FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
[Section 10, and Rule 13]

TITLE OF THE INVENTION:
PROCESS FOR THE PREPARATION OF PERAMPANEL
APPLICANT(S):
Name: Torrent Pharmaceuticals Limited Nationality: Indian
Address: Torrent House, Off Ashram Road, Near Dinesh Hall, 009, Gujarat, India Ahmedabad 380
The following specification particularly describes the invention and the is to be performed. manner in which

PROCESS FOR THE PREPRATION OF PERAMPANEL
FIELD OF THE INVENTION
The present invention relates to a method for producing a l,2-dihydropyridine-2-one compound of formula (I) comprises reacting a compound of formula (II) with a boronic acid derivative of formula (III) in the presence of a palladium compound, a phosphorus compound, a cesium compound and a base.
The present invention also relates to a process for the preparation of Perampanel.
BACKGROUND OF THE INVENTION
The compound of formula (I) represented by 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridine-2-one is useful as, for example, a therapeutic agent for diseases such as Parkinson's disease, multiple sclerosis, epilepsy, etc. Perampanel is chemically 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one.
When in each of the methods using a palladium catalyst described as the production method 2 and production method 3 in WO 01/96308, the reaction is carried out in the presence of, for example, "palladium acetate catalyst-cesium carbonate-water", there are various problems such as the following problems: a considerable amount of compounds are produced as by-products by the cleavage of the carbon-boron bond of a compound (II) (Yoshio Urawa and three others, Pharmacia, 35(7), 706-710 (1999)) and the hydrolysis of a substituent such as a nitrile group proceeds. Therefore, an industrial method for producing a compound represented by formula (III) is desired.
U.S. 8,304,548 (also referred to herein as "the '548 patent") describes another process for preparing Perampanel. The process is based on the eight step synthesis described in the '571 patent (scheme 1), however it doesn't utilize methyl protection

of the oxygen in the 5'-bromo-6'-rnethoxy-2,3'-tbipyridine intermediate prior to the coupling with the benzonitrile moiety, and its later removal. The process, which comprises six synthetic steps and the use.of metal catalyst, can be illustrated by the following scheme 3. The '548 patent discloses the reaction of 5'-bromo-l'-phenyl-[2,3'-bipyridin]-6'(l'H)-one with 2-(l,3,2-dioxaborinan-yl) benzonitrile in the presence of palladium compound, a copper compound, a phosphorus compound and a base to form perampanel of Formula (I). Also discloses the crystalline hydrate, anhydrous crystal Form I, anhydrous crystal Form II, & anhydrous crystal Form V of perampanel of Formula (I).U.S. Published Patent Application No.20160039759 describes the process for the preparation of perampanel.
The prior art processes for the preparation of perampanel involve heavy metal catalyst such as copper iodide and tedious methods like performing filtration at higher temperature, usage of high concentrated ammonia for washing at higher temperature, sodium chloride washing at higher temperature, and multiple distillations. Accordingly, these processes are not suitable for industrial scale. The inventors of a present invention have developed a simple, safe, efficient, economical, industrially feasible process for the preparation of perampanel.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a method for producing a compound represented by formula (I):
wherein A1, A2, A3, A4 and A5 are as defined below, or a salt thereof, which comprises reacting a compound represented by formula (II):
wherein each of A1, A2, A3 and A4, which may be the same or different, is a hydrogen atom, an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered

heteroaromatic ring group, and X is a leaving group, or a salt thereof with a compound represented by formula (III):
wherein A5 is an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered heteroaromatic ring group; and R1 and R2 are as follows: 1) each of R1 and R2, which may be the same or different, is a hydrogen atom or a C1-6 alkyl group, and 2) the compound of formula (II) may form boroxine (a trimer) when both R1 and R2 are hydrogen atoms, or 3) R1, R2, the oxygen atoms and the boron atom, when taken together, form a 5- or 6-membered ring group optionally substituted by one to four C1-6 alkyl groups, in the presence of a palladium compound, a phosphorus compound, cesium compound and a base.
2) A production method according to 1) above, wherein each of A2 and A4 is a hydrogen atom.
3) A production method according to 1) or 2) above, wherein each of Ai, A3 and A5 is a phenyl group, a pyridyl group, a pyrimidyl group, a thienyl group or a furyl group.
4) A production method according to any one of 1) to 3) above, wherein a compound represented by formula (I-a):
wherein the ring A, ring B and ring C are as defined below, or a salt thereof is produced by reacting a compound represented by formula (Il-a):
wherein the ring A is an optionally substituted 2-pyridyl group, the ring B is an optionally substituted phenyl group, and X is a leaving group, or a salt thereof with a compound represented by formula (III-a):

wherein the ring C is an optionally substituted phenyl group; and R1 and R2 are as follows: 1) each of R1 and R2, which may be the same or different, is a hydrogen atom or a C1-6 alkyl group, and 2) the compound of formula (III-a) may form boroxine (a trimer) when both R1 and R2 are hydrogen atoms, or 3) R1, R2, the oxygen atoms and the boron atom, when taken together, form a 5- or 6-membered ring group optionally substituted by one to four C1-6 alkyl groups, in the presence of a palladium compound, a phosphorus compound, cesium compound, and a base.
5) A production method according to 4) above, wherein a compound represented
by formula (I-b):

or a salt thereof is produced by reacting a compound represented by formula (II-b):

wherein X is a leaving group, or a salt thereof with a compound represented by formula (III-b):

wherein Ri and R2 are as defined above, in a solvent in the presence of a palladium compound, a phosphorus compound, cesium compound, and a base.
6) A production method according to 5) above, wherein the compound (Ill-b) is a
compound represented by formula (III-b-1), formula (III-b-2), formula (III-b-3) or
formula (III-b-4):
III-b-1 III-b-2: III-b-3: or III-b-4:


