FIELD OF INVENTION
The present invention relates to novel compounds of Formula I

Y
o
Formula I
wherein said compounds of Formula I can be used for the preparation of angiotensin-II receptor blocker i.e. Azilsartan and its derivatives and pharmaceutical acceptable salts thereof. The present invention further relates to the process of preparation of novel compounds of Formula I, wherein M represents organic amine.
BACKGROUND OF THE INVENTION
Azilsartan medoxomil, chemically known as (5-methyl-2-oxo-l, 3-dioxol-4-yl)methyl-2-ethoxy-l-{[25-(5-oxo-4,5-dihydro-l,2,4-oxadiazol-3-yl)biphenyl-4yl]methyl}-l//-benzimidazole-7-carboxylate is a derivative of Azilsartan which is an ATi-subtype angiotensin-II receptor blocker (ARB). Angiotensin II receptor antagonist can be effective therapeutic drug for circulatory diseases such as hypertension and the like. Azilsartan medoxomil keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.
Azilsartan is known from United states patent 5,583,141 which discloses preparation of Azilsartan (Scheme-1) starting from methyl l-((2'-cyanobiphenyl-4-yl)methyl)-2-ethoxy-l//-benzo[d]imidazole-7-carboxylate (II). This compound, which is a well-known intermediate of candesartan, is first transformed, by a reaction with hydroxylamine hydrochloride to methyl 2-ethoxy-1 -((2' -((hydroxy amino)-iminomethyl)biphenyl-4-yl)methyl)-1 //-benzo [d] imidazole-7-carboxylate (III), and then converted to methyl 2-ethoxy-l-((2'-(5-oxo-4,5-dihydro-l,2,4-oxaxiazol-3-yl)biphenyl-4-yl)methyl)-l//-benzo[d]imidazole-7-carboxylate (IV) followed by conversion to azilsartan (V) through saponification. Scheme-1

NH2OH.HCI/
MeONa

K 1

HO

(H)

(III)

alkyl chlorocarbonate TEA/THF



HO "O
LiOH/MeOH

O "O

>0 °V°-
Vo T N

(V)

(IV)

EP 2,508,522 Al discloses azilsartan organic amine salt which is prepared by dissolving organic amine and azilsartan acid form in organic solvent wherein the organic amine is preferably ethanol amine. Other organic amines disclosed in this patent application are methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, ethanolamine, piperazidine, dibenzylethylenediamine, meglumine, tromethamine, tetramethyl quaternary ammonium, tetraethyl quaternary ammonium and choline.
Similarly, CN 105037341 discloses crystalline form of azilsartan alcohol ammonia crystal form and a preparation method thereof wherein the organic amine salt is ethanol amine HC1 salt.
CN 104119326 discloses process of preparation of azilsartan alkali metal salt and use of said compound in preparation of azilsartan wherein the alkali metal salt is selected from sodium, potassium or lithium. It is disclosed that the azilsartan alkali metal salt is prepared by dissolving aqueous alkali hydroxide to solvent such as Dimethyl formamide (DMF) followed by addition of azilsartan methyl ester. After completion of reaction, filtered the cake and washed it with ketone solvent to get metal alkali salt of azilsartan as a white salt.
US 9,233,955 B2 discloses process of preparation of azilsartan ester by reacting methyl-2-ethoxy[(2'-(hydroxyamidino)biphenyl-4-yl]methyl]-lH-benzimidazole-7-carboxylate with

carbonyl source such as N,N-carbonyldiimidazole in presence of base like DBU. The azilsartan ester thus formed is used for preparation of azilsartan and its salts thereof
IN 3002/MUM/2012, discloses process of preparation of azilsartan as mentioned in scheme-2, by reacting imidoxime (VI) with ethyl chloro formate solution in solvent in presence of base. The intermediate (VII) so obtained is taken in DMF and is heated to cyclize the intermediate in absence of base to get azilsartan ester (VIII) which is converted to azilsartan (V) by saponification. The azilsartan thus obtained is used for preparation of azilsartan medoxomil and salts. Scheme-2



r^^N
alkylchloroformate NH2 /TEA/solvent
(VI)

DMF
in absence of base

N ] OVQ

HO ^O
NaOH
(VIII)
It can be seen that there are several processes known in the literature to achieve Azilsartan and its salts thereof. However, prior art processes suffer from the drawback such as impurity formation during the process which ultimately results into the low isolation yield of Azilsartan. There are several impurities formed during the formation of compounds like III and VII which are carried to Azilsartan ester during cyclization process. These impurities required tedious work ups and purification steps to provide pure Azilsartan ester and Azilsartan per se.
In view of the above, it is therefore, desirable to provide an efficient process for the preparation substantially pure Azilsartan which is achieved by preparation of a novel intermediate i.e. Azilsartan ester organic amine adduct.

