PART-I

STUDIES ON

1H-PYRAZOLO[34-b]PYRIDINE

Studies on Some Heterocyclic Entities

16

INTRODUCTION When pyrazolo and pyridine ring systems are fused together various condensed

fused systems may arise from such fusion The pyrazolopridine comprise of five isomers

NN

[15-a](I)

N NH

N

[34-b](II)

N

NH

N

[43-b](III)

NNH

N

[34-c]

(IV)

N

NH

N

[43-c](V)

The pyrazolo[34-b]pyridine system has shown many interesting biological and

pharmacological properties such as antitubercular activity[12] activity against gram

positive and negative bacteria[3] Interest in the synthesis of condensed pyrazoles has

recently revived because of the wide variety of their biological properties[4-6] Although

the pyrazolo[34-b]pyridine ring system has proved to be an interesting class in

heterocyclic chemistry it has received little attention in the literature Some of its

derivatives are important as anticancer agents with low toxicity[78] as anti-

inflammatories[9] as blood platelet aggregation inhibitors[9]as bone metabolism

improvers[10] as adenosine antagonists[1112] and as controlling herbicides[13] They also

show antifungal and antiparasitic activities[1415] In addition they are used as disperse

dyes[16] and as fluorescents[17]From all the benefits mentioned above and in continuation

of our interest directed towards the synthesis of new pyrazine heterocycles[1415]

We would like to report herein a synthesis of new pyrazolo[34-b]pyridine

members along with studies of the effect of some of them as antifungal and as

antibacterial agents

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

17

However few publications are devoted to chemistry of pyrazolo[34-b]

pyridines[18] and [19] as indole or indazole isosteres We report here the synthesis of 3-amino

pyrazolo[34-b]pyridines by cyclisation of 2-chloronicotinonitrile with hydrazines

SYNTHETIC ASPECT

Many polysubstituted derivatives of pyrazolo-[34-b]pyridines have been

synthesized A recent review describes in detail the chemistry of pyrazolo-[34-b]pyridine

ring system Pyrazolopyridines have continued to attract interest because of their

biological activity and structural relationship to indoles and azaindiles [pyrrolopyridines]

Various synthetic approaches have been used to obtain these ring systems some

of which are given in the following

1 The most important synthetic method is the condensation of aminopyrazole with

αβ-unsaturated compounds reported by J Quiroga[20-29]

NN

Ph

NH2 Ar1 Ar2

O

ZnCl2

MWIN

N N

Ph

Ar1

Ar2

2 S Abdullah El-Assiery et al[30] Synthesis of some new annulated

pyrazolopyridine derivatives

N

N

O

Ar

p-CH3OC6H6H4CHO

CH2(CN)2CH3COONH4N

N

N

Ar

Ar

CN

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

16

INTRODUCTION When pyrazolo and pyridine ring systems are fused together various condensed

fused systems may arise from such fusion The pyrazolopridine comprise of five isomers

NN

[15-a](I)

N NH

N

[34-b](II)

N

NH

N

[43-b](III)

NNH

N

[34-c]

(IV)

N

NH

N

[43-c](V)

The pyrazolo[34-b]pyridine system has shown many interesting biological and

pharmacological properties such as antitubercular activity[12] activity against gram

positive and negative bacteria[3] Interest in the synthesis of condensed pyrazoles has

recently revived because of the wide variety of their biological properties[4-6] Although

the pyrazolo[34-b]pyridine ring system has proved to be an interesting class in

heterocyclic chemistry it has received little attention in the literature Some of its

derivatives are important as anticancer agents with low toxicity[78] as anti-

inflammatories[9] as blood platelet aggregation inhibitors[9]as bone metabolism

improvers[10] as adenosine antagonists[1112] and as controlling herbicides[13] They also

show antifungal and antiparasitic activities[1415] In addition they are used as disperse

dyes[16] and as fluorescents[17]From all the benefits mentioned above and in continuation

of our interest directed towards the synthesis of new pyrazine heterocycles[1415]

We would like to report herein a synthesis of new pyrazolo[34-b]pyridine

members along with studies of the effect of some of them as antifungal and as

antibacterial agents

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

17

However few publications are devoted to chemistry of pyrazolo[34-b]

pyridines[18] and [19] as indole or indazole isosteres We report here the synthesis of 3-amino

pyrazolo[34-b]pyridines by cyclisation of 2-chloronicotinonitrile with hydrazines

