DESC:FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules 2003
COMPLETE SPECIFICATION
(see sections 10 & rule 13)
1. TITLE OF THE INVENTION
“A METHOD FOR SYNTHESIZING DEFEROXAMINE AND/OR IT’S SALT”
2. APPLICANT (S)
NAME NATIONALITY ADDRESS
CLEARSYNTH LABS LIMITED
INDIAN 17th Floor, Lotus Nilkamal Business Park, New Link Road, Andheri [West], Mumbai 400053, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION

COMPLETE SPECIFICATION
The following specification particularly describes the invention and the manner in which it is to be performed

FIELD OF INVENTION
The present invention relates a method for synthesising Deferoxamine or its salt. Most particularly, it relates to method for synthesising Deferoxamine mesylate salt with improved yield and purity.

BACKGROUND OF INVENTION
Deferoxamine, also known as Desferal, has been approved for various indications over time, with the initial approval dating back to 1968. Deferoxamine is a naturally occurring compound produced by the bacterium Streptomyces pilosus. It is a small molecule with a high affinity for ferric iron (Fe3+). When deferoxamine binds to iron, it forms a stable complex that is then excreted from the body in the urine.
Deferoxamine mesylate is the salt form of deferoxamine. It is more soluble in water than deferoxamine, and this makes it easier to administer by injection. Deferoxamine mesylate is the most commonly used form of deferoxamine. Many preparation methods of deferoxamine involve such as condensation reactions between acetonylacetone and the chosen amine, often using a suitable catalyst. Different condensation reactions, such as Mannich reactions or Pictet-Spengler reactions, may be employed depending on the desired product.
Deferoxamine and its salt, deferoxamine mesylate, are vital drugs used to treat iron overload conditions like thalassemia and hemochromatosis. Several patents exist for their synthesis, each aiming to improve upon efficiency, purity, or cost-effectiveness. Here's a summary of key patent points:
US6858414B2focuses on purification of deferoxamine B which is produced by microbial fermentation. It uses adsorption chromatography to remove impurities followed by precipitation and recrystallization for high purity. This method is not economically feasible for industrial production due to chromatographic separation.
CN1433399Adiscloses purification of deferoxamine B from fermentation broth. It uses adsorption/desorption on a resin and direct precipitation to obtain the mesylate salt free of other polyhydroxamates and chloride ions.
US5374771A describes purification of deferoxamine B salts from fermentation liquors. It involves adsorption onto an ion exchange resin, elution, concentration, and salting out to obtain high-purity salts.
US20030059905A1 discloses conversion of deferoxamine B hydrochloride to the mesylate salt. It involves passing the solution through an anion exchange resin, adding methanesulfonic acid, and purifying the final product.
Synthesis methods of deferoxamine is associated with several problems. Said methods suffer from low overall yield, meaning significant material and cost are wasted, making production commercially less viable.Multi-step and complex processes (involve multiple complex steps, increasing the risk of errors and impurities, further impacting yield and purity); starting material availability (some methods rely on source or expensive starting materials, limiting production scalability and affordability); presence of byproducts (fermentation processes used to produce deferoxamine can generate undesired byproducts like other polyhydroxamates, contaminating the final product and requiring elaborate purification steps); difficulties in achieving stringent pharmaceutical purity standards can be challenging, especially for removing trace impurities; multi-step processes can generate significant waste, creating disposal challenges and environmental impact.
Therefore, there is a need to provide novel approaches for synthesising Deferoxamine or its mesylate salt to overcome these challenges.
Thus, the present invention provides a method for synthesizing deferoxamine or its salt with improved reaction route with fewer steps and higher yields are being developed, often using alternative starting materials or catalysts. Furthermore, it provides enhanced purification techniques i.e. novel purification strategies are employed to remove impurities more effectively and efficiently as well as adopting greener solvents and reagents to minimize environmental impact.
Overall, the focus of the present invention lies in developing more efficient, cost-effective, and environmentally friendly method for synthesizing deferoxamine and its mesylate salt, ultimately ensuring their wider availability and affordability for patients.

