Synthetic Studies on Formamidopyrimidines Related to Clofarabine |
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Authors: | William R. Cantrell Jr. Dennis Lovett Tracy Engles Bruce Anderson William E. Bauta Paul C. Wolstenholme-Hogg |
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Affiliation: | 1. Genzyme Corporation, Quality and Technical Operations , San Antonio, Texas, USA;2. Genzyme Corporation, Chemical Development, Genzyme Ltd. , Haverhill, Suffolk, United Kingdom |
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Abstract: | 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. |
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Keywords: | Purine degradation NMR characterization |
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