Field of the invention:

The present invention relates to an improved process for the preparation of 3-isobutyryl-2-
isopropyl pyrazolo[l,5-a] pyridine compound represented by the structural formula-1.

Background of the invention:

3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine and process for its preparation was first disclosed in US3850941. The disclosed process involves refluxing a mixture of l-amino-2-methyl pyridinium bromide, isobutyric anhydride and potassium carbonate for 8-10 hrs to provide 3- isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine. In this process high vacuum distillation technique is required to collect the fraction of the final product from the reaction mixture. High vacuum distillation on commercial scale is not advisable. Hence there is a need in the art to provide a simple and safe process for the preparation of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine.

Advantages of the present invention:

• Avoids the high vacuum distillation of the reaction mixture to collect the fraction of 3-
isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1.

• The present invention involves the isolation and purification of l-isobutyramido-2-methyl
pyridinium bromide intermediate compound of formula-7 to get' pure compound of formula-7, which in turn enhances the purity of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1.

• Provides a simple and safe process for the preparation of 3-isobutyryl-2-isopropyl
pyrazolo[l,5-a] pyridine compound of formula-1.

Brief description of the invention:

The first aspect of the present invention is to provide an improved process for the preparation of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulfonic acid compound of formula-3 in a suitable solvent to provide hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating it with hydrobromic acid to provide l-amino-2-methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido -2-
methyl pyridinium bromide compound of formula-7,

d) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent,

e) reacting the compound of formula-7 with isobutyric anhydride in presence of a suitable base to provide 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1,

f) crystallizing the compound of formula-1 from a suitable solvent to provide crystalline compound of formula-1.

The second aspect of the present invention is to provide a process for the preparation of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in a suitable solvent to provide hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating with hydrobromic acid to provide l-amino-2-methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido -2-methyl pyridinium bromide compound of formula-7,

d) isolating the compound of formula-7 from the reaction mixture,

e) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent.

The third aspect of the present invention is to provide crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 as per the process of the present invention which is characterized by its PXRD, IR and DSC patterns as depicted in fig-1, fig-2 and fig-3 respectively.

The fourth aspect of the present invention is to provide a process for the isolation of 3-isobutyryl-2-isopropyl pyrazolo [l,5-a]pyridine compound of formula-1 from the reaction mixture obtained by the reaction of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7 with isobutyric anhydride, comprising of;

a) Distilling off the traces of isobutyric anhydride from the reaction mixture,

b) cooling the reaction mixture,

c) adding water and then basifying the reaction mixture using a suitable base,

d) extracting the compound with a suitable water immiscible solvent,

e) subjecting the organic layer to carbon treatment,

f) filtering the reaction mixture followed by distillation of solvent from the filtrate to obtain the compound of formula-1.

Brief description of the drawings:

Figure-1: Illustrates the X-Ray powder diffraction pattern of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1. Figure-2: Illustrates the IR spectrum of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1. Figure-3: Illustrates the DSC thermogram of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1.

Detailed description of the invention:

The term "suitable solvent" used in the present invention refers to "hydrocarbon solvents" such as n-hexane, n-heptane, cyclohexane, pet ether, benzene, toluene, xylene and the like; "ether solvents" such as dimethylether, diethylether, methyl tert-butyl ether, tetrahydrofuran and the like;

"ester solvents" such as methyl acetate, ethylacetate, isopropyl acetate and the like; "polar-aprotic
solvents such as dimethylacetamide, dimethylformamide, dimethylsulphoxide, dioxane,

acetonitrile and the like; "chlorinated hydrocarbon solvents" such as dichloromethane,

dichloroethane, chloroform and the like; "ketone solvents such as acetone, methyl ethyl ketone,

methyl isobutyl ketone and the like; "alcoholic solvents" such as methanol, ethanol, isopropanol,
n-butanol and the like; "polar solvents" such as water; and/or their mixtures thereof.

As used herein the present invention the term "suitable base" refers to "alkali metal carbonates" such as sodium carbonate, potassium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate and the like; "alkali metal hydroxides" such as sodium hydroxide, potassium hydroxide and the like; and organic bases like diisopropyl amine, diisobutyl amine, triethylamine, pyridine and/or their mixtures thereof.