7) A production method according to any one of 1) to 6) above, wherein X is a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group.
In one aspect, the present invention provides a method for producing a 1,2-dihydropyridine-2-one compound of formula (I,I-a,I-b) comprises reacting a compound of formula (II,II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound, and a base.
In one aspect, the present invention provides a method for producing a 1,2-dihydropyridine-2-one compound of formula (I, I-a, I-b) comprises reacting a compound of formula (II,II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound , cesium compound, and a base.
In one aspect, the present invention provides a method for producing a 1,2-dihydropyridine-2-one compound of formula (I, I-a, I-b) comprises reacting a compound of formula (II, Il-a, Il-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3; III-b-4) in the presence of a palladium acetate, triphenyl phosphine, cesium fluoride, and potassium carbonate.
In one aspect, the present invention provides a method for producing a perampanel comprising:
a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),

e) optionally adding forth solvent to step (d).
f) isolating perampanel.
In one aspect, the present invention provides a method for producing an anhydrous Perampanel comprising:
a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),
e) optionally adding forth solvent to step (d).
f) isolating anhydrous perampanel.
In one aspect, the present invention provides to a method for producing a perampanel hydrate comprising:
a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),
e) optionally adding forth solvent to step (d),
f) isolating perampanel hydrate.
In one aspect, a method for producing a perampanel, anhydrous perampanel, perampanel hydrate, step d) or step e) is not optional.
In one aspect, a method for producing a perampanel, anhydrous perampanel, perampanel hydrate, a solvent in step a) or step b) is same or different.
In one aspect, a method for producing a perampanel, anhydrous perampanel, perampanel hydrate, step a) is washed with a solution.
DESCRIPTION OF THE EMBODIMENTS

The term "6- to 14-membered aromatic hydrocarbon ring group" means an aromatic hydrocarbon ring group comprising 6 to 14 carbon atoms and also includes fused-ring groups such as monocyclic groups, bicyclic groups, tricyclic groups, etc. Specific examples of said group are phenyl group, indenyl group, 1-naphthyl group, 2-naphthyl group, azulenyl group, heptalenyl group, biphenyl group, indacenyl group, acenaphthyl group, fluorenyl group, phenalenyl group, phenanthrenyl group, anthracenyl group, etc.
The term "5- to 14-membered heteroaromatic ring group" means a monocyclic, bicyclic or tricyclic 5- to 14-membered heteroaromatic ring group containing one or more heteroatoms selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom. Specific examples of said group are 1) nitrogen-containing heteroaromatic ring groups such as pyrrolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, triazolyl group, tetrazolyl group, benzotriazolyl group, pyrazolyl group, imidazolyl group, benzimidazolyl group, indolyl group, isoindolyl group, indolizinyl group, purinyl group, indazolyl group, quinolyl group, isoquinolyl group, quinolizinyl group, phthalazyl group, naphthyridinyl group, quinoxalyl group, quinazolinyl group, cinnolinyl group, pteridinyl group, imidazotriazinyl group, pyrazinopyridazinyl group, acridinyl group, phenanthridinyl group, carbazolyl group, carbazolinyl group, perimidinyl group, phenanthrolinyl group, phenazinyl group, imidazopyridinyl group, imidazopyrimidinyl group, pyrazolopyridinyl group, etc., 2) sulfur-containing heteroaromatic ring groups such as thienyl group, benzothienyl group, etc., 3) oxygen-containing heteroaromatic ring groups such as furyl group, pyranyl group, cyclopentapyranyl group, benzofuryl group, isobenzofuryl group, etc., and 4) heteroaromatic ring groups containing two or more heteroatoms of different kinds, such as thiazolyl group, isothiazolyl group, benzothiazolyl group, benzthiadiazolyl group, phenothiazinyl group, isoxazolyl group, furazanyl group, phenoxazinyl group, oxazolyl group, isoxazolyl group, benzoxazolyl group, oxadiazolyl group, pyrazoloxazolyl group, imidazothiazolyl group, thienofuranyl group, furopyrrolyl group, pyridoxazinyl group, etc.

Each of A1, A2, A3 and A4 is a hydrogen atom, an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered heteroaromatic ring group. More preferably, each of A2 and A4 is a hydrogen atom and each of Ai and A3 is an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered heteroaromatic ring group. Most preferably, each of A1 and A3 is, for example, an optionally substituted phenyl, pyridyl, pyrimidinyl, thienyl or furyl group.
A5 is an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered heteroaromatic ring group. A5 is more preferably, for example, an optionally substituted phenyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, thiazolyl, furyl, naphthyl, quinolyl, isoquinolyl, indolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, imidazopyridyl or pyrrolidinyl group. A5 is most preferably, for example, an optionally substituted phenyl, pyridyl, pyrimidinyl, thienyl or furyl group.
When the group represented by any of A1, A2, A3, A4 and A5 in the above formula is an optionally substituted 6- to 14-membered aromatic hydrocarbon ring group or an optionally substituted 5- to 14-membered hetero aromatic ring group, it may have one to four substituents which may be the same or different and are selected from the following substituents.
In the above formula, the ring A is an optionally substituted 2-pyridyl group and each of the ring B and the ring C is an optionally substituted phenyl group. The ring A, ring B and ring C may also have one to four substituents which may be the same or different and are selected from the following substituents.
The substituents include, for example, hydroxyl group, nitrile groups, halogen atoms, C1-6 alkyl groups, C2-6 alkenyl groups, C2-6 alkynyl groups, C3-8 cycloalkyl groups, C1-6 alkoxy groups, C1-6 alkyithio groups, C1-6 alkoxycarbonyl groups, C1-6

