本文選題：抗腫瘤藥 + PLK抑制劑　； 參考：《中國醫(yī)藥工業(yè)雜志》2015年11期

【摘要】：(R)-2-氯-7-乙基-8-異丙基-5-甲基-7,8-二氫蝶呤-6(5H)-酮(6)與3-甲氧基-4-氨基苯甲酸(7)反應(yīng)制得關(guān)鍵中間體(R)-4-[(7-乙基-8-異丙基-5-甲基-6-氧代-5,6,7,8-四氫蝶呤-2-基)氨基]-3-甲氧基苯甲酸(8)。1-(環(huán)丙基甲基)-哌嗪(2)經(jīng)還原胺化、水解、成鹽制得(1R,4R)-4-[4-(環(huán)丙基甲基)哌嗪-1-基]環(huán)己胺鹽酸鹽(5)。5和8經(jīng)縮合反應(yīng)制得volasertib,總收率約47%(以2計),純度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.
【作者單位】： 中國醫(yī)藥工業(yè)研究總院上海醫(yī)藥工業(yè)研究院化學(xué)制藥新技術(shù)中心;上海藥物合成工藝過程工程技術(shù)研究中心;
【分類號】：R914.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 孫善亮;張亮;劉海春;盧帥;陸濤;;PLK1激酶域抑制劑的構(gòu)效關(guān)系與作用模式[J];中國醫(yī)藥工業(yè)雜志;2013年10期

2 董憲U，

本文編號：2016414