Synthesis and characterization of some important indazolyl derivatives

Article abstract of DOI:10.1002/jhet.5570440203

(Chemical Equation Presented) A series of some important indazolyl derivatives of pyrazoles, diazepines, thiopyrimidines, thiazines and chromones were synthesized and characterized with the help of spectral data. Some of the synthesized compounds are test

Full text of DOI:10.1002/jhet.5570440203

Synthesis and Characterization of Some Important Indazolyl Derivatives.
Mar-Apr 2007
289
*
S. B. Kale and B. K. Karale
P. G. Dept. of Chemistry, S. S. G. M. College, Kopargaon, Ahmednagar-423601.India
E-Mail:bkkarale@yahoo.com
Received February 27, 2006
A series of some important indazolyl derivatives of pyrazoles, diazepines, thiopyrimidines, thiazines and
chromones were synthesized and characterized with the help of spectral data. Some of the synthesized com-
pounds are tested for antimicrobial and antioxidant activities.
J. Heterocyclic Chem., 44, 289 (2007).
INTRODUCTION
atives are associated with anti-inflammatory, oral male
contraceptive and antimicrobial activities [13-16].
Chromones having heterocyclic substituents at the 2-
position have been reported to possess antitumor, antibac-
terial and antifungal activities and also to exhibit good
phosphodiesterase IV inhibition activity and some
flavones have potential HIV-integrase inhibition activity
[17-20, 39].
Pyrazole and variously substituted pyrazoles exhibit a
wide range of biological activities like antiviral, antipyretic,
antioxidant, antivassive, antidepressant, anti-inflammatory
and blood pressure lowering. Pyrazoles are also used as
agrochemicals, dyestuff and sunscreen materials [21-24].
Benzodiazepines are an important class of psychothera-
peutic compounds. In recent years some examples of hete-
rocyclic rings fused to the seven member diazepine ring
system have been synthesized which exhibit psychotropic
activities [25-31,40].
Nature contains widespread molecules with het-
eroatom rings. It is known that a number of heterocyclic
compounds like chromones, pyrazoles, diazepines,
thiopyrimidines and thiazines possess important biologi-
cal activities.
According to the literature survey, indazole com-
pounds are associated with various physiological and
biological properties and thus, find important use in
medicine. Indazole compounds are capable of mediating
tyrosine kinase signal transduction and thereby inhibit
unwanted cell proliferation [1-2]. Indazole derivatives
are examined for analgesic and anti-inflammatory activ-
ities [3]. A ruthenium coordination complex (RuInd) is
one of the most effective anticancer [4] ruthenium com-
pounds; poisoning [5] of Topoisomerase II by indazole
complex was analyzed. Indazole ring was used as the
initial template to test the hypothesis in order to
increase potency as Leukotriene receptor antagonists
[6-8]. Indazole containing inhibitor series for
SAH/MTA nucleosidase are inhibitors with broad spec-
trum antimicrobial activity [9]. Indazole derivatives are
used as anti-inflammatory agents, anticancer [10-11]
agents and also used as sunscreens [12]. Indazole deriv-
Benzothiazines constitute an important class of hetero-
cyclic compounds which possess a wide spectrum of phar-
macological and biological activities. Thiazines also show
antimalarial, antitubercular, anti-inflammatory, antibacter-
ial and antifungal activities [32-34].
Pyrimidine and its derivatives have been studied for its
pharmacological properties. Thiopyrimidines and its

290
S. B. Kale and B. K. Karale
Vol. 44
derivatives have antibacterial activity and also act as anti-
infective agents [20,35-38].
Compounds 4 on treatment with o-phenylene diamine in
presence of acetic acid yielded 2-[4-(1-isopropyl-1H-inda-
zol-3-yl)-3H-benzo[b][1,4]diazepin-2-yl]-phenols 7.
Compound 4 on reaction with ortho-aminothiophenol in
DMSO gave [2-(2-hydroxy-phenyl)-4H-benzo[1,4]thiazin-
3-yl]-(1-isopropyl-1H-indazol-3-yl)-methanones 8.
Owing to the biological importance of chromones, pyra-
zoles, indazoles, diazepines, thiopyrimidines, thiazines
and in continuation of our work to synthesize biologically
important heterocyclic compounds we report herein the
synthesis of some chromones, diazepines, thiopyrimidines,
thiazines, pyrazoles containing indazole moiety.
The structures of compounds 6, 7 and 8 are confirmed
1
1
by spectral techniques (ms, ir and H nmr). The H nmr
spectra of compounds 6 shows disappearance of the signal
at 10.71 δ and 11.2 δ as they are used in cyclization, a new
signal at 2.5 δ appears due to C-2 methyl group and also
confirmed by their ir and mass spectra. The ir spectra of
RESULTS AND DISCUSSION
In the present work 2-hydroxy acetophenones 1 were
treated with 1-isopropyl indazole 3-carboxylic acid 2 in the
presence of phosphorous oxychloride and pyridine to yield
the corresponding 2-acetyl-phenyl-1-isopropyl-1H-inda-
zole-3-carboxylate 3. Compound 3 on treatment with
potassium hydroxide in the presence of pyridine gave 1-(2-
hydroxyphenyl)-3-(1-isopropyl-1H-indazol-3-yl)-
propane-1,3-dione 4. Compound 4 on treatment with
Conc. HCl undergoes cyclization and afforded 2-(1-iso-
propyl-1H-indazol-3-yl)-chromon-4-one 5.
-
compounds 7 shows disappearance of the band at 1620 cm
1
-1
due to –C=O group and bands at 1595 and 1540 cm
1
appears due to C=N bond. H nmr shows the disappear-
ance of enolic proton signals and the structures are also
confirmed by mass spectra. Structures of compounds 8
were confirmed by ir spectra which shows a broad band at
3316 cm due to –N-H and –OH functionality and at 1644
cm due to –C=O group. Structures of compounds 8 are
-1
-1
1
The structures of compounds 3, 4 and 5 are confirmed
also confirmed by H nmr and mass spectra.
1
by spectral techniques (ms, ir, H nmr). The ir absorption
Compounds 5 on treatment with hydrazine hydrate
undergoes γ-pyrone ring opening followed by cyclization
-1
spectra (cm ) of compounds 3 show a strong absorption
1
band at 1728 for O-C=O group and H nmr spectra show a
to yield 2-[5-(1-isopropyl-1H-indazol-3-yl)-2H-pyrazol-3-
yl]-phenol 9. Compounds 5 on reaction with thiourea
undergo 1,4 addition followed by γ-pyrone ring opening
and subsequently undergoes cyclization to yield the
compounds 10.
sharp singlet at around 2.5 δ for -CO-CH . The ir spectra
of compounds 4 show a strong and characteristic band for
1,3 diketone linkage at 1620-1599 cm . The H nmr of
compound 4 shows disappearance of singlet at around 2.5
δ and also shows a singlet at 10.76 δ and 11.26 δ due to
phenolic and enolic protons of 1,3 diketone. The forma-
3
-1
1
The structures of compounds 9 are confirmed by spec-
1
tral techniques (ms, ir and H nmr). In their ir spectra, the
1
-1
tions of compounds 5 are confirmed by H nmr as it shows
band at 1643 cm due to –C=O group are not observed
-1
the disappearance of the signal at 10.76 δ and 11.2 δ due to
–OH protons as they are used in cyclization. The structures
of 3, 4 and 5 are confirmed by mass spectra.
Compounds 4 on reaction with acetic anhydride in pres-
ence of sodium acetate affords 3-(1-isopropyl-1H-inda-
zole-3-carbonyl)-2-methyl-chromon-4-ones 6.
and a new bands at 3160 cm due to the –OH group are
1
observed. The H nmr spectra show a signal at 10.9 δ due
to –OH proton. Structures are also confirmed by mass
spectra. The structures of compounds 10 are also
confirmed by ir spectra in which a new band due to –OH
-1
and -NH functionality are observed at 3250 and 3180 cm .

