Field of Invention:

The present invention relates to an improved process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-difluoro phenyl) tetrahydro-5-(lH-l,2,4-triazol-l-ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl]phenyl]-2-[(lS,2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1 is represented by the following structure:

Formula-1 Background of the Invention:

The triazole antifungal drug 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl) tetrahydro-5-(lH-l,2,4-triazol-l-ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl] phenyl]-2-[(lS,2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1 is commonly known as posaconazole.

U.S. Patent No. 5,661,151 (herein referred to as '151) discloses several substituted tetrahydrofuran antifungal compounds, including posaconazole. The patent discloses several processes for the preparation of posaconazole.

International Publication Numbers WO/95/ 17407(published 29 Jun. 1995 and WO 96/38443 (published 5 Dec. 1996) disclosed the methods of making the compound of formula I and its use in the treatment of antifungal infections in mammals. These International Patent Publications do not disclose or refer to, or even suggest the possible existence of a crystalline polymorph of the compound of formula I; the synthetic procedures disclosed therein produce the compound of formula I as an amorphous solid.

Three polymorphic forms of posaconazole designated as forms I, II and III are described and characterized in WO 99/18097 (US-B-6,713,481, US-B-6,958,337). Crystalline forms II and III were found to be unstable under the conditions investigated, so that crystalline form I was considered to be useful in the development of a pharmaceutical product.

Amorphous form of posaconazole produced as per the process disclosed in US5661151 by using 6N HC1 in methanol is not stable. As of the date, there is no process available in the art for the preparation of stable amorphous posaconazole.

Hence there is a need to develop an alternative process for the preparation of amorphous form of posaconazole, which is more stable when used in a pharmaceutical composition and/or which have properties that make them suitable for bulk preparation and handling.

Further, there is a need for an alternative process for the preparation of posaconazole which consistently provides amorphous form, which is eco-friendly, economical, easy to scale up for commercial levels and also avoids the above mentioned prior art problems.

Advantages of the present Invention:

Provides a novel process for the preparation of amorphous posaconazole Easy removal of residual solvent by using low boiling non-polar solvents like n-pentane. The present process consistently provides amorphous form which is free from crystallinity. Eco-friendly and easy to scale up process.

Brief Description of the Invention:

The present invention is to provide a novel process for the preparation of amorphous 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(lH-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl]phenyl]-2-[(lS,2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1.

Accordingly, the first aspect of the present invention is to provide a novel process for the preparation of amorphous 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetra hydro-5-( 1H-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy]phenyl]-1 -piperazinyl]phenyl]-2-[(1 S,2S)-1 -ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Dissolving the compound of formula-1 in a suitable solvent,
b) filtering the reaction mixture,
c) adding the filtrate to a suitable non-polar anti-solvent,
d) stirring the reaction mixture,
e) filtering the solid and then drying to get amorphous form of compound of formula-1.

The second aspect of the present invention is to provide a one-pot process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5-(2,4-difluoro phenyl)tetrahydro-5-(lH-l,2,4-triazol-l-ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl]phenyl]-2-[(lS,2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Reacting the 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one with Pd/C under hydrogen pressure in the presence of mineral acid in a suitable solvent,

b) filtering the reaction mixture and adding organic solvent to the filtrate,

c) " cooling the reaction mixture and adjusting the pH of the reaction mixture,

d) adding water to the reaction mixture,

e) filtering the precipitated solid,

f) adding organic solvent to the solid, obtained in step-(e) and heating the reaction mixture,

g) filtering the reaction mixture,

h) adding water to the filtrate and stirring the reaction mixture, i) filtering the precipitated solid, j) optionally purifying the obtained solid in step-(i), k) adding chlorosolvent to the solid,

1) slowly adding the mixture obtained in step-(k) to hydrocarbon solvent,

m) stirring the reaction mixture,

n) filtering the solid and then drying to get amorphous form of compound of formula-1.

