DESC:Title of The Invention
Improved process for the preparation of Elagolix Sodium.

Field of The Invention
The present invention relates to a process for the preparation of Elagolix Sodium having the structural formula (I).

The present invention also relates to novel intermediates which are useful in the preparation of Elagolix Sodium.

Background of the Invention

Elagolix Sodium is a gonadotropin releasing hormone antagonist (GnRH antagonist) used in the treatment of pain associated with endometriosis in women. It is also in phase III clinical trials for the treatment of uterine fibroids in women. Endometriosis is a frequent cause of infertility, connected with a chronic pelvic and pre-menstrual pain.

Elagolix Sodium is chemically known as Sodium 4-({(1R)-2-[5-(2-fluoro-3-methoxyphenyl) -3-{[2-fluoro-6-(trifluoro methyl) phenyl]methyl}-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H) -yl]-1-phenylethyl}amino) butanoate. Food and Drug Administration granted marketing Authorisation for Elagolix Sodium in United States under the brand name “ORILISSA” for the treatment of endometriosis-associated pain.

Elagolix was first disclosed in WO 2005007165 A1. In example-1H of the said application, Elagolix fee acid is described as a white gel and it is passed through a DOWEX MSC-1 macroporous strong cation exchange column to convert the acid to its sodium salt. Finally, lyophilization gives the Elagolix Sodium as a white solid.

The reported processes for the preparation of Elagolix Sodium utilizes cation exchange column which makes it difficult for bulk manufacturing as well as it effects the overall yield making the process uneconomical.

In view of all these disadvantages, there is a significant need to develop a stable, commercially viable process for the preparation of highly pure Elagolix Sodium with good yield.

Summary of The Invention

The present invention provides a cost effective, novel and an efficient process for the preparation of Elagolix Sodium with higher yields and purity.

In one embodiment, the present invention provides a process for the preparation of Elagolix Sodium of formula-I.

which comprises:
a) coupling of compound of formula-II

with compound of formula-III

in presence of a base and solvent to obtain compound of formula-IV;

b) condensation of compound of formula-IV with compound of formula-V

in presence of a base and solvent to obtain compound of formula-VI;

c) chiral reduction of compound of formula-VI using reducing agent to obtain compound of formula-VII;

d) protecting compound of formula-VII with a hydroxy protecting group in presence of a base and solvent to obtain compound of formula-VIII;
pg = hydroxy protecting group
e) condensation of compound of formula-VIII with compound of formula-IX

in presence of a base to obtain compound of formula-X;

f) ring opening of compound of formula-X in presence of concentrated hydrochloric acid to obtain Elagolix free acid of formula-XI;

g) salt formation of Elagolix free acid of formula-XI with dicyclo hexyl amine in an organic solvent to obtain compound of formula-XII;

h) neutralization of compound of formula-XII with an acid followed by salt formation with sodium hydroxide in an organic solvent to obtain Elagolix Sodium of formula-I.

In yet another embodiment, the present invention provides a process for the preparation of Elagolix Sodium compound of formula-I.

which comprises:
a) chiral reductive amination of compound of formula-VI

with a reducing agent in a solvent to obtain compound of formula-XIV;

b) condensation of compound of formula-XIV with 4-bromo butyric acid in presence of a base to obtain compound of formula-XI;

c) salt formation of compound of formula-XI with sodium hydroxide in a solvent to obtain Elagolix sodium of formula-I.

In yet another embodiment, the present invention provides the following novel intermediate which are useful in the preparation of Elagolix Sodium.

In yet another embodiment, the present invention provides amorphous form of Elagolix salicylic acid salt of formula XII(a).

Detailed Description of the Invention

Accordingly, the present invention provides various processes for the preparation of Elagolix Sodium of formula-I.

The main embodiment of the present invention provides an improved process for the preparation of Elagolix Sodium of formula (I) as shown in the Scheme-I given below.

