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Degradation of clofarabine (3) in 0.9% saline solution at 100°C afforded three degradation products which were determined to be formamidopyrimidines 4-6.Compounds 4 and 5 were assigned as C1' 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(PPh3)4 and dimedone. A synthesis of compound 6 from 4 is also described. [ABSTRACT FROM AUTHOR]

The reaction between 2-fluoroadenine ( 3 ) and 1,3,5-tri- O -benzyl-1- α -d-chloroarabinofuranose ( 4 ) with potassium t- amylate was evaluated in various solvents to afford 9- β -d-(2,3,5-tri- O -benzyl-arabinofuranosyl)-2-fluoroadenine ( 5 ) and the corresponding α -anomer ( 6 ). In addition, 7- β -d-(2,3,5-tri- O -benzyl-arabinofuranosyl)-2-fluoroadenine ( 7 ) and an unusual “ bis -fluoroadenine” nucleoside ( 8 ) were isolated as by-products. The highest anomeric ratio (β/α > 10) and conversion (>80%) were observed with the highly polar solvent sulfolane. This reaction was demonstrated on gram scale as a practical laboratory synthesis of 5 , a known intermediate in the synthesis of fludarabine. [ABSTRACT FROM AUTHOR]