Synthesis of pyrazolo-annelated heterocyclic ring compounds such as pyrazolo[3,4-b]pyridines and pyrazolo[4′,3′:5,6]-pyrido[2,3-d] pyrimidines

Article abstract of DOI:10.1002/jhet.5570440210

(Chemical Equation Presented) A series of pyrazolo[3,4-b]pyridines has been synthesized by Friedlaender condensation of 5-amino-pyrazole-4-carbaldehyde 1 with active methylene compounds in basic medium. Pyrazolo[4′3′:5, 6]pyrido-[2,3-d]pyrimidines have be

Full text of DOI:10.1002/jhet.5570440210

Mar-Apr 2007
343
Synthesis of Pyrazolo-Annelated Heterocyclic Ring Compounds
Such As Pyrazolo[3,4-b]pyridines and Pyrazolo[4',3':5,6]-
pyrido[2,3-d]pyrimidines
Madhukar N. Jachak* [1], Appasaheb B. Avhale [1], Ragunath B. Toche [1],
Ram W. Sabnis [2]
[1] Post Graduate Department of Chemistry, K. R. T. Arts, B. H. Commerce and A. M. Science College,
Gangapur Road, Nashik-422 002, India.
[2] Ascadia Inc, 3947 Thames Avenue Eagan, MN 55123, USA
Received May 21, 2006
R
R
R
X
N
R3
R4
CHO
NH2
R1
R2
N
N
N
N
N
N
N
N
N
A series of pyrazolo[3,4-b]pyridines has been synthesized by Friedländer condensation of 5-amino-
pyrazole-4-carbaldehyde 1 with active methylene compounds in basic medium. Pyrazolo[4'3':5,6]pyrido-
[2,3-d]pyrimidines have been synthesized from pyrazolo[3,4-b]pyridines using substituted urea and acetic
anhydride.
J. Heterocyclic Chem., 44, 343 (2007).
Pyrazolo-annelated heterocycles have demonstrated
eluent. Structures of 3a and 4a were confirmed by 1H nmr
which indicated that 3a showed two methoxy singlets at
3.79 and 3.89 ppm together with singlet of methylene at
4.48 ppm, whereas 4a showed one methyl singlet at 3.01
ppm due to the decarboxylation of CO2CH3 group at
position 6. All other signals of aromatic protons are nearly
identical. Similarly, the structures of bromo derivatives 3b
and 4b were confirmed.
Cyclocondensation of compound 1 with methylene
active nitriles such as phenylacetonitrile was carried out
using strong base such as sodium ethoxide in ethanol to
furnish 3-(4-halophenyl)-1,5-diphenyl-1H-pyrazolo[3,4-
b]pyridin-6-amine derivatives 5, (Scheme 1) while
piperidine was used as base for the condensation with
malononitrile and cyanoacetamide in ethanol which gave
6-amino-3-(4-halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitrile derivatives 6, and 6-amino-3-(4-
halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbox-
amide derivatives 7, respectively (Scheme 2). Various
synthetic methodologies using ortho-aminocarbonitriles
and ortho-aminocarboxamides as starting materials for the
synthesis of pendant and fused heterocycles have been
extensively studied [13-22], which prompted us to
evaluate the synthetic utility of compounds 6 and
compound 7 for the design and synthesis of novel fused
heterocycles.
wide spectrum of agriculture and pharmacological
activities [1,2]. We have extensively studied two major
classes of pyrazolo-annelated heterocycles which include
pyrazolo[3,4-b]pyridines and pyrazolo[4',3':5,6]pyrido-
[2,3-d]pyrimidines.
Pyrazolo[3,4-b]pyridines
are
promising candidates in organic synthesis due to their
significant medicinal activities, such as diagnosis of brain
disorders [3], treatment of coronary heart disease [4], viral
diseases [5], central nervous system diseases [6] and show
pharmacological efficacy [7]. Pyrazolopyridopyrimidines
showed
wide spectrum applications such
as
anticonvulsant agents [8], colorants [9], spectrochemical
absorption agents [9], heat/moisture resistant agents [10]
thermal transfer printing agent [10], photographic
couplers [11]. We have recently reported [12] the use of
5-aminopyrazole-4-carbaldehyde 1 as a key component
for the synthesis of fused heterocycles which prompted us
to evaluate its potential applications in the preparation of
various pyrazolo-annelated
heterocycles, namely,
pyrazolo[3,4-b]pyridine and pyrazolopyridopyrimidine
derivatives.
