873 (C-H str.), 1710 (C=O), 1460 (C=C str.),
2
2H, J = 7.8 Hz, J = 7.0 Hz, CH CH CH ), 4.06 (s, 3H, NCH ),
2
2
3
3
1532 (CH bend.), 1388, 1359 (CH bend.), 1245 (C-N str.), 617
2
3
5.55 (br s, 2H, CONH ), 7.36-7.42 (overlapped m, 2H, H-4'/
-1 1
2
(C-Br str.) cm ; H nmr (CDCl , 300 MHz): δ 0.96 (t, J = 7.4 Hz,
3H, CH -CH -CH ), 1.68 (m, 2H, CH -CH -CH ), 2.80 (dd, J =
3
H-5'), 7.83 (dd, 1H, J = 8.6 Hz, J = 1.2 Hz, H-3'), 7.89 (br s,
2
2
3
2
2
3
1H, CONH), 8.30 (dd, 1H, J = 8.6 Hz, J = 1.2 Hz, H-6'); EIMS:
7.1Hz, 7.6 Hz, 2H, CH -CH -CH ), 2.85 (br s, 2H, -NH ), 3.92
2
2
3
2
+
+
m/z 331 (M , 18), 286 (5), 181 (4), 149 (100), 121 (67), 93
(s, 3H, N1-CH ); EIMS: m/z 248 (M , 22), 246 (25), 231 (13),
3
(26), 65 (11%).
203 (35), 189 (10), 167 (100), 141 (19), 110 (48), 97 (11), 71
(16), 44 (5%).
Anal. Calcd. for C H N O : C, 54.38; H, 5.17; N, 21.14.
15 17
5 4
Found: C, 54.38; H, 5.16; N, 21.15.
Anal. Calcd. for C H BrN O: C, 39.04; H, 4.91; N, 17.07.
8
12
3
Found: C, 39.01; H, 4.89; N, 17.10.
4-[(3-Nitrobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (12).
General Procedure for the Synthesis of Compounds (10-22) and
Compounds (23-35).
This compound was obtained as light yellow crystals; Yield
Microwave Irradiation Method.
17%; mp 177-178 °C; R = 0.49 (AcOEt); ir. (potassium bro-
f
mide): ν
3397, 3333, 3305 (NH), 1675, 1646 (C=O), 1595,
max
Various aroylamides (1 mmol) and 4-bromo-1-methyl-3-
propyl-1H-pyrazole-5-carboxamide (9) (1 mmol) was adsorbed
on basic alumina (≈ 1 g). The reaction mixture enclosed in closed
vessel of Teflon was irradiated inside the microwave oven for 5-
7 min. at 2,450 MHz. The reaction mixture was cooled down to
-1
1
1366 (NO ) cm ; H nmr (CDCl , 400 MHz): δ 0.99 (t, J = 7.1
2
3
Hz, 3H, CH CH CH ), 1.55-1.71 (m, 2H, CH CH CH ), 2.51
(dd, 2H, J = 7.5 Hz, J = 7.3 Hz, CH CH CH ), 4.05 (s, 3H,
2
2
3
2
2
3
2
2
3
NCH ), 5.54 (br s, 2H, CONH ), 7.84 (td, 1H, J = 8.3 Hz, J = 1.5
3
2
Hz, H-5'/), 7.88 (br s, 1H, CONH), 8.41 (dd, 1H, J = 8.3 Hz, J =
1.5 Hz, H-6'), 8.45 (dd, 1H, J = 8.3 Hz, J = 1.5 Hz, H-4'), 8.01 (d,
1H, J = 8.3 Hz, J = 1.5 Hz, H-2'); EIMS: m/z 331 (M , 23), 285
(11), 181 (9), 149 (100), 121 (70), 93 (22), 65 (11%).
Anal. Calcd. for C H N O : C, 54.38; H, 5.17; N, 21.14.
Found: C, 54.40; H, 5.17; N, 21.14.
room temperature and eluted with CH Cl (3 x 15 mL). The elu-
2
2
ent was evaporated to dryness and subjected to the column chro-
matography (CH Cl :AcOEt, increasing polarity) to afford the
+
2
2
title compounds 10-22 (17-25%) and compounds 23-35 (58-
76%). The compounds 10-22 which were obtained as one of the
reaction products were recycled by subjecting to the 1-2 min
microwave irradiations following the same reaction protocol into
compounds 23-35 in 97-100% yields. The structures of the com-
pounds 10-22 and 23-35 were determined by the spectroscopic
analysis.
15 17
5 4
4-[(4-Nitrobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (13).
This compound was obtained as yellow needles; Yield 25%;
mp 191-192 °C; R = 0.43 (AcOEt); ir. (potassium bromide):
f
Conventional Heating Method for the Preparation of Compounds
23-35.
