CLAIMS
1. One pot process for the preparation of amorphous form of 4-[4-[4-[4-[[ (3R,5R)-5-
(2,4-difluorophenyl)tetrahydro-5(lH-l,2,4-triazol-l-ylmethyl)-3-
5 furanyl] methoxy]phenyl] -1 -piperazinyl] phenyl] -2- [(1 S,2S)-1 -ethyl-2-
hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one of the structural formula (IV) comprising of:
a) Treating 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluoro
phenyl)tetrahydrofuran -3-yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-
10 2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one of the structural formula
(III) with concentrated hydrochloric acid and stirring the reaction mixture at an elevated temperature
b) Cooling the reaction mixture and adding a halogenated hydrocarbon solvent
c) Separating the layers
15 d) Adding a halogenated hydrocarbon solvent to the aqueous layer and adjusting the
pH to 8 - 12.
e) Partially concentrating the organic layer and optionally adding an aliphatic ketone
solvent to the reaction mixture
f) Mixing the reaction mixture of step e) and an aliphatic hydrocarbon solvent at a
20 lower temperature
g) Filtering and optionally washing with aliphatic hydrocarbon solvent to provide
amorphous compound of the structural formula IV.
2. One pot process according to claim 1 for the preparation of amorphous form of 4-[4-
[4-[4-[[ (3R,5R)-5- (2,4-difluorophenyl)tetrahydro-5(lH-l,2,4-triazol-l-ylmethyl)-3-
25 furanyl] methoxy]phenyl] -1 -piperazinyl] phenyl] -2- [(1 S,2S)-1 -ethyl-2-
hydroxypropyl]-2,4-dihydro-3H-l,2,4-triazol-3-one of the structural formula (IV) comprising of:
a) Treating 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluoro phenyl)tetrahydrofuran -3-yl)methoxy)phenyl)piperazin-1 -yl)phenyl)-1 -((2S,3S)-
30 2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one of the structural formula

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(III) with concentrated hydrochloric acid and stirring the reaction mixture at a temperature of 55 - 70 °C
b) Cooling the reaction mixture and adding dichloromethane
c) Separating the layers
5 d) Adding dichloromethane to the aqueous layer and adjusting the pH to 8 - 12.
e) Partially concentrating the organic layer and optionally adding acetone to the
reaction mixture
f) Mixing the reaction mixture of step e) and cyclohexane at a temperature of 10-
25°C.
10 g) Filtering and optionally washing with cyclohexane to provide amorphous
compound of the structural formula IV.
3. A process for preparation of crystalline B-3 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-
1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-
yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-
15 lH-l,2,4-triazol-5(4H)-one (III) comprising of:
a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
hydroxyphenyl)piperazin-l-yl)phenyl)-lH-l,2,4-triazol-5(4H)-one (II) in a polar
organic solvent under nitrogen atmosphere with an alkali solution at a lower
temperature
20 b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)
tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding an aliphatic ester solvent and water to the solution of step b)
d) Separating the layers
e) Partially concentrating the organic layer and adding an aliphatic hydrocarbon 25 solvent at a lower temperature
f) Stirring the reaction mass of step e) at elevated temperature
g) Cooling the reaction mass of step f), filtering and optionally washing with
aliphatic hydrocarbon solvent to provide compound III in crystalline Form B-3.
4. A process for preparation of crystalline B-3 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-
30 1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-

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yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (III) as claimed in claim 3 comprising of:
a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
hydroxyphenyl)piperazin-1 -yl)phenyl)- 1H-1,2,4-triazol-5(4H)-one (II) in
5 dimethyl sulfoxide under nitrogen atmosphere with sodium hydroxide solution at
10-20°C
b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)
tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding ethyl acetate and water to the solution of step b)
10 d) Separating the layers
e) Partially concentrating the organic layer to 4 - 7 volumes and adding n-Heptane at 20 to 30°C
f) Stirring the reaction mass of step e) at 40 to 50°C
g) Cooling the reaction mass of step f), filtering and optionally washing with n-
15 Heptane to provide compound of the structural formula III in crystalline Form B-3
5. A crystalline B-3 form of 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 (III) characterized by
its powder X-ray diffractogram having peaks at about 7.07, 14.49, 15.68, 16.50,
20 18.05, 20.13, 20.87, 22.85 and 24.42 ± 0.2 degrees of 20.
6. A crystalline B-3 form of 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 (III) as claimed in
claim 5 characterized by a XRD pattern as depicted in Figure 3.
25 7. A process for preparation of crystalline B-1 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (III) comprising of: a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
30 hydroxyphenyl)piperazin-l-yl)phenyl)-lH-l,2,4-triazol-5(4H)-one (II) in a polar
organic solvent with an alkali solution at a lower temperature