OBJECTS OF THE INVENTION
One of the objects of the present invention is to provide a method for synthesising Deferoxamine or Deferoxamine mesylate salt.
Another object of the present invention is to provide a method for synthesising Deferoxamine or its salt with improved yield and purity.
Another object of the present invention is to provide novel purification strategies that are employed to remove impurities more effectively and efficiently as well as adopting greener solvents and reagents to minimize environmental impact.
Another object of the present invention is to provide pharmaceutical compositions.
Another object of the present invention is to provide lab-scale synthesis or large-scale industrial production by using variations in specific reagents or catalysts.
Yet another object of the present invention is to provide a method for synthesising Deferoxamine or its mesylate salt with improved reaction route with fewer steps and higher yields.
Yet still another object of the present invention is to utilise appropriate solvents and catalysts that are essential for efficient reaction progress and product yield.

BRIEF DESCRIPTION OF DRAWING
Figure 1 shows HPLC purity of crude tert-butyl (3-acetyl-14,25-bis(benzyloxy)-10,13,21,24-tetraoxo-1-phenyl-2-oxa-3,9,14,20,25-pentaazatriacontan-30-yl)carbamate (compound 1).

SUMMARY OF THE INVENTION
Main aspect of the present invention provides a method for synthesising Deferoxamine or its salt, the method comprising:
i. contacting a compound of formula 1 with an acid in a solvent at 0oC to 40oC for period from about 2 hrs to about 10 hrs to obtain a compound of formula 2;

ii. treating the compound of formula 2 with an alkanesulfonic acid at a temperature ranging from about 10oC to about 40oC for period ranging from about 10hrs to 20 hrs in a solvent to obtain a compound of formula 3;

iii. hydrogenating the compound of formula 3 in presence of an agent under hydrogen (H2) pressure in a solvent at a temperature from about 20oC to about 50oC for period from about 30min to about 180min to obtain compound of formula 4.

Another aspect of the present invention provides a method for synthesising compound of formula 4, wherein the compound of formula 4 is Deferoxamine or its salt.

DETAILED DESCRIPTION OF THE INVENTION
For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art.
The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.
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 disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described.
Detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, specific functional and structural details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure.
In the specification different terms are used for describing the invention. The definitions of the terms are provided below.
The term ‘alkanesulfonic acid’ used herein refers to alkanesulfonic acids of formula R-SO3H, where R represents a saturated and linear or branched hydrocarbon chain comprising from 1 to 4 carbon atoms. The alkanesulfonic acids include such as but is not limited to methanesulfonic acid, ethanesulfonic acid, n-propanesulfonic acid, isopropanesulfonic acid, n-butanesulfonic acid, isobutanesulfonic acid, sec-butanesulfonic acid, tent-butanesulfonic acid and the mixtures of two or more of them in all proportions.
The term ‘solvent’ used herein refers to a substance that can dissolve another substance, or in which another substance is dissolved, forming a solution. The solvent used in the present invention can be polar or nonpolar solvent. The said solvent may be used in anhydrous form. The solvent may include deuterated form of above-mentioned solvent(s).
The term, ‘acid’ used herein refers to the acid that may use for deprotection of tert-butoxycarbonyl (BOC) protected compound 1 of the present invention. The acid may be used including such as but is not limited to conc. hydrochloric acid (HCl), or trifluoroacetic acid (TFA), or any known reagent used in the prior art.
The term, ‘agent’ used herein refers to any hydrogenating agent that are used to deprotect O-protected benzyl group. The hydrogenating agent may include such as but is not limited to typically iridium, nickel, palladium, platinum, rhodium, or ruthenium, with or without activated carbon.
One of the embodiments of the present invention provides a method for synthesis of Deferoxamine or its salt, the method comprising:
i. contacting a compound of formula 1 with an acid in a solvent at 0oC to 40oC for period from about 2 hrs to about 10 hrs to obtain a compound of formula 2;

ii. treating the compound of formula 2 with an alkanesulfonic acid at a temperature from about 10oC to about 40oC for time period from about 10hrs to 20 hrs in a solvent to obtain a compound of formula 3; and