Mar-Apr 2007
Synthesis and Characterization of Some Important Indazolyl Derivatives
291
In addition to this, the ir spectra of 10 shows a band due to
Antimicrobial activity. The in vitro antimicrobial activ-
ity of the test compounds were assessed against 24 hr cul-
tures of several selected bacteria and fungi. The bacteria
used were Escherichia coli, Staphylococcus aureus and
-1
1
–C=S group in the region 1210-1270 cm . The H nmr
spectra show singlets at 13.4 δ and 8.06 δ due to –OH and
–NH functionality.
Table 1
Compd. Yield
Substitution
Compd. Yield
M.P.
M.P.
Compd. Yield
M.P
R
R
R
3
No.
(%)
(0°C)
No.
(%)
(0°C)
No.
(%)
(0°C)
1
2
Cl
H
H
Me
H
H
H
H
H
Cl
H
H
Me
H
H
H
H
H
Cl
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
Me
Me
H
H
H
Cl
Cl
Me
Me
H
Cl
Br
F
3a
3b
3c
3d
3e
3f
3g
3h
3i
6a
6b
6c
6d
6e
6f
6g
6h
6i
9a
9b
9c
9d
9e
9f
9g
9h
9i
65
72
60
64
65
68
70
69
71
79
70
72
71
69
68
72
75
69
75
72
74
69
66
67
71
75
69
104
80
105
139
103
99
87
86
95
212
181
186
215
158
228
184
176
173
234
224
218
222
187
227
209
237
252
4a
4b
4c
4d
4e
4f
4g
4h
4i
7a
7b
7c
7d
7e
7f
7g
7h
7i
10a
10b
10c
10d
10e
10f
10g
10h
10i
80
82
78
83
79
70
75
74
68
89
80
-
-
78
-
70
72
-
67
70
69
85
75
78
83
68
66
146
128
135
196
133
163
146
127
133
219
236
-
5a
5b
5c
5d
5e
5f
5g
5h
5i
8a
8b
8c
8d
8e
8f
8g
8h
8i
-
-
-
-
-
-
-
-
-
74
71
68
76
72
69
70
73
67
68
72
73
70
75
69
74
72
70
-
-
-
-
-
-
-
-
-
178
175
168
200
167
198
174
201
165
157
122
155
195
112
144
119
140
118
-
-
-
-
-
-
-
-
-
H
Cl
Cl
Me
Me
H
Cl
Br
F
-
205
-
241
212
-
251
292
263
196
256
277
273
265
235
H
Cl
Cl
Me
Me
H
Cl
Br
F
Me
H
H
H
H
H
H

