FORM 2
THE PATENT ACT, 1970
(39 OF 1970)
AND
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. TITLE OF THE INVENTION:
"NOVEL PROCESS FOR THE PREPARATION OF TENELIGLIPTIN AND ITS NOVEL INTERMEDIATES"
2. APPLICANTS)
(a) Name: UNICHEM LABORATORIES LIMITED
(b) Nationality: An Indian Company
(c) Address: Unichem Bhavan, Prabhat Estate, Off. S.V. Road, Jogeshwari (W), Mumbai-400102, Maharashtra, India
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be performed.

NOVEL PROCESS FOR THE PREPARATION OF TENELIGLIPTIN AND ITS NOVEL INTERMEDIATES
FIELD OF THE INVENTION:
The present invention is related to novel intermediates for preparation of Teneligliptin, methods for their preparation and a method for preparation of Teneligliptin using theses novel intermediates.
BACKGROUND OF THE INVENTION:
Teneligliptin is a novel, potent and long-lasting dipeptidyl peptidase-4 inhibitor
for the treatment of type 2 diabetes. Teneligliptin hemipentahydrobromide
hydrate is approved in Japan since 2012 and marketed by Mitsubishi Tanabe as
20mg tablets with brand name TENELIA®. Teneligliptin is chemically defined as
3-{(2S, 4S)-4-[4-(3-methyl-l -phenyl -5-pyrazolyl)-l-piperazinyI]-2-
pyrrolidinylcarbonyl}-l, 3-thiazolidine compound of formula (1) having below chemical structure.
U.S. patent No. 7,074,794 disclosed process for the preparation of Teneligliptin by reacting l-(3-methyl-l-phenyl-5-pyrazolyl)piperazine compound of formula (7) with 3-((S)-l-tert-butoxycarbonyl-4-oxo-2-pyrrolidinylcarbonyl)-l,3-thiazolidine compound of formula (11) in presence of STAB in MDC to obtained compound of formula (12). By deprotecting compound of formula (12) in presence of hydrochloric acid-1, 4-dioxane in mixture of solvent system (MeOH/MDC) to obtain Teneligliptin trihydrochloride. The synthetic route is depicted below in scheme (1).

U.S. Patent No. 8,003,790 disclosed preparation of Teneligliptin hemipentahydrobromide hydrate by is dissolving Teneligliptin in EtOH and adding 48% HBr at refluxing temperature and then cooling to room temperature, filtering the product, dried it at 45°C.
US'794 also disclosed the process for preparation of l-(3-methyl-l-phenyl-5-pyrazolyl) piperazine compound of formula (7) by reacting 1-tert-Butoxycarbonylpiperazine with diketene in presence of DMF to obtain 1-acetoacetyl-4-tert-butoxycarbonylpiperazine which is dissolved in EtOH and then reacted with phenylhydrazine in methansulfonic acid and then with POCl3 to get l-tert-butoxycarbonyl-4-(3-methyl-l-phenyl-5-pyrazolyl)piperazine as an oil. By deprotecting l-tert-butoxycarbonyl-4-(3-methyl-l-phenyl-5-pyrazolyl) piperazine with TFA in MDC was obtained l-(3-methyl-l-phenyl-5-pyrazolyl) piperazine compound of formula (7). The synthetic route is depicted below in scheme (2).

Said patent discloses the use of diketene which is flammable and reactive chemical. Jts instability makes it difficult to handle. Process also involves time consuming reaction of the use of phosphorous oxychloride as cyclizing agent. Resultant product is of low purity and low yield.
Chinese patent application no. 103880750 disclosed the process for preparation of l-(3-methyl-l-phenyl-5-pyrazolyl) piperazine compound of formula (7) by reacting 3-methyI-l-phenyl-lH-pyrazol-5-amine compound of formula (2) with N-benzyl-2-chloro-N-(2-chloroethyI)ethanamine to get 1-benzyl-4-(3-methyl-1-phenyl-lH-pyrazol-5-yl)piperazine which after deprotection gives l-(3-methyl-l-phenyl-5-pyrazolyl) piperazine compound of formula (7). The synthetic route is depicted below in scheme (3).
U.S. Patent No. 7,807,671 disclosed the process for preparation of 1-(3-methyl-1-phenyl-5-pyrazolyl) piperazine compound of formula (7) by reacting 5-chloro-3-methyl-1-phenyl-lH-pyrazole compound of formula (11) with piperazine in presence of n-BuLi in THF to obtain compound of formula (7). U.S. Patent application No. 2013/0310396 described preparation of compound of formula (7) by using same starting material as used in US'671. Instead of n-BuLi, US'396 used Pd/(OAc)2 w hich yield 75% of compound of formula (7). The

