DESC:FIELD OF THE INVENTION
The present application provides a novel and cost effective process for the preparation of Sitagliptin intermediate (3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride) which is suitable to manufacture in commercial scale.

BACKGROUND OF THE INVENTION
Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Dipeptidyl peptidase 4 (DPP-4 inhibitors) inhibitors are generally called as gliptins a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4) and used to treat diabetes mellitus type 2. Sitagliptin, is an anti-diabetic medication used to treat type 2 diabetes, which is safe and most potent gliptin in DPP-4 class of inhibitors. FDA approved Sitagliptin 2006, Merck sold under the brand name JANUVIA (Sitagliptin alone) and JANUMET (Sitagliptin /Metformin-Fixed dose combination). Sitagliptin having the IUPAC name (R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and has the following chemical structure.

The triazolo intermediate having IUPAC name 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride plays a major role in the process for the preparation of Sitagliptin. The intermediate has the following structure with CAS no: 762240-92-6

US 6699871 discloses the below processes for the preparation of Sitagliptin triazolo intermediate. The process involves the costly raw materials like 2- chloropyrazine and
2,3-Dichloropyrazine. The process mainly uses polyphosphoric acid at elevated temperatures for cyclization, reducing agents like palladium and Platinum. So, the process is not commercially viable and not environment eco-friendly.

US 7468459 discloses the below process for the preparation of Sitagliptin triazolo intermediate. The process involves hydrazine reacts with trifluoroacetic acid and chloro acetyl chloride which gives substituted acetyl substituted hydrazide which undergoes dehydrative cyclization in presence of POCl3 at higher temperature gives substituted oxadiazole. Oxadiazole derivative further reacts with ethylenediamine transforms to substituted pyrazine derivative which finally undergoes cyclization in presence of acid gives the corresponding Sitagliptin intermediate.

The main disadvantages of the process are, in stage 1 after completion of the reaction, lot of acetonitrile (nearly 60 volumes) was used to remove the water which is present in hydrazine and ethanol the by-product formed in stage 1. The inventors of the present application are observed formation of dihydrazide impurity (2,2,2-trifluoro-N'-(2,2,2-trifluoroacetyl)acetohydrazide) if we try to distil the ethanol and water at higher temperatures. In stage 2 POCl3 was used for dehydrative cyclization. So, the process was commercially not viable to produce the corresponding intermediate in tonnage levels.

Organic Process Research & Development 2005, 9, 634-639 discloses the below process for the preparation of Sitagliptin triazolo intermediate. The process involves hazardous reagents like superphosphoric acid for cyclization and metal reagents like Pd/C which is not eco-friendly for reduction and gives overall yield of 51%, which is not a commercially viable process.

CN101973997 B patent discloses the below process for the preparation of Sitagliptin triazolo intermediate. The process involves piperazin-2-one reacts with Lawessons reagent to form piperazine-2-thione, which further reacts with trifluorohydrazide to form corresponding intermediate. The disadvantage of the below process is Lawessons is not eco-friendly reagent and lot hypochlorite solution is required to destroy the foul smell. Apart from this preparation of starting material 2-Oxopiperazine obtains in very low yields and the overall conversion yields are low.

Therefore, still there is need for the development of commercially viable, eco-friendly, and cost-effective process for the preparation of Sitagliptin triazolo intermediate.

OBJECTS OF THE INVENTION
It is an object of the present disclosure to provide a process for the preparation of Sitagliptin intermediate (3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride).
It is an object of the present disclosure to provide a cost-effective process for the preparation of Sitagliptin intermediate.
It is an object of the present disclosure to provide an easily scalable process for the preparation of Sitagliptin intermediate for manufacturing commercially.

SUMMARY OF THE INVENTION
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in Detailed Description section. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
The present invention provides a novel process for the preparation of Sitagliptin intermediate of formula (I) which is cost effective and suitable for industrial production.
In an aspect the present application provides a process for preparation of compound of formula I

formula (I)
which comprises
a) reacting compound of formula (II)

formula (II)
with sodium azide, lithium azide, aluminium azide, trimethyl silylazide or Diphenylphosphoryl azide in presence or absence of a lewis acid in suitable solvent to form compound of formula (III); wherein R1 is selected from chloro, bromo or iodo;

formula (III)
b) reacting compound of formula (III) with trifluoro acetic anhydride, trifluoro acetyl chloride, trifluoro aceticacid or CF3C(O)O-R2 with or without base in suitable solvent to form compound of formula (IV); wherein R1 is chloro, bromo or iodo and R2 is C1-C4 alkyl;

formula (IV)
c) reacting compound of formula (IV) with ethylene diamine in suitable solvent at lower temperature to form compound of formula (V);

formula (V)
d) compound of formula (V) undergoes cyclization in presence of acid in suitable solvent to form compound of formula (I);

formula (I)
e) optionally purifying the compound of formula (I) in a suitable solvent.

