DESC:

FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003

COMPLETE SPECIFICATION
(See section 10 and rule 13)

PROCESS FOR THE PREPARATION OF LESINURAD AND ITS INTERMEDIATES

Dr. Reddy’s Laboratories Limited
An Indian company having its registered office at
8-2-337, Road No. 3, Banjara hills,
Hyderabad – 500034,
Telangana
India

The following specification particularly describes the invention and the manner in which it is to be performed.

PROCESS FOR THE PREPARATION OF LESINURAD AND ITS INTERMEDIATES
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of Lesinurad intermediates and their use in preparation of Lesinurad or its pharmaceutically acceptable salts thereof.
BACKGROUND
Lesinurad is a selective uric acid re-absorption inhibitor (SURI). Lesinurad or its salt is used for reducing serum uric acid level and for the treatment of gout and hyperurecemia. Lesinurad is chemically known as 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid and has following structural formula (I):

(I)
Lesinurad, described for the first time in US patent 8,003,681, is a URAT1 inhibitor indicated in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. Lesinurad is marketed under the trade name of ZURAMPIC.
Process for the preparation of Lesinurad (I) and its intermediates have been disclosed in US8084483B2 and US8173690B2, which is shown in scheme 1: Scheme-1:

CN102040546A discloses the synthesis of isothiocyanate derivative as an intermediate in the preparation of lesinurad. The disclosed process starts from 4-cyclopropyl-1-naphthaldehyde and involves three steps, to get isothiocyanate derivative as an intermediate and thus avoiding the use of thiophosgene.

CN104447589 assigned to Sunshine Lake Pharma, discloses that process for purification of Lesinurad by reacting low purity Lesinurad with organic amine, followed by treating the salt with acid to provide Lesinurad with high purity.
The process available in the literature suffer from low yield and low purity of Lesinurad, keeping in view of the importance of lesinurad as a medicament, there remains a need to provide a novel process for the preparation of Lesinurad of formula (I), its related compounds and its intermediates from simple, economical and commercially viable starting materials.

SUMMARY OF THE APPLICATION
In first embodiment, the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) treating a compound of formula (VI) with a compound of formula (VII) to form a compound of formula (II);

wherein Z is chloro, bromo, iodo, triflate and tosylate; Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4;
b) optionally, purifying the compound of formula (II);
c) brominating a compound of formula (II) with a brominating agent to form a compound of formula (III);

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.
d) hydrolysing the compound of formula (III) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In second embodiment, the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) treating a compound of formula (VI) with a compound of formula (VIII) to form a compound of formula (IV);

wherein Z is chloro, bromo, iodo, triflate and tosylate;
b) optionally, purifying the compound of formula (IV);
c) brominating a compound of formula (IV) with a brominating agent to form a compound of formula (V);

d) hydrolysing the compound of formula (V) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In third embodiment, the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) converting a compound of formula (IX) to 4-cyclopropylnaphthalen-1-amine of formula (X);

wherein Z is chloro, bromo, iodo, triflate and tosylate;
b) optionally purifying a compound of formula (X);
c) converting a compound of formula (X) to Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In fourth embodiment of the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) brominating a compound of formula (XI) with a brominating agent to form Lesinurad of formula (I) or its pharmaceutically acceptable salts;

b) optionally purifying Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In fifth embodiment of the present invention provides a process for the preparation of compound of formula (III), which comprises brominating a compound of formula (II) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (III).

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.
In sixth embodiment of the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

In seventh embodiment of the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with a brominating agent to form a compound of formula (V).

In eighth embodiment of the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with brominating agent in the presence of tertiary amine, optionally using quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

In ninth embodiment of the present invention provides a compounds of formulae (II), (III), (IV) and (V).

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.

In tenth embodiment of the present invention provides the use of compounds of formula (II), (III), (IV) and (V) in the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In eleventh embodiment, the present invention provides a purification process of Lesinurad comprising:
a) providing a solution/suspension of Lesinurad of Formula (I) in a solvent;
b) optionally, heating the solution of step (a);
c) isolating pure form of Lesinurad of Formula (I)..
In twelveth embodiment, the present invention provides a purification process of Lesinurad comprising:
a) providing a solution/suspension of Lesinurad (I) in isopropanol and water;
b) optionally, heating the solution of step (a);
c) isolating pure form of Lesinurad of Formula (I).
In thirteenth embodiment of the present application provides pharmaceutical compositions comprising Lesinurad of formula (I) or its pharmaceutically acceptable salts thereof prepared according to processes of the present application together with one or more pharmaceutically acceptable excipient, carrier and diluents.
DETAILED DESCRIPTION
In first embodiment of the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) treating a compound of formula (VI) with a compound of formula (VII) to form a compound of formula (II);

wherein Z is chloro, bromo, iodo, triflate and tosylate; Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4;
b) optionally, purifying the compound of formula (II);
c) brominating a compound of formula (II) with a brominating agent to form a compound of formula (III);

