FIELD OF THE INVENTION
The present invention relates to novel compounds of Formula-1 and process of preparation thereof,

wherein R is a N-protecting group.
The present invention further relates to use of compounds of Formula-1 as an intermediate for the preparation of serotonin 5-HT2A receptor antagonists such as pimavanserin and/ or pharmaceutically acceptable salts thereof
BACKGROUND OF THE INVENTION
Parkinson's disease (PD) is a common progressive neurodegenerative disorder; where patients experiences symptoms such as rest tremor, bradykinesia, rigidity, and disturbances of balance and posture. Psychotic symptoms occur in 20% to 40% of patients with PD in advanced stages of the disease. Parkinson's disease psychosis (PDP) is a particularly devastating neuropsychiatric complication of Parkinson's disease that affects a majority of the patient population with advanced disease. Antipsychotics and dopamine receptor antagonists can be effective in ameliorating psychotic symptoms wherein one of such antipsychotics is pimavanserin.
Pimavanserin tartarate, marketed under the trade name Nuplazid, is a non-dopaminergic atypical antipsychotic used for the treatment of Parkinson's disease psychosis and schizophrenia.

Pimavanserin is known from PCT publication number WO 2001/066521 Al which generically discloses pimavanserin. The basic chemistry for preparation of pimavanserin tartrate of formula-8 is disclosed in WO 2004/064738.
The synthetic method disclosed in WO'738 is mentioned under scheme-1:
Scheme-1:






DPPA
Proton Sponge THF reflux

HoN
,N.
+
O
i-BuBr K2C03 DMF O 80°C
Step 2

NaBH3CN
HOAc
MeOH
Stepl
KOH MeOH-H20
Step 3
L-(+)-Tartaric acid EtOH
Step 6
>. Tartarate

Formula-8
US patent 7,790,899 discloses a process for preparation of pimavanserin wherein said process involves reacting 4-hydroxybenzaldehyde with isobutylbromide in the presence of dimethylformamide, potassium iodide and potassium carbonate to produce 4-isobutoxybenzaldehyde followed by reacting the 4-isobutoxybenzaldehyde with

about 1.5 equivalents of NH2OH to produce 4-isobutoxybenzoxime. The 4-isobutoxybenzoxime so obtained is hydrogenated with hydrogen in the presence of Raney-Ni and NH3 to produce (4-isobutoxyphenyl)methanamine which upon addition of acetic acid produced (4-isobutoxyphenyl)methanamine acetate. The (4-isobutoxyphenyl)methanamine acetate so obtained is treated with about 30% NaOH and extracting with toluene to produce (4-isobutoxyphenyl)methanamine which is reacted with HC1 and COCh in the presence of toluene to produce l-isobutoxy-4-(isocyanatomethyl)benzene. The l-isobutoxy-4-(isocyanatomethyl)benzene is then reacted with N-(4-fluorobenzyl)-1 -methylpiperidin-4-amine to produce N-( 1 -methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N'-(4-(2-methylpropyloxy)phenyl methyl)carbamide (pimavanserin).
Chinese patent application CN 105906551 discloses a process of preparation of pimavanserin as mentioned in scheme-2:
Scheme-2:




acid chloride reagent
»
Step 2
inorganic base Stepl

Step 3

TBAB
NaN3


OCN

CN 105820110 A discloses a process for preparation of pimavanserin by using various salts of N-(4-fluorobenzyl)-l-methylpiperidin-4-amine as intermediates. Preparation of various salts of N-(4-fluorobenzyl)-l-methylpiperidin-4-amine adds up a reaction step in the whole process leading to increase in time required for production of pimavanserin.
WO 2017/054786 discloses a process for the preparation of pimavanserin by
reacting N-(4-fluorobenzyl)-l-methylpiperidine-4-amine with 4-
isobutoxybenzylamine. The crude pimavanserin so obtained is crystallized by treating with organic solvent and a solution of p-toluenesulfonic monohydrate.
Although there are several process known in the prior referenced publications for the preparation of pimavanserin, however the known processes involve use of reagents which are either toxic or require peculiar conditions to be used at large scale production. The 4-isobutoxy, benzyl isocyanate as used in prior art processes is highly reactive and is an expensive reagent. Further, the processes known in published literature uses toxic chemicals such as phosgene and diphenyl phosphoryl azide which are highly explosive and unsafe to be used at large scale.
r
Hence, in view of the processes known from prior publications, there is a need to develop a process that leads to pimavanserin and its pharmaceutical acceptable salts in high yields and purity. Based on aforesaid, the present invention is focussed towards development of a novel process for preparation of pimavanserin or its pharmaceutical acceptable salts via novel intermediate that requires less toxic and inexpensive reagents making the process more economical for large scale production.
OBJECT OF THE INVENTION