292
S. B. Kale and B. K. Karale
Vol. 44
Table 2
Compounds 3a-i
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
1
1
+
C
H
N
3a
1733
1695
1610
1580
754
8.50 to 7.26 (m, 6H), 4.95
(m, 1H), 2.47(s, 3H), 1.45 (d, 6H)
390
(58.35)
58.33
(4.10)
4.12
(7.15)
7.16
3b
1730
1690
1603
1574
753
8.49 to 7.25 (m, 7H), 5.35
(m, 1H), 2.55(s, 3H), 1.65(d, 6H)
356
63.96
(63.95)
4.80
(5.81)
7.85
(7.84)
3c
3d
3e
3f
1728
1685
1605
1577
1725
1680
1601
1571
1724
1683
1603
1576
1725
1688
1600
1578
751
8.11 to 7.31 (m, 7H), 5.25
(m, 1H), 2.50(s, 3H), 2.4(s, 3H),
1.5 (d, 6H)
336
350
336
370
71.41
(71.40)
5.99
(5.97)
8.33
(8.34)
8.28 to 7.25 (m, 6H), 5.25
(m, 1H), 2.5(s, 3H), 2.30(s, 3H),
2.45(s, 3H), 1.55 (d, 6H)
71.98
(71.96)
6.33
(6.32)
7.99
(7.95)
8.21 to 7.15 (m, 7H), 5.22
(m, 1H), 2.55(s, 3H), 2.31(s, 3H),
1.42 (d, 6H)
71.41
(71.39)
5.99
(5.96)
8.33
(8.35)
8.43 to 7.25 (m, 6H), 4.82
(m, 1H), 2.35(s, 3H), 2.25(s, 3H),
1.45 (d, 6H)
64.78
(64.79)
5.16
(5.15)
7.55
(7.56)
3g
3h
3i
1729
1683
1604
1572
680
1732
1693
1615
1579
1050
1720
1678
1600
1574
8.41 to 7.29 (m, 7H), 5.32
(m, 1H), 2.45(s, 3H), 1.60 (d, 6H)
400
340
322
56.87
(56.85)
4.27
(4.28)
6.98
(6.99)
8.51 to 7.26 (m, 7H), 5.35
(m, 1H), 2.57(s, 3H), 1.65 (d, 6H)
67.05
(67.07)
5.03
(5.04)
8.23
(8.22)
7.05 to 8.19 (m, 8H), 5.20
(m, 1H), 2.30(s, 3H), 1.32 (d, 6H)
70.79
(70.80)
5.63
(5.60)
8.69
(8.67)
Streptococcus faecium; the fungi used were Candida albi-
cans, Candida krusei, Candida glabrata and Aspergillus
fumigatus.
The antimicrobial activity was performed by agar diffu-
sion method at 1 mg/ml conc. in DMSO. Nutrient agar and
potato dextrose agar were used to culture the bacteria and
fungi respectively.
against some of the test organisms. Antimicrobial screen-
ing data is given in Table 10 and Table 11.
Antioxidant activity. The antioxidant activity of the
test compounds was determined by DPPH method by
using Trolox as a reference standard. Amongst, the com-
pounds screened for antioxidant activity none of the com-
pounds showed promising activity as shown in Table 12.
Fluconazole, Amphotericin, Vancomycin and Linezolid
were prepared in DMSO and used as standards for com-
parison of antibacterial and antifungal activities respec-
tively. The activity is reported by measuring the diameter
of the inhibition zone in mm.
Amongst, the compounds screened for antimicrobial
activity 4b and 4c have shown activity against almost all
the test organisms. All the compounds are showing activity
EXPERIMENTAL
All the recorded melting points were determined in open capil-
lary tubes and are uncorrected. IR spectra were recorded on
Perkin-Elmer FTIR spectrophotometer in KBr disc. H nmr spec-
tra were recorded on Varian 300 MHz spectrophotometer in
DMSO as a solvent and TMS as an internal standard. Peak values
1

Mar-Apr 2007
Synthesis and Characterization of Some Important Indazolyl Derivatives
293
are shown in δ ppm. Mass spectra were obtained by Finnigan
mass spectrometer.
2-Acetyl-phenyl-1-isopropyl-1H-indazole-3-carboxylates
(3a-i). Equimolar amount (0.01 mole) of acetophenones 1 and 1-
isopropyl-indazole-3-carboxylic acid 2 were dissolved in 10 ml
dry pyridine. Contents were cooled to 0°C in ice bath. To this
reaction mixture (0.01 mole) of phosphorous oxychloride was
added dropwise maintaining the temperature below 5°C. After
complete addition of phosphorous oxychloride the reaction mix-
ture was kept overnight and then poured into crushed ice. The
product obtained was separated by filtration and washed with
cold 1% NaOH solution folowed by water. The product was crys-
Table 3
Compounds 4a-i
Compd. IR
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
H
1
1
+
No.
(cm )
C
N
4a
2975
1613
1590
1530
755
2975
1615
1595
1531
751
11.38(s, 1H), 10.88(s, 1H) 8.38 to
6.90 (m, 6H), 5.26 (m, 1H),
4.98 (s, 1H), 2.70 (d, 6H)
390
356
58.33
(58.30)
4.12
(4.11)
7.16
(7.12)
4b
11.35(s, 1H), 10.85(s, 1H), 8.35 to
6.89 (m, 7H), 5.24 (m, 1H),
4.95 (s, 1H), 2.75 (d, 6H)
63.96
(63.92)
4.80
(4.79)
7.85
(7.87)
4c
4d
4e
4f
2978
1620
1599
1536
2975
1618
1595
1533
2975
1615
1595
1532
2978
1618
1597
1535
752
11.26(s, 1H), 10.71(s, 1H), 8.23 to
6.87 (m, 7H), 5.13 (m, 1H),
4.84 (s, 1H), 3.3 (s, 3H), 2.52 (d, 6H)
336
350
336
370
71.41
(71.39)
5.99
(5.98)
8.33
(8.36)
11.28(s, 1H), 10.75(s, 1H), 8.25 to
6.82 (m, 6H), 5.15 (m, 1H),
4.85 (s, 1H), 3.52 (s, 3H),
2.68 (s, 3H), 2.54 (d, 6H)
11.21(s, 1H), 10.70(s, 1H), 8.19 to
6.80 (m, 7H), 5.10 (m, 1H),
4.92 (s, 1H), 3.32 (s, 3H),
2.55 (d, 6H)
11.23(s, 1H), 10.72(s, 1H), 8.25 to
6.84 (m, 6H), 5.13 (m, 1H),
4.89 (s, 1H), 3.37 (s, 3H),
2.59 (d, 6H)
71.98
(71.99)
6.33
(6.31)
7.99
(7.94)
71.41
(71.36)
5.99
(5.94)
8.33
(8.36)
64.78
(64.73)
5.16
(5.11)
7.55
(7.59)
4g
4h
4i
2987
1631
1606
1539
688
2986
1629
1602
1537
1020
2973
1612
1590
1531
11.37(s, 1H), 10.88(s, 1H), 8.39 to
6.90 (m, 7H), 5.27 (m, 1H),
4.97 (s, 1H), 2.69 (d, 6H)
400
340
322
56.87
(56.89)
4.27
(4.26)
6.98
(6.94)
11.34(s, 1H), 10.84(s, 1H), 8.36 to
6.87 (m, 7H), 5.24 (m, 1H),
4.98 (s, 1H), 2.70 (d, 6H)
67.05
(67.09)
5.03
(5.06)
8.23
(8.20)
11.19(s, 1H), 10.65(s, 1H), 8.16 to
6.77 (m, 8H), 5.06 (m, 1H),
4.89 (s, 1H), 2.47 (d, 6H)
70.79
(70.82)
5.63
(5.59)
8.69
(8.71)
Table 4
Compounds 5a-i
Compd. IR
Spectral Data
H NMR δ (ppm)
Mass Elemental Analysis
1
1
+
No.
(cm )
M
Calcd % (Found %)
C
H
N
5a
1650
1620
1563
1485
8.20 to 7.12 (m, 7H), 4.91
(m, 1H), 1.71 (d, 6H)
372
61.14
(61.09)
3.78
(3.67)
7.51
(7.54)

