FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of 2-n-butyl-3-[[2'-(lH-tetrazol-5-yl)[l,l'-biphenyl]-4-yl]-l,3- diazaspiro[4.4]non-l-en-4-one of Formula (I).

This relates to an invention disclosed and claimed in our co-pending application no. 745/CHE/2006, wherein the present process is an improvement for the preparation of Irbesartan.
BACKGROUND OF THE INVENTION
2-n-Butyl-3-[[2' -(1 H-tetrazol-5-yl)[ 1,1' -biphenyl]-4-yl]-1,3-diazaspiro[4.4]non-1 - en-4-one, is generically known as Irbesartan. Irbesartan is a non-peptide angiotensin II antagonist, which antagonizes the physiologic effects of angiotensin II by inhibiting the action of angiotensin II on its receptors; the compounds particularly prevent increase in blood pressure produced by the receptor interaction. Irbesartan is approved for the treatment of Hypertension and is marketed in the US with the Brand Name, Avapro.
Elf Sanofi, first time disclosed Irbesartan and its pharmaceutically acceptable salts in US Patent No. 5,270,317.
US 5,399,578 describes two different processes for the preparation of Irbesartan and subsequently claimed in US 5,559,233. One of the processes involves the reaction of 2-n-butyl-4-spirocylopentane-2-imidazolin-5-one (II) with 4- bromomethyl-2-cyanobiphenyl (III) in the presence of NaH, followed by a column chromatography separation to yield l-[(2'-cyanobiphenyl-4-yl)methyl]-2- n-butyl-4- spirocyclopentane-2-imidazolin-5-one (IV). This compound (IV) is further reacted with tributyltin azide and the product treated with trityl chloride and separated by column chromatography. Finally, trityl protected irbesartan (V) is de-protected with HCI and the final Irbesartan product is isolated.
The process is as shown in Scheme-I below:
SCHEME I:

The second process described in this patent for the preparation of Irbesartan, is as shown in Scheme-II below:
SCHEME II:
The major disadvantages with the above processes for the preparation of Irbesartan, involve large no of steps such as protection and deprotection and tedious work-up procedures to isolate the required product. This results in more production times, which in turn renders the process more costly and less eco friendly. Further the above processes are low yielding and with less purity. WO 2005/113518 A1 describes an another alternative process for the preparation of Irbesartan process which involves reacting N- pentanoylaminocyclopentanecarboxylic acid (XI) with 2-(4- aminomethylphenyl)benzonitrile (VII) using dicyclohexyl- carbodiimide and 1- hydroxybenzotriazole as a catalyst to produce the 4-[(a-N- pentanoylamino)cyclopentamidomethyl]-2-cyanobiphenyl (XII), and then cyclising using trifluoroacetic acid to result l-[(2'-cyanobiphenyl-4-yl)methyl]-2- n-butyl-4- spirocyclopentane-2-imidazolin-5-one (IV), which is finally converted to Irbesartan (I) by reaction with tributyl tin chloride and sodium azide.
The process is as shown in Scheme-Ill below:
SCHEME III:
o ^
There is no disadvantage in the prior-art process, but the present invention is novel and commercially viable process.
In the instant invention, it has been found that the reaction of 4-aminomethyl-l,l'- biphenyl-2' -carboxamide (XIII) with N-pentanoylaminocyclopentanecarboxylic acid (XI) is simple, easy work-up, good quality of product and plant friendly process.
OBJECTIVE OF INVENTION
The main objective of the present invention is to provide a simple and effective and industrially feasible process for the preparation of Irbesartan with high purity and good yields on a commercial scale.
SUMMARY OF THE INVENTION
Accordingly, the present invention relates to an improved process for the preparation of 2-n-butyl-3-[[2'-(lH-tetrazol-5-yl)[l,l'-biphenyl]-4-yl]-l,3- diazaspiro[4.4]non-l-en-4-one (Irbesartan) of Formula (I),
which comprises,
(i) condensing the compound (XI)
with 4-aminomethyl-l,r-biphenyl-2'-carboxamide (XIII);
in presence of condensing agent and in presence or absence of base in a solvent to produce 4-[(a-JV-pentanoylamino)cyclopentamidomethyl]-2'- carboxamidobiphenyl (XIV),
(ii) cyclising a compound (XIV) in presence of acid in a solvent to produce 1- [(2'-carboxamidobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2- imidazolin-5-one (XV),
(iii) converting the compound (XV) to Irbesartan (I). DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an improved process for the preparation of 2-n- butyl-3 - [ [2' -(1 H-tetrazol-5-yl) [1,1' -biphenyl-4-yl]methyl] -1,3- diazaspiro[4.4]non-1 -en-4-one (Irbesartan).