The main aspect of the present invention is to develop novel compounds of Formula-1 that can be used for the preparation of serotonin 5-HT2A receptor antagonists such as pimavanserin and its pharmaceutical acceptable salts.
NH
OH Formula-1
Another aspect of the present invention is to develop a novel process for the preparation of substantially pure pimavanserin and its pharmaceutical acceptable salts by using compounds of Formula-1.
SUMMARY OF THE INVENTION
The main aspect of the present invention is to provide a novel and economical process for the preparation of substantially pure pimavanserin and/or its pharmaceutical acceptable salts through novel compounds of Formula-1.
Accordingly, the present invention provides novel compounds of Formula-1,
^-y N—( N-R 0=< ^ NH
k
OH Formula-1
wherein R is N-protecting group.

The present invention further provides a process of preparation of compound(s) of Formula-1, wherein said process comprising of:
a) converting acid chloride of Formula-2 to isocyanate of Formula-3 in presence of sodium azide in an organic solvent,
OH OH

NCO O
Formula-2 Formula-3. d
b) adding N-protected piperidine compound of Formula-4 to get compound of Formula-1,

Formula-4
F ~ OH


OCN
Formula-3 Formula-1
wherein R is N-protecting group.
The present invention furthermore provides a process of preparation of substantially pure pimavanserin and/ or its pharmaceutical acceptable salts, wherein said process comprising the steps of:
a) alkylating compound of Formula-1 with an alkylating agent in presence of base in an organic solvent to get compound of Formula-5,

Formula-1 Formula-5
b) de-protecting compound of Formula-5 in presence of a solvent to get compound of Formula-6,

Formula-5 Formula-6
c) methylating compound of Formula-6 in presence of a reducing agent to get pimavanserin of Formula-7,


Formula-6 Formula-7 . ^
d) optionally converting compound of Formula-7 to its pharmaceutical^ acceptable salts.
DETAILED DESCRIPTION
Brief Description of the accompanying drawing
Fig. 1, represents the X-ray (powder) diffraction (XRD) pattern of the crystalline
form of pimavanserin tartarate.
Fig. 2, represents the X-ray (powder) diffraction (XRD) pattern of the amorphous
form of pimavanserin tartarate.
The present invention will now be explained in details. While the invention is susceptible to various modifications and alternative forms, specific embodiment thereof will be described in detail below. It should be understood, however that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the invention is to cover all modifications, equivalents, and alternative falling within the scope of the invention as defined by the appended claims.
The steps of a method may be providing more details that are pertinent to understanding the embodiments of the present invention and so as not to obscure

the disclosure with details that will be readily apparent to those of ordinary skill in the art having benefit of the description herein.
Further characteristics and advantages of the process according to the invention will result from the description herein below of preferred exemplary embodiments, which are given as indicative and non-limiting examples.
Accordingly, in one aspect, the present invention provides novel compounds of Formula-1,
^—^ N—< N-R NH
k
OH Formula-1
wherein R is N-protecting group.
In one embodiment, the N-protecting group is a temporary substituents which protect a potentially reactive amino functional group from undesired chemical transformations.
In another embodiment, the N-protecting group may be any group used for protection of amino group. Preferably, the N-protecting group is selected, but not limited to, any carbon containing or silyl containing moiety.
In another aspect, the present invention provides a process for preparation of compound(s) of Formula-1, wherein said process comprises the steps of: a) converting acid chloride of Formula-2 to isocyanate of Formula-3 in presence of sodium azide in an organic solvent,



O Formula-2
NCO
Formula-3. md b) adding N-protected piperidine of Formula-4 to get compound of Formula-1,



OCN

Formula-4

Formula-3

Formula-1

wherein R is a N-protecting group.
In another embodiment, the conversion of acid chloride of Formula-2 to isocyanate of Formula-3 is performed in presence of sodium azide and organic solvent selected from the group comprising of dimethyl acetamide, dimethyl formamide, N-methyl pyrrolidine, dimethyl sulfoxide, hexamethyl phosphoramide, ethyl acetate, tetrahydrofuran, toluene, methylene dichloride, ethylene dichloride, xylene and mixture thereof. The preferred solvent is dimethyl acetamide.
In another embodiment, the present invention provides process for preparation of compound of Formula-1 wherein the process involves preparation of intermediate, Formula-3 which is not isolated from the reaction mixture.