294
S. B. Kale and B. K. Karale
Vol. 44
Table 4 (Continued)
Compd. IR
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
1
1
+
No.
(cm )
C
H
N
5b
1648
1619
1563
1484
749
8.29 to 7.14 (m, 8H), 4.99
(m, 1H), 1.71 (d, 6H)
338
67.36
(67.32)
4.46
(4.49)
8.27
(8.30)
5c
5d
5e
5f
1633
1603
1545
1474
1635
1607
1551
1475
1640
1610
1554
1477
1643
1613
1557
1480
742
8.20 to 7.11 (m, 8H), 4.91
(m, 1H), 2.13 (s, 3H), 1.59 (d, 6H)
318
332
318
352
75.45
(75.41)
5.70
(5.66)
8.80
(8.77)
8.22 to 7.13 (m, 7H), 4.93
(m, 1H), 2.38 (s, 3H), 2.49 (s, 3H),
1.62 (d, 6H)
75.88
(75.84)
6.06
(6.09)
8.43
(8.39)
8.28 to 7.20 (m, 8H), 4.99
(m, 1H), 2.52 (s, 3H), 1.68 (d, 6H)
75.45
(75.39)
5.70
(5.73)
8.80
(8.87)
8.26 to 7.19 (m, 7H), 4.98
(m, 1H), 2.55 (s, 3H), 1.66 (d, 6H)
68.09
(68.12)
4.86
(4.89)
7.94
(7.88)
5g
5h
5i
1646
1617
1561
1481
686
1647
1619
1560
1479
1022
1648
1617
1561
1483
8.29 to 7.16 (m, 8H), 4.96
(m, 1H), 1.70 (d, 6H)
382
322
304
59.55
(59.51)
3.95
(3.99)
7.31
(7.27)
8.28 to 7.18 (m, 8H), 4.97
(m, 1H), 1.69 (d, 6H)
70.80
(70.76)
4.69
(4.73)
8.69
(8.73)
8.24 to 7.15 (m, 9H), 4.95
(m, 1H), 1.63 (d, 6H)
74.98
(74.93)
5.30
(5.27)
9.20
(9.23)
Table 5
Compounds 6a-i
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
1
1
+
C
H
N
6a
1642
1618
1590
1497
753
1640
1615
1588
1496
750
8.39 to 7.46 (m, 6H), 5.19 (m, 1H),
2.50 (s, 3H), 1.58 (d, 6H)
414
380
60.74
(60.69)
3.88
(3.91)
6.75
(6.72)
6b
8.35 to 7.43 (m, 7H), 5.17 (m, 1H),
2.49 (s, 3H), 1.57 (d, 6H)
66.23
(66.19)
4.50
(4.53)
7.36
(7.39)
6c
1636
1611
1582
1486
1639
1612
1586
1492
8.27 to 7.38 (m, 7H), 5.13 (m, 1H),
2.51 (s, 3H), 2.45 (s, 3H),
1.52 (d, 6H)
360
374
73.32
(73.37)
5.59
(5.62)
7.77
(7.81)
6d
8.31 to 7.40 (m, 6H), 5.15 (m, 1H),
2.5 (s, 3H), 2.41 (s, 3H), 2.4 (s, 3H),
1.54 (d, 6H)
73.78
(73.75)
5.92
(5.96)
7.48
(7.51)