ν
3398, 3331, 3302 (NH), 1674, 1646 (C=O), 1581, 1365
(NO ) cm ; H nmr (CDCl , 400 MHz): δ 1.00 (t, J = 7.0 Hz,
max
-1
1
2
3
3H, CH CH CH ), 1.55-1.72 (m, 2H, CH CH CH ), 2.55 (dd,
Potassium t-butoxide (2 mmol) was added to a stirred suspen-
sion of the amides 10-22 (1 mmol) in t-butyl alcohol (10 mL).
The resulted mixture was refluxed for 10 h at 95 °C (oil bath),
and then allowed to cool at room temperature. Water (15 mL) was
added and then the solution was neutralized with HCl (5%) to pH
≈ 7, and cooled to about 5-10 °C. The precipitated solid product
was collected by suction filtration, washed with cold water and
dried. This afforded the title compounds 23-35 in 80-93% yields.
2
2
3
2
2
3
2H, J = 7.8 Hz, J = 7.2 Hz, CH CH CH ), 4.03 (s, 3H, NCH ),
5.49 (br s, 2H, CONH ), 7.91 (br s, 1H, CONH), 8.20 (d, 2H, J
= 9.2 Hz, H-2'/ H-6'), 8.35 (d, 1H, J = 9.2 Hz, H-3'/ H-5');
EIMS: m/z 331 (M , 9), 285 (3), 181 (8), 149 (100), 121 (67),
93 (26), 65 (17%).
Anal. Calcd. for C H N O : C, 54.38; H, 5.17; N, 21.14.
Found: C, 54.35; H, 5.18; N, 21.13.
2
2
3
3
2
+
15 17
5 4

1090
K. M. Khan, G. M. Maharvi, M. I. Choudhary, A.-ur-Rahman, and S. Perveen
Vol. 42
4-[(2-Bromobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (14).
4-[(Isonicotinoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-car-
boxamide (18) [33].
This compound was obtained as a brown powder; Yield 22%;
This compound was obtained as yellow powder; Yield 19%; mp
mp 188-189 °C; R = 0.52 (AcOEt: CH Cl , 9:1); ir. (potassium
197.5-198.5 °C; R = 0.48 (AcOEt: CH Cl , 8:2); ir. (potassium
f
2
2
f 2 2
-1
bromide): ν
3399, 3335, 3306 (NH), 1677, 1647 (C=O), 610
bromide): ν
3399, 3335, 3306 (NH), 1677, 1647 (C=O) cm ;
max
-1
max
1
1
(C-Br) cm ; H nmr (CDCl , 400 MHz): δ 0.93 (t, J = 7.0 Hz,
H nmr (CDCl , 400 MHz): δ 0.95 (t, J = 7.1 Hz, 3H,
3
3
3H, CH CH CH ), 1.57-1.69 (m, 2H, CH CH CH ), 2.56 (dd,
CH CH CH ), 1.53-1.71 (m, 2H, CH CH CH ), 2.53 (dd, 2H, J =
2
2
3
2
2
3
2
2
3
2
2
3
2H, J = 7.7 Hz, J = 7.2 Hz, CH CH CH ), 4.00 (s, 3H, NCH ),
7.6 Hz, J = 7.3 Hz, CH CH CH ), 4.01 (s, 3H, NCH ), 5.49 (br s,
2
2
3
3
2
2
3
3
5.57 (br s, 2H, CONH ), 7.20 (td, 1H, J = 7.7 Hz, J = 1.2 Hz, H-
2H, CONH ), 7.90 (br s, 1H, CONH), 7.97 (d, 2H, J = 7.3 Hz, H-
2'/ H-6'), 8.89 (d, 2H, J = 7.3 Hz, H-3'/ H-5'); EIMS: m/z 287 (M ,
17), 285 (6), 181 (3), 149 (100), 121 (74), 93 (22), 65 (34%).
2
2
+
4'), 7.35 (dd, 1H, J = 7.7 Hz, J = 1.2 Hz, H-3'), 7.42 (td, 1H, J =
7.7 Hz, J = 1.2 Hz, H-5'), 7.62 (dd, 1H, J = 7.7 Hz, J = 1.2 Hz, H-
+
6'), 7.89 (br s, 1H, CONH); EIMS: m/z 367 (M , 20), 365 (18),
Anal. Calcd. for C H N O : C, 58.52; H, 5.96; N, 24.38.
14 17
5 2
285 (6), 181 (3), 149 (100), 121 (82), 93 (21), 65 (23%).
Found: C, 58.56; H, 5.94; N, 24.38.
