FIELD OF THE INVENTION:
The present invention relates to novel processes for the preparation of 4-isopropylamino-butan-1-ol of formula (1), a precursor for Selexipag.
BACKGROUND OF THE INVENTION:
2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropyl-amino]butyloxy}-N-(methyl sulfonyl) acetamide (herein "Selexipag") also known as Uptravi®, has a CAS number of 475086-01-2, a molecular formula of C26H32N4O4S, the molecular weight of 496.6 and it is structurally represented by formula (2). Uptravi (selexipag) was approved on 21st Dec, 2015 by U.S. Food and Drug Administration for treating adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or result in the need for transplantation.
Selexipag, originally discovered and synthesized by Nippon Shinyaku, is a potent, orally available, selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH).
U.S.Patent No. 7,205,302 (hereafter US'302) describes the synthesis of Selexipag as depicted in Scheme-1.

Scheme -1
US'302 also describes processes for preparing Selexipag and its pharmaceutical!;/ acceptable salts.
CN102020574 discloses a process for preparation of compound of formula (14) as depicted in scheme - II below, wherein, 4-aminobutanoic acid of formula (15) is condensed with acetone with successive reduction of imine using H2/Pd in Methanol to obtain 4-isopropyl-amino-butyric acid of formula (14). The process reported in CN'574 involves the use of hazardous and tedious hydrogenation reaction, which is not industrially feasible. Further, CN'574 does not disclose the process for preparation of 4-isopropylamino-butan-1-ol of formula (1).

Bioorganic & Medicinal Chemistry, 15(21), 6692-6704; 2007 discloses the process for preparation of 4-isopropylamino-butan-1-ol of formula (1) as depicted in scheme - III below, wherein, 4-aminobutan-1-ol (11) is condensed with acetone followed by reduction of carbonyl moiety using H2,'Pt02 in presence of ethanol. The reported process involves use of expensive reducing agent like platinum oxide, and involves hydrogenation step, which makes the process tedious.
Organic & Bio-molecular Chemistry, 10(32), 6504-6511; 2012 discloses the process for preparation of 4-isopropylamino-butan-1-ol of formula (1) depicted in scheme -IV below. The reported process is complex, expensive time consuming and results in low yield.
Scheme - IV
Journal of Organic Chemistry, 26, 1744-7; 1961 discloses reduction of 4-(isopropylamino)-4-oxobutanoic acid of formula (12) to obtain 4-isopropylamino-butan-1-ol of formula (1) in THF as depicted in scheme - V below. The reported process is a complex, expensive, time consuming and results in lower yield.
Hence, there remains a need for providing efficient, industrially feasible and economically viable process for the manufacture of compound of formula (1), a Selexipag precursor to substantially eliminate the problems associated with

the prior art, and that will be suitable for large-scale production such that the process will be cost effective, safe to handle, simple and easy to carry out with high yield and purity of the product.
OBJECTS OF THE PRESENT INVENTION:
The primary object of the present invention is to provide novel processes for preparation of 4-isopropylamino-butan-1-ol of formula (1), a Selexipag precursor.
Yet another object of the present invention is to provide an efficient, industrially viable and cost effective process for preparation of 4-isopropylamino-butan-1-ol of formula (1).
DETAILED DESCRIPTION OF THE INVENTION:
Before the present invention is described, it is to be understood that this invention is not limited to particular methodologies and materials described, as these may vary as per the person skilled in the art. It is also to be understood that the terminology used in the description is for the purpose of describing the particular embodiments only, and is not intended to limit the scope of the present invention.
Before the present invention is described, it is to be understood that unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Further, it is to be understood that the present invention is not limited to the methodologies and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described, as

these may vary within the specification indicated. Unless stated to the contrary, any use of the words such as "including," "containing," "comprising," "having" and the like, means "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth the appended claims. Further the terms disclosed in the embodiments are merely exemplary methods of the invention, which may be embodied in various forms.
As used herein in the present application, the term "reflux temperature" means the temperature at which the solvent or solvent system refluxes or boils at atmospheric pressure.
The present invention provides a process for the preparation of 4-isopropylamino-butan-1-ol (1), wherein the said process comprises:
a) reacting compound of formula (8) with compound of formula (9) to obtain compound of formula (10); and
Wherein: X= Halogen or a leaving group selected from -OH, -OTs, -OCF3, -OBOP, -OPyBrOP, OSO2CH3, OSO2CF3, OBs, OCH2OCH3, OC(CH3)3, OCH2Ph, O-p-methoxybenzyl, OTMS, OTES, OTBDMS, OTBDPS, OTIPS,OCPh3, OR; R is selected from the group consisting of alkyl, aryl, substituted aryl, and the like;

