FORM 2
THE PATENT ACT, 1970
(39 of l970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"A NOVEL PROCESS OF PREPARING CINACALCET HYDROCHLORIDE"
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17th Floor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada. Navi Mumbai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

A NOVEL PROCESS OF PREPARING C1NACALCET HYDROCHLORIDE FIELD OF THE INVENTION:
The present invention relates to a novel process of preparing cinacalcet hydrochloride.
BACKGROUND OF THE INVENTION:
Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. The chemical designation is N-[l-(R)-(-)-(1-naphthyl) ethyl]-3-[3-(trifluoromethyl) phenyl]-1-aminopropane hydrochloride. It is knowr from U.S. Patent Nos. 6,011,068 and 6,211.244 and is represented by compound of structura formula I.

Cinacalcet hydrochloride is a calcium-sensing receptor agonist and sold in USA market under the trade name "SENSIPAR" indicated for:
• Secondary Hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) on dialysis.
• Hypercalcemia in patients with Parathyroid Carcinoma (PC).
• Severe hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy.
U.S. Patent No. 6,011,068 discloses inorganic ion receptor activity, especially calcium receptor-active molecules, such as those having the general structure of cinacalcet.

U.S. Patent No.6,211,244 describes processes of preparing cinacalcet base compound of structural formula II as shown below in scheme nos. 1, 2 and 3.



U.S. Patent No.7,250,533 describes a process of preparing cinacalcet base compound of structural formula II as shown below in scheme no. 4.


U.S. Patent No.7,449,603 describes a process of preparing cinacalcet base compound of structural formula II as shown below in scheme no. 5.

U.S. Patent Publication No.2012/0053362 describes a process of preparing cinacalcet base compound of structural formula II or its salts thereof as shown below in scheme no. 6.


There is a need for the commercially viable synthetic process of preparing cinacalcet hydrochloride compound of structural formula I. Accordingly the present invention provides a commercially viable novel synthetic process of preparing cinacalcet hydrochloride compound of structural formula I.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide a novel process of preparing cinacalcet hydrochloride.
A second aspect of the present invention is to provide a novel process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XX,

b. converting hydroxy group of compound of structural formula XX into good leaving group to get compound of structural formula XXI

c. reacting compound of structural formula III with compound of structural formula XXI to get compound of structural formula VI.


d. resolving compound of structural formula VI to get cinacalcet base compound of structural formula II and,

e. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein, X is halogen or -OSO2R2 group, wherein R2 is selected from the group comprising of optionally substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole.
A third aspect of the present invention is to provide a novel process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XXII.

b. converting hydroxy group of compound of structural formula XXII into good leaving group to get compound of structural formula XXIII,


c. reacting compound of structural formula III with compound of structural formula XXIII to get cinacalcet base compound of structural formula II and,

d. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein, X is halogen.
A fourth aspect of the present invention is to provide a novel process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XXII,

b. converting hydroxy group of compound of structural formula XXII into good leaving group to get compound of structural formula XXIV.


c. reacting compound of structural formula III with compound of structural formula XXIV to get cinacalcet base compound of structural formula II and,

d. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein,R1 is -SO2R2 group, wherein R2 is selected from the group comprising of optionally substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole.
DETAIL DESCRIPTION OF THE INVENTION:
In one embodiment the present invention provides a novel process of preparing cinacalcet hydrochloride.
The reduction of compound of structural formula IV with of reducing agent may be carried out in polar aprotic solvent to get compound of structural formula XX-