synthetic route is depicted below in scheme (4). Formation of dimer impurity is the drawback of this reaction.
PCT application No. 2014/041560 disclosed alternative route for synthesis of compound of formula (7), in which reaction of compound of formula (12) with 1-tert-Butoxycarbonylpiperazine is carried out in presence of K2CO3 to obtain compound of formula (13) and converted it into compound of formula (7). The synthetic route is depicted in scheme (5).
Above said process's disclosed use of hazardous chemicals such as diketene, n-
BuLi and Pd/ (OAc)2 which is difficult to handle at plant level and resulting lower
yield.
Although there are few processes available for the preparation Teneligliptin and
its intermediates, there is a need for simple and cost effective processes as well as
industrial and environmental friendly improved process for preparing
Teneligliptin and its intermediates.
OBJECT OF THE INVENTION:
The main object of the present invention is to provide novel intermediate compounds of formula (4) and compound of formula (10).

Another object of the present invention is to provide the process to prepare
compounds of formula (4) and compound of formula (10).
Another object of the present invention is to provide the process for the
preparation of compound of formula (7) or salts thereof.
Yet another object of the present invention is related to process for preparation of
Teneligliptin compound of formula (1) or pharmaceutically acceptable salts
thereof.
SUMMARY OF THE INVENTION:
The main object of the present invention is to provide novel intermediate compounds of formula (4) and (10); wherein X is as defined hereafter.
Another object of the present invention is to provide novel process for the preparation of compound of formula (4) comprising steps of;
(a) reacting compound of formula (3) with reducing agent in the presence of suitable solvent to form reaction mixture;

(b) reacting compound of formula (2) or (10) with the reaction mixture obtained in step (a) to obtain compound of formula (4); wherein X1 and X are as defined hereafter.
Another object of the present invention is to provide novel process for the preparation of compound of formula (4) comprising reacting compound of formula (10) with compound of formula (14) in presence of suitable base and suitable solvent; wherein X is as defined hereafter.
Another object of the present invention is to provide novel process for the preparation of compound of formula (10) comprising steps of;
(a) reacting compound of formula (3) with reducing agent in the presence of suitable solvent to form reaction mixture;
(b) reacting compound of formula (2) with the reaction mixture obtained in step (a) to obtain compound of formula (10); wherein Xi and X are as defined hereafter.

Another object of the present invention is to provide novel process for the preparation of compound of formula (7) comprising steps of;
(a) reacting compound of formula (4) with compound of formula (5) in presence of suitable base and suitable solvent to obtain compound of formula (6);
(b) optionally isolating compound of formula (6);
(c) deprotecting compound of formula (6) to obtain compound of formula (7), wherein X is as defined hereafter and P is protecting group;
(d) optionally converting compound of formula (7) into its salts.
Another object of the present invention is to provide novel process for the preparation of compound of formula (7) comprising reaction of compound of formula (4) with ammonia; wherein X is as defined hereafter and optionally converting compound of formula (7) into its salts.
Yet another object of the present invention is to provide novel process for the preparation of Teneligliptin compound of formula (1) or its pharmaceutically acceptable salts thereof comprising steps of;

(a) reacting compound of formula (4) with compound of formula (8) in presence of suitable base and suitable solvent to obtain compound of formula (9), followed by deprotection of compound of formula (9) to obtain Teneligliptin compound of formula (1); wherein P is protecting group and X is as defined hereafter; OR
(b) reacting compound of formula (4) with compound of formula (8) to obtain Teneligliptin compound of formula (1); wherein P is hydrogen and X is as defined hereafter;
(c) optionally isolating compound of formula (9);
(d) optionally converting Teneligliptin compound of formula (1) into its pharmaceutically acceptable salts thereof.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention provides novel intermediate compounds of formula (4) and (10) useful for the preparation of DPP-IV inhibitor i.e. Teneligliptin;