In another embodiment, the present invention provides a process for preparation of substantially pure pimavanserin and/or its pharmaceutical acceptable salts, wherein said process comprising the steps of:
a) alkylating compound of Formula-1 with an alkylating agent in presence of base in an organic solvent to get compound of Formula-5,



Formula-1
b) de-protecting compound of Formula-5 in presence of a solvent to get compound of Formula-6,

Formula-5 Formula-6
c) methylating compound of Formula-6 in presence of a reducing agent to get pimavanserin of Formula-7,


Formula-6 Formula-7 . and
d) optionally converting compound of Formula-7 to its pharmaceutical^ acceptable salts.
In another embodiment, the solvent(s) used in the preparation of pimavanserin or its pharmaceutical acceptable salts is selected from the group comprising, but not limited to, ketones, esters, amides, halogenated solvents, aliphatic hydrocarbons, aromatic hydrocarbons, ethers, pyrrolidones, sulfoxides, amides, water and mixture thereof. Preferably the solvent is selected from the group comprising of toluene, xylene, dimethyl acetamide, dimethyl formamide, N-methyl pyrrolidine, dimethyl sulfoxide, hexamethyl phosphoramide, tetrahydrofuran, dioxane, methyl-tetrahydrofuran, diethyl ether, isopropyl ether, isobutyl acetate, methyl tert-butyl ether, acetone, methyl isobutyl ketone, methyl ethyl ketone, methanol, ethanol, methyl tert-butyl ketone, methyl acetate, ethyl acetate, isopropyl acetate, t-butyl acetate, dichloromethane, ethylene dichloride, chloroform, dichlorobenzene, diethyl ether, isopropyl ether, heptane, hexane, pentane, water, and mixture thereof.
In one another embodiment, the alkylation of compound of Formula 1 with alkylating agent is carried out in presence of solvent selected from the group comprising of dimethyl acetamide, dimethyl formamide, N-methyl pyrrolidine, dimethyl sulfoxide, hexamethyl phosphoramide, tetrahydrofuran, dioxane, methyl-

tetrahydrofuran, acetone, methyl ethyl ketone, methyl isobutyl ketone and mixture thereof. The most preferred solvent is dimethyl acetamide.
In another embodiment, the alkylation of compound of Formula 1 with alkylating • agent is carried out in presence of base selected from the group comprising of sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, cesium acetate, sodium acetate, potassium acetate, sodium bicarbonate, potassium carbonate, sodium carbonate, and potassium bicarbonate.
In another embodiment, the said alkylating agent is selected from isobutyl bromide, isobutyl tosylate and isobutyl mesylate. Preferably isobutyl bromide and isobutyl tosylate is used for alkylation of compound of Formula I.
In another embodiment, the N-deprotecting reagents used for deprotection of piperidine group is selected from trifluoroacetic acid, hydrochloric acid, aqueous phosphoric acid and other mild acids.
In one another embodiment, the deprotection of compound of Formula-5 is carried out in presence of solvent selected from the group comprising of halogenated solvents such as dichloromethane, chloroform, dichlorobenzene; ethers such as tetrahydrofuran, methyl tetrahydrofuran; dioxane or mixture thereof.
In another embodiment, the reducing agent is selected from the group comprising of sodium borohydride, lithium borohydride, sodium triacetoxyborohydride, lithium aluminium hydride, vitride and sodium cyanoborohydride.
In a preferred embodiment, the N-methylation process is performed in presence of acetic acid and formaldehyde along with the reducing agent.
In further embodiment, the pimavanserin is optionally converted to its pharmaceutically acceptable salts wherein the pharmaceutically acceptable salts are

