Synthesis of Novel Pyrido[3′,2′:4,5]furo[3,2‐ d ]pyrimidine Derivatives and Their Cytotoxic Activity

The 3‐amino‐6‐(trifluoromethyl)furo[2,3‐ b ]pyridine‐2‐carbohydrazide ( 5 ) was prepared from 3‐cyano‐6‐trifluoromethyl‐2(1 H )pyridone ( 2 ) in series of steps via selective O ‐alkylation , Thorpe–Ziegler cyclization followed by reaction with hydrazine hydrate. The 2‐carbohydrazide ( 5 ) was further reacted with aliphatic acids under different reaction temperatures to form a series of novel N ‐acylfuro[2,3‐ b ]pyridine‐2‐carbohydrazide ( 6 ) and pyrido[3′,2′:4,5]furo[3,2‐ d ]pyrimidine derivatives ( 7 ). All the compounds 6 and 7 were screened for cytotoxic activity against breast carcinoma MD Anderson‐Metastatic Breast (MDA‐MB) 231 (aggressive) cell lines at 10 µM concentration. Compounds 6a , 6b , and 6c showed promising activity.