Xiangrui Jiang, Qiang Zhang, Yongjun Mao
Dec 1, 2011
Citations
0
Influential Citations
10
Citations
Journal
Heterocycles
Abstract
New route for the preparation of N-(3-cyano-7-ethoxy-1,4dihydro-4-oxoquinolin-6-yl)acetamide (1), a key intermediate for the synthesis of selective EGFR kinase inhibitors, was described. 4(1H)-Quinolones are a series of important intermediates for the synthesis of anticancer, antimalarial, antidiabetic, antiviral agents and reversible (H/K) ATPase inhibitors. N-(3-Cyano-7-ethoxy-1,4dihydro-4-oxoquinolin-6-yl)acetamide (1, Figure 1) was a key intermediate for either EKB-569 (2) or neratinib (3) , both of which were developed as dual irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (EGFR-2) protein tyrosine kinases. In the previous reports, 1 was prepared using 2-amino-5-nitrophenol (4) as starting material. 5 was synthesized by acelytion, ethylation and reduction of 4 (Scheme 1), and then reacted with ethyl (E)-2-cyano-3-ethoxypropenoate to furnish 6. In the following thermal cyclization, the reaction mixture was heated at 260 °C for 20 h to give 1 with 35% yield.