Scheme-I

In step-1, coupling of compound of formula-II with compound of formula-III in presence of a base and a reagent to obtain compound of formula-IV.
The base used in the reaction is selected from inorganic base such as alkali metal hydroxides, alkali metal carbonates and alkali metal bicarbonates or organic base such as triethylamine, diisopropylethylamine and pyridine, preferably using sodium carbonate.
The coupling reagent used in the reaction is selected from Tetrakis (triphenyl phosphine) palladium, palladium acetate, Tris (dibenzylidene acetone) dipalladium, preferably using Tetrakis (triphenyl phosphine) palladium.
The reaction temperature may range from 50-80 °C and preferably at a temperature in the range from 50-70 °C. The duration of the reaction may range from 8-12 hours, preferably for a period of 8-10 hours.
Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; ketone solvents such as acetone, methyl tert-butyl ketone; aromatic organic solvents such as toluene, xylene; dimethyl formamide, water or its mixture thereof; preferably using acetone-water.

In step-2, condensation of compound of formula-IV with compound of formula-V in presence of a base and solvent to obtain compound of formula-VI.

Base used in the reaction is selected from inorganic base such as alkali metal hydroxides, alkali metal carbonates and alkali metal bicarbonates or organic base such as triethylamine, diisopropylethylamine and pyridine, preferably using potassium carbonate.
Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene and dimethyl formamide; preferably using dimethyl formamide.

In step-3, reduction of compound of formula-VI with keto reductase enzyme or sulfinamine or borane dimethyl sulphide complex or Chloro diisopino campheyl borane or 2-(R)-methyl CBS in presence of a solvent to obtain compound of formula-VII.
Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene; ether solvent such as tetrahydrofuran; preferably tetrahydrofuran.

In step-4, protection of compound of formula-VII with a hydroxy protecting group in presence of a base and solvent to obtain compound of formula-VIII.
Hydroxy protecting group used in the reaction may be selected from benzyloxycarbonyl, C1-C6 straight chain or branched chain alkoxy carbonyl such as methoxycarbonyl, ethoxy carbonyl, tert-butyloxycarbonyl, acetyl, trichloroacetyl, trifluoroacetyl, 1-ethoxyethyl, benzoyl, benzyl, p-methoxybenzyl, methylthiomethyl, pivaloyl, trityl (triphenylmethyl), methoxy-iso-propanyl, tri (C1-C6 straight chain or branched chain alkyl) silyl groups such as trimethyl silyl (TMS), tri-ethyl silyl, triisopropylsilyl, tri-iso-propylsilyloxy methyl, tert-butyl-dimethylsilyl, tert-butyl- biphenylsilyl, furanidinyl, dihydropyran, tetrahydropyran, trichloroethoxy carbonyl and methane sulfonyl; preferably using methane sulfonyl group.

Base used in the reaction is selected from inorganic base such as alkali metal hydroxides, alkali metal carbonates and alkali metal bicarbonates or organic base such as triethylamine, diisopropylethylamine and pyridine, preferably using triethylamine.

Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene; ketone solvents such as acetone, methyl isobutyl ketone; preferably using acetonitrile.
Optionally the protecting group may be deprotected by treating with sodium azide followed by reduction to obtain required amine compound.

In step-5, coupling of compound of formula-VIII with compound of formula-IX in presence of a base to obtain compound of formula-X.

Base used in the reaction is selected from alkali metal carbonates such as sodium carbonate, potassium carbonate and alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; alkali metal alkoxides such as sodium methoxide and potassium methoxide Preferably, sodium methoxide.
The reaction temperature may range from 20-40 °C and preferably at a temperature in the range from 25-35 °C. The duration of the reaction may range from 05-20 hours, preferably for a period of 10-12 hours.

In step-6, ring opening reaction of compound of formula-X with concentrated hydrochloric acid to obtain compound of formula-XI.

In step-7, salt formation of Elagolix free acid of formula-XI with an appropriate base such as Dicyclohexyl amine, triethyl amine, tri ethanol amine in an organic solvent to obtain Elagolix salt of formula-XII; preferably using base is dicyclohexylamine.

Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene; preferably using toluene.