alkanoyl groups (C1-6 alkylcarbonyl groups), C1-6 alkylsulfonyl groups, amino group optionally substituted by a C1-6 alkyl group, amino group optionally substituted by a formyl group, amino group optionally substituted by a C1-6 alkanoyl group, amino group optionally substituted by a C1-6 alkylsulfonyl group, carbamoyl group optionally substituted by one or two C1-6 alkyl groups, and C1-6 alkoxyimino groups. Of these, the nitrile groups and halogen atoms are preferable. The term "halogen atoms" means a fluorine atom, chlorine atom, bromine atom, iodine atom and the like. The halogen atoms are preferably a chlorine atom and a bromine atom.
The term "C1-6 alkyl groups" means alkyl groups of 1 to 6 carbon atoms. Preferable examples of these groups are linear or branched alkyl groups such as methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, tert-butyl group, n-pentyl group, i-pentyl group, neopentyl group, n-hexyl group, 1-methylpropyl group, 1,2-dimethylpropyl group, 2-ethylpropyl group, 1-methyl-2-ethylpropyl group, l-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 2-ethylbutyl group, 1,3-dimethylbutyl group, 2-methylpentyl group, 3-methylpentyl group, etc.
The term "C2-6 alkenyl groups" means alkenyl groups of 2 to 6 carbon atoms. Preferable examples of these groups are linear or branched alkenyl groups such as vinyl group, allyl group, 1-propenyl group, isopropenyl group, 1-buten-l-yl group, l-buten-2-yl group, l-buten-3-yl group, 2-buten-l-yl group, 2-buten-2-yl group, etc.
The term "C2-6 alkynyl groups" means alkynyl groups of 2 to 6 carbon atoms. Preferable examples of these groups are linear or branched alkynyl groups such as ethynyl group, 1 -propynyl group, 2-propynyl group, butynyl group, pentynyl group, hexynyl group, etc.

The term "C3-8 cycloalkyl groups" means cyclic alkyl groups of 3 to 8 carbon atoms. Preferable examples of these groups are cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, etc.
The term "C1-6 alkoxy groups" means groups formed by the replacement of a hydrogen atom of an alkyl group of 1 to 6 carbon atoms by an oxygen atom. Preferable examples of said groups are methoxy group, ethoxy group, n-propoxy group, i-propoxy group, sec-propoxy group, n-butoxy group, i-butoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, i-pentyloxy group, sec-pentyloxy group, tert-pentyloxy group, n-hexyloxy group, i-hexyloxy group, 1,2-dimethylpropoxy group, 2-ethylpropoxy group, l-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy group, 1,1,2-trimethylpropoxy group, 1,1-dimethylbutoxy group, 2,2-dimethylbutoxy group, 2-ethylbutoxy group, 1,3-dimethylbutoxy group, 2-methylpentyloxy group, 3-methylpentyloxy group, hexyloxy group, etc.
The term "C1-6 alkylthio groups" means groups formed by the replacement of a hydrogen atom of an alkyl group of 1 to 6 carbon atoms by a sulfur atom. Preferable examples of said groups are methylthio group, ethylthio group, n-propylthio group, i-propylthio group, n-butylthio group, i-butylthio group, tert-butylthio group, n-pentylthio group, i-pentylthio group, neopentylthio group, n-hexylthio group, 1-methylpropylthio group, etc.
The term "Cl-6 alkoxycarbonyl groups" means groups formed by bonding of a carbonyl group to any of the above-exemplified alkoxy groups. Preferable examples of said groups are methoxycarbonyl group, ethoxycarbonyl group, etc. The term "Cl-6 alkanoyl groups (Cl-6 alkylcarbonyl groups)" means groups formed by the replacement of a hydrogen atom of an alkyl group of 1 to 6 carbon atoms by a carbonyl group. Preferable examples of said groups are acetyl group, propionyl group, butyryl group, etc.

The term "C1-6 alkylsulfonyl groups" means groups formed by the replacement of a hydrogen atom of an alkyl group of 1 to 6 carbon atoms by a sulfonyl group. Preferable examples of said groups are methanesulfonyl group, ethanesulfonyl group, etc.
The term "amino group optionally substituted by a C1-6 alkyl group" means an amino group that may have an alkyl group of 1 to 6 carbon atoms bonded thereto. Preferable examples of such an amino group are amino group, methylamino group, ethylamino group, propylamino group, etc.
"Amino group optionally substituted by a formyl group" includes, for example, amino group, formylamino group, etc.
The term "amino group optionally substituted by a C1-6 alkanoyl group" means an amino group that may have an alkanoyl group of 1 to 6 carbon atoms bonded thereto. Preferable examples of such an amino group are acetylamino group, propionylamino group, butyrylamino group, etc.
The term "amino group optionally substituted by a C1-6 alkylsulfonyl group"
means an amino group that may have an alkylsulfonyl group of 1 to 6 carbon atoms
bonded thereto. Preferable examples of such an amino group are amino group,
methanesulfonylamino group, ethanesulfonylamino group, n-
propanesulfonylamino group, n-butanesulfonylamino group, N-methylmethanesulfonylamino group, etc.
The term "carbamoyl group optionally substituted by one or two CI-6 alkyl groups" means a carbamoyl group one or two hydrogen atoms of which may be replaced by one or two, respectively, C1-6 alkyl groups. Preferable examples of said groups are N-methylcarbamoyl group, N,N-dimethylcarbamoyl group, N-ethylcarbamoyl group, N,N-diethylcarbamoyl group, etc.