DETAILED DESCRIPTION OF THE INVENTION
The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
In some embodiments, numbers have been used for quantifying amount, percentages, weights, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.
All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.
The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.
The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
The term "or", as used herein, is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.
In one embodiment the present invention particularly describes process for the preparation of Sitagliptin intermediate compound of formula (I)

Formula (I)
In another embodiment the following scheme (A) describe the process for the preparation of Sitagliptin intermediate compound of formula (I).
Scheme (A)

In one embodiment the present invention discloses a process for the preparation of compound of formula (I)

formula (I)
which comprises
a) reacting compound of formula (II)

formula (II)
with sodium azide, lithium azide, aluminium azide, trimethyl silylazide or Diphenylphosphoryl azide in presence or absence of a lewis acid in suitable solvent to form compound of formula (III); wherein R1 is selected from chloro, bromo or iodo;

formula (III)
b) reacting compound of formula (III) with trifluoro acetic anhydride, trifluoro acetyl chloride, trifluoro aceticacid or CF3C(O)O-R2 in presence or absence of a base in suitable solvent to form compound of formula (IV); wherein R1 is chloro, bromo or iodo and R2 is C1-C4 alkyl;

formula (IV)
c) reacting compound of formula (IV) with ethylene diamine in suitable solvent at lower temperature to form compound of formula (V);

formula (V)
d) compound of formula (V) undergoes cyclization in presence of acid in suitable solvent to form compound of formula (I);
e) optionally purifying the compound of formula (I) in a suitable solvent.
In another embodiment the present invention discloses the preparation of compound of formula (I)

formula (I)
which comprises
a) reacting compound of formula (II)

formula (II)
with sodium azide in presence of AlCl3 in suitable solvent to form compound of formula (III); wherein the suitable solvent is THF or 1,2 dimethoxy ethane;

formula (III)
b) reacting compound of formula (III) with trifluoro acetic anhydride, in suitable solvent to form compound of formula (IV); wherein the suitable solvent is dichloromethane, chloroform, diethylether, diisopropyl ether or MTBE;

formula (IV)
c) reacting compound of formula (IV) with ethylene diamine in suitable solvent at lower temperature to form compound of formula (V); wherein the suitable solvent is methanol, ethanol, or isopropanol and at a temperature of -40 0C to 0 0C;

formula (V)
d) compound of formula (V) undergoes cyclization in presence of acid in suitable solvent to form compound of formula (I); wherein the suitable solvent is methanol, ethanol, or isopropanol, and the acid is aq HCl, methanolic HCl, ethanolic HCl or IPA.HCl;
e) optionally purifying the compound of formula (I) in a suitable solvent.
In another embodiment stage (a) of the present process involves, chloroacetonitrile of formula (II) undergoes cyclization to form chloro substituted tetrazole compound of formula (III) in presence or absence of a lewisacid and azide reagent in a suitable solvent; wherein the lewis acid is selected form AlCl3, FeCl3, TiCl4, SnCl2 or SnCl4 and the azide reagents are selected form sodium azide, Lithium azide, trimethyl silylazide or Diphenyl phosphoryl azide; and the solvents are selected from THF, toluene, methyl THF, 1,2 dimethoxy ethane, MTBE or mixtures thereof.

In another embodiment stage (b) of the present process involves, chloro substituted tetrazole compound of formula (III) undergoes rearrangement to form 2,5-disubstituted-1,3,4-oxadiazole compound of formula (IV) in presence of trifluoro acetic anhydride, trifluoro acetyl chloride, trifluoro acetic acid, ethyl trifluoro acetate, methyl trifluoro acetate and in presence of solvents like, dichloromethane, chloroform, carbon tetrachloride, hexane, heptane, toluene, xylene, THF, methyl THF, MTBE, Di isopropyl ether and methyl tertiary butyl ether or mixtures thereof.

In another embodiment stage (c) of the present process involves, 2,5-disubstituted-1,3,4-oxadiazole compound of formula (IV) reacts with ethylene diamine in presence of suitable solvents at lower temperatures to form trifluorohydrazide substituted piperazine compound of formula (V); wherein the suitable solvent is selected from methanol, ethanol, propanol, isopropanol, or n-butanol; wherein the suitable lower temperature is -40 0C to 0 0C.

