富马酸替诺福韦二吡呋酯杂质的合成

Synthesis of The Impurities of Tenofovir Disoproxil Fumarate

为控制富马酸替诺福韦二吡呋酯的产品质量,以腺嘌呤为起始物料,合成了5种杂质:(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-醇,(R)-【{[1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧基}甲基】磷酸,【【{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基】(羟基)磷酸】氧】甲基异丙基碳酸酯,【【【{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基】(异并氧基)磷】氧】甲基异并氧基碳酸酯和(R)-异丙基【9-【2-【【双{[(异丙氧羰基)氧]甲氧}磷】甲氧基】丙】-9H-嘌呤-6-基】氨基碳酸酯,其结构经UV-Vis,1H NMR,13C NMR,MS(ESI)和元素分析确证。

To control the quality of the tenofovir disoproxil fumarate,five impurities including(R)-1-(6-amino-9H-purin-9-yl)propan-2-ol,(R)-{{[1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl}phosphonic acid,{{{{[(R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl}(hydroxy)phosphoryl}oxy}methyl isopropyl carbonate,{{{{[(R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl}(isopropoxy)phosphoryl}oxy}methyl isopropyl carbonate and(R)-isopropyl{9-{2-{{bis{[(isopropoxycarbonyl)oxy]methoxy}phosphoryl}methoxy}propyl}-9H-purin-6-yl}carbamate were synthesized from the starting material adenine.The structures were confirmed by UV-Vis,^1H NMR,^13C NMR,MS(ESI)and elemental analysis.