The term "C1-6 alkoxyimino groups" means groups formed by the replacement of a hydrogen atom of an imino group by a C1-6 alkoxy group. Preferable examples of said groups are methoxyimino group, ethoxyimino group, etc.
The passage "X is a leaving group" means that X is a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group.
The passage "X is a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group" means that X is a halogen atom such as fluorine atom, chlorine atom, bromine atom or iodine atom; an alkylsulfonyloxy group such as trifluoromethanesulfonyloxy group; or an arylsulfonyloxy group such as phenylsulfonyloxy group. X is preferably a halogen atom such as chlorine atom or bromine atom, or an alkylsulfonyloxy group such as trifluoromethanesulfonyloxy group.
The sentence "Rl and R2 are as follows: 1) each of Rl and R2, which may be the same or different, is a hydrogen atom or a C1-6 alkyl group, and 2) the compound (III) may form boroxine (a trimer) when both Rl and R2 are hydrogen atoms, or 3) Rl, R2, the oxygen atoms and the boron atom, when taken together, form a 5- or 6-membered ring group optionally substituted by one to four C1-6 alkyl groups" in the case of the compound (III) means that the compound (III) is, for example, a phenylboronic acid derivative in which the hydrogen atom of the hydroxyl group may be replaced by a C1-6 alkyl group; a 2-phenyl-[l,3,2]-dioxoboronate the ring-forming methylene groups of which may be substituted by one to four Cl-6 alkyl groups; or a 2-phenyl-[l,3,2]-dioxoboronate derivative the ring-forming methylene groups of which may be substituted by one to four C1-6 alkyl groups.In particular, the passage "the compound (III) may form boroxine (a trimer) when both Rl and R2 are hydrogen atoms" means that when both Rl and R2 are hydrogen atoms, the compound (III) may be a monomer or may form a cluster such as a dimer or boroxine (a trimer).

A palladium compound, a copper compound and a phosphorus compound" may be a combination of a palladium compound selected from the palladium compounds described hereinafter, a copper compound selected from the copper compounds described hereinafter, and a phosphorus compound selected from the phosphorus compounds described hereinafter.
The compound (Il-a) is included in the compound represented by formula (II) and corresponds to a compound of formula (II) in which A1 is an optionally substituted phenyl group, each of A2 and A4 is a hydrogen atom, and A3 is an optionally substituted 2-pyridyl group.
The compound (II-b) is included in the compound represented by formula (Il-a) and corresponds to a compound of formula (Il-a) in which Ai is a phenyl group, each of A2 and A4 is a hydrogen atom, and A3 is a 2-pyridyl group.
The compound (III-a) is included in the compound represented by formula (III) and corresponds to a compound of formula (III) in which A5 is an optionally substituted phenyl group.
The compound (III-b) is included in the compound represented by formula (Ill-a) and corresponds to a compound of formula (Ill-a) in which A5 is a 2-cyanophenyl group.
The compounds (III-b-1), (III-b-2), (III-b-3) and (III-b-4) are included in the compound represented by formula (III-b). Each of the compounds (III-b-1), (III-b-2) and (III-b-3) corresponds to a compound of formula (Ill-b) in which Rl, R2, the oxygen atoms and the boron atom are taken together to form a 5- or 6-membered ring group optionally substituted by one to four C1-6 alkyl groups. The compound (III-b-4) corresponds to boroxine (a trimer) formed by a compound of formula (III-b) in which both Rl and R2 are hydrogen atoms.

The compound (I-a) is included in the compound represented by formula (I) and corresponds to a compound of formula (I) in which each of Ai and As is an optionally substituted phenyl group, each of A2 and A4 is a hydrogen atom, and A3 is an optionally substituted 2-pyridyl group.
The compound (I-b) is included in the compound represented by formula (I-a) and corresponds to a compound of formula (I-a) in which the ring A is a 2-pyridyl group, the ring B is a phenyl group and the ring C is a 2-cyanophenyl group.
In one aspect, the present invention relates to a method for producing a 1,2-dihydropyridine-2-one compound of formula (I,I-a,I-b) comprises reacting a compound of formula (II,II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound ,and a base.
In one aspect, the present invention relates to a method for producing a 1,2-dihydropyridine-2-one compound of formula (I,Ia,I-b) comprises reacting a compound of formula (II,II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound , a cesium compound and a base.
In one aspect, the present invention relates to a method for producing a 1,2-dihydropyridine-2-one compound of formula (I,I-a,I-b) comprises reacting a compound of formula (II,II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium acetate , triphenyl phosphine,potassium carbonate and cesium fluoride.
This reaction may be carried out also in a stream or atmosphere of an inert gas such as nitrogen, argon or the like.

The reaction is preferably carried out in a solvent. The solvent for reaction used is not particularly limited so long as it dissolves the starting materials to a certain degree and does not inhibit the reaction. As the solvent, there can be used, for example, organic solvents including ether solvents (e.g. tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether and dioxane), aromatic hydrocarbon solvents (e.g. benzene, toluene and xylene), amide solvents (e.g. N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone), dimethyl sulfoxide, etc.; and mixtures of any of these organic solvents and water. The solvent is, for example, 1,2-dimethoxyethane.
In general, the palladium may be formed in-situ by using palladium precursors and a necessary ligand or may be introduced as palladium catalyst.
A "palladium compound" may be for example,
tetrakis(triphenylphosphine)palladium, . tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, tetrakis(tri-tert-butylphosphine)palladium, palladium acetate, dichlorobis(triphenylphosphine)palladium, dichlorobis(tri-o-tolylphosphine)palladium, dichlorobis(tricyclohexylphosphine)palladium, 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium, palladium chloride, palladium hydroxide, palladium nitrate, di-.mu.-chlorobis(.eta.-allyl)palladium, bis(acetylacetonato)palladium,dichlorobis(benzonitrile)palladium,dichlorobis(acet onitrile)palladium or the like. The palladium compound is suitably palladium acetate, palladium chloride, palladium hydroxide or the like.
A "phosphorus compound" may be, for example, triphenylphosphine, tri(2-
methylphenyl)phosphine,bis(diphenylphosphino)methane,bis(diphenylphosphino)
ethane,bis(diphenylphosphino)propane,bis(diphenylphosphino)butane,bis(dipheny
lphosphino)pentane, bis(diphenylphosphino)hexane, 2,2'-bis(diphenylphosphino)-
1,1 '-binaphthyl,tri-tert-butylphosphine,tri(4 methylphenyl) phosphine,
tricyclohexylphosphine,2-(di-tert-butylphosphino)biphenyl,2(dicyclohexylphos phino)biphenyl, l,l'-bis(diphenyl-phosphino)ferrocene and the like.

