Process for preparing XPO1 inhibitors and intermediates for use in the preparation of XPO1 inhibitors
Inventors
Austad, Brian C. • Roe, David G.
Assignees
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Publication Number
US-12479806-B2
Publication Date
2025-11-25
Expiration Date
Abstract
The present invention provides an improved process for preparation of the (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (referred to as compound of the structural formula (III)), which is a useful key intermediate for the synthesis of Selinexor ((Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-(pyrazin-2-yl)acrylohydrazide). The process comprises reaction of the compound of the structural formula (I) (as described herein) with the compound of the structural formula (II) (as described herein) in the presence of a catalyst, an organic base and an ether-containing solvent. The subsequent hydrolysis of the formed compound of the structural formula (IIIa) (as described herein) is performed without isolation of the compound of the structural formula (IIIa), providing compound of the structural formula (III) in high yield and stereoselectivity.
Core Innovation
The disclosed invention is a telescoped process for preparing compound III, identified in the partial content as a Selinexor precursor. The process forms intermediate IIIa from compounds I and II, then converts IIIa to compound III without isolating IIIa. The specific reagent selections and operating conditions are [procedural detail omitted for safety].
The partial content reports improved yield and stereoselectivity and fewer isolation steps as benefits of the process. It does not include the patent's background section, so the problem being solved in that section is not explicitly described in patent. The provided content also does not state further context about the need that motivated the process.
Claims Coverage
The provided claims identify one independent claim, claim 1, covering a process for making compound III through formation and subsequent conversion of intermediate IIIa without isolating that intermediate, presenting one inventive feature.
Telescoped preparation of compound III
The claim covers reacting compounds I and II to produce intermediate IIIa, converting IIIa to compound III without isolating IIIa, and isolating compound III. Reagent selections and operating conditions are [procedural detail omitted for safety].
The independent claim centers on producing compound III through a two-stage process in which intermediate IIIa is not isolated before conversion to the final compound.
Stated Advantages
The disclosed process is reported to improve yield and stereoselectivity while reducing isolation steps.
Documented Applications
Preparation of compound III, identified in the partial content as a Selinexor precursor.
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