Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12281110-B2
Publication Date
2025-04-22
Expiration Date
Abstract
Disclosed herein are processes for preparing 8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one and FGFR inhibitor, as well as polymorphs and/or salt forms thereof.
Core Innovation
The invention concerns a FGFR inhibitor identified as 8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (Compound (I)). It addresses preparation of Compound (I) and conversion of Compound (I) to various salt forms, while also disclosing solid forms for Compound (I). Solid forms include a crystalline free base, a hydrate, an amorphous form, and solvate forms, each supported by referenced XRPD and other spectra/thermograms.
The solid-form disclosures include crystalline free base Form 1 characterized by an XRPD peak around 22° 2θ; hydrate Form 3 characterized by an XRPD peak around 6° 2θ; and an amorphous form with a disordered halo around 23° 2θ. Solvate forms (7, 10, 14) are supported by XRPD peaks around 14° 2θ, and hydrochloride and maleate salts are characterized by XRPD peaks around 11° 2θ and about 22.5° 2θ, respectively, with reference to figures/spectra (XRPD, NMR, DSC/thermograms).
The disclosure describes a synthetic process for preparing Compound (d) from an intermediate of formula (6) via acylation/amide formation. The transformation is framed in terms of producing Compound (d) from formula (6) and employs activation and coupling-related reagents, bases, solvents, and catalysts as described in the partial content. The disclosure also specifies an intermediate of formula (6-1) having variable substituents, where R is H or Cl, and X is halo/phosphate/tosylate/mesylate or salts.
Claims Coverage
The claim set covers multiple solid-state materials of a compound of formula, centered on three independent material categories: crystalline free base, amorphous free base, and crystalline hydrochloride or crystalline maleate salts. Across the independent claims, inventive features are characterized by specific XRPD-defined peaks or features and, for one independent claim, by the salt identity.
Crystalline free base with XRPD characteristic peak at about 22° 2θ
A crystalline free base of a compound of formula, characterized by an X-ray powder diffraction (XRPD) pattern that includes a characteristic peak at about 22° 2θ.
Amorphous free base with disordered halo at about 23° 2θ
An amorphous free base of a compound of formula, characterized by an XRPD pattern comprising a characteristic disordered halo at about 23° 2θ.
Crystalline hydrochloride or crystalline maleate salt with XRPD characteristic peaks
A crystalline hydrochloride salt or a crystalline maleate salt of a compound of formula, characterized by an XRPD pattern with a characteristic peak at about 11° 2θ for the hydrochloride salt and about 22.5° 2θ for the maleate salt.
Overall, the independent claim coverage is directed to specific, XRPD-characterized solid-state forms of the FGFR inhibitor compound: a crystalline free base, an amorphous free base, and crystalline salts comprising hydrochloride or maleate.
Stated Advantages
Crystalline free base Form 1 is characterized as substantially anhydrous and maintains phase identity as described with XRPD.
DSC/TGA characterization is provided to support stability behavior for Form 1.
DVS characterization indicates non-hygroscopic behavior.
Documented Applications
Treating FGFR-mediated diseases including multiple cancer types.
Interested in licensing this patent?