Method of preparing camsylate salts of triazolopyrazine derivatives
Inventors
Choi, Jun Young • PARK, Kyung-eui • Kim, Na Young
Assignees
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Publication Number
US-12371437-B2
Publication Date
2025-07-29
Expiration Date
Abstract
Disclosed are a salt (camsylate salt) of D(+)-10-camphorsulfonic acid and a triazolopyrazine derivative of formula (1), pharmaceutical compositions thereof, methods of making the salt, and therapeutic use thereof:
Core Innovation
The disclosure provides D(+)-10-camphorsulfonic acid camsylate salts of triazolopyrazine derivatives of formula (1), together with pharmaceutical compositions comprising the camsylate salts and therapeutic use for inhibiting c-Met kinase. The disclosure characterizes camsylate salt forms including Camp1, Camp2, Camp4, and Camp5/6, and specifies enantiomeric and optical purity preferences for the D(+)-10-camphorsulfonic acid component.
The disclosure further provides physical stability information using HT-XRPD and HR-XRPD, including characteristic 2θ peaks, and reports evidence for physical stability, form conversion, and chemical purity changes during storage. The disclosure also provides analytical characterization and stability evidence for the camsylate salts using methods including TGA/TGMS, DSC, LCMS, 1H-NMR, and DVS.
A manufacturing method is described in which the compound of formula (1) is combined with a solvent, D(+)-10-camphorsulfonic acid is added, and cooling is used to obtain a precipitate of the camsylate salt, with subsequent characterization used to support the salt selection and stability claims.
Claims Coverage
The only independent claim identified in the provided material is a method for manufacturing a camsylate salt of the compound of formula (1). It includes three inventive features: solvent preparation and stirring, adding D(+)-10-camphorsulfonic acid, and cooling to obtain a precipitate.
Adding the compound of formula (1) to a solvent-containing reactor and stirring
A method comprising adding the compound of formula (1) to a reactor containing a solvent and stirring the compound and the solvent.
Adding D(+)-10-camphorsulfonic acid to form the camsylate salt
The method further comprises adding D(+)-10-camphorsulfonic acid to the solution prepared by the stirring step to obtain a solution for precipitation of the camsylate salt.
Cooling to obtain a precipitate of the camsylate salt
The method comprises cooling the solution prepared after adding D(+)-10-camphorsulfonic acid to obtain a precipitate of the camsylate salt.
Across the independent claim, the camsylate salt is manufactured by preparing a solution of the compound of formula (1) in a solvent, adding D(+)-10-camphorsulfonic acid, and cooling to obtain a precipitate of the camsylate salt.
Stated Advantages
Improved salt properties while retaining free-base pharmacokinetics, including solubility and stability improvements as described in the disclosure.
Documented Applications
Therapeutic use for inhibiting c-Met kinase using pharmaceutical compositions comprising the camsylate salts.
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