The reduction of compound of structural formula IV with reducing agent may be carried out at a temperature in the range of -20° to 60° C for a period of 30 minutes to 8 hours.
The examples of reducing agent may include but not limited to sodium borohydride, potassium borohydride, Vitride, tetralkylammonium borohydride. calcium borohydride. zinc borohydride. sodium cyanoborohydride, lithium aluminium hydride or mixtures thereof.
The examples of polar aprotic solvent may include but not limited to dichloromethane. tetrahydrofuran ethyl acetate, acetone, dimethyl formamide acetonitrile dimethylsulfoxide or mixture(s) thereof.
The compound of structural formula XX may be isolated by quenching the reaction mixture with hydrochloric acid followed by separation of organic layer.
The organic layer containing compound of structural formula XX may be washed with water and dried over sodium sulfate.
The organic layer containing compound of structural formula XX may be concentrated under reduced pressure to get compound of structural formula XX.
The hydroxy group of compound of structural formula XX may be converted in to good leaving group by reacting compound of structural formula XX with halogenating agent or HOSO2R2 or halogen-SO2R2, wherein R2 is selected from the group comprising of optionally substituted C|-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group. substituted or unsubstituted naphthyl group, or N-imidazole; halogen is selected from the group comprising of-C1, -Br, -I to get compound of structural formula XXI.
The reaction of compound of structural formula XX with halogenating agent or HOSO2R2 or halogen-SO2R2 may be carried out in presence of an acid or base in non-polar organic solvent at a temperature in the range of -5°C to 60° C for a period of 30 minutes to 12 hours to get compound of structural formula XXI.

The examples of halogenating agent may include but not limited to chlorine, bromine, iodine, potassium chloride, potassium bromide, potassium iodide, sulfuryl choride, thionyl chloride or phosphorous pentachloride.
The examples of non-polar organic solvent may include but not limited to toluene, hexane, I, 4-dioxane. chloroform, diethyl ether, dichloromethane or mixture thereof.
The examples of an acid may include inorganic acids or organic acid.
Inoreanic acid mav include hvdrochloric acid, hvdrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
Organic acid may include formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like.
The examples of base may include inorganic base or organic base.
Inorganic base may include hydroxides of alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide and the like; carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like; and phosphates such as disodium monohydrogenphosphate, dipotassium monohydrogen phosphate, trisodium phosphate, tripotassium phosphate and the like.
Organic base may include tertiary amines such as triethylamine. diisopropylethylamine, tri(n-propyl)amine, tri(n-butyl)amine, cyclohexyldimethylamine, N-methylpiperidine, N-methylpyrrolidine, N-methylmorpholine and the like; and aromatic amines such as pyridine, lutidine, N,N-dimethylaniline and the like.

The compound of structural formula XXI may be isolated by quenching reaction mixture with water followed by separating organic layer.
The organic layer containing compound of structural formula XXI may be washed with water and dried over sodium sulphate.
The organic layer containing compound of structural formula XXI may be concentrated under reduced pressure to get compound of structural formula XXI.
The reaction of compound of structural formula III with compound of structural formula XXI may be carried out in presence above mentioned base in an organic solvent to get compound of structural formula VI.
The examples of an organic solvent may include but not limited to an ester solvent, nitrile solvent, halogenated aliphatic hydrocarbon solvent or mixtures thereof.
The ester solvents may include but not limited to ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof
The nitrile solvents may include but not limited to acetonitrile, propionitrile or mixture(s) thereof.
The halogenated aliphatic hydrocarbon solvents may include but not limited to dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof.
The reaction of compound of structural formula III with compound of structural formula XXI may be carried at a temperature in the range 20°C to 95°C for a period of 30 minutes to 10 hours to get compound of structural formula VI.
The compound of structural formula VI may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.

The resolution of compound of structural formula VI may be carried out by the methods known in the art to get cinacalcet base compound of structural formula II.
The cinacalcet base compound of structural formula II may be converted in to cinacalcet hydrochloride compound of structural formula I by the methods known in the art.
In another embodiment the present invention provides a novel process of preparing cinacalcet hydrochloride.
The reduction of compound of structural formula VI with reducing agent may be carried out in presence of chiral catalyst in polar aprotic solvent at a temperature in the range of -5°C to 45°C for a period of 1 hour to 12 hours to get compound of structural formula XXII.
The examples of reducing agent may include but not limited to sodium borohydride. borane-tetrahydrofuran (BTHF) or dimethyl sulfide borane (DMSB).
The examples of chiral catalysts may include but not limited to CBS catalyst (Corey-Bakshi-Shibata catalyst), trans-RuCl2 (DMSO)4 or [Rh (COD) Cl]2.
The examples of polar aprotic solvent may include but not limited to dichloromethane. tetrahydrofuran ethyl acetate, acetone, dimethyl formamide acetonitrile dimethylsulfoxide or mixture(s) thereof.
The compound of structural formula XXII may be isolated by quenching the reaction mixture with hydrochloric acid followed by separation of organic layer.
The organic layer containing compound of structural formula XXII may be washed with water and dried over sodium sulfate.