Detailed Description of Invention:

As used herein the present invention the term "suitable solvents" refers to solvents selected from "ester solvents" like ethyl acetate, methyl acetate, isopropyl acetate; "ether solvents" like tetrahydrofuran, diethyl ether, methyl tert-butyl ether; "hydrocarbon solvents" like toluene, n-pentane, hexane, heptane and cyclohexane; "polar aprotic solvents" like dimethyl acetamide, dimethyl formamide, dimethyl sulfoxide; "ketone solvents" like acetone, methyl ethyl ketone, methyl isobutyl ketone; "alcoholic solvents" like methanol, ethanol, n-propanol, isopropanol, n-butanol and isobutanol; "chloro solvents" like dichloromethane, chloroform and ethylene dichloride; "nitrile solvents" like acetonitrile and propionitrile; polar solvents like water; and mixtures thereof.

As used herein the present invention, the term "anti-solvent" refers to a solvent which is used to precipitate the solid from a solution and the suitable anti-solvent used herein the present invention is hydrocarbon solvent.

As used herein the term suitable "mineral acid" is selected from hydrochloric acid, hydrobromic acid, hydroiodic acid and sulfuric acid.

Accordingly, the first aspect of the present invention is to provide a novel process for the preparation of amorphous 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl) tetrahydro-5-( 1H-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy]phenyl]-1 -piperazinyl]phenyl]-2-[(1 S,2S)-1 -ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l ,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Dissolving the compound of formula-1 in a suitable solvent,

b) filtering the reaction mixture,

c) adding the filtrate to a suitable anti-solvent such as non-polar solvent,

d) stirring the reaction mixture,

e) filtering the solid and then drying to get amorphous form of compound of formula-1.

Wherein, the suitable solvent used is selected from chloro solvents, ketone solvents, ester solvents, ether solvents, alcoholic solvents and the suitable anti-solvent is selected from non-polar solvents such as hydrocarbon solvents.

In a preferred embodiment of the present invention to provide a novel process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5-(2,4-difluoro phenyl) tetrahydro-5-(1H-1,2,4-triazol-1 -ylmethyl)-3 furanyl]methoxy]phenyl]-1 -piperazinyl]phenyl]-2-[( 1S, 2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Dissolving the compound of formula-1 in dichloromethane,

b) filtering the reaction mixture,

c) adding the filtrate to the n-pentane,

d) stirring the reaction mixture,

e) filtering the solid and then drying to get amorphous form of compound of formula-1.

The second aspect of the present invention is to provide a one-pot process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-difluoro phenyl) tetrahydro-5-(lH-l,2,4-triazol-l-ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl]phenyl]-2-[(lS, 2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Reacting the 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one with Pd/C under hydrogen pressure in presence of mineral acid in a suitable solvent,

b) filtering the reaction mixture and adding organic solvent to the filtrate,

c) cooling the reaction mixture and adjusting the pH of the reaction mixture,

d) adding water to the reaction mixture,

e) filtering the precipitated solid,

f) adding organic solvent to the solid, obtained in step-(e) and heating the reaction mixture,

g) filtering the reaction mixture,

h) adding water to the filtrate and stirring the reaction mixture,

i) filtering the precipitated solid,

j) optionally, purifying the obtained solid in step-(i),

k) adding chlorosolvent to the solid,

1) slowly adding the mixture obtained in step-(k) to hydrocarbon solvent,

m) stirring the reaction mixture,

n) filtering the solid and then drying to get amorphous form of compound of formula-1.

Wherein, the suitable solvent used in step-(b) & (f) is selected from ketone solvents, preferably acetone; the suitable solvent used in step-(k) is selected from chloro solvents, preferably dichloromethane; and the suitable solvent used in step-(l) is selected from non-polar solvents such as hydrocarbon solvents, preferably n-pentane.