Anal. Calcd. for C H BrN O : C, 49.33; H, 4.69; N, 15.34.
Found: C, 49.29; H, 4.70; N, 15.35.
15 17
4 2
4-[(4-Hydroxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-
5-carboxamide (19).
4-[(3-Bromobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (15).
This compound was obtained as white crystals; Yield 23%; mp
183-184 °C; R = 0.46 (AcOEt); ir. (potassium bromide): ν
f
max
-1 1
This compound was obtained as brown crystals; Yield 20%;
mp 185-186 °C; R = 0.50 (AcOEt: CH Cl , 9:1); ir. (potassium
3388, 3337, 3309 (NH), 1675, 1639 (C=O) cm ; H nmr (CDCl ,
3
400 MHz): δ 1.00 (t, J = 7.2 Hz, 3H, CH CH CH ), 1.55-1.73 (m,
f
2
2
2
2
3
bromide): ν
3405, 3328, 3298 (NH), 1676, 1646 (C=O), 619
2H, CH CH CH ), 2.55 (dd, 2H, J = 7.7 Hz, J = 7.3 Hz,
max
-1
2
2
3
1
(C-Br) cm ; H nmr (CDCl , 400 MHz): δ 0.95 (t, J = 6.9 Hz,
CH CH CH ), 4.04 (s, 3H, NCH ), 5.56 (br s, 2H, CONH ), 6.92
3
2
2
3
3
2
3H, CH CH CH ), 1.53-1.66 (m, 2H, CH CH CH ), 2.51 (dd,
(d, 2H, J = 8.2 Hz, H-3'/ H-5'), 7.77 (d, 2H, J = 8.2 Hz, H-2'/ H-6'),
2
2
3
2
2
3
+
2H, J = 7.5 Hz, J = 7.1 Hz, CH CH CH ), 4.01 (s, 3H, NCH ),
7.90 (br s, 1H, CONH); EIMS: m/z 302 (M , 25), 285 (4), 272 (9),
2
2
3
3
5.56 (br s, 2H, CONH ), 7.06 (td, 1H, J = 7.9 Hz, J = 1.6 Hz, H-
181 (8), 149 (100), 121 (77), 93 (24), 65 (19%).
2
5'), 7.37 (dd, 1H, J = 7.9 Hz, J = 1.6 Hz, H-4'), 7.53 (d, 1H, J = 1.6
Hz, H-2'), 8.01 (dd, 1H, J = 7.9 Hz, J = 1.6 Hz, H-6'), 7.84 (br s,
1H, CONH); EIMS: m/z 367 (M , 20), 365 (18), 285 (6), 181 (3),
Anal. Calcd. for C H N O : C, 59.59; H, 6.00; N, 18.53.
Found: C, 59.55; H, 6.01; N, 18.51.
15 18
4 3
+
4-[(4-Methoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-
5-carboxamide (20).
149 (100), 121 (82), 93 (21), 65 (23%).
Anal. Calcd. for C H BrN O : C, 49.33; H, 4.69; N, 15.34.
15 17
4 2
This compound was obtained as white powder; Yield 21%; mp
Found: C, 49.31; H, 4.71; N, 15.33.
174.2-175.4 °C; R = 0.49 (AcOEt: CH Cl , 9:1); ir. (potassium
f
2
2
4-[(4-Bromobenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (16).
-1
bromide): ν
3391, 3340, 3310 (NH), 1670, 1641 (C=O) cm ;
max
1
H nmr (CDCl , 400 MHz): δ 1.01 (t, J = 7.1 Hz, 3H,
3
This compound was obtained as brown crystals; Yield 18%;
mp 182.5-183.5 °C; R = 0.51 (AcOEt: CH Cl , 9:1); ir. (potas-
CH CH CH ), 1.57-1.71 (m, 2H, CH CH CH ), 2.53 (dd, 2H, J
2
2
3
2
2
3
= 7.8 Hz, J = 7.1 Hz, CH CH CH ), 3.61 (s, 3H, OCH ), 4.01 (s,
f
2
2
2
2
3
3
sium bromide): ν
3399, 3334, 3300 (NH), 1670, 1641 (C=O),
3H, NCH ), 5.51 (br s, 2H, CONH ), 6.93 (d, 2H, J = 8.8 Hz, H-
max
3
2
-1
1
619 (C-Br) cm ; H nmr (CDCl , 400 MHz): δ 0.97 (t, J = 7.4
2'/ H-6'), 7.79 (d, 2H, J = 8.8 Hz, H-3'/ H-5'), 7.88 (br s, 1H,
3
+
Hz, 3H, CH CH CH ), 1.51-1.65 (m, 2H, CH CH CH ), 2.54
CONH); EIMS: m/z 316 (M , 22), 285 (6), 181 (8), 149 (100),
2
2
3
2
2
3
(dd, 2H, J = 7.8 Hz, J = 7.1 Hz, CH CH CH ), 4.03 (s, 3H,
121 (77), 93 (24), 65 (19%).