The first aspect of the present invention provides an improved process for the preparation
of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in a suitable solvent provides hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating it with hydrobromic acid provides l-amino-2- methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride provides l-isobutyramido-2-
methyl pyridinium bromide compound of formula-7,

d) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent,

e) reacting the compound of formula-7 with isobutyric anhydride in presence of a suitable base
provides 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1,

f) crystallizing the compound of formula-1 from a suitable solvent provides crystalline compound
of formula-1.

Wherein, in step-a) the suitable solvent is selected from "chlorinated hydrocarbon solvents"; preferably dichloromethane;

in step-b) the suitable solvent is selected from "polar solvents" such as water;

in step-d) the suitable solvent is selected from alcoholic solvents, preferably isopropanol;

in step-e) the suitable base used is selected from alkali metal carbonates and alkali metal bicarbonates;

preferably potassium carbonate;

in step-f) the suitable solvent used is selected from hydrocarbon solvents and ether solvents; preferably n-hexane.

In the present invention the intermediate compound of formula-7 is isolated and purified by recrystallizing it from a suitable solvent to get pure compound of formula-7. The usage of pure intermediate in the synthesis of API always enhances the purity of final product.

The second aspect of the present invention provides a process for the preparation of pure l-isobutyramido-2-methyl pyridinium bromide compound of formula-7, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in a suitable solvent provides hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating with hydrobromic acid provides l-amino-2-methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride provides 1-isobutyramido -2- methyl pyridinium bromide compound of formula-7,

d) isolating the compound of formula-7 from the reaction mixture,

e) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent provides pure compound of formula-7.

Wherein in step-a) the suitable solvent is selected form chlorinated hydrocarbon solvents; preferably dichloromethane.

In step-b) the suitable solvent is selected form polar solvents preferably water. In step-e) the suitable solvent is selected form ketone and alcoholic solvents.

The third aspect of the present invention provides the crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1 obtained as per the process of the present invention, which is characterized by its PXRD, IR and DSC patterns. This crystalline form of compound of formula-1 is herein after designated as form-M.

The crystalline form-M of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 produced by the process of the present invention is characterized by the X-Ray powder diffraction pattern having the peaks at about 7.0, 8.6, 9.7, 12.4, 13.4, 14.1, 14.7, 15.3, 18.3, 19.7, 20.1, 21.3, 21.7, 22.9, 24.1, 27.9, 28.3, 31.2, 33.8 and 43.5 ± 0.2 degrees of 2-theta values as shown in fig-1 and is further characterized by its IR and DSC patterns as depicted in fig-2 and fig- 3 respectively.

In order to overcome the problems associated with prior-art processes such as high vacuum distillation for the collection of fraction of compound of formula-1 from the reaction mixture, the present inventors developed an improved workup procedure to get the final product without using high vacuum distillation technique.

The fourth aspect of the present invention provides a process for the isolation of 3-isobutyryl-2-isopropyl pyrazolo [l,5-a]pyridine compound of formula-1 from the reaction mixture obtained by the reaction of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7 with isobutyric anhydride, comprising of;

a) Distilling off the traces of isobutyric anhydride from the reaction mixture,

b) cooling the reaction mixture,

c) adding water and then basifying the reaction mixture with a suitable base upto pH of the reaction mixture reaches to 8-12,

d) extracting the compound with a suitable water-immiscible solvent,

e) subjecting the organic layer to carbon treatment,

f) filtering the reaction mixture followed by distillation of solvent from the filtrate to obtain the compound of formula-1.

Wherein in step-c) the suitable base is selected from alkali metal hydroxides and alkali metal carbonates; preferably sodium hydroxide,

in step-d) the suitable water-immiscible solvent is selected from dichloromethane, toluene and ethylacetate; preferably dichloromethane.

Differential scanning calorimetric (DSC) analysis was performed with Q10 V9.6 Build 290 calorimeter. Samples of about 2 to 3 milligrams, held in a closed pan, were analyzed at a heating rate of 10° per minute.

3-Isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 obtained by the present invention was analyzed by HPLC under the following conditions;

Apparatus: A liquid chromatograph equipped with variable wavelength UV detector; Column: Inertsil ODS-3V, 150x4.6 mm, 5jim or equivalent; Flow rate: 0.8 ml/min; Wavelength: 254 nm; Column temperature: Ambient; Injection volume: 20 |xL; Run time: 25 min; Diluent: Mobile phase; Mobile phase: A degassed mixture of methanol and water in the ratio of 800:200(v/v); Elution: Isocratic.