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4;
d) hydrolysing the compound of formula (III) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
The process for the preparation of starting material compound of formula (VI) may be performed by any suitable process disclosed in the prior art references. Alternatively, the said starting material may be procured from commercial sources to perform the present invention.
Step (a) may be carried out in the presence of one or more suitable bases. Suitable base that may be used in step (a) include, but are not limited to organic bases like pyridine, piperidine, pyrimidine, triethylamine, tributylamine, N-methylmorpholine, N,N-diisopropylethylamine, diethylamine, 1,1,3,3-tetramethylguanidine, DBU, DABCO and the like; or inorganic bases like metal carbonates such as sodium carbonate, cesium carbonate, potassium carbonate; metal bicarbonates such as sodium bicarbonate, potassium bicarbonate, metal hydroxide like sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide and magnesium hydroxide, the like. The base can also be basic alumina, any alkali or alkaline earth metal fluoride coated on alumina, and also any basic resins such as amberlyst resin, or any anion exchange resins etc.
Suitable reagent that may be used in step a) include, but are not limited to metal halides like sodium iodide, potassium iodide, sodium bromide, potassium bromide, tetrabutyl ammonium iodide, tetrabutyl ammonium bromide, tetrabutyl ammonium hydrogen sulphate, any quaternary ammonium salt which can act as phase transfer catalyst, copper iodide, copper bromide, sodium chloride, potassium chloride, and the like.
Step (b) which involves the isolation and purification of compound of formula (II) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
Suitable brominating agent that may be used in step (c) include, but are not limited to such as for example phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS) or liquid bromine, N-bromoacetamide, N-bromophthalimide, N-bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) and the like.
Suitable base that may be used in step (d) include, but are not limited to organic bases like pyridine, piperidine, pyrimidine, triethylamine, tributylamine, N-methylmorpholine, N,N-diisopropylethylamine, diethylamine, 1,1,3,3-tetramethylguanidine, DBU, DABCO and the like; or inorganic bases like metal carbonates such as sodium carbonate, potassium carbonate; metal bicarbonates such as sodium bicarbonate, potassium bicarbonate; metal hydroxide like sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide and the like.
Suitable acid that may be used in step (d) include, but are not limited to inorganic acids like hydrochloric acid, sulphuric acid, hydrobromic acid, acetic acid or the like; or any other suitable acids.
Step (a), step (c) and step (d) may be carried out in one or more suitable solvents. Suitable solvent that may be used in step (a) and/or step (c) and/or step (d) include, but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; water or mixtures thereof.
The temperature at which the above steps may be carried out in between about 0°C and about 200°C, preferably at about 0°C and about 150°C, most preferably at about 0°C and about 100°C, based on the solvent or mixture of solvent used in particular step.
The intermediates obtained in the present invention may be directly used for the next step with or without isolation or it may be further purified, if isolated, to improve the purity of the product.
In second embodiment of the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of;
a) treating a compound of formula (VI) with a compound of formula (VIII) to form a compound of formula (IV);

wherein Z is chloro, bromo, iodo, triflate and tosylate;
b) optionally, purifying the compound of formula (IV);
c) brominating a compound of formula (IV) with a brominating agent to form a compound of formula (V);

d) hydrolysing the compound of formula (V) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
The process for the preparation of starting material compound of formula (VI) may be performed by any suitable process disclosed in the prior art references. Alternatively, the said starting material may be procured from commercial sources to perform the present invention.
The reagents, solvents and reaction conditions for steps (a), (b), (c) and (d) may be selected from one or more suitable reagents, solvents and process conditions as described in the step of first embodiment of the present invention.
The temperature at which the above steps may be carried out in between about 0°C and about 200°C, preferably at about 0°C and about 150°C, most preferably at about 0°C and about 100°C, based on the solvent or mixture of solvent used in particular step.
The intermediates obtained in the present invention may be directly used for the next step with or without isolation or it may be further purified, if isolated, to improve the purity of the product.
In third embodiment, the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) converting a compound of formula (IX) to 4-cyclopropylnaphthalen-1-amine of formula (X);