2
2
3
NCH ), 5.57 (br s, 2H, CONH ), 7.38 (d, 2H, J = 8.5 Hz, H-3'/ H-
Anal. Calcd. for C H N O : C, 60.75; H, 6.37; N, 17.71.
3
2
16 20
4 3
5'), 7.60 (d, 2H, J = 8.5 Hz, H-2'/ H-6'), 7.90 (br s, 1H, CONH);
Found: C, 60.71; H, 6.35; N, 17.70.
+
EIMS: m/z 367 (M , 20), 365 (18), 285 (6), 181 (3), 149 (100),
4-[(3,4,5-Trimethoxybenzoyl)amino]-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide (21).
121 (82), 93 (21), 65 (23%).
Anal. Calcd. for C H BrN O : C, 49.33; H, 4.69; N, 15.34.
15 17
4 2
This compound was obtained as white powder; Yield 24%; mp
Found: C, 49.36; H, 4.69; N, 15.35.
167.5-168.5 °C; R = 0.51 (AcOEt: CH Cl , 8:2); ir. (potassium bro-
f
2
2
4-[(Nicotinoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-car-
boxamide (17).
-1
1
mide): ν
3395, 3329, 3299 (NH), 1670, 1649 (C=O) cm ; H
max
nmr (CDCl , 400 MHz): δ 0.99 (t, J = 7.3 Hz, 3H, CH CH CH ),
3
2
2
3
This compound was obtained as yellow crystals; Yield 20%;
mp 200-201 °C; R = 0.47 (AcOEt: CH Cl , 8:2); ir. (potassium
1.53-1.67 (m, 2H, CH CH CH ), 2.52 (dd, 2H, J = 7.7 Hz, J = 7.1
2
2
3
Hz, CH CH CH ), 3.78 (s, 3H, OCH ), 3.84 (s, 6H, OCH ), 4.05 (s,
f
2
2
2
2
3
3
3
-1
bromide): ν
3389, 3333, 3298 (NH), 1671, 1642 (C=O) cm ;
3H, NCH ), 5.54 (br s, 2H, CONH ), 7.27 (s, 2H, H-2'/ H-6'), 7.85
max
3
2
1
+
H nmr (CDCl , 400 MHz): δ 0.99 (t, J = 7.4 Hz, 3H,
(br s, 1H, CONH); EIMS: m/z 376 (M , 18), 345 (3), 315 (5), 285
(2), 181 (3), 149 (100), 121 (82), 93 (21), 65 (23%).
3
CH CH CH ), 1.53-1.67 (m, 2H, CH CH CH ), 2.56 (dd, 2H, J
2
2
3
2
2
3
= 7.7 Hz, J = 7.0 Hz, CH CH CH ), 4.07 (s, 3H, NCH ), 5.57 (br
Anal. Calcd. for C H N O : C, 57.44; H, 6.43; N, 14.88.
2
2
3
3
18 24
4 5
s, 2H, CONH ), 7.60 (t, 1H, J = 7.8 Hz, H-5'), 7.87 (br s, 1H,
Found: C, 57.42; H, 6.44; N, 14.87.
2
CONH), 8.33 (d, 1H, J = 7.8 Hz, H-6'), 8.65 (d, 1H, J = 7.8 Hz,
4-[(2-Ethoxybenzoyl)amino]-1-methyl-3-propyl-1H-pyrazole-5-
carboxamide (22).
+
H-4'), 9.09 (s, 1H, H-2'); EIMS: m/z 287 (M , 12), 285 (8), 181
(7), 149 (100), 121 (55), 93 (31), 65 (26%).
Anal. Calcd. for C H N O : C, 58.52; H, 5.96; N, 24.38.
The structure of the compound 22 was determined by the spec-
14 17
5 2
Found: C, 58.50; H, 5.97, N, 24.36.
troscopic analysis and was found in agreement with the reported

Sep-Oct 2005
Efficient Synthesis of Variably Substituted Pyrazolo[4,3-d]pyrimidin-7-ones
1091
literature values [25a,25b].
(4), 268 (21), 191 (23), 166 (17), 136 (11), 120 (24), 102 (21), 91
(70), 67 (100), 56 (43%).
5-Phenyl-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]-
pyrimidin-7-one (23) [25a,31,34].
Anal. Calcd. for C H N O : C, 57.50; H, 4.83; N, 22.35.
15 15
5 3
Found: C, 57.55; H, 4.80; N, 22.35.