SYNTHETIC ASPECT

Many polysubstituted derivatives of pyrazolo-[34-b]pyridines have been

synthesized A recent review describes in detail the chemistry of pyrazolo-[34-b]pyridine

ring system Pyrazolopyridines have continued to attract interest because of their

biological activity and structural relationship to indoles and azaindiles [pyrrolopyridines]

Various synthetic approaches have been used to obtain these ring systems some

of which are given in the following

1 The most important synthetic method is the condensation of aminopyrazole with

αβ-unsaturated compounds reported by J Quiroga[20-29]

NN

Ph

NH2 Ar1 Ar2

O

ZnCl2

MWIN

N N

Ph

Ar1

Ar2

2 S Abdullah El-Assiery et al[30] Synthesis of some new annulated

pyrazolopyridine derivatives

N

N

O

Ar

p-CH3OC6H6H4CHO

CH2(CN)2CH3COONH4N

N

N

Ar

Ar

CN

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

17

However few publications are devoted to chemistry of pyrazolo[34-b]

pyridines[18] and [19] as indole or indazole isosteres We report here the synthesis of 3-amino

pyrazolo[34-b]pyridines by cyclisation of 2-chloronicotinonitrile with hydrazines

SYNTHETIC ASPECT

Many polysubstituted derivatives of pyrazolo-[34-b]pyridines have been

synthesized A recent review describes in detail the chemistry of pyrazolo-[34-b]pyridine

ring system Pyrazolopyridines have continued to attract interest because of their

biological activity and structural relationship to indoles and azaindiles [pyrrolopyridines]

Various synthetic approaches have been used to obtain these ring systems some

of which are given in the following

1 The most important synthetic method is the condensation of aminopyrazole with

αβ-unsaturated compounds reported by J Quiroga[20-29]

NN

Ph

NH2 Ar1 Ar2

O

ZnCl2

MWIN

N N

Ph

Ar1

Ar2

2 S Abdullah El-Assiery et al[30] Synthesis of some new annulated

pyrazolopyridine derivatives

N

N

O

Ar

p-CH3OC6H6H4CHO

CH2(CN)2CH3COONH4N

N

N

Ar

Ar

CN

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

18

N

N

O

Ar

p-CH3OC6H6H4CHO

N

N

N

Ar

Ar

CH3CH3COONH4

CH3COCH2COOC2H5

Ar = 24-(NO2)2C6H3

THERAPEUTIC IMPORTANCE

Pyrazolo[34-b]pyridines are potential bioactive agents due to their wide spectrum

of therapeutic importance A large number of substituted Pyrazolo[34-b]pyridine

derivatives are prepared and tested for varieties of biological activities such as

1 Antitubercular Antagonist[12]

2 Antiviral[31]

3 Anti-inflammatories[32]

4 Antifungal and Antiparasitic[3334]

5 Blood platelet aggregation inhibitors[32]

6 Bone metabolism improvers[32]

7 Adenosine antagonists[3536]

8 Controlling herbicides[37]

9 Fungicidal[38]

10 Vasodilatory Activities[39]

11 Bactericidal[40]

Ashutosh Jamloki etal[41] have been synthesized some pyrazolo[34-b]

pyridine(VI) carried out a structural activity relationship study on 6-aryl-pyrazolo[34-b]

pyridine and cited that pyrazolo[34-b]pyridine gives many inhibitory activity

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

19

N NH

N

R

HN

O

R

(VI)

Andreas B J Parusel et al[42] have been studies on Geometries conformational

energies and activation barriers for rotations about the single bonds connecting the

various subunits of a new class of bulky electron donorndashacceptor systems derived from

the bis-pyrazolopyridine chromophore are characterized for several representatives by

semiempirical methods

N N

NHHN

N

R

(VII)

Qing Ye et al[43] have been prepared series of novel 7-azaindazolyl-indolyl-maleimides

(VIII) and evaluated for their antiproliferative activity in vitro against various human

cancer cell lines and protein kinase C inhibitory activity

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

20

N

N

N

N

N

R2

O

O

(CH2)n

R1

(VIII)

