阿卡替尼合成路线图解

Graphical synthetic routes of acalabrutinib

阿卡替尼(acalabrutinib,ACP-196,1),化学名称为4-{8-氨基-3-[(2S)-1-(1-氧代-2-丁炔-1-基)-2-吡咯烷基]咪唑并[1,5-a]吡嗪-1-基]-N-(吡啶-2-基)苯甲酰胺,分子式:C26H23N7O2,分子量:465.507,CAS登记号:1420477-60-6,由美国Acerta制药公司研制,2016年被英国阿斯利康制药公司收购,于2017年10月获得美国FDA批准上市,商品名为Calquence,是一种新型的不可逆的第二代BTK抑制剂,用于治疗慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)和套细胞淋巴瘤(mantle cell lymphoma,MCL)。

Acalabrutinib (ACP-196) is a second-generation BTK inhibitor and has great potential for inhibiting the occurrence and development of B cell malignant tumors.5 Different synthetic routes according to different raw materials were summarized in this work:moreover,expensive raw materials were used in Method A and Method D,which is not conducive to scale-up production;reaction routes of M ethod B and Method C were long and low yield;Method E is cheap and easy to obtain starting mate-rials,not only the yield is high,but the reaction process is mild,which is economical and environmentally friendly for industrial production.