The Friedländer condensation of 5-aminopyrazole-4-
carbaldehyde 1 with propiophenone in refluxing ethanolic
potassium hydroxide solution afforded 3-(4-aryl)-5-
methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine
derivatives 2. Analog condensation of 1 with dimethyl
1,3-acetonedicarboxylate yielded mixtures of compounds
3 and 4. This mixture of compound 3 and 4 was separated
by column chromatography using toluene/hexane as the
Thus, the reaction of compound 6 with N-substituted
ureas at 260-270 °C gave 3-(4-halophenyl)-5-imino-6-
alkyl-1-phenyl-1,5,6,8-tetrahydro-7H-pyrazolo[4',3':5,6]-
pyrido[2,3-d]pyrimidin-7-one derivatives 8. Long range

344
M. N. Jachak, A. B. Avhale, R. B. Toche, R. W. Sabnis
Vol 44
Scheme 1
R
O
N
N
N
N
N
2a-b
R
R
R
COOMe
COOMe
COOMe
COOMe
CHO
NH2
COOMe
O
N
N
N
+
N
N
N
N
3a-b
4a-b
1a-b
R
N
N
N
NH2
1a, 2a, 3a, 4a, 5a: R = Cl; 1b, 2b, 3b, 4b, 5b: R = Br
5a-b
Scheme 2
R
R
NH
CN
HN
R1
CN
N
R1
H2N
O
N
N
N
N
N
N
N
H
O
N
NH2
R
CHO
NH2
8a-f
N
6a-b
N
R
R
CONH2
CONH2
NHCOCH3
CONH2
NH2
O(COCH3)2
N
1a-b
N
N
N
N
N
N
9a-b
7a-b
AcOH
R
O
N
NH
N
N
N
1a, 6a, 7a, 9a, 10a: R = Cl; 1b, 6b, 7b, 91, 10b: R = Br
8a: R = Cl, R1 = H; 8b: R = Cl, R1 = CH3; 8c: R = Cl, R1 = Ph; 8d: R = Br, R1 = H; 8e: R = Br, R1 = CH3; 8f: R = Br, R1 = Ph
10a-b

Mar-Apr 2007
Synthesis of Pyrazolo-Annelated Heterocyclic Ring Compounds
345
collected by filtration then dried. The product showed two
compounds on TLC analysis (Rf values: 0.85 and 0.71 in
toluene). The product was dissolved in acetone and separated by
column chromatography using toluene/cyclohexane 5:100 as an
eluent. The elution volume for (3) was 230-250 ml and for (4)
was 430-450 ml. The TLC analysis showed pure products.
Methyl-3-(4-chlorophenyl)-6-(2-methoxy-2-oxoethyl)-1-
phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (3a). This
compound was obtained as colorless prisms (ethyl acetate), 0.22
g (26%), mp 146-147°C; ir (potassium bromide): 1738, 1715,
coupling observed between imino and N-methyl or N-
benzyl substituted compounds . Reaction of compound 7
with acetic anhydride in acetic acid within 15 minute
furnished open chain compound 6-(acetylamino)-3-(4-
halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-car-
boxamide derivatives 9, which was cyclized using acetic
acid to 3-(4-halophenyl)-7-methyl-1-phenyl-1,6-dihydro-
5H-pyrazolo[4',3':5,6]-pyrido[2,3-d]pyrimidin-5-one
derivatives 10 (Scheme 2).
1
1595, 1556 cm-1; H nmr (CDCl3): δ 3.79 (s, 3H, OCH3), 4.00
(s, 3H, OCH3), 4.48 (s, 2H, CH2), 7.29-7.41 (m, 5H, Ph-H), 8.02
(d, J = 8.4 Hz, 2H, ArH), , 8.38 (d, J = 8.4 Hz, 2H, ArH), 9.08
(s, 1H, Ar-H). Anal. Calcd. for C23H18ClN3O4: C, 63.38; H, 4.16;
N, 9.64. Found: C, 63.51; H, 4.34; N, 9.86.
