FIELD OF INVENTION
The present invention relates to a process for purifying SGLT2 inhibitors or pharmaceutically acceptable salts thereof.
BACK GROUND OF THE INVENTION
Diabetes Mellitus continues to be a major non-communicable disease with global burden of 366 million at present and projected to increase to 439 to 552 million by 2030. Treatment of type 2 diabetes (T2DM) continues to present challenges, with significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron, principally via the sodium-glucose cotransporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action.
Canagliflozin (Invokana, Janssen), Dapagliflozin (Farxiga, AstraZeneca) and Empagliflozin (Jardiance, Boehringer-Ingelheim) are all selective sodium glucose-cotransporter 2 (SGLT-2) inhibitors, which block the reabsorption of glucose in the kidneys and promote excretion of excess glucose in the urine. Through this mechanism, Canagliflozin, Dapagliflozin and Empagliflozin may help control glycaemia independently of insulin pathways.
US 7,943,788 B2 (US 788) discloses Canagliflozin, (2S,3R,4R,5S,6R)-2-{3-[5-[4-Fluoro-phenyl)-thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol having the Formula I or its pharmaceutically acceptable salts.

US 788 patent discloses the formation of esters or amides of formula I with a-amino acid or a P-amino acid. Further this patent also discloses the pharmaceutically acceptable salts with acidic amino acids such as aspartic acid, glutamic acid, etc.
US '788 patent discloses the preparation of Canagliflozin as follows.
US 2012/0289694 Al discloses the co-crystals of Canagliflozin with L-proline and Citric acid and process for their preparation.

US 6,515,117 B2 (US ' 117 ) discloses Dapagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl) phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol having the formula II or its pharmaceutically acceptable salts thereof.
i v1 inuia ii
US'l 17 discloses a processes for the purification of Dapagliflozin, comprising the step of acetylating crude dapagliflozin to 2,3,4,6-tetra-0-acetyl-l,5-anhydro-l-[4-chloro-3-(4-ethoxybenzyl)phenyl]-D-glucitol in pyridine and thereafter hydrolyzing acetylated

Dapagliflozin in the presence of an alkali metal hydroxide such as lithium hydroxide or sodium hydroxide.
US 7,919,598 B2 discloses Dapagliflozin crystalline solvates and complexes with (S)-propylene glycol ((S)-PG) hydrate (Form SC-3), (R)-propylene glycol ((R)-PG) hydrate (Form SD-3), EtOH dihydrate (Form SA-I), ethylene glycol (EG) dihydrate (Form SB-I), ethylene glycol (EG) dihydrate (Form SB-2), 1:2 L-proline complex (Form 3), 1:1 L-proline complex (Form 6), 1:1 L-proline hemihydrate complex (Form H.5-2), and 1:1 L-phenylalanine complex (Form 2), butyne-diol, dimethanol and further discloses a process for their preparation.
CN 102167715 A discloses co-crystals of Dapagliflozin with chiral amino acids selected from L-proline, L-tryptophan or L-phenylalanine.
US 2010/0167988 Al discloses deuteriated Dapagliflozin pharmaceutically acceptable salts with acylated amino acids, L-aspartic acid, L-glutamic acid, hippuric acid, L-pyroglutamic acid, L-arginine.
US 2010/0063141 Al discloses the composition with deuteriated SGLT inhibitors with amino acids.
US 2013/0267694 Al discloses purification of Dapagliflozin by co-crystallization with L -proline.
WO 2015/044849 Al discloses processes for the purification of Dapagliflozin, comprising the step of acetylating crude Dapagliflozin to 2,3,4,6-tetra-0-acetyl-l,5-anhydro-l-[4-chloro-3-(4-ethoxybenzyl)phenyl]-D-glucitol of Formula III in the absence of pyridine and further deacetylation in the presence of Lithium hydroxide.
CN 104045613 A discloses Dapagliflozin L-proline co-crystal form and process for its preparation.

US 9,006,188 B2 discloses Dapagliflozin lactose co-crystal, asparagine co-crystal and process for its preparation.
US 2014/0323417 discloses the purification of Dapagliflozin by crystallization of amorphous form of Dapagliflozin.
WO 2015/040571 discloses processes for the preparation of Dapagliflozin substantially free of impurity at RRT 1.61 by hydrolyzing an acetylated Dapagliflozin in the presence of an amine base.
Dapagliflozin obtained from these processes (US 6,515, 117, US 7,375,213, US 7,932,379 and US 7,919,598 ) has a significant level of an impurity detected at a relative retention time (RRT) of 1.61 when measured by high performance liquid chromatography (HPLC).
US 7,579,449 B2(US'449) discloses Empagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol having the formula III or.its pharmaceutical^ acceptable salts thereof.