This compound was obtained as a white powder; Yield:
Scheme 4 (76%); Scheme 5 (100%); cumulative (88%); mp 203-
5-(2-Bromophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (27).
204 °C; R = 0.59 (CH Cl ); ir. (potassium bromide): ν
3306
f
2
2
max
-1 1
(N-H), 2933, 2873 (C-H), 1703 (C=O), 1244 (C-N) cm ; H nmr
This compound was obtained as a brown powder; Yield:
Scheme 4 (60%); Scheme 5 (98%); cumulative (79%); mp 193-
194 °C; R = 0.53 (CH Cl :AcOEt, 9:1); ir. (potassium bromide):
(CDCl , 400 MHz): δ 1.02 (t, J = 7.3 Hz, 3H, CH -CH -CH ),
3
2
2
3
1.79 (m, 2H, CH -CH -CH ), 3.03 (dd, J = 7.6 Hz, J = 7.2 Hz,
2
2
3
f
2
2
2H, CH -CH -CH ), 4.25 (s, 3H, N1-CH ), 7.42-7.77 (m, 5H,
ν
3311 (N-H), 2930, 2873 (C-H), 1700 (C=O), 1240 (C-N),
2
2
3
3
max
+
-1 1
Ar-H), 12.30 (s, 1H, NH); EIMS: m/z 268 (M , 20), 254 (6), 192
(23), 166 (17), 136 (11), 120 (24), 102 (21), 91 (70), 67 (100), 56
(43%).
619 (C-Br) cm ; H nmr (CDCl , 400 MHz): δ 0.99 (t, J = 7.3 Hz,
3
3H, CH -CH -CH ), 1.73 (m, 2H, CH -CH -CH ), 3.01 (dd, J =
7.6 Hz, J = 7.2 Hz, 2H, CH -CH -CH ), 4.25 (s, 3H, N1-CH ),
2
2
3
2
2
3
2
2
3
3
Anal. Calcd. for C H N O: C, 67.15; H, 6.01; N, 20.88.
Found: C, 67.11; H, 6.01; N, 20.87.
7.35 (td, 1H, J = 7.8 Hz, J = 1.5 Hz, H-4'), 7.57 (td, 1H, J = 7.8 Hz,
J = 1.5 Hz, H-5'), 7.65 (dd, 1H, J = 7.8 Hz, J = 1.5 Hz, C3'-H), 7.94
(dd, 2H, J = 7.8 Hz, J = 1.5 Hz, H-6_), 12.30 (s, 1H, NH); EIMS:
m/z 349 (M , 17), 347 (20), 268 (43), 192 (23), 178 (17), 152 (7),
137 (11), 125 (24), 110 (21), 84 (70), 64 (100), 56 (43%).
15 16
4
5-(2-Nitrophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (24) [25a].
+
This compound was obtained as yellow crystals; Yield:
Scheme 4 (71%); Scheme 5 (98%); cumulative (85%); mp 215-
Anal. Calcd. for C H BrN O: C, 51.89; H, 4.35; N, 16.14.
Found: C, 51.85; H, 4.37; N, 16.15.
15 15
4
216 °C; R = 0.51 (CH Cl : AcOEt, 8:2); ir. (potassium bromide):
f
2
2
5-(3-Bromophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (28).
ν
3300 (N-H), 2936, 2870 (C-H), 1707 (C=O), 1365 (NO ),
max
2
-1
1
1240 (C-N) cm ; H nmr (CDCl , 400 MHz): δ 1.01 (t, J = 7.3
3
Hz, 3H, CH -CH -CH ), 1.78 (m, 2H, CH -CH -CH ), 3.07 (dd,
This compound was obtained as light brown crystals; Yield:
Scheme 4 (62%); Scheme 5 (97%); cumulative (80%); mp 197.5-
198.5 °C; R = 0.51 (CH Cl :AcOEt, 9:1); ir. (potassium bro-
2
2
3
2
2
3
J = 7.5 Hz, J = 7.1 Hz, 2H, CH -CH -CH ), 4.24 (s, 3H, N1-
2
2
3
CH ), 7.86-7.99 (m, 3H, H-3', H-4', H-5'), 8.32 (d, 2H, J = 8.4
3
f
2
2
+
Hz, H-6'), 12.15 (s, 1H, NH). EIMS: m/z 313 (M , 17), 298 (4),
mide): ν
3305 (N-H), 2933, 2876 (C-H), 1708 (C=O), 1241
max
-1
1
268 (21), 191 (23), 166 (17), 136 (11), 120 (24), 102 (21), 91
(70), 67 (100), 56 (43%).