In step-8, neutralization of Elagolix salt of formula-XII with an acid such as acetic acid followed by salt formation with aqueous sodium hydroxide or sodium hydroxide flakes to obtain Elagolix Sodium of compound of formula-I.

In yet another embodiment the present invention provides an improved process for the preparation of Elagolix Sodium of formula (I) as shown in the scheme-III given below:

Scheme-III
In step-1, reduction of compound of formula-VI with a reducing agent to obtain compound of formula-XIV. The reducing agent used in this reaction is selected from keto reductase enzyme, Sodium cyanoborohydride, sodium triacetoxy borohydride, borane dimethyl sulphide complex or InCl3/Et3SiH/Methanol or [RuCl2(p-cymene)]2/Ph2SiH2 catalytic system is very efficient for the reductive amination of carbonyl compounds.
Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene; preferably using methanol.

In step-2, condensation of compound of formula-XIV with 4-bromobutyric acid in presence of a base to obtain compound of formula-XI.
Solvent used in the reaction is selected from alcoholic solvents such as methanol, ethanol, propanol; chlorinated solvents such as dichloromethane, carbon tetrachloride; nitrile solvent such as acetonitrile, propionitrile; ester solvents such as ethyl acetate, isopropyl acetate; aromatic organic solvents such as toluene, xylene; preferably using dimethyl formamide.
Base used in the reaction is organic or inorganic base. Inorganic base selected from alkali metal carbonates such as sodium carbonate, potassium carbonate and alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; alkali metal alkoxides such as sodium methoxide and potassium methoxide; organic base is selected from triethyl amine, diisopropyl ethyl amine, preferably using diisopropyl ethyl amine.
In step-3, salt formation of compound of formula-XI with aqueous sodium hydroxide or sodium hydroxide flakes to obtain Elagolix Sodium of compound of formula-I.

In yet another embodiment, the present invention provides Elagolix salicylic acid salt of formula XII(a).

The present invention provides amorphous form of Elagolix salicylic acid of formula-XII a.

Elagolix free acid of formula-XI may react with an appropriate acid such as hydrochloric acid, hydrobromic acid, acetic acid, sulfuric acid, trifluoro acetic acid, phosphoric acid, formic acid, methane sulfonic acid, para-toluene sulfonic acid, salicylic acid, oxalic acid, succinic acid, benzoic acid, maleic acid, fumaric acid, Pamoic acid, citric acid, uric acid, malic acid to obtain corresponding salt.
The corresponding salt can be neutralized by using an appropriate base such as sodium hydroxide flakes or aqueous sodium hydroxide solution to obtain pure Elagolix sodium.

Scheme-IV
Elagolix ethyl ester undergoes ester hydrolysis by using aqueous sodium hydroxide solution to obtain Elagolix free acid, which is further converted into salicylic acid salt by using methanol and salicylic acid.
Neutralization of Elagolix salt of formula-XII a with a base like aqueous sodium hydroxide or sodium hydroxide flakes to obtain Elagolix Sodium of compound of formula-I.

EXPERIMENTAL PORTION

The details of the invention are given in the examples provided below, which are given to illustrate the invention only and therefore should not be construed to limit the scope of the invention.

Example-1: Process for the preparation of Elagolix Sodium

Stage-1: Synthesis of compound of formula-IV
Aqueous potassium hydroxide solution (10 mL) is added to a mixture of (2-fluoro-3-methoxy phenyl) boronic acid (10 grams), 5-bromo-1-(2-fluoro-6-(Trifluoromethyl) benzyl)-6-methyl pyrimidine-2,4(1H,3H)-dione (5.35 grams), acetone and water at 25-30 °C and stirred for 10 minutes at the same temperature. Tri-tert-butyl phosphonium tetrafluoroborate (80 mg) and Tetrakis (triphenyl phosphine) palladium was added to the reaction mixture at 25-30 °C. Heated the reaction mixture to 65-70 °C and stirred for 10 hours at the same temperature. Cooled the reaction mixture to 25-30 °C and acetic acid was added to the reaction mixture at the same temperature. Filtered the precipitated solid and dried to get the title compound.
Yield: 76 %.