wherein Z is chloro, bromo, iodo, triflate and tosylate;
b) optionally purifying a compound of formula (X);
c) converting a compound of formula (X) to Lesinurad of formula (I) or its pharmaceutically acceptable salts.
Conversion of a compound of formula (IX) may be carried out in the presence of a suitable reagent to provide a compound of formula (X).
Suitable reagent that may be used in step a) include, but are not limited to copper iodide, copper bromide, copper (I) oxide, copper cyanide, metallic copper, copper sulfate, copper acetate, copper stearate, copper triflate, copper Nitrate or any Cu(I) salts which can undergo oxidative coupling or can generate Cu(II) in situ under specific reaction conditions, ammonium acetate, ammonia, formamide, ammonium formate, ammonium chloride, ammonium hydroxide, ammonium carbonate or mixtures thereof.
Step (a) may be carried out in one or more suitable solvents. Suitable solvent that may be used in step (a) but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin, and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, hexafluoroisopropyl alcohol, ethylene glycol, 1-propanol, 1-butanol, 2-butanol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; water or mixtures thereof.
Step (b) which involves the isolation and purification of compound of formula (X) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
The compound of formula (X) may be converted to Lesinurad of formula (I) or its pharmaceutically acceptable salts by hydrolysis methods known in the literature.
The intermediates obtained in the present invention may be directly used for the next step with or without isolation or it may be further purified, if isolated, to improve the purity of the product.
The temperature at which the above steps may be carried out in between about 0°C and about 200°C, preferably at about 0°C and about 150°C, most preferably at about 0°C and about 100°C, based on the solvent or mixture of solvent used in particular step.
In fourth embodiment, the present invention provides a process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) brominating a compound of formula (XI) with a brominating agent to form Lesinurad of formula (I) or its pharmaceutically acceptable salts;

b) optionally purifying Lesinurad of formula (I) or its pharmaceutically acceptable salts.
Suitable brominating agent that may be used in step (a) include, but are not limited to such as for example phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS) or liquid bromine, N-Bromoacetamide, N-Bromophthalimide, N-Bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) and the like.
Step (a) may be carried out in one or more suitable solvents. Suitable solvent that may be used in step (a) include, but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin, and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; water or mixtures thereof.
The temperature at which the above steps may be carried out in between about 0°C and about 200°C, preferably at about 0°C and about 150°C, most preferably at about 0°C and about 100°C, based on the solvent or mixture of solvent used in particular step.
In fifth embodiment, the present invention provides a process for the preparation of compound of formula (III), which comprises brominating a compound of formula (II) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (III).

Wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.
Suitable brominating agent that may be used in the fifth embodiment include, but are not limited to phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS), liquid bromine, N-Bromoacetamide, N-Bromophthalimide, N-Bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) or any other suitable brominating agent known in the art.
Quaternary ammonium based phase transfer catalyst that may be used in the fifth embodiment include, but are not limited to tetrabutyl ammonium iodide, tetrabutyl ammonium bromide, tetrabutyl ammonium hydrogen sulphate, benzyltriethylammonium chloride, Tetraethylammonium chloride, any quaternary ammonium salt and the like.
Suitable solvent that may be used in the fifth embodiment include, but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin, and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; water or mixtures thereof.
The temperature used in the fifth embodiment may be carried out in between about -20°C and about 100°C, preferably at about -20°C and about 70°C, preferably at about -20°C and about 50°C, most preferably -20°C and about 30°C, based on the solvent or mixture of solvent used in particular step.
The isolation of compound of formula (III) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
In sixth embodiment, the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

The reagents, quaternary ammonium based phase transfer catalyst, solvents and reaction conditions for this embodiment may be selected from one or more suitable reagents, solvents and process conditions as described in the fifth embodiment of the present invention.
The temperature used in the sixth embodiment may be carried out in between about -20°C and about 100°C, preferably at about -20°C and about 70°C, preferably at about -20°C and about 50°C, most preferably -20°C and about 30°C, based on the solvent or mixture of solvent used in particular step.
The isolation of compound of formula (V) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
In seventh embodiment of the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with a brominating agent to form a compound of formula (V).

