Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate and its method of preparation

Description

1 / 32 DESCRIPTIVE REPORT “AZETIDIN-1-YL{8-[(2,6-DIMETHYLBENZYL)AMINO]-2,3-DIMETHYLIMIDAZO[1,2-A]PYRIDIN-6-YL}METHANONE CITRATE AND ITS PREPARATION METHOD” FIELD OF THE ART

[001] The present invention relates to an innovative salt of the imidazo[1,2a]pyridine compound, a crystalline form thereof and a method of preparation. BACKGROUND

[002] Inflammatory gastrointestinal diseases or diseases related to gastric acid, such as peptic ulcer, gastric / duodenal ulcer, gastritis, gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), etc., are the most common digestive problems affecting most of the world's population, including Korea.

[003] To address the problem of conventional proton pump inhibitors (PPIs), there is a growing interest in and need for potassium-competitive acid-blocking (P-CAB, acid pump antagonist) drugs that have a reversible binding mechanism to the K+ binding site of H+ / K+-ATPase to inhibit acid secretion through competitive potassium inhibition among proton pump inhibitors (PPIs). In particular, unlike an irreversible proton pump inhibitor (PPI), a reversible proton pump inhibitor (P-CAB) is expected to have rapid efficacy in terms of mechanism, be easily taken regardless of when it is administered—before and after meals—and be very effective in improving nighttime symptoms, which are a problem with irreversible proton pump inhibitors.

[004] Meanwhile, a compound needs to have not only preferential biological properties, but also sufficient physical properties to allow its use in the preparation of a pharmaceutical composition, so that the compound can be considered a candidate material to be developed as a drug. In addition, it is preferable that this compound have a solid phase in order. Petition 870250005638, dated 01 / 24 / 2025, pp. 114 / 166 2 / 32 of being easily prepared and formulated in a stable manner.

[005] Consequently, the present inventors have made intensive research efforts to find a form that has stability in several respects and can be industrially processed to use the imidazo[1,2-a]pyridine compound in a pharmaceutical form and, as a result, have confirmed a new salt exhibiting a remarkable effect that could not be predicted, thus completing the present invention. RELATED TECHNICAL REFERENCES PATENT DOCUMENTS

[006] Publication Document for Registered Patent No. KR 10-1777971 DETAILED DESCRIPTION OF THE INVENTION PROBLEM OF THE TECHNIQUE

[007] One objective of the present invention is to provide an innovative salt of the imidazo[1,2-a]pyridine compound.

[008] Another objective of the present invention is to provide a crystalline form of an innovative salt of the imidazo[1,2-a]pyridine compound.

[009] Yet another objective of the present invention is to provide a method for the preparation of an innovative salt of the imidazo[1,2-a]pyridine compound. SOLUTION OF THE INNOVATIVE SALT TECHNIQUE OF THE IMIDAZO[1,2-A]PYRIDINE COMPOUND

[010] (1) An innovative salt of the imidazo[1,2-a]pyridine compound, according to the present invention, is azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate.

[011] Hereafter in this document, the term citrate of chemical formula I or citrate used herein simply means azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate.

[012] Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone is represented by the chemical formula I below: CHEMICAL FORMULA I Petition 870250005638, dated 01 / 24 / 2025, pp. 115 / 166 3 / 32

[013] (2) Above (1), in azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, a molar ratio of azetidin-1yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid can be from 1:0.3 to 1:1.3. As an example, the molar ratio can be from 1:0.5 to 1:1.

[014] (3) Above (1) or (2), azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate of the present invention can be represented by chemical formula II below: CHEMICAL FORMULA II

[015] In chemical formula II above, n represents 0.3 to 1.3.

[016] In one embodiment, n of chemical formula II above can be from 0.5 to 1.

[017] (4) In any of the above items (1) to (3), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be anhydrous.

[018] (5) In any of the above items (1) to (4), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be crystalline or amorphous.

[019] (6) In any of the above items (1) to (5), azetidin-1-yl{8 citrate Petition 870250005638, dated 01 / 24 / 2025, pp. 116 / 166 4 / 32 [(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone can be anhydrous crystalline.

[020] (7) In any of the above items (1) to (6), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be Crystalline Form A which shows a powder X-ray diffraction pattern including at least three diffraction peaks where a 2Θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 5.46°, 7.14°, 10.61°, 11.82°, 18.27° and 25.77°.

[021] (8) Above (7), the powder X-ray diffraction pattern of Crystalline Form A may additionally include at least one diffraction peak where the value 2Θ (±0.2°) is selected from the group consisting of 10.93°, 13.11°, 14.15°, 15.84°, 16.35°, 19.79° and 24.21°.

[022] (9) Above (7) or (8), Crystalline Form A may have an endothermic peak of Differential Scanning Calorimetry (DSC) at 88.69 °C, 135.61 °C and 154.84 °C (±0.5 °C) when the heating rate is 10 °C / min.

[023] (10) In any of the above items (1) to (6), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be Crystalline Form B which shows a powder X-ray diffraction pattern including at least three diffraction peaks where a 2Θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 7.03°, 7.69°, 9.47°, 13.21°, 14.86° and 21.13°.

[024] (11) Above (10), Crystalline Form B may have an endothermic peak of Differential Scanning Calorimetry (DSC) at 144.57 °C (±0.5 °C) when the heating rate is 10 °C / min.

[025] (12) In any of the above items (1) to (6), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be the C1 Crystalline Form which shows a powder X-ray diffraction pattern including at least three diffraction peaks where a 2θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 7.35°, 15.31°, 17.42° and Petition 870250005638, dated 01 / 24 / 2025, pp. 117 / 166 5 / 32 22.26°.

[026] (13) Above (12), the X-ray diffraction pattern of Crystalline Form powder C1 may additionally include at least one diffraction peak where the 2Θ (±0.2°) value is selected from the group consisting of 10.23°, 12.90°, 14.68°, 15.97°, 18.21°, 21.22° and 26.00°.

