新型叶酸拮抗剂吡啶并嘌呤衍生物的环合反应研究

Cyclization Reaction of Pyridanopurine Derivatives as Novel Antifolate

将6-取代-2,4-二氨基哌啶并[3,2-d]嘧啶衍生物与N,N-二甲基甲酰胺、三氯乙酰氯在25℃反应2h,"一锅法"环合反应生成7-取代-2-氨基-7,8-二氢-6H-吡啶并[1,2,3-gh]嘌呤衍生物,利用NMR、HRMS确定目标化合物的结构。考察了不同底物、反应底物比例、反应时间、温度对反应产率的影响,并提出可能的反应机理。该反应条件温和、效率高、操作简单。

7-Substituted 2-amine-8,9-dihydro-7 H-pyrido[1,2,3-gh]purin derivatives were synthesized by onepot reaction with 6-substituted-2,4-diaminopyrido[3,2-d] pyrimidine,DMF and trichloroacetyl chloride at 25 ℃ for2 h. The effects of different substrate,reaction substrate ratio,reaction time and temperature on reaction yield were investigated. The structures of the products were determined by NMR and HRMS, and the possible reaction mechanism was proposed. The reaction conditions are mild and easy to operate.