b) reducing the obtained compound of formula (10) in a solvent and in presence of a suitable reducing agent optionally in combination with a suitable catalyst to obtain compound of formula (1).
The compound of formula (10) can be optionally isolated from the reaction mass and further purified by involving at least one of the following methods like solvent extraction, precipitation or distillation methods.
The step (a) of the present invention can be optionally carried out in a solvent and a base.
The solvent used in step (a) is selected from the group comprising of esters such as alkyl acetate including but not limited to ethyl acetate, isopropyl acetate and the like; aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to dichloromethane, chloroform, and ethylene dichloride; dialkylformamides such as but not limited to dimethyl formamide; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether, di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; alcohols such as but not limited to methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, n-pentanol, ethylene glycol, and diethylene glycol; ketones such as but not limited to acetone, methyl

ethyl ketone, and methyl isobutyl ketone; dialkylsulfoxides such as but limited to dimethyl sulfoxide; dialkylacetamides such as but not limited to N,N-dimethyl acetamide; nitriles such as but not limited to acetonitrile, and propionitrile; ionic liquids, hexamethylphosphorous triamide, hexamethylphosphoramide, water or mixtures thereof.
Preferably, the solvent used in step (a) is ethers and hydrocarbons. More preferably, the solvent used is cyclic ethers such as tetrahydrofuran and halogenated hydrocarbons such as dichloromethane.
The solvent used in step (b), is selected from the group comprising of aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, naphthalene; halogenated aliphatic hydrocarbons such as but not limited to dichloromethane, chloroform, and ethylene dichloride; dialkylformamides such as but not limited to dimethyl formamide; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether, di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; dialkylsulfoxides such as but limited to dimethyl sulfoxide; dialkylacetamides such as but not limited to N,N-dimethyl acetamide; or mixtures thereof.
Preferably, the solvent used in step (b) is ethers. More preferably, the solvent used is cyclic ethers such as tetrahydrofuran.
The base used in step (a) is selected from inorganic bases such as alkali metal carbonates such as but not limited to potassium carbonate, sodium

carbonate, and cesium carbonate; alkali metal bicarbonates such as but not limited to sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as but not limited to sodium hydroxide, potassium hydroxide, barium hydroxide, and lithium hydroxide; metal hydrides; metal alkoxides such as but not limited to sodium methoxide, sodium ethoxide, and potassium tert-butoxide; alkali metal amide such as but not limited to lithium amide, sodium amide, potassium amide, cesium amide and rubidium amide; alkali metal hydrides such as but not limited to sodium hydride, potassium hydride, lithium and calcium hydride; amidines such as but not limited to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) ; 1,4-diazabicyclo[2.2.2]octane (DABCO); and organic bases such as primary amines such as but not limited to methylamine, ethanolamine aniline, propyl amine, 2-propyl amine, butyl amine, 2-amino ethanol; secondary amines such as but not limited to N,N-diisopropyl amine, dimethylamine, diethyl amine, N-methyl propyl amine, pyrrole methylethanolamine,; tertiary amines like triethylamine, N,N-dimethyl aniline, N,N-diisopropyl ethyl amine, trimethyl amine, pyridine, pyrimidine, N,N-dimethylethyl amine and mixtures thereof.
Preferably, the base used in step (a) is tertiary amines. More preferably, the base used is triethyl amine.
The suitable Reducing agent used in step (b) is selected from the diborane, borane-dimethyl sulfide, borane-THF complex, sodium triacetoxyborohydride, sodium cyanoborohydride, Diisobutylaluminum hydride (DIBAL-H), Lithiumaluminiumhydride (LiAlhU), Sodium borohydride (NaBhU), NaBHU/BFs-etherate, Lithiumborohydride (LiBhU), Sodiumcyanoborohydrie (NaCNBH4), Raney-Nickel, Sodium bis(2-methoxyethoxy)aluminumhydride (Vitride), and