The present invention thereby extends to the process for the preparation of Azilsartan which can be used for the preparation of Azilsartan medoxomil and its potassium salt.
Taking into account the drawbacks of the aforementioned prior art methods, the present invention provides novel compounds and their process of preparation, which can be effectively used as intermediate for the synthesis of Azilsartan and Azilsartan medoxomil and pharmaceutical acceptable salts thereof. The process of the present invention provide Azilsartan in high yield with high purity without involving any tedious purification process.
OBJECT AND SUMMARY OF THE INVENTION
The principal object of the present invention is to provide a novel compound of formula I that can be used as an intermediate for the preparation of angiotensin-II receptor blocker (ARB) i.e. Azilsartan and its salts thereof.
Another object of the present invention is to provide a process of preparation of compound of formula I with high yield and purity.
Another object of the present invention is to provide a process of preparation of Azilsartan kamedoxomil by using compounds of the present invention.
In accordance to one embodiment, the present invention provides compounds of formula I

Y O
Formula I
wherein R is C1-C8 alkyl or, substituted or unsubstituted aryl, and M is an organic amine.
In accordance to another embodiment, the present invention provides a process of preparation of compounds of formula I,

Formula I
wherein R is C1-C8 alkyl or, substituted or unsubstituted aryl, and M is an organic amine, wherein said process comprising the steps of:
a) reacting hydroxyamidino compounds of formula IX with alkyl/ aryl chloroformate in presence of base;

HO NH2 Formula IX
to give compounds of formula X;

wherein R' is C1-C4 alkyl or, substituted or unsubstituted aryl, R is as defined above; and b) cyclization of compounds of formula X in presence of organic amine to get compounds of Formula I.
In accordance with specific embodiment of the present invention, there is provided the use of compound(s) of Formula 1 for the manufacture of angiotensin-II receptor blocker (ARB) i.e. Azilsartan and its derivatives and salts thereof.

In accordance to another embodiment, the present invention provides a process of preparation of Azilsartan kamedoxomil by using a novel compound of Formula I,

Formula I
wherein R and M are as defined above, wherein said process comprising the steps of:
a) condensing N-protected compound of Formula XI with 4'-(bromomethyl)biphenyl-2-carbonitrile of Formula XII to get compound of Formula XIII;


O

Formula XI Formula XII Formula XIII
wherein R is as defined above;
b) reducing compound of Formula XIII in presence of Raney Nickel and catalyst in an organic
solvent to get compound of Formula XIV;

^^
Formula XIV
wherein R is as defined above;
c) hydrolysing compound of Formula XIV in presence of acid to get compound of Formula
XV;


Formula XV
wherein R is as defined above;
d) cyclizing compound of Formula XV in presence of tetra ethyl ortho carbonate to get
compound of Formula XVI;

Formula XVI
wherein R is as defined above;
e) reacting compound of Formula XVI with hydroxyl amine hydrochloride to get
hydroxyamidino compound of Formula IX;

Formula IX
wherein R is as defined above;
f) reacting hydroxyamidino compound of Formula IX with alkyl/ aryl chloroformate in
presence of base to give compound of Formula X;

^^v-N

wherein R' and R, are as defined above;
g) cyclization of compound of Formula X in presence of organic amine to get compound of
Formula I;

Formula I
wherein R and M are as defined above;
h) hydrolysing compound of Formula I to get Azilsartan of Formula XVII;