Suitable brominating agent that may be used in the seventh embodiment include, but are not limited to phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS), liquid bromine, N-Bromoacetamide, N-Bromophthalimide, N-Bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) or any other suitable brominating agent known in the art.
Suitable solvent that may be used in the seventh embodiment include, but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin, and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; water or mixtures thereof.
The temperature used in the seventh embodiment may be carried out in between about -20°C and about 100°C, preferably at about -20°C and about 70°C, preferably at about -20°C and about 50°C, most preferably -20°C and about 30°C, based on the solvent or mixture of solvent used in particular step.
The isolation of compound of formula (V) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
In eighth embodiment of the present invention provides a process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with brominating agent in the presence of tertiary amine, optionally using quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

Suitable brominating agent that may be used in the eighth embodiment include, but are not limited to phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS), liquid bromine, N-Bromoacetamide, N-Bromophthalimide, N-Bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) or any other suitable brominating agent known in the art.
Tertiary amine that may be used in the eighth embodiment include, but are not limited to n-alklyl piperdine such as n-methyl piperdine and the like; n-alkyl morpholine such as n-methyl morpholine and the like; n-alkyl pyrrolidine such as n-methyl pyrrolidine and the like, N,N’-piperazine, pyridine, quinolone, isoquinoline, acridine, pyrazine, phenanthroline and the like.
Quaternary ammonium based phase transfer catalyst that may be used in the eighth embodiment include, but are not limited to tetrabutyl ammonium iodide, tetrabutyl ammonium bromide, tetrabutyl ammonium hydrogen sulphate, benzyltriethylammonium chloride, Tetraethylammonium chloride, any quaternary ammonium salt and the like.
Suitable solvent that may be used in the eight embodiment include, but are not limited to ketone solvents, such as, for example, acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, C3-C6 ketones and the like; aromatic hydrocarbon solvents, such as, for example, toluene, xylene, chlorobenzene, tetralin, and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; alcoholic solvents like methanol, ethanol, isopropyl alcohol and the like; aliphatic hydrocarbon solvents, such as n-pentane, n-hexane, n-heptane and the like; ether solvents, such as, for example, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 2-methoxyethanol, 2-ethoxyethanol, anisole, 1, 4-dioxane, and the like; nitrile solvent, such as, for example, acetonitrile, propionitrile, C2-C6 nitriles and the like; ester solvents, such as, for example, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propanoate, ethyl propanoate, methyl butanoate, ethyl butanoate, or the like; polar aprotic solvents such as dimethyl formamide, dimethylacetamide, N-methylpyrrolidine (NMP), formamide, acetamide, propanamide, dimethyl sulfoxide and the like; water or mixtures thereof.
The temperature used in the eighth embodiment may be carried out in between about -20°C and about 100°C, preferably at about -20°C and about 70°C, preferably at about -20°C and about 50°C, most preferably -20°C and about 30°C, based on the solvent or mixture of solvent used in particular step.
The isolation of compound of formula (V) may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
In ninth embodiment of the present invention provides a compound of formulae (II), (III), (IV) and (V).

Wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.

