FIELD OF THE INVENTION

The present invention relates to a purification process of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of Formula (II). l-(3-Benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)-propyl]-2,3-dihydro-l//-indole-7-carbonitrile (II) is the key intermediate in the synthesis of Silodosin of Formula (I).

BACKGROUND OF THE INVENTION

Silodosin is chemically known as l-(3-hydroxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoro ethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carboxamide. Silodosin is a selective antagonist of post-synaptic alpha-1 adrenoreceptors, which are located in the human prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra. Blockade of these alpha-1 adrenoreceptors can cause smooth muscle in these tissues to relax, resulting in an improvement in urine flow and a reduction in BPH symptoms. Silodosin is approved for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) and is marketed under the brand name Rapaflo®. Silodosin is disclosed in US 5,387,603. This patent also discloses a process for the preparation of Silodosin using a multiple-step method, by condensing l-acetyl-5-(2- aminopropyl)indoline-7-carbonitrile (III) with 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate (IVa) or 2-[2-(2,2,2 trifluoroethoxy) phenoxy] ethyl bromide (IVb) in presence of a base to produce racemic l-acetyl-5-[2-[2-[2-(2,2,2-trifiuoroethoxy)phenoxy] ethylamino]propyl]indoline-7-carbonitrile (V). Resolution of the obtained racemic Compound (V) is carried out using (+)-mandelic acid to produce R-isomer of Compound (V), which is further treated with di-tert-butyl dicarbonate (Boc) to produce (R)-l-acetyl-5-[2-pSI-Boc-2-(2,2,2-trifluoroethoxyphenoxy)ethylamino]propyl]indoline-7-carbonitrile (VI).

The obtained Compound (VI) is deacetylated to produce (R)-5-[2-[N-Boc-2-(2,2,2 trifluoroethoxyphenoxy)ethylamino]propyl]indoline-7-carbonitrile (VII), which is hydrolyzed in the presence of peroxide in an alkaline environment to produce (R)-5-[2-[N-Boc-2-(2,2,2-trifluoroethoxyphenoxy]ethylamino]propyl]indoline-7-carboxamide (VIII). The obtained Compound (VIII) is reacted with 3-tert-butyldimethylsilyloxypropylalcohol nosylate to produce (R)-5-[2-[N-Boc-2-(2,2,2-trifluoroethoxyphenoxy]ethylamino]propyl-l-(3-tert-butyldimethyl- silyloxy)propyl]indoline-7-carboxamide (IX), which is further reacted with tetrabutylammonium fluoride (TBAF) to produce (R)-5-[2-[N-Boc-2-(2,2,2-trifluoroethoxyphenoxy]ethylamino]propyl]-l-(3-hydroxypropyl)indoline-7-carboxamide (X), followed by treating the obtained Compound (X) with trifluoroacetic acid to produce Silodosin.

The process as shown below:

The above process is not particularly suitable for large-scale production, because it involves the more number of steps. This results in more production times, which in turn renders the process more costly and less eco friendly. Further the above process is low yielding and with less purity. JP 4634560 discloses a variant process for the preparation of Silodosin, by reacting l-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl) indoline (XI) with hydrogen peroxide in the presence of potassium carbonate to produce l-(3-benzoyloxypropyl)-7-cyano-5-(2-oxopropyl)indoline (XII). The obtained keto Compound XII was further converted to amine compound, by treating with L-2-phenylglycinol and then subjected to catalytic reduction in the presence of platinum oxide (PtC^) to produce diastereomeric mixture, which is further undergoes catalytic reduction in the presence of palladium on carbon (Pd/C) to produce 5-[(2R)-2-aminopropyl]-l-[3-(benzoyloxy)propyl]-2,3-dihydro-lH-indole-7-carbonitrile (XIII). Compound (XIII) is treated with tartaric acid to produce enantiomerically pure tartrate salt of compound (XIII) and the obtained tartrate salt of compound (XIII) is condensed with Compound (IV) to produce l-(3-benzyoloxypropyl)-5-[(2^)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile (II). Oxidation of the Compound (II) to produce l-(3-benzyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carboxamide (XIV), which on hydrogenation using Pd/C to produce Silodosin (I).