[027] (14) Above (12) or (13), the Crystalline Form C1 may have an endothermic Differential Scanning Calorimetry (DSC) peak at 168.93 °C (±0.5 °C) when the heating rate is 10 °C / min.

[028] (15) In any of the above items (1) to (6), azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate may be the Crystalline Form C2 showing a powder X-ray diffraction pattern including at least three diffraction peaks where a 2Θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 5.63°, 8.90°, 9.51° and 13.01°.

[029] (16) Above (15), the powder X-ray diffraction pattern of the Crystalline Form C2 may additionally include at least one diffraction peak where the 2Θ (±0.2°) value is selected from the group consisting of 12.31°, 14.34°, 14.80°, 18.38°, 18.75° and 19.62°.

[030] (17) Above (15) or (16), the Crystalline Form C2 may have an endothermic Differential Scanning Calorimetry (DSC) peak at 161.48 °C (±0.5 °C) when the heating rate is 10 °C / min.

[031] (18) In any of the above items (1) to (5), the amorphous form of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone citrate can have an endothermic Differential Scanning Calorimetry (DSC) peak at 161.42 °C (±0.5 °C) when the heating rate is 10 °C / min.

[032] (19) In any of the above items (1) to (11), in each of the Forms Crystalline citrate A and B according to the present invention, a molar ratio of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid can be 1:0.5.

[033] (20) In any of the items above (1) to (6) and (12) to (17), in each one Petition 870250005638, dated 01 / 24 / 2025, pp. 118 / 166 6 / 32 of the C1 and C2 Crystalline Forms of citrate, according to the present invention, a molar ratio of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone and citric acid can be 1:1.

[034] The azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, can exhibit unexpectedly very excellent bioavailability and, therefore, can be used as an active ingredient in the pharmaceutical composition, so as to exhibit a very excellent effect in the prevention or treatment of inflammatory gastrointestinal diseases or diseases related to gastric acid.

[035] Furthermore, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, may have the advantages of being easily prepared by means of a simple process and obtained with high purity and high yield of 90% or more.

[036] Furthermore, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, can be used to formulate drugs, since various Crystalline Forms are generated due to small differences in reaction temperature, reaction rate, etc., even under similar solvent conditions, and these Crystalline Forms have excellent photostability, heat / moisture stability, long-term storage stability, etc.

[037] The pharmaceutical composition of the present invention includes a therapeutically effective amount of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate.

[038] The pharmaceutical composition of the present invention can treat or prevent selected diseases from the group consisting of peptic ulcer, gastric / duodenal ulcer, ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), Helicobacter pylori infection, functional dyspepsia, Zollinger-Ellison syndrome, gastritis, gastroesophageal reflux disease (GERD) and non-erosive reflux disease (NERD). Petition 870250005638, dated 01 / 24 / 2025, pp. 119 / 166 7 / 32 METHOD FOR PREPARING AN INNOVATIVE SALT OF THE IMIDAZO[1,2-A]PYRIDINE COMPOUND

[039] (21) A method for the preparation of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, includes preparing citrate by the reaction of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid.

[040] (22) In the preparation of citrate, according to above (21), azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid can be reacted in the presence of at least one solvent selected from an alcohol with one to three carbon atoms, acetone, acetonitrile, tetrahydrofuran (THF), dichloromethane, dimethylformamide (DMF), N-methylpyrrolidone (NMP), and purified water.

[041] (23) Above (21) or (22), azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone can be synthesized according to reaction formula 1 below: REACTION FORMULA 1

[042] (24) In reaction formula 1 above, according to (23) above, 8(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid can be obtained as described in Registered Patent Publication Document No. KR 101 777971, and a specific process of reaction formula 1 above can also be carried out according to the content disclosed therein.

[043] (25) In any of the above items (21) to (24), in the citrate preparation, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone may be a non-solvate, a solvate, or a mixture thereof.

[044] (26) In any of the above items (23) to (25), the solvate, the non-solvate, Petition 870250005638, dated 01 / 24 / 2025, pp. 120 / 166 8 / 32 or a mixture thereof obtained by crystallization of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone obtained according to reaction formula 1 above in an alcohol solvent with one to three carbon atoms, followed by vacuum drying, can be reacted with citric acid. The solvate of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone can be obtained by vacuum drying at about 20 °C or more to about 35 °C or less. The non-solvate of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone can be obtained by vacuum drying at about 45 °C or higher and about 60 °C or lower. The solvate and non-solvate mixture can be obtained by vacuum drying at a temperature of more than about 35 °C and less than about 45 °C.

[045] (27) In any of the above items (21) to (26), in the preparation of citrate, citrate may be prepared wherein azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid are included in a molar ratio of about 1:0.3 to about 1:1.3. For example, in the preparation of citrate, citrate may be prepared wherein the molar ratio of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid is about 1:1 or about 1:0.5.

[046] (28) In any of the above items (21) to (27), in the preparation of citrate, the solvate, the non-solvate, or the mixture thereof obtained from azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid may be mixed to have a weight ratio of about 1:1.3 to about 1:0.3.

[047] (29) In any of the above items (21) to (28), the preparation of the citrate may include mixing a first solution including the solvate, the non-solvate, or a mixture thereof obtained from azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and a first solvent, and a second solution including citric acid and a second solvent.

[048] (30) Above (29), the first solution can be, firstly, stirred in Petition 870250005638, dated 01 / 24 / 2025, pp. 121 / 166 9 / 32 a reactor and then the second solution can be added, or the second solution can first be stirred in the reactor and then the first solution can be added.

[049] (31) Above (29) or (30), the first or second solvents may each independently include at least one solvent selected from an alcohol with one to three carbon atoms, acetone, acetonitrile, THF, dichloromethane, DMF, NMP, and purified water.

[050] (32) In any of the above items (29) to (31), the first solvent may be a single solvent of purified water or a mixed solvent including at least one organic solvent selected from an alcohol with one to three carbon atoms, acetone, acetonitrile, THF, dichloromethane, DMF, and NMP together with purified water. In this case, the second solvent may be a single solvent of purified water or a mixed solvent including at least one organic solvent selected from an alcohol with one to three carbon atoms, acetone, acetonitrile, THF, dichloromethane, DMF, and NMP together with purified water. Under the condition of the first and second solvents, the citrate, according to the present invention, may be Crystalline Form A.