In tenth embodiment of the present invention provides the use of compound of formulae (II), (III), (IV) and (V) in the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts.
In tenth embodiment, the present invention provides a purification process of Lesinurad comprising:
a) providing a solution/suspension of Lesinurad of Formula (I) in a solvent;
b) optionally, heating the solution of step (a);
c) isolating pure form of Lesinurad.
Suitable solvent that may be used in step (a) include, but are not limited to methanol, ethanol, n-propanol, isopropanol, water or mixtures thereof;
The temperature at which the above steps may be carried out in between about -10 °C and about 100 °C, based on the solvent or mixture of solvent used in particular step.
The isolation of step c) may be effected by methods such as, removal of solvent, crash cooling, flash evaporation, rotational drying, spray drying, precipitation, filtration, centrifugation, extraction, acid-base treatment, conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures or any other suitable fast evaporation technique.
The isolated Lesinurad may be optionally washed with a solvent or a mixture of solvents.
Suitable temperatures for isolation may be less than about 75°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 10°C, less than about 0°C, less than about -10°C, less than about -40°C or any other suitable temperatures.
In twelveth embodiment, the present invention provides a purification process of Lesinurad comprising:
a) providing a solution/suspension of Lesinurad (I) in isopropanol and water;
b) optionally, heating the solution of step (a);
c) isolating pure form of Lesinurad.
The temperature at which the above steps may be carried out in between about -10 °C and about 100 °C, based on the solvent or mixture of solvent used in particular step.
The isolation of step c) may be effected by methods such as, removal of solvent, crash cooling, flash evaporation, rotational drying, spray drying, precipitation, filtration, centrifugation, extraction, acid-base treatment, conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures or any other suitable fast evaporation technique.
The isolated Lesinurad may be optionally washed with a solvent or a mixture of solvents.
Suitable temperatures for isolation may be less than about 60°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 10°C, less than about 0°C, less than about -10°C, less than about -40°C or any other suitable temperatures.
The isolation and purification of Lesinurad (I) of all embodiments of the present invention may be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, centrifugation, extraction, acid-base treatment, crystallization, conventional isolation and refining means such as concentration, concentration under reduced pressure, solvent-extraction, crystallization, phase-transfer chromatography, column chromatography, or by a combination of these procedures.
Lesinurad used as a starting material in the present application is having a purity of at least about 95% or about 95.5% or about 96% or about 96.5% or about 97% or about 97.5%.or about 98.5% or about 99%.
Lesinurad used as a starting material may be amorphous form, crystalline form 1 or crystalline form 2 or an alternate crystalline form of Lesinurad known in the art.
In thirteenth embodiment of the present invention provides pharmaceutical compositions comprising Lesinurad of formula (I) or its pharmaceutically acceptable salts thereof prepared according to processes of the present application together with one or more pharmaceutically acceptable excipient, carrier and diluents.
In an embodiment, Lesinurad of formula (I) or its pharmaceutically acceptable salt obtained in the present invention may be further subjected to known purification techniques to get the required purity for qualifying ICH grade material.
The process of the present invention is easy to handle, environment friendly, provides better yield and purity; and it may also be practiced on industrial scale.
DEFINITIONS
The following definitions are used in connection with the present application unless the context indicates otherwise.
The terms "about," "general, ‘generally," and the like are to be construed as modifying a term or value such that it is not an absolute. Such terms will be defined by the circumstances and the terms that they modify as those terms are understood by those of skill in the art. This includes, at very least, the degree of expected experimental error, technique error and instrument error for a given technique used to measure a value.
The term “optional” or “optionally” is taken to mean that the event or circumstance described in the specification may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
Certain specific aspects and embodiments of the present application will be explained in more detail with reference to the following examples, which are provided for purposes of illustration only and should not be construed as limiting the scope of the present application in any manner.