The main disadvantage with the above process is that it requires three steps to convert nitro compound (XI) to amino compound (XIII). After the reaction of Compound (XIII) and Compound (IV), the product obtained Compound (II) contains the N,N-dialkyl impurity (XV) is included in the product around 5 to 20% usually, though it is different depending on the reaction condition.US 7,834,193 discloses a process for the preparation of Silodosin (I), by treating l-(3-benzyoloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile (II) with oxalic acid to produce monooxalate salt of compound (II). Hydrolysing the obtained monooxalate compound (II) to produce l-(3-hydroxypropyl)-5 - [(2R)-2-( {2- [2-(2,2,2-trifluoroethoxy)phenoxy] ethyl} amino)propyl] -2,3-dihydro-lH-indole-7-carbonitrile (XVI), which is further reacted with hydrogen peroxide (H2O2) to produce Silodosin (I). WO 2012/147019 discloses a process for the preparation of Silodosin (I), by treating l-(3-benzyoloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl] -2,3-dihydro-lH-indole-7-carbonitrile (II) with tartaric acid to produce tartrate salt of Compound (II). Hydrolyzing the obtained tartrate salt of Compound (II) to produce l-(3-hydroxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile (XVI), which is further reacted with hydrogen peroxide (H2O2) to produce Silodosin (I).

The main disadvantage with the above processes is that the formation of N,N-dialkyl impurity of compound of Formula (XV), during the condensation of Compound (XIII) with Compound (IV), the impurity which is not removable by crystallization method or precipitation technique and column chromatography purification is not suitable for commercial purpose. Hence, there is a need to have simple, easy to handle and cost effective process for the preparation of Silodosin (I) and its intermediates with high chemical purity and higher yields. So considering the importance of Silodosin, the present invention focus on the preparation of pure Silodosin, and found that the isolation of Formula (II) as N-acetyl-L-glutamate salt helps to prepare Silodosin having less than 0.1 % of N,N dialkyl impurity (XV) and with good yield. None of the prior art processes discloses isolation of Formula (II) as N-acetyl-L-glutamate acid addition salt.

OBJECTIVE OF THE INVENTION

The main objective of the present invention is to provide a simple and cost effective process for the preparation of Silodosin (I) with high purity and good yield on commercial scale. Another objective of the present invention is to provide purification process of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of Formula (II). Yet another objective of the present invention is N-acetyl-L-glutamate salt of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl] -2,3-dihydro-lH-indole-7-carbonitrile (Ha), which is precursor in the synthesis of Silodosin (I).

SUMMARY OF THE INVENTION

In one embodiment of the present invention provides an improved process for the preparation of Silodosin of Formula I: which comprises:

(i) treating a compound of Formula (XIII) or its acid addition salts thereof; wherein X is a leaving group; to produce 1 -(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl} amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of Formula (II);

(ii) converting the compound of Formula (II) to its N-acetyl-L-glutamate salt;

(iii) hydrolyzing the N-acetyl-L-glutamate salt of compound (II) to produce l-(3-hydroxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}-amino)propyl] -2,3-dihydro-lH-indole-7-carbonitrile (XVI); and

(iv) converting the compound of Formula (XVI) to Silodosin (I).

In another embodiment of the present invention is the purification process of a compound of Formula (II): which comprises:

a) obtaining a solution of a compound of Formula (II);

b) adding N-acetyl-L-glutamic acid to step (a);

c) isolating N-acetyl-L-glutamate salt of a compound of Formula (II); and

d) optionally, converting N-acetyl-L-glutamate salt to Silodosin (I).

In another embodiment, the present invention provides N-acetyl-L-glutamate salt of a compound of Formula (Ha).

