Synthesis of 2-Substituted Trifluoromethylquinolines for the Evaluation of Leishmanicidal Activity.

Trifluoromethylation of aryl and heteroaryl halides

“…Dade reported the trifluoromethylation of quinolines using methyl chlorodifluoroacetate where 2-propyl-3-trifluoromethylquinoline was prepared in moderate yield (entry 6). 64 While preparing novel aryl sulfonamide and sulfonyl compounds as peroxisome proliferator activated receptor (PPAR) modulators for the treatment of metabolic disorders, Zhao and co-workers carried out trifluoromethylation of an iodopyridazine on a relatively large scale (12 g). Instead of ClCF 2 CO 2 Me, they used ClCF 2 CO 2 Et in the presence of KF and CuI to trifluoromethylate the iodopyridazine.…”

An alternative route for synthesis of o-trifluoroacetylanilines as useful fluorine-containing intermediates

“…Although the otrifluoroacetylanilines do not possess direct biological activities, they are highly valuable synthetic intermediates in the preparation of many trifluoromethylated drugs such as HIV reverse transcriptase inhibitor efavirenz (DMP 266) [22], antiprotozomal drug mefloquine [23] and some antileishmanial compounds [24,25]. Therefore, this class of compounds has highly synthetic value in medicinal chemistry.…”

Highly Efficient Construction of 2‐Fluoroalkyl Quinolines through a Palladium‐Catalyzed 6‐endo‐trig Heck Cyclization Reaction

“…The cyclization of trifluoroacetimidoyl chlorides has been reported to proceed through ar adicalp rocess. [11,15] Therefore, to gain mechanistic insighti nto this intramolecular cyclization re-action, we introduced ar adical scavenger,butylhydroxytoluene (BHT) or (2,2,6,6,-tetramethylpiperidin-1-yl)oxyl (TEMPO), into the reaction mixture under our optimizedc onditions. Neither of these scavengers had an adversee ffect on the reaction of compound 1f,a nd compound 2f was isolated in about 86 % yield in each case (Scheme 3).…”

“…[1] Moreover,2 -fluoroalkyl quinoline derivatives have been found to exhibit enhanced biological properties and these structuresh ave served as popular scaffolds in pharmaceutical research. [2] For example, mefloquine is ac ommercial antiprotozoal drug for the treatmento fmalaria (I;F igure 1), [3] whilst other 2-trifluoromethyl quinolines have been shown to exhibit strong carcinostatic effects (II;F igure 1) [4] and therapeutic properties for dementia and schizophrenia (III;F igure 1). [5] Compound IV has been used as an antituberculosis agent that targets DNA topoisomerase IV and DNA gyrase (Figure 1).…”