N-pentanoylaminocyclopentanecarboxylic acid (XI) is condensed with 4- aminomethyl-l,r-biphenyl-2'-carboxamide (XIII) in presence or absence of base selected from triethylamine, diethylamine, diisopropylethylamine, preferably diisopropyethylamine in a solvent selected from chlorinated hydrocarbon such as methylene chloride, chloroform, 1,2-dichloroethane, preferably methylene chloride. Condensation is carried out in presence of condensing agent such as N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinamide and a catalyst selected from 1-hydroxybenzotriazole at a temperature of about 20°C to about 40°C. After completion of reaction as ascertained by the known detection methods reported in the art, cool the reaction mass to 0-5°C and filter the unwanted salts. The filtrate is washed with saturated sodium bicarbonate solution and evaporates the solvent to 174th volume and filter the obtained solid 4-[(a-JV- pentanoylamino)cyclopentamido-methyl]-2'-carboxamidobiphenyl (XIV).
4-[(a-iV-pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl (XIV) is cyclised in presence of acid selected from trifluoroacetic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic anhydride in a solvent selected from aromatic hydrocarbons such as benzene, toluene, xylene. The cyclisation reaction is carried out at a temperature of about 120°C to about 150°C, preferably at about 135°C to about 140°C. After completion of reaction as ascertained by the known detection methods reported in the art, solvent is removed under reduced pressure and added a solvent selected from ethylacetate, methylene chloride. pH of the reaction mass is adjusted to about 9.0 using a base selected from sodium hydroxide, potassium hydroxide or ammonium hydroxide. Separate the organic layer and distill out the solvent and added second solvent selected from toluene and cool the slurry. Filter the solid to obtain l-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-«-butyl-4-spirocyclopentane- 2-imidazolin-5-one (XV).
Treating 1 -[(2'-carboxamidobiphenyl-4-yl)methyl]-2-«-butyl-4-
spirocyclopentane-2-imidazolin-5-one (XV) with p-toluenesulfonylchloride, benzenesulfonyl chloride, thionyl chloride in presence of organic base selected from pyridine. When the reaction is carried out in presence of a base, the reaction proceeds through a cyano intermediate, which may or may not be isolated. The reaction is carried out at a temperature of about 50°C to about 80°C for 1 hr to about 3 hrs, most preferably 1 hr. After completion of reaction as ascertained by the known detection methods reported in the art, reaction mass is diluted with ethylacetate and water and stir for 15 minutes. Separate the organic layer and distill out the ethyl acetate completely and add fresh ethyl acetate and keep it for overnight to produce a crystalline l-[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-
4- spirocyclopentane-2-imidazolin-5-one (IV).
l-[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-
5- one (IV) is treated with trialkyl tin chloride selected from tributyl tin chloride and alkyl azide selected from sodium azide, potassium azide in a solvent selected from aromatic hydrocarbons selected from benzene, toluene, xylenes, most preferably o-xylene. The reaction is carried out at reflux temperature for about 20 to 24 hrs. After completion of reaction as ascertained by the known detection methods reported in the art, cool the reaction mass to about 15°C to 30°C, preferably 15°C to 20°C and Water, followed by hydrochloric acid is added and stir the reaction mass for 10 to about 30 minutes. Filter the solid and suspended in water, adjust the pH to 12.0 using inorganic base selected from sodium hydroxide, potassium hydroxide or ammonium hydroxide. Wash the resulting solution with solvent selected from ethyl acetate, methylene acetate, butylacetate, and adjust the pH of the aqueous layer to 4.6 to 4.8 using hydrochloric acid. The solid obtained is filtered to produce crude Irbesartan of Formula I.
