Effective Strategy for the Synthesis of Pyrido[1',2':1,2]imidazo[5,4-c]isoquinoline System

Annulation of 3-aceta(benza)mido-2-phenylimidazo[l.2-~pyridines ( 2 a , b ) by phosphorus oxychloride results in the formation o f pyridoimidazoisoquinolines (3a,b) as potent antileukemic structures.An altematwe route for obtaining the isoquinoline framework was centered on the aza-Wittig reaction of iminophosphorane (4) with different isccyanates.Complex carboline compounds often show broad and nch physiological activities and these synthons have been developed as potential chemotherapeutic and pharmacologically active agents.'Recent works have shown that several structural analogues exhibit various pharmacological properties, such as antitumor activity.2In previous papers, we have reported the synthesis and characterization of series of azacarboline alkaloids from iminophosphoranes by tandem aza-Wittig I electrocyclizat~on reaction.3In continuing our chemical studies on azacarboline compounds, we examined the isoquinoline annulation from 3-amino-2-phenylimidazo[1.2-~pyridine(1) prepared by a previously reported procedure.4The use of acetyl chloride in benzene in presence of pyridine at 10°C gave the amde (2a) in a 65 % yield, which was optimized (93 %) by using acetic anhydride at 120°C with (l).5 Interestingly, amide (2a) which was identified by mass (mlz : 251, M+) and nmr spectroscopies occurs as a 11992, 57, 929.,