wherein X is halogen, -S(=0)2R1, -Si (R2)3 aryl or substituted aryl, R\ is C1-C4
alkyl group and R2 is C1-C4 alkyl group, aryl or substituted aryl; wherein
substituted aryl with substituent independently selected from halogen, -OH, -N02,
-CN group.
The novel intermediate compound of formula (4) is produced by following
methods.
Preparation of compound of formula (4):
Method 1: Preparation of compound of formula (4) comprising steps of;
(a) reacting compound of formula (3) with reducing agent in the presence of suitable solvent at the temperature range from 0°C to 100°C to form reaction mixture;
(b) reacting compound of formula (2) or (10) with the reaction mixture obtained in step (a) followed by raising the temperature to reflux temperature; preferably at temperature 60° to 100°C to obtain compound of formula (4); wherein Xi is -OH, -OR|, -CORi, -S(=0)2R1, aryl or substituted aryl and X is halogen, -S(=0)2Ri, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -NO2, -CN group.

Method 2: Reacting compound of formula (10) with compound of formula (14) in the presence of suitable solvent and suitable..base at temperature range.25°C. to 40°C; wherein X is halogen, -S(=0)2R1, -Si (R2K aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -N02, -CN group.
Preparation of compound of formula (10):
A process for preparation of compound of formula (10) comprising steps of;
(a) is same as step (a) of Method (1);
(b) reacting compound of formula (2) with the reaction mixture obtained in step (a) to obtain compound of formula (10); wherein Xi and X are defined as above. The reaction conditions are same as described in step (b) of Method (1).

Compound of formula (7) or its salts is produced by following methods.
Method A: Process for preparation of compound of formula (7) compressing
steps of;
(a) reacting compound of formula (4) with compourid of formula (5) in presence of suitable base and suitable solvent to obtain compound of formula (6);
(b) optionally isolating compound of formula (6);
(c) deprotecting compound of formula (6) to obtain compound of formula (7), wherein X is halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -NO2, -CN group and P is protecting group;
(d) optionally converting compound of formula (7) into its salts.
The above mentioned step (a) is carried out at temperature range 25°C to 100°C. The reaction of compound of formula (4) with (5) is carried out In presence of suitable solvent at temperature about 25°C followed by addition of suitable base and the temperature is raised up to 100°C. The reaction is successfully carried out with or without isolation of compound represented by general formula (6).
Deprotection of compound of formula (6) is carried out in presence of suitable solvent and suitable reagents, depending on the type of protective group and the reagents may be selected from the group consisting of acids like hydrochloric acid, trifluoroacetic acid, hydrobromic acid, sulphuric acid, hydrobromic acid, p-

toluene sulfonic acid, boron tribromide, formic acid; reduction using palladium/carbon, palladium acetate or palladium hydroxide, suitable base such as piperidine, ammonia, methylamine and cyclohexyl amine at temperature range 25°C-100°C to obtain compound of formula (7). The deprotection reaction may be carried out without solvent. After the completion of reaction, the obtained product is quenched into the ice water followed by extraction with any known method in the art. Layers are separated and pH of aqueous layer is adjusted to 10-12 by suitable base.
P protecting groups are as described hereafter in the description. Method B: Process for preparation of compound of formula (7) or its salts comprising, reaction of compound of formula (4) with ammonia; wherein X is halogen, -S(=0)2Ri, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -NO2, -CN group; optionally converting compound of formula (7) into its salts.
In the present invention ammonia source is in the form of ammonia gas,
methanolic ammonia or aqueous ammonia in the presence of alcoholic solvent.
This reaction is carried out under pressure in autoclave at temperature 20°C to
50°C.
Compound of formula (7) may be converted into salt such as acetate salt by
conventional method present in the art. Other acid addition salts may also be
prepared using appropriate acid.
Preparation of Teneligliptin compound of formula (1):
A process for preparation of Teneligliptin compound of formula (1) or its pharmaceutically acceptable salts thereof comprising steps of;

(a) reacting compound of formula (4) with compound of formula (8) in
presence of suitable base and suitable solvent at temperature range
0°C-30°C to obtain compound of formula (9), followed by
deprotection of compound of formula (9) to obtain Teneligliptin
compound of formula (t); wherein P is protecting group and X is
halogen, -S(=0)2R1, -S1(R2)3, aryl or substituted aryl, R1 is H or Ci-
C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted
aryl; wherein substituted aryl with substituent independently selected
from halogen, -OH, -NO2, -CN group;
OR
(b) reacting compound of formula (4) with compound of formula (8) at temperature range 0°C-30°C to obtain Teneligliptin compound of formula (1); wherein P is hydrogen and X is halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 H or is C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -NO2, -CN group;
(c) optionally isolating compound of formula (9);

