6-Methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile → 6-Methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile

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Reaction Steps

6-Methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile was fluorinated as described for 5-fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile. The product was isolated as a 3:1 mixture of 6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile (starting material) and 5-fluoro-6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile. For 5-fluoro-6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile, LCMS E-S (M+H)=221.2. This mixture of nitriles was subjected to the reduction conditions as described above for 3-(Aminomethyl)-5-fluoro-4-isopropyl-6-methylpyridin-2(1H)-one. For fluorinated compound LCMS (ES) (M+H) showed 225.2 and for non-fluorinated analog LCMS (ES) (M+H) showed 207.2. Subsequent coupling reaction was performed with the crude mixture of amines without further purifications. For 3-(ethyl(1-methylpiperidin-4-yl)amino)-N-((5-fluoro-6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(trifluoromethyl)benzamide diformate; 1HNMR (400 MHz, CD3OD) δ ppm 8.32 (s, 2H), 7.50 (s, 1H), 7.34 (s, 1H), 4.59 (s, 2H), 3.40 (br, 2H), 3.18 (br, m, 1H), 3.09 (q, J=6.8, 2H), 2.96 (br, m, 2H), 2.78 (s, 3H), 2.35 (s, 3H), 2.29 (d, J=3.2 Hz, 3H), 1.98 (br, d, J=13.2 Hz, 2H), 1.80 (br, m, 2H), 0.84 (t, J=6.8 Hz, 3H); MS (ES) (M+H) 551.5.

Provenance & Evidence