SYNTHESIS OF NELARABINE WITH PURE beta-ANOMER THROUGH LATE-STAGE C-H NITRATION/NITRO-REDUCTION

摘要

An efficient and pure p-anomer synthesis of the clinical drug nelarabine from the readily available vidarabine has been achieved for the first time. The C6 amino group of vidarabine was transformed to methoxy group by diazotization/chlorination followed by methoxylation using Na2CO3/MeOH system. The formation of C(2)-N bond was achieved via the highly selective C-H bond functionalization by reacting with 2,2,2-trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate. The final product was obtained in total yield of 58.6% by 5 steps-synthesis from vidarabine after the reduction of nitro group to amino group. Moreover, the drug nelarabine could be obtained in 100 grams scale successfully and no chromatography was needed, which made this route more attractive for industrial application.