The phosphorus compound is suitably, for example, triphenylphosphine, tri-tert-
butylphosphine or tri(4-methylphenyl)phosphine,more suitably
triphenylphosphine.
A "base" may be an inorganic base such as sodium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, potassium phosphate, cesium fluoride, potassium fluoride and the like or mixture thereof ; an alkali metal alkoxide such as sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide and the like; or an organic amine such as N-methylmorpholine, N,N-dimethylaniline, DBU, triethylamine and the like or mixture thereof. The base is suitably, for example, sodium carbonate, potassium carbonate, cesium fluoride, cesium carbonate, sodium hydrogencarbonate or potassium hydrogencarbonate, more suitably cesium fluoride and/or potassium carbonate or mixture thereof.
A "cesium compound "includes cesium fluoride, cesium carbonate.
The reaction temperature is usually varied depending on the starting materials, the solvent and other reagents used in the reaction and is suitably 100 °C.to 50°C. (the internal temperature of a reactor), more suitably 90°C.to 60°C. (the internal temperature of the reactor). The reaction time is usually varied depending on the starting materials, the solvent, other reagents used in the reaction and the reaction temperature. It is suitable to conduct stirring for 1 to 10 hours, more suitably about 4 hours, in the above reaction temperature range after the addition of the reagents.
The compound (II) may be used in an amount of 1 to 10 moles, suitably 1 to 3 moles, more suitably 1.5 moles, per mole of the compound (I).
The above-mentioned palladium compound may be used in an amount of 0.001 to 0.1 mole, suitably 0.01 to 0.05 moles, more suitably 0.02 mole, per mole of the compound (I). The above-mentioned copper compound may be used in an amount

of 0.001 to 0.2 mole, suitably 0.01 to 0.1 mole, more suitably 0.05 moles, per mole of the compound (I). The above-mentioned phosphorus compound may be used in an amount of 0.001 to 0.4 mole, suitably 0.01 to 0.2 mole, more suitably 0.05 to 0.1 mole, per mole of the compound (I). The above-mentioned base may be used in an amount of 1 to 10 moles, suitably 1 to 5 moles, more suitably 1.5 moles, per mole of the compound (I).
Perampanel may be crystalline, amorphus, anhydrate, hydrate, solvates, and cocrystals thereof.
In one aspect, the present invention relates to a method of producing perampanel comprising
a) providing a solution of perampanel in a first solvent
b) removing the first solvent completely or partially,
c) adding the second solvent in steb (b),
d) optionally adding third solvent to step (c).
e) optionally adding forth solvent to step (d).
f) isolating perampanel.
In one aspect, the present invention relates to a method of producing anhydrous perampanel comprising
a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding the second solvent in steb (b),
d) optionally adding third solvent to step (c).
e) optionally adding forth solvent to step (d).
f) isolating anhydrous perampanel.
In one aspect, the present invention relates to a method of producing perampanel
hydrates comprising
a) providing a solution of perampanel in a first solvent

b) removing the first solvent completely or partially,
c) adding the second solvent in steb (b),
d) optionally adding third solvent to step (c),
e) optionally adding forth solvent to step (d),
f) isolating perampanel hydrate.
In another embodiment, the first, second, third and forth solvents include any solvents but are not limited methanol, ethanol, n-propanol,isopropanol, butanol acetone, methyl isopropyl ketone,methyl isobutyl ketone diethyl ether, ditert butyl ether tetrahydrofuran, dioxane methyl acetate, ethyl acetate toluene, heptane, hexane, cyclohexane chloroform, methylene chloride, ethylene di chloride, acetonitrile, dimethyl formamide, dimethoxy ethanol; water or mixture thereof.
Perampanel from any source or as synthesized by the process of the present invention or may be obtained by any of the methods known in the literature or obtaining an existing solution from a previous processing step or dissolved in first solvent as mentioned hereinabove or to be used as starting material for the preparation of perampanel of the present invention may be obtained as a solution directly from a reaction in which it is formed and used as such or without isolation. First solvent includes metheyhlene chloride, dimethoxy ethanol, methanol, n-propanol, and water or mixture therof.
In one embodiment, the perampanel is dissolved or obtained in the first solvent at a temperature of about 5°C to the reflux temperature of the solvent used, and more specifically at the room temperature or reflux temperature of the solvent used.
In one embodiment, the step a) can be washed with a solvent. The solvent may be as mentioned herein above or the first solvent as mentioned above or mixture of solvent with water, aqueous ammonia solution, sodium chloride solution. The washing can be carried out at 20 °C to 40 °C,preferably 20 °C to 30 °C.