O^OH

Formula XVII
and
i) converting azilsartan of Formula XVII to azilsartan medoxomil by reacting with 4-(hydroxymethyl)-5-methyl-l ,3-dioxol-2-one followed by reaction with potassium source to get compound of Formula XVIII

rT"V-Nv /
o
u-s-


o^o

Formula XVIII
DETAILED DESCRIPTION
Definitions:
The term "alkyl" as used in context of the present invention, refers to a straight or branched
chain alkyl group.
The term "salts" as used in context of the present invention refers to alkali metal salts such as sodium, potassium, lithium, calcium, magnesium, zinc, barium and the like.
The term "aryl" as used in context of the present invention refers to (un) substituted phenyl or benzyl ring wherein the aryl ring may be substituted with C1-C8 alkyl, C1-C8 alkoxy, halo, amino, hydroxyl, cyano, thio, nitro group and -COR2 wherein R2 is hydrogen, amino, C1-C4 alkyl and halo.
The term "derivatives" as used in context of the present invention refers to medoxomil ester of Azilsartan.
The present invention will now be explained in details. While the invention is susceptible to various modifications and.alternative forms, specific embodiment thereof will be described in detail below. It should be understood, however that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the invention is to cover all modifications, equivalents, and alternative falling within the scope of the invention as defined by the appended claims.
The steps of a method may be providing more details that are pertinent to understanding the embodiments of the present invention and so as not to obscure the disclosure with details that

will be readily apparent to those of ordinary skill in the art having benefit of the description herein.
Further characteristics and advantages of the process according to the invention will result from the description herein below of preferred exemplary embodiments, which are given as indicative and non-limiting examples.
In one embodiment, the present invention provides compounds of Formula I

Formula I
wherein R is C1-C8 alkyl or, substituted or unsubstituted aryl, and M is an organic amine.
In another embodiment, the compound of formula I is an organic amine adduct of azilsartan ester and is represented by the structures as mentioned below:



H9N

OH

Formula l-A

Formula l-B


o o
Formula l-C ancj Formula l-D
wherein R is as defined above.
In one another embodiment, the organic amine is selected from the group comprising of diisopropyl amine, ethanolamine, meglumine, piperidine, benzyl piperazine, diethyl amine, methyl benzyl amine, morpholine and N, N-dibenzyl ethylene diamine.
In another embodiment, the present invention provides a process of preparation of compound of formula I

Formula I
wherein R is C1-C8 alkyl or, substituted or unsubstituted aryl, and M is an organic amine, wherein said process comprising the steps of:
a) reacting hydroxyamidino compound of formula IX with alkyl/ aryl chloroformate in presence of base; *


cr O
i
R

Formula IX
to give compound of formula X;

Formula X
wherein R' is C1-C4 alkyl or, substituted or unsubstituted aryl,
R is as defined above; and
b) cyclization of compound of Formula X in presence of organic amine to get compound of
formula I.
In another embodiment, the alkyl/ aryl chloroformate as used in step a) is selected from the group comprising of methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, benzyl chloroformate, p-nitro phenyl chloroformate, 4-methoxy chloroformate and the like. The most preferred chloroformate used is alkyl chloroformate such as ethyl chloroformate.
In one another embodiment, the base as used in step a) is selected from the group comprising of an organic base like diethylamine, triethylamine, diisopropyl ethyl amine, pyridine, piperidine, DABCO, DBU and the like.
In another preferred embodiment, the reaction step a) is carried out at a temperature in the range of 40-110°C, preferably, 50-60°C.

In one another embodiment, the organic amine used in step b) is selected from the group comprising of diisopropyl amine, ethanolamine, meglumine, piperidine, benzyl piperazine, diethyl amine, methyl benzyl amine, morpholine and N, N-dibenzyl ethylene diamine. Moreover, the reaction step b) is carried out at a temperature in the range of 40-110°C, preferably, 95-100°C.
Further, in one of the preferred embodiment, compound of Formula X is optionally isolated from the reaction mass.
In accordance to another embodiment, the compounds of formula IX can be prepared by any conventional method or by the process of the present invention.
In further embodiment, the present invention provides compounds of formula I in high yields with purity above 98.5%.
In further embodiment, the present invention provides compounds of formula I that can be used as intermediate for preparation of Azilsartan and its derivatives and salts thereof, by any conventional method or by the process of the present invention.
In yet another embodiment, the present invention provides a process of preparation of Azilsartan kamedoxomil by using a novel compound of Formula I,

Formula I
wherein R is as defined above, M is an organic amine,
wherein said process comprising the steps of:
a) condensing N-protected compound of Formula XI with 4'-(bromomethyl)biphenyl-2-
carbonitrile of Formula XII to get compound of Formula XIII;