DETAILED DESCRIPTION OF THE INVENTION

In first embodiment of the present invention relates to an improved process for the preparation of Silodosin of Formula I: which comprises:

(i) treating a compound of Formula (XIII) or its acid addition salts thereof; with a compound Formula (IV) in a solvent and in the presence of a base to produce l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl}amino)propyl]-2,3-dihydro-lH-indole -7-carbonitrile of Formula (II);

(ii) converting the compound of Formula (II) to its N-acetyl-L-glutamate salt in presence of a solvent;

(iii) hydrolyzing the N-acetyl-L-glutamate salt of compound (II) in a solvent and in presence of a base to produce l-(3-hydroxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2- trifluoroethoxy) phenoxy]ethyl} -amino)propyl]-2,3-dihydro-1 H-indole-7- carbonitrile (XVI); and

(iv) treating the compound of Formula (XVI) with hydrogen peroxide in a solvent and in the presence of base to produce Silodosin (I).

The salt of compound of Formula (XIII) in step (i) is tartaric acid salt. The leaving group X of the general formula (IV) is halogen comprises chlorine, bromine, iodine; a lower alkyl sulfonyloxy group comprises methanesulfonyloxy group and the like; an arylsulfonyloxy group comprises benzenesulfonyloxy group or toluenesulfonyloxy group and the like. The solvent used in the condensation step (i) organic solvent, for example is alcohol comprises methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutylalcohol, tert-butylalcohol, isoamylalcohol, 2-methoxyethanol; ketone comprises acetone, methylisobutylketone, 2-pentanone, ethylmethylketone, diethylketone; ester comprises ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate; an aprotic polar solvent comprises dimethylformamide, dimethylsulfoxide, acetonitrile, dichloromethane, or mixture thereof. The base used in the condensation step (i) is organic or inorganic base. The inorganic base comprises sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or mixture thereof and the organic base comprises diisopropylamine, diisopropylethylamine triethylamine, dimethylamine, trimethyl amine, pyridine or mixtures thereof.

The reaction may be usually performed at from room temperature to a boiling point of solvent used for the reaction for 30 minutes to 48 hours. After the reaction, l-(3-benzoyloxypropyl)-5 - [(2i?)-2-( {2- [2-(2,2,2-trifluoroethoxy)phenoxy] ethyl} amino)propyl] -2,3-dihydro-lH-indole-7-carbonitrile (II) can be obtained by a usual procedure. The above-mentioned by-product (XV) is included in the product around 5 to 20% usually, though it is different depending on the reaction condition. The solvent used in the salt formation step (ii) is alcohol comprises methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutylalcohol, tert-butylalcohol, isoamylalcohol, 2-methoxyethanol; ketone comprises acetone, methylisobutylketone, 2-pentanone, ethylmethylketone, diethylketone; ester comprises ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate; acetonitrile, dichloromethane, toluene, xylene or mixture thereof. As the solvent, among them, a lower alcohol is preferable, especially ethanol, isopropyl alcohol and a mixed solvent of water and isopropyl alcohol is preferable. Though it can be depending on the solvent, a preferable amount of N-acetyl-L-glutamic acid to be used is from usually 0.5 to 1.5 equivalents to compound of Formula (II).

A crystal of the N-acetyl-L-glutamate can be crystallized out by leaving the above N-acetyl-L- glutamate solution or optionally seeding crystals of the N-acetyl-L- glutamate or cooling down may be used. Furthermore, the N-acetyl-L- glutamate can be also crystallized out by concentrating the N-acetyl-L- glutamate solution or dropping a poor solvent into the N-acetyl-L- glutamate solution. The amount of by-product (XV) contained can be reduced 0.1% or less by the above-mentioned method, by way of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile N-acetyl-L-glutamate. Therefore, an obtained N-acetyl-L-glutamate can be used in the next reaction directly. The solvent used in hydrolysis step (iii) is water; alcohol comprises methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutylalcohol, tert-butylalcohol, isoamylalcohol, 2-methoxyethanol; ketone comprises acetone, methylisobutylketone, 2-pentanone, ethylmethylketone, diethylketone; ester comprises ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate; acetonitrile, dichloromethane, toluene, xylene or mixture thereof.

