Quinolone analogues 6 [1-5]. Synthesis of 3-halogeno-1-methylpyridazino[3,4-b]quinoxalin-4(1H)-ones

✍ Scribed by Yoshihisa Kurasawa; Waka Satoh; Izumi Matsuzaki; Yuka Maesaki; Yoshihisa Okamoto; Ho Sik Kim

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2003
• Tongue: English
• Weight: 126 KB
• Volume: 40
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570400514

✦ Synopsis

Abstract

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b, whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d, whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d, respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d, whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1__H__)‐ones 6a‐d, respectively. Compounds 6a‐d had antifungal activities in vitro.