iii. hydrogenating the compound of formula 3 in presence of an agent under hydrogen (H2) pressure in a solvent at a temperature from about 20oC to about 50oC for period from about 30min to about 180 min to obtain compound of formula 4;
wherein the compound of formula 4 is deferoxamine or its salt.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein acid including such as but is not limited to p-Toluenesulfonic Acid,ZnBr2, trifluoroacetic acid (TFA), HCl, H2SO4, aqueous phosphoric acid, or Lewis acids such as BF3·OEt2, TMSI, TMSOTf, TiCl4, SnCl4, AlCl3, Sn(OTf)2 and K3PO4·H2Oetc.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein solvent used may be polar and/or non-polar solvent.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein solvent include such as but is not limited to water, ketone solvent such as acetone, methyl ethyl ketone, methylisobutylketone (MIBK) or the like; halogenated hydrocarbon solvent such as dichloromethane, ethylene dichloride, chloroform, or the like; aprotic polar solvents such as N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylacetamide (DMA), acetonitrile or the like; ethers such as diethyl ether, tetrahydrofuran, methyl tetrahydrofuran, or the like; alcohols such as methanol, ethanol, 2-propanol, 2-butanol and mixtures thereof.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein alkanesulfonic acid including such as but is not limited to methanesulfonic acid, ethanesulfonic acid, n-propanesulfonic acid, isopropanesulfonic acid, n-butanesulfonic acid, isobutanesulfonic acid, sec-butanesulfonic acid, tert-butanesulfonic acid and the mixtures of two or more of them in all proportions.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein agent may any hydrogenating agent including such as but is not limited to typically iridium, nickel, palladium, platinum, rhodium, or ruthenium, with or without activated carbon.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein purification of Tri-O-benzyl mesylate (compound 3) may be carried out by using one or more solvents.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein Deferoxamine or its salt and/or intermediate compounds (3,4) may be purified by using known conventional techniques such as but is not limited to crystallisation, recrystallisation, chromatography, precipitation etc.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein Deferoxamine or its salt may be purified in one or more steps.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein Deferoxamine or its salt is purified by using polar and/or non-polar solvents.
In another embodiment of the present invention there is provided a method for synthesising Deferoxamine or its salt, wherein Deferoxamine or its salt is obtained with yield in the range from about 60% to about 99.99% and purity in the range from about 85% to about 99.99%.
In an embodiment, overall yield of method for synthesising Deferoxamine or its salt is about 40% to about 60%.
Another embodiment of the present invention provides a pharmaceutical composition comprising:
a. a therapeutically effective amount of Deferoxamine or a pharmaceutically acceptable salt thereof; and
b. a pharmaceutically acceptable carrier.
Advantages of the present invention:
i. Improved Reaction Routes: The present invention provides new methods with fewer steps and higher yields are being developed, often using alternative starting materials or catalysts.
ii. Enhanced Purification Techniques: Novel purification strategies are employed to remove impurities more effectively and efficiently.
iii. Green Chemistry Approaches: The present invention adopting greener solvents and reagents are emerging to minimize environmental impact.
iv. Overall, the focus of present invention lies in developing more efficient, cost-effective, and environmentally friendly methods for synthesizing deferoxamine and its mesylate salt, ultimately ensuring their wider availability and affordability for patients.
The examples provided in the definitions present in this application are non-inclusive unless otherwise stated. They include but are not limited to the recited examples.
EXAMPLES:
1. Synthesis of tert-butyl (3-acetyl-14,25-bis(benzyloxy)-10,13,21,24-tetraoxo-1-phenyl-2-oxa-3,9,14,20,25-pentaazatriacontan-30-yl) carbamate (compound 2)

Tert-butyl(3-acetyl-14,25-bis(benzyloxy)-10,13,21,24-tetraoxo-1-phenyl-2-oxa-3,9,14,20,25-pentaazatriacontan-30-yl)carbamate (compound 1) was charged into a 5L Round bottom flask at room temperature (30-35°C) under Nitrogen atmosphere.1500 mL chloroform was charged into the above RB flask. The reaction mixture was stirred for 30 min (colourless homogenous solutions was obtained). The above reaction mixture was cooled to 0°C to 15°C under N2 atmosphere. 75ml trifluoroacetic acid was added slowly at 0°C to 5°C for 60 min. The above reaction mixture was for 5hrs to 6hrs at room temperature (RT). Turbid reaction mass was observed. The reaction was monitored by TLC (TLC: 5% MeOH in DCM). The above reaction mass was evaporated under reduced pressure at 40-45°C to get colourless residue. The above residue was diluted with 1000 ml water. Said mixture of residue was basified with 350ml Sat. Na2CO3 solution. The above mixture mass was extracted with chloroform (3X1000 ml). The combined organic layer was washed with 500ml brine solution. The organic soln. was evaporated under reduced pressure at 40-45°C to get pale brown dense liquid as tert-butyl (3-acetyl-14,25-bis(benzyloxy)-10,13,21,24-tetraoxo-1-phenyl-2-oxa-3,9,14,20,25-pentaazatriacontan-30-yl)carbamate, crude. Yield: 90%; Purity: 90-94%.