EXAMPLES
EXAMPLE 1: Preparation of 2-((4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethanone (IV).
2-Chloro-1-morpholinoethanone (VIII; wherein Z is Cl; 0.22g; 1.347 moles), sodium iodide (0.050g; 0.337 moles) and dimethyl formamide (DMF; 3mL) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. 4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole-3-thiol (VI; 0.3g; 1.12 moles) and potassium carbonate (0.543 g; 3.93 moles) were added to the reaction mixture at 25°C and stirred for 3-4 hours. Water (10 mL) and ethyl acetate (15 mL) were added to the reaction mixture at 26°C and stirred for 5-10 minutes. The layers were separated and the organic layer was concentrated at 45-52°C under vacuum to give the title compound. Yield: 0.3 g
EXAMPLE 2: Preparation of 2-((4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethanone (IV).
4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole-3-thiol (VI; 110 g) and dimethyl formamide (DMF; 275 mL) were charged at 23°C and stirred for 5 minutes. Potassium carbonate (114 g) was added to the reaction mixture at 23°C and stirred for 15 minutes. The reaction mass was cooled to 5°C. 2-Chloro-1-morpholinoethanone (VIII; wherein Z is Cl; 81 g) and dimethyl formamide (DMF; 55 mL) were slowly added to the reaction mass at 5°C for a period of 60 minutes and maintained for 2-3 hours. Water (1650 mL) was added to the reaction mass. Filtered the reaction mass and washed with water (550 mL), dried at 75°C for 12-15 hours to give the title compound. The dried compound was slurried in ethyl acetate (550 mL) and stirred for 60 minutes. Filtered the reaction mass and dried at 75°C to give the title compound.
Yield: 120.7 g
1HNMR: (DMSO-d6) d ppm 0.80 - 0.88(m,2H) 1.10 - 1.18 (m,2H) 2.49-2.57 (m, 1H) 3.33 - 3.56 ( m, 8H) 4.27 (s,1H) 7.19 (d, 1H) 7.41 (d, 1H ) 7.56 (d, 1H) 7.61 - 7.65 (t,1H) 7.71 - 7.75 (t,1H) 8.57 (d, 1H) 8.89 (s, 1H).
Mass: 395 (M+1).
EXAMPLE 3: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholino ethanone (IV; 0.2g; 0.507 moles), acetonitrile (5mL) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. N-Bromosuccinimide (0.108g; 0.608 moles) was slowly added to the reaction mixture at 27°C and maintained for 3-4 hours. Water (5 mL) and ethyl acetate (10 mL) were charged into the reaction mass and stirred for 10-15 minutes. The layers were separated and the aqueous layer was washed with ethyl acetate (5 mL). Combined the organic layers and the solvent from the organic layer was concentrated at 40-45°C under vacuum. Ethyl acetate (1 mL) was added to the obtained residue and stirred for 10-20 minutes. Filtered the reaction mass and the obtained filtrate was concentrated at 40-45°C under vacuum to give the title compound. Yield: 0.2 g
EXAMPLE 4: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholino ethanone (IV; 0.5g; 1.267 moles), acetonitrile (10 mL) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. The reaction mixture was heated at 45-47°C. N-Bromosuccinimide (0.271g; 1.521 moles) was slowly added to the reaction mixture at 45-47°C and maintained for 60-90 minutes. The solvent from the reaction mass was concentrated under vacuum at 47 °C. The reaction mass was cooled to 30°C. Dichloromethane (20 mL), 10% aqueous Sodium meta bisulphate solution (10 mL) were added to the above obtained crude and stirred for 5-10 minutes. Layers were separated and the organic layer was washed with sodium bicarbonate solution (10 mL). The solvent from the organic layer was concentrated at 40°C under vacuum. Ethyl acetate (10 mL) was added to the obtained crude and was concentrated under vacuum. Ethyl acetate (10 mL) was added to the obtained crude and stirred for 5-10 minutes. Filtered the reaction mass and washed with ethyl acetate (5 mL) to give the title compound. Yield: 0.3 g
EXAMPLE 5: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholino ethanone (IV; 2 g), acetonitrile (40 mL) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. N-Bromosuccinimide (1.805 g; 0.608 moles) was slowly added to the reaction mixture at 28°C and stirred for 5-10 minutes. Tetrabutyl ammonium bromide (0.326 g) was added to the reaction mixture at 28°C and maintained at 28°C for 11-12 hours. Filtered the reaction mass and washed with acetonitrile (2 mL), dried at 50°C for 3-4 hours to give the title compound. Yield: 83.3%
EXAMPLE 6: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholino ethanone (IV; 50 g), dichloromethane (500 mL) were charged at 30°C and stirred for 5 minutes. 10% aq sodium bicarbonate solution (500 mL) was added to the reaction mixture at 30°C. Layers were separated and the solvent from organic layer was concentrated at 45°C under vacuum. Acetonitrile (500 mL) was added to the obtained crude at 45°C and stirred for 5 minutes. The reaction mixture was cooled to 28°C. Dichloromethane (250 mL) was added to the reaction mass at 28°C and the reaction mass was cooled to -3°C. Pyridine (35.1 g) was added to the reaction mass at -3°C and stirred for 10-20 minutes. Bromine (60.8 g), acetonitrile (50 mL) and dichloromethane (50 mL) were added to the reaction mass at -2.9°C and stirred for 10-15 minutes. The reaction mass temperature was raised to 27°C and maintained for 14 hours. Dichloromethane (250 mL) and water (500 mL) were charged in to the reaction mass and stirred for 5 minutes. Layers were separated and the organic layer was washed with aqueous sodium metabisulphite solution (2X500 mL) and sodium bicarbonate solution (500 ML) and the resultant organic layer was concentrated at 45°C under vacuum. Dimethyl formamide (150 ML) was added to the obtained crude at 45°C and stirred for 30 minutes. Water (150 mL) was added to the reaction mass at 30°C and stirred for 30 minutes. Separated solid was filtered and washed with water (100 mL). The resultant wet compound dissolved in dichloromethane (500 mL) was added to the obtained compound and stirred for 5 minutes. Layers were separated and the solvent from organic layer was concentrated at 43°C under vacuum. Ethyl acetate (150 mL) was added to the obtained crude and was concentrated under vacuum. Ethyl acetate (100 mL) was added to the obtained crude and stirred for 5-10 minutes. Filtered the reaction mass and washed with ethyl acetate (50 mL), dried at 54°C for 3 hours to give the title compound. Yield: 78.83%
EXAMPLE 7: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholino ethanone (IV; 200 g), acetonitrile (1000 mL) were charged at 28°C and stirred for 5 minutes. Pyridine (80 g) was added to the reaction mixture at 28°C and the reaction mixture was heated to 46°C. Tetrabutyl ammonium bromide (123 g) was added to the reaction mixture at 46°C and stirred at 46°C for 30 minutes. N-Bromosuccinimide (271 g) was slowly added to the reaction mixture at 48°C and maintained for 5-6 hours. The reaction mass was cooled to 28°C. Filtered the reaction mass and washed with water (1000 mL), dried at 73°C for 12 hours to give the title compound.
1HNMR: (DMSO-d6) d ppm 0.85 - 0.98(m,2H) 1.12 - 1.17 (m,2H) 2.49 - 2.57 (m, 1H) 3.35 - 3.57 ( m, 8H) 4.27 (s,2H) 7.15 (d, 1H) 7.44 (d, 1H ) 7.63 - 7.67 (m,2H) 7.72 - 7.76 (t,1H) 8.58 (d, 1H);
Mass: 495 (M+1 Na adduct).
EXAMPLE 8: Preparation of 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V).
2-((4-(4-Cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethanone (IV; 2 g), acetonitrile (40 mL) were charged at 31°C under nitrogen atmosphere and stirred for 5-10 minutes. N-Bromosuccinimide (1.805 g) was slowly added to the reaction mixture at 31°C and stirred for 5-10 minutes. Tetrabutyl ammonium bromide (0.816 g) was added to the reaction mixture at 31°C and maintained at 31°C-33°C for 10-11 hours. Filtered the reaction mass and washed with water (20 mL), dried at 50°C for 3-4 hours to give the title compound.
EXAMPLE 9: Preparation of 4-cyclopropylnaphthalen-1-amine (X).
1-bromo-4-cyclopropylnaphthalene (IX; wherein Z is Br; 2.471 g; 10 moles), N-Methyl-2-pyrrolidone (NMP; 10 mL) were charged at room temperature under nitrogen atmosphere. Cuprous oxide (0.286 g; 2 moles) was added to the reaction mixture at 26°C and stirred for 2-5 minutes. Aqueous ammonia (20 mL) was also added to the reaction mixture at 26°C. The above obtained solution was transferred to autoclave at room temperature. The temperature of the autoclave was raised to 90°C-98°C and maintained for 18-20 hours. After completion of the reaction, to the crude material was added distilled water (100 mL). The mixture transferred to separatory funnel. Ethyl acetate (50 mL) was added and mixture partitioned with shaking. Layers were separated and the organic layer was washed with brine solution (50 mL). The solvent from the organic layer was evaporated under reduced pressure at 45°C and the obtained compound was purified by silica gel column chromatography to give the title compound. Yield: 1.45g.
EXAMPLE 10: Preparation of Lesinurad (I).
2-((5-Bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V; 50 mg) water (1mL) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. Aqueous HCl (1 mL) was added to the reaction mixture at 27°C. The reaction mixture was heated at 91-93°C and maintained for 3-4 hours. The reaction mixture was cooled to 30°C. Water (2 mL) and ethyl acetate (1 mL) were added to the reaction mass and stirred for 5-10 minutes. The layers were separated and the solvent from the organic layer was concentrated at 45°C under vacuum. n-Hexane (3mL) was added to the obtained crude and stirred for 10 minutes. Filtered the reaction mass and washed with n-hexane (2mL) to give the title compound. Yield: 30 mg