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b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl) tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding an aliphatic ester solvent and water to the solution of step b)
d) Separating the layers
5 e) Concentrating the organic layer and adding a halogenated hydrocarbon solvent
and an aliphatic hydrocarbon solvent at a lower temperature f) Cooling the reaction mass of step e), filtering and optionally washing with aliphatic hydrocarbon solvent to provide compound of the structural formula III in crystalline Form B-1. 10 8. A process for preparation of crystalline B-1 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (III) as claimed in claim 7 comprising of:
a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
15 hydroxyphenyl)piperazin-l-yl)phenyl)-lH-l,2,4-triazol-5(4H)-one (II) in
dimethyl sulfoxide with sodium hydroxide solution at 5-15° C.
b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)
tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding ethyl acetate and water to the solution of step b)
20 d) Separating the layers
e) Concentrating the organic layer and adding dichloromethane and n-Heptane solvent at a lower temperature
f) Cooling the reaction mass of step e), filtering and optionally washing with n-Heptane to provide compound of the structural formula III in crystalline Form
25 B-1.
9. A crystalline B-1 form of 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 (III) characterized by
its powder X-ray diffractogram having peaks at about 4.14, 6.85, 9.92, 15.28, 15.69,
30 16.59, 17.29, 17.92, 18.27, 18.91,20.63, 19.95, 23.58 and 25.12 ± 0.2 degrees of 20.
10. A crystalline B-1 form of 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 -

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((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (III) as claimed in
claim 9 characterized by a XRD pattern as depicted in Figure 1.
11. A process for preparation of crystalline B-2 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-
1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-
5 yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-
lH-l,2,4-triazol-5(4H)-one (III) comprising of:
a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
hydroxyphenyl)piperazin-l-yl)phenyl)-lH-l,2,4-triazol-5(4H)-one (II) in a
polar organic solvent with an alkali solution at a lower temperature
10 b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)
tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding an aliphatic ester solvent and water to the solution of step b)
d) Separating the layers
e) Partially concentrating the organic layer and adding an aliphatic hydrocarbon 15 solvent at a lower temperature
f) Stirring the reaction mass of step e) at elevated temperature
g) Cooling the reaction mass of step f), filtering and optionally washing with
aliphatic hydrocarbon solvent to provide compound of the structural formula
III in crystalline Form B-2.
20 12. A process for preparation of crystalline B-2 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl) piperazin-l-yl)phenyl)-l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-lH-l,2,4-triazol-5(4H)-one (III) as claimed in claim 11 comprising of:
a) Treating a solution of l-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-
25 hydroxyphenyl)piperazin-l-yl)phenyl)-lH-l,2,4-triazol-5(4H)-one (II) in
dimethyl sulfoxide with sodium hydroxide solution at a lower temperature
b) Adding ((3S,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-(2,4-difluorophenyl)
tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (I) to step a) solution
c) Adding ethyl acetate and water to the solution of step b)
30 d) Separating the layers
e) Partially concentrating the organic layer 2-4 volumes and adding heptane at 25 to 30°C

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f) Stirring the reaction mass of step e) at 40 to 50°C
g) Cooling the reaction mass of step f), filtering and optionally washing with heptane to provide compound of the structural formula III in crystalline Form B-2.
13. A crystalline B-2 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-
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 (III) characterized by its powder X-ray diffractogram having peaks at about 4.20, 9.27, 14.22, 15.46, 15.82, 16.45, 17.31, 19.09, 20.47, 21.18 and 24.74+0.2 degrees of 20.
14. A crystalline B-2 form of 4-(4-(4-(4-(((3R,5R)-5-((lH-l,2,4-triazol-l-yl)methyl)-5-
10 (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 (III) as claimed in claim 13 characterized by a XRD pattern as depicted in Figure 2.