2. Synthesis of N1-(3-acetyl-14-(benzyloxy)-10,13-dioxo-1-phenyl-2-oxa-3,9,14-triazanonadecan-19-yl)-N4-(5-aminopentyl)-N4-(benzyloxy)succinamide mesylate (CRC-4685-113-Mesylate)(compound 3)

130gTert-butyl(3-acetyl-14,25-bis(benzyloxy)-10,13,21,24-tetraoxo-1-phenyl-2-oxa-3,9,14,20,25-pentaazatriacontan-30-yl)carbamate crude obtained from example 1 was charged into a 5 L RBF equipped with overhead stirrer, under N2atmosphere. Ethyl acetate (1.3 L lot1) was charged to the above reaction mass (Turbid reaction mass, slowly becoming solution). The reaction mixture was cooled to 20-25°C. 10ml methane sulphonic acid was added into the above reaction mixture while maintaining the temperature at 20-25°C (heterogeneous suspension) The reaction was stirred for 12-15hrs at RT (30-35°C) [(Reaction mass become suspension, if not, stir vigorously and become precipitate after 5-6 h). Note: if the solid is not formed add 200 mL of acetonitrile (ACN) and continue stirring]. 1.3L ethyl acetate was charged to the above precipitate and stirred for 1hr at the same temperature. The solid obtained was filtered and washed the solid with ethyl acetate (2vo.) followed by hexane (5vol) (become free flow solid). The solid was sucked dry and unloaded the solid. The solid was dried under air for 1h followed by vacuum drying for 2hrs to get powdery off-white Tri –O benzylamine mesylate salt (120g). Yield: 83%; Purity:>92% (by HPLC).

3. Purification of Tri-O-benzyl mesylate (compound 3):
120g Mesylate salt was charged into a 5 Lit RBF equipped with overhead stirrer. Acetonitrile was charged to the above mass (Not completely dissolved, suspension obtained). Ethyl acetate was charged to the above reaction mass (suspension obtained) and stirred at room temperature (RT) for 12hrs. (Off white precipitate obtained). The solid obtained was filtered through Buchner funnel and washed the solid with ethyl acetate (2 vol) followed by hexane (5vol) (nature of the solid become free flow solid). The solid was suck dried and unloaded the solid was dried under air for 1h followed by vacuum drying for 2hrs to get powdery off-white Tri-O benzylamine mesylate salt. Wt.100g; Yield: 85%; Purity: >94% (by HPLC).

4. Synthesis of N1-(5-aminopentyl)-N1-hydroxy-N4-(5-(N-hydroxy-4-((5-(N-hydroxyacetamido)pentyl)amino)-4-oxobutanamido)pentyl)succinamide mesylate (compound 4)

25gN1-(3-acetyl-14-(benzyloxy)-10,13-dioxo-1-phenyl-2-oxa-3,9,14-triazanonadecan-19-yl)-N4-(5-aminopentyl)-N4-(benzyloxy)succinamidewas charged to the hydrogenator apparatus at room temperature (30-35°C). 1000 ml methanol was charged to the above reactor and purged Argon gas for 30 min (pale brown homogenous solution). 10% Pd/C 50% wet (12.5 g) to the above solution was added under inert atmosphere (Ar2). The hydrogenator was closed tightly and hydrogen (H2) pressure (1 bar) was applied to the reaction mass. The reaction mixture was stirred for 1-2h and the reaction was monitored by HPLC. The reaction mass was filtered through celite bed and washed with 300ml methanol. The filtrate was evaporated under reduced pressure at 40-45°C to give 18g off-white solid. Purity: 91.94% (by HPLC).
18g the above off-white solid was charged into a 500 RBF equipped with magnetic stirrer. Water was charged and heated the reaction mixture to 50-60°C (Homogenous solution, not completely dissolved). The reaction mixture was cooled to RT and 300ml MeOH was charged into the solution (homogenous solution). Aq. Ammonia was added into the reaction mixture to reach 10-11pH. (homogenous solution). The reaction mixture was stirred at RT for 2hrs. Solid precipitated obtained was filtered and washed with 20ml Hexane. The solid was suck dried to obtain off-white solid Deferoxamine free base. Wt. 10g; Yield: 66%; purity: 94.7% (by HPLC).
10g of above free base was charged into a 500 mL RB flask. 200ml EtOH was added to the above vessel. Water was charged to the above solution (heterogenous mixture). Reaction mixture was stirred for 30 min (heterogenous mixture). 1.7gMethanesulphonic acid was added slowly to the above reaction mixture (reaction mass become colourless homogenous solution). The reaction mixture was stirred at 0-5°C for 4 hrs and continued stirring at room temperature for 8 hrs (white solid precipitates). The solid obtained was filtered and washed with ice cold ethanol (2 mL) to give 10 g of an off-white solid as Deferoxamine mesylate. Yield: 85%; Purity: 95.6% (by HPLC).