In a preferred embodiment of the present invention to provide a one-pot process for the preparation of amorphous 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl) tetrahydro-5-(l H-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy]phenyl]-1 -piperazinyl]phenyl]-2-[(l S, 2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Reacting the 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one with Pd/C under hydrogen pressure in presence of hydrochloric acid in methanol,

b) filtering the reaction mixture and adding acetone to the filtrate,

c) cooling the reaction mixture and adjusting the pH of the reaction mixture,

d) adding water to the reaction mixture,

e) filtering the precipitated solid,

f) adding acetone to the solid, obtained in step-(e) and heating the reaction mixture,

g) filtering the reaction mixture,

h) adding water to the filtrate and stirring the reaction mixture,

i) filtering the precipitated solid,

j) optionally, purifying the obtained solid in step-(i),

k) adding dichloromethane to the solid,

1) slowly adding the mixture obtained in step-(k) to n-pentane, m) stirring the reaction mixture,

n) filtering the solid and then drying to get amorphous form of compound of formula-1.

The benzylated Posaconazole and Posaconazole compound of formula-1 used in the present invention can be prepared as per the any known methods in the art.

RS/OVI analysis of amorphous posaconazole is carried out on Agilent GC-6850 series-2 with Flame Ionization detector, column AP vac, flow 2 psi and load is 1 μ l, detector temperature is 260°C and carrier gas is helium.

Posaconazole produced by the present invention can be further micronized or milled to get the desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements. Techniques that may be used for particle size reduction include, but not limited to ball, roller and hammer mills, and jet mills. Milling or micronization may be performed before drying, or after the completion of drying of the product.

PXRD analysis of posaconazole and its intermediates was carried out using BRUKER/AXS X-Ray diffractometer using Cu Kα radiation of wavelength 1.5406 A° and continuous scan speed of 0.03°/min.

The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.

Examples:

Example-1: Preparation of amorphous posaconazole compound of formula-1:

Posaconazole (100 g) and dichloromethane (500 ml) were charged into a clean and dry RBF at 25-30°C and the resulting mixture was stirred for 15 minutes at the same temperature to get clear solution. The solution was filtered and the filtrate was slowly added to n-pentane (7500 ml) in another RBF at -30 to -20°C. The resulting mixture was stirred for 2 hrs at the same temperature. The compound obtained was filtered and washed with n-pentane and dried to get the title compound.

Yield: 95%.

Example-2: Preparation of amorphous posaconazole compound of formula-1:

The amorphous posaconazole compound of formula-1 can be obtained by repeating the process exemplified in example-1 at a temperature of 20-3 3°C to get the title compound.

Example-3: One-pot process for the preparation of amorphous posaconazole compound of formula-1:

5N hydrochloric acid (200 ml) and 5% Pd-C (50 g) were added to a solution of 4-(4-(4-(4-(((3R,5R)-5-((l H-1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydro furan-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3 S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (100 g) in methanol (850 ml) in an autoclave. The reaction mixture was hydrogenated for 5 hours under a hydrogen gas pressure of 4 kg/cm2 at 50°C. After completion of the reaction, the reaction mixture was filtered off and washed with methanol. pH of the filtrate was adjusted to 7.0 with aqueous sodium hydroxide solution. Water was added to the reaction mixture and stirred for 1 hour at 25-35°C. Filtered the precipitated solid and washed with purified water. Acetone (1200 ml) was added to the obtained solid and heated to 55-60°C. Stirred the reaction mixture for 30 minutes and filtered on hyflow bed and washed with acetone. 1300 ml of water was slowly added to the filtrate at 30-35°C. Stirred the reaction mixture for 60 minutes at 30-35°C and filtered the precipitated solid and washed the solid with water. The obtained solid was dissolved in 1000 ml of isopropyl alcohol at 60-65°C. Cooled the reaction mixture to 30-35°C and stirred for 2 hours at 30-35°C. The precipitated solid was filtered and washed with isopropyl alcohol. The obtained solid was dissolved in 280 ml of dichloromethane. The obtained solution was filtered and the filtrate was added to 4200 ml of n-heptane at 25-30°C. The reaction mixture was stirred for 2 hours at 25-30°C, filtered the obtained solid and washed with n-heptane. Dried the obtained solid to get amorphous compound of formula-1. Yield: 52 g.