PXRD analysis of 3-Isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine was carried out using BRUKER/AXS X-Ray diffractometer using Cu Ka radiation of wavelength 1.5406 A° and continuous scan speed of 0.037min.

The particle size distribution of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 is measured under the following conditions:

Instrument: Malvern Mastersizer 2000; Measuring range: 0.02 to 2000 |j.m; Wet sampler: Hydro 2000S; Dispersant: water; Absorption index: 0.0001; Refractive Index of water: 1.33; Refractive index of particle: 1.60; Stirrer speed: 2000 rpm; Obscuration range: 10-20%; Sensitivity: normal; Particle shape: Irregular; Measurement time: 10 seconds; Background time: 10 seconds; Internal sonication: 60 sec (Tip displacement-100%); Measurement repeat: 3 times at zero second interval.

The present invention is schematically represented as follows.

The best mode of carrying out the present invention is illustrated by the below mentioned examples. These examples are provided as illustration only and hence should not be construed as limitation of the scope of the invention.

Examples:

Example-1: Preparation of hydroxylamine-O-sulphonic acid (Formula-4)

Dichloromethane (500 ml) and hydroxylamine hydrochloride (100 gm) were charged into a clean and dry RBF at 25-30°C. To this reaction mixture chlorosulphonic acid (200 gm) was slowly added and stirred for 60 minutes at the same temperature. The resulting mixture was heated to reflux temperature and stirred at the same temperature for 60 minutes. The solvent was completely distilled off and the resulting mixture was cooled to 25-30°C. Dichloromethane was added to the reaction mixture at the same temperature and distilled off the solvent completely under reduced pressure. To this mixture 200 ml of dichloromethane was added at 25-30°C and stirred for 30 minutes at the same temperature. The obtained compound was filtered under N2 atmosphere and washed with dichloromethane. To the wet compound, dichloromethane (200 ml) was added and stirred for 15 minutes at 25-30°C. The obtained compound was filtered, washed with dichloromethane and then dried under vacuum at 25-30°C to get the title compound. Yield: 165 gm; M.R: 190-200°C.

Example-2: Preparation of l-amino-2-methyl pyridinium bromide (Formula-6)

200 ml of water was charged into a clean and dry RBF at 25-30°C and cooled to 5-10°C. To this hydroxylamine-O-sulphonic acid (50 gm) was added at the same temperature. 2-Methyl pyridine (100 gm) was slowly added to the resulting solution at 5-10°C. The temperature of the reaction mixture was raised to 25-30°C and stirred for 60 minutes at the same temperature. Heated the reaction mixture to 90-95°C and stirred for 3 hrs at the same temperature. Cooled the reaction mixture to 25-30°C and potassium carbonate was slowly added to it. Distilled off water completely under reduced pressure at below 50°C. Isopropyl alcohol (50 ml) was added to the obtained residue and distilled off the solvent completely under reduced pressure. To the residue isopropyl alcohol (200 ml) was added at 25-30°C and stirred for 1 hr at the same temperature. Filtered the reaction mixture and washed with isopropyl alcohol. Cooled the filtrate to 0-5 °C and 93 gm of 47% HBr was slowly added at the same temperature. The temperature of the reaction mixture was raised to 15-20°C and stirred for 1 hr at the same temperature. The solvent was distilled off completely under reduced pressure at below 50°C. Cooled the reaction mixture to 25-30°C and 150 ml of ethylacetate was added. The reaction mixture was stirred for 60 minutes at the same temperature. Cooled the reaction mixture to 0-5°C and stirred for 90 minutes, at the same temperature. Filtered the precipitated solid, washed with ethylacetate and then dried at 60-70°C to get the title compound. Yield: 45 gm; M.R: 170-176°C.