5. Purification of Deferoxamine mesylate (compound 4):
10g solid Deferoxamine mesylate (95.6% purity) into a 250 ml RBF was charged under positive pressure of argon.100 ml THF (10vol) was charged into the reaction at RT under argon atm. The reaction mixture was refluxed at 75-80°C for 20 min under argon atm. (heterogeneous mixture). Double distilled Milli-Q water (2 ml) was added at 75-80°C and stirred for 30 min at the same temperature (Homogenous solution). The reaction mass was cooled to RT and stirred for 12hrs (Off white solid precipitated). The solid obtained was filtered and washed with 5ml THF. The solid material was unloaded and dried to obtain pure Deferoxamine mesylate. Wt.: 8.5g; Purity: > 96%. Overall yield: 48%.

6. Characterisation of Deferoxamine mesylate (compound 4):
1H NMR (400 MHz, DMSO-d6): d 1.21-1.30(6H, m), 1.34-1.57(4H, m), 1.47-1.55(8H, m),1.96(3H, S), 2.26-2.27(4H, m), 2.49-2.51(4H, m), 2.73-2.75(2H, m), 2.97-3.02(4H, m), 3.43-3.49(6H, m), 7.76-7.81 (4H, m), 9.65-9.69 (2H, d).

We claim:
1. A method for synthesising Deferoxamine or its salt, the method comprising:
i. contacting a compound of formula 1 with an acid in a solvent at 0oC to 40oC for period from about 2 hrs to about 10 hrs to obtain a compound of formula 2;

ii. treating the compound of formula 2 with an alkanesulfonic acid at a temperature ranging from about 10oC to about 40oC for period ranging from about 10hrs to 20 hrs in a solvent to obtain a compound of formula 3;

iii. hydrogenating the compound of formula 3 in presence of an agent under hydrogen (H2) pressure in a solvent at a temperature from about 20oC to about 50oC for period from about 30min to about 180min to obtain compound of formula 4.

Wherein compound of formula 4 is Deferoxamine or its salt.
2. The method as claimed in claim 1, wherein acid is selected from p-Toluenesulfonic Acid, ZnBr2, trifluoroacetic acid (TFA), HCl, H2SO4, aqueous phosphoric acid, BF3·OEt2, TMSI, TMSOTf, TiCl4, SnCl4, AlCl3, Sn(OTf)2 and K3PO4·H2O and combinations thereof.
3. The method as claimed in claim 2, wherein acid is trifluoroacetic acid (TFA).
4. The method as claimed in claim 1, wherein solvent is selected from water, acetone, methyl ethyl ketone, methylisobutylketone (MIBK), dichloromethane, ethylene dichloride, chloroform, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylacetamide (DMA), acetonitrile, diethyl ether, tetrahydrofuran, methyl tetrahydrofuran, methanol, ethanol, 2-propanol, 2-butanol and mixtures thereof.
5. The method as claimed in claim 1, wherein alkanesulfonic acid is selected from methanesulfonic acid, ethanesulfonic acid, n-propanesulfonic acid, isopropanesulfonic acid, n-butanesulfonic acid, isobutanesulfonic acid, sec-butanesulfonic acid, tert-butanesulfonic acid and the mixtures of two or more of them in all proportions.
6. The method as claimed in claim 5, wherein alkanesulfonic acid is methanesulfonic acid.
7. The method as claimed in claim 1, wherein agent is hydrogenating agent selected from iridium, nickel, palladium, platinum, rhodium, or ruthenium, with or without activated carbon.
8. The method as claimed in claim 1, wherein the hydrogenating agent is palladium with activated carbon (10% Pd/C).
9. The method as claimed in claim 1, wherein the compound of formula 4 is Deferoxamine or its salt obtained with yield in the range from about 60% to about 99.99%, and purity in the range from about 85% to about 99.99%.
10. A pharmaceutical composition comprising:
a. a therapeutically effective amount of Deferoxamine or a pharmaceutically acceptable salt thereof; and
b. a pharmaceutically acceptable carrier.