(d) optionally converting Teneligliptin compound of formula (1) into its pharmaceutically acceptable salts.
Deprotection of compound of formula (9) is carried out in presence of suitable solvent and suitable reagents, depending on the type of protective group and the reagents may be selected from the group consisting of acids like hydrochloric acid, trifluoroacetic acid, hydrobromic acid, sulphuric acid, hydrobromic acid, p-toluene sulfonic acid, boron tribromide, formic acid; reduction using palladium/carbon, palladium acetate or palladium hydroxide, suitable base such as piperidine, ammonia, methylamine and cyclohexyl amine at temperature range 0°C-100°C to obtain Teneligliptin compound of formula (1). The deprotection reaction may be carried out without solvent. After the completion of reaction, layers are separated and pH of aqueous layer is adjusted to 9-10 by suitable base. Extract the product with any known method in the art. Teneligliptin compound of formula (1) can be converted into its pharmaceutically acceptable salt such as trihydrochloride or hemipentahydrobromide hydrate salt by process disclosed in prior art.
The terms used in the present invention are explained in the following; The example of suitable solvent may be selected from, but is not limited to halogenated hydrocarbons such as water, methylene chloride, ethylene chloride, chloroform and carbon tetrachloride; alcohols such as methanol, ethanol, 1 -propyl alcohol, 2-propanol, tert-butanol; esters such as ethyl formate, ethyl acetate, isopropyl acetate and butyl acetate; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide; sulfoxides such as dimethyl sulfoxide; nitrile such as acetonitrile, propionitrile; ethers such as diethyl ether, diisopropyl ether, t-butyl methyl ether, 1 ,4-dioxane, tetrahydrofuran, tetrahydropyran; hydrocarbons such as benzene, toluene, cyclohexane, n-hexane and methyl cyclohexane; ketones such as acetone, methyl ethyl ketone; polar aprotic solvents such as l,3-dimethyl-2-imidazolidinone, sulfolane, Hexamethylphosphoramide or mixture(s) thereof.

The example of suitable base may include but not limited to K2CO3, Na2C03, Li2C03, NaHC03, LiHC03, KHCO3, NaOAc, KOAc, KOH, NaOH, LiOH, NH4OH, Potassium tert-butoxide, sodium ethoxide, sodium methoxide, n-BuLi, sec-BuLi, t-BuLi, methyllithium, sodium amide, lithium diisopropylamide, sodium hydride or potassium hydride, LiHMDS, NaHMDS, KHMDS and LiTMP TEA, trimethylamine, DIPEA, pyridine, dimethyl amino pyridine and piperidine or aqueous solution thereof or mixture(s) thereof.
The example of reducing agent includes but not limited to NaBH4, NaBH3 CN and Sodium triacetoxyborohydride (STAB), preferably NaBH4
The example of protecting group includes but not limited to aralkyl such as
benzyl, p-nitrobenzyl, benzhydryl, trityl; acyl such as formyl, acetyl, propionyl,
methoxyacetyl, methoxypropionyl, benzoyl, thienylacetyl, thiazolylacetyl,
tetrazolylacetyl, thiazolylglyoxyloyl, thienylglyoxyloyl; lower alkoxy-carbonyl
such as methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl; aralkyloxy-
carbonyl such as benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 9-
fluorenylmethyloxycarbonyl; lower alkane sulfonyl such as methane sulfonyl,
ethane sulfonyl; aryi sulfonyl such as toluene sulfonyl; tri- (lower alkyl) silyl such
as trimethylsilyl; and triphosgene and other carboxybenzyl (Cbz), 2,2,2,-
trichloroethyl carbamate (Troc), ethyl carbamate, ally carbamate (Alloc), ethyl
caramate, acyl, trifluroacetamide, allyamine, triphenylmethyl, and
trichloromethoxy.
Isolation/Extraction of compound of formula (4), (6), (7), (9), (10) and (1) can be carried out by any method known in the art such as cooling, filtration, centrifugation, washing, drying and using suitable solvent combination thereof. The invention is further defined by reference to the following examples describing in details the preparation of compounds of the invention. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the purpose and interest of this invention. The following examples are set for assist in understanding the invention and should not be construed as specifically limiting the invention described and claimed herein. Such variations of the invention, including the substitution of all

