# US 12,215,083 B2 · Solid forms of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-n-benzylacetamide

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- Number: US 12,215,083 B2
- Document ID: US12215083B2
- Status: Granted
- Kind: B2
- Application number: 17/546,133
- Filed: 2021-12-09
- Published: 2022-03-31
- Granted: 2025-02-04
- Earliest claimed: 2017-09-07
- Assignees: Atnx Spv, LLC
- Applicants: Atnx Spv, LLC
- Inventors: Michael P. Smolinski
- Web page: https://patentgrep.com/patent/US12215083B2

## CPC

- C07D 213/56: Amides
- A61P 35/00: Antineoplastic agents
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present application provides solid forms of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide, and methods of preparing and using the same for the treatment of a cell proliferative disorder in which a tyrosine kinase plays a role.

## Claims

### Claim 1

A method of preparing a Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
slurrying Compound A in chloroform.

### Claim 2

A method of preparing the Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
adding an anti-solvent to a solution of Compound A in chloroform or acetonitrile, wherein the anti-solvent is isopropyl alcohol;
adding an anti-solvent to a solution of Compound A in methanol, wherein the anti-solvent is isopropyl acetate;
adding an anti-solvent to a solution of Compound A in acetone, wherein the anti-solvent is toluene; or
allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol or chloroform, wherein the anti-solvent is methyl tert-butyl ether.

### Claim 3 (depends on 2)

The method of claim 2, wherein the method comprises adding an anti-solvent to a solution of Compound A in chloroform wherein the anti-solvent is isopropyl alcohol.

### Claim 4 (depends on 2)

The method of claim 2, wherein the method comprises adding an anti-solvent to a solution of Compound A in acetonitrile, wherein the anti-solvent is isopropyl alcohol.

### Claim 5 (depends on 2)

The method of claim 2, wherein the method comprises adding an anti-solvent to a solution of Compound A in methanol, wherein the anti-solvent is isopropyl acetate.

### Claim 6 (depends on 2)

The method of claim 2, wherein the method comprises adding an anti-solvent to a solution of Compound A in acetone, wherein the anti-solvent is toluene.

### Claim 7 (depends on 2)

The method of claim 2, wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol or chloroform, wherein the anti-solvent is methyl tert-butyl ether.

### Claim 8 (depends on 7)

The method of claim 7, wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol, wherein the anti-solvent is methyl tert-butyl ether.

### Claim 9 (depends on 8)

The method of claim 8, wherein Compound A in methanol is at a concentration of about 14 g/mL.

### Claim 10 (depends on 7)

The method of claim 7, wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in chloroform, wherein the anti-solvent is methyl tert-butyl ether.

### Claim 11 (depends on 10)

The method of claim 10, wherein Compound A in chloroform is at a concentration of about 52 g/mL.

### Claim 12 (depends on 7)

The method of claim 7, wherein said vapor of said anti-solvent is allowed to diffuse into said solution of Compound A for about 7 days.

### Claim 13

A method of preparing the Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
slowly cooling a solution of Compound A in acetone, isopropyl acetate, 2-Me-THF, ethyl acetate, acetonitrile, a 1:3 mixture of chloroform and heptane, or a 1:3 mixture of dioxane and isopropyl acetate.

### Claim 14 (depends on 13)

The method of claim 13, wherein the method comprises: (i) heating a suspension of Compound A in acetone, isopropyl acetate, 2-Me-THF, ethyl acetate, acetonitrile, a 1:3 mixture of chloroform and heptane, or a 1:3 mixture of dioxane and isopropyl acetate, and (ii) slowly cooling the solution until the Form B polymorph precipitates from said solution.

### Claim 15 (depends on 14)

The method of claim 14, wherein the method comprises heating said suspension to a temperature of about 50° C.

### Claim 16 (depends on 13)

The method of claim 13, wherein the method comprises cooling said solution to a temperature of about 5° C.

### Claim 17 (depends on 13)

The method of claim 13, wherein the method comprises cooling said solution to a temperature of about −20° C.

### Claim 18 (depends on 1)

The method of claim 1, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2η refers to ±0.3°2θ.

### Claim 19 (depends on 1)

The method of claim 1, wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138° C. refers to ±5% of the listed values.

### Claim 20 (depends on 2)

The method of claim 2, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2η C. refers refers to ±0.3°2θ.

### Claim 21 (depends on 2)

The method of claim 2, wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138° C. 133° C. and approximately 138° C. refers to ±5% of the listed values.

### Claim 22 (depends on 13)

The method of claim 13, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2η C. refers refers to ±0.3°2θ.

### Claim 23 (depends on 13)

The method of claim 13, wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138° C. refers to ±5% of the listed values.

### Claim 24 (depends on 1)

The method of claim 1, wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.

### Claim 25 (depends on 1)

The method of claim 1, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.

### Claim 26 (depends on 2)

The method of claim 2, wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.

### Claim 27 (depends on 2)

The method of claim 2, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.

### Claim 28 (depends on 13)

The method of claim 13, wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.

### Claim 29 (depends on 13)

The method of claim 13, wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.