Formula XI Formula XII Formula XIII
wherein R is as defined above;
b) reducing compound of Formula XIII in presence of Raney Nickel and catalyst in an organic
solvent to get compound of Formula XIV;

Formula XIV
wherein R is as defined above;
c) hydrolysing compound of Formula XIV in presence of acid to get compound of Formula
XV;

Formula XV
wherein R is as defined above;
d) cyclizing compound of Formula XV in presence of tetra ethyl ortho carbonate to get
compound of Formula XVI;


Formula XVI
wherein R is as defined above;
e) reacting compound of Formula XVI with hydroxyl amine hydrochloride to get
hydroxyamidino compound of Formula IX;

Formula IX
wherein R is as defined above;
f) reacting hydroxyamidino compounds of Formula IX with alkyl/ aryl chloroformate in
presence of base to give compounds of Formula X;

wherein R5 and R, are as defined above;
g) cyclization of compounds of Formula X in presence of organic amine to get compounds of
Formula I;


Formula I
wherein R and M are as defined above;
h) hydrolysing compound of Formula I to get Azilsartan acid of Formula XVII;

Formula XVII
and
i) converting azilsartan of Formula XVII to azilsartan medoxomil by reacting with 4-(hydroxymethyl)-5-methyl-l ,3-dioxol-2-one followed by reaction with potassium source to get compounds of Formula XVIII

Formula XVIII
In another embodiment, step a) is carried out at a temperature in the range of 50-100°C, preferably in the range of 75-85°C.
In yet another embodiment, the catalyst used in step b) is selected from the group comprising of acetic acid, formic acid, orthophosphoric acid, phosphoric acid and perchloric acid. In

preferred embodiment, the catalyst used in step b) is acetic acid, formic acid and phosphoric acid and most preferably the catalyst selected is acetic acid.
In another embodiment, the acid used in step c) is selected from the group comprising of dioxane. HC1, ethylacetate. HC1, methanolic HC1, ethanolic HO, isopropyl alcoholic HC1, and diethyl ethereal HC1. In preferred embodiment, the acid used is dioxane. HC1 and diethyl ethereal HC1 and most preferably the acid selected is dioxane. HC1.
In another embodiment, the alkyl/ aryl chloroformate as used in step f) is selected from the group as defined above.
In,one another embodiment, the base as used in step f) is selected from the group as defined above.
In one another embodiment, the organic amine used in step g) is selected from the group comprising of diisopropyl amine, ethanolamine, meglumine, piperidine, benzyl piperazine, diethyl amine, methyl benzyl amine, morpholine and N, N-dibenzyl ethylene diamine. In a preferred embodiment, the organic amine selected is diisopropyl amine, meglumine, piperidine and benzyl piperazine. Most preferably, the organic amine selected is diisopropyl amine.
In another embodiment, the hydrolysis in step h) is performed in aqueous medium in presence of base such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like.
In preferred embodiment, the Azilsartan of Formula XVII as obtained in step h) has a purity above 98.5%
In another embodiment, the potassium source as used in step i) is potassium 2-ethyl hexanoate.
Further, the compound(s) of formula XI can be prepared by any of the known methods.
Further, in one of the preferred embodiment, compound of Formula X is optionally isolated from the reaction mass.