Methyl-3-(4-bromophenyl)-6-(2-methoxy-2-oxoethyl)-1-
phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (3b). This
compound was obtained as colorless prisms (ethyl acetate), 0.24
g (25%), mp 158-159°C; ir (potassium bromide): 1742, 1720,
1592, 1554 cm-1; 1H nmr (CDCl3): δ 3.78 (s, 3H, OCH3), 4.01 (s,
3H, OCH3), 4.49 (s, 2H, CH2), 7.30-7.63 (m, 5H, Ph-H), 8.03 (d,
J = 8.4 Hz, 2H, ArH), 8.39 (d, J = 8.4 Hz, 2H, ArH), 9.10 (s, 1H,
Ar-H). Anal. Calcd. for C23H18BrN3O4: C, 57.51; H, 3.78; N,
8.75. Found: C, 57.63; H, 3.94; N, 8.87.
EXPERIMENTAL
Melting points were determined on a Gallenkamp melting
point apparatus and are uncorrected. IR spectra were recorded as
KBr pellets on a Schimadzu IR-408 and Shimadzu FTIR
1
spectrophotometer. H NMR spectra were recorded on a Varian
XL-300 (300 MHz) spectrometer in DMSO-d6 and CDCl3 using
TMS as an internal standard and chemical shifts are expressed in
δ (ppm) values. Elemental analyses were carried out on Hosli
CH-Analyser and are within ±0.4 of the theoretical percentages.
All reactions were monitored by thin layer chromatography,
carried out on 0.2 mm silica gel 60 F-254 (Merck) plates using
UV light (254 and 366 nm) for detection. Column
chromatography was carried out on silica gel (SD Fine
Chemicals, 60-80 mesh). Common reagent-grade chemicals are
either commercially available and were used without further
purification or prepared by standard literature procedures.
Methyl-3-(4-chlorophenyl)-6-methyl-1-phenyl-1H-pyrazolo-
[3,4-b]pyridine-5-carboxylate (4a). This compound was
obtained as colorless prisms (ethyl acetate), 0.39 g (52%), mp
1
162-163 °C; ir (potassium bromide): 1724, 1593, 1552 cm-1; H
nmr (CDCl3): δ 3.01 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 7.34-7.57
(m, 5H, Ph-H), 7.99 (d, J = 8.4 Hz, 2H, Ar-H), 8.38 (d, J = 8.4
Hz, 2H, Ar-H), 8.93 (s, 1H, Ar-H). Anal. Calcd. for
C21H16ClN3O2: C, 66.76; H, 4.27; N, 11.12. Found: C, 66.92; H,
4.48; N, 11.27.
General procedure for the synthesis of 3-(halophenyl)-5-
methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine (2).
A
mixture of (2 mmol) of (1) in propiophenone (0.38 ml, 2 mmol)
was refluxed under stirring in ethanolic potassium hydroxide
solution (10 ml, 2%) for one hour. Completion of the reaction
was monitored by thin layer chromatography (TLC). The
mixture was then cooled to room temperature, the separated
solid product was collected by suction filtration, washed with
ethanol, dried and recrystallized.
Methyl-3-(4-bromophenyl)-6-methyl-1-phenyl-1H-pyrazolo-
[3,4-b]pyridine-5-carboxylate (4b). This compound was
obtained as colorless prisms (ethyl acetate), 0.43 g (51%), mp
1
174-175 °C; ir (potassium bromide): 1722, 1595, 1556 cm-1; H
nmr (CDCl3): δ 3.02 (s, 3H, CH3), 3.97 (s, 3H, OCH3), 7.38-7.55
(m, 5H, Ph-H), 7.96 (d, J = 8.4 Hz, 2H, Ar-H), 8.39 (d, J = 8.4 Hz,
2H, Ar-H), 8.95 (s, 1H, Ar-H). Anal. Calcd. for C21H16BrN3O2: C,
59.73; H, 3.82; N, 9.95. Found: C, 59.86; H, 3.97; N, 9.82.
General procedure for the synthesis of 3-(Aryl)-1,5-
diphenyl-1H-pyrazolo[3,4-b]pyridin-6-amine (5). A mixture
of (2 mmol) of (1), phenylacetonitrile (0.23 ml, 2 mmol) and
sodium ethoxide (0.2 g) in ethanol (10 ml) was refluxed under
stirring in for one hour. Completion of the reaction was
monitored by thin layer chromatography (TLC). The mixture
was then cooled to room temperature, the separated solid
product was collected by suction filtration, washed with ethanol,
dried and recrystallized.