On the other hand one can also proceed directly for preparation of Irbesartan without isolating intermediate l-[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-4- spirocyclopentane-2-imidazolin-5-one (IV). After completion of reaction as ascertained by the known detection methods reported in the art, reaction mass is diluted with solvent selected from aromatic hydrocarbons such as toluene, benzene, xylenes and water and separate the organic layer. Treating organic layer containing l-[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2- imidazolin-5-one (IV), with trialkyl tin chloride selected from tributyl tin chloride and alkyl azide selected from sodium azide, potassium azide in a solvent selected from aromatic hydrocarbons selected from benzene, toluene, xylenes, most preferably o-xylene. The reaction is carried out at reflux temperature for about 20 to 24 hrs. After completion of reaction as ascertained by the known detection methods reported in the art, cool the reaction mass to about 15°C to 30°C, preferably 15°C to 20°C and Water, followed by hydrochloric acid is added and stir the reaction mass for 10 to about 30 minutes. Filter the solid and suspended in water, adjust the pH to 12.0 using inorganic base selected from sodium hydroxide, potassium hydroxide, ammonium hydroxide. Wash the resulting solution with solvent selected from ethyl acetatemethyl acetate, butyl acetate, and adjust the pH of the aqueous layer to 4.6 to 4.8 using hydrochloric acid. The solid obtained is filtered to produce crude Irbesartan of Formula I.
In an another embodiment, alternatively one can also proceed directly for preparation of Irbesartan by reacting l-[(2'-carboxamidobiphenyl-4-yl)methyl]-2- »-butyl-4-spirocyclopentane-2-imidazolin-5-one (XV) with trialkyl tin chloride selected from tributyl tin chloride and alkyl azide selected from sodium azide, potassium azide in a solvent selected from aromatic hydrocarbons selected from benzene, toluene, xylenes, most preferably o-xylene. The reaction is carried out at reflux temperature for about 20 to 24 hrs. After completion of reaction, as ascertained by the known detection methods reported in the art, the reaction mass is cooled to about 15°C to 30°C, preferably 15°C to 20°C and Water, followed by hydrochloric acid is added and stir the reaction mass for 10 to about 30 minutes. The solid precipitated is filtered and suspended in water, the pH is adjusted to 12.0 using inorganic base selected from sodium hydroxide, potassium hydroxide or ammonium hydroxide. The resulting solution is washed with solvent selected from ethyl acetate, methyl acetate, butylacetate, and the pH of the aqueous layer is adjusted to 4.6 to 4.8 using hydrochloric acid. The solid obtained is filtered to produce crude Irbesartan of Formula I.
Crude Irbesartan (I) is purified by suspending in a solvent selected from alcohols selected from methanol, ethanol, isopropanol, butanol at reflux temperature to get clear solution and cool the resulting solution to 10°C to about 15°C, the solid obtained is filtered and dried to produce pure Irbesartan.
The following examples to prepare Irbesartan illustrate the nature of the invention and are provided for illustrative purpose only and should not be construed to limit the scope of the invention:
EXAMPLE 1
Stage I: Preparation of 4-[(a-N-pentanoylamino)cyclopentamidomethyl]-2'- carboxamidobiphenyl (XIV)
4-Aminomethyl-l,r-biphenyl-2'-carboxamide (XIII) (10 g, 0.044 mole), N- pentanoylaminocyclopentanecarboxylic acid (XI) (9.42 g, 0.044 mole), 1- hydroxybenzotriazole (1.15 g, 0.0085 mole) and dicyclohexylcarbodiimide (9.20 g, 0.044 mole were added to acetone (300 ml) at 25-30°C. The reaction mixture was heated to 30-32°C and maintained at this temperature for 24 h. Thereafter, cooled the contents to 0-5°C and filtered the salts. The filtrate obtained was concentrated, methylene chloride (100 ml) was added to the residue and stirred at 20-25°C for 1 h. Solid was filtered, washed with precooled methylene chloride (20 ml, 0-5 °C) and dried to obtain the title compound as a white amorphous powder (12 g, 65% yield).
lH NMR in DMSO-d*: (8 in ppm), 0.83-0.88 (t, 3H), 1.22-1.29 (m, 2H), 1.45-1.50 (m, 2H), 1.62 (m, 4H), 1.87-2.11 (m, 4H), 2.13-2.16 (t, 2H), 4.28-4.30 (d, 2H), 7.22-7.48 (m, 10H), 7.89 (bs, 1H), 8.02-8.06 (t, 1H). Mass (+ve ion mode): 422.