Example-4: One-pot process for the preparation of amorphous posaconazole compound of formula-1:

5N hydrochloric acid (200 ml) and 5% Pd-C (50 g) were added to a solution of 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)tetrahydro furan-3-yl) methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3 S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (100 g) in methanol (850 ml) in an autoclave. The reaction mixture was hydrogenated for 5 hours under a hydrogen gas pressure of 4 kg/cm2 at 50°C. After completion of the reaction, the reaction mixture was filtered off and washed with methanol. pH of the filtrate was adjusted to 7.0 with aqueous sodium hydroxide solution. Water was added to the reaction mixture and stirred for 1 hour at 25-35°C. Filtered the precipitated solid and washed with purified water. Acetone (1200 ml) was added to the obtained solid and heated to 55-60°C. Stirred the reaction mixture for 30 minutes and filtered on hyflow bed and washed with acetone. 1300 ml of water was slowly added to the filtrate at 30-35°C. Stirred the reaction mixture for 60 minutes at 30-35°C and filtered the precipitated solid and washed the solid with water. The obtained solid was dissolved in 300 ml of dichloromethane. The obtained solution was filtered and the filtrate was added to 4500 ml of n-heptane at 25-30°C. The reaction mixture was stirred for 2 hours at 25-30°C, filtered the obtained solid and washed with n-heptane. Dried the obtained solid to get amorphous compound of formula-1. Yield: 55 g.

Example-5: Preparation of crystalline Form-I of posaconazole compound of formula-1:

Posaconazole (100 g) and dichloromethane (500 ml) were charged into a clean and dry RBF at 25-30°C and the resulting mixture was stirred for 15 minutes at the same temperature. The reaction mixture was filtered and 80% of the solvent from the filtrate was distilled off under reduced pressure and co-distilled with isopropanol. The isopropanol (2000 ml) was added to the obtained residue. Heated the reaction mixture to 70-75°C and stirred for 15 minutes at the same temperature. The reaction mixture was cooled to 25-3 0°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid and washed with isopropanol then dried to get crystalline Form-I of Posaconazole. M.R: 168-171°C; Yield: 96%.

The PXRD of the obtained compound matches with prior-art crystalline Form-I of Posaconazole.

Example-6: Preparation of amorphous posaconazole from crystalline Form-I of posaconazole:

Crystalline form-I of Posaconazole (100 g) and dichloromethane (500 ml) were charged into a clean and dry RBF at 25-30°C and the resulting mixture was stirred to get clear solution. The solution was filtered and the filtrate was slowly added to n-pentane (7500 ml) in another RBF at 25 to 30°C. The resulting mixture was stirred for 2 hrs at the same temperature. The precipitated solid was filtered and washed with n-pentane and dried to get the title compound.

Yield: 95%.

Example-7: Preparation of amorphous posaconazole from crystalline Form-I of posaconazole:

The amorphous posaconazole compound of formula-1 can be obtained by repeating the process exemplified in example-6 at a temperature of-30 to -20°C to get the title compound.

Example-8: Preparation of crystalline Form-I of posaconazole from crystalline Form-Ill of posaconazole:

Crystalline form-Ill of Posaconazole (100 g) and isopropanol (2000 ml) were charged into a clean and dry RBF at 25-30°C. The reaction mixture was heated to 70-75°C to get the clear dissolution. The reaction mixture was slowly cooled to 25-30°C and stirred for 2 hours at the same temperature. Filtered the precipitated solid washed with isopropanol and then dried to get crystalline Form-I of Posaconazole. M.R: 168-171°C; Yield: 96%.

The PXRD of the obtained compound matches with prior-art crystalline Form-I of Posaconazole.

Example-9: Preparation of amorphous posaconazole from crystalline Form-Ill of posaconazole:

Crystalline form-Ill of Posaconazole (100 g) and dichloromethane (500 ml) were charged into a clean and dry RBF at 25-30°C and the resulting mixture was stirred to get clear solution. The solution was filtered and the filtrate was slowly added to n-pentane (7500 ml) in another RBF at -30 to -20°C. The resulting mixture was stirred for 2 hrs at the same temperature. Filtered the precipitated solid washed with n-pentane and dried to get the title compound.

Yield: 95%.

The crystalline form-Ill of the posaconazole used as a starting material in example-8 & 9 can be prepared from the process known in the art or from the process disclosed in US 6,958,337 hereinafter incorporated as a reference.