Mar-Apr 2007
Synthesis and Characterization of Some Important Indazolyl Derivatives
295
tallized from ethanol. The compounds synthesized by the above
procedure are listed in Table 1 and their characterization data is
given in Table 2.
1-(2-Hydroxy-phenyl)-3-(1-isopropyl-1H-indazol-3-yl)-
propane-1,3-diones (4a-i). Compound 3 (0.01 mole) was dis-
solved in 15 ml of dry pyridine with 2 g of powdered KOH. The
reaction mixture was stirred at room temperature for 3 hrs.
Contents were poured into crushed ice and acidified with conc.
HCl. The product obtained was separated by filtration and crys-
tallized with alcohol. The compounds synthesized by above pro-
cedure are listed in Table 1 and their characterization data is
given in Table 3.
Table 5 (Continued)
Compd. IR
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
H
1
1
+
No.
(cm )
C
N
6e
1636
1611
1582
1486
1635
1613
1586
1487
752
8.25 to 7.36 (m, 7H), 5.14 (m, 1H),
2.46 (s, 3H), 2.43 (s, 3H),
1.51 (d, 6H)
360
394
73.32
(73.29)
5.59
(5.63)
7.77
(7.81)
6f
8.36 to 7.42 (m, 6H), 5.12 (m, 1H),
2.46 (s, 3H), 2.41 (s, 3H),
1.54 (d, 6H)
66.92
(66.95)
4.85
(4.83)
7.09
(7.12)
6g
6h
6i
1639
1615
1585
1484
681
1638
1617
1586
1489
1060
1635
1609
1581
1485
8.34 to 7.43 (m, 7H), 5.18 (m, 1H),
2.47 (s, 3H), 1.58 (d, 6H)
424
364
346
59.31
(59.37)
4.03
(4.07)
6.59
(6.53)
8.37 to 7.45 (m, 7H), 5.17 (m, 1H),
2.49 (s, 3H), 1.56 (d, 6H)
69.22
(69.27)
4.70
(4.67)
7.69
(7.71)
8.25 to 7.34 (m, 8H), 5.11 (m, 1H),
2.40 (s, 3H), 1.50 (d, 6H)
72.82
(72.79)
5.24
(5.27)
8.09
(8.12)
Table 6
Compounds 7a-i
Compd. IR
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
1
1
+
No.
(cm )
C
H
N
7a
3424
1599
1553
1487
755
3422
1597
1550
1486
750
8.60 (s, 1H), 8.54 to 6.99 (m, 12H),
5.25 (m, 1H), 1.75 (d, 6H)
462
428
64.80
(64.77)
4.35
(4.38)
12.09
(12.12)
7b
8.59 (s, 1H), 8.51 to 6.93 (m, 13H),
5.22 (m, 1H), 1.72 (d, 6H)
70.01
(70.05)
4.93
(4.97)
13.06
(13.01)
7e
7g
3415
1592
1552
1479
3418
1594
1555
1484
680
8.18 (s, 1H), 8.52 to 6.89 (m, 13H),
5.21 (m, 1H), 2.54 (s, 3H),
1.70 (d, 6H)
408
472
76.45
(76.49)
5.92
(5.95)
13.72
(13.68)
8.61 (s, 1H), 8.50 to 6.90 (m, 13H),
5.21 (m,1H), 1.71 (d, 6H)
63.43
(63.38)
4.47
(4.51)
11.84
(11.87)
7h
3416
1595
1551
1480
1035
8.63 (s, 1H), 8.53 to 6.92 (m, 13H),
5.23 (m,1H), 1.72 (d, 6H)
412
72.80
(72.84)
5.13
(5.09)
13.58
(13.61)