In further embodiment, the azilsartan kamedoxomil compound of Formula XVIII as prepared by the process of the present invention is characterized by XRPD peaks at 6.19, 6.71, 10.20, 12.16,12.51,12.68,13.34,14.03,14.49,14.77,15.24,15.50, 16.00,16.44,16.70,17.35,17.79, 18.08,18.72,19.37,19.63,20.30,21.10,21.39,21.70,22.79,23.28,23.77,24.11,24.60,25.06, 25.61,26.12,26.62,26.97,27.52,28.16,28.90,29.21,30.01,30.86,31.32,31.90,32.34,33.02, 33.25, 33.85, 34.96, 36.06 and 37.20 ±0.20.
In further embodiment, the azilsartan kamedoxomil compound of Formula XVIII as prepared by the process of the present invention is characterized by DSC with onset temperature of 219.63°C.
In another embodiment, the present invention further provides a composition comprising azilsartan kamedoxomil compound of Formula XVIII and at least one pharmaceutical acceptable excipients. The above said composition optionally comprises an active pharmaceutical ingredient other than azilsartan kamedoxomil.
In one another embodiment, the present invention provides a method for treatment of hypertension by administration of dosage form comprising azilsartan kamedoxomil.
The present invention is explained below by way of examples. However, the examples are provided as one of the possible way to practice the invention and should not be considered as limitation of the scope of the invention.
EXAMPLES
Example 1. Preparation of 2-(methoxycarbonyl)-6-nitrobenzoic acid
Charged 50.Og of 3-Nitropthalic acid in methanol followed by addition of 30.0 ml of thionyl chloride (30.0 ml). Raised the temperature to 55-60°C. After completion of reaction, distilled the solvent completely under vacuum and added 100 ml of toluene. Filtered the solid and dried to get 51.6 g off-white solid of 2-(methoxycarbonyl)-6-nitrobenzoic acid. Purity: 97.09%
Example 2. Preparation of methyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate Added 50.0 g of 2-(methoxycarbonyl)-6-nitrobenzoic acid in 200 ml of toluene and catalytic amount M iV-dimethyl formamide. Reaction mass so obtained was heated to 70-75°C followed by addition of 31.7g of thionyl chloride (31.7 g). Stirred the reaction mass for 3-5 hours.

Distilled the solvents under vacuum to get concentrated mass of methyl 2-(chlorocarbonyl)-3-
nitrobenzoate. Added 200 ml of toluene and 50 ml of N} N-dimethyl formamide to the reaction
mass and stirred the reaction mixture at 25-30°C. Reaction mass was then cooled to -10°C and
added 50.0 g of sodium azide (50.0 g). Stirred the reaction mass for an hour at -10 to -5°C.
165.0 ml of tertiary butanol was added then to the reaction mass and temperature was raised to
75-80°C gradually and stirred for an hour. Reaction mass was cooled to 25-30°C and added
200 ml of water. Stirred the mass and separated the layers. Distilled out the organic layer under
vacuum and added isopropyl ether (IPE) to the above obtained reaction mass. Cooled to 10°C
and filtered to get 54.Og yellow solid of methyl 2-((tert-butoxycarbonyl)amino)-3-
nitrobenzoate.
Purity: 99.71%
Example 3. Preparation of 4,-(bromomethyl)-[l,l,-biphenyl]-2-carbonitrile
Charged 50.Og of 4-methyl-2-cyano biphenyl in dichloromethane and added catalytic amount
of Azobisiso butyronitrile [AIBN] and 44.0 g of 1,3-dibromo hydantoin. Reaction mass was
heated to 40°C with stirring for 16-18 hours. After completion of reaction, added water to the
reaction mass and separated the layers. Distilled out the organic layer and added 250.0 ml of
isopropyl alcohol. Filtered the solid and dried to get 58.Og of 4'-(bromomethyl)-[l J'-biphenyl]-
2-carbonitrile.
Purity: 98.56%
Example 4. Preparation of methyl 2-((tert-butoxycarbonyl)((2f-cyano-[l,r-biphenyl]-4-
yl)methyl)amino)-3-nitrobenzoate
Added 52.0 g of methyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate and 36.2 g of
potassium carbonate in 150.0 ml of acetonitrile. Added 49.0 g of 4'-(bromomethyl)-[l,l'-
biphenyl]-2-carbonitrile in the above reaction mass and heated the reaction mass to 80-85°C.
Stirred the reaction mas's for 14-15 hour at 80-85°C. Distilled out the solvent completely under
vacuum and cooled the reaction mass to room temperature. Added 500ml of water and filtered
to get 86.5 g of pale yellow solid of methyl 2-((tert-butoxycarbonyl)((2'-cyano-[l,r-biphenyl]-
4-yl)methyl)amino)-3-nitrobenzoate.
Purity: 94.88%
Example 5. Preparation of methyl 3-amino-2-((tert-butoxycarbonyl)((2,-cyano-[l,r-
biphenyl]-4 yl)methyl)amino)benzoate
Added 84.0 g of methyl 2-((tert-butoxycarbonyl)((2'-cyano-[l, 1 '-biphenyl]-4-
yl)methyl)amino)-3-nitrobenzoate and 20.0 g of raney nickel in ethyl acetate in hydrogenator.
Added 20g of Acetic acid and purged hydrogen gas to the reaction mass. Stirred the reaction

