Synthesis of 2-[3-(trifluoromethyl)phenyl]furo[3,2-c]pyridine derivatives

Abstract

Abstract2-[3-(Trifluoromethyl)phenyl]-4,5-dihydrofuro[3,2-c]pyridin-4-one (I) was prepared by a three-step synthesis. Its reaction with phosphorus sulfide rendered thione II which was methylated to 2-[3-(Trifluoromethyl)phenyl]-4-methylsulfanylfuro[3,2-c]pyridine (III). 5-Methyl-2-[3-(trifluoromethyl)phenyl]-4,5-dihydrofuro[3,2-c]pyridin-4-one (IV) was obtained by the reaction of I with methyl iodide in PTC conditions. The chlorine atom in derivate V was replaced with heterocyclic secondary amines via nucleophilic substitution and 4-substituted furopyridines VIa and VIb were thus prepared. 2-[3-(Trifluoromethyl)phenyl]furo[3,2-c]pyridine-4-carboxylic acid (VII) was obtained by hydrolysis of the corresponding carbonitrile Va.

Synthesis, Complex Compounds and Antimicrobial Activity of Some Derivatives of Furo[3,2-C]Pyridine and Their Starting Compounds

“…The acids 1b-1d were synthesized by condensation of the appropriate carbaldehyde with malonic acid under Knoevenagel conditions. The compounds 4b-4f were prepared analogously by cyclisation of appropriated azides (SLEZIAK and KRUTOŠÍKOVÁ, 1996;GAJDOŠ et al, 2006;MOJUMDAR et al, 2009) Reaction of 4b and 4d with phosphorus pentasulfide led to corresponding thiones 5a, 5b, which were methylated in PTC conditions giving 6a and 6b (BRADIAKOVÁ et al, 2009;TARABOVÁ et al, 2010). 2-Methyl[1]benzofuro[3,2-c]pyridine-1-one (4e) and 5-metyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-c]pyridine-4(5H)-one (4f) were obtained by reaction of 4b, 4d with NaH and then methylated with methyl iodide.…”

“…(SLEZIAK and KRUTOŠÍKOVÁ, 1996;BRADIAKOVÁ et al, 2008;GAJDOŠ et al, 2006) Refluxing of appropriate chloroderivatives 7b and 7d with secondary heterocyclic amines gave 8a-8d (BRADIAKOVÁ et al, 2009;MOJUMDAR et al, 2009). The compounds 8f-8j were prepared according (TARABOVÁ et al, 2010;BRADIAKOVÁ et al, 2009;BENCKOVÁ and KRUTOŠÍKOVÁ 1999). N-Oxides 9a, 9b were prepared as it is described in (BRADIAKOVÁ et al, 2009).…”

“…The 4-substituted furo[3,2-c]pyridines were prepared by various methods. One method used as the starting compounds of the 4-chlorofuro[3,2-c]pyridines in which the chlorine atom was substituted with several nucleophiles (BOBOŠÍK et al, 1995;BÚDOVÁ et al, 2006;BRADIAKOVÁ et al, 2009). The reaction with sodium alkoxides in appropriate alcohol afforded the corresponding 4-alkoxyfuro[3,2c]pyridines (BÚDOVÁ et al, 2006).…”

One Pot Multicomponent Synthesis of Anti-inflammatory Active Tetrahydrofuro[3,2-c]pyridinone-2-carboxylate Derivatives

“…Column chromatography was performed on silica gel (100-200 mesh, SRL Chemicals) using increasing percentage of ethyl acetate in hexanes. 1 H NMR spectra (400 MHz) and 13 C NMR (100 MHz) and DEPT-135 spectra were recorded for CDCl3 + CCl4 (2:1) solutions on a Bruker-400 spectrometer with tetramethylsilane (TMS) as internal standard; J values are given in Hz. IR spectra were recorded as KBr solid solution on a Nicolet-6700 spectrometer.…”

“…Furopyridines are very similar to such skeletons as quinoline and isoquinoline which are present in many compounds exhibiting biological activity [1]. Furo [3,2-c]pyridinone alkaloids are widespread among the Rutaceae family of plants and display important biological activities.…”