Sodium bis(2-methoxyethoxy) aluminumhydridepyrolidine (Red-ALP), Lithium triethylborohydride (LiBHEt3), magnesium tetrahydroborate [Mg(BH4)2], Aluminum borohydride [AI(BH4)3], Calcium borohydride [Ca(BH4)3], Zinc borohydride [Zn(BH4)2], Cerium borohydride Ce(BH4)3, Sodium triacetoxyborohydride [NaBH(OAc)3], Sodium cyanoborohydride [NaBI-foCIM], Mg(BH4)2(NaBH4+AICI3), AI(BH4)3(NaBH4+AICI3), Ca(BH4)3(NaBH4+CaCI2), Zn(BH4)2(NaBH4+ZnCl2), Ce(BH4)3(NaBH4+CeCI3), NaBH3CN(NaBH4+HCN), or their mixtures thereof. Preferably, the reducing agent used in step (b) is Lithiumaluminiumhydride (UAIH4).
The reducing agent used in step (b) is in the molar ratio of 0.8 to 4.
Step (a) of the embodiment is carried out at a temperature of 0°C to the reflux temperature of the solvent. More preferably temperature is 5°C to 20°C.
Step (b) of the embodiment is carried out at a temperature of -10°C to the
reflux temperature of the solvent. More preferably temperature is -5°C to
5°C.
Suitable catalyst used in step (b) may be selected from Lewis acid, acid as a
catalyst, catalyst or their mixtures thereof.
Lewis Acid used in step (b) is selected from Aluminum Chloride (AICI3-), Zinc chloride (ZnCI2), Boron trifluoride (BF3), Boron trialkoxide (B(OR)3), Trimethylaluminium (AI(CH3)3), Sn2+B(CH3)3, lodine(l2>, Bromine(Br2), Carbenes, Hydrogen ion(H+), Lithium ion(Li+), Sodium ion(Na+), Potassium ion(K+), Aluminum ion (Al3+), Magnesium ion (Mg2+), Calcium ion(Ca2+), Ferrous ion (Fe2+), Cobalt ion (Co2+), Copper ion (Cu2+), Zinc ion (Zn2+), Lead

ion (Pb2+), Copper ion (Cu+), Silver ion (Ag+), mercury ion(Hg+), Palladium ion(Pd2+), Acetic acid and the like.
Acid used in step (b) may be an organic acid, or an inorganic acid, selected from sulfuric acid (H2SO4), Trifluoroacetic acid (TFA), Trichloroacetic acid (CCbCOOH), Dichloroacetic acid (CHCI2COOH), Trifluoroacetic acid (CF3COOH), Methanesulfonic acid (CH3SO3H), Trifluoromethanesulfonic acid (CF3SO3H), and p-toluene sulfonic acid (P-CH3C6H4SO3H), Nitric acid (HNO3), hydroiodic acid (HI), Hydrobromic acid (HBr), Perchloric acid (HCIO4), Chloric acid (HCIO3), Hydrochloric acid (HCI) and the like.
Catalyst used in step (b) is selected from Iodine (I2), Trialkyl amine, Dimethyl selane (SiH2Me2), trimethylsilyl chloride (MesSiCI), Titanium chloride (T1CI4), dialkyl silane (R2Se2), and MeSe20H.
The step (a) further comprises isolation and purification of compound of formula (10); wherein the said process comprises the steps of: i. treating the reaction mass of step (a) with water and organic solvent; ii. acidifying the reaction mass of step (i); iii. separating the organic layer and aqueous layer of step (ii); iv. adjusting the pH of aqueous layer of step (iii) to 9-12 with 10 % sodium
hydroxide solution; v. extracting the product from reaction mass of step (iv) with an organic
solvent; and vi. concentrating the organic layer of step (v) to obtain the compound of
formula (10). The organic solvent used in steps (i) and (v) of isolation process is selected from the group comprising of esters such as alkyl acetate including but not

limited to ethyl acetate, isopropyl acetate; aromatic hydrocarbons such as but not limited to toluene, xylene, naphthalene; halogenated aliphatic hydrocarbons such as but not limited to dichloromethane, chloroform, ethylene dichloride; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether and di-methyl ether, methyl butyl ether; or mixtures thereof.
Preferably, the organic solvent used in steps (i) & (v) is halogenated aliphatic hydrocarbons. More preferably, the solvent used is dichloromethane.
The step (b) further comprises isolation and purification of compound of
formula (1); wherein the said process comprises the steps of:
i. treating the reaction mass of step (b) with water or optionally with mixture
of alcohol and water; ii. extracting the reaction mass of step (i) with an organic solvent; iii. separating the organic layer of step (ii) followed by washing it with water;
and iv. concentrating the organic layer of step (iii) to obtain the compound of
formula (1).
Alcohol used in step (i) is selected from but not limited to methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, n-pentanol, ethylene glycol, diethylene glycol and the like.
The organic solvent used in step (ii) isolation process is selected from the group comprising of esters such as alkyl acetate including but not limited to ethyl acetate, isopropyl acetate; aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, pentane; aromatic

