【药物名称】PD-166285
化学结构式(Chemical Structure):
参考文献No.486504
标题:2-Substituted aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure-activity relationships against selected tyrosine kinases and in vitro and in vivo anticancer activity
作者:Klutchko, S.R.; Hamby, J.M.; Boschelli, D.H.; Wu, Z.; Kraker, A.J.; Amar, A.M.; Hartl, B.G.; Shen, C.; Klohs, W.D.; Steinkampf, R.W.; Driscoll, D.L.; Nelson, J.M.; Elliott, W.L.; Roberts, B.J.; Stoner, C.L.; Vincent, P.W.; Dykes, D.J.; Panek, R.L.; et al.
来源:J Med Chem 1998,41(17),3276
合成路线图解说明:

The reaction of chloropyrimidine (I) with methylamine in the presence of triethylamine in THF yielded aminopyrimidine (II). The reduction of the ester group of (II) with LiAlH4 gave benzylic alcohol (III), which was oxidized to aldehyde (IV) with MnO2. This was condensed with 2,6-dichlorophenylacetonitrile (V) in DMF at 105 C in the presence of K2CO3 to provide pyridopyrimidine (VI). The imino group of (VI) was then acetylated with Ac2O, and the resulting N-acetylimine (VII) was hydrolyzed in boiling 6 N HCl to provide pyridopyrimidinone (VIII). Oxidation with two equivalents of m-chloroperbenzoic acid gave sulfone (IX), which was displaced with aniline (X) in refluxing AcOH to furnish (XI). Finally, (XI) was dissolved in boiling isopropanol and converted to the dihydrochloride by addition of an isopropanolic solution of HCl.

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