5-Trifluoromethyl-1,6-naphthyridin-4 -ones

Heating 6-bromo- and 6-chloro-2-halomethyl- (99JHC1065) and 6-bromo-, 6-chloro- and 6-fluoro-2-phenyl-4/f-pyrido[l, 2-u]pyrimidin-4-ones (00JMC2814) in phenyl ether at 220 °C for 10 min yielded the appropriate 7-halo-1,8-naphthyridin-4-ols. 6-Amino-2-trifluoromethyl-4//-pyrido[l, 2-a]-pyrimidin-4-one was transformed into 7-amino-2-trifluoromethyl-l,4-dihy-dro-l,8-naphthyridin-4-one in 90% yield (98EJM383). 

Amino-2-trifluoromethyl-4//-pyrido[l,2-a pyrimidin-4-one (69) gave 7-amino-2-trifluoromethyl-1,8-naphthyridin-4(l//)-one (70) (PI12O, reflux 90%).533... 

An ingenious method for the construction of the 1,6-naphthyridine system with the use of chelate methodology was developed (1994IZV1510). Thus, the reaction of 3-acetyl-4-amino-5,5,5-trifluoro-3-penten-2-one 99 with Ph2BOBu afforded a chelate complex, which reacted with primary amines and then with two equivalents of dimethylformamide dimethyl acetal to give 5-trifluoromethyl-l,6-naphthyridin-4(17Z)-ones 100. 

Suzuki, H. Sakai, N. Iwahara, R. Fujiwaka, T. Satoh, M. Kakehi, A. Konakahara, T. Novel synthesis of 7-fluoro-8-(trifluoromethyl)-l/f-l,6-naphthyridin-4-one derivatives intermolecular cyclization of an A-silyl-l-azaallyl anion with perfluoroalkene and subsequent intramolecular skeletal transformation of the resulting pentasubstituted pyridines. J. Org. Chem. 2007, 72(15),5878-5881. 

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