Breaking and Making of Rings: A Method for the Preparation of 4‐Quinolone‐3‐carb­oxylic Acid Amides and the Expensive Drug Ivacaftor

Abstract

A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop-Winterfeldt type oxidation)

Accessing 1,8-Naphthyridone-3-carboxylic Acid Derivatives and Application to the Synthesis of Amfonelic Acid

“…Following GP 6 , using 10af (120 mg, 0.36 mmol), the title compound was obtained (101 mg, 100% yield) as a yellow solid. The spectroscopic data are consistent with those previously reported . TLC: R f = 0.21 (PE:EA = 1:1).…”

Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor

“…Yang's approach started from o-nitrobenzoyl acid (10a), while Laurus Pharma initiated the synthesis with o-fluoro-benzoyl acid (10b). In approach D, Vasudevan and co-authors reported the synthesis of ivacaftor using the Witkop-Winterfeldt oxidation of indolyl group 14 to form the quinoline through ozone oxidation [31,32]. For amide bond coupling with quinoline, Vertex employed aniline 5a in the initial route or 5-amino-2,4-di-tert-butylphenyl methyl carbonate (5b) in the second improved route, both derived from di-tert-butyl-phenol (15).…”

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

“…The common denominator for three of the routes (Grohe and Heitzer [29], Gould and Jacobs [30] and Long [31]) is that they consist of ring-closure reactions to form the quinolone ring system. The fourth one (Reddy) utilizes oxidative ring cleavage of the indole ring followed by condensation [32]. Some of these routes suffer from harsh reactions conditions and there is clearly room for novel methods complementary to those already present.…”