mass at 60°C till completion of reaction. After completion of reaction, filtered the reaction mass
through celite and distilled the mother liquor under vacuum to get crude methyl-3-amino-2-
((tert-butoxycarbonyl)((2'-cyano-[l,r-biphenyl]-4-yl)methyl)amino)benzoate.
Example 6. Preparation of methyl 3-amino-2-(((2f-cyano-[l,i!-biphenyl]-4-
yl)methyl)amino)benzoate
Dissolved above obtained methyl-3-amino-2-((tert-butoxycarbonyl)((2'-cyano-[l,r-biphenyl]-
4-yl)methyl)amino)benzoate dissolved in 160.0 ml of 1,4 Dioxane and cooled to 0-5°C
followed by addition of 120.0 ml of 1,4-dioxane. HC1 solution. Stirred the reaction mass for at
25-30°C till completion of reaction. After completion of reaction, distilled the solvents under
vacuum. Added 400.0 ml of ethyl acetate to the residue and basified with 15% aqueous sodium
carbonate. Separated the layers and distilled the organic layers under vacuum at 50- 55°C. 60.0
g of concentrated mass of methyl 3-amino-2-(((2'-cyano-[l,r-biphenyl]-4-
yl)methyl)amino)benzoate (60.0) so obtained was proceeded to the next step without
purification.
Example 7. Preparation of methyl l-((2v-cyano-[l9lf-biphenyl]-4-yl)methyI)-2-ethoxy-lH-
benzo[d]imidazole-7-carboxylate
Charged 180.0 ml of toluene to the concentrated mass of methyl 3-amino-2-(((2'-cyano-[l,r-
biphenyl]-4-yl)methyl)amino)benzoate (60.0 g) and added 41.94g of tetraethyl orthocarbonate
and 2.54 ml of acetic acid to the reaction mass. Raised the temperature to 90-100°C and stirred
till completion of reaction. After reaction completion, distilled the solvent under vacuum.
Added methanol to the reaction mass, cooled and filtered the off white solid and dried to get
51.0 g of methyl l-((2'-cyano-[l,r-biphenyl]-4-yl)methyl)-2-ethoxy-lH-benzo[d]imidazole-7-
carboxylate.
Purity: 98.0%
Example 8. Preparation of methyl-2-ethoxy-l-((2'-(N!-hydroxycarbamimidoyl)-[l,l'-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate
Added 1 OO.Og of methyl 1 -((2'-cyano- [1,1 '-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate and 258.0 g of sodium carbonate in 1000.0 ml of isopropyl alcohol. Temperature of the reaction mass was raised to 60-65°C and added 135.0 g of hydroxylamine hydrochloride (135.0 g) at 60°C and stirred the reaction mass for 24 hours at 85-90°C. Distilled the isopropyl alcohol under vacuum and added water to the reaction mass, filtered the solid, crystallized in methanol and dried to get 80.0 g of white solid of methyl-2-ethoxy-1 -((2'-(N'-hydroxycarbamimidoyl)- [1,1 '-biphenyl]-4-yl)methyl)-1H-benzo[d~|imidazole-7-carboxylate.