In another embodiment stage (d) of the present process involves, cyclization of trifluorohydrazide substituted piperazine compound of formula (V) to sitagliptin intermediate compound of formula (I) in presence of an acid and a suitable solvent at favourable temperature; wherein the acid is selected from aq HCl, methanolic HCl, ethanolic HCl, IPA.HCl or gaseous HCl and the solvents are methanol, ethanol, propanol, isopropanol di isopropyl ether or MTBE; wherein the favourable temperature is 40 0C. to 55 0C.

In another embodiment Sitagliptin intermediate compound of formula (I) is optionally purified by using a suitable solvent; wherein the suitable solvent is selected form diethyl ether, methyl tertiary butyl ether, acetone, cyclohexane, ethyl acetate, acetonitrile, ethanol, methanol, hexane, water, or mixtures thereof.

In another embodiment the term “alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to eight carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl) or n-butyl.
In another embodiment the below are the abbreviations are used in the specification.
THF-Tetrahydrofuran, MTBE-Methyl tertiary butyl ether, 1,2 DME- 1,2 dimethoxy ethane, HCl- Hydrochloric acid, g- Grams, mL-millilitres, °C- degrees centigrade, Eq-Equivalent, HCl-Hydrochloric acid, Na2SO4-Sodium Sulphate, POCl3-Phosphorous oxy chloride, Pd/C- Palladium on carbon, TFAA, trifluoro acetic anhydride, IPA, Isopropyl alcohol, NaN3-Sodium azide, AlCl3- Aluminium chloride, FeCl3- Iron chloride, TiCl4- Titanium tetrachloride, SnCl2 Stannous chloride, Mg2SO4-Magnesium Sulphate, TLC-Thin layer Chromatography, and HPLC-High performance Liquid Chromatography.
In some embodiments, Sitagliptin intermediate of formula (I) produced according to the present invention is having purity more than 90% by HPLC.
While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
The advantages and other parameters of the present invention is illustrated by the below given examples. However, the scope of the present invention is not limited by the examples in any manner. It will be appreciated by any person skilled in this art that the present invention includes aforesaid examples and further can be modified and altered within the technical scope of the present invention
EXAMPLES
The present disclosure is further explained in the form of following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention.
Example 1
Preparation of 5-(Chloromethyl)-2H-tetrazole:

Method 1:
To a solution of AlCl3 (100 gm, 1 eq) in THF (1000 mL) was added NaN3 (241 gm, 2.8 eq). The reaction mixture was stirred at 60 0C for 2hrs after colling to 20 0C chloroacetonitrile (100 gm, 1 eq) was added and the reaction mixture was heated to 70 0C and maintained at same temperature for 24hrs. After completion of the reaction by TLC, the reaction mass was cooled to 0 to 5 0C, then ethyl acetate was added. The pH of the reaction mass was adjusted to pH 2 by aq. HCl (37%) to pH 2. The organic layer was separated dried over Na2SO4 and concentrated under vacuum to provide 5-(chloromethyl)-2H-tetrazole (130 gm, 83 %) as a white solid. Purity by HPLC: 97.04%.
Method 2:
To a solution of AlCl3 (100 gm, 0.5 eq) in 1,2-DME (200 mL) was added NaN3 (120.5 gm, 1.4 eq). The reaction mixture was stirred at 60 0C for 2hrs after colling to 20 0C chloroacetonitrile (100 gm, 1 eq) was added and the reaction mixture was heated to 70 0C and maintained at same temperature for 24hrs. After completion of the reaction by TLC, the reaction mass was cooled to 0 to 5 0C, then ethyl acetate was added. The pH of the reaction mass was adjusted to pH 2 by aq. HCl (37%) to pH 2. The organic layer was separated dried over Na2SO4 and concentrated under vacuum to provide 5-(chloromethyl)-2H-tetrazole (148 gm, 95 % yield) as a white solid. The crude product was used directly in the next step without further purification. Purity by HPLC: 96.2%.
Method 3:
To a solution of AlCl3 (100 gm, 1eq) in 1,2-DME (200 mL) was added NaN3 (120.5 gm, 2.8 eq). The reaction mixture was stirred at 60 0C for 2hrs after colling to 20 0C chloroacetonitrile (100 gm, 1 eq) was added and the reaction mixture was heated to 70 0C and maintained at same temperature for 24hrs. After completion of the reaction by TLC, the reaction mass was cooled to 0 to 5 0C, then ethyl acetate was added. The pH of the reaction mass was adjusted to pH 2 by aq. HCl (37%) to pH 2. The organic layer was separated dried over Na2SO4 and concentrated under vacuum to provide 5-(chloromethyl)-2H-tetrazole (154 gm, 99 % yield) as a white solid. The crude product was used directly in the next step without further purification. Purity by HPLC: 97%.
Method -4:
To a solution of NaN3 (120.5 gm, 1.4 eq). in THF (1000 mL) was stirred at 60 0C for 2hrs. After colling to 20 0C chloroacetonitrile (100 gm, 1 eq) was added and the reaction mixture was heated to 70 0C and maintained at same temperature for 24hrs. After completion of the reaction by TLC, the reaction mass was cooled to 0 to 5 0C, then ethyl acetate was added. The pH of the reaction mass was adjusted to pH 2 by aq. HCl (37%) to pH 2. The organic layer was separated dried over Na2SO4 and concentrated under vacuum to provide 5-(chloromethyl)-2H-tetrazole (63 gm, 41 %) as a white solid. Purity by HPLC: 92.5%.
Example 2:
Preparation of 2-(Chloromethyl)-5-(trifluromethyl)-1,3,4-oxadiazole:

