The identification of clofarabine process impurities and their subsequent isolation, synthesis, and characterization is described. Two isomeric process impurities resulting from N 6 -attachment of a fluoroarabinose to clofarabine were found. Clofarabine's base degradation products, which were different from the process impurities, were also synthesized and characterized. These compounds resulted from modifications to the sugar moiety, the purine ring, or both. A mechanistic rationale for the formation of the
Degradation of clofarabine (3) in 0.9% saline solution at 100 degrees C afforded three degradation products which were determined to be formamidopyrimidines 4-6. Compounds 4 and 5 were assigned as C(1') anomers on the basis of one-dimensional and two-dimensional NMR experiments, whereas 6 was found to be the formamidopyrimidine lacking the sugar moiety. An improved procedure for the synthesis of formamidopyrimidines was developed, wherein benzoylated clofarabine (11) was treated with allyl chloroformate, followed by deprotection of the alloc group with catalytic Pd(PPh(3))(4) and dimedone. A synthesis of compound 6 from 4 is also described.
Hydroxylation O 0216Hydrogen Peroxide Promoted Hydroxylation of Haloarenes and Heteroarenes.-It is demonstrated that the addition of aqueous hydrogen peroxide promotes the SNAr reaction of electron-deficient haloarenes. The method can be used to produce the degradation product (X) of clofarabine (IX). -(CANTRELL, W. R. J.; BAUTA*, W. E.; ENGLES, T.; Tetrahedron Lett. 47 (2006) 25, 4249-4251; Ther. Manuf. Dev., Genzyme Corp., San Antonio, TX 78245, USA; Eng.) -Mais 39-049
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.