The organic layer containing compound of structural formula XXII may be concentrated under reduced pressure to get compound of structural formula XXII.
The hydroxy group of compound of structural formula XXII may be converted in to good leaving group by reacting compound of structural formula XXII with halogenating agent or HOSO2R2 or halogen-SO2R2, wherein R? is selected from the group comprising of optionally-substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole; halogen is selected from the group comprising of-CI. -Br, -I to get compound of structural formula XXIII or compound of structural formula XXIV.
The reaction of compound of structural formula XX with halogenating agent or HOSO2R2 or halogen-SO2R2 may be carried out in presence of an acid or base in non-polar organic solvent at a temperature in the range of -5°C to 60° C for a period of 30 minutes to 12 hours to get compound of structural formula XXIII or compound of structural formula XXIV.
The examples of halogenating agent may include but not limited to chlorine, bromine, iodine, potassium chloride, potassium bromide, potassium iodide, sulfuryl choride, thionyl chloride or phosphorous pentachloride.
The examples of non-polar organic solvent may include but not limited to toluene, hexane, 1, 4-dioxane, chloroform, diethyl ether, dichloromethane or mixture thereof.
The examples of an acid may include inorganic acids or organic acid.
Inorganic acid may include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
Organic acid may include formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like.

The examples of base may include inorganic base or organic base.
Inorganic base may include hydroxides of alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide and the like; carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like; and phosphates such as disodium monohydrogenphosphate, dipotassium monohydrogen phosphate, trisodium phosphate, tripotassium phosphate and the like.
Organic base may include tertiary amines such as triethylamine, diisopropylethylamine, tri(n-propyl)amine, tri(n-butyl)amine, cyclohexyldimethylamine, N-methylpiperidine, N-methylpyrrolidine, N-methylmorpholine and the like; and aromatic amines such as pyridine, lutidine, N.N-dimethylaniline and the like.
The compound of structural formula XXIII or compound of structural formula XXIV may be isolated by quenching reaction mixture with water followed by separating organic layer.
The organic layer containing compound of structural formula XXIII or compound of structural formula XXIV may be washed with water and dried over sodium sulphate.
The organic layer containing compound of structural formula XXIII or compound of structural formula XXIV may be concentrated under reduced pressure to get compound of structural formula XX111 or compound of structural formula XXIV.
The reaction of compound of structural formula III with compound of structural formula XXIII or compound of structural formula XXIV may be carried out in presence above mentioned base in an organic solvent to get cinacalcet base compound of structural formula II.
The examples of an organic solvent may include but not limited to an ester solvent, nitrile solvent, halogenated aliphatic hydrocarbon solvent or mixtures thereof.

The ester solvents may include but not limited to ethyl acetate, propyl acetate, isopropyl acetate. butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof
The nitrile solvents may include but not limited to acetonitrile, propionitrile or mixture(s)
thereof.
The halogenated aliphatic hydrocarbon solvents may include but not limited to dichloromethane. dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof.
The reaction of compound of structural formula III with compound of structural formula XXIII or compound of structural formula XXIV may be carried at a temperature in the range 20°C to 95°C for a period of 30 minutes to 10 hours to get cinacalcet base compound of structural formula II.
The cinacalcet base compound of structural formula II may be isolated by the steps of filtration, centrifugation. washing, drying or the combinations thereof.
The cinacalcet base compound of structural formula II may be converted in to cinacalcet hydrochloride compound of structural formula I by the methods known in the art.
The example of compound of structural formula XXI may include l-(l-chloroethyl) naphthalene compound of structural formula XXV or l-(naphthalen-l-yl) ethyl methanesulfonate compound of structural formula XXVI.


The example of compound of structural formula XXIII may include (R)-l-(l-chloroethyl) naphthalene compound of structural formula XXVII.

The example of compound of structural formula XXIV may include (S)-l-(naphthalen-l-yl) ethyl methanesulfonate compound of structural formula XXVIII.