3-(4-Chlorophenyl)-5-methyl-1,6-diphenyl-1H-pyrazolo-
[3,4-b]pyridine (2a). This compound was obtained as white
prisms (ethyl acetate), 0.65
g (82%), mp 201-202°C; ir
(potassium bromide): 2341, 1598, 1550 cm-1; 1H nmr
(CDCl3): δ 2.53 (s, 3H, CH3), 7.25-7.67 (m, 10H, Ph-H), 8.00 (d,
J = 8.4 Hz, 2H, Ar-H), 8.21 (s, 1H, Ar-H), 8.43 (d, J = 8.4 Hz,
2H, Ar-H). Anal. Calcd. for C25H18ClN3: C, 75.84; H, 4.58; N,
10.61. Found: C, 75.92; H, 4.66; N, 10.83.
3-(4-Bromophenyl)-5-methyl-1,6-diphenyl-1H-pyrazolo-
[3,4-b]pyridine (2b). This compound was obtained as colorless
prisms (ethyl acetate), 0.71
g (81%), mp 210-211°C; ir
(potassium bromide): 2285, 1598, 1550 cm-1; 1H nmr
(CDCl3): δ 2.53 (s, 3H, CH3), 7.46 (m, 5H, Ph-H), 7.65 (m, 5H,
Ph-H), 7.94 (d, J = 8.4 Hz, 2H, Ar-H), 8.21 (s, 1H, Ar-H), 8.43
(d, J = 8.4 Hz, 2H, Ar-H). Anal. Calcd. for C25H18BrN3: C,
68.19; H, 4.12. Found: C, 68.23; H, 4.27.
3-(4-Chlorophenyl)-1,5-diphenyl-1H-pyrazolo[3,4-b]pyrid-
in-6-amine (5a). This compound was obtained as colorless
prisms (ethyl acetate), 0.58
g (74%), mp 205-206°C; ir
(potassium bromide): 3471, 1592, 1552 cm-1; H nmr (CDCl3):
δ 4.98 (bs, 2H, NH2, exchangeable with D2O), 7.29-7.57 (m,
10H, Ph-H), 7.96 (d, J = 8.4 Hz, 2H, Ar-H), 7.98 (s, 1H, Ar-H),
8.35 (d, J = 8.4 Hz, 2H, Ar-H). Anal. Calcd. for C24H17ClN4: C,
72.63; H, 4.32; N, 14.12. Found: C, 72.76; H, 4.56; N, 14.38.
3-(4-Bromophenyl)-1,5-diphenyl-1H-pyrazolo[3,4-b]pyrid-
in-6-amine (5b). This compound was obtained as colorless
1
General procedure for the synthesis of Methyl-3-(4-
halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (3) and (4).
A
mixture of (2 mmole) of (1) in dimethyl 1,3-
acetonedicarboxylate (0.30 ml, 2 mmole) was refluxed under
stirring in ethanolic potassium hydroxide solution (10 ml, 2%)
for one hour. Completion of the reaction was monitored by thin
layer chromatography (TLC). The mixture was then cooled to
room temperature and the separated colorless solid product was
prisms (ethyl acetate), 0.63 g (72%), mp 216-217°C; ir
1
(potassium bromide): 3470, 1595, 1551 cm-1; H nmr (CDCl3):

346
M. N. Jachak, A. B. Avhale, R. B. Toche, R. W. Sabnis
Vol 44
δ 4.96 (bs, 2H, NH2, exchangeable with D2O), 7.29-7.62 (m,
10H, Ph-H), 7.87 (d, J = 8.4 Hz, 2H, Ar-H), 7.94 (s, 1H, Ar-H),
8.31 (d, J = 8.4 Hz, 2H, Ar-H). Anal. Calcd. for C24H17BrN4: C,
65.32; H, 3.88; N, 12.69. Found: C, 65.58; H, 3.97; N, 12.84.