hydrocarbons such as but not limited to toluene, xylene, naphthalene; halogenated aliphatic hydrocarbons such as but not limited to are dichloromethane, chloroform, ethylene dichloride; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether and di-methyl ether, methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; ketones such as but not limited to acetone, methyl ethyl ketone, methyl isobutyl ketone; or mixtures thereof. Preferably, the organic solvent used in step (ii) is hydrocarbons. More preferably, the organic solvent is halogenated aliphatic hydrocarbons such as dichloromethane.
Another embodiment of the present invention provides a process for preparation of 4-isopropylamino-butan-1-ol of formula (1), wherein the said process comprises of:
A. reacting a compound of formula (10) with a suitable base in a solvent to obtain compound of formula (14); and
B. reducing the compound of formula (14) using a suitable reducing agent in a solvent to obtain compound of formula (1);
The compound of formula (14) can be optionally isolated from the reaction mass and further purified by solvent extraction, precipitation or distillation method.

The reducing agent used in step (B) is in the molar ratio of 0.8 to 4.
Step (A) of the embodiment is carried out at a temperature of 0°C to the reflux temperature of the solvent.
Step (B) of the embodiment is carried out at a temperature of -10°C to the reflux temperature of the solvent.
The solvent used in step (A) is selected from the group comprising of esters such as alkyl acetate including but not limited to ethyl acetate, and isopropyl acetate; aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to are dichloromethane, chloroform, and ethylene dichloride; dialkylformamides such as but not limited to dimethyl formamide; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether, di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; alcohols such as but not limited to methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, n-pentanol, ethylene glycol, and diethylene glycol; ketones such as but not limited to acetone, methyl ethyl ketone, and methyl isobutyl ketone; dialkylsulfoxides such as but limited to dimethyl sulfoxide; dialkylacetamides such as but not limited to N,N-dimethyl acetamide; nitriles such as but not limited to acetonitrile, and propionitrile; ionic liquids, hexamethylphosphorous triamide , hexamethylphosphoramide, water or mixtures thereof.

The solvent used in step (B) is selected from the group comprising of aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to dichloromethane, chloroform, and ethylene dichloride; dialkylformamides such as but not limited to dimethyl formamide; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether, di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; or mixtures thereof.
The base used in step (A) is selected from inorganic bases such as but not limited to alkali metal carbonates such as but not limited to potassium carbonate, sodium carbonate, and cesium carbonate; alkali metal bicarbonates such as but not limited to sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as but not limited to sodium hydroxide, potassium hydroxide, barium hydroxide, and lithium hydroxide; metal hydrides, metal alkoxides such as but not limited to sodium methoxide, sodium ethoxide, and potassium tert-butoxide; alkali metal amide such as but not limited to lithium amide, sodium amide, potassium amide, cesium amide and rubidium amide; alkali metal hydrides such as but not limited to sodium hydride, potassium hydride, lithium and calcium hydride; amidines such as but not limited to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) ; 1,4-diazabicyclo[2.2.2]octane (DABCO); and organic bases such as but not limited primary amines such as but not limited to methylamine, ethanolamine aniline, propyl amine, 2-propyl amine, butyl amine, 2-amino ethanol; secondary amines such as but not limited to N,N-diisopropyl amine, dimethylamine, diethyl amine, N-methyl

propyl amine, pyrrole methylethanolamine,; tertiary amines like triethylamine, N,N-dimethyl aniline, N,N-diisopropyl ethyl amine, trimethyl amine, pyridine, pyrimidine, N,N-dimethylethyl amine and mixtures thereof.
The suitable Reducing agent used in step (B) is selected from the diborane, borane-dimethyl sulfide, borane-THF complex, sodium triacetoxyborohydride, sodium cyanoborohydride, Diisobutylaluminum hydride (DIBAL-H), Lithiumaluminiumhydride (LiAim), Sodium borohydride (NaBHU), NaBhWBFa-etherate, Lithiumborohydride (UBH4), Sodiumcyanoborohydrie (NaCNBH4), Raney-Nickel, Sodium bis(2-methoxyethoxy)aluminumhydride (Vitride), and Sodium bis(2-methoxyethoxy) aluminumhydridepyrolidine (Red-ALP), Lithium triethylborohydride (LiBHEt3), magnesium tetrahydroborate [Mg(BH4)2], Aluminum borohydride [AI(BH4)3], Calcium borohydride [Ca(BH4)3], Zinc borohydride [Zn(BH4)2], Cerium borohydride Ce(BH4)3, Sodium triacetoxyborohydride [NaBH(OAc)3], Sodium cyanoborohydride [NaBhbCN], Mg(BH4)2(NaBH4+AICI3), AI(BH4)3(NaBH4+AICl3), Ca(BH4)3(NaBH4+CaCI2), Zn(BH4)2(NaBH4+ZnCl2), Ce(BH4)3(NaBH4+CeCl3)) NaBH3CN(NaBH4+HCN), or their mixtures thereof.
The step (B) of the said embodiment further comprises isolation and purification of the crude compound of formula (1); wherein the said process for isolation and purification comprises the steps of: I. treating the reaction mass of step (B) with an alcohol and water;
II. extracting the reaction mass of step (I) with an organic solvent;
III. separating the organic layer of step (II) followed by washing it with water; and
IV. concentrating the organic layer of step (III) to obtain the compound of formula (1).