selected from the group comprising of hydrochloric acid salt, hydrobromic acid salt,
phosphate, tartrate, sulphate, nitrate, diphosphate, bicarbonate, carbonate,
clavulanate, isothionate, borate, halide, nitrate, acetate, succinate, lactate,
lactobionate, laurate, mandelate, malate, citrate, fumarate, maleate, oleate, oxalate,
ascorbate, nicotinate, benzoate, mesylate, salicylate, stearate, tannate , tosylate,
valerate, methanesulfonate, ethanesulfonate, pivalate, benzenesulfonate, p-
toluensulfonate, 2-ethane disulfonate, edisylate and naphthalenesulfonate. The
pharmaceutical acceptable salts may further includes pharmaceutical acceptable
bases such as metal salts including alkali metal or alkaline earth metal salts for
example sodium, potassium, magnesium, calcium or zinc salts, ammonium salts;
organic amines such as benethamine, benzathine, diethanolamine, ethanolamine,
4(2-hydroxy-ethyl)morpholine, l-(2-hydroxyethyl)pyrrolidine, ' N-methyl
glucamine, piperazine, triethanol amine and the like.
In a preferred embodiment, the pharmaceutical acceptable salt is a tartrate salt. In above mentioned step d), the pimavanserin of Formula-7 is converted to pimavanserin tartarate of Formula-8 as represented below:

I
0
^ ^
^

N^i - L-(+)-Tartaric acid
(X Jv solvent
H
V
0
Formula-7

H +. ,NYN
0

OH 0 0 OH

Formula-8
In yet another embodiment, the pimavanserin tartarate produced by the process of the present invention is crystalline in nature.
In further embodiment, the present invention provides a substantially pure and stable crystalline form of the pimavanserin tartarate

In a preferred embodiment, the crystalline form of pimavanserin tartarate is characterized by X-Ray powder diffraction pattern comprising peaks at about 4.71, 5.04,5.31,8.64,9.47,10.70,11.48,11.81,12.66,12.92,13.72,14.11,14.48,14.90, 15.11, 15.98, 17.14, 17.55, 17.88, 18.45, 18.82, 19.08, 19.66, 19.89, 20.24, 21.14, 21.54, 22.27, 22.78, 22.93, 23.47, 23.73, 24.19, 25.54, 26.46, 26.97, 27.70, 29.13, 29.78, 30.31, 30.64, 32.22, 34.69, 36.12, 37.O5±O.2°20.
In another embodiment, the present invention provides a substantially pure amorphous form of the pimavanserin tartarate, wherein said amorphous form is substantially free of any crystalline form.
In an embodiment, the present invention also provides stable amorphous solid dispersions of pimavanserin tartrate and its pharmaceutical acceptable salts together with a pharmaceutically acceptable carrier, processes for preparation thereof, and pharmaceutical compositions prepared therefrom.
In further embodiment, the pimavanserin or its pharmaceutical acceptable salts as obtained by the process of the present invention are substantially free of impurities wherein each impurity is not more than 0.5% w/w.
In further embodiment, the pimavanserin or its pharmaceutical acceptable salts as obtained by the process of the present invention is substantially pure with purity above 99.0% and, preferably 99.5% and above and, most preferably 99.9% and above.
Moreover, the pimavanserin and/or its pharmaceutical acceptable salts as obtained by the process of the present invention is characterized by particle size distribution wherein d9o is between 0.1 (im to 200|im. More preferably pimavanserin and/or its pharmaceutical acceptable salts as obtained by the process of the present invention is characterized by particle size distribution wherein d90 is between 2.0 (am to 150^ni.

The present invention is explained below by way of examples. However, the examples are provided as one of the possible way to practice the invention and should not be considered as limitation of the scope of the invention.
EXAMPLES
Example 1: Synthesis of N-Boc-4-[(4'-fluorophenyl) methyl] amino piperidine
To a solution of N-Boc-piperidone (20g) in methanol (60 ml) was added 4-Fluorobenzylamine (12.6 g). The solution so obtained was cooled to 5-10°C. Added Acetic acid (10 g) in methanol (10 ml) to the reaction solution followed by dropwise addition of sodium cyanoborohydride (17g) in methanol (50 ml) at 5-10°C. Reaction mass was then stirred at room temperature for 3-4 hours. After completion of reaction, evaporated the methanol till volume reduced to l/3rd and added 10% aq. NaOH solution and extracted with compound with Dichloromethane (200ml). The organic layer was separated and washed with DM water (100 ml). Finally, distilled off the organic layer to get N-Boc-4-[(4'-fluorophenyl) methyl] amino piperidine (25 g) as product.
Example-2: Synthesis of Pimavanserin Tartrate
Step-01: Preparation of p-Hydroxy phenyl acetic acid chloride
■ To the solution of p-Hydroxy phenyl acetic acid (5g) in THF (10 ml) and N,N-
dimethyl formamide (0.5 ml) was added thionyl chloride (2.7 ml) and stirred the
reaction at 25°C for 30 min. After completion of reaction, distilled off the solvents
to get p-Hydroxy phenyl acetic acid chloride.
Step-02: Synthesis of tert-butyl 4-(l-(4-fluorobenzyl)-3-(4-hydroxybenzyl) ureido)piperidine-l-carboxylate (compound of Formula-1 with R = Boc)

