新产品编号:2482667
Chemical Name: 4-[9-[N-(2,2,2-Trifluoroethyl)carbamoyl]-9H-fluoren-9-yl]butylphosphonic acid bis(6-methylpyridin-2-ylmethyl) diester
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Alkylation of the dilithio derivative of fluorene-9-carboxylic acid (I) with diethyl 4-bromobutylphosphonate (II) affords adduct (III).After conversion of acid (III) to the corresponding acid chloride (IV),condensation with 2,2,2-trifluoroethylamine (V) affords amide (VI).The phosphonate ethyl ester (VI) is cleaved by means of bromotrimethylsilane yielding phosphonic acid (VII),which is further activated as the phosphonic acid chloride (VIII) by using oxalyl chloride in the presence of DMF.Finally,condensation of acid chloride (VIII) with (6-methylpyridin-2-yl)methanol (IX) leads to the target bis-pyridinylmethyl ester.
📌 参考资料/链接：
参考文献标题:Microsomal triglyceride transfer protein inhibitors: Discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents
文献作者:Magnin,D.R.; Biller,S.A.; Wetterau,J.; Robl,J.A.; Dickson,J.K.Jr.; Prakash,T.; Harrity,T.W.; Lawrence,R.M.; Sun,C.-Q.; Wang,T.; Logan,J.; Fryszman,O.; Connolly,F.; Jolibois,K.; Kunselman,L.
参考来源:Bioorg Med Chem Lett 2003,13(7),1337