Stage II: Preparation of l-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-n-butyl- 4-spirocyclopentane-2-imidazolin-5-one (XV)
4-[(a-jV-Pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl (15 g, 0.036 mole) was suspended in o-Xylene (75 ml) and trifluoroacetic acid (8.20 g, 0.072 mole) was added at 25-30°C. The reaction mixture was heated to reflux (139-140°C) and continued the stirring at reflux temperature for 15 h. Solvent was removed under reduced pressure and added ethyl acetate (150 ml) followed by water (75 ml) at 65-70°C and cooled to 25-30°C. pH was adjusted to 9.0 with ammonium hydroxide (5 ml, 20% w/v) and stirred for 10 min. Aqueous layer was separated and extracted with ethyl acetate (15 ml). The combined ethyl acetate was washed with water (100 ml) at 25-30°C and dried over sodium sulfate. Ethyl acetate extract was distillated off under reduced pressure at below 60°C and toluene (75 ml) was added at 45-50°C. The slurry obtained was cooled to
0-5°C and stirred for 30 min. Solid was filtered, washed with precooled toluene (15 ml, 5°C) and dried to obtain the title compound as an off-white crystalline powder (10.85 g, 75.8% yield).
!H NMR in DMSO-de: (8 in ppm), 0.79-0.83 (t, 3H), 1.26-1.29 (m, 2H), 1.48-1.53 (m, 2H), 1.67-1.85 (m, 8H), 4.71 (s, 2H), 7.15-7.66 (m, 10H). Mass (+ve ion mode): 404.5.
Stage III: Preparation of l-[(2'-cyanobiphenyl-4-yl)methyl]-2-n-butyl-4- spirocyclopentane-2-imidazolin-5-one (IV)
1 - [(2' -carboxamidobiphenyl-4-yl)methyl] -2-«-butyl-4-spirocyclopentane-2- imidazolin-5-one (5 g, 0.0124 mole), pyridine (3.50 g, 0.044 mole), p- toluenesulfonylchloride (3.76 g, 0.0197 mole) were added respectively and heated the mixture to 70-75°C. Stirred the reaction mass at 70-75°C for 1 h and cooled to 45-50°C. Ethyl acetate (50 ml) and water (50 ml) were added and stirred for 10 min. Aqueous layer was separated and extracted with ethyl acetate (25 ml) at 25- 30°C. The combined ethyl acetate extract was washed with water (25 ml) and dried over sodium sulfate. Ethyl acetate was completely distilled under reduced pressure at below 50°C, the residue was dissolved in ethyl acetate (5 ml), cooled to -20°C to -25°C and kept for overnight. The crystals formed were collected by filtration, washed with precooled ethyl acetate (5 ml, -10°C) and dried to obtain the title compound as an off-white crystalline powder (2.20 g, 46% yield).
Stage IV: Preparation of Irbesartan (I)
l-[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin- 5-one (2 g, 0.0052 mole), tributylitin chloride (2.42 g, 0.0074 mole), sodium azide (0.48 g, 0.0074 mole) were added respectively to o-xylene at 25-30°C. The mixture was heated to reflux temperature (144-146°C) for 24 h and cooled to 20°C. Water (2 ml) was added follwed by hydrochloric acid (1.8 ml, 15% w/v) at 18-20°C and the slurry obtained was stirred for 15 min at 18-20°C. Solid was filtered, washed with water (6 ml) followed by toluene (6 ml, 40°C). Finally, washed with water (6 ml). The wet solid (3.6 g) was suspended in water (15 ml) at 25-30°C and adjusted the pH to 12.0 with 5% w/v aqueous sodium hydroxide (4.7 ml) in 5 min and treated with carbon for 30 minutes and filtered. The filtrate was washed with ethyl acetate (12 ml). PH of the aqueous layer was adjusted to 4.6-4.8 with hydrochloric acid (0.5 ml, 15% w/v) at 25-30°C. The slurry obtained was stirred for 30 min at 25-30°C. Solid was filtered, washed with water (5 ml, 35-40°C) and dried to get the crude Irbesartan as an off-white powder (1.47 g, 66.2% yield).
