FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
A PROCESS FOR PREPARATION OF 4-AMINO-5-METHYL-1H-PYRIDINE-2-ONE.
2. APPLICANT:
(a) NAME: Aventus Labs LLP
(b) NATIONALITY: An Indian Company incorporated under the Indian Companies ACT 1956.
(c) ADDRESS: A-514, 1st floor, TTC Industrial Area, Mahape, Navi Mumbai, Maharashtra 400701, India.
3. PREAMBLE TO THE DESCRIPTION:
COMPLETE
The following specification particularly describes the invention and manner in which it is to be performed.

FIELD OF THE INVENTION:
The present invention relates to an improved, cost effective and greener process for preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I an intermediate of Finerenone.
BACKGROUND OF THE INVENTION:
Finerenone is a non-steroidal mineralocorticoid receptor antagonist with the chemical name (4S)-4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-l,4-dihydro-l,6-naphthyridine-3-carboxamide and is represented by formula-II.
Formula-II
Conventional processes for the preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I from Chloro-methyl-aminopyridine of formula-Ill under basic conditions in alcoholic solvents.

U.S. Patent No. 2022/0153699 (EP3935045) describes and discloses process for preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I by reacting Chloro-methyl-aminopyridine of formula-Ill with KOH in methanol in an autoclave at elevated temperature.
Formula-Ill Formula-I
Tetrahedron 55 (1999), Page No. 11985-11996 describes a similar type of reaction in sodium hydroxide in methanol. Unfortunately the reaction of Formula-Ill under these conditions afforded a mixture of Formula-I and the 2 - Methyl ether of formula-IV.
Formula-III Formula I Formula IV
Solvent purification is very difficult to achieve purity more than 99%, it requires multiple solvent purifications and / or column chromatography to remove 2-Methyl ether of formula-IV from a mixture of compounds. In purification, yield losses are ~20-30% and it is not viable at commercial scale batches.
In the Prior art process, reaction of formula-Ill is carried out with potassium hydroxide and methanol at temperature 160-200°C in the autoclave reactor.
In Prior art process observed the challenges in the reaction steps such use of volatile organic solvents at higher temperature 160-200°C and high pressure 22-25kg/cm conditions. Additionally the prior art process requires tedious workup procedure and isolation steps to get the desired quality and yield.
In summary, there are few preparation routes feasible currently, and the costs thereof are high. So the development of synthetic routes with simple, enviro-friendly greener process, mild reaction conditions and high purity are of very high importance. It can greatly improve

their preparation efficiency, reduce cost, decrease the pollution and improve the social and economic benefits.
OBJECTIVE OF THE INVENTION:
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
• It is an object of the present disclosure to improve one or more problems of the prior art or to at least provide a useful alternative.
• Another object of the present disclosure is to provide a simple process for preparing 4-Amino-5-methyl-1H-pyridine-2-one of formula-I.
• Still another object of the present disclosure is to provide a process for preparing 4-Amino-5 -methyl-1H-pyridine-2-one of formula-I with high purity.
• Yet another object of the present disclosure is to provide a process involving convenient operations and environment friendly with low production costs.
• Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide an improved, commercially viable process and environment friendly process for preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I.
Another aspect of the present invention is to provide an improved process for preparation of 4-amino-5-methyl-1H-pyridine-2-one of formula I comprising the step of:
a) Alkaline hydrolysis of Chloro-methyl-aminopyridine of formula-III by heating under
basic conditions at suitable temperature in aqueous media to obtain 4-Amino-5-
methyl-1H-pyridine-2-one of formula-I.

Another aspect of the present invention is to provide a process for preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I comprising the step of:
a) Alkaline hydrolysis of Chloro-methyl-aminopyridine of formula-Ill by heating under basic conditions at suitable temperature in aqueous media to obtain 4-Amino-5-methyl-1H-pyridine-2-one of formula-I.
b) Optionally purifying Methyl 4-amino-5-methyl-1H-pyridine-2-one of formula-I.

DETAILED DESCRIPTION OF THE INVENTION:
The starting material i.e. Chloro-methyl-aminopyridine of formula-Ill is prepared by the methods known in the art or such as those described in US7462612 using Iron powder in acetic acid at elevated temperature.
In one embodiment, the present invention provides a simple and commercially viable and greener process for preparing 4-Amino-5-methyl-1H-pyridine-2-one of fonnula-1 with very high purity and yield.
In another embodiment, the present invention provides an improved process for preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I comprising the steps of:
a) Alkaline hydrolysis of chloro-methyl-aminopyridine of formula-Ill by heating under basic conditions at suitable temperature in aqueous media to obtain 4-Amino-5-methyl-7i?-pyridine-2-one of formula-L
b) Optionally purifying 4-Amino-5-methyl-1H-pyridine-2-one of formula-L
The schematic representation of the process of the present invention is provided below:
The hydrolysis reaction is carried out in water in the range of 3 to 15 times/volume; preferably 4-8 times/volumes and preferably 5-6 times/volumes.
In the hydrolysis reaction, the mole ratio of potassium hydroxide is in the range of 4 to 8 mole ratio; preferably the mole ratio of potassium hydroxide is 6 to 7 and more preferably the mole ratio of potassium hydroxide is 6.4 to 6.8.
The hydrolysis reaction is carried out at temperature in the range of 165°C to 190°C; preferably 175-185°C and more preferably 178-182°C.