General procedure for the synthesis of 6-Amino-3-
(halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbo-
nitrile (6). A mixture of (2 mmol) of (1) in malononitrile (0.13
g, 2 mmol) was refluxed under stirring in ethanol (10 ml) and
piperidine (0.5 ml) for one hour. Completion of the reaction was
monitored by thin layer chromatography (TLC). The mixture
was then cooled to room temperature, the separated solid
product was collected by suction filtration, washed with ethanol,
dried and recrystallized.
6-Amino-3-(4-chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitrile (6a). This compound was obtained as
colorless prisms (ethanol:DMF), 0.47 g (68%), mp 201-202 °C;
ir (potassium bromide): 3476, 1592, 1554 cm-1; 1H nmr
(CDCl3): δ 5.42 (bs, 2H, NH2, exchangeable with D2O), 7.33-
7.54 (m, 5H, Ph-H), 7.85 (d, J = 8.4 Hz, 2H, Ar-H), 8.16 (d, J =
8.4 Hz, 2H, Ar-H), 8.38 (s, 1H, Ar-H). Anal. Calcd. for
C19H12ClN5: C, 66.00; H, 3.50; N, 20.25. Found: C, 66.14; H,
3.78; N, 20.56.
olo[4',3':5,6]-pyrido[2,3-d]pyrimidin-7-one (8). A mixture of
(1 mmol) of (6) in substituted urea (2 mmol) was heated at 250-
260°C for 30 minutes. Completion of the reaction was
monitored by thin layer chromatography (TLC). The mixture
was then cooled to room temperature, the separated solid
product was suction filtered, washed with ethanol, dried and
recrystallized.
3-(4-Chlorophenyl)-5-imino-6-methyl-1-phenyl-1,5,6,8-
tetrahydro-7H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-7-
one (8a). This compound was obtained as yellow prisms
(DMF), 0.514 g (64%), mp < 300 °C dec.; ir (potassium
bromide): 3338, 3219, 1631, 1502 cm-1; 1H nmr (DMSO-
d6): δ 1.15 (d, J = 20.4 Hz, 3H, CH3), 7.35-7.66 (m, 5H, Ph-H),
8.11 (d, J = 8.4 Hz, 2H, Ar-H), 8.31 (d, J = 8.4 Hz, 2H, Ar-H),
8.75 (d, J = 3.6 Hz, 1H, NH), 9.23 (s, 1H, Ar-H), 11.28 (bs, 1H,
NH). Anal. Calcd. for C21H15ClN6O: C, 62.61; H, 3.75; N, 20.86.
Found: C, 62.81; H, 3.89; N, 20.98.
3-(4-Chlorophenyl)-6-ethyl-5-imino-1-phenyl-1,5,6,8-tetra-
hydro-7H-pyrazolo[4',3':5,6]-pyrido[2,3-d]pyrimidin-7-one
(8b). This compound was obtained as yellow prisms (DMF),
0.27 g (65%) mp < 300 °C dec.; ir (potassium bromide): 3338,
1
3220, 1602, 1550 cm-1; H nmr (DMSO-d6): δ 1.06 (t, J = 7.2
6-Amino-3-(4-bromophenyl)-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine-5-carbonitrile (6b). This compound was obtained as
colorless prisms (ethanol:DMF), 0.51 g (66%) mp 258-259°C; ir
(potassium bromide): 3473, 1593, 1552 cm-1; 1H nmr
(CDCl3): δ 5.42 (bs, 2H, NH2, exchangeable with D2O), 7.33-
7.67 (m, 5H, Ph-H), 7.79 (d, J = 8.4 Hz, 2H, Ar-H), 8.16 (d, J =
8.4 Hz, 2H, Ar-H), 8.38 (s, 1H, Ar-H). Anal. Calcd. for
C19H12BrN5: C, 58.48; H, 3.10; N, 17.95. Found: C, 58.24; H,
3.34; N, 18.12.
Hz, 3H, CH3), 3.92 (q, J = 7.2 Hz, 2H, CH2), 7.18-7.45 (m, 5H,
Ph-H), 7.92 (d, J = 8.4 Hz, 2H, Ar-H), 8.13 (d, J = 8.4 Hz, 2H,
Ar-H), 8.55 (s, 1H, NH), 9.06 (s, 1H, Ar-H), 11.10 (bs, 1H, NH).