296
S. B. Kale and B. K. Karale
Vol. 44
2-(1-Isopropyl-1H-indazol-3-yl)-chromon-4-ones (5a-i).
and their characterization data is given in Table 6.
Compound 4 (0.001 mole) was dissolved in 10 ml. of ethanol
with 1 ml of conc. HCl. Reaction mixture was then heated under
reflux for 1 hr. Contents were cooled and poured into crushed ice.
The product obtained was separated by filtration and crystallized
with alcohol. The compounds synthesized by above procedure
are listed in Table 1 and their characterization data is given in
Table 4.
3-(1-Isopropyl-1H-indazole-3-carbonyl)-2-methyl-
chromon-4-ones (6a-i). Compound 4 (0.001 mole) was dis-
solved in 10 ml of acetic anhydride with excess of anhydrous
sodium acetate (1 gm). Reaction mixture was then heated under
reflux for 2 hrs. Reaction mixture was then cooled, poured into
crushed ice, separated by filtration and crystallized with alcohol.
Compounds synthesized by above procedure are listed in Table 1
and their characterization data is given in Table 5.
2-[4-(1-Isopropyl-1H-indazol-3-yl)-3H-benzo[b]-
[1,4]diazepin-2-yl]-phenols (7a-i). Compound 4 (0.001 mole)
was dissolved in 15 ml of alcohol with (0.001 mole) o-phenylene
diamine. Reaction mixture was heated under reflux for 3 hrs then
AcOH (1 ml) was added and the contents were refluxed for
another 7 hrs. The product crystallizes on cooling and was sepa-
rated by filtration and purified by crystallization with acetic acid.
Compounds synthesized by above procedure are listed in Table 1
[2-(2-Hydroxy-phenyl)-4H-benzo[1,4]thiazin-3-yl]-(1-iso-
propyl-1H-indazol-3-yl)-methanones (8a-i). ortho-
Aminothiophenol (0.002 mole) was dissolved in 10 ml of
dimethyl sulphoxide. Reaction contents were stirred at room tem-
perature for 2 hrs. To this reaction mixture compound 4 (0.001
mole) was added and the contents were heated under reflux for 2
hrs. Reaction mixture was cooled and poured into crushed ice.
The product obtained was separated by filtration and crystallized
from alcohol. Compounds synthesized by above procedure are
listed in Table 1 and their characterization data is given in Table
7.
2-[5-(1-Isopropyl-1H-indazol-3-yl)-2H-pyrazol-3-yl]-phe-
nols (9a-i). Compound 5 (0.001 mole) was taken with hydrazine
hydrate (0.002 mole) and dissolved in 15 ml of alcohol. Reaction
mixture was heated under reflux for 3 hrs. Contents were cooled,
poured into crushed ice and acidified with conc. HCl. The prod-
uct obtained was separated by filtration and crystallized from
alcohol. Compounds synthesized by the above procedure are
listed in Table 1 and their characterization is given in Table 8.
6-(2-Hydroxy-phenyl)-4-(1-isopropyl-1H-indazol-3-yl)-1H-
pyrimidine-2-thione (10 a-i). Compound 5 (0.001 mole) and
thiourea (0.002 mole) were dissolved in 15 ml of alcohol. To this
reaction mixture potassium hydroxide (0.001 mole) was added.
Table 7
Compounds 8a-i
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
1
1
+
Calcd % (Found %)
C
H
N
8a
3316
1644
1596
754
3314
1642
1595
750
8.59 (s, 1H), 8.57 (s, 1H), 7.52 to
6.80 (m, 10H), 4.91 (m, 1H),
1.35 (d, 6H)
495
461
60.49
(6052)
3.86
(3.89)
8.46
(8.40)
8b
8.57 (s, 1H), 8.55 (s, 1H), 7.44 to
6.78 (m, 11H), 4.92 (m, 1H),
1.34 (d, 6H)
65.00
(65.06)
4.36
(4.33)
9.10
(9.14)
8c
3312
1648
1599
3319
1650
1600
8.55 (s, 1H), 8.53 (s, 1H), 7.49 to
6.77 (m, 11H), 4.91 (m, 1H),
2.53 (s, 3H), 1.32 (d, 6H)
8.52 (s, 1H), 8.51 (s, 1H), 7.51 to
6.76 (m, 10H), 4.89 (m, 1H),
2.54 (s, 3H), 2.51 (s, 3H),
1.30 (d, 6H)
441
455
70.72
(70.75)
5.25
(5.22)
9.52
(9.49)
8d
71.18
(71.15)
5.53
(5.49)
9.22
(9.27)
8e
8f
3317
1647
1593
3315
1644
1590
748
8.54 (s, 1H), 8.52 (s, 1H), 7.50 to
6.75 (m, 11H), 4.90 (m, 1H),
2.51 (s, 3H), 1.31 (d, 6H)
8.58 (s, 1H), 8.56 (s, 1H), 7.55 to
6.78 (m, 10H), 4.95 (m, 1H),
2.54 (s, 3H), 1.33 (d, 6H)
441
475
70.72
(70.69)
5.25
(5.19)
9.52
(9.57)
65.61
(65.57)
4.66
(4.69)
8.83
(8.79)
8g
8h
8i
3314
1645
1598
678
3319
1648
1604
1025
3314
1643
1592
8.60 (s, 1H), 8.59 (s, 1H), 7.59 to
6.81 (m, 11H), 4.99 (m, 1H),
1.36 (d, 6H)
505
445
427
59.29
(59.33)
3.98
(4.01)
8.30
(8.27)
8.62 (s, 1H), 8.60 (s, 1H), 7.62 to
6.83 (m, 11H), 5.12 (m, 1H),
1.39 (d, 6H)
67.40
(67.37)
4.52
(4.57)
9.43
(9.45)
8.57 (s, 1H), 8.54 (s, 1H), 7.59 to
6.80 (m, 12H), 4.90 (m, 1H),
1.33 (d, 6H)
70.24
(70.29)
4.95
(4.93)
9.83
(9.86)

Mar-Apr 2007
Synthesis and Characterization of Some Important Indazolyl Derivatives
297
Table 8
Compounds 9a-i
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
1
1
+
C
H
N
9a
3156
1569
1235
752
3154
1571
1235
747
10.88 (s, 1H), 8.19 to 7.19 (m, 8H),
4.91 (m, 1H), 1.65(d, 6H)
386
352
58.93
(58.89)
4.16
(4.19)
14.47
(14.51)
9b
10.85 (s, 1H), 8.16 to 7.15 (m, 9H),
4.88 (m, 1H), 1.63(d, 6H)
64.48
(64.51)
4.86
(4.83)
15.88
(15.91)
9c
9d
9e
9f
3157
1573
1238
3155
1570
1235
3156
1574
1237
3157
1571
1236
745
10.83 (s, 1H), 8.15 to 7.12 (m, 9H),
4.85 (m, 1H), 2.58 (s,3H),
1.61 (d, 6H)
10.81 (s, 1H), 8.15 to 7.11 (m, 8H),
4.84 (m, 1H), 2.59 (s,3H),
2.54 (s, 3H), 1.60(d, 6H)
10.81 (s, 1H), 8.14 to 7.13 (m, 9H),
4.86 (m, 1H),2.55 (s,3H),
1.59(d, 6H)
332
346
332
366
72.27
(72.30)
6.06
(6.03)
16.86
(16.89)
72.81
(72.86)
6.40
(6.37)
16.17
(16.19)
72.27
(72.31)
6.06
(6.10)
16.86
(16.81)
10.84 (s, 1H), 8.17 to 7.14 (m, 8H),
4.89 (m, 1H),2.54 (s,3H),
1.61(d, 6H)
65.48
(65.51)
5.27
(5.23)
15.27
(15.30)
9g
9h
9i
3160
1573
1239
685
3162
1574
1241
1055
3159
1570
1239
10.82 (s, 1H), 8.15 to 7.00 (m, 9H),
4.82(m, 1H), 1.61(d, 6H)
396
336
318
57.44
(57.39)
4.31
(4.29)
14.10
(14.17)
10.84 (s, 1H), 8.19 to 7.05 (m, 9H),
4.86(m, 1H), 1.63(d, 6H)
67.84
(67.87)
5.09
(5.07)
16.66
(16.69)
10.80 (s, 1H), 8.11 to 6.98
(m, 10H), 4.80 (m, 1H),
1.57(d, 6H)
71.68
(71.71)
5.70
(5.67)
17.60
(17.63)
Table 9
Compounds 10a-i
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
H
1
1
+
C
N
10a
10b
3241
1569
1233
751
3245
1571
1234
749
13.46 (s, 1H), 8.10 (s, 1H), 8.39 to
to 6.81 (m, 7H), 5.07 (m, 1H),
1.66 (d, 6H)
430
396
55.69
(55.73)
3.74
(3.71)
12.99
(12.97)
13.44 (s, 1H), 8.08 (s, 1H), 8.37 to
to 6.80 (m, 8H), 5.02 (m, 1H),
1.64 (d, 6H)
60.52
(60.55)
4.32
(4.37)
14.12
(14.07)
10c
10d
3255
1565
1244
3259
1563
1247
13.35 (s, 1H), 8.03 (s, 1H), 8.36 to
to 6.78 (m, 8H), 4.98 (m, 1H),
2.58 (s, 3H), 1.61 (d, 6H)
13.33 (s, 1H), 8.01 (s, 1H), 8.34 to
to 6.75 (m, 7H), 4.95 (m, 1H),
2.55 (s, 3H), 2.51(s, 3H),
376
390
67.00
(67.07)
5.35
(5.31)
14.88
(14.91)
67.67
(67.71)
5.68
(5.63)
14.35
(14.33)
1.59 (d, 6H)
10e
3256
1564
1244
13.35 (s, 1H), 8.02 (s, 1H), 8.38 to
to 6.77 (m, 8H), 4.96 (m, 1H),
2.57 (s, 3H), 1.60(d, 6H)
376
67.00
(67.03)
5.35
(5.37)
14.88
(14.91)
The contents were heated under reflux for 3 hrs. Reaction mix-
ture was cooled and poured into crushed ice, acidified with acetic
acid. The product obtained was separated by filtration and crys-
tallized from alcohol. Compounds synthesized by the above pro-

