Razaxaban is an oral Factor Xa inhibitor that is being developed for the treatment of thromboembolic disorders. When the API (Active Pharmaceutical Ingredient) was exposed to ICH photo-stability conditions, a degradant at ca. 1.5 A.P. was observed in the HPLC profile. Initial LC-MS and LC-MS-MS analyses suggested that the degradant was an isomer of razaxaban containing a structural modification at the “isoxazole” moiety of the molecule. In order to establish the exact structure, a pure sample of the degradant was isolated by preparative HPLC from an enriched sample of razaxaban, which had been exposed to high intensity UV light for 15 days. Comprehensive analysis of 1D and 2D NMR data, including 1H-15N HMQC and HMBC in comparison with the comparable data for the API and commercially available compounds, benzooxazol-2-ylamine and 1,2-benzisoxazol-3-amine, led to a novel structure assignment for the degradant. A plausible mechanistic pathway for the formation of the photodegradant is proposed.
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