[051] (33) In any of the above items (29) to (31), the first solvent may be an organic solvent, and the second solvent may be a single solvent of purified water, or a mixed solvent including at least one organic solvent together with purified water. Under the condition of the first and second solvents, the citrate, according to the present invention, may be Crystalline Form A.

[052] (34) In any of the above items (29) to (31), the first solvent may be an organic solvent, the second solvent may be an organic solvent and the first and second solvents may be the same. Citrate, according to the present invention, may be in Crystalline Form B on the condition that the first and second solvents are alcohols with one to three carbon atoms as an organic solvent.

[053] (35) In any of the above items (29) to (31), the first solvent may Petition 870250005638, dated 01 / 24 / 2025, pp. 122 / 166 10 / 32 being acetone or a mixed solvent in which at least one organic solvent other than acetone and acetone are mixed, and the second solvent may be acetone. Under the condition of the first and second solvents, the citrate, according to the present invention, may be the C1 Crystalline Form or the C2 Crystalline Form.

[054] (36) In any of the above items (21) to (33), in the preparation of citrate, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid can be reacted at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C, and a subsequent stirring process can be carried out continuously at the same temperature. Under the temperature conditions, the citrate according to the present invention can be Crystalline Form A.

[055] (37) In any of the above items (21) to (31) and (34), in the preparation of citrate, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid may be reacted at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C, and then cooled and stirred at about 0 °C to about 10 °C, preferably at about 0 °C to about 5 °C. Under the process condition, the citrate, according to the present invention, may be Crystalline Form B.

[056] (38) In any of the above items (21) to (31) and (35), in the preparation of citrate, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid can be reacted at about 45 °C to about 60 °C, preferably at about 50 °C to about 55 °C and then cooled and stirred at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C. Under the process condition, the citrate, according to the present invention, can be the C1 Crystalline Form.

[057] (39) In any of the above items (21) to (31) and (35), in the preparation of citrate, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid may be reacted at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C and then cooled and stirred Petition 870250005638, dated 01 / 24 / 2025, pp. 123 / 166 11 / 32 at about 0 °C to about 10 °C, preferably at about 0 °C to about 5 °C. Here, it can be carried out at about 10 °C to about 30 °C in a short period of time in which the time required to introduce citric acid into azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone is set to 15 minutes, preferably 10 minutes. Under the process conditions, citrate can be obtained as C1 Crystalline Form.

[058] (40) In any of the above items (21) to (31) and (35), in the preparation of citrate, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid may be reacted at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C and then heated and stirred at about 45 °C to about 60 °C, preferably at about 50 °C to about 55 °C and then cooled and stirred at about 10 °C to about 30 °C, preferably at about 20 °C to about 25 °C. Here, the time required to introduce citric acid into azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone can be at least 30 minutes, preferably at least 60 minutes. Under the process conditions, the citrate, according to the present invention, can be the C2 Crystalline Form.

[059] (41) In any of the above items (21) to (40), the preparation of citrate may include: filtering a solid, i.e., citrate, produced from a reaction between azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone and citric acid; washing; and drying. Filtration and washing may be carried out by a method carried out in a conventional salt preparation. Drying may be carried out at about 35 °C to about 50 °C, preferably about 35 °C to about 45 °C, and may be carried out by vacuum drying or nitrogen drying. ADVANTAGEOUS EFFECTS

[060] In an innovative salt of the imidazo[1,2-a]pyridine compound of the present invention, the Crystalline Form thereof and a method for preparing the same, the citrate of the imidazo[1,2-a]pyridine compound of the present invention may exhibit a Petition 870250005638, dated 01 / 24 / 2025, pp. 124 / 166 12 / 32 unexpected bioavailability is very excellent and therefore it can be used as an active ingredient in pharmaceutical compositions, so as to exhibit a very excellent effect in the prevention or treatment of inflammatory gastrointestinal diseases or diseases related to gastric acid.

[061] Furthermore, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, may have the advantages of being easily prepared by means of a simple process and obtained with high purity and high yield of 90% or more.

[062] Furthermore, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, can be used to formulate drugs, since various Crystalline Forms are generated due to small differences, such as reaction temperature, reaction rate, etc., even under similar solvent conditions, and these Crystalline Forms have excellent photostability, heat / moisture stability, long-term storage stability, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[063] Figures 1, 2, and 3 are shown which display the results of the analyses of XRD, DSC, and TGA in the Crystalline Form A of citrate, according to the present invention, respectively.

[064] Figures 4, 5, and 6 are shown which display the results of the analyses of XRD, DSC, and TGA in the Crystalline Form B of citrate, according to the present invention, respectively.

[065] Figures 7, 8, and 9 are views that show the results of the analyses of XRD, DSC, and TGA in the C1 Crystalline Form of citrate, according to the present invention, respectively.

[066] Figures 10, 11, and 12 are views showing the results of XRD, DSC, and TGA analyses on the C2 Crystalline Form of citrate, according to the present invention, respectively.

[067] Figures 13, 14 and 15 are shown which display the results of the analyses. Petition 870250005638, dated 01 / 24 / 2025, pp. 125 / 166 13 / 32 of XRD, DSC and TGA in the amorphous citrate form, according to the present invention, respectively.