Purification of Irbesartan crude:
Irbesartan-crude, as obtained above (1.3 g), was suspended in ethanol (absolute alcohol, 15 ml) and heated to reflux temperature (82°C) to get a clear solution. Carbon (90 mg) was added and stirred at 82°C for 30 min. Carbon was filtered, washed with hot ethanol (5 ml, 60°C). The filtrate was cooled to 25-30°C and stirred for 1 h. Thereafter, cooled the slurry to 10-12°C and stirred for 90 min at 10-12°C. Solid was filtered, washed with precooled ethanol (5 ml, 5°C) and dried to obtain Irbesartan as a white crystalline powder (1.05 g).
EXAMPLE II
Preparation of 4-[(a-N-pentanoylamino)cyclopentamidomethyl]-2'- carboxamidobiphenyl (XIV) 4-Aminomethyl-l,r-biphenyl-2'-carboxamide hydrochloride (XIII) (15 g, 0.0571 mole), ,/V-pentanoylaminocyclopentanecarboxylic acid (XI) (12.17 g, 0.057 mole), 1-hydroxybenzotriazole (1.5 g, 0.011 mole), diisopropylethylamine (8.17 g, 0.062 mole) and dicyclohexylcarbodiimide (12.95 g, 0.0062 mole) were added to methylene chloride (375 ml) at 25-30°C and warmed the mixture to 32-33°C. Thereafter, stirring was continued for 6 h at 32-33°C. The slurry was cooled to 0- 5°C and filtered the salts. The filtrate was washed with saturated sodium bicarbonate solution (120 ml), concentrated to 75 ml volume under reduced pressure at below 50°C and cooled to 0-5°C. Precipitated solid was filtered, washed with precooled methylene chloride (30 ml, 0°C) and dried to give the title compound as white amorphous powder (18 g, 74.8% yield).
'H NMR in DMSO-d*: (8 in ppm), 0.83-0.88 (t, 3H), 1.22-1.29 (m, 2H), 1.45-1.50 (m, 2H), 1.62 (m, 4H), 1.87-2.16 (m, 6H), 4.28-4.30 (d, 2H), 7.22-7.62 (m, 10H), 7.89 (s, 1H), 8.06 (t, 1H). Mass (+ve ion mode): 422.
EXAMPLE III:
Preparation of Irbesartan (I)
1 - [(2' -Carboxamidobiphenyl-4-yl)methyl] -2-«-butyl-4-spirocyclopentane-2- imidazolin-5-one(XIV) (10 g, 0.0248 mole), pyridine (5 g, 0.063 mole), p- toluenesulfonyl chloride (7.5 g, 0.039 mole) were added respectively and heated to 70-75°C. Thereafter, the reaction mixture was stirred at 70-75°C for 1 h. o- Xylene (50 ml) and water (25 ml) were added at 70-75°C and stirred for 10 min. Organic layer was separated, washed with water (25 ml) and dried over sodium sulfate. Sodium sulfate was washed with o-xylene (20 ml). Tributyltinchloride (11.70 g, 0.036 mole) and sodium azide (2.34 g, 0.036 mole) were added respectively to the xylene layer at 25-30°C. The reaction mixture was heated to reflux at 136-137°C for 60 h. Thereafter, cooled to 10-15°C and water (100 ml) was added. PH was adjusted to 11.5-12 with 10% w/w sodium hydroxide solution and stirred the reaction mass for 1 hour. Organic layer was separated and again extracted with water (100 ml). The combined aqueous layer was washed with ethyl acetate (2x25 ml) at 10-15°C. The aqueous layer pH was adjusted to 4.6-4.8 with 15% w/w hydrochloric acid at 25-30°C. Precipitated solid was filtered, washed with water (100 ml) and dried to obtain Irbesartan-crude as an off-white powder (5 g, 45% yield). It was purified as per the method given in Example I.
EXAMPLE IV:
Preparation of Irbesartan (I)
1 - [2'-Carboxamidobiphenyl-4-yl)methyl] -2-n-butyl-4-spirocyclopentane-2- imidazolin-5-one (XV) (5 g, 0.0124 mole) was added to a mixture of tributyl tin chloride (8.48 g, 0.026 mole) and o-xylene (5 ml) at 25-30°C. Sodium azide (1.69 g, 0.026 mole) was added to the above suspension and heated to reflux. Thereafter, reflux was continued till completion of the reaction. The reaction mass was cooled to 20-25°C and o-xylene (10 ml), water (60 ml) were added followed by the addition of methylene chloride (60 ml) at 20-25°C. Hydrochloric acid (3 ml, 35% w/w) was added in 15 min at 20-25°C and continued the stirring for 2 h at the same temperature. Thereafter, pH was adjusted to 4.5-4.8 with aqueous ammonia solution at 20-25°C and continued the stirring for 2 h. Product was filtered, washed with a 1:3 v/v mixture of o-xylene and methylene chloride (10 ml). Product was dried at 70-75°C under reduced pressure (10 mm Hg). The dried product was suspended in water (50 ml), heated to 50°C and stirred for 30 min at 45-50°C. Product was filtered, washed with water (50 ml) and dried to afford Irbesartan as a white solid. (4.1 g, 77% yield).