Method 1:
To a solution of 5-(chloromethyl)-2H-tetrazole (100 gm, 1 eq) in diethyl ether (500 mL) at 25 -30 0C was added trifluoroacetic anhydride (190 gm 1.07 eq). After completion of evolution of nitrogen in the reaction, the reaction mass was cooled to 10 – 15 0C. The pH of the reaction mass was adjusted to pH 9 by 20% sodium hydrogen carbonate solution. The organic layer was separated dried over Na2SO4 concentrated under vacuum to obtain 2-(Chloromethyl)-5-(trifluromethyl)-1,3,4-oxadiazole 133 gm yield: 85%, Purity by HPLC 98%.
Method 2:
To a solution of 5-(chloromethyl)-2H-tetrazole (100 gm, 1 eq) in dichloromethane (500 mL) at 25 -30 0C was added trifluoroacetic anhydride in dichloromethane (190 gm 1.07 eq). After completion of evolution of nitrogen in the reaction, the reaction mass was cooled to 10 – 15 0C. The pH of the reaction mass was adjusted to pH 9 by 20% sodium hydrogen carbonate solution. The organic layer was separated dried over Na2SO4 concentrated under vacuum to obtain 2-(Chloromethyl)-5-(trifluromethyl)-1,3,4-oxadiazole 149 gm yield: 95%, Purity by HPLC 97.5%.
Example 3
Preparation of Trifluoroacetic acid(2Z)-piperazinylidenehydrazide

Method-1:
To solution of ethylenediamine (65 gm, 2 eq) in 1000 mL methanol at -20 0C was added 2-(Chloromethyl)-5-(trifluromethyl)-1,3,4-oxadiazole (100 g, 1.0 eq). The reaction was maintained at same temperature for 1 hr. To the reaction mass 1000 mL of methanol were then charged, and the reaction mass was slowly warmed to -5 0C. The reaction was maintained at -5 0C for 1 hr. The reaction mass was filtered at -50C. The solid was collected to obtain Trifluoroacetic acid(2Z)-piperazinylidenehydrazide 110 gm, 97% yield and purity by HPLC 99.5% and mp.141.
Method-2:
To solution of ethylenediamine (39 gm, 1.2 eq) in 1000 mL methanol at -20 0C was added 2-(Chloromethyl)-5-(trifluromethyl)-1,3,4-oxadiazole (100 g, 1.0 eq). The reaction was maintained at same temperature for 1 hr. To the reaction mass 1000 mL of methanol were then charged, and the reaction mass was slowly warmed to -5 0C. The reaction was maintained at -5 0C for 1 hr. The reaction mass was filtered at -50C. The solid was collected to obtain Trifluoroacetic acid(2Z)-piperazinylidenehydrazide 108 gm, 95% yield and purity by HPLC 99.5% and mp.141.
Example 4:
Preparation of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazole[4,3-a]pyrazine hydrochloride:

