Synthetic study on novel immunosuppressant KF20444

The two new synthetic routes to 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H -benzo[6,7]cyclohepta[1,2-b]-quinoline-8-carboxylic acid (1). a novel immun osuppressant KF20444, are described. The seven-membered ring construction f rom 2-[4-(2-fluorophenyl)phenyl]-3-(2-carboxyethyl)-4-chloromethyl-6-fluoro quinoline (17c) was achieved by intramolecular Friedel-Crafts reaction unde r acidic conditions as the key step, Subsequently, the oxidation of 4-chlor omethyl group followed by reduction of carbonyl group on the seven-membered ring afforded 1. This route provides a new method for the synthesis of 1. (C) 2001 Elsevier Science Ltd. All rights reserved.