equivalents now known or later developed, which would be within the purview of those skilled in the art, a changes in experimental design, is to be considered to fall within the scope of the invention incorporated herein.
Examples:
Example No. 1: N,N-bis(2-chloroethyl)-3-methyl-l-phenyl-lH-pyrazol-5-amine
Sodium borohydride (35.0 gm, 0.989 moles) was added portion wise to stirred solution of chloroacetic acid (170.0 gm, 1.8 moles) in mixture of Toluene (350.0 ml) and THF (270.0 ml) at 0°C-100°C. The reaction mixture was stirred for 45 min (till no further evolution of hydrogen gas was observed) and 5-amino-3-methyl-1-phenyl-lH-pyrazole (20.0 gm, 0.1149 moles) was added. Reaction temperature was slowly raised to reflux temperature (80-85° C). Reaction process was monitored by TLC (solvent system- 30:70 Ethyl acetate:Hexane). After completion, stopped heating and cooled to room temperature. Added 10% solution of sodium bicarbonate and extracted with (2 x 200ml) Ethyl acetate. The combined organic layer was washed with water (2 x 200ml) and separated the layers. Solvent was removed from the organic layer to obtained crude product. Yield: 33 gm
Example No. 2: l-(3-methyl-l-phenyl-lH-pyrazol-5-yl)-4-tosylpiperazine
The title compound of example no. 1 (16.0 gm, 0.053 moles) and p-toluenesulfonamide (23.0gm, 0.134 moles) was added in N,N-dimethyl

formamide (35ml) at 25°C. Added potassium carbonate (43.8gm, 0.318) and heated reaction mass to 90°C-95°C. Reaction was monitored by TLC (50:50% Ethyl acetate: hexane). After completion, reaction mixture was cooled to room temperature. Added Ethyl acetate (150 ml) and water (160ml), stirred for 15 min. Organic layers were separated. Aqueous layer was washed with Ethyl acetate (100ml) and separated the layers. Combined organic layer and washed with water (2 x 150ml) and 100ml brine solution and separated the layers. Solvent was removed under reduced pressure below 40deg. to give the titled compound (crude). Yield 19 gm
Example No. 3: I-(3-methyl-!-phenyl-lH-pyrazol-5-yl)piperazine compound of formula (7)
The title compound of example no. 2 (5.0gm, 0.013 moles) was added in Cone. H2SO4 (15 ml) at 25-30°C and stirred for 10 min. The reaction mixture was allowed to heat up to 90°-95°C for 3-5 hr. Reaction monitored by TLC (1:7:4, Methanol: MDC: Hexane). After completion of reaction, stopped the heating and cooled to room temperature and quenched in crushed ice water (100ml). The reaction mixture was extracted with (2x 50ml) ethyl acetate and separated the layers. Aqueous layer was basified by using 2N NaOH solution up to pH 10-12 and extracted with ethyl acetate (2x 50ml). Separated and combined the layers. Solvents were removed to obtain title compound of formula (7). Yield 2.2 gm

Example No. 4: Synthesis of Teneligliptin
To a stirred solution of sodium hydride (60% dispersion in mineral oil, 75gm,
2mol), and DMF (500 ml) was slowly added 3-((2S,4R)-4-amino-l-tert-
butoxycarbonyl-2-pyrrolidinylcarbonyl)-l,3-thiazolidine (90 gm , 0.3molin 100ml
DMF) at 0-5°C, and stirred for an hr. The 5,5'(2-chloroethyl) amino-3-methyl-l-
phenyl-(lH)-pyrazole (141.5gm, 0.65mol solution in DMF) was added to reaction
mass at 0-5°C and stirred overnight at 25-30°C. The reaction mass slowly
quenched in ice water and then filtered. The aqueous layer is basified with NaOH
solution and extracted with ethyl acetate. Organic layer dried over magnesium
sulphate and concentrated under reduced pressure to get crude protected
Teneligliptin. Yield-1 lOgm. '
Deprotection:
MDC 400 ml was added to 40 gm protected Teneligliptin. To the solution charged SO m! trifluoro acetic acid at 0-10°C. After completion of reaction added 200 ml water and layers were separated. Aqueous layer was washed with MDC and pH was adjusted to 9 using sodium hydroxide solution. Extracted with MDC 400ml and washed with water. Organic layer dried over sodium suphate and evaporated to get solid product. Yield 26 gm.
Example 5: N-(2-chloroethyl)-3-methyl-l-phenyl-lH-pyrazol-5-amine
Sodium borohydride (17.0 gm, 0.45 moles) was added portion wise to stirred solution of chloroacetic acid (85.0 gm, 0.9 moles) in mixture of Toluene (350.0 ml) and THF (270.0 ml) at 0°C-100°C. The reaction mixture was stirred for 45 min (till no further evolution of hydrogen gas was observed) and 5-amino-3-