WE CLAIM:
1. An improved process for the preparation of 2-n-butyl-3-[[2'-(lH-tetrazol-5- yl)[l,r-biphenyl]-4-yl]-l,3-diazaspiro[4.4]non-l-en-4-one (Irbesartan) of Formula (I),
which comprises, (ii) condensing the compound (XI)

with 4-aminomethyl-l,r-biphenyl-2'-carboxamide (XIII);

in presence of condensing agent and in presence or absence of base in a solvent to produce 4-[(a-iV-pentanoylamino)cyclopentamidomethyl]-2'- carboxamidobiphenyl (XIV),
(ii) cyclising a compound (XIV) in presence of acid in a solvent to produce 1 -[(2'-carboxamidobiphenyl-4-yl)methyl]-2-w-butyl-4- spirocyclopentane-2-imidazolin-5-one (XV),

(iii) converting the compound (XV) to Irbesartan (I).
2. The process according to claim 1, wherein condensing agent used in step (i) is
selected from N,N'-dicyclohexylcarbodiimide, N-hydroxysuccinamide.
3. The process according to claim 1, wherein condensation step is carried out in
presence of catalyst selected from 1-hydroxybenzotriazole.
4. The process according to claim 1, wherein base used in step (i) is selected from
organic bases such as triethylamine, diethylamine, diisopropylethyl amine, butylamine or inorganic base such as aqueous solution of alkali metal carbonate such as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, most preferably aqueous sodium carbonate.
5. The process according to claim 1, wherein solvent used in condensation step is
selected from chlorinated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane.
6. The process according to claim 1, wherein acid used in cyclisation step (ii) is
selected from trifluoroacetic acid, trifluoromethanesulfonic acid, p- toluenesulfonic acid, trifluoromethanesulfonic anhydride.
7. The process according to claim 1, wherein solvent used in cyclisation step (ii) is
selected from aromatic hydrocarbons such as benzene, toluene, xylenes.
8. The process according to claim 1, wherein compound (XV) is converted to Irbesartan (I), by a process, which comprises;
reacting l-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-«-butyl-4- spirocyclo-pentane-2-imidazolin-5-one (XV) with an acid chloride in presence of organic base to produce l-[(2'-Cyanobiphenyl-4-yl)methyl]-2- n-butyl-4-spirocyclopentane-2-imidazolin-5-one (IV);

- treating 1 -[(2'-Cyanobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopen- tane-2-imidazolin-5-one (IV) with trialkyl tin chloride and alkylazide in a solvent to produce Irbesartan (I).
9. The process according to claim 7, wherein acid chloride is selected from p- toluenesulfonylchloride, benzenesulfonyl chloride or thionyl chloride.
10. The process according to claim 7, wherein organic base is selected from pyridine.
11. The process according to claim 7, wherein trialkyl tin chloride is selected from tributyl tin chloride.
12 The process according to claim 7, wherein alkyl azide is selected from sodium azide, potassium azide.
13. The process according to claim 7, wherein solvent selected from aromatic hydrocarbons such as benzene, toluene, xylenes.
14. The process according to claim 1, wherein compound (XV) is converted to Irbesartan (I), by reacting l-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-«-butyl- 4- spirocyclo-pentane-2-imidazolin-5-one (XV) with trialkyl tin chloride and alkyl azide in a solvent.
15. The process according to claim 10, wherein trialkyl tin chloride is selected from tributyl tin chloride.
16. The process according to claim 10, wherein alkyl azide is selected from sodium azide, potassium azide.
17. The process according to claim 10, wherein solvent selected from aromatic hydrocarbons such as benzene, toluene, xylenes.