Anal. Calcd. for C22H17ClN6O: C, 63.38; H, 4.11; N, 20.16.
Found: C, 63.54; H, 4.32; N, 20.38.
6-Benzyl-3-(4-chlorophenyl)-5-imino-1-phenyl-1,5,6,8-
tetrahydro-7H-pyrazolo[4',3':5,6]pyrido [2,3-d]pyrimidin-7-
one (8c). This compound was obtained as yellow prisms (DMF),
0.31 g (65%) mp < 300 °C dec.; ir (potassium bromide): 3352,
1
General procedure for the synthesis of 6-Amino-3-
(halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbox-
amide (7). A mixture of (2 mmol) of (1) in cyanoacetamide (0.1
g, 2 mmol) was refluxed under stirring in ethanol (10 ml) and
piperidine (0.5 ml) for one hour. Completion of the reaction was
monitored by thin layer chromatography (TLC). The mixture
was then cooled to room temperature, the separated solid
product was collected by suction filtration, washed with ethanol,
dried and recrystallized.
3227, 1614, 1556 cm-1; H nmr (DMSO-d6): δ 4.83 (d, J = 4.8
Hz, 2H, CH2), 7.20-7.36 (m, 5H, Ph-H), 7.47-7.52 (m, 5H, Ph-
H), 8.08 (d, J = 8.4 Hz, 2H, Ar-H), 8.31 (d, J = 8.4 Hz, 2H, Ar-
H), 9.11 (d, J = 0.6 Hz, 1H, NH), 9.35 (s, 1H, Ar-H), 11.16 (bs,
1H, NH). Anal. Calcd. for C27H19ClN6O: C, 67.71; H, 4.00; N,
17.54. Found: C, 67.86; H, 4.29; N, 17.82.
3-(4-Bromophenyl)-5-imino-6-methyl-1-phenyl-1,5,6,8-
tetrahydro-7H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-7-
one (8d). This compound was obtained as yellow prisms
(DMF), 0.28 g (62%) mp < 300 °C dec.; ir (potassium bromide):
3338, 3219, 1631, 1502 cm-1; 1H nmr (DMSO-d6): δ 1.17 (d, J =
20.4 Hz, 3H, CH3), 7.34-7.83 (m, 5H, Ph-H), 8.11 (d, J = 8.4 Hz,
2H, Ar-H), 8.25 (d, J = 8.4 Hz, 2H, Ar-H), 8.78 (d, J = 3.6 Hz,
1H, NH), 9.28 (s, 1H, Ar-H), 11.31 (bs, 1H, NH). Anal. Calcd.
for C21H15BrN6O: C, 56.39; H, 3.38; N, 18.79. Found: C, 56.61;
H, 3.58; N, 18.93.
6-Amino-3-(4-chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine-5-carboxamide (7a). This compound was obtained as
colorless prisms (ethanol:DMF), 0.50 g (69%), mp 250-251°C;
ir (potassium bromide): 3473, 3417, 3354, 3305, 1592, 1556
1
cm-1; H nmr (DMSO-d6): δ 6.76 (bs, 1H, NH), 7.17 (t, J = 7.8
Hz, 1H, Ph-H), 7.28 (bs, 1H, NH), 7.36 (m, 4H, Ar-H), 7.72 (bs,
1H, NH), 8.02 (d, J = 8.4 Hz, 2H, Ar-H), 8.12 (bs, 1H, NH),
8.22 (d, J = 8.4 Hz, 1H, Ar-H), 8.63 (s, 1H, Ar-H). Anal. Calcd.
for C19H14ClN5O: C, 62.73; H, 3.88; N, 19.25. Found: C, 62.95;
H, 4.17; N, 19.56.
3-(4-Bromophenyl)-6-ethyl-5-imino-1-phenyl-1,5,6,8-tetra-
hydro-7H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-7-one
(8e). This compound was obtained as yellow prisms (DMF),
0.29 g (63%) mp < 300 °C dec.; ir (potassium bromide): 3338,
6-Amino-3-(4-bromophenyl)-1-phenyl-1H-pyrazolo[3,4-b]-
pyridine-5-carboxamide (7b). This compound was obtained as
colorless prisms (ethanol:DMF), 0.55 g (67%) mp 270-271 °C;
ir (potassium bromide): 3417, 3419, 3315, 3363, 1594, 1554
1
3220, 1602, 1550 cm-1; H nmr (DMSO-d6): δ 1.14 (t, J = 7.2
Hz, 3H, CH3), 3.96 (q, J = 7.2 Hz, 2H, CH2), 7.33-7.73 (m, 5H,
Ph-H), 8.01 (d, J = 8.4 Hz, 2H, Ar-H), 8.23 (d, J = 8.4 Hz, 2H,
Ar-H), 8.76 (s, 1H, NH), 9.33 (s, 1H, Ar-H), 11.29 (bs, 1H, NH).