Method 1:
To a solution of Trifluoroacetic acid(2Z)-piperazinylidenehydrazide (100 gm, 1 eq) in methanol 400 mL was added conc. HCl (41.2ml, 37 wt%) for a period of 1 hr. The reaction mass was heated to 55 0C and maintained at same temperature for 1 hr. The reaction mass was cooled to 20 0C then MTBE 200 mL was added to the reaction mass at same temperature. The reaction mass was cooled to 50C and stirred for additional 1 hr. The white solids filtered to obtain 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazole[4,3-a]pyrazine hydrochloride 104 gm, and purity by HPLC 99.5%, M.P:264 0C.
The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention
,CLAIMS:1. A process for the preparation of compound of formula (I)

formula (I)
which comprises
a) reacting compound of formula (II)

formula (II)
with sodium azide, lithium azide, aluminium azide, trimethyl silylazide or Diphenylphosphoryl azide in presence or absence of a lewis acid in suitable solvent to form compound of formula (III); wherein R1 is selected from chloro, bromo or iodo;

formula (III)
b) reacting compound of formula (III) with trifluoro acetic anhydride, trifluoro acetyl chloride, trifluoro aceticacid or CF3C(O)O-R2 in presence or absence of a base in suitable solvent to form compound of formula (IV); wherein R1 is chloro, bromo or iodo and R2 is C1-C4 alkyl;

formula (IV)
c) reacting compound of formula (IV) with ethylene diamine in suitable solvent at lower temperature to form compound of formula (V);

formula (V)
d) compound of formula (V) undergoes cyclization in presence of acid in suitable solvent to form compound of formula (I);
e) optionally purifying the compound of formula (I) in a suitable solvent.
2. The process as claimed in claim 1, wherein the compound of formula (II) undergoes cyclization to form chloro substituted tetrazole compound of formula (III) in presence of a Lewis acid or azide reagent in a suitable solvent.
3. The process as claimed in claim 2, wherein the Lewis acid is selected form a group comprising AlCl3, FeCl3, TiCl4, SnCl2 and SnCl4.
4. The process as claimed in claim 2, wherein the azide reagents are selected form a group comprising sodium azide, Lithium azide, trimethyl silylazide and Diphenyl phosphoryl azide.
5. The process as claimed in claim 2, wherein the solvents are selected form a group comprising THF, toluene, methyl THF, 1,2 dimethoxy ethane, MTBE or mixtures thereof.
6. The process as claimed in claim 1, wherein the chloro substituted tetrazole compound of formula (III) undergoes rearrangement to form 2,5-disubstituted-1,3,4-oxadiazole compound of formula (IV).
7. The process as claimed in claim 1, wherein the 2,5-disubstituted-1,3,4-oxadiazole compound of formula (IV) reacts with ethylene diamine in presence of suitable solvents at lower temperatures to form trifluorohydrazide substituted piperazine compound of formula (V).
8. The process as claimed in claim 7, wherein the suitable solvent is selected from a group comprising methanol, ethanol, propanol, isopropanol, or n-butanol.
9. The process as claimed in claim 7, wherein the suitable lower temperature is -40°C to 0°C.
10. The process as claimed in claim 1, wherein the cyclization of trifluorohydrazide substituted piperazine compound of formula (V) to sitagliptin intermediate compound of formula (I) is in presence of acid selected from a group comprising aq HCl, methanolic HCl, ethanolic HCl, IPA.HCl and gaseous HCl and the solvents are methanol, ethanol, propanol, isopropanol di isopropyl ether or MTBE.
11. The process as claimed in claim 1, wherein the cyclization of trifluorohydrazide substituted piperazine compound of formula (V) to sitagliptin intermediate compound of formula (I) is in a favourable temperature ranging from 40°C to 55°C.
12. The process as claimed claim 1, for the preparation of compound of formula (I)

formula (I)
which comprises
a) reacting compound of formula (II)

formula (II)
with sodium azide in presence of AlCl3 in suitable solvent to form compound of formula (III); wherein the suitable solvent is THF or 1,2 dimethoxy ethane;

formula (III)
b) reacting compound of formula (III) with trifluoro acetic anhydride, in suitable solvent to form compound of formula (IV); wherein the suitable solvent is dichloromethane, chloroform, diethylether, diisopropyl ether or MTBE;

formula (IV)
c) reacting compound of formula (IV) with ethylene diamine in suitable solvent at lower temperature to form compound of formula (V); wherein the suitable solvent is methanol, ethanol, or isopropanol and at a temperature of -40 0C to 0 0C;

formula (V)
d) compound of formula (V) undergoes cyclization in presence of acid in suitable solvent to form compound of formula (I); wherein the suitable solvent is methanol, ethanol, or isopropanol, and the acid is aq HCl, methanolic HCl, ethanolic HCl or IPA.HCl;
e) optionally purifying the compound of formula (I) in a suitable solvent.