6-Methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile → 6-Methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile
Reaction equation
[CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.[F:15]C1C(C(C)C)=C(C#N)C(=O)NC=1C>>[CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([C:11]([F:14])([F:12])[F:13])[CH:3]=1.[F:15][C:3]1[C:4]([C:11]([F:14])([F:12])[F:13])=[C:5]([C:9]#[N:10])[C:6](=[O:8])[NH:7][C:2]=1[CH3:1]Participants
Reactant 2
Product 2
Procedure
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.
Sources & evidence
- ORD record
- ord-117c3d24d38b4260bf934509723b1ca7
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376422B2
Reaction notes
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