Alcohol used in step (I) is selected from but not limited to methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, n-pentanol, ethylene glycol, diethylene glycol and the like.
The organic solvent used in step (II) isolation process is selected from the group comprising of esters such as al.kyl acetate including but not limited to ethyl acetate, and isopropyl acetate; aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to are dichloromethane, chloroform, and ethylene dichloride; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether, di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; esters; ketones such as but not limited to acetone, methyl ethyl ketone, and methyl isobutyl ketone; or mixtures thereof.
BEST MODE OF THE INVENTION
The present invention is described in the examples given below; further these are provided only to illustrate the invention and therefore should not be construed to limit the scope of the invention.
EXAMPLE-1: Preparation of 4-isopropylamino-butyric acid ethyl ester
Ethyl 4-bromobutyrate (50 g; 0.26mol) was added to isopropyl amine (45.45 g; 0.76mol) at below 10 °C, stirred to 6-8 hrs. at below 10 °C. Upon completion of the reaction (monitored by TLC), the contents of the reaction

mass were distilled out at a temperature below 50 °C under vacuum, the volatiles were removed in vacuum and the crude product was dissolved in tetrahydrofuran, cooled and filtered to afford the title compound. [Yield = 37.0 q (83.31%): Purity (HPLC) = 89.71 %1
EXAMPLE-2: Preparation of 4-isopropylamino-butyric acid ethyl ester
Ethyl 4-bromobutyrate (100.0 g; 0.512 mol) was added to isopropyl amine (90.91 g; 1.53 mol) at 10-15 °C and maintain the reaction mixture at 10-15 °C for 20-22 hrs. Upon completion of the reaction monitored by HPLC, the contents of the reaction mass was distilled out at temperature below 55 °C under reduced pressure to obtain the residue. Obtained residue was diluted in purified water (200 ml) and pH of aqueous layer was adjusted to less than 2 using 1N hydrochloric acid solution (100 ml), followed by extracting impurities in MDC (2 * 200 ml). Further the pH of aqueous layer was adjusted to 9-12 using 10% sodium hydroxide solution ( 120.0 ml) followed by extracting the product in MDC (3 * 200 ml). The resultant organic layer was concentrated under reduced pressure to obtain the pure oil of compound. fYield = 56 g (63.03%); Purity {HPLC) = 98.20%1
EXAMPLE-3: Preparation of 4-isopropylamino-butvric acid ethyl ester
To the stirred solution of isopropyl amine (90.91 g; 1.53 mol) in tetrahydrofuran (200 ml), ethyl 4-bromobutyrate (100.0 g; 0.512 mol) was added at 10-15 °C and maintain the reaction mixture at 10-15 °C for 20 hrs. Upon completion of the reaction monitored by HPLC, the contents of the reaction mass was distilled out at temperature below 55 °C under reduced pressure to obtain the residue. Obtained residue was diluted in purified water (200 ml) and pH of aqueous layer was adjusted to less than 2 using 1N hydrochloric acid solution (100 ml), followed by extracting impurities in MDC

