CAJ | 학술논문

目的：改进抗叶酸类药物关键中间体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。方法：6-乙酰氧基甲基-2，4，-二氧代吡啶并[3，2-d]嘧啶（1）经过水解反应、氯代反应、对氨基苯甲酰谷氨酸二乙酯缩合、氨解反应生成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（5）。结果：改进了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路线，该合成路线共4步反应，分别为水解反应、氯代反应、对氨基苯甲酰谷氨酸二乙酯缩合反应和氨解反应，4步反应总收率为36．7％，化合物通过磁共振氢谱、磁共振碳谱和质谱分析法鉴定后结构正确。新路线避免了溴化反应产物的不稳定，改善了氨解反应苛刻的反应条件。结论：新合成路线改善了反应条件和中间体的稳定性，增加了化合物的衍生化范围，对抗叶酸类抗肿瘤抑制剂的合成研究具有重要意义。
목적：개진항협산류약물관건중간체N-[4-（2，4-이안기필정병[3，2-d]밀정-6-갑안기）-분갑선]-L-곡안산이을지적합성방법。방법：6-을선양기갑기-2，4，-이양대필정병[3，2-d]밀정（1）경과수해반응、록대반응、대안기분갑선곡안산이을지축합、안해반응생성N-[4-（2，4-이안기필정병[3，2-d]밀정-6-갑안기）-분갑선]-L-곡안산이을지（5）。결과：개진료N-[4-（2，4-이안기필정병[3，2-d]밀정-6-갑안기）-분갑선]-L-곡안산이을지적합성로선，해합성로선공4보반응，분별위수해반응、록대반응、대안기분갑선곡안산이을지축합반응화안해반응，4보반응총수솔위36．7％，화합물통과자공진경보、자공진탄보화질보분석법감정후결구정학。신로선피면료추화반응산물적불은정，개선료안해반응가각적반응조건。결론：신합성로선개선료반응조건화중간체적은정성，증가료화합물적연생화범위，대항협산류항종류억제제적합성연구구유중요의의。
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 .