An Improved Convergent Approach for Synthesis of Erlotinib, a Tyrosine Kinase Inhibitor, via a Ring Closure Reaction of Phenyl Benzamidine Intermediate

Bulletin of the Korean chemical society

Javid Shahbazi Mojarrad¹  Ayuob Aghanejad¹  Davoud Asgari¹ 

关键词: Erlotinib;    Phenyl benzamidine;    EGFR-tyrosine kinase;    Non-small-cell lung cancer;    Dimroth rearrangement;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

An improved convergent and economical method has been developed for the synthesis of erlotinib, a 4-anilinoquinazoline and an EGFR-tyrosine kinase inhibitor for treatment of non-small-cell lung cancer. The final two steps for the formation of this 4-anilinoquinazoline from suitable 2-aminobenzonitrile intermediate and 3-ethynylaniline were modified and were performed in a simple one-pot reaction. The ring-closing mechanism for the formation of erlotinib from the suitable formamidine intermediate and 3-ethynylaniline was investigated and determined to proceed via the formation of phenyl benzamidine intermediate rather than involving Dimroth rearrangement reported earlier. The new benzamidine intermediate was isolated for the first time and characterized.

【 授权许可】

Unknown