[068] Figure 16 is a view showing the results of XRD analysis in citrate, according to the present invention, after 36 months of storage. MODALITY FOR INVENTION

[069] Hereafter in this document, all terms used herein, including technical or scientific terms, have the same meaning commonly understood by persons of ordinary skill in the art to which the present invention relates, unless otherwise defined. Such terms as those defined in a general-purpose dictionary should be interpreted as having meanings equal to the contextual meanings in the relevant art, and should not be interpreted as having ideal or overly formal meanings, unless clearly defined in the present application. MEASUREMENT METHOD

[070] A measurement method as follows can be commonly applied to each of the Examples according to the present invention. 1. X-RAY POWDER DIFFRACTION (XPRD)

[071] A powder X-ray diffraction pattern was obtained by means of a solid phase detector in a range of 2° to 40° of a diffraction angle (2θ) with a step of 0.02° using D8 Focus (Bruker ASX). 2. Thermal Analysis (DSC)

[072] Differential scanning calorimetry (DSC) was performed using DSC 8000 (PerkinElmer). The samples were evaluated using a linear heating ramp of 10 °C / min in the range of 30 °C to 300 °C. 3. Thermogravimetric Analysis (TGA)

[073] Thermogravimetric analysis was performed from 30 °C to 900 °C using TGA 8000 (PerkinElmer), in which 0.5 mg to 2 mg of samples were weighed into a ceramic crucible and measured under the condition of 5 °C / min. 4. NMR ANALYSIS Petition 870250005638, dated 01 / 24 / 2025, pp. 126 / 166 14 / 32

[074] A nuclear magnetic resonance (NMR) analysis was performed using Varian Mercury 400. 5. MEASUREMENT / ANALYSIS OF MOISTURE CONTENT

[075] The moisture content of the sample obtained was measured with a Karl-Fischer 870KF Titrino Plus moisture meter (Metrohm). PREPARATION EXAMPLE 1: SYNTHESIS OF COMPOUND I

[076] Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone was synthesized in the same manner as in the method of preparation of the compound of Example 6 in Registered Patent Publication Document No. KR 10-1777971. 1H NMR (400 MHz, CDCI3); δ7.63^, J=1.2 Hz, 1H), 7.13(dd, J=8.4, 6.8 Hz, 1H), 7.06-7.04(m, 2H), 6.42(d, J= 1.2 Hz, 1H), 4.86-4.84(m, 1H), 4.41-4.28(m, 4H), 4.37(d, J =4.4Hz, 2H), 3.75-3.69(m, 1H), 2.43-2.34(m, 13H) PREPARATION EXAMPLE 2: PREPARATION OF THE SOLVATE OF COMPOUND I

[077] Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone obtained in Preparation Example 1 was crystallized in an alcohol solvent (isopropyl alcohol, IPA) and dried under vacuum at about 30 °C to 35 °C, in order to obtain a solvate of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone. EXAMPLE 1(1): PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM A

[078] To a reactor, 10 g of the solvate of compound I obtained in Example of Preparation 2 above and 211 g of purified water or a mixed solvent (dichloromethane, DMF, NMP or acetone) with purified water were added and then stirred at 20 °C to 25 °C for 10 minutes. Subsequently, a solution prepared by dissolving 42.3 g of purified water in 4.9 g of citric acid was added at approximately 20 °C to 25 °C to confirm that a solid was produced and then stirred continuously at the same temperature for two hours, after which the resulting solid Petition 870250005638, dated 01 / 24 / 2025, pp. 127 / 166 15 / 32 was filtered, washed with 25.4 g of purified water and dried under vacuum or dried under nitrogen at about 40 °C, in order to prepare 9.70 g of azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate. EXAMPLE 1(2): PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM A

[079] A solution prepared by dissolving 16.9 g of purified water or a mixed solvent of purified water (acetone, DMF or NMP) in 9.8 g of citric acid was added to a reactor and then stirred at 20 °C to 25 °C for 10 minutes. Subsequently, a solution prepared by dissolving 90 g of dichloromethane in 20 g of the solvate of compound I obtained in Preparation Example 2 above was added at the same temperature to confirm that a solid was produced and then stirred continuously at the same temperature for two hours, after which the resulting solid was filtered, washed with 50.0 g of purified water and dried under vacuum or dried under nitrogen at about 40 °C, so as to prepare 19.4 g of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone citrate. ANALYSIS 1 - RESULTS OF XRD, DSC AND TGA MEASUREMENTS OF CRYSTALLINE FORM A

[080] Referring to Figure 1 and Table 1 below, a 2Θ value (unit: °) of the XRD pattern of Crystalline Form A, according to the present invention, can be confirmed. Specifically, the XRD pattern of Crystalline Form A, according to the present invention, includes a diffraction peak where a 2Θ value is 5.46°, 7.14°, 10.61°, 10.93°, 11.82°, 13.11°, 14.15°, 15.84°, 16.35°, 18.27°, 19.79°, 24.21° and 25.77°.

[081] Referring to Figure 2, Crystalline Form A shows an endothermic DSC peak at 88.69 °C, 135.61 °C and 154.84 °C.

[082] Referring to Figure 3, as a result of the TGA measurement, it is confirmed that Crystalline Form A is decomposed in three stages. Specifically, it was found that the decomposition occurs in a first stage from about 56.98 °C to 72.37 °C, a second stage from about 161.59 °C to 196.61 °C, and a third stage of Petition 870250005638, dated 01 / 24 / 2025, pp. 128 / 166 16 / 32 approximately 301.27 °C to 350.19 °C, and a maximum inflection point to be decomposed is confirmed at approximately 67.85 °C, 179.58 °C and 330.88 °C, respectively.

[083] Meanwhile, it can be confirmed through the moisture content that Crystalline Form A is anhydrous.

[084] Furthermore, it has been confirmed that Crystalline Form A, according to the present invention, is that in which azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid are linked in a molar ratio of about 1:0.5. TABLE 1 Diffraction angle (20°, unit: °) Relative intensity 5.46 Strong 7.14 Strong 9.12 Weak 9.37 Weak 10.61 Strong 10.93 Moderate 11.82 Strong 13.11 Moderate 14.15 Moderate 15.84 Moderate 16.35 Moderate 17.04 Weak 18.27 Strong 19.79 Moderate 21.16 Weak 24.21 Moderate Petition 870250005638, dated 01 / 24 / 2025, pp. 129 / 166 17 / 32 25.77 Strong EXAMPLE 2: PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM B

[085] To a reactor, 166.2 g of IPA and 10 g of the solvate of compound I obtained in Preparation Example 2 above were added and then stirred for 10 minutes. Subsequently, a solution in which 33.2 g of IPA were dissolved in 4.9 g of citric acid was added at 20 °C to 25 °C to confirm that a solid was produced and then stirred continuously at the same temperature for one hour, cooled to 0 °C to 5 °C and stirred again for one hour. The resulting solid was filtered and washed with 19.9 g of IPA to obtain 9.63 g of azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate. ANALYSIS 2 - RESULTS OF XRD, DSC AND TGA MEASUREMENTS OF CRYSTALLINE B FORM

[086] Referring to Figure 4 and Table 2 below, a 2Θ value (unit: °) of the XRD pattern of Crystalline Form B, according to the present invention, can be confirmed. Specifically, the XRD pattern of Crystalline Form B, according to the present invention, includes a diffraction peak where a 2Θ value is 7.03°, 7.69°, 9.47°, 13.21°, 14.86° and 21.13°.

