Improved synthesis process of diethyl N-[4-[(2,4-diaminopyrido[3,2-d] pyrimidin-6-yl) methylamino] benzoyl]-L-glutamate
10.3969/j.issn.1671-167X.2015.05.022
- VernacularTitle:N-［4-（2，4-二氨基吡啶并［3，2-d］嘧啶-6-甲氨基）-苯甲酰］-L-谷氨酸二乙酯的合成方法改进
- Author:
Xin LIU
;
Yiqing DU
;
Yuanxin LI
;
Meng WANG
;
Zhili ZHANG
;
Xiaowei WANG
;
Junyi LIU
;
Chao TIAN
- Publication Type:Journal Article
- Keywords:
Folic acid diethylester derivatives;
Antineoplastic agents;
Chemical synthesis;
Halogena-tion;
Folic acid antagonists
- From:
Journal of Peking University(Health Sciences)
2015;(5):842-845
- CountryChina
- Language:Chinese
-
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 syn-thesized 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.Re-sults:A new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methyl-amino]benzoyl]-L-glutamatewas 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 1 H nuclear magnetic resonance , 13 C nu-clear magnetic resonance and mass spectrometry .This synthetic route avoid the unstable brominated re-action product and improves the harsh condition of ammonolysis reaction .Conclusion: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 .