(2 x 200 ml). Further the pH of aqueous layer was adjusted to 9-12 using 10% sodium hydroxide solution (120.0 ml) followed by extracting the product in MDC (3 * 200 ml). The resultant organic layer was concentrated under reduced pressure to obtain the pure oil of the title compound. meld = 51.0 g (57.43%); Purity (HPLC) = 98.50%1
EXAMPLE-4: Preparation of 4-isopropyl-amino-butyric acid
Ethanol (20 ml) and aqueous solution of sodium hydroxide (2.61 ml; 1N) were added to 389 mg of 4-isopropyl-amino]-butyric acid ethyl ester, and was stirred at room temperature for 4 hrs at room temperature. The mixture was further stirred at 50°C for 10 minutes and neutralized with 1N hydrochloric acid. The crystals precipitated were recovered by filtration to obtain the 4-isopropyl-amino]-butyric acid. fYield = 305 mg; Purity (HPLC) = 86.01%1
EXAMPLE-5: Preparation of 4-isopropyl -aminobutan-1-ol
To a mixture of LiAIH4 (6.0 g) in anhydrous THF (105 ml), a solution of 4-isopropylamino-butyric acid ethyl ester (15 g) was added in anhydrous MDC (75 ml) at -0 to -10 °C under nitrogen atmosphere. The reaction mass was stirred for 1-2 hrs, and then allowed to reach the temperature to 20-25'°C and stirred overnight. The reaction mass was chilled to 0 to -10 °C and MeOH (75 ml) was added. The reaction mass was extracted with MDC and purified water, MDC layer containing the product was separated and the product was extracted from aqueous layer using MDC. The combined organic MDC layers were concentrated under reduced pressure to afford required 4-isopropyl -amino]-butan-1-ol. lYield = 7.0 g (62%): Purity (HPLC) = 96%1
EXAMPLE-6: Preparation of 4-isopropyl -aminobutan-1-ol

To a mixture of LiAIH4 (15.33 g; 0.40 mol.) in anhydrous THF (525 ml), a solution of 4-isopropylamino-butyric acid ethyl ester (35.0 g; 0.20 mol.) was added in anhydrous THF (70 ml) at 0 to -5 °C under nitrogen atmosphere. The reaction mass was maintained at same temperature for 2-3 hrs. After completion of reaction by GC reaction mass quenched with purified water (350.0 ml) and maintain the reaction mass at 25-30 °C for 2 hrs. Filter the reaction mass and wash the filter bed with MDC (70 ml). Concentrate the filtrate under reduced pressure to obtain residue. The obtained residue was diluted in purified water (175 ml) and pH of aqueous layer was adjusted to 12-14 using 10% sodium hydroxide solution (120 ml), followed by extracting product in MDC (3 * 175 ml). The MDC layer was washed with purified water (175 ml) and resultant organic layer was concentrated under reduced pressure to obtain the pure oil compound. lYield = 22.0 q (83.0%); Purity (HPLC) = 97.0%1
EXAMPLE-7: Preparation of 4-isopropyl -aminobutan-1-ol
To a mixture of LiAIH4 (760 mg) in anhydrous THF (45 ml) was added a solution of 4-isopropyl-amino]-butyric acid (14) (1.75 g) in anhydrous THF (5 ml) at 0 °C under nitrogen atmosphere. The mixture was allowed to warm to room temperature. After stirring for 10 hrs, the reaction was quenched with 6 ml_ of 20% aqueous NaOH solution at 0 °C and then filtered. The filtered cake was washed with ethyl acetate (10 mL x 4). The combined organic layers were concentrated under reduced pressure. The residue was isolated using 9:1 heptane and ethyl acetate to obtain 4-isopropyl amino-butan-1-ol. fYield = 1.54 g; Purity (HPLC) = 96%1

We claim:
1. A process for preparing compound of formula (1), the said process comprising:
a) reacting a compound of formula (8) with a compound of formula (9) to obtain a compound of formula (10); and
Wherein, X= Halogen or a leaving group selected from -OH, -OTs, -OCF3, -OBOP, -OPyBrOP, OSO2CH3, OSO2CF3, OBs, OCH2OCH3, OC(CH3)3, OCH2Ph, O-p-methoxybenzyl, OTMS, OTES, OTBDMS, OTBDPS, OTIPS,OCPh3, OR; R is selected from the group consisting of alkyl, aryl, and substituted aryl b) reducing the obtained compound of formula (10) in a solvent and in presence of a suitable reducing agent optionally in combination with a suitable catalyst to obtain compound of formula (1).
2. The process of claim 1, wherein step (a) is optionally carried out in a solvent and in presence of a base.
3. The process of claim 2, wherein the solvent used in step (a) is selected from the group comprising of esters such as alkyl acetate including but not limited to ethyl acetate, and isopropyl acetate; aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but