[087] Referring to Figure 5, Crystalline Form B shows an endothermic DSC peak at 144.57 °C.

[088] Referring to Figure 6, as a result of the TGA analysis, it is confirmed that Crystalline Form B is decomposed in two stages. Specifically, it was found that the decomposition occurs in a first stage from about 163.24 °C to 196.32 °C and a second stage from about 305.85 °C to 342.24 °C, and a maximum inflection point to be decomposed is confirmed at about 180.52 °C and 331.48 °C, respectively.

[089] Meanwhile, it can be confirmed through the moisture content that the Crystalline form B is anhydrous. Petition 870250005638, dated 01 / 24 / 2025, pp. 130 / 166 18 / 32

[090] Furthermore, it has been confirmed that Crystalline Form B, according to the present invention, is that in which azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid are linked in a molar ratio of about 1:0.5. TABLE 2 Diffraction angle (20, unit: °) Relative intensity 7.03 Strong 7.69 Strong 8.31 Weak 9.47 Moderate 13.21 Strong 14.24 Weak 14.86 Strong 17.20 Weak 17.93 Weak 18.74 Weak 21.13 Strong 22.53 Weak 23.97 Weak EXAMPLE 3(1): PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM C1

[091] To a reactor, 167.2 g of acetone and 10 g of the solvate of compound I obtained in Preparation Example 2 above were added and then heated to 50 °C to 55 °C and stirred for 10 minutes. Subsequently, a solution in which 33.4 g of acetone were dissolved in 4.9 g of citric acid was added and stirred at the same temperature for one hour, and then cooled to 20 °C to 25 °C and stirred again. Petition 870250005638, dated 01 / 24 / 2025, pp. 131 / 166 19 / 32 for one hour. The resulting solid was filtered and washed with 20.1 g of acetone and then dried under vacuum at about 40 °C to obtain 11.75 g of azetidin-1yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate. EXAMPLES 3(2) TO 3(4): PREPARATION OF COMPOUND I CITRATE CRYSTALLINE FORM C1

[092] The azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrates, according to Examples 3(2) to 3(4) of the present invention, were obtained, respectively, substantially in the same process as the process for preparing the citrate of compound I described in Example 3(1) except that the solvent shown in Table 3 below was used as a mixed solvent along with acetone as a solvent added along with a solvate to a reactor. TABLE 3 Solvent classification Quantity to be used Example 3(2) Ethanol 80 g Example 3(3) Methanol 70 g Example 3(4) IPA 80 g EXAMPLE 3(5): PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM C1

[093] To a reactor, 167.2 g of acetone or 32.1 g of dichloromethane and 10 g of the solvate of compound I obtained in Preparation Example 2 above were added, and then stirred at 10 °C to 30 °C for 10 minutes. Then, a solution was added in which 33.4 g of acetone were dissolved in 4.9 g of citric acid over 10 minutes and stirred at the same temperature for one hour. Subsequently, the resulting mixture was cooled to 0 °C to 5 °C and stirred again for one hour. The resulting solid was filtered and washed with 20.1 g of acetone and then dried under vacuum at about 40 °C to obtain 11.74 g of azetidin-1-yl{8-[(2,6 Petition 870250005638, dated 01 / 24 / 2025, pp. 132 / 166 20 / 32 dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone. ANALYSIS 3 - RESULTS OF XRD, DSC AND TGA MEASUREMENTS OF THE C1 CRYSTAL FORM

[094] Referring to Figure 7 and Table 4 below, a value of 20 (unit: °) of the XRD pattern of the C1 Crystalline Form of the present invention can be confirmed. Specifically, the XRD pattern of the C1 Crystalline Form, according to the present invention, includes a diffraction peak where a value of 20 is 7.35°, 10.23°, 12.90°, 14.68°, 15.31°, 15.97°, 17.42°, 18.21°, 21.22°, 22.26° and 26.00°.

[095] Referring to Figure 8, Crystalline Form C1 shows an endothermic DSC peak at 168.93 °C.

[096] Referring to Figure 9, as a result of the TGA analysis, it is confirmed that the C1 Crystalline Form is decomposed in two stages. Specifically, it was found that the decomposition occurs in a first stage from about 172.76 °C to 192.20 °C and a second stage from about 297.93 °C to 337.46 °C, and a maximum inflection point to be decomposed is confirmed at 178.36 °C and 324.77 °C, respectively.

[097] Meanwhile, it can be confirmed through the moisture content that the C1 Crystalline Form is anhydrous.