The solvent can be removed partially or completely by using any techniques such as decantation, filtration by gravity or suction, centrifugation, or the solvent can be evaporated from the mass to obtain the desired product, and optionally the solid can be washed with a solvent. The solvent may be as mentioned herein above or the first solvent as mentioned above or mixture of solvent with water.
After partial or complete removal of solvent, second solvent may be added to step b) at a temperature of about 5 °C to the reflux temperature of the solvent used, and more specifically at the room temperature or reflux temperature of the solvent used. Second solvent includes metheylene chloride, dimethoxy ethanol, methanol, ethyl aceate,n-propanol,acetone,water or mixture therof.
In an embodiment of the process, the first solvent and the second solvent is same or different.
Third solvent may be added to step c). Third solvent may be added to step c at a temperature of about 5°C to the reflux temperature of the solvent used, and more specifically at the room temperature or reflux temperature of the solvent used. Third solvent includes metheylene chloride, dimethoxy ethanol, methanol, ethylaceate, n-propanol, acetone, and water or mixture therof.
Fourth solvent may be added to step c. Forth solvent may be added to step c at a temperature of about 5 °C to the reflux temperature of the solvent used, and more specifically at the room temperature or reflux temperature of the solvent used. Fourth solvent includes metheylene chloride, dimethoxy ethanol, methanol, ethyl aceate, n-propanol, acetone, water or mixture therof.
In one embodiment, a solvent used in step d) or step e) is optional.
In one embodiment, a solvent used in step d) or step e) is not optional.

The perampanel can be isolated by using any techniques such as decantation, filtration by gravity or suction, centrifugation, or the solvent can be evaporated from the mass to obtain the desired product, and optionally the solid can be washed with a solvent. In embodiments, Perampanel can be isolated by evaporating solvents or filtration.
In embodiments, Perampanel after isolation can be dried at suitable temperature, and atmospheric or reduced pressure, for about 1-50 hours, or longer, using any types of drying equipment, such as a tray dryer, vacuum oven, air oven, fluidized bed dryer, spin flash dryer, flash dryer, and the like. Drying temperatures and times will be sufficient to achieve desired product purity. The temperature may be 30°C to 70 °C, preferably 40°C to 60 °C.
Perampanel prepared by the process may be crystalline, amorphus, anhydrate, hydrate, solvates, and co crystals thereof.
TPL process for the preparation of Perampanel reduce time cycle and reduces the cost for overall preparation of Perampanel.
The present invention is further illustrated by the following examples which is provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modification and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
EXAMPLES:
Example-l: Preparation of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-
dihydro pyridin-2-one
100 gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-one, 119 gm of 2-(2-cyanophenyl ) -l,3,2-dioxaborolan,60.8 gm of potassium carbonate,6.6 gm of triphenyl phosphine,2.4 gm of cesium fluoride, 1.41 gm of palladium acetate and 1400 ml of 1,2-dimethoxy ethane were charged into flask under nitrogen

atmosphere. The reaction mass was heated up to reflux temperature and maintained for 3-4 hours, There after ,1500 ml of 1,2-dimethoxy ethane was added to the reaction mixture at 45±5°C and the resulting mixture was filtered and precipitate was washed with 600 ml of 1,2-dimethoxy ethane. Filtrate ml charged in round bottam flask and slowly charged 2.5 % ammonia solution (2500 ml) over 60-70 minutes below 40°C. Stirred the mass at 35±5°C for 20-30 minutes and cool the mass at 15±3°C and stirred for 1 hour. The reaction mixture was filtered under reduced pressure and precipitate was washed with 1:1 mixture of water and 1, 2-dimethoxy ethane (400 ml) after suck dry, collect wet cake in ethyl acetate (1200 ml) at 40-45°C and cooled at 15±3°C and stirred for 1 hour and filter the precipitate under reduced pressure and was washed with ethyl acetate and suck dry to obtain 3-(2-cyanophenyl)-5-(2-pyridyi)-l-phenyl-l, 2-dihydropyridin-2-one and dried (Dry weight: 85 gm) (Purity by HPLC: 99.79%).
Example-2: Preparation of 3-(2-cyanophenyI)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one
l0gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-one, 12gm of 2-(l,3,2-dioxaborolan-2-yl) benzonitrile, 9.5gm of cesium fluoride 0.14 gm of palladium acetate, 0.66gm of triphenylphosphine in 140 ml of 1, dimethoxymethane were charged at 25±3°C under nitrogen atmosphere, the mass was heated to reflux temperature in 30-35 minutes at reflux temperature (84±2°C) for 6 hours. After completion of reaction, the mass was cooled to 45-50°C and charged 60ml of 1,2-dimethoxyethane, stirred it for 30 minutes at 40-45°C, the salt was filtered and washed with 10 ml of 1,2-dimethoxyethane at 40-45 °C, filtrate ml collected in round bottam flask and dilute ammonia solution (125 ml) (Water-100 ml + Con. ammonia 25 ml) was added slowly at below 40°C in 60-75 minutes. The mass was stirred for 20-30 minutes at 35±5°C and the mass cooled to 20-25°C for 1 hour at 20-25°C, the product was filtered and washed with mixture of water(20 ml)+l,2-dimethoxy ethane(20ml) at 20-25 °C and wet cake was collected and charged in round bottom flask with 120 ml of ethyl acetate. The mass was heated it up to 40-45°C and maintained for 15-20 minutes at 40-45°C. The mass was cooled to 15-