Thus the important role displayed by Pyrazolo[34-b]pyridine and its derivatives

for various therapeutic and biological activities prompted us to synthesize some Schiff

bases Thiazolidinone derivatives bearing pyrazolo[34-b]pyridine moiety in order to

achive compounds having better therapeutic activities

SECTION I

SYNTHESIS AND SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-

3-AMINE

REACTION SCHEME

N

CN

Cl

H2N NH2 H2OMethanol

4 Hrs RefluxN N

H

N

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

21

MECHANISM

The reaction proceeds by way of addition of hydrazine hydrate to 2-chloro-3-cyno

pyridine in a manner of 14-addition (Michael addition) followed by cyclization and

aromatization

Cyclocondensation with 2-chloro-3-cyano pyridine might proceed by two distinct

pathways in two stages initial nucleophilic hydrazinodechlorination followed by

intramolecular attack by the hydrazine component on the electron-deficient carbon of the

cyano group yielding 3-aminopyrazolo[34-blpyridines alternatively initial reaction may

be nucleophilic addition of hydrazines to the cyano function generating an amidrazone

moiety (-NH(NHNH2)) that then intramolecularly displaces the halogen

N Cl

C N

+ H2N NH2 H2O

N NH

C N

N

H

H

H+

H+

N NH

N

NH

H

N NH

N

NH2

- HCl

The constitution of the synthesized product have been characterized by using

infrared and 1H-nuclear magnetic resonance spectroscopy and further supported by mass

spectroscopy

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

22

IR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

N NH

N

NH2

Instrument SHIMADZU FTIR 8400 Spectrophotometer Frequency range 4000-400 cm-1 (KBr disc)

Frequency cm-1

Type Vibration

Mode Observed Reported Ref

Aromatic

C-H str

C=C str

C-H ip def

C-H oop def

3070

1524

1063

809

3100-3000

1585-1480

1125-1090

860-810

44

rdquo

rdquo

rdquo

Amine

N=C str

C-N str

N-H str

N-H def

1613

1295

3422

1613

1650-1580

1350-1200

3450-3380

1650-1580

rdquo

rdquo

rdquo

rdquo

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

19

N NH

N

R

HN

O

R

(VI)

Andreas B J Parusel et al[42] have been studies on Geometries conformational

energies and activation barriers for rotations about the single bonds connecting the

various subunits of a new class of bulky electron donorndashacceptor systems derived from

the bis-pyrazolopyridine chromophore are characterized for several representatives by

semiempirical methods

N N

NHHN

N

R

(VII)

Qing Ye et al[43] have been prepared series of novel 7-azaindazolyl-indolyl-maleimides

(VIII) and evaluated for their antiproliferative activity in vitro against various human

cancer cell lines and protein kinase C inhibitory activity

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

20

N

N

N

N

N

R2

O

O

(CH2)n

R1

(VIII)

Thus the important role displayed by Pyrazolo[34-b]pyridine and its derivatives

for various therapeutic and biological activities prompted us to synthesize some Schiff

bases Thiazolidinone derivatives bearing pyrazolo[34-b]pyridine moiety in order to

achive compounds having better therapeutic activities

SECTION I

SYNTHESIS AND SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-

3-AMINE

REACTION SCHEME

N

CN

Cl

H2N NH2 H2OMethanol

4 Hrs RefluxN N

H

N

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

21

MECHANISM

The reaction proceeds by way of addition of hydrazine hydrate to 2-chloro-3-cyno

pyridine in a manner of 14-addition (Michael addition) followed by cyclization and

aromatization

Cyclocondensation with 2-chloro-3-cyano pyridine might proceed by two distinct

pathways in two stages initial nucleophilic hydrazinodechlorination followed by

intramolecular attack by the hydrazine component on the electron-deficient carbon of the

cyano group yielding 3-aminopyrazolo[34-blpyridines alternatively initial reaction may

be nucleophilic addition of hydrazines to the cyano function generating an amidrazone

moiety (-NH(NHNH2)) that then intramolecularly displaces the halogen

N Cl

C N

+ H2N NH2 H2O

N NH

C N

N

H

H

H+

H+

N NH

N

NH

H

N NH

N

NH2

- HCl

The constitution of the synthesized product have been characterized by using

infrared and 1H-nuclear magnetic resonance spectroscopy and further supported by mass

spectroscopy

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

22

IR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

N NH

N

NH2

Instrument SHIMADZU FTIR 8400 Spectrophotometer Frequency range 4000-400 cm-1 (KBr disc)