Purity: 97.30%
Example 9. Preparation of methyl 2-ethoxy-l-((2f-(5-oxo-4,5-dihydro-l,2,4-oxadiazol-3-yI)-[l,l'-biphenyl]-4-yI)methyl)-lH-benzo[d]imidazole-7-carboxylate Diisopropyl amine adduct (Azilsartan ester DIPA adduct)
Charged 78.0 g of methyl-2-ethoxy-l-((2'-(N'-hydroxycarbamimidoyl)-[l5r-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate in 480.0 ml of toluene followed by addition of 26.6 g of triethylamine. Stirred the reaction mass at 50-55°C. Added 22.87 g of ethylchloroformate (22.87 g) at same temperature. Added 78.0 ml of diisopropyl amine and stirred the reaction mass at 95-100°C till completion of reaction. After completion of reaction, water was added to reaction mass, filtered and dried the solid to get 84g of methyl 2-ethoxy-l-^'-(S-oxo^^-dihydro-l^^-oxadiazol-S-yO-tlJ'-biphenyH^-yOmethyO-lH-benzo[d]imidazole-7-carboxylate DIPA adduct. Purity: 98.71% 'HNMRCDMSOde):
81.148(12H,d); 1.415(3H,t); 3.275(2H,multiplet); 3.689(3H,s); 4.616(2H3q); 5.484(2H3s); 6.872(2H3d3aromatic); 7.163-7.497(8H3multiplet3aromatic); 7.686(lH,d); 8.137(broadpeak). Example 10. Preparation of 2-ethoxy-l-((2?-(5-oxo-4,5-dihydro-l,2,4-oxadiazol-3-yl)-[l,l'-biphenyI]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylic acid (Azilsartan) Charged 80.0 g of methyl 2-ethoxy-l-((2'-(5-oxo-435-dihydro-l,254-oxadiazol-3-yl)-[l;r-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate DIPA adduct in 560.0 ml of water and added 20.5 g of sodium hydroxide followed by heating the reaction mass at 50-55°C. After completion of reaction, added 80.0 ml of acetic acid followed by addition of 160.0 ml of acetone and stirred the reaction mass for an hour at 5-10°C. Filtered and dried the wet solid to get 66.0 g of 2-ethoxy-l-((2,-(5-oxo-4,5-dihydro-l3234-oxadiazol-3-yl)-[l,l'-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylic acid. Purity 98.72%
Example 11. Preparation of 4-(Hydroxymethyl)-5-methyl-l,3-dioxol-2-one Charged 33.0 g of Medoxomil chloride and 22.82g of sodium formate in 33.0 ml of N,N-dimethyl acetamide. Heated the reaction mass to 75-80°C and stirred for 5-7 hours. Reaction mass was then cooled and diluted with ethyl acetate (165.0 ml). Filtered and distilled the ethyl acetate layer to get oily mass of (5-methyl-2-oxo-l33-dioxol-4-yl)methyl formate. Added 3.0.0 ml of methanol and 1.0 ml of cone. Hydrochloric acid and stirred the reaction mass at 40°C till completion of reaction. Distilled the methanol under high vacuum to get 48.0 g of 4-

(Hydroxymethyl)-5-methyl-l,3-dioxol-2-one. The compound so obtained was used in-situ in next step as a solution in A^A^-dimethyl acetamide. GC Purity: 94.9%
Example 12. Preparation of (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 2-ethoxy-l-((2'-(5-oxo-4,5-dihydro-l,2,4-oxadiazol-3-yl)-[l,lf-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate (Azilsartan medoxomil)
Charged 65.0 g of 2-ethoxy-l-((2'-(5-oxo-435-dihydro-l3254-oxadiazol-3-yl)-[l,l,-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylic acid and 48.0 g of 4-(Hydroxymethyl)-5-methyl-l,3-dioxol-2-one in 195.0 ml of Af N-dimethyl acetamide. Added 38.2 g of p-toluene sulfonyl chloride and 3.2 g of 4-dimethyl amino pyridine at room temperature. After completion of reaction, cooled the reaction mass to 10-15°C and added 27.4g of potassium carbonate. Stirred at room temperature till completion of reaction followed by dilution of reaction mass with 500 ml of water. Adjusted the pH of reaction mass to 5.0 by using cone, hydrochloric acid. Reaction mass was stirred under cooling, then filtered to get wet solid. Solid was then suspended in acetone in ice cooling bath and stirred for an hour. Filtered and dried the solid to get 68.5 g of (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 2-ethoxy-l-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[ 1,1 '-biphenyl]-4-yl)methyl)-1 H-benzo[d]imidazole-7-carboxylate (Azilsartan medoxomil) Purity: 98.7%
Example 13. Preparation of (5-methyl~2-oxo-l,3-dioxol-4-yl)methyl 2-ethoxy-l-((2'-(5-oxo-4,5-dihydro-l,2,4-oxadiazol-3-yl)-[l,l'-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate potassium salt )Azilsartan kamedoxomil) Charged 64.0 g of (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 2-ethoxy-l-((2'-(5-oxo-435-dihydro-l,2,4-oxadiazol-3-yl)-[ljr-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate in 1170.0 ml of acetone and heated the reaction mass to get clear solution. Filtered the reaction mass through celite and distilled the acetone by half of volume. Reaction mass was then cooled to 25-30°C and added solution of potassium-2-ethyl hexanoate [potassium-2-ethyl hexanoate (20.50 g) in acetone (65.0 ml)] at 25-30°C. Reaction mass was stirred for 3-4 hours then filtered to get wet cake. The wet cake so obtained was dried under vacuum to get 52.8g of (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 2-ethoxy-l-((2,-(5-oxo-435-dihydro-l52,4-oxadiazol-3-yl)-[l,r-biphenyl]-4-yl)methyl)-lH-benzo[d]imidazole-7-carboxylate potassium salt. Purity: 99.8%