However, the present inventors found that the use of amino acids in the purification of SGLT2 inhibitors provides highly pure compound which have adequate stability characteristics enabling their incorporation into a variety of different formulations particularly suitable for pharmaceutical utility.
Further the present inventors have found that the SGLT2 inhibitors obtained by co-crystal formation with amino acids are substantially free of acetyl impurity.
. In view of this the present inventors have found SGLT2 inhibitors amino acid co-crystals which are stable and industrially viable.
OBJECTIVES OF THE INVENTION
The objective of the present invention is to provide a purification process for preparing SGLT2 inhibitors.
Another objective of the present invention is to provide a process for preparing SGLT2 inhibitors having high yield and high purity.
Another objective of the present invention is to provide purification process SGLT2 inhibitors by using amino acids.

Another embodiment of the present invention is to provide a process for the preparation of SGLT2 inhibitors or pharmaceutical^ acceptable salts which is commercially viable and industrially applicable.
SUMMARY OF THE INVENTION
The present invention provides a process for the purification of SGLT2 inhibitor by treating SGLT2 inhibitor with amino acids.
The present invention provides a process; for the purification of SGLT2 inhibitor which comprises:
a. treating SGLT2 inhibitor in a solvent;
b. adding a solution of amino acid;
c. optionally filtering the SGLT2 inhibitor amino acid co-crystal;
d. dissolving SGLT2 inhibitor amino acid co-crystal in alcohol;
e. adjusting the pH using 1NHC1; and
f. isolating SGLT2 inhibitor.
In another embodiment the present invention provides pure SGLT2 inhibitor substantially free of acetyl impurity.
In another embodiment the present invention provides highly pure SGLT2 inhibitor.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a process for the purification of SGLT2 inhibitor comprises treating SGLT2 inhibitor with amino acid in solvent selected from alcohol, water or mixtures thereof.
In another embodiment of the present invention, the reaction of SGLT2 inhibitor with amino acid involves heating and thereafter cooling of the reaction mixture to isolate the compounds of formulae I, II and III.

In another embodiment of the present invention, heating is carried out at a temperature in the range of20°C to 100° C.
In another embodiment of the present invention, cooling is carried out at a temperature in the rangeof200Cto-20°C.
In another embodiment of the present invention, the SGLT2 inhibitor is selected from Canagliflozin, Dapagliflozin and Empagliflozin.
In another embodiment of the present invention, the amino acid refers to a compound comprising an amino functional group and a carboxylic functional group.
In another embodiment of the present invention, amino acids are natural amino or synthetic amino acids which may have L-configuration, D-configuration or DL-isomeric mixture thereof.
In another embodiment of the present invention, the amino acids are selected from the group comprising of L-Alanine, L-Cysteine, L-Serine, L-Threonine, L-Aspartic Acid, L-Glutamic Acid, L-Asparagine, L-Glutamine, L-Histidine, L-Arginine, L-Lysine, L-Isoleucine, L-Leucine, L-Methionine, L-Valine, L-Phenylalanine, L-Tyrosine, L-Tryptophan, L-Glycine, L-Proline, DL-Phenylalanine, DL-Alanine, DL-Methionine, L-Pyroglutamic acid, DL-Valine, DL-Pipecolinic acid, DL-alfa-aminobutyric acid, DL-Serine, DL-Norleucine, DL-Norvaline, DL-Proline, DL-Asparatic acid, DL-Phenylglycine.
In another embodiment of the present invention, alcohols are selected from the group comprising of aliphatic alcohols or aromatic alcohols; wherein aliphatic alcohols used throughout the invention are selected from the group comprising of methanol, ethanol, n-propanol, isopropanol, n-butanol, pentanol, isobutanol, tertiary butanol, cyclopropanol, cyclobutanol, cyclopentanol, cyclohexanol or mixtures thereof, aromatic alcohols used throughout the invention are selected form the group comprising of phenols, benzylalcohol or mixtures thereof.

In another embodiment of the present invention, dissolving SGLT2 inhibitor amino acid co-crystal with alcohol selected from the group comprising of aliphatic alcohols or aromatic alcohols wherein aliphatic alcohols used throughout the invention are selected from the group comprising of methanol, ethanol, n-propanol, isopropanol, n-butanol, pentanol, isobutanol, tertiary butanol, cyclopropanol, cyclobutanol, cyclopentanol, cyclohexanol or mixtures thereof, aromatic alcohols used throughout the invention are selected form the group comprising of phenols, benzylalcohol or mixtures thereof.
In another embodiment of the present invention, the pH adjustment with IN HC1 is carried out in the range of 2-4.
In another embodiment of the present invention, isolation of the compound is carried out by conventional methods such as filtration, centrifugation and evaporation.