not limited to dichloromethane, chloroform, and ethylene dichloride;
dialkylformamides such as but not limited to dimethyl formamide; ethers
such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di¬
ethyl ether and di-methyl ether, and methyl butyl ether; cyclic ethers such
as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic
ethers such as but not limited to 2-methyl tetrahydrofuran; alcohols such
as but not limited to methanol, ethanol, n-propanol, iso-propanol, n-
butanol, iso-butanol, n-pentanol, ethylene glycol, and diethylene glycol;
ketones such as but not limited to acetone, methyl ethyl ketone, and
methyl isobutyl ketone; dialkylsulfoxides such as but limited to dimethyl
sulfoxide; dialkylacetamides such as but not limited to N,N-dimethyl
acetamide; nitriles such as but not limited to acetonitrile, and propionitrile;
ionic liquids, hexamethylphosphorous triamide,
hexamethylphosphoramide, water or mixtures thereof.
4. The process of claim 1, wherein the solvent used in step (b) is selected from the group comprising of aliphatic hydrocarbons such as but not limited to cyclohexane, n-hexane, n-heptane, and pentane; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to are dichloromethane, chloroform, and ethylene dichloride; dialkylformamides such as but not limited to dimethyl formamide; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether di-methyl ether, and methyl butyl ether; cyclic ethers such as but not limited to tetrahydrofuran, and 1,4-dioxane; substituted cyclic ethers such as but not limited to 2-methyl tetrahydrofuran; dialkylsulfoxides such as but limited to dimethyl sulfoxide; dialkylacetamides such as but not limited to N,N-dimethyl acetamide; or mixtures thereof.

5. The process of claim 1, wherein the base used in step (a) is selected from inorganic bases such as alkali metal carbonates such as but not limited to potassium carbonate, sodium carbonate, and cesium carbonate; alkali metal bicarbonates such as but not limited to sodium bicarbonate, and potassium bicarbonate; alkali metal hydroxides such as but not limited to sodium hydroxide, potassium hydroxide, barium hydroxide, and lithium hydroxide; metal hydrides; metal alkoxides such as but not limited to sodium methoxide, sodium ethoxide, and potassium tert-butoxide; alkali metal amide such as but not limited to lithium amide, sodium amide, potassium amide, cesium amide and rubidium amide; alkali metal hydrides such as but not limited to sodium hydride, potassium hydride, lithium and calcium hydride; amidines such as but not limited to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN); 1,4-diazabicyclo[2.2.2]octane (DABCO); and organic bases such as primary amines such as but not limited to methylamine, ethanolamine aniline, propyl amine, 2-propyl amine, butyl amine, and 2-amino ethanol; secondary amines such as but not limited to N,N-diisopropyl amine, dimethylamine, diethyl amine, N-methyl propyl amine, and pyrrole methylethanolamine; tertiary amines like triethylamine, N,N-dimethyl aniline, N,N-diisopropyl ethyl amine, trimethyl amine, pyridine, pyrimidine, N,N-dimethylethyl amine and mixtures thereof.
6. The process of claim 1, wherein the reducing agents used in step (b) is selected from the diborane, borane-dimethyl sulfide, borane-THF complex, sodium triacetoxyborohydride, sodium cyanoborohydride, Diisobutylaluminum hydride (DIBAL-H), Lithiumaluminiumhydride (LiAlhU), Sodium borohydride (NaBhU), NaBhU/BFa-etherate, Lithiumborohydride

(LiBhU), Sodiumcyanoborohydrie (NaCNBH4), Raney-Nickel, Sodium
bis(2-methoxyethoxy)aluminumhydride (Vitride), and Sodium bis(2-
methoxyethoxy) aluminumhydridepyrolidine (Red-ALP), Lithium
triethylborohydride (UBHEt3), magnesium tetrahydroborate [Mg(BH4)2],
Aluminum borohydride [AKBHUb], Calcium borohydride [Ca(BH4)3], Zinc
borohydride [Zn(BH4)2], Cerium borohydride Ce(BH4)3, Sodium
triacetoxyborohydride [NaBH(OAc)3], Sodium cyanoborohydride
[NaBHsCN], , Mg(BH4)2(NaBH4+AICI3), AI(BH4)3(NaBH4+AICI3),
Ca(BH4)3(NaBH4+CaCI2), Zn(BH4)2(NaBH4+ZnCI2)J
Ce(BH4)3(NaBH4+CeCI3), NaBH3CN(NaBH4+HCN), or their mixtures thereof.
7. The process of claim 1, wherein the catalyst used in step (b) is selected from Lewis acid, acid as a catalyst, catalyst or their mixture thereof.
8. The process of claim 7, wherein the catalyst used in step (b) is selected from Lewis acid such as Aluminum Chloride (AlCb-XZinc chloride (ZnCb), Boron trifluoride (BF3), Boron trialkoxide (B(OR)3), Trimethylaluminium
(AI(CH3)3), Sn2+B(CH3)3, lodinefk), Bromine(Br2), Carbenes, Hydrogen ion(H+), Lithium ion(Li+), Sodium ion(Na+), Potassium ion(K+), Aluminum ion (Al3+), Magnesium ion (Mg2+), Calcium ion(Ca2+), Ferrous ion (Fe2+), Cobalt ion (Co2+), Copper ion (Cu2+), Zinc ion (Zn2+), Lead ion (Pb2+), Copper ion (Cu+), Silver ion (Ag+), mercury /on(Hg+), Palladium ion(Pd2+), and acetic acid.
9. The process of claim 7, wherein the catalyst used in step (b) is selected
from acid such as an organic acid, or an inorganic acid, selected from
sulfuric acid (H2SO4), Trifluoroacetic acid (TFA), Trichloroacetic acid