EXAMPLE 11: Preparation of Lesinurad (I).
2-((5-Bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)-1-morpholinoethan-1-one (V; 0.3 g; 0.634 moles), water (0.5 mL) and LiOH.H2O (0.040 g; 0.953 moles) were charged at room temperature under nitrogen atmosphere and stirred for 5-10 minutes. Tetrahydrofuran (2 mL) was added to the reaction mixture at 27°C and stirred for 10 minutes. The reaction mixture was heated at 70°C and maintained for 20-21 hours. The solvent from the reaction mass was concentrated under vacuum. Water (3 mL) and dichloromethane (10 mL) were added to the obtained crude at room temperature. The reaction mass was cooled to 2-3°C and adjusted the reaction mass pH by using aqueous HCl solution (5 mL). The layers were separated and the organic layer was concentrated completely under vacuum. Ethyl acetate (2X5 mL) was added to the obtained crude, stirred for 5-10 minutes and concentrated under vacuum to give the title compound. Yield: 0.24 g.
EXAMPLE 12: Preparation of Lesinurad (I).
2-((4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acid (XI; 1.0 g; 3.07 moles), tetrahydrofuran (5 mL) and n-heptane (3 mL) were charged at room temperature under nitrogen atmosphere. N-Bromosuccinimide (1.914 g; 10.76 moles) was slowly added to the reaction mixture at 26°C and maintained for 3-4 hours. The solvent from the reaction mass was completely evaporated under vacuum. Water (5 mL) and ethyl acetate (10 mL) were added to the reaction mass at room temperature. The layers were separated and the organic layer was concentrated at 32-35°C under vacuum to give the title compound. Yield: 1.1 g
EXAMPLE-13: Purification process of Lesinurad.
Lesinurad (66 g), isopropanol (250 mL) and water (100 mL) were charged at 28°C under nitrogen atmosphere. The temperature of the reaction mass was raised to 75°C and maintained for 15-30 minutes. The reaction mass was cooled to 28°C and maintained for 12 hours. The obtained solid was filtered and washed with isopropanol (66 mL), dried under vacuum at 75°C to provide pure Lesinurad.
Yield: 76%; Purity: 98.9%

