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

• Main Authors: Marcos A. P. Martins, Nilo Zanatta, Nícolas Krüger, Rosália Andrighetto, Helio G. Bonacorso
• Format: Article
• Language: English
• Published: MDPI AG 2011-03-01
• Series: Molecules
• Subjects: trifluoromethylated heterocyles; quinolines; naphthyridines; cycloalka[b][1,8]-naphthyridines; aminonaphthyridines
• Online Access: http://www.mdpi.com/1420-3049/16/4/2817/

A convenient and general method for the synthesis in 26–73% yields of a new series of 7-alkyl(aryl/heteroaryl)-2-amino-5-trifluoromethyl-1,8-naphthyridines from direct cyclocondensation reactions of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF3C(O)CH=C(R1)OR, where R1 = H, Me, Ph, 4-MePh, 4-OMePh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl, 2-thienyl and R = Me, Et] with 2,6-diaminopyridine (2,6-DAP), under mild conditions, is described. Another synthetic route also allowed the synthesis of 2-amino-5-trifluoromethyl-cycloalka[b][1,8]naphthyridines in 33–36% yields, from direct or indirect cyclo-condensation reactions of five-, six- and seven-membered 2-trifluoroacetyl-1-methoxy-cycloalkenes with 2,6-DAP.