The obtained 4-Amino-5-methyl-1H-pyridine-2-one of formula-I is optionally purified in Polar aprotic solvents, alcoholic solvent or mixture of alcoholic and aqueous.
The examples of polar aprotic solvent can be selected from N, N-dimethylacetamide, N,N-dimethylformamide, Dimethyl sulfoxide etc.
The examples of an alcoholic solvent can be selected from aliphatic C1-C8 linear and branched such as Methanol, Ethanol, Isopropanol, Butanol, Isobutanol, Pentanol etc.
The examples of a mixture of aqueous solvent can be selected from aq. Methanol, aq. Ethanol, aq. Isopropanol, aq. Butanol, aq. Isobutanol, aq. Pentanol etc.
The examples of an alcoholic solvent can be selected from aliphatic C1-C8 linear and branched preferably Methanol, Ethanol, Isopropanol, Butanol, Isobutanol, Pentanol etc and most preferably Ethanol and Isopropanol.
The process of present invention provides 4-Amino-5-methyl-1H-pyridine-2-one of formula-I having purity in the range of 99.0% to 99.9%.
Thus, the process of the present invention provides 4-Amino-5-methyl-///-pyridine-2-one of formula-I with high purity without the need for a purification step.
The process of the present invention uses commonly available and inexpensive reagents and fluid media. Furthermore, the process of the present invention has convenient reaction conditions for operations, easy purification, and high purity and low production costs, this makes it commercially viable.
4-Amino-5-methyl-1H-pyridine-2-one of formula-I can be converted in to Finerenone of formula II and the process for the preparation thereof are described in WO 2008/104306 and ChemMedChem 2012, 7, 1385 and also in WO2016/016287 Al (Bayer Pharma AG).

EXAMPLES:
[0015] The following examples are presented to illustrate the working of the present invention with best mode, but are not limiting the scope of the individual embodiment presented.
Example-1: Preparation of 2-Chloro-5-methyl-4-aminopyridine of formula-Ill:
Charged water (50L), Iron powder (24.84Kg) in a reactor, added dropwise acetic acid (1.27Kg) at 25-30°C. Charged ethyl acetate (10L) and heat to 60-65°C. Slowly or lot wise added 2-Chloro-5-methyl-4-nitro pyridine-1-oxide (20Kg). Raised the temperature to 80-85°C and maintained till completion of reaction. After completion of reaction, cool the reaction to 25-30°C and adjust the pH to 6-7 by using caustic lye solution. Charged ethyl acetate (100L) and filtered the insoluble solid and washed with ethyl acetate (25L). Separated organic layer distilled up to stirrable volume, charged toluene (56L) and heated to 75-80°C for Ih. Cool the reaction to 0-5°C, filtered and washed with ethyl acetate (7L) and dried the solid at 45°C for 5-10 hrs to get 2-Chloro-5-methyl-4-aminopyridine of formula-Ill (12.3Kg, 0.62w/w). Yield 81.3% purity of product > 98% by HPLC.
Example-2: Laboratory process: Preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I.
Charged water (2.5L), 2-Chloro-5-methyl-4-aminopyridine of formula-Ill (0.5Kg) and
potassium hydroxide (3.12Kg) in the reactor. The reaction mixture was heated to
temperature 178-182°C and maintained till completion of reaction. pH adjusted to 7 using dil.
hydrochloric acid and distilled out the water under vacuum at temperature 50-55°C. Residue
azeotroped with ethanol (2L X 5) and evaporated up to dryness. Charged methanol (5L) in a
residue and stir at ambient temperature and filter the inorganic salt. The filtrate was distilled
up to dryness under vacuum.
The evaporated residue was purified from methanol followed by N,N-dimethyl acetamide and
dried at 50°C under vacuum to obtain 4-Amino-5 -methyl-///-pyridine-2-one of formula-I
(0.34 Kg, 0.68w/w).
Yield 78.2% with purity of product >99.5% by HPLC.

Example-3: Scale-up Process: Preparation of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I.
Charged water (135L), 2-Chloro-5-methyl-4-aminopyridine of formula-Ill (27Kg) and potassium hydroxide (84.34Kg) in the reactor. The reaction mixture was heated to temperature 178-182°C and maintained till completion of reaction. pH adjusted to 7 using dil. hydrochloric acid and distilled out the water under vacuum at temperature 50-55°C. Residue azeotroped with ethanol (100L X 5) and evaporated up to dryness. Charged methanol (270L) in a residue, stir and filter the inorganic salt. The filtrate was distilled up dryness under vacuum.
The evaporated residue was purified from methanol and dried at 50°C under vacuum to obtain 4-Amino-5-methyl-1H-pyridine-2-one of formula-I (18.9 Kg, 0.7w/w). Yield 80.46% with purity of product >99% by HPLC,

CLAIMS:
We claim,
Comprising reacting 2-Chloro-5-methyl-4-aminopyridine of formula-Ill.

1) Process for the preparation of 4-Amino-5 -methyl-1H-pyridine-2-one of formula-I

with base in presence of water.
2) According to claim 1, wherein the reaction is carried out in base such as potassium hydroxide, lithium hydroxide, Sodium hydroxide etc.
3) According to claim 1, wherein the reaction is carried out in water in the range of 3 to 15 times/volumes.
4) According to claim 3, wherein the reaction is carried out in water; preferably 5 to 6 times/volumes.
5) According to claim 1, mole ratio of potassium hydroxide is in the range of 4 to 8 mole ratio.
6) According to claim 5, preferably mole ratio of potassium hydroxide is in the range of6.4 to 6.8.
7) According to claim 1, reaction is carried out at temperature in the range of 165°C to 190°C.
8) According to claim 7, preferably reaction is carried out at temperature in the
rangeof l78°C to l82°C.
9) Process for the purification of 4-Amino-5-methyl-1H-pyridine-2-one of formula-I in polar aprotic solvents.
10) According to claim 9, polar aprotic solvent can be selected from N,N-dimethyl acetamide, N,N-dimethylformamide, Dimethyl sulfoxide etc.