methyl-1-phenyl-lH-pyrazole (20.0 gm, 0.1149 moles) was added. Reaction temperature was slowly raised to reflux temperature (80-85° C). Reaction process was monitored by TLC (solvent system- 30:70 Ethyl acetate:Hexane). After completion, stopped heating and cooled to room temperature. Added 10% solution of sodium bicarbonate and extracted with (2 x 200ml) Ethyl acetate. The combined organic layer was washed with water (2 x 200ml) and separated the layers. Solvent was removed from the organic layer to obtained crude product. Yield: 13 gm.
Example 6: N,N-bis(2-chloroethyl)-3-methyl-l-phenyl-lH-pyrazol-5-amine
Method 1: Sodium borohydride (17.0 gm, 0.45 moles) was added portion wise to stirred solution of chloroacetic acid (85.0 gm, 0.9 moles) in mixture of Toluene (350.0 ml) and THF (270.0 ml) at 0°C-100°C. The reaction mixture was stirred for 45 min (till no further evolution of hydrogen gas was observed) and 5 N-(2-chloroethyl)-3-methyl-l-phenyl-lH-pyrazol~5-amine (20.0 gm, 0.1149 moles) was added. Reaction temperature was slowly raised to reflux temperature (80-85° C). Reaction process was monitored by TLC (solvent system- 30:70 Ethyl acetate:Hexane). After completion, stopped heating and cooled to room temperature. Added 10% solution of sodium bicarbonate and extracted with (2 x 200ml) Ethyl acetate. The combined organic layer was washed with water (2 x 200ml) and separated the layers. Solvent was removed from the organic layer to obtained crude product. Yield: 20 gm
Method 2: To a N-(2-chloroethyl)-3-methyl-l-phenyl- lH-pyrazol-5-amine ( 10 gm) in acetonitrile 100 ml. Charge potasiurm carbonate and cooled to 15-20 C

Charged mono chloro bromo ethane at 15-20°C. Raised temperature to 40-45°C. After completion of reaction, solvent was distilled out under reduced pressure and charged 100ml water to residue. Extracted the product in MDC and washed with water. Organic layer dried over sodium sulphate and solvent was distilled out under reduced pressure to give crude product. Yield 6.8 gm

We Claim:
1. A process preparation of compound of formula (4) comprising steps of;
(a) reacting compound of formula (3) with reducing agent in the presence of suitable solvent to form reaction mixture;
(b) reacting compound of formula (2) or (10) with the reaction mixture obtained in step (a) to obtain compound of formula (4); wherein X| is -OH, -OR,, -COR1 -S(=0)2R1, aryl or substituted aryl and X is halogen, -S(=0)2Ri, -Si (R2K aryl or substituted aryl, Rj is H or d-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent independently selected from halogen, -OH, -NO2, -CN group.
2. A process for preparation of compound of formula (4) comprising reaction of compound of formula (10) with compound of formula (14) in presence, of suitable base and suitable solvent; wherein X is halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, R] is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -NO2, -CN group.

3. A process for preparation of compound of formula (10) comprising steps of;
(a) reacting compound of formula (3) with reducing agent in the presence of suitable solvent to form reaction mixture;
(b) reacting compound of formula (2) with the reaction mixture obtained in step (a) to obtain compound of formula (10); wherein X1 is -OH, -OR], -COR-1, -S(=0)2R|, aryl or substituted aryl and X is halogen, -S(=0)2R1, -S1 (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C 1 -C4 al kyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -N02, -CN group.
4. A process for preparation of compound of formula (7) or its salts compressing steps of;