To the solution of p-Hydroxy phenyl acetyl chloride as obtained from step 01 of example 2 in dimethyl acetamide (25 ml) was added sodium azide (4.3 g) and stirred at 0-5°C for 1 hours. After completion of reaction, added N-Boc-4-[(4'-fluorophenyl) methyl] amino piperidine (6.08 g) to the reaction mass and heated the reaction mass to 70-80°C for 8-10 hours. After completion of reaction, quenched the reaction with water and extracted with ethyl acetate. Ethyl acetate layer was then separated, concentrated and dried to get 6.0 g of tert-butyl 4-(l-(4-fluorobenzyl)-3-(4-hydroxybenzyl)ureido)piperidine-1 -carboxylate. 1HNMR (DMSO): 6 9.18 (1H, s), 7.24-7.22 (2H, m), 7.21-7.08 (2H, t), 6.99-6.97 (2H, d), 6.85-6.82 (1H, m), 6.67-6.64 (2H, d), 4.40 (2H, s), 4.15-4.14 (2H, d), 4.09-4.05 (1H, m), 3.94-3.91 (2H, m), 2.68-2.66 (2H, m), 1.49-1.46 (2H, m), 1.42-1.38 (2H, m) and 1.35 (9H,s) Mass (M+l): 458
Step-03A: Preparation of tert-butyl 4-(l-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)ureido)piperidine-l-carboxylate of Formula 5 (R = Boc)
Charged tert-butyl 4-(l -(4-fluorobenzyl)-3-(4-hydroxybenzyl)ureido)piperidine-1 -carboxylate (14.0 g) in DMF (40 ml) and added potassium hydroxide (12.3 g) and Isobutyl bromide (18 g) and stirred the reaction mass at 25°C for 5-6 hours. After completion of reaction, quenched the reaction mass with DM water and filtered the precipitates so obtained. Dried the precipitates to get 21.0 g of tert-butyl 4-(l-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)ureido)piperidine-l-carboxylate.
Step-03B: Preparation of tert-butyl 4-(l-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)ureido)piperidine-l-carboxylate of Formula 5 (R = Boc)
Charged tert-butyl 4-(l -(4-fluorobenzyl)-3-(4-hydroxybenzyl)ureido)piperidine-1 -carboxylate (12.2 g) in DMF (25 ml) and added potassium hydroxide (7.5 g) and Isobutyl tosylate (7.5 g) and stirred the reaction mass at 25°C for 5-6 hours. After completion of reaction, reaction mass is cooled and quenched with DM water and

ethyl acetate .Ethyl acetate layer separated and concentrated to get 13.2 g of tert-butyl 4-( 1 -(4-fluorobenzyl)-3 -(4-isobutoxybenzyl)ureido)piperidine-1 -carboxylate
Step-04: Preparation of N-(4-Fluorobenzyl)-N-(piperidin-4-yl)-N'-(4-isobutyloxybenzyl) carbamide
To the solution of tert-butyl 4-(l -(4-fluorobenzyl)-3-(4-
isobutoxybenzyl)ureido)piperidine-l-carboxylate (21.0 g) in Dichloromethane (80 ml) was added trifluoroacetic acid (75 ml) dissolved in Dichloromethane (75 ml) and stirred the reaction mass at 5-10°C for 1-2 hours. After completion of reaction, reaction mass was quenched with DM water (300 ml) and pH was adjusted to 7.0-8.0 with 10% aq. sodium carbonate solution. Separated the Dichloromethane layer and distilled off completely to get 19.6 g of N-(4-Fluorobenzyl)-N-(piperidin-4-yl)-N'-(4-isobutyloxybenzyl) carbamide.
Step-05: Preparation of l-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-l-(l-methylpiperidin-4-yl) urea (Pimvanserin)
To the solution of N-(4-Fluorobenzyl)-N-(piperidin-4-yl)-N'-(4-isobutyloxybenzyl) carbamide (19.6 g) in methanol (100 ml) was added acetic acid (0.5 ml) and formaldehyde (37%) solution (19.2g) and cooled the reaction mass at 0-5°C followed by addion of sodium borohydride (4.0 gm) lot wise. After addition, allowed the reaction mass to reach to room temperature and stirred for 1-2 hours. After completion of reaction, distilled off the methanol to get crude compound. The crude compound was diluted with DM water and extracted with ethylacetate. Ethyl acetate layer was then separated and distilled off to get 17.0 g of pimavanserine free base.
Step-06: Preparation of l-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-l-(l-methyIpiperidin-4-yl) urea tartrate (Pimavanserin tartrate, compound of formula-8)