Anal. Calcd. for C22H17BrN6O: C, 57.28; H, 3.71; N, 18.22.
Found: C, 57.52; H, 3.94; N, 18.37.
1
cm-1; H nmr (DMSO-d6): δ 6.76 (bs, 1H, NH), 7.17 (t, J = 7.8
Hz, 1H, Ph-H), 7.28 (bs, 1H, NH), 7.36 (m, 4H, Ar-H), 7.72 (bs,
1H, NH), 8.02 (d, J = 8.4 Hz, 2H, Ar-H), 8.12 (bs, 1H, NH),
8.22 (d, J = 8.4 Hz, 2H, Ar-H), 8.63 (s, 1H, Ar-H). Anal. Calcd.
for C19H14BrN5O: C, 55.90; H, 3.46; N, 17.15. Found: C, 56.08;
H, 3.64; N, 17.34.
6-Benzyl-3-(4-bromophenyl)-5-imino-1-phenyl-1,5,6,8-
tetrahydro-7H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-7-
one (8f). This compound was obtained as yellow prisms (DMF),
0.34 g (65%) mp < 300 °C dec.; ir (potassium bromide): 3352,
General procedure for the synthesis of 3-(4-halophenyl)-5-
imino-6-(alkyl/aryl)-1-phenyl-1,5,6,8-tetrahydro-7H-pyraz-
1
3227, 1614, 1556 cm-1; H nmr (DMSO-d6): δ 4.80 (d, J = 4.8

Mar-Apr 2007
Synthesis of Pyrazolo-Annelated Heterocyclic Ring Compounds
347
Hz, 2H, CH2), 7.28-7.41 (m, 5H, Ph-H), 7.56-7.81 (m, P5H, h-
H), 8.08 (d, J = 8.4 Hz, 2H, Ar-H), 8.34 (d, J = 8.4 Hz, 2H, Ar-
H), 9.29 (d, J = 0.6 Hz, 1H, NH), 9.39 (s, 1H, Ar-H), 11.39 (bs,
1H, NH). Anal. Calcd. for C27H19BrN6O: C, 61.96; H, 3.66; N,
16.06. Found: C, 62.14; H, 3.87; N, 16.28.
General procedure for the synthesis of 6-Acetylamino-3-
(halophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbox-
amide (9). A mixture of (1 mmol) of (7) in acetic anhydride
(1.5 ml) and acetic acid (1.5 ml) was refluxed under stirring
for 15 minutes. Completion of the reaction was monitored by
thin layer chromatography (TLC). The mixture was then
cooled to room temperature, the separated solid product was
collected by suction filtration, washed with ethanol, dried and
recrystallized.
7.59 (m, 5H, Ph-H), 8.07 (d, J = 8.4 Hz, 2H, Ar-H), 8.37 (d, J =
7.8 Hz, 2H, Ar-H), 9.21 (s, 1H, Ar-H), 12.58 (bs, 1H, NH).
Anal. Calcd. for C21H14BrN5O: C, 58.35; H, 3.26; N, 16.20.
Found: C, 58.61; H, 3.49; N, 16.42.
Acknowledgement. The authors thanks to the University Grants
Commission for financial support and Principal, K. T. H. M.
College, Nashik, India.
