Preparation of new 2‐amino‐ and 2,3‐diamino‐pyridine trifluoroacetyl enamine derivatives and their application to the synthesis of trifluoromethyl‐containing 3H‐pyrido[2,3‐b][1,4] diazepinols

Abstract

The synthesis of a novel series of the intermediates N2(N3)‐[1‐alkyl(aryl/heteroaryl)‐3‐oxo‐4,4,4‐trifluoroalk‐1‐en‐1‐yl]‐2‐aminopyridines [F3CC(O)CHCR1(2NHC5H3N)] and 2,3‐diaminopyridines [F3CC(O)CHCR1(2‐NH2‐3‐NHC5H3N)], where R1 = H, Me, C6H5, 4‐FC6H4, 4‐CIC6H4, 4‐BrC6H4, 4‐CH3C6H4, 4‐OCH3C6H4, 4,4′‐biphenyl, 1‐naphthyl, 2‐thienyl, 2‐furyl, is reported. The corresponding series of 2‐aryl(heteroaryl)‐4‐trifluoromethyl‐3H‐pyrido[2,3‐b][1,4]diazepin‐4‐ols obtained from intramolecular cyclization reaction of the respective trifluoroacetyl enamines or from the direct cyclocondensation reaction of 4‐methoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,3‐diaminopyridine, under mild conditions, is also reported.

Synthesis and photophysical, thermal and antimycobacterial properties of novel 6-amino-2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl) quinolines

“…The structural assignments for 3a-f are consistent with the spectral data described in the literature for similar compounds. [26][27][28][29][30] The E-isomers can be distinguished from the Z-isomers by the 1 H-NMR spectra, because the N-H signals of the E-form (in 4-8 ppm) appear at a much higher magnetic field than those of the Z-form (in 9-13 ppm), indicating the presence of an intramolecular hydrogen interaction. The 1 H-NMR chemical shift of the enamino hydrogens for 3a-f was observed in the range of 3.44 to 3.87 ppm, allowing one to assume that the enaminoketones 3a-f exist in the Z-form in CDCl 3 , which is stabilized by an intramolecular N-HÁ Á ÁOQC interaction.…”

Unsaturated polyfluoroalkyl ketones in the synthesis of nitrogen-bearing heterocycles

“…When reaction proceeds at low temperature (MeOH, 0 C), they can be isolated in high yield. 124 Subsequent long heating of reaction mixture in methanol leads to formation of diazepinols 75. The target heterocycles 75 can be obtained in one step from initial alkoxyenones in yield 54-71%.…”

General Pathway for a Convenient One-Pot Synthesis of Trifluoromethyl-Containing 2-amino-7-alkyl(aryl/heteroaryl)-1,8-naphthyridines and Fused Cycloalkane Analogues

“…We also reported the synthesis of 5 H -thiazolo[3,2- a ]pyrimidi-5-ones from the reactions of β-alkoxyvinyl trichloromethyl ketones and 2-aminothiazole [ 30 ]. Unfortunately, reactions using β-alkoxyvinyl trifluoromethyl ketones and 2-aminopyridine in an attempt to obtain the respective cyclic structure only resulted in the isolation of trifluoroacetylenamine derivatives [ 32 ]. On the other hand, reactions using β-alkoxyvinyl trifluoro(chloro)methyl ketones and 2,3-diaminopyridine have been successfully employed in the synthesis of 3 H -pyrido[2,3- b ][1,4]diazepinols [ 31 , 32 ] or diazepinones [ 31 , 33 ].…”

“…Although the reactions of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones with primary and secondary amines have been well documented [ 28 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], there are no reports in the literature dealing with β-alkoxyvinyl trifluoromethyl ketones as electrophilic precursors and 2,6-diaminopyridine (2,6-DAP) as nucleophilic precursor. Considering the importance of trifluoromethylated heterocycles, as an extension of our research the purpose of this paper is to report the results of a chemical behavior study of the reactions of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones and 2-trifluoroacetyl-1-methoxycycloalkenes 1 with 2,6-DAP, a symmetrical heteroaromatic diamine, aiming at the synthesis of new nitrogen-containing trifluoromethylated heterocycles with conventional procedures ( Scheme 1 ).…”