title: [Improved synthesis process of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate].
abstract: OBJECTIVE
  To establish a new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate.
  
  
  METHODS
  Target compound (5) was synthesized by the use of (2,4-dioxo-tetrahydropyridopyrimidin-6-yl)methyl acetate (1) as starting material via hydrolysis, chlorination, condensation with diethyl (p-aminobenzoyl)glutamate and aminolysis.
  
  
  RESULTS
  A new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate was established. This synthetic route has hydrolysis reaction, chlorination, diethyl N-(p-aminobenzoyl)-L-glutamate condensation reaction and ammonolysis reaction. The total yield is 36.7%.The structures of those compounds have identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance and mass spectrometry. This synthetic route avoid the unstable brominated reaction product and improves the harsh condition of ammonolysis reaction.
  
  
  CONCLUSIONS
  The new synthetic route has improved the reaction condition and the stability of the intermediate, and increased the extent of the derivative compounds, which has great significance to anti-folic acid of anti-tumor inhibitor synthesis.
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Yi-qing
authors.initials: YQ
authors.lastname: Du
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Yuan-xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Zhi-li
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Xiao-wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China; Peking University State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Jun-yi
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
mesh_terms: D005971:Glutamates / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy
chemical_list: D005971:Glutamates