[098] Furthermore, it has been confirmed that the Crystalline Form C1, according to the present invention, is that in which azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid are linked in a molar ratio of about 1:1. TABLE 4 Diffraction angle (20, unit: °) Relative intensity 7.35 Strong 10.23 Moderate 10.50 Weak 12.05 Weak Petition 870250005638, dated 01 / 24 / 2025, pp. 133 / 166 21 / 32 12.90 Moderate 14.68 Moderate 15.31 Strong 15.97 Moderate 17.42 Strong 18.21 Moderate 21.22 Moderate 22.26 Strong 23.46 Weak 24.30 Weak 25.74 Weak 26.00 Moderate EXAMPLE 4(1): PREPARATION OF COMPOUND I CITRATE - CRYSTALLINE FORM C2

[099] To a reactor, 167.2 g of acetone and 10 g of the solvate of compound I obtained in Preparation Example 2 above were added and then stirred at 20 °C to 25 °C for 10 minutes. Then, a solution in which 33.4 g of acetone were dissolved in 4.9 g of citric acid was added slowly dropwise over 60 minutes or more and stirred at the same temperature for one hour. Subsequently, the resulting mixture was heated to 50 °C to 55 °C and stirred again for one hour. The resulting mixture was cooled to 20 °C to 25 °C and stirred for a further hour, after which the resulting solid was filtered and washed with 20.1 g of acetone and then dried under vacuum at 40 °C to obtain 11.76 g of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate. EXAMPLES 4(2) TO 4(4): PREPARATION OF COMPOUND I CITRATE CRYSTALLINE FORM C2 Petition 870250005638, dated 01 / 24 / 2025, pp. 134 / 166 22 / 32

[0100] The azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrates, according to Examples 4(2) to 4(4) of the present invention, were obtained, respectively, substantially in the same process as the citrate preparation process described in Example 4(1) except that the solvent shown in Table 5 below was used as a mixed solvent along with acetone as a solvent added along with a solvate to a reactor. TABLE 5 Classification Solvent Quantity to be used Example 4(2) Ethanol 70 g Example 4(3) Methanol 80 g Example 4(4) IPA 80 g ANALYSIS 4 - RESULTS OF XRD, DSC AND TGA MEASUREMENTS OF THE C2 CRYSTAL FORM

[0101] Referring to Figure 10 and Table 6 below, a value of 20 (unit: °) of the XRD pattern of the C2 Crystalline Form of the present invention can be confirmed. Specifically, the XRD pattern of the C2 Crystalline Form, according to the present invention, includes a diffraction peak where a value of 20 is 5.63°, 8.90°, 9.51°, 12.31°, 13.01°, 14.34°, 14.80°, 18.38°, 18.75° and 19.62°.

[0102] Referring to Figure 11, Crystalline Form C2 shows an endothermic DSC peak at 161.48 °C.

[0103] Referring to Figure 12, as a result of the TGA analysis, it is confirmed that the C2 Crystalline Form is decomposed in two stages. Specifically, it was found that the decomposition occurs in a first stage from about 166.37 °C to 191.88 °C and a second stage from about 282.15 °C to 311.08 °C, and a maximum inflection point to be decomposed is confirmed at 173.44 °C and 304.81 °C, respectively.

[0104] Furthermore, it was confirmed that the C2 Crystalline Form, according to the Petition 870250005638, dated 01 / 24 / 2025, pp. 135 / 166 23 / 32 of the present invention is that in which azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid are linked in a molar ratio of about 1:1. TABLE 6 Diffraction angle (2Θ, unit: °) Relative intensity 4.44 Weak 5.63 Strong 6.94 Weak 7.36 Weak 8.03 Weak 8.90 Strong 9.51 Strong 12.31 Moderate 13.01 Strong 14.34 Moderate 14.80 Moderate 16.07 Weak 17.31 Weak 18.38 Moderate 18.75 Moderate 19.62 Moderate 21.62 Weak 22.21 Weak 23.11 Weak EXAMPLE 5(1): PREPARATION OF COMPOUND I CITRATE - FORM Petition 870250005638, dated 01 / 24 / 2025, pp. 136 / 166 24 / 32 Amorphous

[0105] In a reactor, 237.6 g of methanol were added to 10 g of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone citrate prepared according to Example 3(1), and then stirred at 20 °C to 25 °C for 20 minutes to dissolve. Then, a solid obtained by concentration was dried under vacuum at about 40 °C to obtain 9.8 g of the amorphous form of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone citrate. EXAMPLES 5(2) AND 5(3): PREPARATION OF COMPOUND I CITRATE AMORPHOUS FORM

[0106] Amorphous forms of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrates, according to Examples 5(2) and 5(3) of the present invention, were obtained, respectively, substantially in the same process as the process for preparing the citrate of compound I described in Example 5(1), except that the alcohol solvent shown in Table 7 below was used instead of methanol. TABLE 7 Classification Solvent Quantity to be used Example 5(2) Ethanol 710.1 g Example 5(3) IPA 3144 g ANALYSIS 5 - RESULTS OF DSC AND TGA MEASUREMENT OF THE AMORPHOUS FORM

[0107] Referring to Figure 13, it can be confirmed that the azetidin-1yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrates, according to Examples 5(1) to 5(3) of the present invention, are amorphous.

[0108] Referring to Figure 14, the amorphous form of compound I of the present invention shows an endothermic DSC peak at 161.42 °C. Petition 870250005638, dated 01 / 24 / 2025, pp. 137 / 166 25 / 32

[0109] Referring to Figure 15, as a result of the TGA analysis, it is confirmed that the amorphous form of the present invention is decomposed in three stages. Specifically, it was found that the decomposition occurs in a first stage from about 79.55 °C to 118.51 °C, a second stage from about 165.24 °C to 190.12 °C and finally a third stage from about 289.01 °C to 333.88 °C, and a maximum inflection point to be decomposed is confirmed at 105.71 °C, 175.22 °C and 315.61 °C, respectively.

