Volasertib的合成

发布时间：2018-06-14 06:19

本文选题：抗肿瘤药 + PLK抑制剂　；参考：《中国医药工业杂志》2015年11期

【摘要】：(R)-2-氯-7-乙基-8-异丙基-5-甲基-7,8-二氢蝶呤-6(5H)-酮(6)与3-甲氧基-4-氨基苯甲酸(7)反应制得关键中间体(R)-4-[(7-乙基-8-异丙基-5-甲基-6-氧代-5,6,7,8-四氢蝶呤-2-基)氨基]-3-甲氧基苯甲酸(8)。1-(环丙基甲基)-哌嗪(2)经还原胺化、水解、成盐制得(1R,4R)-4-[4-(环丙基甲基)哌嗪-1-基]环己胺盐酸盐(5)。5和8经缩合反应制得volasertib,总收率约47%(以2计),纯度99.7%。
[Abstract]:Synthesis of a key intermediate, RPU -4- [7-ethyl-8-isopropyl -5-methyl-7-dihydropterin -6-dihydropterin -6H-keto-ketone] -3-methoxy -4-aminobenzoic acid) -3-methoxybenzenetrimethylamino _ 3-methoxybenzoic acid) by the reaction of r-2-chloro-2-ethyl-8-isopropyl -5-methyl-7-dihydropterin (6-dihydropterin -2-yl) amino group] -3- methoxybenzomethyl methoxybenzene-7- [7-ethyl-8-isopropyl-5-methyl-6-oxy -6-oxy-6-trihydropterin -2-yl] -3-methoxy benzophenyl) The acid was reduced to amination. Volasertib was synthesized by hydrolysis and salt formation, and volasertib was obtained by condensation reaction of 5.5 and 8 with a total yield of about 47g (in 2 units), the purity was 99.70.The total yield of volasertib was about 4RX 4R 4- [4-( cyclopropyl methyl) piperazine -1-yl] cyclohexylamine hydrochloride 5.5 and 8 by condensation reaction.
【作者单位】：中国医药工业研究总院上海医药工业研究院化学制药新技术中心;上海药物合成工艺过程工程技术研究中心;
【分类号】：R914.5

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