Stage-2: Synthesis of compound of formula-VI
Compound obtained in stage-1 (50 grams) was dissolved in N,N-dimethylformamide (150 mL) at 25-30 °C and bromo phenyl acetate (28 grams) was added to it at the same temperature. Stirring the resulting reaction mixture for 4 hours at 25-30°C. water was added to the reaction mixture. Filtered the precipitated solid and dried to get the title compound.
Yield: 85 %

Stage-3: Synthesis of compound of formula-VII
Compound obtained in stage-2 (50 grams) was dissolved in tetrahydrofuran (300 mL) and stirred for 10 minutes at the same temperature. Borane dimethyl sulphide complex was added to the reaction mixture at 0-10 °C and stirred for 2-3 hours at the same temperature. After completion of reaction, methanol and diluted hydrochloric acid were added to the reaction mixture. Filtered the precipitated solid and dried to get the title compound.
Yield: 80 %.

Stage-4: Synthesis of compound of formula-VIII
Compound obtained in stage-3 was dissolved in acetonitrile (350 mL) at 25-30°C and stirred for 10 minutes at the same temperature. Triethylamine (19.5 grams) was added to the resulting reaction mixture at 25-30°C. Methane sulfonyl chloride (11 grams) was added to the reaction mixture at 0-10°C and stirred for 6-8 hours at the same temperature. Volatiles were removed from the reaction mixture under reduced pressure. The obtained residue was dissolved in methanol and water at 25-30°C and stirred for 30 minutes at the same temperature. Filtered the solid and dried to get the title compound.
Yield: 90 %.

Stage-5: Synthesis of compound of formula-X
Compound obtained in stage-4 was dissolved in acetonitrile (80 mL) at 25-30°C. Sodium methoxide solution (62 mL) and 2-Pyrrolidinone (6.1 grams) was added to the resulting reaction mixture within 2 hours at 25-30°C and stirred for 10-12 hours at the same temperature. After consumption of starting material, volatiles were removed from the reaction mixture under reduced pressure. Dichloromethane was added to the obtained residue and stirred for 10 minutes at the same temperature. Volatiles were removed from the reaction mixture under reduced pressure. Ethyl acetate was added to the obtained compound at 25-30°C. Filtered the precipitated solid and dried to get the title compound.
Yield: 79 %.

Stage-6: Synthesis of compound of formula-XI
Compound obtained in stage-5 was dissolved in methanol (20 mL) and diluted hydrochloric acid (50 mL) was added to it at 25-30°C. Heated the reaction mixture to 60-65°C and stirred for 2-4 hours at the same temperature. After completion of the reaction, cooled the reaction mixture to 25-30°C. Filtered the precipitated solid and washed with water to get the title compound.
Yield: 85 %.

Stage-7: Synthesis of compound of formula-XII
Compound obtained in stage-6 (15 grams) was dissolved in dichloromethane (150 mL) at 25-30°C. Aqueous sodium carbonate solution (45 mL) was added to the resulting reaction mixture and stirred for 15 minutes. Both the aqueous and organic layers were separated and volatiles were removed from the organic layer under reduced pressure. The obtained residue was dissolved in toluene and cyclohexylamine added to the resulting reaction mixture. Heated the reaction mixture to 100-110 °C and stirred for 60 minutes at the same temperature. Cooled the reaction mixture to 25-30 °C. Filtered the precipitated solid and washed with toluene to get the title compound.
Yiled: 85 %

Stage-8: Synthesis of Elagolix Sodium
Compound obtained in stage-7 (10 grams) was dissolved in dichloromethane (100 mL) at 25-30°C and stirred for 10 minutes at the same temperature. The reaction mixture pH was adjusted to 4 to 4.5 using 10 % acetic acid. Both organic and aqueous layers were separated and volatiles were removed from the organic layer under reduced pressure. Resulting residue was dissolved in methanol and aqueous sodium hydroxide solution was added to the reaction mixture at 25-30°C. Activated carbon was added to the reaction mixture and stirred for 60 minutes at the same temperature. Filtered the reaction mixture and volatiles were removed from the obtained filtrate under reduced pressure. The obtained residue was dissolved in methyl isobutyl ketone and heptane at 25-30 °C. Stirred the resulting reaction mixture for 10-12 hours at 25-30°C. Filtered the precipitated solid and washed with heptane to get the title compound.
Yield: 90 %