Frequency cm-1

Type Vibration

Mode Observed Reported Ref

Aromatic

C-H str

C=C str

C-H ip def

C-H oop def

3070

1524

1063

809

3100-3000

1585-1480

1125-1090

860-810

44

rdquo

rdquo

rdquo

Amine

N=C str

C-N str

N-H str

N-H def

1613

1295

3422

1613

1650-1580

1350-1200

3450-3380

1650-1580

rdquo

rdquo

rdquo

rdquo

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

20

N

N

N

N

N

R2

O

O

(CH2)n

R1

(VIII)

Thus the important role displayed by Pyrazolo[34-b]pyridine and its derivatives

for various therapeutic and biological activities prompted us to synthesize some Schiff

bases Thiazolidinone derivatives bearing pyrazolo[34-b]pyridine moiety in order to

achive compounds having better therapeutic activities

SECTION I

SYNTHESIS AND SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-

3-AMINE

REACTION SCHEME

N

CN

Cl

H2N NH2 H2OMethanol

4 Hrs RefluxN N

H

N

NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

21

MECHANISM

The reaction proceeds by way of addition of hydrazine hydrate to 2-chloro-3-cyno

pyridine in a manner of 14-addition (Michael addition) followed by cyclization and

aromatization

Cyclocondensation with 2-chloro-3-cyano pyridine might proceed by two distinct

pathways in two stages initial nucleophilic hydrazinodechlorination followed by

intramolecular attack by the hydrazine component on the electron-deficient carbon of the

cyano group yielding 3-aminopyrazolo[34-blpyridines alternatively initial reaction may

be nucleophilic addition of hydrazines to the cyano function generating an amidrazone

moiety (-NH(NHNH2)) that then intramolecularly displaces the halogen

N Cl

C N

+ H2N NH2 H2O

N NH

C N

N

H

H

H+

H+

N NH

N

NH

H

N NH

N

NH2

- HCl

The constitution of the synthesized product have been characterized by using

infrared and 1H-nuclear magnetic resonance spectroscopy and further supported by mass

spectroscopy

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

22

IR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

N NH

N

NH2

Instrument SHIMADZU FTIR 8400 Spectrophotometer Frequency range 4000-400 cm-1 (KBr disc)

Frequency cm-1

Type Vibration

Mode Observed Reported Ref

Aromatic

C-H str

C=C str

C-H ip def

C-H oop def

3070

1524

1063

809

3100-3000

1585-1480

1125-1090

860-810

44

rdquo

rdquo

rdquo

Amine

N=C str

C-N str

N-H str

N-H def

1613

1295

3422

1613

1650-1580

1350-1200

3450-3380

1650-1580

rdquo

rdquo

rdquo

rdquo

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

21

MECHANISM

The reaction proceeds by way of addition of hydrazine hydrate to 2-chloro-3-cyno

pyridine in a manner of 14-addition (Michael addition) followed by cyclization and

aromatization

Cyclocondensation with 2-chloro-3-cyano pyridine might proceed by two distinct

pathways in two stages initial nucleophilic hydrazinodechlorination followed by

intramolecular attack by the hydrazine component on the electron-deficient carbon of the

cyano group yielding 3-aminopyrazolo[34-blpyridines alternatively initial reaction may

be nucleophilic addition of hydrazines to the cyano function generating an amidrazone

moiety (-NH(NHNH2)) that then intramolecularly displaces the halogen

N Cl

C N

+ H2N NH2 H2O

N NH

C N

N

H

H

H+

H+

N NH

N

NH

H

N NH

N

NH2

- HCl

The constitution of the synthesized product have been characterized by using

infrared and 1H-nuclear magnetic resonance spectroscopy and further supported by mass

spectroscopy

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

22

IR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

N NH

N

NH2

Instrument SHIMADZU FTIR 8400 Spectrophotometer Frequency range 4000-400 cm-1 (KBr disc)

Frequency cm-1

Type Vibration

Mode Observed Reported Ref

Aromatic

C-H str

C=C str

C-H ip def

C-H oop def

3070

1524

1063

809

3100-3000

1585-1480

1125-1090

860-810

44

rdquo

rdquo

rdquo

Amine

N=C str

C-N str

N-H str

N-H def

1613

1295

3422

1613

1650-1580

1350-1200

3450-3380

1650-1580

rdquo

rdquo

rdquo

rdquo

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

22

IR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

N NH

N

NH2

Instrument SHIMADZU FTIR 8400 Spectrophotometer Frequency range 4000-400 cm-1 (KBr disc)