20°C and maintained 1 hour at 15-20 °C. the solid was filtered and washed with pre cooled ethyl acetate(20 ml), wet cake(23 gm) dried at 50°C in air tray dryer for 6-8 hours. Dry weight (4.0 gm), (Purity by HPLC; 96.87%)
Example-3: Preparation of 3-(2-Cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one
50 gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-one, 59.4 gm of 2-(2-cyanophenyl)-l,3,2-dioxaborolan,30.4 gm of potassium carbonate,3.3 gm of triphenyl phosphine, 1.2 gm of cesium fluoride,0.705 gm of palladium acetate and 1400 ml of 1,2-dimethoxy ethane were charged into flask under nitrogen atmosphere. The reaction mass was heated up to reflux temperature and maintained for 3-4 hours, After the reaction was completed, cool the reaction mass at 30-35°C and added 250 ml of methylene chloride and filter the solid and wash with 150 ml of methylene chloride, collected the filtrate ml and distilled out solvent under reduced pressure to get solid residue, which was isolate after addition 600 ml of water and 250 ml of Ethyl acetate at 45±3°C for 15-20 minutes. The mass was cooled after at 20°C and stir for 1 hour, the solid mass was filtered under reduced pressure and precipitate was washed with 150 ml of ethyl acetate to obtain crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-1, 2-dihydropyridin-2-one as a wet cake, dried the material in air tray dryer at 60°C for 8-10 hours (Dry weight -43.5 gm).
Example-4: Preparation of 3-(2-Cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one
50 gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-one, 59.4 gm of 2-(2-cyanophenyl)-l,3,2-dioxaborolan,30.4 gm of potassium carbonate,3.3 gm of triphenyl phosphine, 1.2 gm of cesium fluoride,0.705 gm of palladium acetate and 1400 ml of toluene were charged into flask under nitrogen atmosphere. The reaction mass was heated up to reflux temperature and maintained for 3-4 hours, After completed the reaction, cool the reaction mass at 30-35°C and added 250 ml of methylene chloride and filter the solid and wash with 150 ml of methylene chloride

collected filtrate ml and distilled out solvent under reduced pressure to get solid residue, which was isolate after addition 500 ml of water and 100 ml of ammonia solution and cool the mass after at 20°C and stir for 1 hour The solid mass was filtered under reduced pressure and precipitate was washed with 200 ml of water and collected solid material was heated in 600 ml of ethyl acetate at 50±3°C for 15-20 minutes and cooled the mass at 20°C. Then,l hour stirred the mass at 20±3°C, filter the precipitate and wash with 150 ml of ethyl acetate to obtain crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-1, 2-dihydropyridin-2-one as a wet cake, dried the material in Air tray dryer at 60°C for 8-10 hours (Dry weight -43.5 gm).
Example-5: Preparation of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one
20 gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-One, 23.77 gm of 2-(2-cyanophenyl)-l,3,2-dioxaborolan, 12.16 gm of potassium carbonate, 1.32 gm of triphenyl phosphine, 0.48 gm of cesium fluoride, 0.28 gm of palladium acetate and 280 ml of toluene were charged into flask under nitrogen atmosphere. The reaction mass was heated up to reflux temperature and maintained for 3-4 hours, There after 300 ml of toluene was added to the reaction mixture at 55±5°C and the resulting mixture was filtered and precipitate was washed with 100 ml of 1,2-dimethoxy ethane. Filtrate was distilled under vacuum and 100ml of methanol and 20ml ammonia were charged in round bottam flask and reaction mass was heated up to 45-50°C, Stir the mass at 45±5°C for 20-30 minutes and cool the mass at 20±3°C and stirred for 30minute. Solid was filtered under reduced pressure and washed with mixture of methanol (30ml) : water (60ml) after suck dry, collect wet cake in ethyl acetate (200 ml) at 40-45°C and cooled at 15±3°C and stirred for 1 hour and filter the precipitate under reduced pressure and was washed with ethyl acetate and suck dry to obtained 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-1, 2-dihydropyridin-2-one as a wet cake (Dry weight-17.2 gm) Purity by HPLC: 99.80%.
Example-6: Preparation of 3-(2-cyanophenyI)-5-(2-pyridyl)-l-phenyI-l, 2-dihydro pyridin-2-one hydrate crystal.

285 gm of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one and 2565 ml of methylene chloride were charged into the flask and stir, washed the organic later with 1140 ml of water, back washed of aqueous layer with 285 ml of methylene chloride and combined organic layer treated with 14.25 gm of activated charcoal and filter through hyflo® and wash 285 ml of methylene chloride. Filtrate ml distilled out under reduced pressure and stripped with 855 ml of acetone to get solid residue, which was dissolved in 6555 ml of acetone at reflux temperature, After 3135 ml of water addition at 50-55°C, solid was precipitated, the contents were cooled to 20-25 °C and filter the contents to isolate the solid, under reduced pressure and wash with cooled 400 ml of 50% acetone-water and suck dried to obtain crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one hydrate (Perampanel hydrate ) as a wet cake, dried the material in air tray dryer at 60°C for 8-10 hours.Dry weight of Perampanel hydrates 255 gm (water by KF: 3.92% w/w, Purity by HPLC: 99.94%).
ExampIe-7: Preparation of 3-(2-Cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one hydrate crystal
35 gm of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one and 315 ml of methylene chloride were charged into the flask at 27±3°C and stir, washed the organic layer with 140 ml of water, organic layer treated with 1.75 gm of activated charcoal and filter through hyflo® and wash 35 ml of methylene chloride. Filtrate ml distilled out under reduced pressure and stripped with 105 ml of acetone to get solid residue, which was dissolve in 875 ml of acetone at 52±3°C, After 420 ml of water addition at 52±3°C, gradually cool the mass at 20±3°C and stirred for 1 hour. Filter the precipitate under reduced pressure and wash with cooled 140 ml of 50% acetone-water and suck dry to obtain crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-1, 2-dihydropyridin-2-one hydrate (Perampanel hydrate) as a wet cake, dried the material in air tray dryer at 60°C for 8-10 hours .Dry weight of Perampanel hydrate- 31.2 gm.HPLC purity -99.86%