(CCbCOOH), Dichloroacetic acid (CHCI2COOH), Trifluoroacetic acid (CF3COOH), Methanesulfonic acid (CH3SO3H), Trifluoromethanesulfonic acid (CF3SO3H), and p-toluene sulfonic acid (P-CH3C6H4SO3H), Nitric acid (HNO3), hydroiodic acid (HI), Hydrobromic acid (HBr), Perchloric acid (HCIO4), Chloric acid (HCIO3), and Hydrochloric acid (HCI).
10. The process of claim 7, wherein the catalyst used in step (b) is selected from Iodine (I2), Trialkyl amine, Dimethyl selane (SiH2Me2), trimethylsilyl chloride (MesSiCI), Titanium chloride (TiCU), dialkyl silane (R2Se2), and MeSe20H.
11. The process of claim 1, wherein the compound of the formula (10) is isolated and purified from reaction mass of step (a) comprises the step of: i. treating the reaction mass of step (a) with water and organic solvent;
ii. acidifying the reaction mass of step (i);
iii. extracting the impurities from reaction mass of step (ii) with an organic
solvent; iv. separating the organic layer and aqueous layer of step (iii); v. adjusting the pH of aqueous layer of step (iv) to 9-12 with 10 %
sodium hydroxide solution; vi. extracting the product from reaction mass of step (v) with an organic
solvent; and vii. concentrating the organic layer of step (vi) to obtain the compound of
formula (10).
12. The process of claim 11, wherein the solvent used in step (i), (iii) and (vi)
of isolation process is selected from the group comprising of esters such
as alkyl acetate including but not limited to ethyl acetate, and isopropyl

acetate; aromatic hydrocarbons such as but not limited to toluene, xylene, and naphthalene; halogenated aliphatic hydrocarbons such as but not limited to dichloromethane, chloroform, and ethylene dichloride; ethers such as but limited to methyl tertiary butyl ether, di-isopropyl ether, di¬ethyl ether and di-methyl ether, methyl butyl ether; or mixtures thereof.
13. The process of claim 1, wherein, the compound of the formula (1) is
isolated and purified from reaction mass of step (b) comprises the steps
of:
i. treating the reaction mass of step (b) with water or optionally with
mixture of alcohol and water; ii. extracting the reaction mass of step (i) with an organic solvent; iii. separating the organic layer of step (ii) followed by washing it with
water; and iv. concentrating the organic layer of step (iii) to obtain the compound of formula (1).
14. The process of claim 13, wherein the solvent used in step (ii) is selected
from the group comprising of esters such as alkyl acetate including but
not limited to ethyl acetate, isopropyl acetate; aliphatic hydrocarbons such
as but not limited to cyclohexane, n-hexane, n-heptane, pentane;
aromatic hydrocarbons such as but not limited to toluene, xylene,
naphthalene; halogenated aliphatic hydrocarbons such as but not limited
to are dichloromethane, chloroform, ethylene dichloride; ethers such as
but limited to methyl tertiary butyl ether, di-isopropyl ether, di-ethyl ether
and di-methyl ether, methyl butyl ether; cyclic ethers such as but not
limited to tetrahydrofuran, 1,4-dioxane; substituted cyclic ethers such as
but not limited to 2-methyl tetrahydrofuran; ketones such as but not

limited to acetone, methyl ethyl ketone, methyl isobutyl ketone; or mixtures thereof.