Example-2: Process for the preparation of Elagolix Sodium

Stage-1: Synthesis of compound of formula-XIV
A mixture of Nicotinamide adenine dinucleotide phosphate (NADP+) (0.25 grams), compound of formula-VI (5 grams), ketone reductase (0.3 grams), glucose (7.2 grams), Glutamate Dehydrogenase (GDH) (0.25 grams) and phosphate buffer (60 mL) was stirred for 14 hours at 25-30 °C. After completion of reaction, aqueous sodium chloride solution was added to the reaction mixture. Extracted the resulting reaction mixture twice with ethyl acetate. Combined the organic layer and volatiles were removed from the organic layer under educed pressure. The obtained residue was dissolved in methanol. Cooled the reaction mixture to 0-10 °C. Methane sulfonyl chloride was slowly added to the reaction mixture. After consumption of starting material, water and ethyl acetate were added to the resulting reaction mixture. Both the organic and aqueous layers were separated. Acetic acid and methanolic ammonia were added to aqueous layer and stirred for 6 hours at the same temperature. Extracted the reaction mixture with ethyl acetate and volatiles were removed from the organic layer under reduced pressure to get the title compound.
Yield: 84 %.

Strage-2: Synthesis of compound of formula-XI
Compound obtained in stage-1 (145 grams) was dissolved in N, N-dimethylformamide (146 mL) at 25-30 °C. 4-bromo butyrate (53 grams) and diisopropylethylamine (41.6 grams) were added to the resulting reaction mixture. Heated the reaction mixture to 55-60 °C and stirred for 12 hours at the same temperature. Cooled the reaction mixture to 25-30 °C. Ethyl acetate and water were added to the resulting reaction mixture. Both aqueous and organic layers were separated and organic layer was washed with phosphoric acid solution. The combined phosphoric acid solution was washed with ethyl acetate. Dichloromethane was added to aqueous phosphate layer followed by addition of aqueous potassium carbonate solution. Organic and aqueous layers were separated. Volatiles were removed from the organic layer under reduced pressure. Isopropanol and hydrochloric acid were added to the obtained crude at 25-30 °C. Heated the reaction mixture to 70-75 °C and stirred for 2 hours at the same temperature. Cooled the reaction mixture to 25-30 °C. Filtered the precipitated solid and dried to get the title compound.
Yield: 65 %

Stage-3: Synthesis of Elagolix Sodium
Aqueous sodium hydroxide solution (338 mL) was added to a mixture of compound obtained in stage-2 (103.9 grams) and ethanol (472 mL) at 25-30 °C and stirred for 2 hours at the same temperature. Distilled off the ethanol under reduced pressure from the reaction mixture and water added to the reaction mixture. Filtered the reaction mixture and washed with methyl isobutyl ketone. Both the organic and aqueous layers were separated and volatiles were removed from the organic layer under reduced pressure to obtain foam. Lyophilized the obtained foam to get the title compound.
Yield: 85 %.

Example-4: Process for the preparation of Elagolix free acid salicylic acid:
Aqueous sodium hydroxide solution was added to a mixture of ethanol and Elagolix ethyl ester at 25-30°C and stirred for 2 hours at the same temperature. After consumption of starting material, the resulting reaction mixture was distilled under reduced pressure.
Water was added to the obtained residue at 25-30°C and stirred for 30 minutes at the same temperature. Isopropyl acetate and aqueous sodium hydroxide solution were added to the resulting reaction mixture at 25-30°C and stirred for 10 minutes at the same temperature. Both aqueous and organic layers were separated. Evaporate the volatiles from the organic layer under reduced pressure. The obtained crude was dissolved in methanol at 25-30°C and stirred for 10 minutes at the same temperature. Acetic acid was added to the resulting mixture at 25-30°C and stirred for 10 minutes at the same temperature. Filtered the reaction mixture and washed with methanol. Salicylic acid was added to the obtained filtrate at 25-30°C and stirred for 30 minutes at the same temperature. Water was added to the reaction mixture at 25-30°C and stirred for 60 minutes at the same temperature. Filtered the precipitated solid and dried to get the title compound.
Yield: 85 %.
,CLAIMS:
1. An improved process for the preparation of Elagolix Sodium of formula-I.