We Claim:

1. A process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-difluoro phenyl)tetrahydro-5-(l H-1,2,4-triazol- l-ylmethyl)-3furanyl]methoxy]phenyl]-l -piperazinyl]phenyl]-2-[(l S,2S)-1 -ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1,

Formula-1 which comprising of:

a) Dissolving the compound of formula-1 in a suitable solvent,

b) filtering the reaction mixture,

c) adding filtrate to a suitable anti-solvent,

d) stirring the reaction mixture,

e) filtering the solid and then drying to get amorphous form of compound of formula-1.

2. The process according to claim-1, wherein, the suitable solvent used is selected from chloro solvents, ketone solvents, ester solvents, ether solvents, alcoholic solvents and the suitable anti-solvent is selected from non-polar solvents such as hydrocarbon solvents.

3. A process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-difluoro phenyl)tetrahydro-5-(lH-l,2,4-triazol-l-ylmethyl)-3furanyl]methoxy]phenyl]-l-piperazinyl]phenyl]-2-[(lS,2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Dissolving the compound of formula-1 in dichloromethane,
b) filtering the reaction mixture,
c) adding filtrate to the n-pentane,
d) stirring the reaction mixture,

e) filtering the solid and then drying to get amorphous form of compound of formula-1.

4. A one-pot process for the preparation of amorphous 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-
difluorophenyl)tetrahydro-5-(l H-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy] phenyl]-l -piperazinyl]phenyl]-2-[(l S, 2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H- l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Reacting the 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one with Pd/C under hydrogen pressure in presence of mineral acid in a suitable solvent,

b) filtering the reaction mixture and adding organic solvent to the filtrate,
c) cooling the reaction mixture and adjusting the pH of the reaction mixture,
d) adding water to the reaction mixture,
e) filtering the precipitated solid,
f) adding organic solvent to the solid, obtained in step-(e) and heating the reaction mixture,
g) filtering the reaction mixture,
h) adding water to the filtrate and stirring the reaction mixture, i) filtering the precipitated solid, j) optionally, purifying the obtained solid in step-(i), k) adding chlorosolvent to the solid,

1) slowly adding the mixture obtained in step-(k) to hydrocarbon solvent, m) stirring the reaction mixture,

n) filtering the solid and then drying to get amorphous form of compound of formula-1.

5. The process according to claim-4, the suitable solvent used in step-(b) & (f) is selected from ketone solvents, preferably acetone; the suitable solvent used in step-(k) is selected from chloro solvents, preferably dichloromethane; and the suitable solvent used in step-(l) is selected from non-polar solvents such as hydrocarbon solvents, preferably n-pentane.

6. A one-pot process for the preparation of amorphous 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(l H-1,2,4-triazol-1 -ylmethyl)-3furanyl]methoxy] phenyl]-l-piperazinyl]phenyl]-2-[(lS, 2S)-l-ethyl-2-hydroxypropyl]-2,4-dihydro-3H- l,2,4-triazol-3-one compound of formula-1, which comprising of:

a) Reacting the 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difiuorophenyl)tetrahydrofuran-3 -yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one with Pd/C under hydrogen pressure in presence of hydrochloric acid in methanol,

b) filtering the reaction mixture and adding acetone to the filtrate,
c) cooling the reaction mixture and adjusting the pH of the reaction mixture,
d) adding water to the reaction mixture,
e) filtering the precipitated solid,
f) adding acetone to the solid, obtained in step-(e) and heating the reaction mixture,
g) filtering the reaction mixture,

h) adding water to the filtrate and stirring the reaction mixture, i) filtering the precipitated solid, j) optionally, purifying the obtained solid in step-(i), k) adding dichloromethane to the solid, 1) slowly adding the mixture obtained in step-(k) to n-pentane, m) stirring the reaction mixture,

n) filtering the solid and then drying to get amorphous form of compound of formula-1.

7. The amorphous compound of formula-1, obtained from any of the preceding claims can be useful as a medicament for the preparation of pharmaceutical composition.