[0110] Meanwhile, it can be confirmed through the moisture content that the amorphous form is also anhydrous. EXPERIMENTAL EXAMPLE 1: BIOAVAILABILITY EVALUATION

[0111] Bioavailability was evaluated with respect to azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention and azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone obtained, according to Preparation Example 1, as a comparative example. Specific pharmacokinetic experiments and evaluation methods are as follows. ADMINISTRATION AND BLOOD COLLECTION

[0112] Fasting male beagle dogs received capsules at a dose of 10 mg / kg orally and bled at 0.08, 0.25, 0.5, 1, 3, 5, 8 and 24 hours after administration. Blood collected in the amount of 3 ml each from the jugular vein was centrifuged to separate the plasma and stored frozen in a cryogenic freezer before analysis. PLASMA PRETREATMENT

[0113] Plasma pretreatment was performed using the protein precipitation method. 300 µl of acetonitrile containing an internal standard (200 ng / ml carbamazepine) were added to 100 µl of a plasma sample and mixed. After sufficient mixing, the resulting mixture was centrifuged at 12000 rpm for 10 minutes, after which the supernatant was transferred to an assay bottle and injected into an LC-MS / MS to analyze the blood concentration of the compound. Petition 870250005638, dated 01 / 24 / 2025, pp. 138 / 166 26 / 32 LC-MS / MS ANALYSIS CONDITIONS LC High-Performance Liquid Chromatography (HPLC) System Agilent 1260 Series equipped with online degasser, binary pump, autosampler and column compartment Waters Xterra MS C18 column (2.1x50 mm, 3.5 µm) Column oven 30 °C Mobile phase Linear gradient from 0.1% formic acid / 2% acetonitrile / 98% water DL to 0.1% formic acid / 98% acetonitrile / 2% water DL Flow rate 0.35 ml / min Injection Volume 5 µl MS System MS System API4000 LC / MS / MS Ion source Turbo V Ion sprayer (600 °C) Polarity Positive MRM m / z363>119 Internal standard m / z 237>194 Pharmacokinetic Evaluation

[0114] The parameters time to maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), and area under the plasma concentration-time curve (AUCo-t, AUCo-inf) were obtained using the PK solution. The results are shown in Table 8 below. TABLE 8 Item Unit Comparative Example: Compound I (free base) Example: Compound I Citrate Petition 870250005638, dated 01 / 24 / 2025, pp. 139 / 166 27 / 32 Tmax (h) 5.0 1.0 Cmax (ng / ml) 262.0 3033.3 AUCo-t (h.ng / ml) 2628.1 14968.1 AUC0-inf (h.ng / ml) 2818.0 15203.4

[0115] Referring to Table 8 above, it can be confirmed that azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone citrate, according to the present invention, reached maximum plasma concentration in a remarkably shorter time than compound I (free base), which was the Comparative Example, and was remarkably increased 11 times or more than that of the Comparative Example, and it can be confirmed that the AUC was also remarkably improved five times or more than that of the Comparative Example. In other words, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate, according to the present invention, exhibits significantly excellent bioavailability that notably exceeds a conventionally predictable level.

[0116] Consequently, azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, can exhibit very excellent bioavailability that the present inventors could not foresee and, therefore, can be used as an active ingredient of the pharmaceutical composition, so as to exhibit a very excellent effect in the prevention or treatment of inflammatory gastrointestinal diseases or diseases related to gastric acid. EXPERIMENTAL EXAMPLE 2: EVALUATION OF PHOTOSTABILITY

[0117] With respect to azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention, a sample was finely spread on a Petri dish and then irradiated with Visible light having a quantity of 35 k lux to achieve a total irradiation quantity of 1200 k lux under the condition of 25 °C and humidity of Petition 870250005638, dated 01 / 24 / 2025, pp. 140 / 166 28 / 32% using a photostability chamber (CARON 6542-2), while the sample was finely spread on a Petri dish and then irradiated with UV light at a rate of 35 W to achieve a total irradiation of 200 watts under conditions of 25 °C and 60% humidity using a photostability chamber (CARON 6542-2), and then the discoloration was observed with the naked eye. The results are shown in Table 9 below. It is considered suitable only when the white to yellowish-white powder form is maintained as a solid property. TABLE 9 Condition: Compound Citrate I color. Initial value: White. UV: 200 watts. Whitish. 1200 k lux visible: Slightly whitish.

[0118] Referring to Table 9, it can be confirmed that the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, is maintained as suitable for a property standard in a whitish or slightly whitish color degree, even when ultraviolet and visible light are irradiated. Thus, it can be observed that the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, possesses excellent photostability. EXPERIMENTAL EXAMPLE 3: EVALUATION OF SHORT-TERM STORAGE STABILITY (HEAT / HUMIDITY)

[0119] The purity of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention, was measured and then the purity was measured after being left at 60 °C for four days. The purity measurements were performed by HPLC. In addition, with Petition 870250005638, dated 01 / 24 / 2025, pp. 141 / 166 29 / 32 with respect to azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention, the purity was measured after being left for two days under conditions of 75 to 90% humidity (RH). The results of this are shown in Table 10 below. TABLE 10 Condition Purity (%) Citrate of Compound 1 Initial Value 99.955 Temperature 60 °C, Day 4 99.974 Humidity 75~90 %, Day 2 99.976

[0120] Referring to Table 10, it can be confirmed that the purity of the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, is not substantially altered even when left under high temperature or high humidity conditions. Thus, it can be observed that the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, exhibits stability to heat and humidity, respectively. EXPERIMENTAL EXAMPLE 4: EVALUATION OF LONG-TERM STORAGE STABILITY

[0121] Immediately after the preparation of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention, the properties were confirmed visually, and the moisture content, purity and XRD were measured, respectively. Subsequently, it was first sealed in a polyethylene bag and then secondarily sealed in an aluminum bag, and then the properties were confirmed visually and the moisture content, purity and XRD were also measured in Petition 870250005638, dated 01 / 24 / 2025, pp. 142 / 166 30 / 32 12, 24 and 36 months after being stored under conditions of 25±2 °C and 60±5 % RH. The results are shown in Table 11 below and in Figure 16. TABLE 11 Test Item Criteria Storage Period Immediately after preparation (baseline value) 12 months 24 months 36 months Properties White to off-white yellowish powder Suitable Suitable Suitable Suitable Moisture 1.0% or less 0.74% 0.52% 0.45% 0.60% Purity 99.0% or more 99.96% 99.96% 99.97% 99.96% XRD (Comparison with baseline value) Same Same Same Same

[0122] Referring to Table 11, it can be confirmed that azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, is maintained stably even at a time point 36 months after preparation.