REFERENCES AND NOTES
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6-Acetylamino-3-(4-chlorophenyl)-1-phenyl-1H-pyrazolo-
[3,4-b]pyridine-5-carboxamide (9a). This compound was
obtained as colorless prisms (ethanol:DMF), 0.35 g (86%) mp
228-229 °C; ir (potassium bromide): 3361, 3253, 3203, 1645,
1
1606 cm-1; H nmr (DMSO-d6): δ 2.41 (s, 3H, CH3), 7.28-7.52
(m, 5H, Ph-H), 7.93 (bs, 1H, NH), 8.16 (d, J = 8.4 Hz, 2H, Ar-
H), 8.36 (d, J = 7.8 Hz, 2H, Ar-H), 8.62 (bs, 1H, NH), 8.98 (s,
1H, Ar-H), 12.14 (bs, 1H, NH). Anal. Calcd. for C21H16ClN5O2:
C, 62.15; H, 3.97; N, 17.26. Found: C, 62.33; H, 4.21; N, 17.54.
6-(Acetylamino)-3-(4-bromophenyl)-1-phenyl-1H-pyrazolo-
[3,4-b]pyridine-5-carboxamide (9b). This compound was
obtained as white prisms (ethanol:DMF), 0.37 g (84%) mp 237-
238 °C; ir (potassium bromide): 3327, 3166, 1674, 1593 cm-1;
1H nmr (DMSO-d6): δ 2.39 (s, 3H, CH3), 7.34-7.60 (m, 5H, Ph-
H), 7.92 (bs, 1H, NH), 8.11 (d, J = 8.4 Hz, 2H, Ar-H), 8.28 (d, J
= 7.8 Hz, 2H, Ar-H), 8.61 (bs, 1H, NH), 8.97 (s, 1H, Ar-H),
11.91 (bs, 1H, NH). Anal. Calcd. for C21H16BrN5O2: C, 56.01; H,
3.58; N, 15.55. Found: C, 56.28; H, 3.76; N, 15.76.
General procedure for the synthesis of 3-(4-halophenyl)-7-
methyl-1-phenyl-1,6-dihydro-5H-pyrazolo[4',3':5,6]pyrido-
[2,3-d]pyrimidin-5-one (10). A mixture of (1 mmol) of (9) in
acetic acid (5 ml) was refluxed under stirring for 7 hours.
Completion of the reaction was monitored by thin layer
chromatography (TLC). The mixture was then cooled to room
temperature, the separated solid product was collected by
suction filtration, washed with ethanol, dried and recrystallized.
3-(4-Chlorophenyl)-7-methyl-1-phenyl-1,6-dihydro-5H-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-5-one (10a). This
compound was obtained as colorless prisms (DMF), 0.28 g
(74%), mp < 300 °C dec.; ir (potassium bromide): 3325, 3170,
[12] M. Jachak, A. Avhale, C. Tantak, R. Toche, C. Reidlinger
and W. Stadlbauer, J. Heterocyclic Chem., 42, 1311 (2005).
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(1980).
[14] Y. Imai, S. Sato, R. Takasawa and M. Ueda, Synthesis, 35
(1981).
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11, 474 (1995).
1
1674, 1593 cm-1; H nmr (DMSO-d6): δ 2.46 (s, 3H, CH3), 7.36-
[19] Y. Mohamed, M. Zahran, M. Ali, A. El-Agrody and U. El-
Said, J. Chem. Res. Synopsis, 8, 322 (1995).
[20] G. Singh, A. Yadav and A. Mishra A, Indian J. Chem., 41B,
430 (2002).
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1208 (1996); V. Ahluwalia and his coworkers have done similar type of
reactions on different Pyrazoles.
[22] V. Ahluwalia, B. Goyal, Synth. Comm., 26, 1341 (1996); V.
Ahluwalia and his coworkers have done similar type of reactions on
different Pyrazoles.
7.62 (m, 5H, Ph-H), 8.12 (d, J = 8.4 Hz, 2H, Ar-H), 8.36 (d, J =
7.8 Hz, 2H, Ar-H), 9.19 (s, 1H, Ar-H), 12.57 (bs, 1H, NH).
Anal. Calcd. for C21H14ClN5O: C, 65.04; H, 3.64; N, 18.06.
Found: C, 65.26; H, 3.81; N, 18.34.
3-(4-Bromophenyl)-7-methyl-1-phenyl-1,6-dihydro-5H-
pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidin-5-one (10b). This
compound was obtained as colorless prisms (DMF) 0.31 g
(72%) mp < 300 °C dec.; ir (potassium bromide): 3326, 3173,
1
1672, 1596 cm-1; H nmr (DMSO-d6): δ 2.47 (s, 3H, CH3), 7.36-