EXAMPLE-14: Purification process of Lesinurad.
Lesinurad (63 g), n-propanol (315 mL) and water (8.5 mL) were charged at 28°C under nitrogen atmosphere. The temperature of the reaction mass was raised to 65°C and maintained for 20-30 minutes. The reaction mass was cooled to 45°C and seeded with Lesinurad API. The reaction mixture was then maintained for 3-5 hours, further cooled to 5-10 °C. The obtained solid was filtered and washed with n-propanol (25 mL). The wet product was again reslurried in n-propanol (315 mL) and stirred for 30 minutes, filtered the solid, and dried at 45°C.
Yield: 41%; Purity: 99.8% ,CLAIMS:WE CLAIM:
1) A process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of:
a) treating a compound of formula (VI) with a compound of formula (VII) to form a compound of formula (II);

wherein Z is chloro, bromo, iodo, triflate and tosylate; Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4;
b) optionally, purifying the compound of formula (II);
c) brominating a compound of formula (II) with a brominating agent to form a compound of formula (III);

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.
d) hydrolysing of compound of formula (III) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
2) A process for the preparation of Lesinurad of formula (I) or its pharmaceutically acceptable salts comprising the steps of;
a) treating a compound of formula (VI) with a compound of formula (VIII) to form a compound of formula (IV);

wherein Z is chloro, bromo, iodo, triflate and tosylate;
b) optionally, purifying the compound of formula (IV);
c) brominating a compound of formula (IV) with a brominating agent to form a compound of formula (V);

d) hydrolysing of compound of formula (V) in the presence of suitable acid or suitable base to provide Lesinurad of formula (I) or its pharmaceutically acceptable salts.
3) A process for the preparation of compound of formula (III), which comprises brominating a compound of formula (II) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (III).

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.
4) A process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with a brominating agent in the presence of a quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

5) A process for the preparation of compound of formula (V), which comprises brominating a compound of formula (IV) with brominating agent in the presence of tertiary amine, optionally using quaternary ammonium based phase transfer catalyst to form a compound of formula (V).

6) The process according to any of the claims above, wherein brominating agent is selected from phosphorus tribromide, aluminum tribromide, N-bromosuccinimide (NBS), liquid bromine, N-Bromoacetamide, N-Bromophthalimide, N-Bromosaccharin, Benzyltrimethylammonium Tribromide, Trimethylphenylammonium Tribromide, 1,3-Dibromo-5,5-Dimethylhydantoin, (DBDMH) or mixtures thereof.
7) The process as claimed in claim 3, 4 or 5, wherein quaternary ammonium based phase transfer catalyst is selected from tetrabutyl ammonium iodide, tetrabutyl ammonium bromide, tetrabutyl ammonium hydrogen sulphate, benzyltriethylammonium chloride, tetraethylammonium chloride or mixtures thereof.
8) The process as claimed in claim 5, wherein tertiary amine is selected from n-alklyl piperdine, n-alkyl morpholine, n-alkyl pyrrolidine, N,N’-piperazine, pyridine, quinolone, isoquinoline, acridine, pyrazine, phenanthroline or mixtures thereof.
9) Compounds of formula (II), (III), (IV) and (V),

wherein Y is N, O, S; n is 0,1,2,3,4 and m is 1,2,3 and 4.

10) A purification process of Lesinurad comprising:
a) providing a solution/suspension of Lesinurad (I) in water, C1-4 alcohol or a mixture thereof;
b) optionally, heating the solution of step (a);
c) Isolating pure form of Lesinurad of formula (I).