The base used in hydrolysis step (iii) is organic or inorganic base. The inorganic base comprises sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or mixture thereof and the organic base comprises diisopropylamine, diisopropylethylamine, triethylamine, dimethylamine, trimethyl amine, pyridine or mixtures thereof. The hydrolysis reaction may be performed usually at from 0°C to a boiling point of an used solvent for 30 minutes to 48 hours, and then l-(3-hydroxypropyl)-5-[(27?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}-amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile (XVI) can be obtained by a usual procedure. The obtained compound (XVI) may be used in the next reaction directly or optionally after further purification. The solvent used in step (iv) is water; a lower alcohol such as methanol, ethanol, propanol, isopropyl alcohol and the like; a water soluble organic solvent such as acetone, tetrahydrofuran, dioxan, dimethylsulfoxide and the like; and a mixture of solvents selected from the same and the like can be illustrated. Among them, a mixed solvent of water and dimethylsulfoxide is preferable.

The base used in step (iv) is organic or inorganic base. The inorganic base comprises sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or mixture thereof and the organic base comprises diisopropylamine, diisopropylethylamine, triethylamine, dimethylamine, trimethyl amine, pyridine or mixtures thereof. The hydrolysis reaction may be performed at from 0°C to 100°C for 30 minutes to 48 hours, and then Silodosin can be obtained by a usual procedure. In another embodiment of the present invention relates to purification process of l-(3-benzoyloxypropyl)-5-[(2/?)-2-({2-[2-(2,2,2 trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of a compound of Formula (II): which comprises:

a) obtaining a solution of a compound of Formula (II);

b) adding N-acetyl-L-glutamic acid to step (i) in a solvent;

c) isolating N-acetyl-L-glutamate salt of a compound of Formula (II); and

d) optionally, converting N-acetyl-L-glutamate salt to Silodosin (I).

The solvent used in step (b) is alcohol comprises methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutylalcohol, tert-butylalcohol, isoamylalcohol, 2-methoxyethanol; ketones comprises acetone, methylisobutylketone, 2-pentanone, ethylmethylketone, diethylketone; esters comprises ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate; acetonitrile, dichloromethane, toluene, xylene or mixture thereof. The amount of N-acetyl-L-glutamic acid to be used is from usually 0.5 to 1.5 equivalents to compound of Formula (II). Isolation of the N-acetyl-L-glutamate salt of Compound (II) from the reaction mixture by crystallized out by leaving the above N-acetyl-L- glutamate solution or optionally seeding crystals of the N-acetyl-L- glutamate or cooling down may be used. Furthermore, the N-acetyl-L- glutamate can be also crystallized out by concentrating the N-acetyl-L-glutamate solution or dropping a poor solvent into the N-acetyl-L- glutamate solution. The amount of by-product (XV) contained can be reduced 0.1% or less by the above-mentioned method, by way of l-(3-benzoyloxypropyl)-5-[(2/?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile N-acetyl-L-glutamate. Therefore, an obtained N-acetyl-L-glutamate salt of Compound (II) can be used in the next reaction directly.

N-acetyl-L-glutamate salt of Compound (II) obtained by the present invention is converted to Silodosin as defined above. Common method like crystallization and column chromatography are fails to remove the above said impurity and hence not viable for commercial purpose. US 7,834,193 disclose monooxalate salt of compound of Formula (II) with 0.9 % dialkyl impurity (XV). WO 2012/147019 of Orchid Chemicals discloses tartrate salt of compound of Formula (II) with 0.2 % dialkyl impurity (XV). None of the prior arts produces the compound of Formula (II) with less than 0.1 % dialkyl impurity. Applicant diligently did research to identify a process for compound (II) with less or free of N,N dialkyl impurity and found that preparing as its N-acetyl-L-glutamate salt yielded compound of Formula (II) with reduced amount of N,N dialkyl impurity less than 0.1%. No prior art teaches or motivates the invention provided in the present application. Thus the present invention provides the good process to eliminate the impurities particularly N,N-dialkyl impurity (XV). The starting material for the preparation of Formula (II) is 5-[(2R)-2-aminopropyl]-l-[3-(benzoyloxy)propyl]-2,3-dihydro-lH-indole-7-carbonitrile L-tartrate (XIII) is prepared by the process disclosed in JP 4634560. Another starting material for the preparation of Formula (II) is Compound (IV) is prepared by the process disclosed in US 5,387,603. The following examples illustrate the nature of the invention and are provided for illustrative purposes only and should not be construed to limit the scope of the invention.

