摘要
目的优化二肽基肽酶-Ⅳ(DPP-4)抑制剂安奈格列汀的合成工艺。方法以3-氨基-5-甲基吡唑和3,3-二乙氧基丙酸乙酯为起始原料,经环合、水解得到中间体2-甲基吡唑[1,5-a]嘧啶-6-羧酸,该中间体与(S)-1-[(2-氨基-1,1-二甲基乙基)氨基乙酰基]吡咯烷-2-甲氰盐酸盐缩合得到安奈格列汀。结果与结论目标化合物结构经质谱、氢谱和碳谱确证,总收率为25.8%(以3-氨基-5-甲基吡唑计),纯度为99.7%(HPLC)。本工艺反应条件更温和、操作简捷,更适合工业化生产。
Anagliptin is a new dipeptidyl peptidase-Ⅳ(DPP-4)inhibitor.In this paper,the synthetic process of anagliptin was studied.The key intermediate 2-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid(5)was prepared from 3-amino-5-methylpyrazole and ethyl 3,3-diethoxypropionate through cyclization and hydrolysis.The anagliptin was obtained by condensation of intermediate 5 and(S)-1-[(2-amino-1,1-dimethylethyl)aminoacetyl]pyrrolidine-2-methyl cyanide hydrochloride.The total yield was 25.8%(based on 3-amino-5-methylpyrazole)and the purity of the final product was 99.7%(HPLC).The structure of anagliptin was confirmed by ESI-MS,1H-NMR and 13C-NMR.The process has milder reaction conditions,simple operation and is more suitable for industrial production.
作者
何秋
华庆松
范庆玉
李霞
俞波
HE Qiu;HUA Qing-song;FAN Qing-yu;LI Xia;YU Bo(Jiangsu Lianhuan Pharmaceutical Co.,Ltd.,Yangzhou 225000,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2020年第5期289-291,共3页
Chinese Journal of Medicinal Chemistry
