Synthetic studies on formamidopyrimidines related to clofarabine.
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.
Cantrell
William R
WR
Genzyme Corporation, Quality and Technical Operations, San Antonio, Texas78229, USA.
Lovett
Dennis
D
Engles
Tracy
T
Anderson
Bruce
B
Bauta
William E
WE
Wolstenholme-Hogg
Paul C
PC
D000227:Adenine Nucleotides / Q000737:chemistry*; D001087:Arabinonucleosides / Q000737:chemistry*; D000077866:Clofarabine; D005559:Formamides / Q000138:chemical synthesis*; D005561:Formates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis*
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D005559:Formamides; D005561:Formates; D011743:Pyrimidines; D000077866:Clofarabine; C042113:allyl chloroformate