EXAMPLES

EXAMPLE -1

Stage-I: PREPARATION OF l-[3-BENZOLOXY)PROPYL]-5-[(2R)-2-[[2-[2-(2,2,2 TRIFLUOROETHOXY)PHENOXY]ETHYL]AMINO]PROPYL]-2,3DIHYDRO-1H-INDOLE-7-CARBONITRILE N-ACETYL-L-GLUTAMATE SALT (Ha) 5-[(2R)-2-Aminopropyl]-l-[3-(benzoyloxy)propyl]-2,3-dihydro-lH-indole-7-carbonitrile L-tartrate (XIII) (100 g) was suspended in DM water and basified with 20% aqueous sodium carbonate solution to pH 8. The reaction mixture was extracted with ethyl acetate (800 ml). The combined organic phase was washed with saturated sodium bicarbonate solution (500 ml) followed by saturated sodium chloride solution. The ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tert-butanol and to the solution, 2-[2-(2,2,2-trifluoroethoxy)phenoxy]-ethanol- 1-methanesulfonate (IVa) (103.79 g, 0.33 moles) was added followed by sodium carbonate (26.85 g, 0.25 moles). The reaction mixture was refluxed for 40 h, cooled to 25-30°C and saturated aqueous sodium bicarbonate solution (1000 ml) was added. The contents were extracted with ethyl acetate (2 x 500 ml), the extract was washed with aqueous sodium bicarbonate and brine solution successively and dried over anhydrous sodium sulfate. The organic layer was filtered and concentrated under reduced pressure. The crude 1 -[3-benzoloxy)propyl]-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl] amino]propyl]-2,3-dihydro-lH-indole-7-carbonitrile (II) product was obtained as an oil (139 g).

Chromatographic Purity: 67.65% (by HPLC) Formula (XV) impurity: 22.71% (by HPLC) N-acetyl-L-glutamic acid (38.26 g, 0.2 moles) and 2-propanol (1390 ml) were added to the above obtained oil (139 g) and the resultant mixture was refluxed at 83-85°C till a clear solution was formed. The contents were stirred for 15-20 min and cooled to 25-30°C in ~lh. The precipitated salt was stirred for 2h, the solid was filtered and washed with chilled 2-propanol (420 ml). It was dried under reduced pressure at 40-45°C to furnish the crude product l-[3-benzoyloxy)propyl]-2-3-dihydro-5-[(2R)-2-[[2-(2,2,2-trifluoroethoxy) phenoxy]ethyl]amino]propyl]-lH-indole-7-carbonitrile N-acetyl-L-gultamate. It was dissolved in isopropyl alcohol (1012ml) at 85-89°C and cooled to 25-30°C. The solid precipitate was filtered, washed with isopropyl alcohol (276ml) and dried under reduced pressure to furnish 86g of product having a purity of 99.84% by HPLC. Chromatographic Purity: 99.84% (by HPLC) Formula (XV) impurity: 0.08% (by HPLC)