To the solution of 1 -(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-1 -(1 -methylpiperidin-4-yl) urea (17.0 g) in 140 ml of acetone was added L-(H-)-Tartaric acid (3.2 g) and stirred the reaction mass for 1 hour at 55-60°C which is then allowed to cool down to room temperature over next 3-4 hours. Filtered the precipitates so obtained and washed with 20 ml of acetone and then suck dried under vacuum. Added 75ml of ethanol to the wet cake so obtained and heated to 75-80°C. Cooled the reaction mass to room temperature and filtered the solid mass. Wet solid is dried at 50-55°C under vacuum to get l-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-l-(l-methylpiperidin-4-yl) urea tartrate (Crystalline Pimavanserin tartrate) (12.9 g) as product.

WE CLAIM
1. Compounds of Formula-1,

OH Formula-l
wherein R is N-protecting group.
2. The compound as claimed in claim 1, wherein said N-protecting group is selected from the group comprising of tert butoxy carbonyl, carbazol carbonyl, benzoyl, benzyl carbonyl, benzoic acid, trifluoro methylene carbonyl, fluorenylmethyloxy carbonyl, trifluoroacetamide, allyl carbonyl, benzyloxy carbonyl, trichloroethyl carbonyl and benzyl group.,
3. A process for preparation of compound(s) of Formula-1, wherein said process comprises the steps of:
a) converting acid chloride of Formula-2 to isocyanate of Formula-3 in presence of
sodium azide in an organic solvent,
OH OH
if NCO
O
Formula-2 Formula-3. and
b) adding N-protected piperidine of Formula-4 to get compound of Formula-1,



OCN

HNr-i
Formula-4

Formula 3 Formula 1
wherein R is a N-protecting group.
4. The process as claimed in claim 3, wherein said organic solvent is selected from the group comprising of dimethyl acetamide, dimethyl formamide, N-methyl pyrrolidine, dimethyl sulfoxide, hexamethyl phosphoramide, ethyl acetate, tetrahydrofiiran, toluene, methylene dichloride, ethylene dichloride, xylene and mixture thereof.
5. The process as claimed in claim 3, wherein said compound of Formula-3 is not isolated.
6. A process for preparation of substantially pure pimavanserin and/or its
pharmaceutical acceptable salts, wherein said process comprising the steps of:
a) alkylating compound of Formula-1 with an alkylating agent in presence of base in an organic solvent to get compound of Formula-5,

Formula-1 Formula-5
5
b) de-protecting compound of Formula-5 in presence of a solvent to get compound of Formula-6,


Formula-6
c) methylating compound of Formula-6 in presence of a reducing agent to get pimavanserin of Formula-7,


Formula-6 Formula-7 . ancj
d) optionally converting compound of Formula-7 to its pharmaceutical^ acceptable
salts.
7. The process as claimed in claim 6, wherein said solvent used in step a) is selected
from the group comprising of dimethyl acetamide, dimethyl formamide, N-methyl
pyrrolidine, dimethyl sulfoxide, hexamethyl phosphoramide, tetrahydrofuran,
dioxane, methyl-tetrahydrofuran, acetone, methyl ethyl ketone, methyl isobutyl
ketone and mixture thereof; and
wherein said base used in step a) is selected from the group comprising of sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, cesium acetate, sodium acetate, potassium acetate, sodium bicarbonate, potassium carbonate, sodium carbonate, and potassium bicarbonate.
8. The process as claimed in claim 6, wherein said reducing agent is selected from the group comprising of sodium borohydride, lithium borohydride, sodixim triacetoxyborohydnde, lithium aluminium hydride, vitride, and sodium cy anoborohy dride.
9. The process as claimed in claim 6, wherein said alkylating agent is selected from the group comprising of isobutyl bromide/isobutyl tosylate and isobutyl mesylate.

10. The process as claimed in claim 6, wherein said pimavanserin or its pharmaceutical acceptable salts are substantially free of impurities wherein each impurity is not more than 0.5% w/w.