Example-3: Preparation of l-isobutyramido-2-methyl pyridinium bromide (Formula-7)

Isobutyric anhydride (415 gm) was charged into a clean and dry RBF at 25-30°C. To this 100 gm of l-amino-2-methyl pyridinium bromide was added at the same temperature. The reaction mixture was slowly heated to 120-130°C and stirred for 60 minutes, at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 60 minutes, at the same temperature. Filtered the reaction mixture and washed with isopropyl alcohol. 750 ml of isopropyl alcohol was added to the wet compound and the reaction mixture was slowly heated to reflux temperature. After dissolution of the compound, carbon was added to the reaction mixture and stirred for 20-30 min. at reflux temperature. Filtered the reaction mixture through hyflow bed and washed with isopropyl alcohol. Cooled the filtrate to 25-30°C and stirred for 60 minutes, at the same temperature. Filtered the precipitated solid, washed with isopropyl alcohol and then dried to get the title compound. Yield: 105 gm; M.R: 200-204°C.

Example-4: Preparation of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine (Formula-1)

Isobutyric anhydride (365 gm) was charged into a clean and dry RBF at 25-30°C. To this 75 gm of l-isobutyramido-2-methyl pyridinium bromide followed by 120 gm of potassium carbonate were added at the same temperature. The reaction mixture was slowly heated to 120 - 130°C and stirred for 10 hrs at the same temperature. Cooled the reaction mixture to 25-30°C, dichloromethane (200 ml) was added to it and stirred for 15 minutes at the same temperature.

Filtered the unwanted compound and washed with dichloromethane. The solvent was completely distilled off from the filtrate and then the traces of isobutyric anhydride were distilled off. The obtained residue was cooled to 25-30°C and 190 ml of water was added to it. The pH of the reaction mixture was adjusted to 12.0 with 6N NaOH solution at 25-30°C. 150 ml of dichloromethane was added to the reaction mixture and stirred for 15 minutes at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. Both the organic layers were combined and washed with water. Carbon was added to the organic layer at 25-30°C and stirred for 15 minutes, at the same temperature. Filtered the reaction mixture through hyflow bed and washed with dichloromethane.

Distilled off the solvent completely from the filtrate to get the title compound as a residue.

n-Hexane (100 ml) was added to the above obtained residue and heated the reaction mixture to 50-60°C.

Carbon was added to the reaction mixture at 50-60°C and stirred for 15 minutes at the same temperature. Filtered the reaction mixture through hyflow bed and washed with n-hexane. The filtrate was cooled to -10 to -5°C and stirred for 45 minutes, at the same temperature. Filtered the precipitated solid, washed with n-hexane and then dried to get crystalline 3-isobutyryl-2-isopropyl pyrazolo[ 1,5-a]pyridine. Yield: 40 gm; M.R: 48-50°C; Purity by HPLC: 99.71%.

Particle Size Distribution: D(0.1) is 17.64 |im; D(0.5) is 45.87 nm; D(0.9) is 96.40 |im

Example-5: Process for the preparation of crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5- ajpyridine (Formula-l)

n-Hexane (100 ml) was added to the 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine(50 gm) and heated the reaction mixture to 50-60°C. Carbon was added to the reaction mixture at 50-60°C and stirred for 10-15 min. at the same temperature. Filtered the reaction mixture through hyflow bed and washed with n-hexane. The filtrate was cooled to -10 to -5°C and stirred for 30-45 min. at the same temperature. Filtered the precipitated solid, washed with n-hexane and then dried to get crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine. Yield: 45 gm; M.R: 48-50°C; Purity by HPLC: 99.75%.

We Claim:

1. An improved process for the preparation of crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1, comprising of;

(a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3

in a suitable solvent to provide hydroxylamine-O-sulphonic acid compound of formula-4,

(b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating with hydrobromic acid to provide l-amino-2- methyl pyridinium bromide compound of formula-6,

(c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido-
2-methyl pyridinium bromide compound of formula-7,

(d) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent,

(e) reacting the compound of formula-7 with isobutyric anhydride in presence of a suitable base to provide 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1,

(f) crystallizing the compound of formula-1 from a suitable solvent to provide crystalline compound of formula-1.

2. The process according to claim 1, wherein

in step-a) the suitable solvent is selected from chlorinated hydrocarbon solvents; preferably dichloromethane,

in step-b) the suitable solvent is selected from polar solvents; preferably water, in step-d) the suitable solvent is selected from alcoholic solvents; preferably isopropanol, in step-e) the suitable base is selected from alkali metal carbonates and alkali metal bicarbonates; preferably K2CO3,

in step-f) the suitable solvent is selected from hydrocarbon solvents and ether solvents; preferably n-hexane.