298
S. B. Kale and B. K. Karale
Vol. 44
Table 9 (Continued)
Compd.
No.
IR
(cm )
Spectral Data
H NMR δ (ppm)
Mass
M
Elemental Analysis
Calcd % (Found %)
H
1
1
+
C
N
10f
10g
10h
10i
3255
1573
1241
745
3250
1573
1239
684
3251
1571
1240
1021
3247
1577
1235
13.38 (s, 1H), 8.04 (s, 1H), 8.30 to
to 6.79 (m, 7H), 4.97 (m, 1H),
2.58 (s, 3H), 1.63(d, 6H)
410
61.38
(61.41)
4.66
(4.67)
13.63
(13.59)
1340 (s, 1H), 8.07 (s, 1H), 8.31 to
to 6.77 (m, 8H), 4.98 (m, 1H),
1.68 (d, 6H)
440
380
362
54.43
(54.39)
3.88
(3.93)
12.69
(12.71)
13.39 (s, 1H), 8.06 (s, 1H), 8.32 to
to 6.79 (m, 8H), 5.03 (m, 1H),
1.71 (d, 6H)
63.14
(63.11)
4.50
(4.47)
14.73
(14.77)
13.36 (s, 1H), 8.05 (s, 1H), 8.27 to
to 6.76 (m, 9H), 4.93 (m, 1H),
1.61 (d, 6H)
66.28
(66.31)
5.01
(5.03)
15.46
(15.41)
Table 10
Antibacterial activity of the compounds.
All the compounds were dissolved in DMSO and tested at 1 mg/ml concentration. In each well 50 µl sample was loaded.
The zone of inhibition is expressed as diameter of zone in mm.
Comp.No
R
R
R
Staphylococcus
Aureus 209P
Escherichia
Coli ESS
Streptococcus
Faecium 323
1
2
3
3a
3b
3c
3d
3g
4a
4b
4c
4d
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5h
6a
6b
6c
6d
6e
6f
6g
7a
7b
7g
7i
Cl
H
H
Me
H
Cl
H
H
Me
H
H
H
H
H
Cl
H
H
Me
H
H
H
Cl
H
H
H
H
H
H
H
H
H
Cl
Cl
Me
Me
Br
Cl
Cl
Me
Me
H
-
-
-
-
-
11
11
sl
-
sl
-
-
-
-
-
12
12
slh
-
9
slh
12
10
9
12
-
-
-
-
-
-
9
-
-
-
-
-
-
-
-
11
12
sl
-
-
-
12
10
10
12
-
-
-
-
-
-
-
-
-
-
12
-
-
12
-
H
Me
Me
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
Me
Me
H
Cl
Br
F
-
9
11
10
12
-
11h
-
-
-
-
-
10h
11h
12h
13
11h
10h
12
-
H
Cl
Cl
Me
Me
H
Cl
F
Cl
Cl
Me
Me
H
Cl
Br
Cl
Cl
Br
H
H
Me
H
H
H
Cl
H
H
-
-
-
11
-
H
H
H
H
-
-
-
-
-
-
H
cedure are listed in Table 1 and their characterization is given in
Table 9.
Acknowledgement. Authors are thankful to Dr. G. T. Sangle,
the Principal S.S.G.M. College, Kopargaon, Ahmednagar for his
constant encouragement and providing necessary facilities. The
authors are also thankful to Dr. Saji George, the Principal Research
Scientist of Natural Products, Nicholas Piramal Research Centre,
Mumbai, for valuable help in biological screening.