Example-8: Preparation of 3-(2-cyanophenyI)-5-(2-pyridyI)-l-phenyI-l, 2-dihydropyridin-2-one hydrate crystal
35 gm of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one and 315 ml of methylene chloride were charged into the flask at 27±3°C and stir, washed the organic later with 140 ml of dilute ammonia solution, 140 ml of 10% sodium chloride solution and then washed with 140 ml of water, organic layer treated with 1.75 gm of activated charcoal and filter through hyflo® and wash 35 ml of methylene chloride. Filtrate ml distilled out under reduced pressure and stripped with 105 ml of acetone to get solid residue, which was dissolve in 875 ml of acetone at 52±3°C, After 455 ml of water addition at 52±3°C, gradually cool the mass a at 20±3°C and stirred for 1 hour. Filter the precipitate under reduced pressure and wash with cooled 140 ml of 50% acetone-water and suck dry to obtain crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l, 2-dihydropyridin-2-one hydrate (Perampanel hydrate ) as a wet cake, dried the material in air tray dryer at 60°C for 6-8 hours.Dry weight of Perampanel hydrate- 31.4 gm.HPLC purity -99.96%
Example-9: 3-(2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one hydrate crystal
50 gm of 3-bromo-5-(2-pyridyl)-l,2-dihydropyridin-2-One, 59.44 gm of 2-(2-cyanophenyl)-l,3,2-dioxaborolan, 30.40 gm of potassium carbonate, 3.3gm of triphenyl phosphine, 1.20 gm of Cesium fluoride, 0.705 gm of palladium acetate and 700 ml of 1,2-dimethoxy ethane were charged into flask under nitrogen atmosphere. The reaction mass was heated up to reflux temperature and maintained for 3-4 hours, Thereafter, 750 ml of 1,2-dimethoxy ethane was added to the reaction mixture at 45±5°C and the resulting mixture was filtered and precipitate was washed with 300 ml of 1,2-dimethoxy ethane. Filtrate ml charged in RBF and slowly charged 2.5 % ammonia solution (1250 ml) over 60-70 minutes below 40°C, Stir the mass at 35±5°C for 20-30 minutes and cool the mass at 17±3°C and stirred for 1 hour. The reaction mixture was filtered under reduced pressure and precipitate was washed with 1:1 mixture of water and 1,2-dimethoxy ethane (200 ml) after suck dry, collect wet cake in ethyl acetate (600 ml) at 45±2°C for 15 minutes and

cooled at 17±3°C and stirred for 1 hour and filter the precipitate under reduced pressure and was washed with ethyl acetate (150 ml) and suck dry to obtain 3-(2-cyanophenyl)-5-(2-pyridyl)-l -phenyl-1, 2-dihydropyridin-2-one (41 gm) as a hydrate form after drying at 60°C for 6-8 hours.HPLC purity-99.91%. Water content-3.86%.
Example-10: Preparation of Perampanel anhydrous from Perampanel hydrate
8.0 gm of Perampanel hydrate dissolve in 80 ml of methylene chloride at room temperature. The organic layer was washed with 30 ml of water and 4.0 gm of sodium sulphate treatment to the organic layer, distilled out methylene chloride under reduced pressure below 40°C and degas for 20-30 minutes, charge 80 ml of water at 40-45°C and stir 5-10 minutes, Charge 16 ml of methanol and 80 ml of water at same temperature. Cool the mass to room temperature and filter the mass after 30-40 minutes stirring at room temperature and wash with mixture of water (40 ml) + Methanol (4 ml) and suck dry to obtain 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1, 2-dihydropyridin-2-one (41 gm) as a Anhydrous Form after drying at 60°C for 6-8 hours. HPLC purity: 99.96%.Water content: 0.32%.
Example-11: Preparation of Perampanel hydrate
7.0 gm of perampanel was charged in 140 ml of 1,2-dimethoxy ethane and heated upto 55°C to dissolve the material, after 10-15 minutes stirred at clear solution, slowly add 140 ml of water at 55±3°C in 40-60 minutes to precipitate solid and stirred at 15-20 minutes at same temperature , cooled the mass at 20°C and stirred for 1 hour at 20±3°C, the solid was filter and washed with mixture of 14 ml of 1,2-dimethoxy ethane and 14 ml of water and suck dry to obtain perampanel hydrate after drying at 60°C for 6-8 hours. Water content: 3.4%.

We Claim:
1. A method for producing a 1,2-dihydropyridine-2-one compound of formula (I, I-a, I-b) comprises reacting a compound of formula (II, II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-1 ,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound, and a base.
2. A method for producing a 1,2-dihydropyridine-2-one compound of formula (I, I-a, I-b) comprises reacting a compound of formula (II, II-a,II-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3 III-b-4) in the presence of a palladium compound, a phosphorus compound, cesium compound and a base.
3. A method for producing a 1,2-dihydropyridine-2-one compound of formula (I, I-a, I-b) comprises reacting a compound of formula (II, Il-a, Il-b) with a boronic acid derivative of formula (III,III-a ,III-b ,III-b-l,III-b-2,III-b-3, III-b-4) in the presence of a palladium acetate, triphenyl phosphine, cesium fluoride, and potassium carbonate.
4. A method for producing a perampanel comprising:

a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),
e) optionally adding forth solvent to step (d).
f) isolating perampanel.
5. A method for producing an anhydrous Perampanel comprising:
a) providing a solution of perampanel in a first solvent,

b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),
e) optionally adding forth solvent to step (d).
f) isolating anhydrous perampanel.
6. A method for producing a perampanel hydrate comprising:
a) providing a solution of perampanel in a first solvent,
b) removing the first solvent completely or partially,
c) adding a second solvent to step (b),
d) optionally adding a third solvent to step (c),
e) optionally adding forth solvent to step (d),
f) isolating perampanel hydrate.
7. The method for producing a perampanel according to claim 4, 5, and 6,
wherein the solvent in step a) or step b) is same or different.