【药物名称】
化学结构式(Chemical Structure):
参考文献No.725746
标题:Microsomal triglyceride transfer protein inhibitors: Discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents
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.
来源:Bioorg Med Chem Lett 2003,13(7),1337
合成路线图解说明:

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.

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