Mar-Apr 2007
Synthesis and Characterization of Some Important Indazolyl Derivatives
299
Table 10 (Continued)
All the compounds were dissolved in DMSO and tested at 1 mg/ml concentration. In each well 50 µl sample was loaded. The zone
of inhibition is expressed as diameter of zone in mm.
Comp.No
R
R
R
Staphylococcus
Aureus 209P
Escherichia
Coli ESS
Streptococcus
Faecium 323
1
2
3
9a
9c
9d
9e
Cl
H
Me
H
H
H
H
Me
H
Cl
Me
Me
H
-
-
-
-
-
-
-
-
-
-
-
13h
10h
12h
-
9h
H
F
Vancomycin
(10 µg/ml)
Linezolid
(10 µg/ml)
-
-
-
-
-
-
13
14
15
14
13h
13
h = hazy, sl = slightly, slh = slightly hazy, NT = not tested.
Table 11
Antifungal activity of the compounds.
All the compounds were dissolved in DMSO and tested at 1 mg/ml concentration. In each well 50 µl sample was loaded. The zone of
inhibition is expressed as diameter of zone in mm.
Comp.No
R
R
R
3
Candida Candida Candida
Candida
krusei
GO3 F
Candida
glabrata
HO4 F
Candida
glabrata
HO5 F
Aspergillus
fumigatus
1
2
albicans albicans
CO9
krusei
GO6 F
S
R
S
R
3a
3b
3c
3d
3g
4a
4b
4c
4d
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5h
6a
6b
6c
6d
6e
6f
6g
7a
7b
7g
7i
9a
9c
9d
9e
9h
Cl
H
H
Me
H
Cl
H
H
Me
H
H
H
H
H
Cl
H
H
Me
H
H
H
Cl
H
H
Me
H
H
H
Cl
H
H
H
Cl
H
H
H
H
H
H
H
H
H
Cl
Cl
11
13
12
12
13
-
12
10
-
-
-
13
-
-
10
10
11
10
10
-
9h
-
-
-
-
10
-
-
12
12
12
13
12
10h
11
11
11
11
11
12
12
10h
10
10
-
11
10h
12
-
10h
10
-
10
-
11
11
10
10h
-
11
11
12
12
10
10
-
11h
14
13
10
15
-
13
11h
-
-
-
15
-
-
11h
13
12
11h
14
-
12
11h
10h
-
10h
12
10h
11h
12h
10h
10h
10h
10h
10h
10h
13
-
-
-
-
-
-
-
-
-
-
-
-
10
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Me
Me
Br
Cl
Cl
Me
Me
H
H
-
Me
Me
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
H
Me
H
10h
10h
13
-
11
Cl
Br
F
H
Cl
Cl
Me
Me
H
-
-
-
11
-
-
-
9h
11h
-
-
-
10h
10h
10h
10h
11
11
12
-
10h
10h
11h
11
12
11
10h
10h
10h
10h
11
10h
10h
10h
10h
10h
10h
10h
10h
10h
10h
10h
10h
-
10h
10h
10h
10h
10h
-
10h
10h
10h
10h
10h
-
Cl
F
-
Cl
Cl
Me
Me
H
Cl
Br
Cl
Cl
Br
H
10h
10
11
10h
10
-
10h
10h
10
10h
10h
10h
11
10
11
11
-
-
-
-
10h
10h
10h
-
-
-
10
10h
-
12h
-
-
-
11
10h
12h
12h
-
10h
11
11
10
-
-
-
Cl
Me
Me
H
10h
10h
10h
-
Me
H
H
11
11
10h
-
-
-
F
10h
Fluconazole
(125 µg/ml)
Amphotericin
B (1 µg/ml)
-
-
-
-
-
-
28h
10
10h
12
30h
10
12h
9
15h
11
10h
13
-
10h
h = hazy, sl = slightly, slh = slightly hazy, NT = not tested.

300
S. B. Kale and B. K. Karale
Vol. 44
Table 12
% Antioxidant activity of the compounds at different concentrations is analyzed.
Compd. No.
R1
R2
R3
Concentration
250µg/ml
26.30
16.76
31.59
40.32
40.73
26.81
-1.35
-9.10
0.24
1mg/ml
39.79
-44.25
49.71
49.76
58.71
45.46
-1.54
-0.87
_0.17
-0.22
-0.34
7.99
8.62
7.61
6.93
1.30
2.17
8.13
500µg/ml
31.34
9.58
40.71
49.13
49.81
37.02
-0.12
-0.05
0.72
-1.47
-0.07
7.56
9.53
7.22
-0.51
1.20
2.38
6.40
22.70
8.59
12.76
56.87
80.58
21.90
24.12
125µg/ml
21.88
16.74
24.09
30.03
31.13
19.78
0.14
62.5µg/ml
17.20
14.43
16.11
24.24
22.90
12.20
1.03
4a
4d
4e
4f
4h
4i
5c
5d
5e
5f
5h
6a
6b
6c
6d
6e
6f
6g
7a
7g
9a
9c
9d
9e
9h
Cl
Me
H
H
H
H
H
Me
H
H
H
Cl
H
H
Me
H
H
H
Cl
H
Cl
H
H
H
Me
Me
H
H
H
H
Me
Me
H
H
H
H
H
Me
Me
H
Cl
Me
H
Cl
F
H
Me
Me
H
Cl
F
-1.23
0.00
0.12
-0.84
8.78
-0.63
-1.06
-0.53
-1.93
7.99
-0.63
-0.70
9.07
9.36
7.03
-1.01
1.66
1.90
6.40
19.76
8.38
10.47
44.74
69.27
16.03
19.28
Cl
Cl
Me
Me
H
Cl
Br
Cl
Br
Cl
Me
Me
H
7.08
7.44
6.88
7.51
-0.14
1.56
0.39
2.31
0.58
5.80
-2.89
6.69
H
H
H
H
H
Me
H
28.26
10.20
15.48
67.68
87.00
29.00
27.65
14.03
7.12
11.31
6.64
8.93
7.73
34.37
55.33
10.76
10.52
23.97
41.23
8.04
Me
H
H
F
7.65
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