We Claim
1. A compound of Formula I

Formula I
wherein R is C1-C8 alkyl or, substituted or unsubstituted aryl, and M is an organic amine.
2. The compound as claimed in claim 1, wherein organic amine is selected from the group comprising of diisopropyl amine, ethanolamine, meglumine, piperidine, benzyl piperazine, diethyl amine, methyl benzyl amine, morpholine and N, N-dibenzyl ethylene diamine.
3. A process of preparation of compound of Formula I,

Formula I
wherein R and M are as defined above,
wherein said process comprising the steps of:
a) reacting hydroxyamidino compound of formula IX with alkyl/ aryl chloroformate in
Formula IX
presence of base;


to give compound of formula X;

R' Formula X
wherein R' is C1-C4 alkyl, or substituted or unsubstituted aryl,
R is as defined above; and
b) cyclization of compound of formula X in organic amine to get compound of formula I.
4. The process as claimed in claim 3, wherein said alkyl/ aryl chioroformate in step a) is selected from the group comprising of methyl chioroformate, ethyl chioroformate, propyl chioroformate, isopropyl chioroformate, isobutyl chioroformate, benzyl chioroformate, p-nitro phenyl chioroformate and 4-methoxy chioroformate.
5. The process as claimed in claim 3, wherein said base in step a) is selected from the group comprising of diethylamine, triethylamine, diisopropyl ethyl amine, pyridine, piperidine, morpholine, DABCO and DBU.
6. A process of preparation of Azilsartan kamedoxomil by using a novel compound of Formula I,

O Formula I
wherein R and M are as defined above, wherein said process comprising the steps of:

a) condensing N-protected compound of Formula XI with 4'-(bromomethyl)biphenyl-2-carbonitrile of Formula XII to get compound of Formula XIII;

Formula XI Formula XII Formula XIII
wherein R is as defined above;
b) reducing compound of Formula XIII in presence of Raney Nickel and catalyst to get
compound of Formula XIV;

Formula XIV
wherein R is as defined above;
c) hydrolysing compound of Formula XIV in presence of acid to get compound of Formula
XV;

Formula XV
wherein R is as defined above;
d) cyclizing compound of Formula XV in presence of tetra ethyl ortho carbonate to get
compound of Formula XVI;

Formula XVI
wherein R is as defined above;
e) reacting compound of Formula XVI with hydroxyl amine hydrochloride to get
hydroxyamidino compound of Formula IX;

Formula IX
wherein R is as defined above;
f) reacting hydroxyamidino compound of Formula IX with alkyl/ aryl chloroformate in
presence of base to give compound of Formula X;


rT^V

wherein R5 and R, are as defined above;
g) cyclization of compound of Formula X in presence of organic amine to get compound of
Formula I;

Formula I
wherein R and M are as defined above;
h) hydrolysing compound of Formula 1 to get Azilsartan acid of Formula XVII;


Cr OH

Formula XVII
and
i) converting Azilsartan of Formula XVII to Azilsartan medoxomil by reacting with 4-(hydroxymethyl)-5-methyl-l,3-dioxol-2-one followed by reaction with potassium source to get compound of Formula XVIII

Formula XVIII
7. The process as claimed in claim 6, wherein said catalyst used in step b) is selected from the group comprising of acetic acid, formic acid, orthophosphoric acid, phosphoric acid and perchloric acid.

8. The process as claimed in claim 6, wherein said acid as used in step c) is selected from the group comprising of dioxane.HCl, ethylacetate. HO, methanolic HC1, ethanolic HC1, isopropyl alcoholic HC1, and diethyl ethereal HC1.
9. The process as claimed in claims 3 and 6, wherein said organic amine is selected from the group comprising of diisopropyl amine, ethanolamine, meglumine, piperidine, benzyl piperazine, diethyl amine, methyl benzyl amine, morpholine and N, N-dibenzyl ethylene diamine.
10. Use of compound of Formula I for the preparation of Azilsartan and its derivatives and salts
thereof.