Isoquinolinone synthesis by SNAr reaction:: a versatile route to imidazo[4,5-h]isoquinolin-9-ones

Reaction of 2-chlorobenzonitriles with beta-ketoesters in an SNAr reaction, followed by cyclization in acid provides a versatile route to isoquinolones. Starting from 2,6-dichloro-3-nitrobenzonitrile 7, sequential displacement of the chlorines by an amine and a beta-ketoester leads to imidazo[4,5-h]isoquinolin-9-ones 1, a new class of kinase inhibitor. (C) 2002 Elsevier Science Ltd. All rights reserved.