(a) reacting compound of formula (4) with compound of formula (5) in presence of suitable base and suitable solvent to obtain compound of formula (6);
(b) optionally isolating compound of formula (6);
(c) deprotecting compound of formula (6) to obtain compound of formula (7), wherein X is halogen, -S(=0)2R1, -S1 (R2K aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -NO2, -CN group and P is protecting group;
(d) optionally converting compound of formula (7) into its salts.
5. A process for preparation of compound of formula (7) or its salts comprising; reaction of compound of formula (4) with ammonia; wherein X is halogen, -S(=0)2R1, -S1 (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -NO2, -CN group; optionally converting compound of formula (7) into its salts.
6. A process for preparation of Teneligliptin compound of (1) or its pharmaceutically acceptable salts thereof comprising steps of;

(a) (i) reacting compound of formula (4) with compound of formula (8) in
presence of suitable base and suitable solvent to obtain compound of
formula (9), (ii) optionally isolating compound of formula (9) (iii)
deprotecting compound of formula (9) to obtain Teneligliptin
compound of formula (1); wherein P is protecting group and X is
halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, Ri is H or C\-
C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted
aryl; wherein substituted aryl with substituent is selected from halogen,
-OH, -N02, -CN group;
OR
(b) reacting compound of formula (4) with compound of formula (8) to obtain Teneligliptin compound of formula (1); wherein P is hydrogen and X is halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 H or is C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -NO2, -CN group;
(c) optionally converting Teneligliptin compound of formula (1) into its pharmaceutical acceptable salts.

7. Compounds of formula;
wherein X is halogen, -S(=0)2R1, -Si (R2)3, aryl or substituted aryl, R1 is H or C1-C4 alkyl group and R2 is H or C1-C4 alkyl group, aryl or substituted aryl; wherein substituted aryl with substituent is selected from halogen, -OH, -NO2, -CN group.
8. The process according to claim 1, 2, 3, 4 and 6; wherein suitable solvent is selected form the group consisting of water, methylene chloride, ethylene chloride, chloroform and carbon tetrachloride; alcohols such as methanol, ethanol, 1 -propyl alcohol, 2-propanol, tert-butanol; esters such as ethyl formate, ethyl acetate, isopropyl acetate and butyl acetate; amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide; sulfoxides such as dimethyl sulfoxide; nitrile such as acetonitrile, propionitrile; ethers such as diethyl ether, diisopropyl ether, t-butyl methyl ether, 1 ,4-dioxane, tetrahydrofiiran, tetrahyd ropy ran; hydrocarbons such as benzene, toluene, cyclohexane, n-hexane and methyl cyclohexane; ketones such as acetone, methyl ethyl ketone; polar aprotic solvents such as l,3-dimethyl-2-imidazolidinone, sulfolane, Hexamethylphosphoramide or mixture(s) thereof.
9. The process according to claim 1 and 3; wherein reducing agent is selected form the group consisting of NaBFU, NaBHsCN and Sodium triacetoxyborohydride (STAB).

10. The process according to claim 2, 4 and 6; wherein suitable base is selected form the group consisting of K2CO3, Na2C03, Li2CO3, NaHCC>3, LiHCC>3, KHCO3, NaOAc, KOAc, KOH, NaOH, LiOH, NH4OH, Potassium tert-butoxide, sodium ethoxide, sodium methoxide, n-BuLi, sec-BuLi, t-BuLi, methyllithium, sodium amide ,lithium diisopropylamide, sodium hydride or potassium hydride, LiHMDS, NaHMDS, KHMDS and LiTMP TEA, trimethylamine, DIPEA, pyridine, dimethyl amino pyridine and piperidine or aqueous solution thereof or mixture(s) thereof.
11. The process according to claim 4 and 6; wherein protecting group is selected form the group consisting of benzyl, p-nitrobenzyl, benzhydryl, trityl,formyl, acetyl, propionyl, methoxyacetyl, methoxypropionyl, benzoyl, thienylacetyl, thiazolylacetyl, tetrazolylacetyl, thiazolylglyoxyloyl, thienylglyoxyloyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, meth ane sulfonyl, ethane sulfonyl, toluene sulfonyl, trimethylsilyl; and triphosgene and other carboxybenzyl (Cbz), 2,2,2,-trichloroethyl carbamate (Troc), ethyl carbamate, ally carbamate (Alloc), ethyl caramate, acyl, trifluroacetamide, allyamine, triphenylmethyl, and trichloromethoxy.