(C-N), 615 (C-Br) cm ; H nmr (CDCl , 400 MHz): δ 1.00 (t, J
3
= 7.3 Hz, 3H, CH -CH -CH ), 1.80 (m, 2H, CH -CH -CH ),
2
2
3
2
2
3
Anal. Calcd. for C H N O : C, 57.50; H, 4.83; N, 22.35.
3.07 (dd, J = 7.7 Hz, J = 7.1 Hz, 2H, CH -CH -CH ), 4.20 (s, 3H,
15 15
5 3
2
2
3
Found: C, 57.54; H, 4.84; N, 22.33.
N1-CH ), 7.38 (td, 1H, J = 8.0 Hz, J = 1.6 Hz, H-5'), 7.72 (td, 1H,
3
J = 8.0 Hz, J = 1.6 Hz, H-4'), 7.91 (dd, 1H, J = 8.0 Hz, J = 1.6 Hz,
5-(3-Nitrophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (25) [34].
C6'-H), 8.33 (d, 1H, J = 1.6 Hz, H-2'), 12.11 (s, 1H, NH); EIMS:
+
m/z 349 (M , 17), 347 (20), 268 (43), 192 (23), 178 (17), 152 (7),
This compound was obtained as yellow crystals; Yield:
Scheme 4 (75%); Scheme 5 (99%); cumulative (87%); mp 208-
209 °C; R = 0.49 (CH Cl : AcOEt, 8:2); ir. (potassium bromide):
137 (11), 125 (24), 110 (21), 84 (70), 64 (100), 56 (43%).
Anal. Calcd. for C H BrN O: C, 51.89; H, 4.35; N, 16.14.
15 15
4
Found: C, 51.87; H, 4.34; N, 16.16.
f
2
2
ν
3310 (N-H), 2928, 2868 (C-H), 1708 (C=O), 1361 (NO ),
max
2
5-(4-Bromophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (29).
-1
1
1242 (C-N) cm ; H nmr (CDCl , 400 MHz): δ 1.05 (t, J = 7.3
3
Hz, 3H, CH -CH -CH ), 1.75 (m, 2H, CH -CH -CH ), 3.06 (dd,
2
2
3
2
2
3
J = 7.6 Hz, J = 7.0 Hz, 2H, CH -CH -CH ), 4.20 (s, 3H, N1-
This compound was obtained as brown crystals; Yield:
Scheme 4 (58%); Scheme 5 (98%); cumulative (78%); mp 190-
2
2
3
CH ), 7.88 (td, 1H, J = 8.3 Hz, J = 2.3 Hz, H-5'), 8.31 (dd, 1H, J
3
= 8.3 Hz, J = 2.3 Hz, H-4'), 8.43 (d, 1H, J = 2.3 Hz, H-2'), 8.31
191 °C; R = 0.52 (CH Cl : AcOEt, 9:1); ir. (potassium bromide):
f 2 2
(dd, 1H, J = 8.3 Hz, J = 2.3 Hz, H-6'), 12.15 (s, 1H, NH); EIMS:
m/z 313 (M , 17), 298 (4), 268 (21), 191 (23), 166 (17), 136 (11),
120 (24), 102 (21), 91 (70), 67 (100), 56 (43%).
ν
3315 (N-H), 2928, 2869 (C-H), 1708 (C=O), 1239 (C-N),
max
+
-1 1
615 (C-Br) cm ; H nmr (CDCl , 400 MHz): δ 0.98 (t, J = 7.3
3
Hz, 3H, CH -CH -CH ), 1.82 (m, 2H, CH -CH -CH ), 3.07 (dd,
2 2 3 2 2 3
Anal. Calcd. for C H N O : C, 57.50; H, 4.83; N, 22.35.
J = 7.7 Hz, J = 7.4 Hz, 2H, CH -CH -CH ), 4.22 (s, 3H, N1-
15 15
5
3
2 2 3
Found: C, 57.47; H, 4.81; N, 22.36.
CH ), 7.37 (d, 2H, J = 8.6 Hz, H-3'/5'), 7.72 (d, 2H, J = 8.6 Hz, H-
2'/6'), 12.11 (s, 1H, NH); EIMS: m/z 349 (M , 17), 347 (20), 268
(43), 192 (23), 178 (17), 152 (7), 137 (11), 125 (24), 110 (21), 84
(70), 64 (100), 56 (43%).
3
+
5-(4-Nitrophenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (26).
This compound was obtained as light yellow crystals; Yield:
Scheme 4 (65%); Scheme 5 (97%); cumulative (81%); mp 202.5-
Anal. Calcd. for C H BrN O: C, 51.89; H, 4.35; N, 16.14.
Found: C, 51.87; H, 4.34; N, 16.16.