EXAMPLES:
In the following examples, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example 1: Preparation of l-(naphthalen-l-yl) ethanol compound of structural formula XX.
A solution of l-(naphthaien-l-yl) ethanone compound of structural formula IV (20 gm) in dichloromethane (100 ml) was added sodium borohydride (5 gm) at 0-5°C and then the temperature of reaction was raised to 10- 20°C. The resulting reaction mixture was stirred for 3

hours at the same temperature. The resulting reaction mixture was quenched with 2% aqueous hydrochloric acid (15 ml concentrated hydrochloric acid diluted with 235 ml water) and extracted with toluene (2 x 200 ml) to get organic layer. The resulting organic layer was washed with water (40 ml), dried over sodium sulfate (20 gm) and concentrated under reduced pressure to get title compound. Yield: 20.2 gm
Example 2: Preparation of i-(l-chloroethyl) naphthalene compound of structural formula XXV.
A solution of l-(naphthalen-l-yl) ethanol compound of structural formula XX (20 gm) in dichloromethane (60 ml) was added thionyl chloride (14 ml) at 0-5°C and then the resulting reaction mixture was stirred at 20-25°C for 10 hours. The resulting reaction mixture was quenched with water (50 ml) and extracted with dichloromethane (2x30 ml). The resulting organic layer was washed with water (30 ml), dried over sodium sulfate (20 gm) and concentrated under reduced pressure to get title compound. Yield: 22.1 gm
Example 3: Preparation of l-(naphthalen-l-yl) ethyl methanesulfonate compound of structural formula XXVI.
A solution of l-(naphthalen-l-yl) ethanol compound of structural formula XX (20 gm) in toluene (120 ml) was added triethyl amine (32.3 ml), methane sulfonyl chloride (18 ml) at -5°C to 0°C and then the reaction mixture was stirred for 12 hours at 20-25°C. The resulting reaction mixture was quenched with water (100 ml) and extracted with toluene (2x60 ml). The resulting organic layer was washed with water (60 ml), dried over sodium sulfate (40 gm) and concentrated under reduced pressure to get title compound. Yield: 21.9 gm

Example 4: Preparation of N-(l-(naphthalen-l-yI) ethyl)-3-(3-(trifluoromethyl) phenyl) propan-1-amine compound of structural formula VI.
A solution of l-(l-chloroethyl) naphthalene compound of structural formula XXV (10 gm) in acetonitrile (100 ml) was added potassium carbonate (15 gm). 3-(3-(trifluoromethyl)phenyl)propan-l-amine compound of structural formula III (8 gm) at 20-25°C and the reaction mixture was stirred for 3 hours at 75°C. The resulting reaction mixture was filter and cooled to 20-25°C. The resulting solids were filtered and washed with acetonitrile (10 ml) and dried at 40-45°C under reduced pressure to get title compound. Yield: 18.7 gm
Example 5: Preparation of N-(l-(naphthalen-l-yI) ethyl)-3-(3-(trifiuoromethyi) phenyl) propan-1-amine compound of structural formula VI.
A solution of l-(naphthalen-l-yl) ethyl methanesulfonate compound of structural formula XXVI (10 gm) in acetonitrile (100 ml) was added potassium carbonate (15 gm), 3-(3-(trifluoromethyl)phenyl)propan-l-amine compound of structural formula III (9 gm) at 20-25°C and the reaction mixture was stirred for 4 hours at 80°C. The resulting reaction mixture was filter and cooled to 20-25°C. The resulting solids were filtered and washed with acetonitrile (10 ml) and dried at 40-45°C under reduced pressure to get title compound. Yield: 18.4gm
Example 6: Preparation of (S)-l-(naphthalen-l-yl) ethanol compound of structural formula XXII.
A solution of l-(naphthalen-l-yl) ethanone compound of structural formula IV(25 gm) in 125 ml tetrahydrofuran (125 ml) was added dimethyl sulfide borane (17.6 ml) and Corey-Bakshi-Shibata catalyst (7.8 ml) at 0-10°C for a period of 2 hours. The resulting reaction mixture was stirred for 2 hours at 10-15°C and then reaction mixture was quenched with 2% aqueous hydrochloric acid (15 ml concentrated hydrochloric acid diluted with 235 ml water)and extracted with toluene (2 x 250 ml) to get organic layer. The resulting organic layer was washed with water (50 ml), dried over sodium sulfate (30 gm) and concentrated under reduced pressure to get title compound. Yield: 24 gm