[0123] Furthermore, referring to Figure 16, which is a result of XRD analysis after 36 months, it can be confirmed that the XRD pattern was maintained without a substantial change, specifically, without a shift of each diffraction peak from that of the citrate of the present invention immediately after preparation, as shown in Figure 10. In other words, it can be confirmed that the citrate, Petition 870250005638, dated 01 / 24 / 2025, pp. 143 / 166 31 / 32 according to the present invention, has excellent long-term storage stability. EXPERIMENTAL EXAMPLE 5: EVALUATION OF THERMAL AND HUMIDITY STABILITY (ACCELERATED CONDITIONS)

[0124] Immediately after preparation of azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to Example 4(1) of the present invention, the properties were confirmed visually, and the moisture content, purity and XRD were measured, respectively. Subsequently, the same was first sealed in a polyethylene bag and then secondarily sealed in an aluminum bag, and then the properties were confirmed visually and the moisture content, purity and XRD were also measured at one and six months after being stored under an accelerated condition of 40±2 °C and 75±5 % RH. The results of this are shown in Table 12 below. TABLE 12 Test Item Criteria Storage Period Immediately after preparation (initial value) 1 month 6 months Property White to off-white yellowish powder Suitable Suitable Suitable Moisture 1.0% or less 0.74% 0.75% 0.15% Purity 99.0% or more 99.96% 99.97% 99.96% Petition 870250005638, dated 01 / 24 / 2025, pp. 144 / 166 32 / 32 XRD (Comparison with initial value) Equal Equal Equal

[0125] Referring to Table 12, it can be confirmed that the azetidin-1-yl{8[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to the present invention, is maintained stably under accelerated conditions, even at a time point six months after preparation.

[0126] The present invention has been described herein with reference to preferred exemplary embodiments, but it will be understood by those skilled in the art that the present invention can be altered and modified in various ways without departing from the spirit and field of the present invention, as described in the scope of patent claims below. Petition 870250005638, dated 01 / 24 / 2025, pp. 145 / 166

Claims

1 / 4 CLAIMS 1. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate.

2. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, characterized in that the molar ratio between azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid is 1:0.5 or 1:

1.

3. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, characterized in that the citrate is anhydrous.

4. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, characterized in that the citrate is crystalline.

5. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, characterized in that the citrate is anhydrous crystalline.

6. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being Crystalline Form A including at least three diffraction peaks in which a 2Θ (±0.2°) value of a powder X-ray diffraction pattern is selected from the group consisting of 5.46°, 7.14°, 10.61°, 11.82°, 18.27° and 25.77°.

7. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 6, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being Crystalline Form A, further including at least one diffraction peak wherein the 2θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 10.93°, 13.11°, 14.15°, 15.84°, 16.35°, 19.79° and 24.21°.

8. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 6, wherein the azeti ... Petition 870260047475, dated 19 / 05 / 2026, page. 58 / 63 2 / 4 a]pyridin-6-yl}methanone is characterized by having an endothermic Differential Scanning Calorimetry (DSC) peak at 88.69 °C, 135.61 °C and 154.84 °C (±0.5 °C) when a heating rate of 10 °C / min.

9. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being Crystalline Form B including at least three diffraction peaks where a 2Θ (±0.2°) value of a powder X-ray diffraction pattern is selected from the group consisting of 7.03°, 7.69°, 9.47°, 13.21°, 14.86° and 21.13°.

10. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 9, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by having an endothermic Differential Scanning Calorimetry (DSC) peak at 144.57 °C (±0.5 °C) when a heating rate of 10 °C / min.

11. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being the C1 Crystalline Form including at least three diffraction peaks where a 2θ (±0.2°) value of a powder X-ray diffraction pattern is selected from the group consisting of 7.35°, 15.31°, 17.42° and 22.26°.

12. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 11, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being the C1 Crystalline Form further including at least one diffraction peak wherein the 2θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 10.23°, 12.90°, 14.68°, 15.97°, 18.21°, 21.22° and 26.00°.

13. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 11, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate is characterized by having an endothermic Differential Scanning Calorimetry (DSC) peak at 168.93 °C (±0.5 °C) when a heating rate of 10 °C / min.

14. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being the C2 Crystalline Form including at least three diffraction peaks where a 2Θ (±0.2°) value of a powder X-ray diffraction pattern is selected from the group consisting of 5.63°, 8.90°, 9.51° and 13.01°.

15. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 14, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by being the C2 Crystalline Form further including at least one diffraction peak wherein the 2θ (±0.2°) value of the powder X-ray diffraction pattern is selected from the group consisting of 12.31°, 14.34°, 14.80°, 18.38°, 18.75° and 19.62°.

16. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 14, wherein the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone citrate is characterized by having an endothermic Differential Scanning Calorimetry (DSC) peak at 161.48 °C (±0.5 °C) when a heating rate of 10 °C / min.

17. Azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, according to claim 1, characterized in that the citrate is amorphous.

18. Method for preparing azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone citrate, wherein the method is characterized by comprising: reacting azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2a]pyridin-6-yl}methanone and citric acid in the presence of at least one solvent selected from an alcohol with one to three carbon atoms, acetone, acetonitrile, tetrahydrofuran (THF), dichloromethane, dimethylformamide (DMF), N-methylpyrrolidone (NMP) and purified water. Petition 870260047475, dated 19 / 05 / 2026, pp. 60 / 63 4 / 4 19. Method according to claim 18, characterized in that the azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6yl}methanone for the reaction with citric acid in the step is a solvate.

20. Method according to claim 18, characterized in that, in the step, citrate in which a molar ratio between azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and citric acid is 1:0.5 or 1:1 is prepared.

21. Method according to claim 18, characterized in that the step includes mixing a first solution including azetidin-1-yl{8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}methanone and a first solvent and a second solution including citric acid and a second solvent, wherein the first solvent is a single solvent of acetone or a mixed solvent including acetone and at least one selected from an alcohol with one to three carbon atoms, acetonitrile, tetrahydrofuran (THF), dichloromethane, dimethylformamide (DMF), and N-methylpyrrolidone (NMP), and the second solvent is acetone. Petition 870260047475, dated 05 / 19 / 2026, pp. 61 / 63

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