which comprises:
a) coupling of compound of formula-II

with compound of formula-III

in presence of a base and solvent to obtain compound of formula-IV;

b) condensation of compound of formula-IV with compound of formula-V

in presence of a base and solvent to obtain compound of formula-VI;

c) chiral reduction of compound of formula-VI using reducing agent to obtain compound of formula-VII;

d) protecting compound of formula-VII with a hydroxy protecting group in presence of a base and solvent to obtain compound of formula-VIII;
pg = hydroxy protecting group
e) condensation of compound of formula-VIII with compound of formula-IX

in presence of a base to obtain compound of formula-X;

f) ring opening of compound of formula-X in presence of concentrated hydrochloric acid to obtain Elagolix free acid of formula-XI;

g) salt formation of Elagolix free acid of formula-XI with dicyclo hexyl amine in an organic solvent to obtain compound of formula-XII;

h) neutralization of compound of formula-XII with an acid followed by salt formation with sodium hydroxide in an organic solvent to obtain Elagolix Sodium of formula-I.

2. The process as claimed in claim 1, wherein said base is selected from the group consisting of inorganic base or organic base; wherein said solvent is selected from group consisting of alcoholic solvent, ketonic solvent, ester solvent, polar aprotic solvent, ether solvent, hydrocarbon solvent, chlorinated solvent, water or its mixture.

3. The process as claimed in claim 1, wherein said hydroxy protecting group is selected from the group consisting of benzyloxycarbonyl, C1-C6 straight chain or branched chain alkoxy carbonyl such as methoxycarbonyl, ethoxy carbonyl, tert-butyloxycarbonyl, acetyl, trichloroacetyl, trifluoroacetyl, 1-ethoxyethyl, benzoyl, benzyl, p-methoxybenzyl, methylthiomethyl, pivaloyl, trityl (triphenylmethyl), methoxy-iso-propanyl, tri (C1-C6 straight chain or branched chain alkyl) silyl groups such as trimethyl silyl (TMS), tri-ethyl silyl, triisopropylsilyl, tri-iso-propylsilyloxy methyl, tert-butyl-dimethylsilyl, tert-butyl- biphenylsilyl, furanidinyl, dihydropyran, tetrahydropyran, trichloroethoxy carbonyl and methane sulfonyl.

4. The process as claimed in claim 1, wherein said reducing agent is selected from keto reductase enzyme or chiral sulfinamine or chiral reducing agents like DIP chloride or 2-(R)-methyl CBS.

5. The process as claimed in claim 1 and claim 2, wherein said acid is selected from hydrochloric acid or acetic acid.

6. A process for the preparation of Elagolix Sodium compound of formula-I.

which comprises:
a) chiral reductive amination of compound of formula-VI

with a reducing agent in a solvent to obtain compound of formula-XIV;

b) condensation of compound of formula-XIV with 4-bromo butyric acid in presence of a base to obtain compound of formula-XI;

c) salt formation of compound of formula-XI with sodium hydroxide in a solvent to obtain Elagolix sodium of formula-I.

7. The process as claimed in claim 1, wherein said reducing agent is selected from keto reductase enzyme or sodium cyanoborohydride or sodium triacetoxy borohydride or Indium trichloride in presence of trimethylsilyl hydride or Dichloro(p-cymene)ruthenium complex
8. A compound of formula-XII a

9. A process for the preparation of compound of formula-XII a by ester hydrolysis of Elagolix ethyl ester in presence of sodium hydroxide followed by reacting with salicylic acid in methanol.
10. Amorphous form of compound of formula-XII a.