Frequency cm-1

Type Vibration

Mode Observed Reported Ref

Aromatic

C-H str

C=C str

C-H ip def

C-H oop def

3070

1524

1063

809

3100-3000

1585-1480

1125-1090

860-810

44

rdquo

rdquo

rdquo

Amine

N=C str

C-N str

N-H str

N-H def

1613

1295

3422

1613

1650-1580

1350-1200

3450-3380

1650-1580

rdquo

rdquo

rdquo

rdquo

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

23

1HNMR SPECTRAL STUDIES OF 1H-PYRAZOLO[34-b] PYRIDINE-3-AMINE

Internal Standard TMS Solvent CDCl3 + DMSO Instrument BRUKER

Spectrometer (300 MHz)

Signal

No

Signal

Position

δppm

Relative No

of Protons Multiplicity Inference

1

2

3

4

700-704

794-797

846-847

419-425

1H

1H

1H

2H

multiplet

doublet

doublet

singlet

Ar-H(b)

Ar-H(c) (J=78 Hz)

Ar-H(a)(J=36 Hz)

Ar-NH2

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

24

EXPANDED AROMATIC REGION

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

25

MA

SS S

PEC

TR

UM

OF

1H-P

YR

AZ

OL

O[3

4-b

]PY

RID

INE

-3-A

MIN

E

N

NNHNH2

MZ

= 1

35

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

26

EXPERIMENTAL

[A] SYNTHESIS OF 1H-PYRAZOLO[34-b]PYRIDINE-3-AMINE

A solution of 2-chloro-3-cyno pyridine (001 mol 138 gm) in hot methanol (150

ml) is prepared in a three-necked round-bottom flask fitted with a stirrer at room

temperature drop wise added hydrazine hydrate (25 eq 125 gm) over a period of 5

minutes stirr the reaction mass for 30 min at room temperature and reflux for 40 hrs in

water bath Completion of reaction was checked by TLC using mobile phase

EthylacetateHexane (46) ml After completion of the reaction cool the reaction mass the

crude product was isolated and crystallized from absolute ethanol Yield 91 MP

1780C

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

27

REFERENCES

1 I Sekikawa J Nishie S Tono-oka Y Tanaka and S Kakimoto J Heterocycl

Chem 10 931 (1973)

2 L Kukzynski A Mrizikiewic W Banaszkiewicz and K P Pol J Pharmacol

Pharm 31 217 (1979)

3 A M Kamal A A Atalla T A Mohamed A A Geies and Z Naturforsch B

Chem Sci 46 541 (1991)

4 M H Elnagdi N Al-Awadi and AW Erian In A R Katritzky C W Rees and

E FV Scriven Editors Comprehensive Heterocyclic Chem II 4 Pergamon p

431 Oxford (1996)

5 S M Desenko S A Komykhov V D Orlov and H Meier J Heterocycl

Chem 35 989ndash990 (1998)

6 J Quiroga B Insuashy S Craz P Hernandez A Bolafios R Moreno A

Homoza and R H de Almedias J Heterocycl Chem 35 333ndash338 (1998)

7 S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 172 988[90 172 988] (Cl

C07D48704) (4 Jul 1990) Chem Abstr 113 218276t (1990)

8 S S Suzuki and A Inoue Jpn Kokai Tokkyo Koho JP 02 240084 [90 240 084]

(Cl C07D48704) (25 Sep 1990) Chem Abstr 114 178382m (1991)

9 T Sado and A Inoue Jpn Kokai Tokkyo Koho JP 02 101 078[90 101 078] (Cl

C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

10 K Imaizumi and T Sado Jpn Kokai Tokkyo Koho JP 06 80 570[94 80 570] (Cl

A61K31495) (22 Mar 1994) Chem Abstr 121 91797w (1994)

11 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl(2001) 69 pp CODEN PIXXD2 WO 2001040230 Al20010607

Chem Abstr 135 33489a (2001)

12 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co LtdJapan) A PCT W

JP Chem Abstr 138 24732a (2003)

13 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276]

(ClC07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

28

14 T I El-Emary A M El-Dean Kamal H S El-Kashef Farmaco 53 383

(1998)

15 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie 55(8) 572 (2000)

16 D W Rangnekar and S V Dhamnaskar J Chem TechnolBiotechnol 49 311

(1990)