Example 7: Preparation of (R)-l-(l-chloroethyl) naphthalene compound of structural formula XXVII.
A solution of (S)-l-(naphthalen-l-yl) ethanol compound of structural formula XXII (20 gin) in dichloromethane (80 ml) was added thionyl chloride (14 ml) at 0-5°C and then the resulting reaction mixture was stirred at 20-25°C for 8 hours. The resulting reaction mixture was quenched with water (40 ml) and extracted with dichloromethane (2x50 ml). The resulting organic layer was washed with water (20 ml), dried over sodium sulfate (20 gm) and concentrated under reduced pressure to get title compound. Yield: 21.8 gm
Example 8: Preparation of (S)-l-(naphthalen-l-yl) ethyl methanesulfonatc compound of structural formula XXVIII.
A solution of (S)-l-(naphthalen-l-yl) ethanol compound of structural formula XXII (20 gm) in toluene (120 ml) was added triethyl amine (32 ml) at -5°C to 0°C and then methane sulfonyl chloride (18 ml) was added to the reaction mixture at -5°C to 0°C over a period of 30 minutes. The resulting reaction mixture was stirred for 4 hours at 20-25°C. The resulting reaction mixture was quenched with water (100 ml) and then organic layer was separated. The resulting organic layer was washed with water (100 ml), dried over sodium sulfate (40 gm) and concentrated under reduced pressure to get title compound. Yield: 18gm
Example 9: Preparation of cinacalcet base compound of structural formula II.
A solution of (R)-l-(l-chloroethyl) naphthalene compound of structural formula XXVII (10 gm) in acetonitrile (100 ml) was added potassium carbonate (15 gm), 3-(3-(trifluoromethyl)phenyl)propan-l-amine compound of structural formula III (9 gm) at 20-25°C and the reaction mixture was stirred for 4 hours at 80°C. The resulting reaction mixture was filter

and cooled to 20-25°C. The resulting solids were filtered and washed with acetonitrile (20 ml) and dried at 40-45°C under reduced pressure to get title compound. Yield: 18.6 gm
Example 10: Preparation of cinacalcet base compound of structural formula 1L
A solution of (S)-l-(naphthalen-l-yl) ethyl methanesulfonate compound of structural formula XXVIII (10 gm) in acetonitrile (100 ml) was added potassium carbonate (15 gm), 3-(3-(trifluoromethyl)phenyl)propan-l-amine compound of structural formula III (8 gm) at 20-25°C and the reaction mixture was stirred for 3 hours at 75°C. The resulting reaction mixture was filter and cooled to 20-25°C. The resulting solids were filtered and washed with acetonitrile (10 ml) and dried at 40-45°C under reduced pressure to get title compound. Yield: 18.0 gm

ABSTRACT
The present invention provides a novel process of preparing cinacalcet hydrochloride.

WE CLAIM:
1. A process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XX,

b. converting hydroxy group of compound of structural formula XX into good leaving group to get compound of structural formula XXL

c. reacting compound of structural formula III with compound of structural formula XXI to get compound of structural formula VI,

d. resolving compound of structural formula VI to get cinacalcet base compound of structural formula II and.


e. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein, X is halogen or -OSO2R2 group, wherein R2 is selected from the group comprising of optionally substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole.
2. A process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XXII,

b. converting hydroxy group of compound of structural formula XXII into good leaving group to get compound of structural formula XXIII,


c. reacting compound of structural formula III with compound of structural formula XXIII to get cinacalcet base compound of structural formula II and.

d. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein, X is halogen.
3. A process of preparing cinacalcet hydrochloride comprising the steps of:
a. reducing compound of structural formula IV to get compound of structural formula XXII,


b. converting hydroxy group of compound of structural formula XXI1 into good leaving group to get compound of structural formula XXIV.

c. reacting compound of structural formula III with compound of structural formula XXIV to get cinacalcet base compound of structural formula II and.

d. converting cinacalcet base compound of structural formula II into cinacalcet hydrochloride compound of structural formula I.

