Crystalline forms of bempedoic acid

Patent metadata

Field	Value
Publication number	US-12528759-B2
Application number	US-202017765956-A
Country	US
Kind code	B2
Filing date	Oct 2, 2020
Priority date	Oct 3, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The presented invention relates to crystalline Form A and Form B of Bempedoic acid, a process for preparation thereof and a composition comprising the Form A or Form B.

First claim

The invention claimed is:

1 . A process for the preparation of a crystalline form of a compound of formula (1)

wherein the crystalline form is characterized by an XRPD pattern having 2θ values 10.3°, 17.5° and 18.0° degrees 2 theta (±0.2 degrees 2 theta), which process comprises:
a) dissolving the compound of formula (1) in an organic solvent selected from the group consisting of ethanol, propanol, 2-propanol, isopropanol, butanol, 2-butanol, pentanol, 2-pentanol, hexanol, acetone, an acetate, dimethylsulfoxide, tetrahydrofuran, 2-methyl-tetrahydrofurate, and acetic acid to obtain a solution; and
b) isolating the solid form by cooling the solution or concentration of the solution or addition of an antisolvent.

2 . The process according to claim 1 wherein the acetate is selected from the group consisting of methyl acetate, ethyl acetate, propyl acetate, and butyl acetate.

3 . The process according to claim 1 wherein the compound of formula (1) is dissolved at a temperature between 10° C. and the reflux temperature of the organic solvent.

4 . A process for the preparation of a crystalline form of a compound of formula (1)

wherein the crystalline form is characterized by an XRPD pattern having 2θ values 10.3°, 17.5° and 18.0° degrees 2 theta (±0.2 degrees 2 theta), which process comprises:
a) mixing of the compound of formula (1) with an organic solvent selected from the group consisting of acetonitrile, toluene, 1,4-dioxane, a chlorinated solvent, and a mixture thereof to obtain a mixture;
b) heating the mixture to dissolve the compound of formula (1) to obtain a solution; and
c) isolating the solid form.

5 . The process according to claim 4 wherein the isolating step comprises cooling the solution to a temperature between −50° C. and 0° C.

6 . The process according to claim 5 wherein the solution is cooled to a temperature between −30° C. and −10° C.

7 . The process according to claim 4 wherein the isolating step comprises concentrating the solution to ⅔ or ½ or ⅓ or ¼ of the original volume or the solution is evaporated to dryness.

8 . The process according to claim 4 wherein the isolating step comprises adding an antisolvent selected from an alkane or an aromatic solvent or water.

9 . The process according to claim 8 wherein the antisolvent is selected from the group consisting of pentane, heptane, hexane, octane, cyclohexane, cycloheptane, cyclooctane, and toluene.

10 . A process for the preparation of a crystalline form of a compound of formula (1)

wherein the crystalline form is characterized by an XRPD pattern having 2θ values 10.3°, 17.5° and 18.0° degrees 2 theta (±0.2 degrees 2 theta), which process comprises: stirring the compound of formula (1) in water.

11 . The process according to claim 10 wherein the concentration of compound of formula (1) in water is between 30 and 50 g/L.

12 . The process according to claim 10 wherein the stirring is for between 1 to 10 days.

Assignees

• Synthon Bv

Inventors

• Hegedus Michal
• Westheim Raymond

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C51/43 Primary

  by change of the physical state, e.g. crystallisation · CPC title