15 15
4
203.5 °C; R = 0.50 (CH Cl : AcOEt, 8:2); ir. (potassium bro-
f
2
2
5-(3-Pyridinyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (30) [33].
mide): ν
3310 (N-H), 2929, 2871 (C-H), 1707 (C=O), 1365
max
-1 1
(NO ), 1240 (C-N) cm ; H nmr (CDCl , 400 MHz): δ 1.02 (t, J
2
3
= 7.4 Hz, 3H, CH -CH -CH ), 1.80 (m, 2H, CH -CH -CH ),
This compound was obtained as yellow shiny needles; Yield:
Scheme 4 (72%); Scheme 5 (98%); cumulative (85%); mp 218-
2
2
3
2
2
3
3.07 (dd, J = 7.7 Hz, J = 7.1 Hz, 2H, CH -CH -CH ), 4.21 (s, 3H,
2
2
3
219 °C; R = 0.48 (CH Cl ); ir. (potassium bromide): ν
3306
N1-CH ), 7.90 (d, 2H, J = 8.1 Hz, H-2'/H-6'), 8.27 (d, 2H, J = 8.1
Hz, H-3'/H-5'), 12.15 (s, 1H, NH); EIMS: m/z 313 (M , 17), 298
f
2
2
max
-1 1
3
+
(N-H), 2933, 2873 (C-H), 1703 (C=O), 1244 (C-N) cm ; H nmr

1092
K. M. Khan, G. M. Maharvi, M. I. Choudhary, A.-ur-Rahman, and S. Perveen
Vol. 42
(CDCl , 400 MHz): δ 1.06 (t, J = 7.1 Hz, 3H, CH -CH -CH ),
°C; R = 0.54 (CH Cl : AcOEt, 9:1); ir. (potassium bromide):
3
2
2
3
f
2
2
1.78 (m, 2H, CH -CH -CH ), 3.05 (dd, J = 7.7 Hz, J = 6.9 Hz,
ν
3303 (N-H), 2943, 2863 (C-H), 1703 (C=O), 1234 (C-N)
2
2
3
max
-1 1
2H, CH -CH -CH ), 4.23 (s, 3H, N1-CH ), 7.63 (td, 1H, J = 7.7
cm ; H nmr (CDCl , 400 MHz): δ 1.07 (t, J = 6.9 Hz, 3H, CH -
2
2
3
3
3
2
Hz, J = 1.3 Hz, H-5'), 8.46 (dd, 1H, J = 7.7 Hz, J = 1.3 Hz, H-6'),
9.16 (dd, 1H, J = 7.7 Hz, J = 1.3 Hz, H-4'), 9.33 (d, 1H, J = 1.3
CH -CH ), 1.82 (m, 2H, CH -CH -CH ), 3.05 (dd, J = 7.7 Hz, J
2 3 2 2 3
= 7.2 Hz, 2H, CH -CH -CH ), 3.76 (s, 6H, OCH ), 3.83 (s, 3H,
2
2
3
3
+
Hz, H-2'), 12.11 (s, 1H, NH); EIMS: m/z 269 (M , 20), 254 (6),
OCH ) 4.20 (s, 3H, N1-CH ), 7.00 (d, 2H, J = 8.9 Hz, H-2'/6'),
3 3
+
191 (23), 176 (4), 166 (17), 136 (11), 120 (24), 102 (21), 91 (70),
67 (100), 56 (43%).
12.11 (s, 1H, NH); EIMS: m/z 358 (M , 11), 344 (3), 328 (8), 313
(16), 297 (6), 284 (21), 268 (12), 192 (23), 166 (17), 136 (11),
120 (24), 102 (21), 91 (70), 67 (100), 56 (43%).
Anal. Calcd. for C H BrN O: C, 62.44; H, 5.61; N, 26.01.
14 15
5
Anal. Calcd. for C H N O : C, 60.32; H, 6.19; N, 15.63.
Found: C, 62.44; H, 5.62; N, 26.00.
18 22
4 4
Found: C, 60.37; H, 6.18; N, 15.63.
5-(4-Pyridinyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (31) [33].
5-(2-Ethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (35).
This compound was obtained as pale yellow crystals; Yield:
Scheme 4 (75%); Scheme 5 (99%); cumulative (87%); mp 221.5-
The structure of the compound 35 was determined by the spec-
troscopic analysis and was found in agreement with the reported
literature values [25a,25b].
222.5 °C; R = 0.50 (CH Cl ); ir. (potassium bromide): ν
3309
f
2
2
max
-1 1
(N-H), 2939, 2866 (C-H), 1703 (C=O), 1238 (C-N) cm ; H nmr
(CDCl , 400 MHz): δ 0.97 (t, J = 7.0 Hz, 3H, CH -CH -CH ),
3
2
2
3
Acknowledgement.