wherein, R1 is -SO2R2 group, wherein R2 is selected from the group comprising of optionally substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole.
4. The process according to claim no. 1, wherein the reduction of compound of structural formula IV is carried out with reducing agent such as sodium borohydride, potassium borohydride, vitride. tetralkylammonium borohydride, calcium borohydride, zinc

borohydride, sodium cyanoborohydride. lithium aluminium hydride or mixtures thereof in polar aprotic solvent such as dichloromethane, tetrahydrofuran ethyl acetate, acetone, dimethyl formamide acetonitrile dimethylsulfoxide or mixture(s) thereof at a temperature in the range of -20° to 60° C for a period of 30 minutes to 8 hours to get compound of structural formula XX.
5. The process according to claim nos. 2 and 3, wherein the reduction of compound of structural formula VI is carried out with reducing agent such as sodium borohydride, borane-tetrahydrofuran (BTHF) or dimethyl sulfide borane (DMSB) is carried out in presence of chiral catalyst such as CBS catalyst (Corey-Bakshi-Shibata catalyst), trans-RuCl2 (DMSO)4 or [Rh (COD) Cl]2in polar aprotic solvent such as dichloromethane, tetrahydrofuran ethyl acetate, acetone, dimethyl formamide acetonitrile dimethylsulfoxide or mixture(s) thereof at a temperature in the range of -5°C to 45°C for a period of 1 hour to 12 hours to get compound of structural formula XXII.
6. The process according to claim nos. 1, 2 and 3, wherein the hydroxy group of compound of structural formula XX or compound of structural formula XXII is converted in to good leaving group by reacting compound of structural formula XX or compound of structural formula XXII with halogenating agent or HOSO2R2 or halogen-SO2RR2.wherein R2 is selected from the group comprising of optionally substituted C1-C4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl group, substituted or unsubstituted naphthyl group, or N-imidazole; halogen is selected from the group comprising of-C1, Br, -I, in the presence of an acid or base in non-polar organic solvent such as toluene, hexane, 1, 4-dioxane, chloroform, diethyl ether, dichloromethane or mixture thereof at a temperature in the range of -5°C to 60° C for a period of 30 minutes to 12 hours.
7. The process according to claim no. 6, wherein an acid is selected from the group comprising of inorganic acid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid or organic acid such as formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid,

citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid; base is selected from the group comprising of inorganic base like hydroxides of alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide and the like; carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like: and phosphates such as disodium monohydrogenphosphate, dipotassium monohydrogen phosphate, trisodium phosphate, tripotassium phosphate and the like or organic base like tertiary amines such as triethylamine, diisopropylethylamine. tri(n-propyl)amine, tri(n-butyl)amine, cyclohexyldimethylamine, N-methylpiperidine, N-methylpyrrolidine, N-methyhnorpholine and the like: and aromatic amines such as pyridine, lutidine. N.N-dimethylaniline and the like.
8. The process according to claim no. 1, wherein the reaction of compound of structural formula III with compound of structural formula XXI is carried out in the presence of base at a temperature in the range 20°C to 95°C for a period of 30 minutes to 10 hours in an organic solvent to get compound of structural formula VI.
9. The process according to claim nos. 2 and 3, wherein the reaction of compound of structural formula III with compound of structural formula XXIII or compound of structural formula XXIV is carried out in the presence of base at a temperature in the range 20°C to 95°C for a period of 30 minutes to 10 hours in an organic solvent to get cinacalcet base compound of structural formula II.
10. The process according to claim nos. 8 and 9, wherein the base is selected from the group comprising of inorganic base like hydroxides of alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide and the like; carbonates of alkali metal or alkaline earth metal such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like; and phosphates such as disodium monohydrogenphosphate, dipotassium monohydrogen phosphate, trisodium phosphate.

tripotassium phosphate and the like or organic base like tertiary amines such as
triethylamine. diisopropylethylamine. tri(n-propyl)amine, tri(n-buly])amine.
cyclohexyldimethylamine, N-methylpiperidine, N-methylpyrrolidine, N-
methylmorpholine and the like; and aromatic amines such as pyridine, lutidine, N.N-dimethylaniline and the like; organic solvent selected from the group comprising of an ester solvent such as ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, tertiary butyl acetate, pentyl acetate or mixture(s) thereof, nitrile solvent such as acetonitrile, propionitrile or mixture(s) thereof, halogenated aliphatic hydrocarbon solvent such as dichloromethane. dichloroethane, chloroform, carbon tetrachloride or mixture(s) thereof.