Stage-II: PREPARATION OF l-(3-HYDROXYPROPYL)-5-[(21?)-2-({2-[2-(2,2,2-TRI FLUOROETHOXY)PHENOXY]ETHYL}AMINO)PROPYL]-2,3-DIHYDRO-1H-INDOLE-7-CARBONITRILE (XVI) l-[3-(Benzoyloxy)propyl]-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]-ethyl]amino] propyl]-2,3-dihydro-lH-indole-7-carbonitrile N-acetyl-L-glutamate (Ha) (50 g, 0.065 moles) was suspended in methanol (200 ml) and cooled to 5-10°C. 5M potassium hydroxide solution (46 ml, 0.22 moles) was added to the reaction mixture and stirring was continued overnight at 25-30°C. Then DM water (750 ml) was added and the contents were extracted with ethyl acetate (1000 ml) at 25-30°C. The organic layer was washed successfully with saturated sodium bicarbonate followed by saturated sodium chloride solution. It was distilled under reduced pressure at 40-45°C. The residue was treated with diisopropyl ether (300 ml) and stirred. The precipitated solid was stirred further, at 5-10°C, filtered and washed with diisopropyl ether (100 ml). After drying under reduced pressure at 35-40°C, 26.3 g of product was obtained having a purity of 99.35% by HPLC.

Stage-Ill: PREPARATION OF SILODOSIN (I) l-(3-Hydroxypropyl)-5-[(2R)-2-[[2-[2-[2,2,2-trifluoroethoxy]phenoxy]ethyl]amino] propyl]-2,3-dihydro-lH-indole-7-carbonitrile [20 g, 0.04 moles] was dissolved in DMSO (240 ml) at 25-30°C. The solution was cooled to 0-10°C followed by the addition of 5M sodium hydroxide solution. Hydrogen peroxide (34% w/w, 10.56 ml, 0.12 moles) was added to the reaction mixture and it was stirred at 25-30°C for 3 h. The reaction mixture was cooled to 0-5°C, sodium sulfite solution was added and the contents were extracted with ethyl acetate (300 ml). The organic extract was treated with 2N hydrochloric acid and the aqueous layer was basified with aqueous sodium carbonate solution. It was then extracted with ethyl acetate (300 ml), the extract was washed with saturated sodium bicarbonate followed by saturated sodium chloride solution. To the organic layer activated carbon was added and it was stirred at 40°C. The suspension was filtered and the filtrate was distilled and ethyl acetate (140 ml) was added to the residue. The solution was cooled to 0-5°C and the precipitated solid was filtered off. It was, washed with ethyl acetate (40 ml) and finally dried under reduced pressure to furnish Silodosin (15.6 gr) having a purity of99.5%byHPLC.

WE CLAIM:

1. N-Acetyl-L-glutamate salt of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2 trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of a Compound of Formula (Ha).

2. A process for the preparation of the Compound of Formula (Ha); which comprises: treating l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl} amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of a Compound of Formula (II); with N-acetyl-L-glutamic acid to produce a Compound of Formula (Ha).

3. A process for the preparation of Silodosin of a Compound of Formula I: which comprises:

a) treating the Compound of Formula (II) with N-acetyl-L-glutamic acid to produce the Compound of Formula (Ha);

b) hydrolyzing the Compound of Formula (Ha) to produce l-(3-hydroxypropyl)-5-[(2/?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}-amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile of a Compound of Formula (XVI); and

c) converting the compound of Formula (XVI) to Silodosin (I).

4. A process according to claim 3, isolating the Compound of Formula (Ila).

5. A process according to claim 3, wherein the hydrolysis step (b) is carried out in presence of a base.

6. A process according to claim 5, wherein the base comprises; sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or mixture thereof.

7. A process according to claim 3, wherein the step (c) is carried out in presence of an oxidizing agent.

8. A process according to claim 7, wherein the oxidizing agent comprises hydrogen peroxide (H2O2).

9. A process for the preparation of l-(3-hydroxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy] ethyl} -amino)propyl] -2,3 -dihydro-1 H-indole-7-carbonitrile of a Compound of Formula (XVI), which comprises hydrolyzing N-acetyl-L-glutamate salt of l-(3-benzoyloxypropyl)-5-[(2i?)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-lH-indole-7-carbonitrile a Compound of Formula (Ila).

10. A process according to claim 2, a process for the preparation of a Compound of Formula (II); which comprises: reacting a compound of Formula (XIII) or its acid addition salts thereof; wherein X is a leaving group; to produce a Compound of Formula (II).