17 J Hofmann D Sicker G Mann Ger (East) DD 276688(Cl C07D48704) (7

Mar 1990) Chem Abstr 113 231409h (1990)

18 L Kuczynski A Mrozikiewicz W Banaszkiewicz and K Poreba Pol J

Pharmacol Pharm 31 217ndash225(1997)

19 BM Lynch MA Khan HC Teo and F Pedrotti Can J Chem 66 420ndash

428(1988)

20 V D Orlov J Quiroga N N Kolos Khim Geterosikl Soedin 1247 (1987)

21 V D Orlov J Quiroga N N Kolos S M Desenko Khim Geterosikl Soedin

962 (1988)

22 J Quiroga B Insuasty R Rincoacuten M Larrahondo N Hanold H Meier J

Heterocycl Chem 31 1333(1994)

23 J Quiroga B Insuasty M Mariacuten A Aguirre H Meier Rev Col Quim 21 29

(1992)

24 J Quiroga B Hormaza C Insuasty C Saitz A Jullian J Heterocycl Chem

35 61 (1998)

25 J Quiroga B Hormaza S Cruz P Hernandez A Bolańos R Moreno A

Hormaza R H Almeida J Heterocycl Chem 35 333 (1998)

26 J Quiroga A Hormaza B Insuasty M Marquez J Heterocycl Chem 35 409

(1998)

27 J Quiroga A Hormaza B Insuasty C Saitz C Jullian J Heterocycl Chem

35 575 (1998)

28 J Quiroga B Insuasty A Hormaza D Gamenara L Domiacutenguez J Saldańa J

Heterocycl Chem 36 11 (1999)

29 J Quiroga B Insuasty A Hormaza P Cabildo R M Claramunt Elguero J

Heterocycl Commun 5 115 (1999)

30 S Abdullah El-Assiery Acta Pharm 54143ndash150 (2004)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

29

31 V F Ferreira A M R Bernardino A MR Souza G A Alves A D Matta and

M R P Oliveira Nucleosides amp Nucleotides15 889 (1996)

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C07D48704) (12 Apr 1990) Chem Abstr 113 78422k (1990)

33 T I El-Emary El-Dean A M Kamal H S El-Kashef Farmaco 53 383

(1998)

34 H S El-Kashef T I El-Emary M Gasquet P Timon-David J Maldonado and

P Vanelle Pharmazie55(8) 572 (2000)

35 A Akahane S Kuroda I Itani S Tabuchi Y Sato N Matsuoka M Tada H

Matsuoka T Oku and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A

PCT Int Appl (2001) 69 CODEN PIXXD2 WO 2001040230 Al 20010607

Chem Abstr 135 33489a (2001)

36 A Akahane and A Tanaka (Fujisawa Pharmaceutical Co Ltd Japan) A PCT

W JP Chem Abstr 138 24732a (2003)

37 Int Appl (2002) 34 pp CODEN PIXXD2 WO 2002100864 Al 20021219

Designated States F Takabe A Shibayama M Yamaguchi M Yamaji R

Hanai and H Sadohara Jpn Kokai Tokkyo Koho JP 09 59 276 [97 59 276] (Cl

C07D47104) (4 Mar 1997) Chem Abstr 126 277477a (1997)

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Wunder D Lang PCT Int Aool Wo 2004009589 Baye Healtheare Ag

Germany

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PTrivedi Asian Journal of Biochemistry 1(3) 236-243 (2006)

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Agnieszka Puchała Danuta Rasała Krystyna Rotkiewicz and Gottfried Koumlhler

Journal of Molecular Structure (Theochem) 419 63ndash75 (1997)

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Bioorganic amp Medicinal Chemistry 17 4763ndash4772 (2009)

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Studies on Some Heterocyclic Entities

30

44 V M Parikh

ldquoAbsorption spectroscopy of organic moleculesrdquo Addition-Wesley Pub Co

London 243258 (1978) A Hand book of spectroscopic data by B D Mishtry 1st

ed ABD Press Jaipur 11-36 (2000)

1H-Pyrazolo[34-b]pyridinehellip

Studies on Some Heterocyclic Entities

30

44 V M Parikh

ldquoAbsorption spectroscopy of organic moleculesrdquo Addition-Wesley Pub Co

London 243258 (1978) A Hand book of spectroscopic data by B D Mishtry 1st

ed ABD Press Jaipur 11-36 (2000)

1H-Pyrazolo[34-b]pyridinehellip