1.80 (m, 2H, CH -CH -CH ), 3.07 (dd, J = 7.8 Hz, J = 7.2 Hz, 2H,
2
2
3
CH -CH -CH ), 4.21 (s, 3H, N1-CH ), 8.13 (d, 2H, J = 7.3 Hz, H-
The authors gratefully acknowledge for the financial supports
of the Pakistan Telecommunication Limited (PTCL) under
“Research Grant Program” and Higher Education Commission
(HEC) Pakistan under “Research Grants Program for
Universities”.
2
2
3
3
2'/H-6'), 8.91 (d, 2H, J = 7.3 Hz, H-3'/H-5'), 12.15 (s, 1H, NH);
+
EIMS: m/z 269 (M , 20), 254 (6), 191 (23), 176 (4), 166 (17), 136
(11), 120 (24), 102 (21), 91 (70), 67 (100), 56 (43%).
Anal. Calcd. for C H BrN O: C, 62.44; H, 5.61; N, 26.01.
14 15
5
Found: C, 62.40; H, 5.59; N, 26.01.
REFERENCES AND NOTES
5-(4-Hydroxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (32).
[1] R. Gedye, F. Smith, K. Westaway, H. Ali and L. Baldisera,
Tetrahedron Lett., 27, 279 (1986).
[2] R. N. Gedye, F. E. Smith and K. C. Westaway, Can. J. Chem.,
66, 17 (1987).
[3] P. LindstrÖm, J. Tierney, B. Wathey and J. Westman,
Tetrahedron, 57, 9225 (2001).
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This compound was obtained as white powder; Yield: Scheme
4 (72%) Scheme 5 (99%); cumulative (86%); mp 207.5-208.5
°C; R = 0.49 (CH Cl ); ir. (potassium bromide): ν 3300 (N-
f
2
2
max
-1
1
H, OH), 2930, 2870 (C-H), 1700 (C=O), 1240 (C-N) cm ; H
nmr (CDCl , 400 MHz): δ 0.99 (t, J = 7.1 Hz, 3H, CH -CH -
3
2
2
CH ), 1.83 (m, 2H, CH -CH -CH ), 3.03 (dd, J = 7.8 Hz, J = 7.3
3
2
2
3
Hz, 2H, CH -CH -CH ), 4.20 (s, 3H, N1-CH ), 6.97 (d, 2H, J =
2
2
3
3
8.4 Hz, H-3'/5'), 7.21 (d, 2H, J = 8.4 Hz, H-2'/6'), 11.99 (s, 1H,
+
NH); EIMS: m/z 284 (M , 15), 270 (6), 267 (12), 192 (28), 166
(19), 136 (15), 120 (29), 102 (21), 91 (70), 67 (100), 56 (48%).
Anal. Calcd. for C H N O : C, 63.73; H, 5.67; N, 19.71.
15 16
4 2
Found: C, 63.68; H, 5.68; N, 19.71.
5-(4-Methoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyra-
zolo[4,3-d]pyrimidin-7-one (33).
This compound was obtained as an off-white powder; Yield:
scheme 4 (70%); Scheme 5 (99%); cumulative (85%); mp 199-
200 °C; R = 0.47 (CH Cl :AcOEt, 9:1); ir. (potassium bromide):
f
2
2
ν
3300 (N-H), 2930, 2870 (C-H), 1700 (C=O), 1240 (C-N)
max
-1 1
cm ; H nmr (CDCl , 400 MHz): δ 1.02 (t, J = 7.4 Hz, 3H, CH -
3
2
CH -CH ), 1.81 (m, 2H, CH -CH -CH ), 3.07 (dd, J = 7.6 Hz, J
2
3
2
2
3
= 7.1 Hz, 2H, CH -CH -CH ), 3.57 (s, 3H, OCH ), 4.21 (s, 3H,
2
2
3
3
N1-CH ), 6.68 (d, 2H, J = 8.9 Hz, H-3'/5'), 7.70 (d, 2H, J = 8.9
3
+
Hz, H-2'/6'), 12.03 (s, 1H, NH); EIMS: m/z 298 (M , 20), 284 (7),
268 (11), 191 (23), 166 (17), 136 (11), 120 (24), 102 (21), 91
(70), 67 (100), 56 (43%).
Anal. Calcd. for C H N O : C, 64.41; H, 6.08; N, 18.78.
16 18
4 2
Found: C, 64.37; H, 6.06; N, 18.77.
5-(3,4,5-Trimethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-
pyrazolo[4,3-d]-pyrimidin-7-one (34).
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4 (68%) Scheme 5 (98%); cumulative (83%); mp 190.5-191.5
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