Dated this: Nov. 1, 2024

Vijaykumar Shivpuje
IN/PA-1096
Agent for the Applicant
To
The Controller of Patents,
The Patent Office, Mumbai

ABSTRACT

“METHOD FOR SYNTHESIZING DEFEROXAMINE AND/OR IT’S SALT”

The present invention provides a method for synthesizing Deferoxamine mesylate salt with improved yield and purity.The said method comprises the steps of: (a) contacting a compound of formula 1 with an acid in a solvent at 0oC to 40oC for period of 2 hrs to 10 hrs to obtain a compound of formula 2; (b) treating the compound of formula 2 with an alkanesulfonic acid at a temperature from about 10oC to about 40oC for time period from about 10hrs to 20 hrs in a solvent to obtain a compound of formula 3; and (c) hydrogenating the compound of formula 3 in presence of 10%Pd/C under hydrogen (H2) pressure in a solvent at a temperature from about 20oC to about 50oC for period from about 30min to about 180min to obtain Deferoxamine mesylate.

,CLAIMS:We claim:
1. A method for synthesising Deferoxamine or its salt, the method comprising:
i. contacting a compound of formula 1 with an acid in a solvent at 0oC to 40oC for period from about 2 hrs to about 10 hrs to obtain a compound of formula 2;

ii. treating the compound of formula 2 with an alkanesulfonic acid at a temperature ranging from about 10oC to about 40oC for period ranging from about 10hrs to 20 hrs in a solvent to obtain a compound of formula 3;

iii. hydrogenating the compound of formula 3 in presence of an agent under hydrogen (H2) pressure in a solvent at a temperature from about 20oC to about 50oC for period from about 30min to about 180min to obtain compound of formula 4.

Wherein compound of formula 4 is Deferoxamine or its salt.
2. The method as claimed in claim 1, wherein acid is selected from p-Toluenesulfonic Acid, ZnBr2, trifluoroacetic acid (TFA), HCl, H2SO4, aqueous phosphoric acid, BF3·OEt2, TMSI, TMSOTf, TiCl4, SnCl4, AlCl3, Sn(OTf)2 and K3PO4·H2O and combinations thereof.
3. The method as claimed in claim 2, wherein acid is trifluoroacetic acid (TFA).
4. The method as claimed in claim 1, wherein solvent is selected from water, acetone, methyl ethyl ketone, methylisobutylketone (MIBK), dichloromethane, ethylene dichloride, chloroform, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylacetamide (DMA), acetonitrile, diethyl ether, tetrahydrofuran, methyl tetrahydrofuran, methanol, ethanol, 2-propanol, 2-butanol and mixtures thereof.
5. The method as claimed in claim 1, wherein alkanesulfonic acid is selected from methanesulfonic acid, ethanesulfonic acid, n-propanesulfonic acid, isopropanesulfonic acid, n-butanesulfonic acid, isobutanesulfonic acid, sec-butanesulfonic acid, tert-butanesulfonic acid and the mixtures of two or more of them in all proportions.
6. The method as claimed in claim 5, wherein alkanesulfonic acid is methanesulfonic acid.
7. The method as claimed in claim 1, wherein agent is hydrogenating agent selected from iridium, nickel, palladium, platinum, rhodium, or ruthenium, with or without activated carbon.
8. The method as claimed in claim 1, wherein the hydrogenating agent is palladium with activated carbon (10% Pd/C).
9. The method as claimed in claim 1, wherein the compound of formula 4 is Deferoxamine or its salt obtained with yield in the range from about 60% to about 99.99%, and purity in the range from about 85% to about 99.99%.
10. A pharmaceutical composition comprising:
a. a therapeutically effective amount of Deferoxamine or a pharmaceutically acceptable salt thereof; and
b. a pharmaceutically acceptable carrier.

Dated this: Nov. 1, 2024

Vijaykumar Shivpuje
IN/PA-1096
Agent for the Applicant
To
The Controller of Patents,
The Patent Office, Mumbai