3. A process for the preparation of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in a suitable solvent to provide hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in a suitable solvent followed by treating with hydrobromic acid to provide l-amino-2-methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido- 2-methyl pyridinium bromide compound of formula-7,

d) optionally purifying the compound of formula-7 by recrystallizing it from a suitable solvent to provide pure compound of formula-7.

4. A process for the preparation of l-isobutyramido-2-hiethyl pyridinium bromide compound of formula-7, comprising of;

a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in dichloromethane to provide hydroxylamine-O-sulphonic acid compound of formula-4,

b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in water followed by treating with hydrobromic acid to provide l-amino-2-methyl pyridinium bromide compound of formula-6,

c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido -2-methyl pyridinium bromide compound of formula-7,

d) optionally purifying the compound of formula-7 by recrystallizing it from isopropyl alcohol to provide pure compound of formula-7.

5. A process for the preparation of crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1, comprising of;

(a) Reacting the hydroxylamine hydrochloride salt compound of formula-2 with chlorosulphonic acid compound of formula-3 in dichloromethane to provide hydroxylamine-O-sulphonic acid compound of formula-4,

(b) reacting the compound of formula-4 with 2-methyl pyridine compound of formula-5 in water followed by treating with hydrobromic acid to provide l-amino-2-methyl pyridinium bromide compound of formula-6,

(c) reacting the compound of formula-6 with isobutyric anhydride to provide 1-isobutyramido-
2- methyl pyridinium bromide compound of formula-7,

(d) purifying the compound of formula-7 by recrystallizing it from isopropyl alcohol,

(e) reacting the compound of formula-7 with isobutyric anhydride in presence of potassium carbonate to provide 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1,

(f) crystallizing the compound of formula-1 from n-hexane to provide crystalline compound of formula-1.

6. A process according to claim 5, the crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 is characterized by the X-Ray powder diffraction pattern having peaks at about 7.0, 8.6, 9.7, 12.4 and 19.7 ± 0.2 degrees of 2-theta as depicted in figure-1 and is further characterized by its IR and DSC patterns as depicted in figure-2 & figure-3 respectively.

7. Process for the isolation of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 from the reaction mixture obtained by the reaction of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7 with isobutyric anhydride, comprising of;

a) Distilling off the traces of isobutyric anhydride from the reaction mixture,

b) cooling the reaction mixture,

c) adding water and then basifying the reaction mixture with a suitable base selected from alkali metal hydroxides and alkali metal carbonates,

d) extraction of the compound using a suitable water-immiscible solvent selected from dichloromethane, ethylacetate and toluene,

e) subjecting the organic layer to carbon treatment,

f) filtering the reaction mixture followed by distillation of solvent from the filtrate to provide
3- isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1.

8. Process for the isolation of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1 from the reaction mixture obtained by the reaction of l-isobutyramido-2-methyl pyridinium bromide compound of formula-7 with isobutyric anhydride, comprising of;

a) Distilling off the traces of isobutyric anhydride from the reaction mixture,

b) cooling the reaction mixture,

c) adding water and then basifying the reaction mixture with 6N sodium hydroxide solution upto pH of the reaction mixture reaches to 8-12,

d) extraction of the compound using dichloromethane,

e) subjecting the organic layer to carbon treatment,

f) filtering the reaction mixture followed by distillation of solvent from the filtrate to provide 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1.

9. Process for the crystallization of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine compound of formula-1, comprising of;

a) Adding a suitable solvent selected from hydrocarbon solvents and ether solvents to 3- isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1,

b) heating the reaction mixture,

c) subjecting the reaction mixture to carbon treatment,

d) filtering the reaction mixture and cooling the filtrate to -10 to -5°C,

e) stirring the reaction mixture for 45-60 min at the same temperature,

f) filtering the precipitated solid,

g) drying the compound to provide crystalline 3-isobutyryl-2-isopropyl pyrazolo[l,5-a] pyridine compound of formula-1.

10. Particle size distribution of 3-isobutyryl-2-isopropyl pyrazolo[l,5-a]pyridine having D90 value less than or equal to 150 μm.